A Case Report: The Effects of Photobiomodulation Therapy and Amniotic Fluid Gel on a Severe Diabetic Foot Ulcer.

Introduction: Diabetic patients frequently experience a serious complication known as impaired wound healing, which increases the likelihood of foot infection and limb amputation. Investigators have been looking for novel methods to treat diabetic foot ulcers (DFUs) recently. Case Report: A 75-year-old woman with type one diabetes mellitus (DM) has been accepted. There was a sizable (40 cm2 full-thickness cutaneous wound) in the plantar part of her right foot (Wagner Ulcer Grade Classification System: grade 3) which had not been treated by the usual treatment for DFUs. In this present case, we used amniotic fluid gel (AF gel) and photobiomodulation therapy (PBMT) (400 mW/cm2; 810 nm, once a week for 16 weeks) to treat and speed up the healing of a harsh DFU. The size of the ulcer area significantly decreased as combination therapy progressed, and within 16 weeks, the wound was healed and the pain was reduced. Conclusion: This revealed contextual analysis demonstrated the useful effect of the mix of PBMT and AF gel on a serious DFU. To confirm the findings, we recommend conducting additional clinical trials in a clinical setting. In addition, it is recommended that additional research using preclinical models uncover the mechanism of action of the combination therapy.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

Assessing the Changes of Cortical Thickness in Alzheimer Disease With MRI Using Freesurfer Software.

Introduction: In this study, we intend to determine the correlation between the thickness of the cerebral cortex and the severity of the cognitive disorder in Alzheimer disease (AD). Methods: A total of 20 (14 women and 6 men) patients diagnosed with AD with a Mean age of 72.95 years, and 10 (7 women and 3 men) cognitively normal (CN) subjects with a Mean age of 70.50 years were included in the study. Of the AD patient and CN subjects, 70% were female, and 30% were male. All individuals underwent 1.5 T Magnetic resonance imaging (MRI). The MRI scanning protocol included 3D MPRAGE (3D-T1W) sequence. All images were analyzed using Freesurfer v5.3, and then the brain cortical thickness in 7 cortical areas (inferior temporal, middle temporal, superior temporal, parahippocampal, pars triangularis, rostral middle frontal, and superior frontal) was calculated. Results: The analysis of covariance (ANCOVA) was conducted to compare the mean thickness of each region between the patient and the control group. There was a significant difference in the mean cortical thickness in all regions. In all cases, the mean cortical thickness in CN subjects was greater than in AD patients. However, the mean thickness of pars triangularis left hand in CN subjects was not significantly greater than that in AD patients. The receiver operating characteristic system (ROC) was designed to evaluate the predictive power of the patients and the healthy people. We have selected a thousand cut-off points from 1.5 to 3.5 mm for cortical thickness. When the cut-off points were within 2.276878-2.299680 mm in the left hemisphere, Youden's index was maximum. The sensitivity and specificity, in this case, were 80%. Also, when the cut-off points were within the range of 2.263278-2.282278 mm in the right hemisphere, the sensitivity and specificity were 90% and 80%, respectively. Conclusion: This study demonstrates the importance of quantifying the cortical thickness changes in the early diagnosis of AD. In addition, examining the pattern of changes and quantifying the reduction in the thickness of the cortex is a crucial tool for displaying the local and global atrophy of the brain. Also, this pattern can be used as an alternative marker for the diagnosis of dementia. Finally, to the best of our knowledge, our study is the first to report finding on the cortical thickness that would help the clinician have a better differential diagnosis. Also, this study has checked the possibility of early diagnosis of the disease. Highlights: The correlation between the thickness of cerebral cortex and the severity of cognitive disorder in Alzheimer's disease was determined.The cortical thickness change is an important factor in early diagnosis of Alzheimers disease.The pattern of reduction in the thickness changes is a crucial tool for displaying the local and global atrophy of the brain. Plain Language Summary: The neurodegenerative disorder Alzheimer's disease (AD) is a fast-growing epidemic in aging populations worldwide. In 2050, one new case of AD is estimated to increase up to every 33 seconds. So the diagnosis of AD in the early stage considerably decreases the progress of dementia and helps identify a correct treatment approach. The cortical thickness measured by structural neuroimaging has received a significant surrogate biomarker that could provide powerful tools for the early diagnosis of AD. Since the sensitivity and specificity of MRI are higher, it offers essential advantages for identifying brain atrophy patterns. The manual cortical thickness measurement methods are time-consuming and require experienced anatomists compared with automated methods. In this regard, Freesurfer software, which is a freely available program and provides information for quantifying the functional and structural features of the brain, is used. The current study demonstrates examining the pattern of changes and quantifying the reduction in the thickness of the cortex. This can also be used as an alternative marker for the early diagnosis of dementia using cortical thickness measurment that would help the physicians.

