Catharanthine, an anticancer vinca alkaloid: an in silico and in vitro analysis of the autophagic system as the major mechanism of cell death in liver HepG2 cells.

Catharanthine, a component of the anticancer drug vinblastine along with vindoline, disrupts the cell cycle by interfering with mitotic spindle formation. Apart from their antioxidant properties, vinca alkaloids like catharanthine inhibit phosphodiesterase activity and elevate intracellular cAMP levels. The aim of this study was to investigate how catharantine affects apoptosis and autophagy. This study conducted experiments on HepG2 liver carcinoma cells with varying doses of catharanthine to evaluate cell death rates and viability and determine the IC50 concentration via MTT assays. The apoptotic and autophagic effects of catharanthine were assessed using flow cytometry with annexin V and PI staining, while the expression of autophagy-related genes was analyzed through quantitative PCR. Additionally, molecular docking and molecular dynamics simulations were employed to further investigate catharanthine's impact on autophagy mechanisms. The study showed that catharanthine reduced oxidative stress and triggered apoptosis in HepG2 cells in a dose-dependent manner. Catharanthine also upregulated the expression of autophagy-related genes like LC3, Beclin1, and ULK1. Notably, catharanthine increased sirtuin-1 levels, a known autophagy inducer, while decreasing Akt expression compared to untreated cells. Molecular docking results indicated rapamycin had a stronger binding affinity with FRB (-10.7 KJ/mol-1) than catharanthine (-7.3 KJ/mol-1). Additionally, molecular dynamics simulations revealed that catharanthine interacted effectively with the FRB domain of mTOR, displaying stability and a strong binding affinity, although not as potent as rapamycin. In summary, besides its cytotoxic and pro-apoptotic effects, catharanthine activates autophagy signaling pathways and induces autophagic necrosis by inhibiting mTOR.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

SIRT1 activation attenuates palmitate induced apoptosis in C2C12 muscle cells.

BACKGROUND: Type 2 diabetes is characterized by insulin resistance, which manifests mainly in skeletal muscles. SIRT1 has been found to play a role in the insulin signaling pathway. However, the molecular underpinnings of SIRT1's function in palmitate fatty acid-induced apoptosis still need to be better understood. METHODS: In this research, skeletal muscle cells are treated with palmitate to be insulin resistant. It is approached that SIRT1 is downregulated in C2C12 muscle cells during palmitate-induced apoptosis and that activating SIRT1 mitigates this effect. RESULTS: Based on these findings, palmitate-induced apoptosis suppressed mitochondrial biogenesis by lowering PGC-1 expression, while SIRT1 overexpression boosted. The SIRT1 inhibitor sirtinol, on the other hand, decreased mitochondrial biogenesis under the same conditions. This research also shows that ROS levels rise in the conditions necessary for apoptosis induction by palmitate, and ROS inhibitors can mitigate this effect. This work demonstrated that lowering ROS levels by boosting SIRT1 expression inhibited apoptotic induction in skeletal muscle cells. CONCLUSION: This study's findings suggested that SIRT1 can improve insulin resistance in type 2 diabetes by slowing the rate of lipo-apoptosis and boosting mitochondrial biogenesis, among other benefits.

Testosterone, ß-estradiol, and hepatocellular carcinoma: stimulation or inhibition? A comparative effect analysis on cell cycle, apoptosis, and Wnt signaling of HepG2 cells.

