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Review Exp Ther Med
. 2020 Jul;20(1):18-23. doi: 10.3892/etm.2020.8619. Epub 2020 Mar 20.
Skin - A Vast Organ With Immunological Function (Review)
Minela Aida Maranduca 1, Loredana Liliana Hurjui 1, Daniel Constantin Branisteanu 2, Dragomir Nicolae Serban 1, Daciana Elena Branisteanu 3, Nicoleta Dima 4, Ionela Lacramioara Serban 1
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PMID: 32508987 PMCID: PMC7271707 DOI: 10.3892/etm.2020.8619
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Abstract
The skin is an organ with multiple functions, where important inflammatory and immunological processes take place. The integrity of the skin barrier is necessary for it to fulfill its roles. An intact skin barrier requires a physiological keratinization process, but also a normal cutaneous microbial flora. Any change in the proliferation and differentiation of keratinocytes entails the disruption of the skin barrier and the triggering of inflammatory and immunological processes at this level, in response to the aggression of external pathogens. Also, there are several specialised immune cells in the skin (Langerhans cells, T regulator cells, T helper cells), that maintain a balance between pro-inflammatory and anti-inflammatory processes at this level. Disturbing the immune homeostasis causes inflammation and allergic skin reaction. Psoriasis and atopic dermatitis are two inflammatory diseases of the skin, characterized by perturbation of the mechanisms of skin barrier formation. The immune system of the skin is also involved in the pathophysiology of vitiligo and pemphigus. The aim of this review is to offer a brief presentation of the inflammatory and immunological processes that occur in the skin.

Keywords: barrier; cytokines; keratinocyte; lymphocytes; skin.

Copyright © 2020, Spandidos Publications.

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2
Exp Ther Med
. 2020 Jun;19(6):3641-3649. doi: 10.3892/etm.2020.8624. Epub 2020 Mar 24.
Tougu Xiaotong Capsule Exerts a Therapeutic Effect by Improving Knee Meniscus in the Early Osteoarthritis Rat Model
Guangwen Wu 1 2, Yunmei Huang 1 3, Wenlie Chen 1 2 3, Junfang Chen 4, Xiaodong Lu 3 4, Xiangxiang Liu 4, Fangfang Feng 3 4, Meiya Huang 1 3, Ruhui Lin 1 3, Zuanfang Li 2 3, Chunjiang Tan 1 2
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PMID: 32373192 PMCID: PMC7197253 DOI: 10.3892/etm.2020.8624
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Abstract
The aim of the study was to observe the effects of Tougu Xiaotong capsule (TGXTC) on the microstructure and ultrastructure of meniscus in rats with early knee osteoarthritis (KOA). A total of 27 Sprague Dawley rats were randomly divided into three groups: The normal group (non-papain-induced KOA; received saline only), the model group (papain-induced KOA; received saline only) and the TGXTC group [papain-induced KOA; received TGXTC (0.31g·kg-1·d-1)]. After 4 weeks treatment, the animals were anesthetized and the sagittal plane of the intact knees (n=6 per group) was obtained and prepared in paraffin section. Following hematoxylin and eosin staining, the degeneration of cartilage structure was evaluated via Mankin score, the microstructure of meniscus was observed and the area of calcification in meniscus was analyzed. Following toluidine blue staining, the content of proteoglycan in meniscus was analyzed. Three samples in each group were obtained and the ultrathin sections of meniscus were observed through a transmission electron microscope. The results showed that compared with the normal group, in the model group the joint space became narrow and the cartilage layer was slightly damaged and the Mankin score was 4.17±0.76, suggesting that the early KOA model was successfully established. After TGXTC treatment, the joint space stenosis and cartilage damage were improved as the Mankin score significantly decreased. Compared with the normal group, in the model group the surface of meniscal cartilage was much more uneven, the area of calcification was significantly increased and the content of proteoglycan of cartilage matrix was significantly decreased. However, following TGXTC treatment, the surface of the meniscal cartilage was much more smooth and flat, and the damage of tissue structure and the calcified area were significantly reduced, and the proteoglycan of cartilage matrix content was significantly increased. Compared with the normal group, the number of cellular processes and organelles, including the rough endoplasmic reticulum, mitochondria and Golgi apparatus of meniscal cartilage were reduced and swollen in the model group. In addition, the nuclei were deformed and heterochromatin agglutinated. The extracellular collagen fibrils became slender, disordered and sparse. Compared with the model group, the TGXTC group had more cell processes and organelles, alleviated swelling and heterochromatin agglutinating. Additionally, the collagen fibrils around the cells were thicker, larger and arranged in an orderly manner. In conclusion, TGXTC exerted its therapeutic effects on the development of KOA via reducing the destruction of the cartilage structure of the meniscus and improving the composition and function of the meniscus cartilage matrix.

Keywords: Tougu Xiaotong Capsule; knee osteoarthritis; meniscus; microstructure; proteoglycan; ultrastructural.

Copyright: © Wu et al.

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3
Exp Ther Med
. 2020 Jul;20(1):61-67. doi: 10.3892/etm.2020.8572. Epub 2020 Feb 27.
Dynamics of Digital Ulcers in Systemic Sclerosis
Carmen Bobeică 1 2, Alin Laurențiu Tatu 3 4, Mihaela Crăescu 2 5, Laura Solovăstru 4 6
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PMID: 32508995 PMCID: PMC7271728 DOI: 10.3892/etm.2020.8572
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Abstract
Systemic sclerosis (SSc) is a collagenosis with insufficiently known etiopathogenesis, characterized by microvasculopathy and excessive fibrosis in the context of an autoimmune disorder. The incompletely elucidated pathogenesis and limited therapeutic options, disabling aspects, skin lesions and pain determine important functional and psychological deficiencies which affect the quality of life. It is imperative to observe and correlate individual clinical and paraclinical data to optimize disease management. A group of 22 patients diagnosed with SSc, hospitalized in a university clinic in Bucharest was included in an observational study. The evolution of digital ulcers was evaluated as an indicator of vasculopathy and their status and dynamics were correlated with clinical elements reflecting the fibrotic aspect of the disease. The present study shows that the Raynaud phenomenon is almost always present during the course of the disease, but its presence is not always associated with digital ulcers. The existing data in the literature show that fibrosis is subsequent to vasculopathy, but this study did not reveal causality between these two aspects of pathogenesis. The presence of microstomia and digital contracture was identified in the presence of digital ulcers, but also in their absence. The etiopathogenic mechanisms with multiple unknown involved factors open the opportunity to investigate many aspects of SSc for optimal aiming of therapeutic interventions.

Keywords: Raynaud's phenomen; digital ulcers; microangiopaty; microstomia; microvasculopathy; systemic sclerosis.

Copyright: © Bobeică et al.

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4
Exp Ther Med
. 2020 Jul;20(1):461-471. doi: 10.3892/etm.2020.8681. Epub 2020 Apr 23.
Differential Long Non-Coding RNA Expression Profiles in the Peripheral Blood and CD4 + T Cells of Patients With Active Rheumatoid Arthritis
Ming Li 1, Kexun Ma 1, Zhe Feng 1, Jing Wang 2, Xueping Zhou 1 3, Lingling Zhou 4
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PMID: 32509015 PMCID: PMC7271723 DOI: 10.3892/etm.2020.8681
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Abstract
The human transcriptome is primarily composed of long non-coding RNAs (lncRNAs), which are key regulatory molecules of multiple biological processes. In the present study, the expression profiles of lncRNAs in the peripheral blood and CD4+ T cells of patients with active rheumatoid arthritis (RA) were determined. Based on the expression profiles, 493 lncRNAs and 374 mRNAs were identified to be differentially expressed in the peripheral blood of active RA patients and healthy donors. Further verification of lncRNAs was performed using reverse transcription-quantitative (RT-q) PCR analysis of peripheral blood from 5 healthy donors and 5 patients with active RA and 14 additional differentially expressed genes were identified. CD4+ T cells in peripheral blood from 12 patients with active RA and 8 healthy donors were isolated using magnetic beads and qPCR was used to assess differentially expressed lncRNAs. The results suggested that 7 lncRNAs were upregulated and 2 were downregulated. The results indicated that these 9 lncRNAs may be involved in the pathogenesis of RA. An increased ratio of Th17: T-regulatory (Treg) cells was also observed. It may be hypothesized that LncRNAs serve important roles in the differentiation of CD4+ T cells. Receiver operating characteristic curve analysis suggested that these 9 lncRNAs are of potential clinical diagnostic value for RA. Pearson correlation analysis indicated that the correlation coefficient between Ensembl transcript (ENST)00000569543 and complement C4 was 0.623 (P<0.05), and that between ENST00000420096 and anti-cyclic citrullinated peptide antibody or disease activity evaluation score, the correlation coefficient was 0.662 and 0.605, respectively (P<0.05 for each). In conclusion, the results of the present study suggest a possible role of lncRNAs in the differentiation of CD4+ T cells and the pathogenesis of RA, as well as the potential value as diagnostic biomarkers for active RA.

Keywords: CD4+ T cell; expression profiles; high-throughput sequencing analysis; long non-coding RNA; rheumatoid arthritis.

Copyright: © Li et al.

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Exp Ther Med
. 2020 Jul;20(1):495-499. doi: 10.3892/etm.2020.8688. Epub 2020 Apr 27.
Lidocaine Improves Cerebral Ischemia-Reperfusion Injury in Rats Through cAMP/PKA Signaling Pathway
Yang Liu 1, Jie Zhang 2, Jingwei Zan 2, Fengxian Zhang 2, Guokai Liu 2, Anshi Wu 1
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PMID: 32509019 PMCID: PMC7271727 DOI: 10.3892/etm.2020.8688
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Abstract
Influence of lidocaine on rats with cerebral ischemia-reperfusion injury (CIRI) was studied to explore its mechanism of action. A total of 30 Sprague-Dawley rats were randomly divided into control group and model group, and the rat model of CIRI was prepared by the suture-occluded method in the model group. Then the rats in the model group were randomly assigned into the model group (n=10) and the lidocaine group (n=10). The neurological function score of rats was evaluated, and the levels of serum B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in rats were determined using ELISA. TUNEL assay was performed to detect the neuronal apoptosis in the brain of rats. The messenger ribonucleic acid (mRNA) and protein expression levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) were measured via RT-PCR and western blotting, respectively. Compared with those in the control group, the rats in the model group had an elevated neurological function score, a raised level of Bcl-2, but a reduced level of Bax in the serum, an obviously increased rate of neuronal apoptosis in the brain and decreased mRNA and protein levels of cAMP and PKA in cerebral tissues. The rats in lidocaine group had a lower neurological function score, a lower level of Bcl-2, but a higher level of Bax in the serum, an evidently lower rate of neuronal apoptosis in the brain and higher mRNA and protein levels of cAMP and PKA in cerebral tissues than those in the model group. Lidocaine can improve the neurological function of rats with CIRI and inhibit neuronal apoptosis in the brain, and its mechanism of action may be related to the activation of the cAMP/PKA signaling pathway.

