The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Although a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its beneficial health effects. Hence, the purpose of this study was to examine the effect of acarbose on inflammatory cytokines and adipokines in adults. METHODS: PubMed, Web of Science, and Scopus were systematically searched until April 2023 using relevant keywords. The mean difference (MD) of any effect was calculated using a random-effects model. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated via the random-effects model. RESULTS: The current meta-analysis of data comprised a total of 19 RCTs. Meta-analysis showed that acarbose significantly decreased tumor necrosis factor-alpha (TNF-α) (weighted mean difference [WMD]) = - 4.16 pg/ml, 95% confidence interval (CI) - 6.58, - 1.74; P = 0.001) while increasing adiponectin (WMD = 0.79 ng/ml, 95% CI 0.02, 1.55; P = 0.044). However, the effects of acarbose on TNF-α concentrations were observed in studies with intervention doses ≥ 300 mg/d (WMD = - 4.09; 95% CI - 7.00, - 1.18; P = 0.006), and the adiponectin concentrations were significantly higher (WMD = 1.03 ng/ml, 95%CI 0.19, 1.87; P = 0.016) in studies in which the duration of intervention was less than 24 weeks. No significant effect was seen for C-reactive protein (CRP; P = 0.134), interleukin-6 (IL-6; P = 0.204), and leptin (P = 0.576). CONCLUSION: Acarbose had beneficial effects on reducing inflammation and increasing adiponectin. In this way, it may prevent the development of chronic diseases related to inflammation. However, more studies are needed.

Frailty syndrome in women with osteoporosis, should physicians consider screening? A cross-sectional study.

Despite its high prevalence and profound impact, frailty syndrome often goes undiagnosed. The study revealed a significant correlation between osteoporosis and frailty syndrome, with predictive accuracy exceeding 75 %. Given these findings and the existing recommendation for osteoporosis screening in older women, we underscore the importance of concurrently screening osteoporotic women for frailty. Introduction: Frailty syndrome, a prevalent and significant geriatric condition, impacts healthcare costs and quality of life. Previous reviews have associated frailty syndrome with osteoporosis, but original research on this link is limited and has produced conflicting results. This study aims to investigate the relationship between frailty syndrome, osteoporosis, bone mineral densitometry T-score, and other influencing factors. Methods: In this cross-sectional study, post-menopausal women underwent screening for osteoporosis and frailty syndrome using bone mineral densitometry and the Fried phenotype. Exclusion criteria included a history of diseases related to bone loss or medications affecting bone metabolism. Bivariate and multivariable tests were used to examine the correlation between frailty syndrome and various covariates, including the diagnosis of osteoporosis. Results: A total of 272 women aged 60 to 89 years (mean age 68.57 ± 6.22) were evaluated. Osteoporosis was prevalent in 44.9 % of participants, and frailty syndrome was identified in 36.4 %. The regression model identified age, menopausal age, and the diagnosis of osteoporosis as variables significantly and independently associated with frailty syndrome. A T-score lower than -2.5 in the femur neck or lumbar spine exhibited a sensitivity of 86.6 % and specificity of 76.5 % in predicting frailty syndrome. Conclusion: Older adults with osteoporosis face an increased risk of frailty syndrome. Therefore, we recommend that primary care providers screen osteoporotic women for frailty syndrome and, when appropriate, refer this group to geriatric specialists for further evaluation.

Inflammatory and metabolic markers and comorbidities remission following sleeve gastrectomy: A single center one-year cohort study.

