Association between colorectal cancer, the frequency of Bacteroides fragilis, and the level of mismatch repair genes expression in the biopsy samples of Iranian patients.

BACKGROUND: Deficient DNA mismatch repair (MMR) can cause microsatellite instability (MSI) and is more common in colorectal cancer (CRC) patients. Understanding the carcinogenic mechanism of bacteria and their impact on cancer cells is crucial. Bacteroides fragilis (B. fragilis) has been identified as a potential promoter of tumorigenesis through the alteration of signaling pathways. This study aims to assess the expression levels of msh2, msh6, mlh1, and the relative frequency of B. fragilis in biopsy samples from CRC patients. MATERIALS AND METHODS: Based on the sequence of mlh1, msh2, and msh6 genes, B. fragilis specific 16srRNA and bacterial universal 16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: Significant increases in the expression levels of mlh1, msh2, and msh6 genes were observed in the cancer group. Additionally, the expression of these MMR genes showed a significant elevation in samples positive for B. fragilis presence. The relative frequency of B. fragilis in the cancer group demonstrated a significant rise compared to the control group. CONCLUSION: The findings suggest a potential correlation between the abundance of B. fragilis and alterations in the expression of MMR genes. Since these genes can play a role in modifying colon cancer, investigating microbial characteristics and gene expression changes in CRC could offer a viable solution for CRC diagnosis.

Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients.

BACKGROUND: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. METHOD: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. CONCLUSION: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.

Wharton's jelly-mesenchymal stem cells treatment for severe COVID 19 patients: 1-year follow-up.

Background: Recently, attention has been focused on mesenchymal stem cells (MSC) because of their unique ability to suppress inflammation induced by cytokine storms caused by COVID-19. Several patients have been successfully treated in this manner. After one year of treatment with Wharton's jelly-derived MSC injections, this study evaluated the safety and efficacy of injecting MSCs intravenously in patients with COVID-19. Methods: This study treated four patients with severe COVID-19 with Wharton's jelly-derived mesenchymal stem cells. In this study, patients were followed up for routine tests, tumor markers, and whole-body imaging (spiral neck CT scan (with contrast), spiral chest CT scan (with & without contrast), and spiral abdominopelvic CT scan (with IV & Oral contrast)) one year after cell therapy. Results: The results indicated that lymphocyte; lymph count significantly increased, and neutrophil, ESR, ferritin, and CRP significantly decreased. LDH showed a non-significant decrease (P-value<0.05). One year after the WJ-MSC injection, the tumor markers were normal, and no tumors were observed in patients after one year. Also, the CT scan result was normal. Conclusions: In patients, no serious complications were observed after a one-year follow-up. After monitoring the patient via laboratory tests, tumor markers, and whole-body imaging, we concluded that the Wharton jelly-derived mesenchymal stem cells did not cause severe complications, including tumor formation, in severe COVID19 patients within a year. More clinical trials with higher sample sizes need to be performed on cell therapy with Wharton jelly-derived mesenchymal stem cells in the future.

Evaluation of the histopathologic status of rectal adenocarcinoma and its regional lymph nodes after neoadjuvant therapy, and its relation to the duration of disease-free survival.

INTRODUCTION: Colorectal cancer is one of the most common malignant tumors and has a relatively poor prognosis. Lymph node involvement is considered the most important prognostic factor. MATERIALS AND METHODS: During a retrospective cohort study, 132 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from 2010 to 2015 in Sina hospital were reviewed. RESULTS: Multivariable analysis was performed and shown the clinical stage was not a representative factor for disease-free survival (P = 0.187), but Dworak Tumor Regression Grading were significantly associated with higher disease-free survival (P = 0.000) in stage II and stage III. The total number of retrieved lymph nodes and involved lymph nodes in the same clinical stage were statistically associated with higher mean disease-free survival in patients (P = 0.000 in both conditions). CONCLUSION: In the same clinical stage, increasing the Dworak Tumor Regression Grading reduced the risk of rectal cancer recurrence. Increasing total number of retrieved lymph nodes and involved lymph nodes, 2.14 times and 3.87 times increased the risk of recurrence, respectively.

Therapeutic approach of adipose-derived mesenchymal stem cells in refractory peptic ulcer.