Keywords: cAMP/PKA signaling pathway; cell apoptosis; cerebral ischemia-reperfusion injury; lidocaine.

Copyright: © Liu et al.

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6
Exp Ther Med
. 2020 Jul;20(1):42-46. doi: 10.3892/etm.2020.8535. Epub 2020 Feb 18.
Inflammatory Marker Alteration in Response to Systemic Therapies in Psoriasis
Cristina Grechin 1, Laura Gheucă Solovăstru 2 3, Dan Vâță 2 3, Adriana Ionela Pătrașcu 3, Alina Ioana Grăjdeanu 2, Elena Porumb-Andrese 2 3
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PMID: 32508991 PMCID: PMC7271695 DOI: 10.3892/etm.2020.8535
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Abstract
Substantial research has focused on the presence of biomarkers involved in both the pathogenesis of psoriasis and its comorbidities. The identification of these biomarkers has a crucial role in establishing the diagnosis and prognosis, in understanding the physiopathological mechanism and in determining the therapeutic response. The aim of this study was to emphasize the alteration in inflammatory markers in response to systemic therapies in psoriasis. Evolution of inflammatory marker alteration was studied in 194 patients with psoriasis, aged between 7 and 87 years. Two groups were set up: the first comprised of patients treated with methotrexate (n=51), while the second comprised patients treated with biological therapy (n=143). Each group was evaluated for blood values of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fibrinogen before and after treatment, the fluctuation of these values according to the treatment, the interrelation between inflammatory markers and inflammatory activity of the disease and the evolution of the disease after treatment. In group I, 46 out of 51 patients had elevated levels of acute phase reactants before treatment. After treatment with methotrexate 7.5 mg/week, 12 out of 46 patients had elevated blood levels of ESR and 18 out of 46 patients of CRP and fibrinogen. Before treatment with biological therapy, 138 patients out of 143 presented abnormal high range for acute phase reactants. After treatment with biological therapy, 18 patients out of 138 had elevated blood levels of ESR and 37 patients out of 138 had elevated CRP and fibrinogen. A favorable evolution was noted in 98 patients out of 138. It was concluded that the systemic treatment with both methotrexate and biological therapy showed a marked decline in the patients with abnormal values of CRP, ESR and fibrinogen, indirectly showing a decline in the inflammatory activity of psoriasis.

Keywords: biological therapy; genetic predisposition; immune dysregulation; inflammatory markers; psoriasis.

Copyright: © Grechin et al.

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Exp Ther Med
. 2020 Jul;20(1):261-268. doi: 10.3892/etm.2020.8667. Epub 2020 Apr 15.
Role of Recombinant Human Brain Natriuretic Peptide Combined With Sodium Nitroprusside in Improving Quality of Life and Cardiac Function in Patients With Acute Heart Failure
Yang Peng 1 2, Han Wei 1 2
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PMID: 32509011 PMCID: PMC7271704 DOI: 10.3892/etm.2020.8667
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Abstract
The present study aimed to investigate the role of recombinant human brain natriuretic peptide (RHBNP) combined with sodium nitroprusside (SN) in improving quality of life and cardiac function in patients with acute heart failure. A total of 96 patients with acute heart failure who were admitted to The First Affiliated Hospital of Yangtze University were included in the current study. A total of 48 patients were treated with RHBNP combined with SN (research group) and 48 patients were treated with SN alone (control group). To assess the efficacy and safety of the two treatments, the study groups were compared in terms of improvement in clinical symptoms and cardiac function indices, including pulmonary capillary wedge pressure and left ventricular ejection fraction, which was measured using a non-invasive cardiac hemodynamic detector; changes in fluid intake and 24 h urine volumes after drug use; cardiac function classification before treatment and three days after treatment; adverse drug reactions during treatment and mortality within 1 month of treatment. Following treatment, compared with the control group, the research group demonstrated significantly higher fluid intake and 24 h urine volume after drug use, improved cardiac function indices, cardiac function classification, biochemical indicators and total effective rate of treatment (all P<0.05); significantly lower total incidence of adverse reactions (P<0.05) and similar mortality within 1 month of treatment. With improvements in cardiac and other organ function, RHBNP combined with SN was found to be effective in the treatment of acute heart failure. RHBNP can effectively promote urination, reduce inflammatory responses and rapidly relieve clinical symptoms without significant adverse reactions, indicating its potential use in further clinical application.

Keywords: acute heart failure; cardiac function; efficacy; quality of life; recombinant human brain natriuretic peptide; sodium nitroprusside.

Copyright: © Peng et al.

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Exp Ther Med
. 2020 Jul;20(1):121-128. doi: 10.3892/etm.2020.8663. Epub 2020 Apr 15.
Influence of Inflammation and Adipocyte Biochemical Markers on the Components of Metabolic Syndrome
Dana Carmen Zaha 1 2, Cosmin Vesa 1 2, Diana Uivarosan 1, Ovidiu Bratu 3, Ovidiu Fratila 4, Delia Mirela Tit 5, Carmen Pantis 2 6, Camelia C Diaconu 7, Simona Bungau 5
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PMID: 32509004 PMCID: PMC7271710 DOI: 10.3892/etm.2020.8663
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Abstract
Metabolic syndrome is associated with increased risk of cardiovascular disease. This study investigated the correlation between adipocyte and inflammation biomarkers, and metabolic syndrome and its components. The study included 80 patients with normal body-mass index and 80 obese patients. The groups were assessed for serum values of adiponectin, leptin and highly sensitive C reactive protein (hsCRP), the homeostatic model assessment of insulin resistance (HOMA-IR), as well as the influence of these biochemical markers on the prevalence of metabolic syndrome and its components. Leptin, HOMA-IR and hsCRP had statistically significant (P<0.01) higher values in the group of obese subjects, while adiponectin had statistically significant (P<0.01) lower values. The prevalence of metabolic syndrome was 35% in the obese group and 5% in the normal weight group. Adiponectin and HOMA-IR were the variables significantly associated with metabolic syndrome (P<0.01), adiponectin/HOMA-IR ratio and leptin/adiponectin ratio were also associated with metabolic syndrome (P<0.01). No relationship was found between metabolic syndrome and hsCRP. Adiponectin and adiponectin/HOMA-IR were associated with all the components of metabolic syndrome and they can be useful to identify patients with high risk of diabetes mellitus and cardiovascular disease.

Keywords: adipocyte biochemical markers; hsCRP; inflammation; leptin; metabolic syndrome.

Copyright © 2020, Spandidos Publications.

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Review Exp Ther Med
. 2020 Jul;20(1):78-86. doi: 10.3892/etm.2020.8620. Epub 2020 Mar 20.
Use of Imaging Techniques for Melanocytic Naevi and Basal Cell Carcinoma in Integrative Analysis (Review)
Ioana-Alina Grajdeanu 1, Dan Vata 1 2, Laura Statescu 1 2, Ioana Adriana Popescu 1 2, Elena Porumb-Andrese 1 2, Adriana Ionela Patrascu 2, Alina Stincanu 2, Tatiana Taranu 3 4, Maria Crisan 5, Laura Gheuca Solovastru 1 2
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PMID: 32508998 PMCID: PMC7271701 DOI: 10.3892/etm.2020.8620
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Abstract
Early detection of skin cancer is essential in order to obtain an improved prognosis. Clinicians need more objective and non-invasive examination methods to support their decision whether to biopsy or not tumoral lesions. These may include several imaging techniques such as dermoscopy, videodermoscopy, also known as sequential digital dermoscopy (SDD), computer-aided diagnosis (CAD), total body photography, imaging and high-frequency ultrasonography (HFUS), reflectance confocal microscopy, multiphoton tomography, electrical impedance spectroscopy, Raman spectroscopy, stepwise two-photon-laser spectroscopy and quantitative dynamic infrared. This review summarizes the current developments in the field of melanocytic lesions, such as naevi and basal cell carcinoma (BCC) imaging techniques. The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo skin tumor diagnosis. Two main methods were focused on, namely videodermoscopy and HFUS, which can be included in daily dermatologists' practice. In skin tumors HFUS allows the assessment of tumoral lesions with depth smaller than 1.5 cm, being described a correlation between ultrasonographic depth and the histologic index.

Keywords: high frequency ultrasonography; imaging techniques; integrative analysis; skin tumors; videodermoscopy.

Copyright: © Grajdeanu et al.

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10
Review Exp Ther Med
. 2020 Jul;20(1):117-120. doi: 10.3892/etm.2020.8664. Epub 2020 Apr 15.
Botulinum Toxin in Low Urinary Tract Disorders - Over 30 Years of Practice (Review)
Arsenie Dan Spinu 1 2, Ovidiu Gabriel Bratu 1 2 3, Camelia Cristina Diaconu 1 4, Ana Maria Alexandra Stanescu 1, Simona Bungau 5, Ovidiu Fratila 6, Roxana Bohiltea 1 7, Dan Liviu Dorel Mischianu 1 2 3
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PMID: 32509003 PMCID: PMC7271717 DOI: 10.3892/etm.2020.8664
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Abstract
Botulinum toxin is a substance produced by Clostridium Botulinum and is responsible for human botulism. This substance is a poison, a neurotoxin, but used in limited quantities it can be a cure for some diseases. It is well connected to a large variety of medical applications. The mechanism of action relies on blocking the acetylcholine at the neuromuscular junction, which blocks the transmission of the nervous impulse with secondary flaccid paralysis. In urology, its role in idiopathic overactive bladder and neurogenic bladder is well known. We performed a thorough review using PubMed and other databases, revising the mechanisms of botulinum toxin action in urologic pathology, treatment procedures and other options. Botulinum toxin is a well-studied substance with a large number of applications in medicine. In urologic pathology, overactive bladder and neurogenic bladder are backed by robust studies that support the therapeutic role of this substance. The toxin has multiple effects, such as inhibition of the nerve growth factor, blocking the bladder sensory afferent pathway and apoptotic effect on the prostate tissue, by inhibiting the substance P, altering the nociceptive pathways. Interstitial cystitis and other rare pathologies show promising results, but further studies are needed. The role of botulinum toxin in benign prostatic hyperplasia is still not elucidated.

Keywords: analysis; botulinum toxin; neurologic bladder; overactive bladder; treatment.

Copyright © 2020, Spandidos Publications.