Unlike breast and prostate cancers, which are specifically affected by estrogens or androgens, hepatocellular carcinoma has been reported to be influenced by both sex hormones. Given the coincidental differences of hepatocellular carcinoma in men and women, we investigated the effects of ß-estradiol and testosterone on the cell cycle, apoptosis, and Wnt signaling in a model of hepatocellular carcinoma to understand the sex hormone-related etiology. To determine the effective concentration of both hormones, an MTT assay was performed. The effects of ß-estradiol and testosterone on cell proliferation and death were evaluated by specific staining and flow cytometry. In addition, gene expression levels of estimated factors involved in GPC3-Wnt survival signaling were analyzed using quantitative real-time polymerase chain reaction. Both hormones inhibited hepatic cell proliferation through arresting the cell cycle at S/G2 and increased the apoptosis rate in HepG2 cells. Both hormones dose-dependently decreased GPC3, Wnt, and DVL expression levels as activators of the Wnt-signaling pathway. In the case of Wnt-signaling inhibitors, the effects of both hormones on WIF were negligible, but they increased DKK1 levels in a dose-dependent manner. In each of the effects mentioned above, ß-estradiol was notably more potent than testosterone. In contrast to the primary hypothesis of the project, in which testosterone was considered a stimulating carcinogenic factor in HCC pathogenesis, testosterone inhibited the occurrence of HCC similarly to ß-estradiol. However, this inhibitory effect was weaker than that of ß-estradiol and requires further study.

Hub genes, key miRNAs and interaction analyses in type 2 diabetes mellitus: an integrative in silico approach.

Diabetes is a rising global metabolic disorder and leads to long-term consequences. As a multifactorial disease, the gene-associated mechanisms are important to know. This study applied a bioinformatics approach to explore the molecular underpinning of type 2 diabetes mellitus through differential gene expression analysis. We used microarray datasets GSE16415 and GSE29226 to identify differentially expressed genes between type 2 diabetes and normal samples using R software. Following that, using the STRING database, the protein-protein interaction network was constructed and further analyzed by Cytoscape software. The EnrichR database was used for Gene Ontology and pathway enrichment analysis to explore key pathways and functional annotations of hub genes. We also used miRTarBase and TargetScan databases to predict miRNAs targeting hub genes. We identified 21 hub genes in type 2 diabetes, some showing more significant changes in the PPI network. Our results revealed that GLUL, SLC32A1, PC, MAPK10, MAPT, and POSTN genes are more important in the PPI network and can be experimentally investigated as therapeutic targets. Hsa-miR-492 and hsa-miR-16-5p are suggested for diagnosis and prognosis by targeting GLUL, SLC32A1, PC, MAPK10, and MAPT genes involved in the insulin signaling pathway. Insight: Type 2 diabetes, as a rising global and multifactorial disorder, is important to know the gene-associated mechanisms. In an integrative bioinformatics analysis, we integrated different finding datasets to put together and find valuable diagnostic and prognostic hub genes and miRNAs. In contrast, genes, RNAs, and enzymes interact systematically in pathways. Using multiple databases and software, we identified differential expression between hub genes of diabetes and normal samples. We explored different protein-protein interaction networks, gene ontology, key pathway analysis, and predicted miRNAs that target hub genes. This study reported 21 significant hub genes and some miRNAs in the insulin signaling pathway for innovative and potential diagnostic and therapeutic purposes.

Biosensors; nanomaterial-based methods in diagnosing of Mycobacterium tuberculosis.

Diagnosis of Mycobacterium tuberculosis (Mtb) before the progression of pulmonary infection can be very effective in its early treatment. The Mtb grows so slowly that it takes about 6-8 weeks to be diagnosed even using sensitive cell culture methods. The main opponent in tuberculosis (TB) and nontuberculous mycobacterial (NTM) epidemiology, like in all contagious diseases, is to pinpoint the source of infection and reveal its transmission and dispersion ways in the environment. It is crucial to be able to distinguish and monitor specific mycobacterium strains in order to do this. In food analysis, clinical diagnosis, environmental monitoring, and bioprocess, biosensing technologies have been improved to manage and detect Mtb. Biosensors are progressively being considered pioneering tools for point-of-care diagnostics in Mtb discoveries. In this review, we present an epitome of recent developments of biosensing technologies for M. tuberculosis detection, which are categorized on the basis of types of electrochemical, Fluorescent, Photo-thermal, Lateral Flow, Magneto-resistive, Laser, Plasmonic, and Optic biosensors.