BACKGROUND AND AIM: Obesity is a global concern with several health-related complications. Bariatric surgeries are major treatment options in patients with obesity and other comorbidities. This study aims to investigate the effects of sleeve gastrectomy on metabolic indexes, hyperechogenic liver changes, inflammatory state, diabetes, and other obesity-related comorbidities remission after the sleeve gastrectomy. METHODS: This prospective study was conducted on patients with obesity candidates for laparoscopic sleeve gastrectomy. Patients were followed for one year after the surgery. Comorbidities, metabolic and inflammatory parameters were assessed before and one- year after the surgery. RESULTS: 137 patients (16 males, 44 in the DM group) underwent sleeve gastrectomy. One year after the study, obesity-related comorbidities improved significantly; diabetes had complete remission in 22.7% and partial remission in 63.6% of patients. Hyper-cholesterolemia, hyper-triglyceridemia, and hyper-uricemia also improved in 45.6%, 91.2%, and 69% of the patients. Metabolic syndrome indexes improved in 17.5% of the patients. Also, the prevalence of hyperechogenic changes in the liver has declined from 21% before the surgery to 1.5% after that. Based on logistic regression analysis, increased levels of HbA1C reduced the chance of diabetes remission by 0.9%. In comparison, every unit of increased BMI before the surgery improved the case of diabetes remission by 16%. CONCLUSION: Laparoscopic sleeve gastrectomy is a safe and effective treatment option in patients with obesity and diabetes. Laparoscopic sleeve gastrectomy alleviates BMI and insulin resistance and effectively improves other obesity-related comorbidities such as Hypercholesterolemia, hyper-triglyceridemia, hyper-uricemia, and hyperechogenic changes of the liver. HbA1C and BMI before the surgery are notable predictors of diabetes remission within the first year after the surgery.

Variations of SARS-CoV-2 in the Iranian population and candidate putative drug-like compounds to inhibit the mutated proteins.

The first cases of the novel coronavirus, SARS-CoV-2, were detected in December 2019 in Wuhan, China. Nucleotide substitutions and mutations in the SARS-CoV-2 sequence can result in the evolution of the virus and its rapid spread across the world. Therefore, understanding genetic variants of SARS-CoV-2 and targeting the conserved elements responsible for viral replication have great benefits for detecting its infection sources and diagnosing and treating COVID-19. In this study, we used the SARS-CoV-2 sequence isolated from a 59-year-old man in Ardabil, Iran, in April 2020 and sequenced using Oxford Nanopore technology. A meta-analysis comparing the sequence under study with other sequences from Iran indicated long nucleotide insertions/deletions (indels) that code for NSP15, the NSP14-NSP10 complex, open reading frame ORF9b, and ORF1ab polyproteins. In addition, replicating the NSP8 protein in the study sequence is another topic that can affect viral replication. Then using the DNA structure of NSP8, NSP15, NSP14-NSP10 complex, and ORF1ab as a genetic target can help find drug-like compounds for COVID-19. Potential drug-like compounds reported in this study for their mechanism of action and interactions with SARS-CoV-2 genes using drug repurposing are resveratrol, erythromycin, chloramphenicol, indomethacin, ciclesonide, and PDE4 inhibitor. Ciclesonide appears to show the best results when docked with chosen viral proteins. Therefore, different proteins isolated from nucleotide mutations in the virus sequence can indicate distinct inducers for antibodies and are important in vaccine design.

A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer.

Breast cancer (BC) is a major human health problem due to its increasing incidence and mortality rate. CC and CXC chemokines are associated with tumorigenesis and the progression of many cancers. Since the prognostic values of CC and CXC families' expression in various types of cancers are becoming increasingly evident, we aimed to conduct a comprehensive bioinformatics analysis elucidating the prognostic values of the CC and CXC families in BC. Therefore, TCGA, UALCAN, Kaplan-Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER were utilized for analysis. We found that high levels of CCL4/5/14/19/21/22 were associated with better OS and RFS, while elevated expression of CCL24 was correlated with shorter OS in BC patients. Also, high levels of CXCL9/13 indicated longer OS, and enhanced expression of CXCL12/14 was linked with better OS and RFS in BC patients. Meanwhile, increased transcription levels of CXCL8 were associated with worse OS and RFS in BC patients. In addition, our results showed that CCL5, CCL8, CCL14, CCL20, CCL27, CXCL4, and CXCL14 were notably correlated with the clinical outcomes of BC patients. Our findings provide a new point of view that may help the clinical application of CC and CXC chemokines as prognostic biomarkers in BC.

Cellular stress response to extremely low-frequency electromagnetic fields (ELF-EMF): An explanation for controversial effects of ELF-EMF on apoptosis.