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11
Exp Ther Med
. 2020 Jul;20(1):235-242. doi: 10.3892/etm.2020.8678. Epub 2020 Apr 22.
Men With Idiopathic Oligoasthenoteratozoospermia Exhibit Lower Serum and Seminal Plasma Melatonin Levels: Comparative Effect of Night-Light Exposure With Fertile Males
Mohammed H Hassan 1, Moustafa A El-Taieb 2, Nahed N Fares 3, Hanan M Fayed 4, Rana Toghan 5, Hassan M Ibrahim 3
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PMID: 32509010 PMCID: PMC7271713 DOI: 10.3892/etm.2020.8678
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Abstract
Melatonin is a darkness hormone secreted by the pineal gland, which serves a role in idiopathic oligoasthenoteratozoospermia (iOAT). The present study aimed to evaluate the seminal plasma and serum melatonin levels of 50 patients with iOAT and 50 normal fertile controls and the effects of exposure to light at night on semen parameters. Semen analyses were performed according to the World Health Organization 2010 guidelines. Measurements of serum and seminal plasma melatonin, serum TSH, FT3, FT4, free testosterone, prolactin, FSH and LH were performed using ELISA. The overall results revealed that the serum and seminal plasma levels of melatonin were lower in patients with iOAT compared with the control subjects (P=0.0004 and 0.01, respectively). Patients with iOAT who were exposed to light at night exhibited lower serum and seminal plasma melatonin levels compared with those who were not exposed to light at night (P<0.0001 and 0.02, respectively). Additionally, similar significant differences were identified in control subjects exposed to light at night when compared to non-exposed controls. There was a significantly positive correlation between serum melatonin levels and sperm motility in the entire iOAT patient cohort (r=0.614; P<0.0001) and a significantly positive correlation between the serum and seminal plasma melatonin levels in the non-exposed iOAT patient subgroup (r=0.753; P<0.001). Thus, darkness and sleep at night may improve the semen parameters of patients with iOAT, as evidenced by the effects of light exposure at night on the serum and seminal plasma levels of melatonin and, consequently, on semen parameters.

Keywords: dark light; infertility; melatonin; semen analyses.

Copyright: © Hassan et al.

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12
Exp Ther Med
. 2020 Jul;20(1):129-133. doi: 10.3892/etm.2020.8662. Epub 2020 Apr 15.
Risk Factors for Adiposity in the Urban Population and Influence on the Prevalence of Overweight and Obesity
Amorin Remus Popa 1 2, Ovidiu Fratila 1, Marius Rus 1, Raluca Anca Corb Aron 3, Cosmin Mihai Vesa 2 3, Carmen Pantis 4, Camelia C Diaconu 5, Ovidiu Bratu 6, Simona Bungau 7, Sebastian Nemeth 7
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PMID: 32509005 PMCID: PMC7271696 DOI: 10.3892/etm.2020.8662
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Abstract
Obesity and overweight are major contributors to the morbidity and mortality of modern civilization. This study determined the prevalence of certain risk factors for adiposity and assesses their impact on overweight/obesity prevalence. Nine hundred individuals were evaluated, aged between 18-65 years, including clinical examination, evaluation of medical history, BMI determination and completion on questionnaires assessing nutritional intake and presence of depression symptoms. Overweight prevalence was 29.56% and obesity prevalence was 21.33%. Fast-food consumption was the most frequent risk factor for adiposity found in 61.67% of individuals, eating <3 meals/day was found in 58.89%, sedentary lifestyle in 53.33%, sleeping time <6 h/day in 44.22%, hypercaloric nutrition in 43.56%, excessive alcohol consumption in 42.89% and depression symptoms in 31.78%. Unhealthy lifestyle a composite risk factor was identified in 67.33% of individuals. Fast-food consumption increases the risk for adiposity by 1.85-fold while sedentary lifestyle by 1.79-fold. Risk factors for adiposity play an important role in increasing the prevalence of overweight and obesity. Public health measures are necessary in order to educate the general population regarding the importance of healthy nutrition and physical exercise.

Keywords: adiposity; lifestyle; obesity; overweight; risk factors.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
. 2020 Jul;20(1):227-234. doi: 10.3892/etm.2020.8686. Epub 2020 Apr 23.
Microarray and Bioinformatics Analysis of Circular RNAs Expression Profile in Traumatic Lung Injury
Yong Jiang 1, Feng Zhu 1, Guo-Sheng Wu 1, Kang-An Wang 1, Chen Wang 1, Qing Yu 1, Bang-Hui Zhu 1, Yu Sun 1, Zhao-Fan Xia 1
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PMID: 32509009 PMCID: PMC7271735 DOI: 10.3892/etm.2020.8686
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Abstract
Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non-coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explore their potential functions in the pathogenesis of TLI. A high-throughput circRNA microarray was used to investigate the expression profile of circRNAs in plasma samples from five patients with TLI and paired control samples. Subsequently, a total of five abnormally expressed circRNAs were investigated using reverse transcription-quantitative PCR (RT-qPCR). A bioinformatics analysis was performed to predict a competitive endogenous RNA (ceRNA) network. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the main biological processes and pathways. Finally, additional samples were tested to identify the expression profiles of the selected circRNAs. Among the 310 circRNAs that were highly expressed in the microarray analysis, 60 were upregulated and 250 were downregulated in patients with TLI. RT-qPCR results indicated that two downregulated circRNAs (circ_102927 and circ_100562) and one upregulated circRNA (circ_101523) matched the microarray results. The bioinformatics analysis constructed a targeting network based on the three validated circRNAs. GO and KEGG analyses identified the top ten enriched annotations. The expression of homo sapiens circular RNA 102927 (hsa_circRNA_102927) in the plasma of patients with TLI was 0.34-fold compared with the control group in expanded size validation. The results of the present study identified the differentially expressed circRNAs in the plasma of patients with TLI and provided evidence that highly expressed circRNAs involved in the ceRNA network may serve a role in the pathophysiology of TLI.

Keywords: acute respiratory distress syndrome; chest trauma; circular RNAs; competitive endogenous RNA network; microarray.

Copyright: © Jiang et al.

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14
Exp Ther Med
. 2020 Jun;19(6):3454-3460. doi: 10.3892/etm.2020.8638. Epub 2020 Apr 2.
Melatonin Inhibits Vascular Smooth Muscle Cell Proliferation and Apoptosis Through Upregulation of Sestrin2
Seunghyeong Lee 1 2, Jun-Kyu Byun 3 4, Mihyang Park 1 2, Sung Woo Kim 5, Sungwoo Lee 6, Jung-Guk Kim 4, In-Kyu Lee 4, Yeon-Kyung Choi 4, Keun-Gyu Park 1 3 4
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PMID: 32373191 PMCID: PMC7197251 DOI: 10.3892/etm.2020.8638
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Abstract
Excessive vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis and restenosis. Furthermore, apoptosis of VSMCs accelerates plaque rupture in the atherosclerotic vessels. Therefore, a strategy that regulates both VSMC proliferation and apoptosis is essential for the development of novel pharmacological tools for the treatment of atherosclerosis. Despite mounting evidence supporting the benefits of melatonin in diverse metabolic diseases, the role of melatonin in VSMC growth remains largely unknown. The present study revealed that melatonin inhibited both proliferation and apoptosis of primary cultured rat VSMCs. Melatonin induced mitochondrial energetic stress in VSMCs and subsequent induction of Sestrin2 via C/EBPβ. Melatonin-induced Sestrin2 suppressed mTORC1 activity in VSMCs, contributing to suppression of VSMC proliferation. Additionally, melatonin-induced upregulation of Sestrin2 blocked apoptosis by preventing excessive ROS generation. The results demonstrated that melatonin controlled VSMC proliferation and apoptosis via Sestrin2-mediated inhibition of mTORC1 and ROS scavenging. Therefore, melatonin should be considered as a lead compound for therapies aimed at preventing vessel lumen constriction during the course of atherosclerosis and restenosis.

Keywords: Sestrin2; apoptosis; melatonin; proliferation; vascular smooth muscle cells.

Copyright: © Lee et al.

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15
Exp Ther Med
. 2020 Jul;20(1):646-654. doi: 10.3892/etm.2020.8672. Epub 2020 Apr 22.
Oncogenic Role of LYN in Human Gastric Cancer via the Wnt/β-catenin and AKT/mTOR Pathways
Rui Su 1 2, Jun Zhang 1
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PMID: 32509024 PMCID: PMC7271702 DOI: 10.3892/etm.2020.8672
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Abstract
LYN kinase (LYN) is a member of the Src tyrosine kinase family, which plays an important role in multiple tumor-related functions. The current study demonstrated that LYN functions as a pro-oncogene in AGS gastric cancer cells. It was found that LYN expression levels were significantly raised in gastric cancer tissue and were significantly associated with the pathological grades of patients with gastric cancer. This was accomplished by knocking down LYN in AGS cells using short hairpin RNA (shRNA) plasmid transfection, with reverse transcription-quantitative PCR detection verifying the effectiveness of RNA interference. It was found that the cell proliferation and colony formation abilities of AGS cells were significantly inhibited, using CCK-8 and clone formation assays, respectively. Furthermore, LYN knockdown was found to induce apoptosis and inhibit both migration and invasion in AGS cells, using flow cytometry and Transwell assays, respectively. A mechanical investigation further suggested that LYN knockdown resulted in the activation of the mitochondrial apoptotic pathway. Likewise, the Wnt/β-catenin pathway was inactivated by LYN knockdown, including decreased levels of Wnt3a, β-catenin, snail family transcriptional repressor (Snail)1 and Snail2. Epithelial-mesenchymal transition mesenchymal markers (including N-cadherin and vimentin) were also found to be downregulated, and E-cadherin was upregulated in LYN-silenced AGS cells. Finally, the AKT/mTOR pathway was found to be downregulated by LYN knockdown in AGS cells, including decreased levels of phosphorylated (p)-AKT (Ser473), p-mTOR (Ser2448), and the down-stream effector p70S6 kinase (p70S6K). Furthermore, the AKT pathway activator, insulin like growth factor-1 (IGF-1), was found to reverse the inhibitory effects of LYN knockdown on the proliferation, migration and invasion of AGS cells. In conclusion, the current study demonstrated that LYN plays an oncogenic role in the proliferation, survival and movement of human gastric cancer cells by activating the mitochondrial apoptotic pathway, and downregulating the Wnt/β-catenin and AKT/mTOR pathways. The current research provides a comprehensive insight into the regulation of LYN in gastric cancer and may help with the development of new tumor treatment strategies.

Keywords: AKT/mTOR; LYN kinase; apoptosis; invasion and migration; proliferation.

Copyright © 2020, Spandidos Publications.