Nanobiosensors for procalcitonin (PCT) analysis.

BACKGROUND: Procalcitonin (PCT) is a critical biomarker that is released in response to bacterial infections and can be used to differentiate the pathogenesis of the infectious process. OBJECTIVE: In this article, we provide an overview of recent advances in PCT biosensors, highlighting different approaches for biosensor construction, different immobilization methods, advantages and roles of different matrices used, analytical performance, and PCT biosensor construction. Also, we will explain PCT biosensors sensible limits of detection (LOD), linearity, and other analytical characteristics. Future prospects for the development of better PCT biosensor systems are also discussed. METHODS: Traditional methods such as capillary electrophoresis, high-performance liquid chromatography, and mass spectrometry are effective in analyzing PCT in the medical field, but they are complicated, time-consuming sample preparation, and require expensive equipment and skilled personnel. RESULTS: In the past decades, PCT biosensors have emerged as simple, fast, and sensitive tools for PCT analysis in various fields, especially medical fields. CONCLUSION: These biosensors have the potential to accompany or replace traditional analytical methods by simplifying or reducing sample preparation and making field testing easier and faster, while significantly reducing the cost per analysis.

Investigation of the effects of catharanthine and Q10 on Nrf2 and its association with MMP-9, MRP1, and Bcl-2 and apoptosis in a model of hepatocellular carcinoma.

Since the role of Nrf2 in cancer cell survival has been highlighted, the pharmacological modulation of the Nrf2-Keap1 pathway may provide new opportunities for cancer treatment. This study purposed to use ubiquinone (Q10) as an antioxidant and catharanthine alkaloid as a cAMP inducer suppressing HepG2 cells by reducing Nrf2 level. The effects of Q10 and catharanthine on HepG2 cells in terms of viability were analyzed by MTT test. MTT results were used to determine the effective concentration of both drugs for the subsequent treatment and analysis. Subsequently, the effects of Q10 and catharanthine in a single and combined manner on oxidant/antioxidant status, apoptosis, metastasis, and drug resistance of HepG2 cells were investigated by related methods. Both Q10 and catharanthine decreased the level of oxidative stress products and increased antioxidant capacity in HepG2 cells. Nrf2 gene expression decreased by Q10, but catharanthine unexpectedly increased it. Following Nrf2 alterations, the expression levels of MMP-9 and MRP1 involved in metastasis and drug resistance were significantly and dose-dependently decreased by Q10, while catharanthine slightly increased both. However, both drugs increased caspase 3/7 activity and apoptosis rate, and the effect of Q10 on apoptosis was stronger than that of catharanthine. Most of the effects of the combination treatments were similar to those of the Q10 single treatment and indicated the dominant effect over the catharanthine component. Despite the antioxidant and apoptotic properties of both agents, Q10 was better than catharanthine in inducing apoptosis, counteracting drug resistance, and metastasis in HepG2 cells.

A State-of-the-Art Review on the Recent Advances of Mesenchymal Stem Cell Therapeutic Application in Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that has widespread clinical and immunological manifestations. Despite the increase in knowledge about the pathogenesis process and the increase in treatment options, however, the treatments fail in half of the cases. Therefore, there is still a need for research on new therapies. Mesenchymal stem cells (MSCs) are powerful regulators of the immune system and can reduce the symptoms of systemic lupus erythematosus. This study aimed to review the mechanisms of immune system modulation by MSCs and the role of these cells in the treatment of SLE. MSCs suppress T lymphocytes through various mechanisms, including the production of transforming growth factor-beta (TGF-B), prostaglandin E2 (PGE2), nitric oxide (NO), and indolamine 2 and 3-oxygenase (IDO). In addition, MSCs inhibit the production of their autoantibodies by inhibiting the differentiation of lymphocytes. The production of autoantibodies against nuclear antigens is an important feature of SLE. On the other hand, MSCs inhibit antigen delivery by antigen-presenting cells (APCs) to T lymphocytes. Studies in animal models have shown the effectiveness of these cells in treating SLE. However, few studies have been performed on the effectiveness of this treatment in humans. It can be expected that new treatment strategies for SLE will be introduced in the future, given the promising results of MSCs application.