Impaired apoptosis is one of the hallmarks of cancer, and almost all of the non-surgical approaches of eradicating tumour cells somehow promote induction of apoptosis. Indeed, numerous studies have stated that non-ionizing non-thermal extremely low-frequency magnetic fields (ELF-MF) can modulate the induction of apoptosis in exposed cells; however, much controversy exists in observations. When cells are exposed to ELF-EMF alone, very low or no statistically significant changes in apoptosis are observed. Contrarily, exposure to ELF-EMF in the presence of a co-stressor, including a chemotherapeutic agent or ionizing radiation, can either potentiate or inhibit apoptotic effects of the co-stressor. In our idea, the main point neglected in interpreting these discrepancies is "the cellular stress responses" of cells following ELF-EMF exposure and its interplay with apoptosis. The main purpose of the current review was to outline the triangle of ELF-EMF, the cellular stress response of cells and apoptosis and to interpret and unify discrepancies in results based on it. Therefore, initially, we will describe studies performed on identifying the effect of ELF-EMF on induction/inhibition of apoptosis and enumerate proposed pathways through which ELF-EMF exposure may affect apoptosis; then, we will explain cellular stress response and cues for its induction in response to ELF-EMF exposure; and finally, we will explain why such controversies have been observed by different investigators.

Anti-cancer impact of Hypericin in B-CPAP cells: Extrinsic caspase dependent apoptosis induction and metastasis obstruction.

Thyroid cancer is the most common type of endocrine-related cancer. According to the literature, its incidence is not very high, but its rate increasing especially in developed countries. With this regard, finding approaches to prevent, and exert anti-tumor activity with the least side effects on the normal cells at the next step after diagnosis is demanded. Herbal medicine is a branch of integrative oncology that seems to be a practically beneficial goddess for cancer treatment in many cases. Here we utilized Hypericin (HYP) to investigate its anti-tumor (apoptotic and anti-metastatic) activity on B-CPAP (a thyroid cancer cell line) and cytotoxicity on TPC-1 (thyroid cancer cell line with wild type TP53) cell lines. To assess whether HYP may exert preventive and anti-tumor effects and does not have a potential side effect, we dubbed the experiments on the fibroblast cells (as a normal cell line). Cytotoxicity and kind of cellular death were examined by MTT and AnnexinV/PI respectively. Extrinsic/intrinsic apoptosis pathway induction was clarified by western blotting on pro/cleaved caspases 9, 8, and 3. According to our data HYP induces an extrinsic apoptosis pathway and no other types (necroptosis, necrosis, etc.) in B-CPAP cells. Moreover, CDH1 mRNA expression calculated to be up-regulated, and that of LGALS3 down-regulated in the B-CPAP cell line after treatment. Besides tumor cytotoxic activity, we suggest that HYP impedes with invasion and/or metastasis process.

Integration of gene expression data identifies key genes and pathways in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumor and prevalent cause of cancer-related death worldwide. In this study, we analyzed the gene expression profiles of patients with CRC with the aim of better understanding the molecular mechanism and key genes in CRC. Four gene expression profiles including, GSE9348, GSE41328, GSE41657, and GSE113513 were downloaded from GEO database. The data were processed using R programming language, in which 319 common differentially expressed genes including 94 up-regulated and 225 down-regulated were identified. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were conducted to find the most significant enriched pathways in CRC. Based on the GO and KEGG pathway analysis, the most important dysregulated pathways were regulation of cell proliferation, biocarbonate transport, Wnt, and IL-17 signaling pathways, and nitrogen metabolism. The protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape software and hub genes including MYC, CXCL1, CD44, MMP1, and CXCL12 were identified as the most critical hub genes. The present study enhances our understanding of the molecular mechanisms of the CRC, which might potentially be applied in the treatment strategies of CRC as molecular targets and diagnostic biomarkers.

Transcriptome analysis evinces anti-neoplastic mechanisms of hypericin: A study on U87 glioblastoma cell line.