Assessment of the Microbiome Role in Skin Protection Against UV Irradiation Via Network Analysis.

Introduction: Diverse microbiotas which have some contributions to gene expression reside in human skin. To identify the protective role of the skin microbiome against UV exposure, proteinprotein interaction (PPI) network analysis is used to assessment gene expression alteration. Methods: A microarray dataset, GEO accession number GSE117359, was considered in this respect. Differential expressed genes (DEGs) in the germ-free (GF) and specific pathogen-free (SPF) groups are analyzed by GEO2R. The top significant DEGs were assigned for network analysis via Cytoscape 3.7.2 and its applications. Results: A total of 28 genes were identified as significant DEGs and the centrality analysis of the network indicated that only one of the seven hub-bottlenecks was from queried genes. The gene ontology analysis of Il6, Cxcl2, Cxcl1, TNF, Il10, Cxcl10, and Mmp9 showed that the crucial genes were highly enriched in the immune system. Conclusion: The skin microbiome plays a significant role in the protection of skin against UV irradiation and the role of TNF and IL6 is prominent in this regard.

Neuroprotective Properties of Photobiomodulation in Retinal Regeneration in Rats: Perspectives From Interaction Levels.

Introduction: Photobiomodulation (PBM) is known as low-level laser (or light) therapy and is applied in different fields of medicine. However, it is required that its molecular and cellular mechanism be investigated. This study aims to assess the neuroprotective properties of PBM in the rat retina. Methods: GSE22818 was downloaded from Gene Expression Omnibus (GEO) and the regulation of the significant differentially expressed genes (DEGs) which are produced by light damage in the rat retina by the pretreatment of PBM application was assessed via network analysis and gene ontology enrichment. Results: The 78 produced DEGs by light-damage in the rat retina were protected via PBM pretreatment action. Among these determined DEGs, 53 individuals were included in the main connected component of the constructed protein-protein interaction (PPI) network. Ccl2, Icam1, Cxcl10, Timp1, and Fos were determined as hub nodes. Eight clusters including 26 regulated biochemical pathways by PBM pretreatment were identified. The critical DEGs based on the action maps were introduced. Conclusion: The finding indicates that PBM treatment protects rat retina against light damage via the prevention of Fos, Ccl2, Icam1, Cxcl10, and Myc dysregulation.

Assessment of Laser Effects on Skin Rejuvenation.

Laser skin resurfacing has changed the approach of facial skin rejuvenation over the past decade. This article evaluates the laser effects on skin rejuvenation by the assessment of laser characteristics and histological and molecular changes, accompanied by the expression of proteins during and after laser-assisted rejuvenation of skin. It is important to note that different layers of skin with different cells are normally exposed to the sun's UV radiation which is the most likely factor in aging and damaging healthy skin. To identify the expression of proteins, using validated databases and reviewing existing data could reveal altered proteins which could be analyzed and mapped to investigate their expression and their different effects on cell biological responses. In this regard, proteomics data can be used for better investigation of the changes in the proteomic profile of the treated skin. Different assessments have revealed the survival and activation of fibroblasts and new keratinocytes with an increase of collagen and elastin fibers in the dermis and the reduction of matrix metalloproteinases (MMPs) and heat shock proteins (HSPs) as a result of different low-power laser therapies of skin. There are a wide range of biological effects associated with laser application in skin rejuvenation; therefore, more safety considerations should be regarded in the application of lasers in skin rejuvenation.

Highlighted role of "IL17 signaling pathway" in gastroesophageal reflux disease.

AIM: The aim of this study is to assess the molecular profile of gastroesophageal reflux disease (GERD) via Protein-protein interaction (PPI) network analysis and gene ontology (GO) investigation. BACKGROUND: GERD which affects the life of about 30% of people is associated with high costs in the human papulation. Several risk factors such as smoking, eating habits, BMI, and dysfunction of lower esophageal sphincter have been reported to contribute to the onset and progression of GERD. The roles of some types of interleukins and inflammatory factors as molecular features of GERD are investigated. METHODS: Genes related to GERD were analyzed by Cytoscape v.3.7.2 and the corresponding plug-ins. ClueGO and CluePedia assessed the gene ontology and action type properties for the central nodes. RESULTS: The results indicated that there are 12 hub-bottlenecks almost all of which except ALB are dispersed in the network clusters 1 and 2. Il17 signaling pathway among 7 identified biochemical pathways was also detected as a most related annotation for these central genes. CONCLUSION: Numbers of 11 critical genes and one pathway (IL17 signaling pathway) were highlighted as the deregulate genes and pathway in GERD. Common molecular features of GERD and cancer appeared.