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16
Exp Ther Med
. 2020 Jul;20(1):505-511. doi: 10.3892/etm.2020.8682. Epub 2020 Apr 23.
Assessment of the Association Between Paraspinal Muscle Degeneration and Quality of Life in Patients With Degenerative Lumbar Scoliosis
Yong Tang 1 2, Sen Yang 1, Can Chen 1, Keyu Luo 1, Yueqi Chen 1, Donggui Wang 1, Jiulin Tan 1, Qijie Dai 1, Chengmin Zhang 1, Wenjie Wu 1, Jianzhong Xu 1, Fei Luo 1
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PMID: 32509021 PMCID: PMC7271738 DOI: 10.3892/etm.2020.8682
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Abstract
The present study aimed to determine the characteristics of multifidus, erector spinae and psoas major degeneration in elderly patients with degenerative lumbar scoliosis (DLS) and the correlation between asymmetric changes and patient quality of life. A total of 49 patients with lumbar scoliosis (DLS group) and 38 healthy individuals (control group) were prospectively examined. The functional cross-sectional area, cross-sectional area difference index (CDI) and fat infiltration rate (FIR) of the multifidus, erector spinae and psoas major at the apical vertebral level were measured using MRI. The visual analogue scale (VAS) score, Oswestry Disability Index (ODI) and 36-item Short Form Health Survey (SF-36) score were used to evaluate patient quality of life. Correlations between the degree of asymmetric muscular degeneration and quality of life were analysed. The CDI of the multifidus, erector spinal and psoas major was higher in the DLS group compared with that in the control group. The CDI of the multifidus was found to be positively associated with the Cobb angle of lumbar scoliosis. Similar results were obtained for fat infiltration between the two groups. In addition, the CDI and FIR difference index of the multifidus was positively correlated with the VAS score and ODI but negatively correlated with the SF-36 score. The quality of life significantly decreased with increasing asymmetric atrophy and fat infiltration in the multifidus. Thus, strategies to enhance the function of the multifidus may have a positive impact on quality of life (Chinese Clinical Trial Registry, registration date, 2018.11.12; registration no. ChiCTR1800019459.).

Keywords: paraspinal muscles; psoas muscles; quality of life; scoliosis.

Copyright: © Tang et al.

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17
Exp Ther Med
. 2020 Jul;20(1):68-72. doi: 10.3892/etm.2020.8474. Epub 2020 Jan 27.
Acquired Angioedema Induced by Angiotensin-Converting Enzyme Inhibitors - Experience of a Hospital-Based Allergy Center
Polliana Mihaela Leru 1 2, Vlad Florin Anton 2, Corina Bocsan 3, Adriana Muntean 4 5, Daniel Boda 6 7
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PMID: 32508996 PMCID: PMC7271703 DOI: 10.3892/etm.2020.8474
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Abstract
Angiotensin-converting enzyme inhibitors (ACEIs) represent an important group of pharmacological compounds, largely prescribed for more than 30 years. They have been extensively evaluated in clinical trials, demonstrating significant reduction of morbidity and mortality of patients with cardiovascular diseases, mainly high blood pressure, myocardial infarction, heart failure and stroke. Besides their beneficial effects and a general good safety profile, it was proven that ACEIs might also induce adverse effects in some patients, most notably angioedema (AE) and chronic cough. The occurrence rate of adverse events induced by ACEIs is low, but the number of suffering patients is relatively high, since ACEIs is one of the most frequently prescribed medication worldwide. The aim of our study was to evaluate clinical pattern, risk factors and general management of ACEI-induced angioedema in a cohort of patients addressed for allergist evaluation in one university hospital in Romania, during a period of 32 months. It was found that ACEI-induced angioedema (ACEI-AE) represented more than half of the total number of patients addressed for angioedema without urticaria, with variable clinical and time-patterns. Most of the patients were referred by general practitioners (GPs) with diagnosis of urticaria or other skin allergy and continued to take ACEIs for months and years after onset of angioedema. We concluded that the awareness of acquired, non-allergic angioedema induced by ACEI therapy in medical practice is still low and there is a need for improved knowledge and interdisciplinary collaboration in this field.

Keywords: acquired angioedema; allergy center; angiotensin-converting enzyme inhibitors; safety profile.

Copyright © 2020, Spandidos Publications.

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18
Exp Ther Med
. 2020 Jul;20(1):325-334. doi: 10.3892/etm.2020.8685. Epub 2020 Apr 23.
κ-Opioid Receptor Agonists May Alleviate Intestinal Damage in Cardiopulmonary Bypass Rats by Inhibiting the NF-κB/HIF-1α Pathway
Xiaoyan Zhang 1 2, Yingjie Sun 2, Dandan Song 2, Yugang Diao 2
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PMID: 32509012 PMCID: PMC7271736 DOI: 10.3892/etm.2020.8685
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Abstract
The aims of the present study were to investigate the protective effect of a κ-opioid receptor (KOR) agonist on intestinal barrier dysfunction in rats during cardiopulmonary bypass (CPB), as well as to examine the role of NF-κB and the transcription factor hypoxia-inducible factor-1α (HIF-1α) signaling pathway in the regulatory mechanism. A total of 50 rats were randomly divided into five groups, with 10 rats in each group: Sham surgery group (group Sham), CPB surgery group (group CPB), KOR agonist + CPB (group K), KOR agonist + specific KOR antagonist + CBP (group NK) and KOR agonist + NF-κB pathway specific inhibitor + CPB (group NF). Intestinal microcirculation was evaluated to determine intestinal barrier dysfunction in rats following CPB surgery. Hematoxylin and eosin (H&E) staining was used to observe intestinal tissue injury in the rats. ELISA was used to detect the inflammatory factors interleukin (IL)-1β, IL-6, IL10 and tumor necrosis factor-α, and the oxidative stress factors superoxidase dismutase, malondialdehyde and nitric oxide in serum. In addition, ELISA was used to investigate the serum levels of the intestinal damage markers D-lactic acid, diamine oxidase and intestinal fatty acid-binding protein. Western blotting was used to investigate the protein expression levels of tight junction proteins zonula occludens-1 and claudin-1. Furthermore, immunohistochemistry was used to examine intestinal injuries and western blotting was used to detect expression levels of NF-κB/HIF-1α signaling pathway-related proteins. H&E staining results suggested that the KOR agonist alleviated intestinal damage in the CPB model rats. This effect was reversed by the addition of a KOR antagonist. Further investigation of inflammatory and oxidative stress factors using ELISA revealed that the KOR agonist reduced the inflammatory and oxidative stress responses in the intestinal tissues of the CPB model rats. The ELISA results of intestinal damage markers and western blotting results of tight junction protein expression suggested that KOR agonist treatment may alleviate intestinal injury in CPB model rats. In addition, the western blotting and immunohistochemistry results suggested that KOR agonists may decrease the expression levels of NF-κB, p65 and HIF-1α in CPB. Collectively, the present results suggested that KOR agonists are able to ameliorate the intestinal barrier dysfunction in rats undergoing CPB by inhibiting the expression levels of NF-κB/HIF-1α signaling pathway-related proteins.

Keywords: NF-κB/hypoxia-inducible factor-1α; intestinal barrier dysfunction; signaling pathway; κ-opioid receptor agonist.

Copyright: © Zhang et al.

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19
Exp Ther Med
. 2020 Jul;20(1):472-478. doi: 10.3892/etm.2020.8669. Epub 2020 Apr 21.
Comparison of Core Decompression and Porous Tantalum Rod Implantation With Conservative Treatment for Avascular Necrosis of the Femoral Head: A Minimum 18 Month Follow-Up Study
Yuan Fang 1, Changrong Ding 2, Yingzhen Wang 1, Haining Zhang 1
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PMID: 32509016 PMCID: PMC7271720 DOI: 10.3892/etm.2020.8669
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Abstract
Porous tantalum rod implantation is a novel surgical method that is used to treat avascular necrosis (AVN) of the femoral head (hip). In the present study, the results of core decompression and tantalum rod implantation were compared with non-surgical treatment for AVN, and the survivorship of the femoral head was evaluated. In total, 60 patients with AVN femoral head were recruited and analysed. Non-surgical treatment was selected by 30 patients (41 hips), 7 with a Ficat score of I and 23 with a score of II. Non-surgical treatment included celecoxib, salvia miltiorrhiza and tetramethylypyrazine and a reduction in weight-bearing activities. Surgical treatment and porous tantalum rod implantation were selected by 30 patients (41 hips), 10 with a Ficat score of I and 20 with a score of II. After follow-up (average: 33.5 months), patients were evaluated by assessing post-operative complications, radiology, hip survivorship and Harris hip score. In the surgical group, pre-operative symptoms were significantly alleviated. No complications, including infection, delayed healing or fractures were reported. Final follow-up rates of femoral head survivorship were 4.9% in the non-surgical group and 36.7% in the surgical group. The Harris hip score was significantly improved following surgery when compared with non-surgical treatment (P<0.05). The results indicated that core decompression and porous tantalum rod implantation are beneficial short- and mid-term treatment methods for AVN of the femoral head.

Keywords: femoral head necrosis; survival rate; tantalum.

Copyright: © Fang et al.

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20
Exp Ther Med
. 2020 Jul;20(1):512-520. doi: 10.3892/etm.2020.8679. Epub 2020 Apr 23.
Adaptive Expression of Biofilm Regulators and Adhesion Factors of Staphylococcus aureus During Acute Wound Infection Under the Treatment of Negative Pressure Wound Therapy in vivo
Tongtong Li 1, Guoqi Wang 2, Peng Yin 3, Zhirui Li 4, Lihai Zhang 4, Peifu Tang 4
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PMID: 32509022 PMCID: PMC7271737 DOI: 10.3892/etm.2020.8679
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Abstract
Negative pressure wound therapy (NPWT) is gaining acceptance as a physical therapy for a wide variety of infected wounds. To gain insight into the response of bacteria to NPWT in vivo, the adaptive expression of biofilm regulators and adhesion factors of Staphylococcus aureus (S. aureus), the most frequently isolated pathogen in the clinic, during acute wound infection was investigated. A 3 cm full-thickness dermal wound was created on each side of a rabbit back and inoculated with green fluorescent protein-labeled S. aureus. NPWT was initiated at 6 h post inoculation, with the wound on the contralateral side as the untreated self-control. The wounds were subjected to a 28 day observation period. Histological analysis, laser scanning confocal microscopy and scanning electron microscopy revealed a transition of S. aureus to a free-living phenotype in tissues treated with NPWT, compared with microcolonies in untreated wounds. Viable bacteria counts showed a modest reduction in the bioburden of NPWT group on day 8 (P<0.001), with ~1x106 colony-forming units/g tissue. Transcript analysis of biofilm- and colonization-related genes were investigated using reverse transcription-quantitative PCR on postoperative days 1, 2, 4 and 8. The poly-beta-1,6-N-acetyl-D-glucosamine synthase locus and holin-like protein CidA/antiholin-like protein LrgA network were less active in the NPWT group compared with the untreated control group. Accordingly, the expression profile switched to an elevated expression of the adhesive factors UDP-phosphate N-acetylglucosaminyl 1-phosphate transferase (at days 0-4) and fibronectin-binding protein A and iron-regulated surface determinant protein A at >4 days during both stages of colonization. Meanwhile, low expression levels of the effector molecule (RNAIII) of the accessory gene regulator type I (agr) system was detected in NPWT group, suggesting that the bacterial density in NPWT-treated wounds was under the threshold for agr activation, thus not leading to an active and invasive infection. The wounds treated by NPWT healed completely on day 28, compared with an average of an 8.11% defect area in the control group (P<0.001). The results of the current study indicated that S. aureus responds to NPWT by regulating gene expression, manifesting a decrease in biofilm formation and an increase in bacterial colonization in vivo, which potentially benefits the wound repair and healing process.

