Examining the effect of Helicobacter pylori cagPAI variety on gene expression pattern related to gastric cancer.

OBJECTIVES: We aimed to determine possible association between heterogeneity of Helicobacter pylori cytotoxin-associated gene pathogenicity island and gene expression profiles in patients with distinct histopathological changes. METHODS: Gastric biopsies were obtained from seventy five patients. Microbiological and pathological examinations were done and intactness of Helicobacter pylori cagPAI was determined by PCR using 11 pairs of primers flanking cagζ-cagA regions and cagPAI empty site. Alterations at mRNA levels of eight genes were investigated by real-time PCR and their association with cagPAI intactness and histopathological changes examined statistically. RESULTS: A larger proportion of cagPAI positive strains colonized patients with SAG (52.4%), followed by CG (33.3%), and IM (14.3%). Intact cagPAI was found in 87.5% of the strains obtained from patients with SAG, while significantly lower frequency was detected among those with CG (12.5%) and IM (0%). No significant difference was found among the studied histological groups and fold changes in gene expression of gastric biopsies of Helicobacter pylori infected patients with distinct cagPAI status. However, in each histological group, the strains with more complete gene cluster induced (ErbB2, CCNE1, CTNNB1, and MMP7 in SAG and IM groups) or reduced (TP53, in CG group) expression of the GC associated genes in relatively higher levels. APC, TP53 and E-cadherin were down-regulated in patients with SAG and IM compared with CG patients, irrespective to the status of cagPAI integrity. CONCLUSIONS: Helicobacter pylori strains that carry more complete cagPAI segment could induce remarkably higher levels of mRNA changes of GC associated genes in all histopathological groups.

Prevalence of enteric adenovirus and co-infection with rotavirus in children under 15 years of age with gastroenteritis in Qom, Iran.

Aim: The current study is the first performed in Qom to determine the prevalence of adenovirus and co-infections with rotavirus in children aged <15 years with gastroenteritis symptoms. Background: Gastroenteritis-associated viral infections are a cause of death among young children worldwide, especially in developing countries. The Adenovirus species F (40 and 41) are responsible for a range of acute diarrhea cases among infants and children. Methods: Over a period of 9 months, a total of 130 children suffering from intestinal problems who referred to the infectious ward of Children's Hospital were enrolled in the current study. After clinical examination and collection of demographic information, fecal samples were obtained from the patients. Viral genomes were extracted with a commercial kit and amplified and typed by adenovirus-specific PCR assay. Adenovirus-positive samples were also evaluated for co-infection with rotavirus. Results: Patients had a mean±SD age of 2.66±2.72 years; 63.1% of patients were male and 36.9% were female. Adenovirus infection was identified in 23 cases (17.7%), 21 (91.0%) and 2 (9.0%) of which were type 41 and type 40, respectively. Fever was the most common clinical manifestation among adenovirus-positive patients. No significant difference was observed between adenovirus infection and clinical symptoms, seasonal pattern, or serum laboratory results. Co-infection was found in only 5 cases (21.7%). Conclusion: This study was the first to demonstrate adenovirus infection with a relatively high prevalence among children, especially infants, in Qom. The findings further revealed co-infection with rotavirus, indicating a health problem in this region.

Association between serum inflammatory parameters and the disease severity in COVID-19 patients.

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.

Following up of Surgical Treated Human Liver Cystic Echinococcosis: A Proteomics Approach.

BACKGROUND: Cystic echinococcosis (CE) is one of the most important parasitic zoonosis in the world. Post-surgery follow up in CE patients is an important non-solved problem up to now. Therefore, the investigations on this problematic issue would be very applicable in the view of CE clinical treatment. METHODS: A total of 24 confirmed liver CE patients sera including eight sera before surgery (BS), eight sera three months post-surgery (3MPS), and eight sera six months post-surgery (6MPS) were used in the present study. Proteomics methods including 2DE and LC-MS/MS were performed on the specimens followed by bioinformatics analysis such as Gene Ontology (GO) and Protein-Protein Interaction (PPI) network analysis. RESULTS: A total of 235 proteins were detected of which 12 differentially expressed proteins (DEP) were identified by LC-MS/MS in all sera. The proteins were presented in BS and suppressed after surgery as follows: HPX, SERPINA1, SERPINC1, CP, HBD, and HBA2. Comparisons of the protein expression in sera of patients BS, 3MPS, and 6MPS revealed that GC, IGJ, AHSG, CD5L, FGG, and APOC3 have been overexpressed in 3MPS and 6MPS. PPI network analysis demonstrated that SERPINC1 and AHSG with more connection in the network could be considered as hub proteins and potential prognostic biomarkers in response to surgical treatment of liver CE. CONCLUSION: Application of proteomics methods on patient's sera could be used as a novel biomarker tool for following-up liver CE patients. In this regards, proteomics and, application of bioinformatics analysis including GO and PPI showed that SERPINC1, AHSG and HPX are of more value as a potential follow up biomarkers in response to surgical treatment.