AIMS: Hypericin (HYP) from Hypericum perforatum has cytotoxic effects on a variety of malignant cell types, but the pattern of gene expression mediating the effect is largely unknown. Here we sought to analyze the response of U87 glioblastoma (GBM) cell lines in response to HYP. MATERIALS AND METHODS: U87 cell line was treated by HYP. Cytotoxicity was assessed using MTT and Annexin V/PI assays. Gene expression profile was obtained using high-throughput sequencing. Enrichment analysis was performed on differentially expressed genes (DEGs). Upstream transcription factors and microRNAs regulating DEGs were predicted. The effects of DEGs on survival of GBM patients were calculated. Protein-protein interaction analysis was conducted to obtain key altered genes. The possible effect of HYP treatment on immunity response was evaluated. KEY FINDINGS: The IC50 of HYP on U87 cell line was determined to be 1.5 µg/ml. The main type of cell death was apoptosis. A total of 312 DEGs were found. Affected Gene Ontology terms and pathways were identified. Analysis of upstream modulators of DEGs pointed out to transcription factors that significantly overlap with GBM stem cell transcription factor. Survival analysis suggested that HYP works best for the mesenchymal subtype patients. Tumor infiltration analysis predicted that HYP may affect Treg and macrophage infiltration in vivo. Using expression pattern of GBM patients and HYP-induced DEGs we suggested Fedratinib as a complementary drug to HYP. SIGNIFICANCE: Our study represents the response of U87 cell line to HYP, with analyses on survival, transcription factors and personalization according to GBM subtype.

Hypericin Induces Apoptosis in AGS Cell Line with No Significant Effect on Normal Cells.

It is of great importance to find an effective approach that not only eliminates gastric cancer cells but also do exhibits significant side effect to normal cells. Some studies have shown the effectiveness of hypericin against cancer cells. In this study, we evaluated the anti-cancer effect of Hypericin in the treatment of gastric cancer. In this study, the AGS cell line was exposed to different concentrations of hypericin for 24 and 48 h. Evaluation of cell death was done by MTT assay. The rate of apoptosis was measured by flow cytometry assay using Annexin V/ Propidium Iodide. The expression rate of Bcl2, p53 and Bax genes was evaluated by Real-time PCR test, and immunocytochemistry (ICC) analysis and western blotting was used for further evaluation of p53. MTT assay test showed that hyepricin induces 50% cell death in the concentration of 1 (µg/mL) and 0.5 (µg/mL) at 24 h and 48 h post-treatment, respectively, however no similar effect seen on fibroblast cells. Annexin/PI test revealed that cell apoptosis after exposure to hypericin for 24 h was 74%. Real-time PCR showed that expression level of Bax, p53 and Bax genes increases and Bcl2 gene decreases in AGS cell lines after treatment by hypericin. ICC analysis and western blotting for p53 confirmed these data. The results of this study indicated that hypericin has the potential to be introduced as an effective treatment for gastric cancer. Therefore, it seems that this substance has potential to be utilized as anti-cancer drug.

Effect of chronic methamphetamine injection on levels of BDNF mRNA and its CpG island methylation in prefrontal cortex of rats.

Methamphetamine (METH) is a highly addictive psychostimulant. Its abuse causes problems in cognition, attention, or psychiatric conditions such as psychosis. Prefrontal cortex is involved in many aspects of drug addiction and in mental disorders similar to those triggered by METH. Brain-derived neurotrophic factor (BDNF), plays important roles in modulating different aspects of addiction, and is implicated in psychiatric conditions reminiscent of those suffered by METH-abusers. Male Wistar rats were intra-peritoneally injected with METH (8 mg/kg/day) for 14 days while control group received normal saline. After extraction of prefrontal cortices, expression of BDNF IV splice variant and methylation level of its CpG island were evaluated. The relative expression of BDNF IV in METH-treated group was 2.15 fold higher than the control group. Seven out of 29 CpG sites were significantly hypomethylated in the METH group, although none survived Bonferroni adjustment. However, the overall methylation level of the 29 CpGs was significantly lower in METH cases than in controls. We discuss the importance of our results and its implications in detail.

Genotyping of multidrug-resistant strains of Pseudomonas aeruginosa isolated from burn and wound infections by ERIC-PCR.