Keywords: Staphylococcus aureus; acute wound; bacterial colonization; biofilm; negative pressure wound therapy.

Copyright: © Li et al.

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21
Exp Ther Med
. 2020 Jul;20(1):375-384. doi: 10.3892/etm.2020.8674. Epub 2020 Apr 22.
Modulation of the Secretion of Mesenchymal Stem Cell Immunoregulatory Factors by Hydrolyzed Fish Collagen
Chao Liu 1, Jiao Sun 1
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PMID: 32509014 PMCID: PMC7271731 DOI: 10.3892/etm.2020.8674
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Abstract
The aim of the present study was to investigate the possible immunomodulatory effects of osteogenically differentiated bone marrow mesenchymal stem cells induced by hydrolyzed fish collagen. Marine biomaterials have attracted significant attention for their environmental friendliness and renewability. Hydrolyzed fish collagen (HFC) has been discovered to induce the osteoblastic differentiation of stem cells, which underlies the foundation for its application in tissue engineering. Stem cells and their biomaterial carriers face acute immune rejection mediated by host macrophages. A potential strategy for combatting rejection in stem cell therapy is to modify the polarization of macrophages. However, whether HFC-induced mesenchymal stem cells maintain their immunomodulatory ability remains to be determined. To understand this phenomenon, a co-culture model of direct contact was established between bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages, where the secretion of nitrous oxide from macrophages was measured using Griess colorimetric assay. ELISAs were performed to measure the secretion of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and IL-10, whilst reverse transcription-quantitative PCR was used to assess the expression levels of IL-1β, IL-6, CD206, resistin-like molecule α (FIZZ1) and prostaglandin E2 receptor 4 (EP4). In addition, the expression levels of relevant proteins in the phosphorylated-cyclic AMP-responsive element-binding protein-CCAAT/enhancer-binding protein β (EBPβ) pathway were investigated using western blotting. HFC-induced BMSCs were found to suppress the expression levels of IL-1β and IL-6, whilst increasing the expression levels of CD206 and FIZZ1 in RAW264.7 macrophages. HFC-induced BMSCs also inhibited the secretion of IL-1β and IL-6, whilst promoting the secretion of TGF-β and IL-10 secretion from RAW264.7 macrophages. Mechanistic studies using western blotting discovered that HFC stimulated the secretion of prostaglandin E2 from BMSCs, which subsequently increased the expression of EP4 on the macrophages. EP4 then increased the expression levels of C/EBPβ and arginase 1 further. In conclusion, results from the present study suggested that following induction with HFC, BMSCs maintain their immunomodulatory activity.

Keywords: fish collagen; immune modulation; inflammatory; macrophages; stem cells; tissue engineering.

Copyright: © Liu et al.

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22
Review Exp Ther Med
. 2020 Jul;20(1):109-116. doi: 10.3892/etm.2020.8606. Epub 2020 Mar 17.
Infection With Hepatitis C Virus in Hemodialysis Patients: An Overview of the Diagnosis and Prevention Rules Within a Hemodialysis Center (Review)
Delia Timofte 1, Dorin Dragos 2 3, Andra-Elena Balcangiu-Stroescu 1 4, Maria-Daniela Tanasescu 2 3, Daniela Gabriela Balan 4, Adelaida Avino 5, Adrian Tulin 6 7, Ovidiu Stiru 8 9, Dorin Ionescu 2 3
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PMID: 32509002 PMCID: PMC7271692 DOI: 10.3892/etm.2020.8606
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Abstract
Increase in the number of patients with chronic kidney disease (CKD) calls for improved management of these patients. In stage 5 CKD, when the initiation of renal replacement therapy (RRT) becomes necessary, there is an increase in the infection risk of the patients and immunological tests for hepatitis C virus (HCV) detection turn positive at an alarmingly higher rate compared to general population. With the introduction into clinical practice of diagnostic tests, the increased prevalence of HCV among CKD patients has been known since the 1990s. Also, the negative impacts of HCV infection on CKD evolution as well as the unfavorable evolution of grafts received by HCV infected patients are known. Chronic hemodialysis patients are a category of patients whose risk of HCV infection is substantial. Currently, in the hemodialysis centers, at the base of the transmission of HCV infection there are a multitude of factors. Infection with HCV has a different impact on patient with end-stage renal disease (ESRD). Comorbidities in this case have significant sources of mortality and morbidity. It was proven that the post transplantations problems were prevented and mortality was reduced for patients who were diagnosed with HCV and in whom the infection was treated before the kidney transplant (KT). Consequently, early detection of the infection and the application of specific treatment has a considerable impact on the outcome of the patients. Another important component of the management of HCV infection in the chronic hemodialysis patients is the prevention of the infection transmission by applying specific methods.

Keywords: HCV infection; chronic kidney disease; hemodialysis; prevention; screening.

Copyright: © Timofte et al.

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23
Exp Ther Med
. 2020 Jul;20(1):617-622. doi: 10.3892/etm.2020.8684. Epub 2020 Apr 23.
Clinical Features and Outcomes of Chinese Patients With Anti-γ-Aminobutyric Acid B Receptor Encephalitis
Xiu-He Zhao 1, Xue Yang 1, Xue-Wu Liu 1, Sheng-Jun Wang 1
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PMID: 32509023 PMCID: PMC7271726 DOI: 10.3892/etm.2020.8684
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Abstract
Antibodies against γ-aminobutyric acid B (GABAB) receptor are associated with limbic encephalitis (LE). It is estimated that ~1/2 of patients with LE have small-cell lung cancer. The present study analyzed the specific GABAB receptor antibodies in serum and cerebrospinal fluid (CSF) samples of 12 patients. The clinical manifestations, therapy and outcome were retrospectively compared. The median onset age was 65.1 years and all patients presented with new-onset seizures. In total, 11 (91.6%) patients had memory deficits, 7 (58.3%) patients had psychiatric problems and 4 (33.3%) patients had a disturbance of consciousness. Furthermore, lung cancer was detected in 7 patients (58.3%) by CT scan. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in 3 (25%) and 4 (33.3%) patients, respectively. Furthermore, MRI scan results identified 4 (33.3%) patients with abnormalities in the mesial temporal region. The lung cancer tissues of 3 patients were positively stained for anti-GABAB receptor on immunohistochemistry. All patients received antiepileptic drugs and immunotherapy. In total, 3 patients with lung cancer were subjected to tumor resection. Those patients without cancer exhibited neurological improvement at the follow-up. The present results suggested that seizures and memory deficits were the major manifestations in Chinese patients with anti-GABAB receptor antibodies who were responsive to immunotherapy. The lung cancer tissues from patients with anti-GABAB receptor antibodies were positively stained for anti-GABAB receptor. Collectively, the present results suggested that patients with underlying lung cancer have a relatively poor prognosis.

Keywords: Chinese; encephalitis; seizure; treatment; γ-aminobutyric acid.

Copyright © 2020, Spandidos Publications.

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24
Exp Ther Med
. 2020 Jul;20(1):24-30. doi: 10.3892/etm.2020.8665. Epub 2020 Apr 15.
Monocyte Chemotactic protein-1 and Nitrotyrosine in Irritable Bowel Syndrome
Alexandra Chira 1, Cornelia Braicu 2, Liviuta Budisan 2, Romeo Ioan Chira 3, Ioana Berindan-Neagoe 2 4 5, Dan Lucian Dumitrascu 1
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PMID: 32508988 PMCID: PMC7271741 DOI: 10.3892/etm.2020.8665
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Abstract
Irritable bowel syndrome (IBS) is one the most frequent and common functional gastrointestinal disorders that has a multifactorial etiopathogenesis. Multiple biomarkers have been tested in search for a reliable and specific biomarker, but there is not yet a specific biomarker for IBS. The aim of this study was to evaluate two biomarkers of different putative pathways of the pathogenesis of IBS: the monocyte chemotactic protein-1 (MCP-1) and nitrotyrosine, in order to establish their role as potential biomarkers. We enrolled 42 consecutive IBS patients diagnosed by Rome III criteria and 35 consecutive healthy controls. Serum concentrations for the two biomarkers (MCP-1 and nitrotyrosine) were determined using commercial ELISA kits. Serum levels of MCP-1 were not statistically significantly higher in IBS patients than in controls (204±130 vs. 174±73 pg/ml; P=0.311). Nitrotyrosine levels were statistically significantly lower in IBS patients than in controls (30±12 vs. 353±14 nM; P=0.050). MCP-1 levels were higher in IBS patients with metabolic syndrome versus IBS patients without metabolic syndrome (239±153 vs. 168±120 pg/ml; P=0.948) and in controls with metabolic syndrome (174±56 pg/ml). MCP-1 serum levels were statistically significantly higher in IBS patients with metabolic syndrome than in controls (239±153 vs. 157±89 pg/ml; P=0.037), suggesting multiple factors being involved, particularly the diet and its relation with the metabolic syndrome, and it suggests that MCP-1 could be a marker of subclinical atherosclerosis. Low-grade inflammation might be related to oxidative stress, which plays an underestimated role in the pathogenesis of IBS.

Keywords: MCP-1; biomarkers; irritable bowel syndrome; nitrotyrosine; oxidative stress.

Copyright © 2020, Spandidos Publications.

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25
Review Exp Ther Med
. 2020 Jul;20(1):73-77. doi: 10.3892/etm.2019.8145. Epub 2019 Oct 30.
Assessment of Suicidal Behavior in Dermatology (Review)
Ana Maria Alexandra Stanescu 1, Alexandra Totan 1, Daniela Mircescu 1, Smaranda Diaconescu 2, Ovidiu Gabriel Bratu 1 3, László Fekete 4, Gyula László Fekete 5, Daniel Boda 6, Camelia Cristina Diaconu 1 7
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PMID: 32508997 PMCID: PMC7271711 DOI: 10.3892/etm.2019.8145
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Abstract
Many diseases that affect physical health can also affect mental health. Many of these diseases are studied in terms of quality of life, depression and suicidal behavior. Dermatological disorders, although having a strong impact on the individual's life, are less studied with regard to suicidal behavior. There is a need to approach several dermatological diseases from the perspective of suicidal behavior in order to intervene early with specific treatment or to prevent suicide. Psoriasis, acne, melanoma, atopic dermatitis and urticaria are scarcely studied from the point of view of suicidal behavior. In addition to these diseases, there are others that require attention in terms of suicidal behavior, such as vitiligo or oculocutaneous albinism, most probably due to a small number of people suffering from these diseases, research is almost non-existent in these cases. We want to draw attention to the importance of early detection of suicidal behavior in dermatological practice and to highlight the need for several studies on this subject.