Exosomes and cancer: from molecular mechanisms to clinical applications.

Exosomes are extracellular nanovesicles secreted from almost all types of normal and cancer cells. Collective evidence suggests that exosomes participate in cell-cell communication via transmitting their cargo, including nucleic acids, proteins, and metabolites to recipient cells. Tumor-derived exosomes (TEXs) play prominent roles in the regulation of molecular pathways in malignancies. Internalization of exosomes by tumor cells affects cellular pathways and several cancer hallmarks, including reprogramming of stromal cells, modulating immune responses, reconstructing extracellular matrix architecture, or even endowing tumor cells with drug features resistance. The unique biogenesis pathways of exosomes, their composition, low immunogenicity, and nontoxicity, together with their ability to target tumor cells, bring them up as an attractive vesicles for cancer therapy. Thus, understanding the molecular mechanisms of exosomes' participation in tumorigenesis will be critical for the next generation of cancer therapeutics. This review aims to summarize the exosomes' roles in different mechanisms underlying cancer progression for the rational design of tailored strategies against this illness. The present study also highlights the new findings on using these smart vesicles as therapeutic targets and potential biomarkers. Recent advances in exosome biology will open up new, more effective, less invasive, and more individualized clinical applications for treating cancer patients.

Assessment of colon cancer molecular mechanism: a system biology approach.

AIM: The current study aimed to assess and compare colon cancer dysregulated genes from the GEO and STRING databases. BACKGROUND: Colorectal cancer is known as the third most common kind of cancer and the second most important reason for global cancer-related mortality rates. There have been many studies on the molecular mechanism of colon cancer. METHODS: From the STRING database, 100 differentially expressed proteins related to colon cancers were retrieved and analyzed by network analysis. The central nodes of the network were assessed by gene ontology. The findings were compared with a GSE from GEO. RESULTS: Based on data from the STRING database, TP53, EGFR, HRAS, MYC, AKT1, GAPDH, KRAS, ERBB2, PTEN, and VEGFA were identified as central genes. The central nodes were not included in the significant DEGs of the analyzed GSE. CONCLUSION: A combination of different database sources in system biology investigations provides useful information about the studied diseases.

The Principal Role of Several Members of HLA and IRF Genes in Prevention of Oral Mucositis After Chemoradiotherapy.

Introduction: One of the chemoradiotherapy (CRT) side effects is oral mucositis (OM). Since photobiomodulation therapy (PBMT) is a public method for the repair process, in the present study the mechanism of PBMT in the prevention of OM is investigated via the bioinformatics approach. Methods: Six validated and significant differentially expressed genes (DEGs) associated with the prevention of OM in head and neck cancer (HNC) patients who had experienced CRT were extracted from the literature. After adding 50 neighbors from STRING, the network was constructed and analyzed. The results of the action map and network analysis were compared and discussed. Results: HLA gene family were identified as central nodes of the analyzed network. Based on action map finding, activation is prominent action and IRF9 was the potent activator. The role of the IRF gene family was highlighted by action map analysis. Conclusion: Regulation of the immune system by HLA and IRF genes family is a crucial factor in the prevention of OM in the studied patients.

Distribution of Human Papillomavirus and Antisperm Antibody in Semen and Its Association with Semen Parameters Among Infertile Men.

BACKGROUND: Sexually transmitted infections (STIs) can be associated with infertility. Human papillomavirus (HPV) has been identified as a potential agent in male infertility. Also, anti-sperm antibodies (ASA) have been detected in men with infertility. The aim of this study was to investigate the prevalence and association of HPV and ASA in infected semen of infertile men. METHODS: This cross-sectional study was performed on 96 infertile men referring to infertility treatment center of Kashan University of Medical Sciences during March 2017 till September 2017 in Iran. Semen analysis and diagnostic PCR test were performed for detection of HPV DNA. The semen parameters in HPV infected and ASA positive samples were compared with HPV non-infected and ASA negative samples. Chi square test was used to determine the correlation between variables and p<0.05 was considered statistically significant. RESULTS: HPV DNA and ASA were detected in 17.4% and 15.2% of 96 semen samples, respectively. Semen volume, sperm count, sperm motility and the normal morphology rate were significantly decreased in HPV-positive subjects (p=0.004, p= 0.016, p<0.001, and p=0.017, respectively). Also, sperm motility was significantly decreased in ASA-positive subjects (p=0.002), also patients with HPV infection had a higher rate of ASA than the non-HPV group. In contrast to ASA, HPV infection had a significant correlation with education level (p=0.039). CONCLUSION: The findings suggest that asymptomatic seminal infection of HPV and ASA by adversely affecting sperm quality, in particular sperm motility and count, may play an important role in male infertility.

Prevalence of astrovirus, adenovirus, and sapovirus infections among Iranian children with acute gastroenteritis.

