Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

MicroRNA-mediated metabolic regulation of immune cells in cancer: an updated review.

The study of immunometabolism, which examines how immune cells regulate their metabolism to maintain optimal performance, has become an important area of focus in cancer immunology. Recent advancements in this field have highlighted the intricate connection between metabolism and immune cell function, emphasizing the need for further research. MicroRNAs (miRNAs) have gained attention for their ability to post-transcriptionally regulate gene expression and impact various biological processes, including immune function and cancer progression. While the role of miRNAs in immunometabolism is still being explored, recent studies have demonstrated their significant influence on the metabolic activity of immune cells, such as macrophages, T cells, B cells, and dendritic cells, particularly in cancer contexts. Disrupted immune cell metabolism is a hallmark of cancer progression, and miRNAs have been linked to this process. Understanding the precise impact of miRNAs on immune cell metabolism in cancer is essential for the development of immunotherapeutic approaches. Targeting miRNAs may hold potential for creating groundbreaking cancer immunotherapies to reshape the tumor environment and improve treatment outcomes. In summary, the recognition of miRNAs as key regulators of immune cell metabolism across various cancers offers promising potential for refining cancer immunotherapies. Further investigation into how miRNAs affect immune cell metabolism could identify novel therapeutic targets and lead to the development of innovative cancer immunotherapies.

Association of fatty acid binding protein-4 (FABP-4) T87C and rs8192688 gene polymorphisms and FABP-4 level with cardiovascular disease susceptibility in type 2 diabetic patients.

Type 2 Diabetes Mellitus (T2DM) is known to cause dyslipidemia and increase the risk of cardiovascular disease (CVD). Fatty acid binding protein (FABP)-4 plays a significant role in various stages of T2DM and CVD. Although it has been demonstrated that genetic variations of the FABP-4 gene can affect insulin sensitivity, the results obtained so far are controversial. The aim of this study was to investigate the possible association between T87C and rs8192688 polymorphisms and serum levels of FABP-4 with CVD susceptibility in T2DM patients. The study included 70 healthy controls, 70 individuals with T2DM, and 70 T2DM patients with CVD. Genomic DNA was extracted, and FABP-4 T87C and rs8192688 gene polymorphic sites were amplified using the ARMS-PCR method. Lipid profile and FABP-4 serum levels were significantly higher in T2DM patients with CVD compared to those with only T2DM (p < 0.05). Additionally, FABP-4 T87C gene polymorphism (TC genotypes) and dominant model (TT vs. TC + CC) were significantly associated with a decreased risk of both T2DM and T2DM with CVD patients (p < 0.05). Patients carrying TC + CC genotypes had significantly lower levels of triglyceride and FABP-4 compared to those carrying the TT genotype (p < 0.05). There was no significant association between FABP-4 rs8192688 polymorphism and either T2DM or CVD disease. It appears that FABP-4 T87C polymorphism decreases FABP-4 levels leading to decreased serum TG levels. Since both T2DM and CVD have inflammatory backgrounds, reducing inflammation can improve insulin sensitivity and lower TG levels in these patients.

Circulating FABP-4 Levels in Patients with Atherosclerosis or Coronary Artery Disease: A Comprehensive Systematic Review and Meta-Analysis.