Keywords: acne; dermatology; melanoma; psoriasis; suicidal behavior.

Copyright © 2020, Spandidos Publications.

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26
Review Exp Ther Med
. 2020 Jul;20(1):31-37. doi: 10.3892/etm.2019.8321. Epub 2019 Dec 12.
Cutaneous Manifestations in Inflammatory Bowel Disease (Review)
Loredana Ungureanu 1, Rodica Cosgarea 1, Mihail Alexandru Badea 2, Alina Florentina Vasilovici 1, Ioana Cosgarea 3, Simona Corina Șenilă 1
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PMID: 32508989 PMCID: PMC7271697 DOI: 10.3892/etm.2019.8321
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Abstract
Inflammatory bowel disease (IBD) is defined as a chronic condition characterized by unpredictable relapsing episodes of gastrointestinal inflammation. IBD is not limited to the gastrointestinal tract and should be considered a systemic disease which can involve any organ. Cutaneous manifestations in IBD are frequent and comprise a broad spectrum of diseases, ranging from mild to severe and sometimes debilitating lesions. Some of the cutaneous manifestations can present signs of an underlying intestinal disease, leading to the screening for non-detected IBD even in the absence of symptoms. Cutaneous EIMs are divided into 4 categories: i) Disease-specific lesions that show the same histopathologic findings as the underlying gastrointestinal disease, ii) reactive lesions which are inflammatory lesions that share a common pathogenetic mechanism but do not share the same pathology with the gastrointestinal disease, iii) associated conditions are more frequently observed in the context of IBD, without sharing the pathogenetic mechanism or the histopathological findings with the underlying disease and iv) drug-related skin reactions.

Keywords: biologic therapy; cutaneous manifestations; drug-related cutaneous manifestations; extraintestinal manifestations; inflammatory bowel disease.

Copyright: © Ungureanu et al.

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27
Exp Ther Med
. 2020 Jul;20(1):103-108. doi: 10.3892/etm.2020.8608. Epub 2020 Mar 17.
Characteristics of Patients at Initiation of Renal Replacement Therapy - Experience of a Hemodialysis Center
Delia Timofte 1, Dorin Dragos 2 3, Andra-Elena Balcangiu-Stroescu 1 4, Maria-Daniela Tanasescu 2 3, Daniela Gabriela Balan 4, Laura Raducu 5 6, Cristian-Radu Jecan 5 6, Ovidiu Stiru 7 8, Lavinia Medrihan 9, Dorin Ionescu 2 3
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PMID: 32509001 PMCID: PMC7271700 DOI: 10.3892/etm.2020.8608
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Abstract
The monitoring and care of patients with chronic kidney disease (CKD) before the dialysis initiation contribute to a better survival rate and an improvement in quality of life. The patients who do not benefit from a good predialysis management have a worse short and long-term prognosis. A retrospective, unicentric study was performed to evaluate the status of patients with stage 5 CKD at the time of initiation of renal replacement treatment. A total of 109 patients were included in the study. The evaluation of the patients included the clinical manifestations leading to hemodialysis initiation, the clinical and laboratory data of the patients when the hemodialysis was started. Based on the obtained data, a statistical analysis was performed using the Chi-square test, Fisher's exact test, ANOVA, and Kruskal-Wallis H test. The mean age of the patients was 64.61±13.59 years. Of the patients 51.38% were women. Vascular nephropathies and diabetes mellitus dominated the etiology of CKD. The comorbidities were high blood pressure, ischemic heart disease, history of myocardial infarction, heart failure, history of stroke, peripheral artery disease or atrial fibrillation. Only 43 (39.45%) of our patients were monitored before the hemodialysis initiation. Hemodialysis was initiated on central venous catheter (in most cases non-tunneled) in 78.90% of the patients. Most of the patients had an altered general status, fatigue/tiredness with poor exercise capacity when hemodialysis was initiated. Most of the patients (98.17%) had anemia, the average level of hemoglobin being 8.69±1.85 g/dl. In conclusion, careful monitoring of patients in the early stages of CKD would result in lower morbidity and mortality. These objectives can be achieved by implementing screening programs and early interventions.

Keywords: arterio-venous fistula; central venous catheters; chronic kidney disease; dialysis initiation; predialysis management; renal replacement treatment.

Copyright: © Timofte et al.

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28
Exp Ther Med
. 2020 Jul;20(1):335-342. doi: 10.3892/etm.2020.8668. Epub 2020 Apr 15.
Glycyrrhizic Acid Exerts Protective Effects Against Hypoxia/Reoxygenation-Induced Human Coronary Artery Endothelial Cell Damage by Regulating Mitochondria
Quan Tang 1, Yuping Cao 1, Wei Xiong 2, Xixian Ke 2, Jian Zhang 2, Yu Xia 2, Daxing Liu 2
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PMID: 32509013 PMCID: PMC7271712 DOI: 10.3892/etm.2020.8668
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Abstract
Hypoxia/reoxygenation (H/R) is one of the main causes of coronary artery disease (CAD), which is primarily induced by damage to coronary artery endothelial cells (CAECs). Glycyrrhizic acid (GA) is a natural and abundant pentacyclic triterpenoid glycoside of the licorice root extract, and it has been reported to elicit protective effects against hypoxia, inflammation and apoptosis in ischemic myocardium; therefore, GA may serve as a promising therapeutic agent for ischemia-associated CAD. In the present study, the protective effects of GA against H/R-induced injury in CAECs were investigated. Treatment with GA during H/R maintained cell viability and decreased H/R-induced cell apoptosis in human CAECs. In addition, H/R-mediated induction of intracellular and mitochondrial reactive oxygen species (ROS) was significantly decreased by GA exposure. Similar to ROS scavengers, GA treatment not only exhibited protective effects, but also maintained the mitochondrial membrane potential after H/R and inhibited H/R-induced mitochondrial dysfunction, including deficits in ATP synthesis, mitochondrial DNA copy number and mitochondrial transcriptional activity. Furthermore, GA decreased autophagy/mitophagy, and its protective effect against H/R was abolished by autophagy promotion. Collectively, the results suggested that GA exhibited protective effects against H/R-induced CAEC injury by decreasing ROS accumulation and maintaining mitochondrial homeostasis. Further investigation into the precise mechanisms underlying the decrease in ROS accumulation induced by GA is required.

Keywords: coronary artery endothelial cells; glycyrrhizic acid; hypoxia/reoxygenation; mitochondrial homeostasis; reactive oxygen species.

Copyright: © Tang et al.

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Exp Ther Med
. 2020 Jul;20(1):38-41. doi: 10.3892/etm.2019.8150. Epub 2019 Oct 30.
Pyoderma Gangrenosum and Suppurative Hidradenitis Association, Overlap or Spectrum of the Same Disease? Case Report and Discussion
Gabriela Turcu 1 2 3, Roxana Ioana Nedelcu 2 4, Iulia Teodora Nedelcu 3, Anastasia Hodorogea 3 4, Mihaela Balaban 2 5, Alice Brinzea 4 6, Luciana Nichita 7, Cristiana Gabriela Popp 7, Sabina Andrada Zurac 7, Razvan Theodor Andrei 7
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PMID: 32508990 PMCID: PMC7271694 DOI: 10.3892/etm.2019.8150
Free PMC article
Abstract
Suppurative hidradenitis and pyoderma gangrenosum are rare disorders that can be seen isolated or even more rare, as part of different autoinflammatory syndromes: Pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH) or psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH). Although they have different clinical features, suppurative hidradenitis and pyoderma gangrenosum seem to share similar pathogenic pathways involving a dysregulated innate immune system, with neutrophilic inflammation, mediated by IL-1β, controlled by NALP3 inflammasome pathway. We report a case of a 53-year-old male patient previously diagnosed with HS in inguinal-scrotal area that developed rapidly after a traumatic injury on his left anterior calf, a painful inflammatory plaque with pustules on the surface that rapidly progressed (24-48 h) to form ulcers. The lesions ended up healing with a large scarring plaque with cribriform openings, multiple fibrous bridges, open comedones, and double-ended pseudo-comedones. Although the clinical aspect at presentation together with the aspect on the first biopsy were suggestive for pyoderma gangrenosum, the healing aspect is more commonly seen in suppurative hidradenitis. Commonly seen in acne, in the healing phase of suppurative hidradenitis but more rarely in pyoderma gangrenosum, the formation of comedones seem to be a complex process and raise the question if these entities represent in our patient an association, an overlap or the spectrum of the same disease.

Keywords: hidradenitis suppurativa; pyoderma gangrenosum.

Copyright © 2020, Spandidos Publications.

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30
Review Exp Ther Med
. 2020 Jul;20(1):47-51. doi: 10.3892/etm.2019.8322. Epub 2019 Dec 12.
Psoriatic Arthritis: A Permanent New Challenge for Dermatologists (Review)
Alina Dinu 1, Stefana Bucur 1, Rodica Olteanu 1, Traian Constantin 2 3, Anca Raducan 4, Mara Baetu 5, Maria-Magdalena Constantin 1 3
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PMID: 32508992 PMCID: PMC7271732 DOI: 10.3892/etm.2019.8322
Free PMC article
Abstract
Considering that most of the patients (>2/3) are diagnosed with psoriasis in the cutaneous form long before the joint damage occurs and, in these conditions, a significant proportion of them is found in the dermatologist's initial records, a question must be asked: when is it necessary to send these patients to a rheumatology consultation? The recognition of psoriatic arthritis in patients with vulgar psoriasis and the dermatologist's ability to differentiate it from other arthritis, offers the opportunity to improve patient prognosis by prompt intervention and close collaboration with the rheumatologist. Diagnosis of early psoriatic arthropathy should be considered when a patient with psoriasis or family history of psoriasis has peripheral inflammatory arthritis (oligoarthritis or distal interphalangeal joints damage), enthesitis, dactylitis, spinal pain of inflammatory type. Given that patients with psoriasis are included in the dermatologists' medical records, it is very important to recognize psoriatic arthritis in patients with cutaneous psoriasis, to differentiate it from other possible arthritis, thus having the possibility to improve patient prognosis by prompt intervention and through collaboration with the rheumatologist.

Keywords: dactylitis; enthesitis; joints pain; psoriasis; psoriatic arthritis.

Copyright © 2020, Spandidos Publications.