Nanomaterial-based methods for sepsis management.

Sepsis is a serious disease caused by an impaired host immune response to infection, resulting in organ dysfunction, tissue damage and is responsible for high in-hospital mortality (approximately 20%). Recently, WHO documented sepsis as a global health priority. Nevertheless, there is still no effective and specific therapy for clinically detecting sepsis. Nanomaterial-based approaches have appeared as promising tools for identifying bacterial infections. In this review, recent biosensors are introduced and summarized as nanomaterial-based platforms for sepsis management and severe complications. Biosensors can be used as tools for the diagnosis and treatment of sepsis and as nanocarriers for drug delivery. In general, diagnostic methods for sepsis-associated bacteria, biosensors developed for this purpose are presented in detail, and their strengths and weaknesses are discussed. In other words, readers of this article will gain a comprehensive understanding of biosensors and their applications in sepsis management.

A novel approach to design a multiepitope peptide as a vaccine candidate for Bordetella pertussis.

Bordetella pertussis is a very contagious pathogen in humans, causing pertussis disease. Pertussis is one of the 10 leading causes of death due to infectious diseases, especially among infants and children. Antibiotic-resistant strains have recently emerged in this bacterium, and despite the high vaccination coverage, the prevalence of this disease has been increasing recently in both developed and developing countries. The objective of this study is to introduce a novel in silico vaccine candidate aimed at countering B. pertussis effectively. Differing from other comparable studies, this research employed a computational screening methodology to assess the genome of 'Bordetella pertussis 18323.' The purpose was to identify an innovative antigen for the development of a vaccine against B. pertussis. Notably, our investigation introduces an innovative antigen distinguished by its elevated immunogenicity score. Importantly, this antigen lacks toxicity and allergenicity, making it recognizable to the immune system and thus capable of inducing a robust immune response. In the subsequent phase, our antigen was utilized to identify potential epitopes conducive to the construction of a B. pertussis vaccine. These epitopes, alongside linkers, his-tag and adjuvants, were amalgamated to form the vaccine candidate. Subsequently, a comprehensive evaluation of the vaccine was conducted, encompassing various computational tests such as secondary and tertiary structure analysis, physicochemical examination, and structural analysis involving docking and molecular dynamics simulations. Importantly, our vaccine successfully passed all in silico tests.Communicated by Ramaswamy H. Sarma.

Nanosensors in the detection of antihypertension drugs, a golden step for medication adherence monitoring.

Hypertension is associated with structural and functional changes in blood vessels with increased arteriosclerosis, vascular inflammation, and endothelial dysfunction. Decreased adherence (compliance) to antihypertensive medications contributes significantly to morbidity and mortality in hypertensive patients. Antihypertensive drugs (AHTDs) and lifestyle changes are the main cornerstones for treating hypertension. Several approaches have been described in the literature for determining AHTDs based on different analytical techniques. Amongst biosensors are one of the most attractive tools due to their inherent advantages. Biosensors are used for the detection of wide range of biomarkers as well as different drugs in past two decades. The main focus of the present study is to review the latest biosensors developed for the detection of AHTDs. Readers of the present study will be able to familiarize themselves with biosensors as advanced and modern diagnostic tools while reviewing the most widely used AHTDs. In the present study, the routine methods are first reviewed and while examining their advantages and disadvantages, biosensors have been introduced as ideal alternative tools.