Light at Night Exposure Effects on Differentiation and Cell Cycle in the Rat Liver With Autonomic Nervous System Denervation.

Introduction: N Exposure to artificial light at night (LAN) affects human health and causes several functional modifications in the body. Obesity, diabetes, and hormonal changes are reported after exposure to LAN in humans. This study aims to highlight the critical features of biological terms that are affected in the liver of rats which received autonomic nervous system denervation. Methods: The liver gene expression profiles of 8 male Wistar rats that received sympathetic plus parasympathetic hepatic denervation and were exposed to LAN from Gene Expression Omnibus (GEO) for 1 hour were compared with 5 controls. The significant differentially-expressed genes (DEGs) were screened by the protein-protein interaction (PPI) network analysis STRING database (an application of Cytoscape software). Also, CuleGO and CleuDedia, the 2 applications of Cytoscape software, were used for more analysis. Results: Among 250 DEGs, 173 characterized genes with fold change more than 2 plus 100 added relevant genes were included in the PPI network. The analysis of the main connected component (MCC) led to introducing 15 hubs and 15 bottlenecks. CCT2, COPS7A, KAT2A, and ERCC1 were determined as hub-bottlenecks. Among hubs and bottlenecks, DHX15, KAT2A, CCT2, HSP90AB1, CCNE1, DHX16, LSM2, WEE1, CWC27, BAZ1B, RAB22A, DNM2, and DHX30 were linked to each other by various kinds of actions. CCT2 and KAT2A, the 2 hub-bottlenecks, were included in the interacted genes in the action map. Four classes of biological terms including negative regulation of non-motile cilium assembly, negative regulation of transforming growth factor beta activation, alpha-tubulin acetylation, and histamine-induced gastric acid secretion were identified as the critical biochemical pathways and biological processes. Conclusion: Several essential functions such as differentiation, cell cycle, ribosome assembly, and splicing are affected by LAN in rat livers with autonomic nervous system denervation.

Comparison Between Three-Dimensional Diffusion-Weighted PSIF Technique and Routine Imaging Sequences in Evaluation of Peripheral Nerves in Healthy People.

INTRODUCTION: The present study aims to evaluate the Three-Dimensional Diffusion-Weighted reversed fast imaging with steady state free precession (3D DW-PSIF) sequence with respect to imaging of the peripheral nerves; the tibial, medial, and lateral plantar nerves in the lower extremity, ulnar and median nerve in the upper extremity, sciatic nerve, brachial plexus, and lumbosacral plexus, and also to compare its usefulness with the current two-dimensional sequences on a 1.5 T MR scanner. METHODS: A total of 25 healthy subjects underwent MR imaging of peripheral nerves, 5 subjects in each area. In each imaging sequence, including T2W SPAIR and 3D DW-PSIF, images were evaluated for ability to identify the nerves in the related area using a 3-score scale (0-2). Then, by summing up the conspicuity scores, a total certainty score was recorded for each sequence. RESULTS: With combining the results of all studies, the conspicuity mean (SD) score was 1.57(0.67) on the 3D DW-PSIF images, and 0.74(0.76) on the T2-weighted images (P<0.001). Regarding the lumbosacral plexus, the corresponding certainty mean (SD) scores were 1.80(0.40) and 1.07(0.74) (P<0.001) and with regard to the brachial plexus, they were 1.23(0.83) and 0.75(0.84), (P<0.001). Regarding the ankle/hind foot they were 1.87(0.35) and 0.40(0.50) (P<0.001) and in the wrist/proximal hand, 1.70(0.48) and 0.50(0.52) (P<0.001). Regarding the sciatic nerve, they were 1.80(0.44) and 0.20(0.44) (P=0.003). CONCLUSION: 3D DW PSIF provides better manifestation of nerves compared to routine imaging sequences particularly fat saturated T2W images. This novel imaging technique can be used in MR neurography examination protocol for exact localization of the nerve and evaluation of the nerve pathology.

Quality of Life of patients with chronic kidney disease in Iran: Systematic Review and Meta-analysis.