Peptic ulcer is one of the most common gastrointestinal tract disorders worldwide, associated with challenges such as refractory morbidity, bleeding, interference with use of anticoagulants, and potential side effects associated with long-term use of proton pump inhibitors. A peptic ulcer is a defect in gastric or duodenal mucosa extending from muscularis mucosa to deeper layers of the stomach wall. In most cases, ulcers respond to standard treatments. However, in some people, peptic ulcer becomes resistant to conventional treatment or recurs after initially successful therapy. Therefore, new and safe treatments, including the use of stem cells, are highly favored for these patients. Adipose-derived mesenchymal stem cells are readily available in large quantities with minimal invasive intervention, and isolation of adipose-derived mesenchymal stromal stem cells (ASC) produces large amounts of stem cells, which are essential for cell-based and restorative therapies. These cells have high flexibility and can differentiate into several types of cells in vitro. This article will investigate the effects and possible mechanisms and signaling pathways of adipose tissue-derived mesenchymal stem cells in patients with refractory peptic ulcers.

Clinical and laboratory findings and PCR results in severe and non-severe COVID19 patients based on CURB-65 and WHO severity indices.

BACKGROUND: The importance of clinicolaboratory characteristics of COVID-19 made us report our findings in the Alborz province according to the latest National Guideline for the diagnosis and treatment of COVID-19 in outpatients and inpatients (trial five versions, 25 March 2020) of Iran by emphasizing rRT-PCR results, clinical features, comorbidities, and other laboratory findings in patients according to the severity of the disease. METHODS: In this study, 202 patients were included, primarily of whom 164 had fulfilled the inclusion criteria. This cross-sectional, two-center study that involved 164 symptomatic adults hospitalized with the diagnosis of COVID-19 between March 5 and April 5, 2020, was performed to analyze the frequency of rRT-PCR results, distribution of comorbidities, and initial clinicolaboratory data in severe and non-severe cases, comparing the compatibility of two methods for categorizing the severity of the disease. RESULTS: According to our findings, 111 patients were rRT-PCR positive (67.6%), and 53 were rRT-PCR negative (32.4%), indicating no significant difference between severity groups that were not related to the date of symptoms' onset before admission. Based on the National Guideline, among vital signs and symptoms, mean oxygen saturation and frequency of nausea showed a significant difference between the two groups (P < 0.05); however, no significant difference was observed in comorbidities. In CURB-65 groups, among vital signs and comorbidities, mean oxygen saturation, diabetes, hypertension (HTN), hyperlipidemia, chronic heart disease (CHD), and asthma showed a significant difference between the two groups (P < 0.05), but no significant difference was seen in symptoms. CONCLUSION: In this study, rRT-PCR results of hospitalized patients with COVID-19 were not related to severity categories. From initial clinical characteristics, decreased oxygen saturation appears to be a more common abnormality in severe and non-severe categories. National Guideline indices seem to be more comprehensive to categorize patients in severity groups than CURB-65, and there was compatibility just in non-severe groups of National Guideline and CURB-65 categories.

Effect of omega-3 and vitamin D co-supplementation on psychological distress in reproductive-aged women with pre-diabetes and hypovitaminosis D: A randomized controlled trial.

PURPOSE: Psychological distresses and pre-diabetes are among the risk factors of developing type-II diabetes. The present study was conducted to determine the effectiveness of omega-3 and vitamin D co-supplementation on psychological distresses in women of reproductive age with pre-diabetes and hypovitaminosis D. METHODS: The present factorial clinical trial was conducted on 168 women of reproductive age with pre-diabetes and hypovitaminosis D. These participants were selected by stratified random sampling and were assigned to four groups for 8 weeks: group 1 (placebo group), group 2 (omega-3 group), group 3 (vitamin D group), and group 4 (co-supplement group). The medication and placebo doses being two 1000-mg tablets each day for omega-3 and 50,000-IU pearls every 2 weeks for vitamin D. Fasting blood glucose and vitamin D were measured at the beginning of the study. The Depression Anxiety Stress Scale-21 and the Pittsburgh Sleep Quality Index were completed by the participants at the start and end of the intervention. RESULTS: A significant difference was observed in terms of reduction in anxiety and improvement in sleep quality in the co-supplementation compared to the other three groups (p < .05). There was also a significant difference between the group receiving both supplements and the group receiving only placebos in terms of reduction in depression and stress (p < .05). CONCLUSION: Vitamin D and omega-3 co-supplementation improved depression, anxiety, and sleep quality in women of reproductive age with pre-diabetes and hypovitaminosis D. Therefore, these two supplements can be recommended for improving the mental health of this group of women. CLINICAL TRIAL REGISTRY: Iranian Registry of Clinical Trials Code: IRCT20100130003226N17. Registered on February 9, 2019.

Cell therapy in patients with COVID-19 using Wharton's jelly mesenchymal stem cells: a phase 1 clinical trial.