AIM: This study aimed to determine the prevalence of Human Astroviruses (HAstVs), enteric Adenoviruses (HAdVs), and Sapoviruses (SaVs) in acute diarrhea patients, as well as their relation to age, sex, and season. BACKGROUND: Acute gastroenteritis is one of the most common diseases affecting children <5 years old and viral agents with approximately >75% are the major causative agent of acute infectious diarrhea. After Rotavirus and Norovirus, the greater viral agents of acute gastroenteritis include HAstVs, HAdVs, and SaVs. To the best of our knowledge, there are sparse studies in Iran detecting at least three enteric viruses as causative agents of diarrhea simultaneously. METHODS: The sample was collected from children referring to pediatric medical centers in Tehran, Iran; they were tested for Astrovirus, enteric Adenovirus, and Sapovirus by conventional PCR method. The association of incidence of viral enteric agents was evaluated with age, sex and seasonal pattern in children <5 years old. RESULTS: The positive case number among acute gastroenteritis patients was 17/120 (14.1%). Patients ranged in age within 1-60 months, but 52.9% were aged ≤ 12 months. Males comprised the majority (70.6), and the male: female ratio was 2.4. HAstV was the most frequently detected virus (6.7%), while SaVs were detected only in 2.5% of cases. Mixed infections were not detected in these samples. The highest rate of HAstV was identified in winter (66.7%), HAdV in fall (66.7%), and SaV in winter (33.3%). CONCLUSION: These findings underscore the importance of monitoring the epidemiology of HAstV, HAdV, and SaV as causative agents of viral diarrhea infections.

The Highlighted Role of GAPDH and Nitric-Oxide Synthase Regulator Activity in Proton Beam Irradiated Melanoma BLM Cells.

Introduction: The human melanoma is a type of invasive tumor the treatment of which is challenging. To better understand the proton irradiation mechanisms as one of the widely applied therapy for this type of cancer, bioinformatics analysis of proteomics outcome could be beneficial. Methods: Protein-protein interaction network analysis of the differentially expressed proteins (DEPs) of melanoma BLM (BRO lung metastasis) cells in the treatment of 3 Gy dosage proton therapy was performed in this study via Cytoscape V.3.7.2. and its integrated plug-ins. Results: Eighteen DEPs were searched for network constructions and limited numbers of query +neighbor proteins were found central. The hub-bottlenecks (i.e. central nodes) were GAPDH, ACTB, ALB, AKT1, TP53, and EGFR. The fist mentioned proteins were from DEPs. The enrichment analysis of these elements identified nitric-oxide synthase regulator activity and the positive regulation of the norepinephrine uptake that may be the key to the mechanisms of proton therapy. Conclusion: In conclusion, the identified central nodes (EGFR, TP53, ALB, AKT1, GAPDH, and ACTB) and the related biological terms are the critical affected genes and biological terms in the irradiated melanoma cells.

Resveratrol: A miraculous natural compound for diseases treatment.

Resveratrol (3, 5, 4'-trihydroxystilbene) is a nonflavonoid polyphenol that naturally occurs as phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, and peanut. This compound has critical roles in human health and is well known for its diverse biological activities such as antioxidant and anti-inflammatory properties. Nowadays, due to rising incidence of different diseases such as cancer and diabetes, efforts to find novel and effective disease-protective agents have led to the identification of plant-derived compounds such as resveratrol. Furthermore, several in vitro and in vivo studies have revealed the effectiveness of resveratrol in various diseases such as diabetes mellitus, cardiovascular disease, metabolic syndrome, obesity, inflammatory, neurodegenerative, and age-related diseases. This review presents an overview of currently available studies on preventive properties and essential molecular mechanisms involved in various diseases.

Pancreatic adenocarcinoma protein-protein interaction network analysis.

AIM: Gene assessment of pancreatic adenocarcinoma disease via protein-protein interaction (PPI) Network Analysis. BACKGROUND: Diagnosis, especially early detection of pancreatic adenocarcinoma as a lethal disease implies more investigation. PPI Network Analysis is a suitable tool to discover new aspects of molecular mechanism of diseases. METHODS: In the present study the related genes to pancreatic adenocarcinoma are studied in the interactome unit and the key genes are highlighted. The significant clusters were introduced by Cluster-ONE application of Cytoscape software 3.4.0. The genes are retrieved from STRING date base and analyzed by Cytoscape software. The crucial genes based on analysis of central parameters were determined and enriched by ClueGO v2.3.5 via gene ontology. RESULTS: The number of 24 key genes among 794 initial genes were highlighted as crucial nodes in relationship with pancreatic adenocarcinoma. All of the key genes were organized in a cluster including 216 nodes. The main related pathways and cancer diseases were determined. CONCLUSION: It was concluded that the introduced 24 genes are possible biomarker panel of pancreatic adenocarcinoma.