INTRODUCTION: Renal diseases are among the major health problems around the world that cause major changes in patients' lifestyle and affect their quality of lives. The aim of this study was to evaluate the quality of life of patients with chronic kidney disease (CKD) in Iran through a meta-analysis. MATERIALS AND METHODS: This study was conducted using authentic Persian and English keywords in the national and international databases including IranMedex, SID, Magiran, IranDoc, Medlib, Science Direct, Pubmed, Scopus, Cochrane, Embase, Web of Science, and Medline. The data were analyzed using meta-analysis (random effects model). Heterogeneity of studies was assessed using I2 index. In this study, SF-36: 36-Item Short Form health-related quality of life (HRQOL), kidney disease quality of life-SF (KDQOL-SF), KDQOL and KDQOL-SFTM questionnaires were used. Data were analyzed using STATA Version 11 software. RESULTS: A total of 17200 individuals participated in 45 reviewed studies, and the mean score of CKD patients' quality of life was estimated by SF-36 (60.31), HRQOL (60.51), and KDQOL-SF (50.37) questionnaires. In addition, meta-regression showed that the mean score of CKD patients' quality of life did not significantly decrease during the past years. CONCLUSION: The mean score of quality of life of patients with CKD was lower in different dimensions in comparison with that of normal people. Therefore, interventional measures should be taken to improve the quality of life of these patients in all dimensions.

Gene expression analysis of colon high-grade dysplasia revealed new molecular mechanism of disease.

AIM: The aim of this research was to find a clear molecular view of dysplasia via network analysis. BACKGROUND: There are some evidence suggest the relationship between dysplasia and colorectal cancer. Understanding of high-grade dysplasia (HGD) could be beneficial for colon cancer management. METHODS: Bioinformatics study of HGD versus healthy subjects was conducted to check the status of differentially expressed genes (DEGs). GSE31106, GPL1261, GSM770092-94 and GSM770101-6 were the sources from gene expression omnibus (GEO) that queried for protein-protein interaction (PPI) network analysis via Cytoscape and its algorithms. Hubs of network were enriched for biochemical pathways and were validated via clustering analysis. RESULTS: Numbers of 46 hub nodes were determined and were included in 12 pathways. A main cluster including 76 nodes was identified containing 45 hubs. 33 hubs among 46 genes were involved in biochemical pathways. IL1B, IL6, TNF, and TRL4 were the most important critical genes. CONCLUSION: Many different genes as hub nodes might influence the trigger and development of advance condition and also colon cancer.

A systems biology analysis protein-protein interaction of NASH and IBD based on comprehensive gene information.

AIM: Analysis reconstruction networks from two diseases, IBD and NASH and their relationship, based on systems biology methods. BACKGROUND: IBD and NASH are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on co-existence of these two diseases. In addition, they have some similar risk factors such as age, obesity, and insulin resistance. Therefore, systems biology approach can help to discover their relationship. METHODS: DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. Based on degree and Betweenness, hubs and bottleneck nodes were defined. RESULTS: Common genes between IBD and NASH construct a network with 99 nodes. Common genes between IBD and NASH were extracted and imported to STRING database to construct PPI network. The resulting network contained 99 nodes and 333 edges. Five genes were selected as hubs: JAK2, TLR2, TP53, TLR4 and STAT3 and five genes were selected as bottleneck including: JAK2, TP53, AGT, CYP3A4 and TLR4. These genes were hubs in analysis network that was constructed from hubs of NASH and IBD networks. CONCLUSION: Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

Oral squamous cell cancer protein-protein interaction network interpretation in comparison to esophageal adenocarcinoma.

AIM: The aim of this study is to present the oral Squamous Cell Cancer protein-protein interaction network interpretation in comparison to esophageal adenocarcinoma. BACKGROUND: Oral squamous cell cancer (OSCC) is a common disease worldwide, with poor prognosis and limited treatment. Thus, introducing molecular markers through network analysis can be helpful. METHODS: STRING database (DB) was applied for network construction through Cytoscape 3.4.0. Clue GO handled the gene annotation for the retrieved clusters. Eight proteins were indicated to be differential in the network constitution. RESULTS: The centrality and clustering analysis indicate that TP53 plays an over-significant role in network integrity among eight most central proteins including TP53, AKT1, EGFR, MYC, JUN, CDH1, CCND1, and CTNNB1. The suggested biomarker set is very similar to the related biomarker panel of esophageal adenocarcinoma. CONCLUSION: The ontology analysis implies that the prominent proteins are involved in regulation of smooth muscle cell proliferation, regulation of fibroblast proliferation, and response to UV-A processes. In conclusion, these proteins and their associated biological processes may be more critical compared to other reported biomarkers for OSCC. Nevertheless, validation studies are required for confirming the pivotal role of potential candidates. Similar biomarker panel of this disease and esophagus adenocarcinoma is corresponded to the origin of the two malignancies.