Effects of gut microbial therapy on lipid profile in individuals with non-alcoholic fatty liver disease: an umbrella meta-analysis study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is closely associated with metabolic conditions such as obesity and diabetes mellitus, which significantly impact human health outcomes. The impaired lipid profiles observed in NAFLD individuals can further contribute to cardiovascular events. Despite the high prevalence of NAFLD, there is currently no confirmed intervention approved for its treatment. This study aimed to summarize the results of meta-analysis studies of randomized control trials assessing the impact of gut microbial therapy (probiotics, synbiotics, and prebiotics) on the lipid profile of individuals with NAFLD. METHODS: A systematic search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library up to November 1, 2022. Meta-analyses surveying the impact of microbial therapy on lipid profile parameters (triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC)) in the NAFLD population were included in our umbrella review. The final effect size (ES) was estimated, and sensitivity and subgroup analyses were performed to explore heterogeneity. RESULTS: Fifteen studies were included in this umbrella review. Microbial therapy significantly reduced TG (ES - 0.31, 95% CI - 0.51, - 0.11, P < 0.01), TC (ES - 1.04, 95% CI - 1.46, - 0.61, P < 0.01), and LDL (ES - 0.77, 95% CI - 1.15, - 0.39, P < 0.01) in individuals with NAFLD. However, the effect on HDL was not statistically significant (ES - 0.06; 95% CI - 0.19, 0.07, P = 0.39). CONCLUSION: Considering the absence of approved treatments for NAFLD and the promising role of microbial therapies in improving the three lipid profiles components in individuals with NAFLD, the use of these agents as alternative treatment options could be recommended. The findings underscore the potential of gut microbial therapy, including probiotics, synbiotics, and prebiotics, in managing NAFLD and its associated metabolic complications. TRIAL REGISTRATION: PROSPERO ( CRD42022346998 ).

Role of the ER-induced UPR pathway, apoptosis, and autophagy in colorectal cancer.

When large amounts of misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER) in response to stress, a process called unfolded protein response (UPR) is activated. The disruption of this process leads to many diseases including diabetes, neurodegenerative diseases, and many cancers. In the process of UPR in response to stress and unfolded proteins, specific signaling pathways are induced in the endoplasmic reticulum and subsequently transmitted to the nucleus and cytoplasm, causing homeostasis and restoring the cell's normal condition with reducing protein translation and synthesis. The UPR response followed by stress enhancement balances cell survival with death, therefore in this condition cells decide either to survive or have the path of apoptosis ahead. However, in some cases, this balance is disturbed and the UPR pathway is chronically activated or not activated and the cell conditions lead to cancer. This study aimed to briefly investigate the association between ER stress, UPR, apoptosis, and autophagy in colorectal cancer (CRC). Moreover, in current study, we will try to demonstrate canonical ways and methods for the treatment of CRC cells with attenuated ER stress.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

An interplay between non-coding RNAs and gut microbiota in human health.

Humans have a complicated symbiotic relationship with their gut microbiome, which is postulated to impact host health and disease broadly. Epigenetic alterations allow host cells to regulate gene expression without altering the DNA sequence. The gut microbiome, offering environmental hints, can influence responses to stimuli by host cells with modifications on their epigenome and gene expression. Recent increasing data suggest that regulatory non-coding RNAs (miRNAs, circular RNAs, and long lncRNA) may affect host-microbe interactions. These RNAs have been suggested as potential host response biomarkers in microbiome-associated disorders, including diabetes and cancer. This article reviews the current understanding of the interplay between gut microbiota and non-coding RNA, including lncRNA, miRNA, and circular RNA. This can lead to a profound understanding of human disease and influence therapy. Furthermore, microbiome engineering as a mainstream strategy for improving human health has been discussed and confirms the hypothesis about a direct cross-talk between microbiome composition and non-coding RNA.

Recent advances in the detection of glioblastoma, from imaging-based methods to proteomics and biosensors: A narrative review.