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31
Exp Ther Med
. 2020 Jul;20(1):97-102. doi: 10.3892/etm.2020.8607. Epub 2020 Mar 17.
Abdominal Aortic Calcification in Predialysis Patients: Contribution of Traditional and Uremia-Related Risk Factors
Delia Timofte 1, Dorin Dragoș 2 3, Andra-Elena Balcangiu-Stroescu 1 4, Maria-Daniela Tănăsescu 2 3, Daniela Gabriela Bălan 4, Laura Răducu 5 6, Adrian Tulin 7 8, Ovidiu Stiru 9 10, Dorin Ionescu 2 3
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PMID: 32509000 PMCID: PMC7271689 DOI: 10.3892/etm.2020.8607
Free PMC article
Abstract
Cardiovascular disease is the main cause of morbidity and mortality in end-stage renal disease (ESRD) patients. Recent population based epidemiological studies demonstrated a correlation between reduced renal function and risk for all causes and cardiovascular mortality, 50% of patients dying before the commencement of renal replacement therapy. Vascular calcifications (VC) and arterial stiffness are major contributors to cardiovascular disease and are independent predictors of cardiovascular mortality in ESRD patients. Scarce information is available on the risk factors and prognosis of predialysis patients with VC. The aim of this study was to evaluate the contribution of traditional and uremia related risk factors to abdominal aortic calcification in predialysis patients. A single center, retrospective study was performed on 305 adult patients monitored at the Bucharest University Emergency Hospital for at least 6 months. Our study reports an increased incidence of VC in predialysis chronic kidney disease (CKD) patients, higher in those with advanced age, history of cardiovascular disease, osteoporosis, and declining renal function.

Keywords: abdominal aortic calcification score; chronic kidney disease; end stage renal disease; lateral plain radiograph of the abdomen; predialysis; vascular calcification.

Copyright: © Timofte et al.

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32
Review Exp Ther Med
. 2020 Jul;20(1):12-17. doi: 10.3892/etm.2019.8342. Epub 2019 Dec 17.
Beneficial Effects of Food Supplements Based on Hydrolyzed Collagen for Skin Care (Review)
Mihaela-Adi Lupu 1, Gratiela Gradisteanu Pircalabioru 1 2, Mariana-Carmen Chifiriuc 2, Radu Albulescu 3 4, Cristiana Tanase 3 5
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PMID: 32508986 PMCID: PMC7271718 DOI: 10.3892/etm.2019.8342
Free PMC article
Abstract
Ageing is a complex, multi-step process which involves, among others loss of collagen and elastin. Collagen is found in large amounts in the body, especially in the dermis layer. These fibers provide the skin's normal strength, hydration and mechanical properties. Collagen is largely available, as it can be extracted from many animal sources, it can be easily absorbed upon topical administration, hence it is largely used in the cosmetic and pharmaceutical industry for the treatment of premature aging. Bioactive peptides, such as collagen hydrolyzate, are among the most used ingredients for the development of nutraceuticals - food or food ingredients that have defined physiological effects. Numerous studies have demonstrated that peptides resulted from ingestion of hydrolysate collagen and detected in the blood stream have chemotactic properties for skin fibroblasts, helping the skin restoration process. The purpose of this minireview is to present an update on the use of hydrolyzed collagen for skin care.

Keywords: hydrolyzed collagen; nutraceuticals; peptide; skin; wrinkles.

Copyright: © Lupu et al.

38 references1 figure
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33
Exp Ther Med
. 2020 Jun;19(6):3650-3656. doi: 10.3892/etm.2020.8659. Epub 2020 Apr 9.
Biomechanical Study of Space Frame Structure Based on Bone Cement Screw
Jintao Xiu 1 2, Tao Bu 3, Yabo Yan 1, Zixiang Wu 1, Zhanhai Yin 2, Wei Lei 1
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PMID: 32373193 PMCID: PMC7197252 DOI: 10.3892/etm.2020.8659
Free PMC article
Abstract
Stability of space frame structures with bone cement screw reinforcement by biomechanical testing was analyzed. Seven complete human spine specimens with osteoporosis were selected. Three specimens were separated into 18 vertebral bodies. Nine vertebral bodies were randomly selected and bone cement screws were implanted on both sides. Bone cement was used to form a bridge at the front end of the two screws (single vertebral group A). The other nine vertebral bodies were implanted with cement screws on both sides, but the front ends of the two screws were not bridged (single vertebral group B). The remaining spine specimens were used for biomechanical testing of the overall stability of the three-dimensional frame. The four specimens were osteotomized, and then two specimens were randomly selected. Bone cement screws were implanted on both sides of the vertebral body, and a bone cement bridge was formed at the front end of the two screws to establish a three-dimensional frame structure (multi-vertebral group A). The other two spine specimens were implanted with cement screws on both sides of the vertebral body, but the front ends of the two screws were not bridged (multi-vertebral group B). A statistical difference was found between the extractive force of bridged and non-bridged specimens. Group B showed some loosening of screws after the test. The stability of the triangle structure screw, which was formed after the bridge was established at the front end of the single-vertebral bone cement screw, was significantly enhanced. Moreover, the stability was significantly improved after the three-dimensional frame structure was established in the multi-vertebral body group, providing a new method for clinical improvement of the stability and reliability of internal fixation in patients with severe osteoporosis and spinal disease.

Keywords: biomechanics; osteoporosis; pedicle screw; polymethylmethacrylate.

Copyright: © Xiu et al.

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34
Exp Ther Med
. 2020 Jul;20(1):500-504. doi: 10.3892/etm.2020.8677. Epub 2020 Apr 22.
Prepregnancy Body Mass Indexes Are Associated With Perinatal Outcomes in Females With Preeclampsia
Lingling Jiang 1, Juan Lin 1, Jianying Yan 1, Xiaoqian Lin 1, Qing Han 1, Huale Zhang 1
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PMID: 32509020 PMCID: PMC7271714 DOI: 10.3892/etm.2020.8677
Free PMC article
Abstract
The present study aimed to determine the clinical characteristics and perinatal outcomes of females with severe preeclampsia according to their pre-pregnancy body mass index (BMI). Data from 233 patients with severe preeclampsia were reviewed from the Inpatient Obstetrics Department. The data were divided into 3 groups according to the patients' pre-pregnancy BMI: Normal (BMI of 18-25 kg/m2; n=134); underweight (BMI <18 kg/m2; n=15); and overweight and obese (BMI >25 kg/m2; n=84). The incidence of dyslipidemia, amniotic fluid abnormalities and neonatal hospitalizations in the group of females who were overweight or obese before pregnancy were higher than those in the other groups (all P<0.05). In conclusion, the presence of dyslipidemia, excessive weight and obesity prior to pregnancy in patients with severe preeclampsia was associated with maternal and perinatal outcomes.

Keywords: free fatty acids; obesity; oxidative stress; preeclampsia.

Copyright: © Jiang et al.

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35
Exp Ther Med
. 2020 Jul;20(1):479-485. doi: 10.3892/etm.2020.8683. Epub 2020 Apr 23.
CHARGE Syndrome Associated With de novo (I1460Rfs * 15) Frameshift Mutation of CHD7 Gene in a Patient With Arteria Lusoria and Horseshoe Kidney
Cristina Gug 1, Eusebiu Vlad Gorduza 2 3, Adrian Lăcătuşu 4, Monica Adriana Vaida 5, Florin Bîrsăşteanu 6, Maria Puiu 1, Dorina Stoicănescu 1
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PMID: 32509017 PMCID: PMC7271729 DOI: 10.3892/etm.2020.8683
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Abstract
CHARGE syndrome is an autosomal dominant condition caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene. The present study reported on the case of a 16-month-old female with plurimalformative syndrome, whose etiology was identified by clinical whole-exome sequencing (WES) analysis. Clinical and follow-up assessments identified multiple craniofacial dysmorphisms, congenital defects and functional symptoms, including dysphagia and Marcus Gunn jaw winking synkinesis. Trio-WES analysis was performed for the patient and their parents and the presence of CHARGE syndrome was further indicated using single-molecule real-time sequencing. A de novo pathogenic variant, c.4379_4380del (p.Ile1460Argfs*15), was identified in exon 19 of the CHD7 gene, which resulted in a premature translational stop signal. Trio-WES analysis was used for further investigation, indicating that neither of the patient's parents had the mutation and confirming its de novo nature. To the best of our knowledge, the case of the present study was the first reported case of CHARGE syndrome in Romania with congenital defects including an aberrant right subclavian artery and a horseshoe kidney. CHARGE syndrome was diagnosed in the patient based on the pathogenic mutation in the CHD7 gene. To the best of our knowledge, the present case report is the first to suggest that the CHD7 gene variant is associated with CHARGE syndrome.

Keywords: CHARGE syndrome; CHD7 gene; arteria lusoria; frameshift mutation; horseshoe kidney.

Copyright: © Gug et al.

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36
Exp Ther Med
. 2020 Jul;20(1):56-60. doi: 10.3892/etm.2019.8260. Epub 2019 Nov 29.
Bacillary Angiomatosis Triggered by Severe Trauma in a Healthy Caucasian Patient: A Case Report
Mihaela Balaban 1 2, Roxana Ioana Nedelcu 1 3, Gabriela Balmes 4, Teodora Adela Todorovic 4, Alice Brinzea 3 5, Luciana Nichita 6, Cristiana Gabriela Popp 6, Razvan Theodor Andrei 6, Sabina Andrada Zurac 6, Daniela Adriana Ion 3, Gabriela Turcu 1 4 7
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PMID: 32508994 PMCID: PMC7271690 DOI: 10.3892/etm.2019.8260
Free PMC article
Abstract
Bacillary angiomatosis represents a cutaneous and systemic infection caused by Bartonella species, typically described in the past in HIV-positive patients or associated with immunodeficiencies. More recent case reports had brought into attention the probability that this entity may manifest in otherwise healthy individuals, triggered by trauma and skin burns. The physiopathology of this neoproliferative process is based on the production of angiogenetic molecules, such as vascular endothelial growth factor (VEGF) and IL-8. In case of an inadequate treatment, the evolution can be fatal, with a systemic dissemination of the abscesses within the gastro-intestinal tract, respiratory tract, brain and bones. The appropriate therapy is with oral erythromycin and doxycycline, but several treatments such as cephalosporins, penicillins, macrolides, aminoglycosides, rifampin, dapsone, ciprofloxacin, have been tried with favorable results. Herein we present the case of a Caucasian patient, seronegative for HIV, who developed multiple vascular papules and nodules on the face, after a severe trauma and which healed after an adequate antibiotic therapy with oral clarithromycin.

Keywords: bacillary angiomatosis; immunocompetent patient; trauma.

Copyright © 2020, Spandidos Publications.

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37
Exp Ther Med
. 2020 Jul;20(1):159-162. doi: 10.3892/etm.2020.8671. Epub 2020 Apr 22.
COVID-19 Related Stress Exacerbates Common Physical and Mental Pathologies and Affects Treatment (Review)
Konstantinos Tsamakis 1 2, Andreas S Triantafyllis 3, Dimitrios Tsiptsios 4, Eleftherios Spartalis 5, Christoph Mueller 2 6, Charalampos Tsamakis 7, Sofia Chaidou 8, Demetrios A Spandidos 9, Lampros Fotis 10, Marina Economou 11, Emmanouil Rizos 1
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PMID: 32509006 PMCID: PMC7271730 DOI: 10.3892/etm.2020.8671
Free PMC article
Abstract
COVID-19 pandemic has caused a global public health emergency resulting in unprecedented individual and societal fear and anxiety. The stress surrounding this biothreat appears to have clinical implications in all aspects of medicine, both in mental and physical health spheres. The impact of COVID-19 related anxiety in Cardiology, Paediatrics, Oncology, Dermatology, Neurology and Mental Health and how it affects treatments is discussed. Moreover, the need for introducing novel communication and therapeutic approaches is highlighted in the new landscape of the COVID-19 era.