Novel materials to enhance corneal epithelial cell migration on keratoprosthesis.

PURPOSE: To introduce a new modification for silicone optical core Keratoprosthesis. METHODS: Using mixtures of 2-hydroxyethyl methacrylate and acrylic acid polydimethylsiloxane (PDMS) films were modified with two-step oxygen plasma treatment, and then type I collagen was immobilised onto this modified surfaces. Both the biocompatibility of the modified films and cell behaviour on the surface of these films were investigated by in vitro tests, and formation of epithelial cell layer was evaluated by implantation of the modified films in the corneas of 10 rabbits. RESULTS: In vitro studies indicated that the number of attached and proliferated cells onto modified PDMS in comparison with the unmodified PDMS significantly increased. Histological studies showed that corneal epithelial cells migrated on the anterior surface of the modified films after 1week. The corneal epithelial cell formed an incomplete monolayer cellular sheet after 10days. A complete epithelialisation on the modified surface was formed after 21days. The epithelial layer persisted on the anterior surface of implant after 1-month and 3-month follow-up. CONCLUSION: This method may have potential use in silicone optical core Keratoprosthesis.

Brain-derived neurotrophic factor as a biomarker in primary open-angle glaucoma.

PURPOSE: To introduce a novel biomarker for screening of primary open-angle glaucoma (POAG) by detecting and measuring brain-derived neurotrophic factor (BDNF) in the serum of normal subjects and patients with early stage of glaucoma. METHODS: Twenty-five glaucoma patients as the case group and 25 age- and sex-matched normal persons as the control group were tested. The control group comprised 19 men and 6 women, with the mean age of 59.32 ± 11.8 years and without any apparent ocular or systemic diseases. The case group comprised 20 men and 5 women, with the mean age of 59.64 ± 11.56 years, who were assessed by routinely performed clinical and paraclinical investigations. BDNF levels in serum were determined by enzyme-linked immunosorbent assay using monoclonal antibodies specific for BDNF. RESULTS: The mean of BDNF levels in the serum was 27.16 ± 5.53 ng/mL in the control subjects and 18.42 ± 4.05 ng/mL in the subjects with the early stage glaucoma. A statistically significant difference was evident between the two groups (p < 0.05). We found no significant differences in serum BDNF levels according to the subjects' age, gender, duration of the glaucoma, mean intraocular pressure, and blood pressure (p > 0.05). Glaucoma patients who had lower serum BDNF concentration had disclosed a significant negative correlation with pattern standard deviations. CONCLUSIONS: We conclude that BDNF in the serum might be a useful biochemical marker for early detection of POAG. We also propose that this might be a reliable, time efficient, and cost-effective method for diagnosis, screening, and assessing the progression of POAG. However, more studies and trials are needed to investigate these factors in greater detail.

Histological study of the toxic effects of solder fumes on spermatogenesis in rats.

OBJECTIVE: Toxic fumes generated during the soldering process contain various contaminants released at sufficient rates to cause both short- and long-term health problems. Studies have shown that these fumes change the quality and quantity of semen fluid in exposed workers. The aim of the present study was to determine the potentially toxic effects of solder fumes on spermatogenesis in seminiferous tubules of rats as an experimental model, with conditioned media in an exposed chamber. MATERIALS AND METHODS: A total number of 48 male Sprague Dawley adult rats were randomly divided into experimental (n=30) and control (n=18) groups. Based on exposure time, each group was further subdivided into two, four and six subgroups. Rats in the experimental groups were exposed to solder fumes in an exposure chamber for one hour/ day. The concentrations of fumes [formaldehyde, stanum (Sn) and lead (Pb)] were measured by a standard method via atomic absorption and spectrophotometry. According to a timetable, under deep anesthesia, the rats of both experimental and control subgroups were killed. After fixation of testes, specimens were weighed and routinely processed. Paraffin sections were stained by hematoxylin and eosin. Spermiogenesis index was calculated and data analyzed by Mann Whitney NPAR test. RESULTS: ANALYSIS OF AIR SAMPLES IN THE EXPOSURE CHAMBER SHOWED THE FOLLOWING FUME CONCENTRATIONS: 0.193 mg/m(3) for formaldehyde, 0.35 mg/m(3) for Sn and 3 mg/m(3) for Pb. Although there was no significant difference in testes weight between control and experimental subgroups, there was only a significant difference in spermiogenesis index between the six week experimental and control subgroups (p<0.02). CONCLUSION: The results of this study showed that solder fumes can change the spermiogenesis index in experimental groups in a time dependent manner.