BACKGROUND: Mesenchymal stem cells (MSCs) have received particular attention because of their ability to modulate the immune system and inhibit inflammation caused by cytokine storms due to SARS-CoV-2. New alternative therapies may reduce mortality rates in patients with COVID19. This study aimed to assess the safety and efficacy of injecting intravenous Wharton's jelly-derived MSCs in patients with COVID-19 as a treatment. METHODS: In this study, five patients with severe COVID-19 were treated with Wharton's jelly-derived mesenchymal stem cells (150 × 106 cells per injection). These patients were subject to three intravenous injections 3 days apart, and monitoring was done on days 0, 3, 6, and 14 in routine tests, inflammatory cytokines, and flow cytometry of CD4 and CD8 markers. A lung CT scan was performed on base and days 14 and 28. In addition, IgM and IgG antibodies against SARS-CoV-2 were measured before and after treatment. RESULTS: The results showed that IL-10 and SDF-1 increased after cell therapy, but VEGF, TGF-ß, IFN-γ, IL-6, and TNFα decreased. Routine hematology tests, myocardial enzyme tests, biochemical tests, and inflammation tests were performed for all patients before and after cell therapy on base and days 3, 6, and 14, which indicated the improvement of test results over time. COVID-19 antibody tests rose in 14 days after WJ-MSC injection. The total score of zonal involvement in both lungs was improved. CONCLUSIONS: In patients, the trend of tests was generally improving, and we experienced a reduction in inflammation. No serious complications were observed in patients except the headache in one of them, which was resolved without medication. In this study, we found that patients with severe COVID-19 in the inflammatory phase respond better to cell therapy. More extensive clinical trials should be performed in this regard. TRIAL REGISTRATION: IRCT, IRCT20190717044241N2 . Registered April 22, 2020.

Clinical and laboratory findings in COVID-19 adult hospitalized patients from Alborz province / Iran: comparison of rRT-PCR positive and negative.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was emergency turned into global public health after the first patients were detected in Wuhan, China, in December 2019. The disease rapidly expanded and led to an epidemic throughout China, followed by the rising number of cases worldwide. Given the high prevalence of COVID-19, rapid and accurate diagnostic methods are immediately needed to identify, isolate and treat the patients as soon as possible, decreasing mortality rates and the risk of public contamination by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). METHODS: This case-control study was conducted in two hospitals in Alborz Province in Iran. All recruited cases in this study were symptomatic adults hospitalized as COVID-19 patients with compatible Computed tomographic (CT) scan findings and available rRT-PCR results. The patients were recruited in this study. The patients were categorized into positive and negative rRT-PCR groups and evaluated for symptoms, initial vital signs, comorbidity, clinical and laboratory findings. Finally, the results were assessed by SPSS software. RESULTS: Between March 5 to April 5, 2020, 164 symptomatic COVID-19 patients were studied. In total, there were 111 rRT-PCR positive (67.6%) and 53 rRT-PCR negative patients (32.4%). In terms of statistics, the frequency of symptoms revealed no difference, except for cough (P.V:0.008), dizziness (PV: 0.048), and weakness (P.V:0.022). Among initial vital signs, PR (P.V:0.041) and O2 Saturation (PV: 0.014) were statistically different between the two groups. Evaluation of comorbidities revealed no difference except for hyperlipidemia (P.V:0.024). In the comparison of laboratory findings, only WBC count (PV: 0.001), lymphocyte count (PV: 0.001), and Hb (P.V:0.008) were statistically different between the two groups. CONCLUSION: In case of the negative rRT-PCR result, it is necessary to take a logical approach, and we recommended that the physician decides according to clinical manifestations, laboratory findings, and positive CT results.

Perspective of placenta derived mesenchymal stem cells in acute liver failure.

Acute Liver failure (ALF) is a life-threatening disease and is determined by coagulopathy (with INR ≥ 1.5) and hepatic encephalopathy as a result of severe liver injury in patients without preexisting liver disease. Since there are problems with liver transplantation including lack of donors, use of immunosuppressive drugs, and high costs of this process, new therapeutic approaches alongside current treatments are needed. The placenta is a tissue that is normally discarded after childbirth. On the other hand, human placenta is a rich source of mesenchymal stem cells (MSCs), which is easily available, without moral problems, and its derived cells are less affected by age and environmental factors. Therefore, placenta-derived mesenchymal stem cells (PD-MSCs) can be considered as an allogeneic source for liver disease. Considering the studies on MSCs and their effects on various diseases, it can be stated that MSCs are among the most important agents to be used for novel future therapies of liver diseases. In this paper, we will investigate the effects of mesenchymal stem cells through migration and immigration to the site of injury, cell-to-cell contact, immunomodulatory effects, and secretory factors in ALF.