PURPOSE: To determine the genetic diversity of MDR P. aeruginosa strains isolated from burn and wound infections in Ahvaz, Iran, by ERIC-PCR. METHODS: From total 99 strains of P. aeruginosa defined as MDR by using drug susceptibility testing, 66 were subjected to ERIC-PCR analysis, comprises 53 strains isolated from burn infection, and 13 randomly selected strains from wound infection with higher resistance to combinations of more numbers of drugs. RESULTS: Eight clusters (I to VIII), and 50 single clones were generated for tested MDR isolates analyzed by ERIC-PCR. The high heterogeneity was observed among the isolates from burn infections including 16 isolates which were categorized in eight clusters and 37 single clones. The isolates in clusters II, III, VI, VIII showed 100% similarity. CONCLUSIONS: The high level of genotypic heterogeneity in P. aeruginosa strains demonstrated no genetic correlation between them. Extremely high drug resistance in isolates from burn, suggests that efficient control measures and proper antibiotic policy should be observed.

Genotyping of multidrug-resistant strains of Pseudomonas aeruginosa isolated from burn and wound infections by ERIC-PCR

ABSTRACT PURPOSE: To determine the genetic diversity of MDR P. aeruginosa strains isolated from burn and wound infections in Ahvaz, Iran, by ERIC-PCR. METHODS: From total 99 strains of P. aeruginosa defined as MDR by using drug susceptibility testing, 66 were subjected to ERIC-PCR analysis, comprises 53 strains isolated from burn infection, and 13 randomly selected strains from wound infection with higher resistance to combinations of more numbers of drugs. RESULTS: Eight clusters (I to VIII), and 50 single clones were generated for tested MDR isolates analyzed by ERIC-PCR. The high heterogeneity was observed among the isolates from burn infections including 16 isolates which were categorized in eight clusters and 37 single clones. The isolates in clusters II, III, VI, VIII showed 100% similarity. CONCLUSIONS: The high level of genotypic heterogeneity in P. aeruginosa strains demonstrated no genetic correlation between them. Extremely high drug resistance in isolates from burn, suggests that efficient control measures and proper antibiotic policy should be observed.

Normalization of miRNA qPCR high-throughput data: a comparison of methods.

Low-density quantitative real-time PCR (qPCR) arrays are often used to profile expression patterns of microRNAs in various biological milieus. To achieve accurate analysis of expression of miRNAs, non-biological sources of variation in data should be removed through precise normalization of data. We have systematically compared the performance of 19 normalization methods on different subsets of a real miRNA qPCR dataset that covers 40 human tissues. After robustly modeling the mean squared error (MSE) in normalized data, we demonstrate lower variability between replicates is achieved using various methods not applied to high-throughput miRNA qPCR data yet. Normalization methods that use splines or wavelets smoothing to estimate and remove Cq dependent non-linearity between pairs of samples best reduced the MSE of differences in Cq values of replicate samples. These methods also retained between-group variability in different subsets of the dataset.

Ondansetron and meperidine prevent postoperative shivering after general anesthesia.

BACKGROUND: Postoperative shivering is one of the common problems following general anesthesia and may lead to multiple complications. The aim of this study was to examine the preventive effects of Ondansetron and Meperidine on postoperative shivering. METHODS: This randomized placebo-controlled double blind clinical trial included 90 patients scheduled for elective gynecologic operations, randomly divided to three groups. Ondansetron (4 mg), Meperidine (0.4 mg/kg) and 2 cc normal saline (as a control group) were administered immediately before the induction of anesthesia. Anesthesia induced equivalently for all. Patients were observed in terms of vital signs, side effects and shivering. RESULTS: Postoperative shivering was observed in 13.3% of patients in Ondansetron group and 20% of Meperidine group, significantly lower than the controls (50%). The reduction of core and dermal temperature during the anesthesia and recovery, changes in systolic and diastolic blood pressure and heart rate were similar in all three groups. The incidence of nausea was similar among the three groups of study while vomiting occurred in 6.7% of the Meperidine group and 3.3% of the controls but none in the patients receiving Ondansetron. CONCLUSION: Ondansetron can effectively reduce post operative shivering.