Glioblastoma (GBM) is an aggressive type of cancer that originates in the cells called astrocytes, which support the functioning of nerve cells. It can develop in either the brain or the spinal cord and is also known as glioblastoma multiform. GBM is a highly aggressive cancer that can occur in either the brain or spinal cord. The detection of GBM in biofluids offers potential advantages over current methods for diagnosing and treatment monitoring of glial tumors. Biofluid-based detection of GBM focuses on identifying tumor-specific biomarkers in blood and cerebrospinal fluid. To date, different methods have been used to detect biomarkers of GBM, ranging from various imaging techniques to molecular approaches. Each method has its own strengths and weaknesses. The present review aims to scrutinize multiple diagnostic methods for GBM, with a focus on proteomics methods and biosensors. In other words, this study aims to provide an overview of the most significant research findings based on proteomics and biosensors for the diagnosis of GBM.

The Impacts and Analysis of Individual and Social Risks of the Stochastic Emission of Benzene from Floating-Roof Tanks Using Response Surface Analysis and MPACT Model.

In the present study, the researchers used an integrated approach composed of response surface analysis (RSM) and MPACT model to predict fatality rates caused by benzene emitted from floating-roof tanks. RSM scenarios were configured in Expert Design (version 7.0) software using the central composite design (CCD) method and five variables of wind speed, relative humidity, atmospheric temperature, failure diameter, and emission height were considered. Continuous Pasquill-Gifford Gaussian model was used to estimate the results of the RSM scenarios. The response values were considered for exposure concentrations above 50 ppm (slight damages), 150 ppm (moderate damage), and 1000 ppm (high damage). The analysis of individual and social risks for each scenario was done using the MPACT model in SAFETI program (version 8.22) by providing two variables of population characteristics and the frequency of tank wall failure. The results showed that atmospheric temperature, wind speed, failure diameter, and emission height have positive effects on the dispersion of the cloud of toxic benzene vapor with a concentration of 1000 ppm. Intolerable individual risk distances were estimated to be lower for indoor environments than for outdoor. Maximum distances of intolerable individual risks for the worst-case scenarios were estimated up to 2500 m from the emission point, which resulted from exposure to a concentration of 1000-ppm benzene. Results regarding the estimation of social risks showed that over 1600 fatalities should be expected under the worst-case scenarios. The three factors of high temperature, low wind speed, and low emission height play a major role in the occurrence of scenarios with the highest fatalities. High wind speed and high emission height were the most important factors in most scenarios with zero fatalities rate. Generally, the findings of this study show the necessity to provide an emergency response plan in the studied industry in both autumn and winter due to low wind speed. However, the coupling of the developed statistical models based on regional meteorological conditions with the MPACT model can help researchers to design an emergency response plan to deal with leakage incidents in petrochemical industries.

Non-coding RNAs: An emerging player in particulate matter 2.5-mediated toxicity.

Exposure to air pollution has been connected to around seven million early deaths annually and also contributing to higher than 3 % of disability-adjusted lost life years. Particulate matters (PM) are among the key pollutants that directly discharged or formed due to atmospheric chemical interactions. Among these matters, due of its large surface area, PM2.5 may absorb a different harmful and toxic substances. One of the outcomes of such environmental disturbance is oxidative stress which affects cellular processes including apoptosis, inflammation, and epithelial mesenchymal transition. Non-coding RNAs (ncRNA) such as, miRNAs, lncRNAs, and circRNAs are classified as non-protein coding RNA's. Over the past few years these small molecules have been gaining so much attention since they participate in variety of physiological and pathological processes and their expression change during disease periods. Regarding epigenetic properties, ncRNAs play an important function in organism's response to environmental stimulus. In this manner, it was revealed that exposure to PM2.5 may cause epigenetic reprogramming, such as, ncRNAs signature's alteration, which can be effective concerning pathophysiology state. In this review, we describe PM2.5 impact on ncRNAs and excavate its roles in toxicity caused by PM2.5.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Background: Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Methods: Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. Results: HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Conclusions: Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.