The effect of omega-3 and vitamin D co-supplementation on glycemic control and lipid profiles in reproductive-aged women with pre-diabetes and hypovitaminosis D: a randomized controlled trial.

BACKGROUND: Prediabetes can predispose the individual to type 2 diabetes in the long-term. The present study was conducted to determine the effectiveness of vitamin D and omega-3 co-supplementation on glycemic control and serum lipid profiles in women of reproductive age with prediabetes and hypovitaminosis D. METHODS: The present factorial, triple-blind, clinical trial was conducted on 168 women of reproductive age with prediabetes and hypovitaminosis D. The participants were assigned to four groups based on block randomization method: the placebo group received omega-3 and vitamin D placebos; the omega-3 group took omega-3 supplements and vitamin D placebos; the vitamin D group received omega-3 placebos and vitamin D supplements and the co-supplementation group. The groups received every 2 weeks 50,000 IU pearls of vitamin D and twice-daily doses of 1000-mg omega-3 tablets or placebos for 8 weeks. Dietary intake, physical activity, anthropometric indices and blood biochemical tests were measured at the beginning and end of the study. Analysis was performed using two-way mixed ANOVA. RESULTS: A significant reduction was observed in fasting glucose, insulin, homeostasis model assessment-beta cell function, weight and waist circumference in the co-supplementation group compared to the other three groups (P < 0.05). Moreover, high-density lipoprotein-cholesterol levels increased significantly in the co-supplementation group compared to the other three groups (P < 0.05). Despite the fact that homeostasis model assessment-insulin resistance, total cholesterol, triglyceride and low-density lipoprotein-cholesterol levels decreased after intervention in the co-supplementation group, there was no significant difference between the groups in these outcomes. CONCLUSION: Vitamin D and omega-3 co-supplementation improved fasting serum glucose, insulin, high-density lipoprotein-cholesterol level, homeostasis model assessment-beta cell function, weight and waist circumference in women of reproductive age with prediabetes and hypovitaminosis D. This co-supplementation can therefore be recommended for glycemic control in these women.Trial registration Iranian Registry of Clinical Trials Code: IRCT20100130003226N17. Registered on 9 Feb. 2019.

The effect of co supplementation of omega-3 and vitamin D on cardio metabolic risk factors and psychological distress in reproductive-aged women with prediabetes and hypovitaminosis D: a study protocol for a randomized controlled trial.

BACKGROUND: A prediabetic state is a risk factor for type 2 diabetes. There are no approved drugs to manage prediabetes. Among the supplements routinely used by individuals, vitamin D and omega-3 have been studied to reduce fasting blood sugar. However, their co-supplementation has not been studied in individuals with prediabetes. This randomized controlled trial is designed to determine the effects of these two supplements on fasting blood sugar, other cardio metabolic risk factors, and psychological distress in reproductive-aged women with prediabetes and hypovitaminosis D. METHODS/DESIGN: This 2 × 2 factorial, triple-blind, randomized, placebo-controlled, clinical trial will be done on 168 women of reproductive age diagnosed with prediabetes and hypovitaminosis D. Participants will be randomly assigned equally to four groups: (1) 1000 mg omega-3 fatty acid twice a day + vitamin D placebo every two weeks; (2) omega-3 fatty acid placebo twice a day + 50,000 IU vitamin D every two weeks; (3) 1000 mg omega-3 fatty acid twice a day + 50,000 IU vitamin D every two weeks; (4) omega-3 fatty acid placebo twice a day + vitamin D placebo every two weeks for eight weeks. At the beginning, participants will provide a self-reported questionnaire on the sociodemographic characteristics. At baseline and post-intervention visits, physical activity, Depression Anxiety Stress Scale 21 and Pittsburgh Sleep Quality Index, and a three-day food record will be collected for each individual. Blood pressure, weight, height, and waist circumference will also be measured. At the beginning and at the end, a blood sample will be used for estimating serum glucose indices (fasting blood sugar and insulin, homeostasis model assessment-insulin resistance, homeostasis model assessment-beta cell function), lipids (triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol), and vitamin D status. Data analysis using Kolmogorov-Smirnov test, paired t-test, one-way analysis of variance, and repeated measures analysis of variance will be conducted through SPSS-24 software. DISCUSSION: The primary aim of the present trial is to determine the effect of vitamin D and/or omega-3 on glycemic indices, lipid profiles, psychological distress, blood pressure, and anthropometric indices in prediabetic women with hypovitaminosis D. The results from this trial will provide evidence on the efficacy of these two supplements for preventing or delaying the onset of type 2 diabetes in high-risk individuals. TRIAL REGISTRATION: Iran Clinical Trials Registry, IRCT20100130003226N17. Registered on 9 February 2019.