Keywords: COVID-19; clinical implications; pandemic; physical and mental pathologies; stress; treatment.

Copyright: © Tsamakis et al.

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38
Exp Ther Med
. 2020 Jul;20(1):186-194. doi: 10.3892/etm.2020.8673. Epub 2020 Apr 22.
T Lymphocytes in IgA Nephropathy
Yuyan Tang 1, Haidong He 1, Pin Hu 1, Xudong Xu 1
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PMID: 32509008 PMCID: PMC7271719 DOI: 10.3892/etm.2020.8673
Free PMC article
Abstract
Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is the main cause of end-stage renal disease. IgAN is characterized by the accumulation of immune complexes in the circulation, which contain abnormal levels of IgA. IgAN primarily results from galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 deposition in the renal mesangium, causing local proliferation and matrix expansion. Gd-IgA1 has been confirmed as one of the key effectors in the pathogenesis of IgAN, but the origin of Gd-IgA1 is not clear. Recent studies have shown that Gd-IgA1 deposition could be the result of mucosally primed plasma cells and is associated with T cell dysregulation. T cells contribute to the IgA response and play an important role in the development of IgAN. In the present review, the latest discoveries regarding the role of T lymphocytes in the pathogenesis of IgAN have been summarized. Understanding these advances will allow novel therapeutic strategies for the treatment of IgAN.

Keywords: B lymphocyte; IgA nephropathy; T lymphocyte; galactose-deficient IgA1; pathogenesis.

Copyright: © Tang et al.

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39
Exp Ther Med
. 2020 Jul;20(1):671-677. doi: 10.3892/etm.2020.8680. Epub 2020 Apr 23.
Hydrogen Sulfide Alleviates Cognitive Deficiency and Hepatic Dysfunction in a Mouse Model of Acute Liver Failure
Da-Sen Yuan 1, Yue-Qi Huang 1, Yuan-Ji Fu 1, Juan Xie 1, Yuan-Lu Huang 1, Shi-Shan Zhou 1, Pei-Yuan Sun 1, Xiao-Qing Tang 1
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PMID: 32509026 PMCID: PMC7271739 DOI: 10.3892/etm.2020.8680
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Abstract
Acute liver failure (ALF) is a devastating clinical syndrome with a high mortality rate if not treated promptly. Previous studies have demonstrated the beneficial effects of hydrogen sulfide (H2S) on the brain and liver. The present study aimed to investigate the potential protective effects of H2S in ALF. A mouse model of ALF was established following treatment with thioacetamide (TAA). Mice with TAA-induced ALF were intraperitoneally injected with 30 or 100 µmol/kg/day sodium hydrosulfide (NaHS; a H2S donor drug) for two weeks. According to results from novel object recognition and Y-maze tests, in the present study, NaHS treatment alleviated cognitive deficiency and preserved spatial orientation learning ability in TAA-induced ALF mice compared with those of untreated mice. In addition, NaHS treatment reduced serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and the concentration of ammonia compared with those that received control treatment, resulting in weight loss prevention. These findings suggested a beneficial effect of H2S on liver function. In conclusion, results from the present study suggested that H2S treatment may alleviate cognitive deficiency and hepatic dysfunction in mice with ALF, indicating the potential therapeutic benefits of applying H2S for the treatment of ALF.

Keywords: Y-maze test; acute liver failure; cognition; hydrogen sulfide; novel object recognition test.

Copyright © 2020, Spandidos Publications.

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40
Exp Ther Med
. 2020 Jul;20(1):486-494. doi: 10.3892/etm.2020.8670. Epub 2020 Apr 21.
Hesperetin Improves Diabetic Coronary Arterial Vasomotor Responsiveness by Upregulating Myocyte Voltage-Gated K + Channels
Yu Liu 1, Lei Zhang 1, Lina Dong 1, Qiying Song 1, Pengmei Guo 1, Yan Wang 1, Zhaoyang Chen 2, Mingsheng Zhang 1
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PMID: 32509018 PMCID: PMC7271715 DOI: 10.3892/etm.2020.8670
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Abstract
Hesperetin (HSP) is a naturally occurring flavonoid. The present study aimed to investigate the potential vasomotor effects and mechanisms of HSP action on rat coronary arteries (RCAs) injured by diabetes or high glucose concentrations. HSP (100 mg/kg/day) was intragastrically administered to the rats for 8 weeks, which were rendered diabetic with a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The vascular tone of RCAs was recorded using a wire myograph. The voltage-dependent K+ (Kv) currents were examined using patch clamping. The expression of Kv channels (Kv1.2 and Kv1.5) was examined by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). Diabetes induced contractile hypersensitivity and vasodilator hyposensitivity in RCAs, both of which were attenuated by the chronic administration of HSP. Patch clamp data revealed that chronic HSP treatment reduced diabetes-induced suppression of Kv currents in the myocytes. Western blot and RT-qPCR analyses revealed that chronic HSP administration increased the expression of Kv1.2, but not Kv1.5, in the RCAs of diabetic rats compared with those from non-diabetic rats. In vitro analysis showed that co-incubation with HSP ameliorated high-glucose-induced suppression of Kv currents and Kv 1.2 protein expression in the myocytes. Taken together, the present study demonstrated that HSP alleviated RCA vasomotor dysfunction as a result of diabetes in rats by upregulating the expression of myocyte Kv channels.

Keywords: coronary artery; diabetes; hesperetin; high glucose; voltage-dependent K+ channel.

Copyright: © Liu et al.

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41
Exp Ther Med
. 2020 Jul;20(1):52-55. doi: 10.3892/etm.2020.8529. Epub 2020 Feb 14.
Excimer Laser for Psoriasis Treatment: A Case Report and Short Review
Valeriu Ardeleanu 1 2 3 4, Diana Sabina Radaschin 4 5 6, Alin Laurentiu Tatu 4 5 6
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PMID: 32508993 PMCID: PMC7271705 DOI: 10.3892/etm.2020.8529
Free PMC article
Abstract
Psoriasis is a common cutaneous disease that has major implications in the quality of life of the patient. It is characterised by a chronic course and in some subtypes, it can be life threatening. Many studies have focused on the pathogenesis concerning this disease therefore improving the therapeutic approaches. Phototherapy represents a well-known treatment option for psoriasis. The depletion of T cells mostly from the epidermis, after exposure to phototherapy, validates the role of this treatment. The 308 nm excimer laser has the ability to treat mild, moderate and even severe but localised psoriasis plaques and plays an important role in the treatment management of psoriasis. In this report, we present the case of a patient diagnosed with plaque psoriasis, resistant to topical ointments, successfully treated with the 308 nm excimer laser. Although further studies are still required to consider the 308 nm excimer laser as a first line therapy, its high response rates have significantly influenced the therapeutic approach in psoriasis.

Keywords: UVB 308 nm; decreased proliferation rate; excimer laser; lymphocytic apoptosis; psoriasis.

Copyright: © Ardeleanu et al.

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42
Exp Ther Med
. 2020 Jul;20(1):87-90. doi: 10.3892/etm.2020.8675. Epub 2020 Apr 22.
Regressive Melanoma in a Female Patient: A Case Report
Florica Sandru 1 2, Carmen-Cristina Draghici 2, Teodora Predescu 3, Maria Magdalena Constantin 1 4, Răzvan-Cosmin Petca 1 5, Traian Constantin 5, Aida Petca 1 6, Mihai Cristian Dumitraşcu 1 7
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PMID: 32508999 PMCID: PMC7271722 DOI: 10.3892/etm.2020.8675
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Abstract
Regressive melanoma is a phenomenon characterized by partial or complete replacement of cutaneous melanoma by fibrotic structures as a result of local host immune response. The dermoscopic features include 'scar-like' depigmentation that can be described as hypopigmented to pigmented macules, pink macules, linear-irregular vessels, globular vessel pattern, hyperpigmented macular remnants, blue gray 'peppered' papular remnants and white transverse bands. Fully regressive melanoma is very rare, and, in majority of cases, the tumor is associated with metastases, so the prognosis is very poor due to this fact. Regressive melanomas are rare since it represents an advance stage of melanoma evolution. Their treatment requires a collaboration between the dermatologist and the oncologist in order to improve the quality of life of the patient and also the survival rate.

Keywords: metastasis; prognostic; regressive melanoma.

Copyright © 2020, Spandidos Publications.

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43
Exp Ther Med
. 2020 Jul;20(1):655-661. doi: 10.3892/etm.2020.8666. Epub 2020 Apr 15.
Assessment of Para-Inflammation in a Wound Healing Model
Guoping Wang 1, Guobo Shen 1, Xiaoshuang Jiang 2, Zhixing Chen 3, Tao Yin 1
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PMID: 32509025 PMCID: PMC7271725 DOI: 10.3892/etm.2020.8666
Free PMC article
Abstract
A thorough understanding of the inflammatory process has substantial biological and clinical relevance. Para-inflammation has been described as an adaptive response of the immune system to low levels of tissue stress. However, the role of para-inflammation in wound repair requires further investigation. In the present study, the expression levels of several para-inflammation genes were assessed in a murine cutaneous wound healing model. The results revealed that the expression levels of the para-inflammation genes were significantly altered. Among the genes that were examined, the expression levels of solute carrier family 7 member 11 (Slc7a11) paralleled those of the M2 macrophage-associated genes. Further investigation indicated that the Slc7a11 gene and its encoded protein cystine/glutamate transporter exhibited increased expression levels in IL-4-induced M2 macrophages. Notably, the inhibition of para-inflammation by sulindac prolonged wound healing process. The present study indicated that para-inflammation exhibited a protective effect in wound healing and provided new insight for host tissue repair.

Keywords: injury; macrophages; para-inflammation; tissue repair; wound healing.

Copyright © 2020, Spandidos Publications.

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44
Exp Ther Med
. 2020 Jul;20(1):173-185. doi: 10.3892/etm.2020.8687. Epub 2020 Apr 24.
Natural Skin-Whitening Compounds for the Treatment of Melanogenesis (Review)
Wenhui Qian 1 2, Wenya Liu 1, Dong Zhu 2, Yanli Cao 1, Anfu Tang 1, Guangming Gong 1, Hua Su 1
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PMID: 32509007 PMCID: PMC7271691 DOI: 10.3892/etm.2020.8687
Free PMC article
Abstract
Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.

Keywords: melanogenesis; natural sources; skin-whitening agents; tyrosinase.

Copyright: © Qian et al.

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