Background: Cardiovascular diseases (CDs), notably coronary artery disease (CAD) due to atherosclerosis, impose substantial global health and economic burdens. Fatty acid-binding proteins (FABPs), including FABP-4, have been recently linked to CDs. This study conducted a systematic review and meta-analysis to examine FABP-4 levels in CAD and atherosclerosis patients, exploring their potential links to these conditions. Methods: A systematic review and meta-analysis were done based on the PRISMA guideline. The international databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, and UpToDate were searched to find all related studies on the effect of FABP-4 on patients with CAD or atherosclerosis which were published till June 2022 without language restriction. The Cochran's Q-test and I2 statistic were applied to assess heterogeneity, a random effect model was used to estimate the pooled standardized mean difference (SMD), a metaregression method was utilized to investigate the factors affecting heterogeneity between studies, and Egger's test was used to assess the publication bias. Results: Of 1051 studies, 9 studies with a sample size of 2327 were included in the systematic review and meta-analysis. The level of circulating FABP-4 in the patient groups was significantly higher than in the control groups (SMD = 0.60 (95% CI: 0.30 to 0.91, I2: 91.47%)). The SMD in female and male patients were 0.26 (95% CI: 0.01 to 0.52, I2: 0%) and 0.22 (95% CI: 0.08 to 0.35, I2: 44.7%), respectively. There was considerable heterogeneity between the studies. The countries had a positive relationship with heterogeneity (coefficient = 0.29, p < 0.001); but BMI, lipid indices, gender, study design, and type of kit had no effect on the heterogeneity. No publication bias was observed (p: 0.137). Conclusion: In summary, this meta-analysis revealed elevated circulating FABP-4 levels in CDs, suggesting its potential as a biomarker for these conditions. Further research is warranted to explore its clinical relevance.

New Association Between Diabetes Mellitus and Pancreatic Cancer.

BACKGROUND: Diabetes mellitus is a global issue that has affected the lives of many people all over the world. This disorder, which is also called the mother of all diseases, possesses high pathogenicity and results in the emergence of many disorders. One of the known correlated diseases is pancreatic cancer which can be accompanied by diabetes mellitus. Therefore, finding the association between these diseases and common genes is urgent. OBJECTIVE: In this study, in order to survey the relationship between diabetes mellitus and pancreatic cancer, the common genes of these disorders were analyzed by bioinformatics tools. METHODS: For this purpose, we screened 17 shared genes from microarray data downloaded from the Gene Expression Omnibus (GEO) database. In addition, the relationship between identified genes was constructed by STRING and DAVID tools. RESULTS: In total, 112 genes were identified to be differentially expressed. Among these, 17 genes were found to be common, including two genes that were down-regulated and others that were upregulated. Other analyses showed that most of the genes were enriched in Vibrio cholera infection and the mTOR signaling pathway. The biological processes of such genes included oxygen and gas transport, phagosome acidification, and GTPase activity. CONCLUSION: In this study, 17 common genes that had not previously been considered in diabetes and pancreatic cancer were screened, which can be further considered for clinical approaches and in vitro studies.

Trehalose and carnosic acid induced LC3I, LC3II ratio, P62 down-regulation and cleaved caspase 3 expression in neural stem cells.

BACKGROUND: Using neural stem cells (NSCs) in cell therapy and regenerative medicine is a growing knowledge. In this study, the protective role of carnosic acid and trehalose against H2O2-induced oxidative stress in autophagy induction and apoptosis inhibition in NSCs was investigated. MATERIAL AND METHODS: The bone marrow stromal cells (BMSCs) were isolated from the femur of the rat and differentiated into NSCs using basic fibroblast and epidermal growth factors (bFGF and EGF), and B27 serum free media. To evaluate the autophagy, the P62 protein was assessed by immunocytochemistry and LC3II / LC3I ratio by Western blotting. Further, we used 3-Methyladenine (3-MA), a widely used autophagy inhibitor to study whether combined treatment of 3-MA with carnosic acid and trehalose modulates autophagy in NSCs. For studying apoptosis, the cleaved caspase-3 protein was evaluated. Carnosic acid and trehalose increased the survival of the NSCs. RESULTS: The H2O2 decreased the autophagy and induced apoptosis with increasing time during 24 hours, however, a pre-treatment with 2 µM carnosic acid and trehalose 3 % induced the autophagy proteins (while increasing the LC3II / LC3I ratio and decreasing the P62) and decreased the apoptosis (while decreasing the expression of the cleaved caspase-3). The results showed that the carnosic acid and trehalose increased the survival of NSCs against the oxidative stress caused by H2O2, decreased apoptosis, and induced autophagy. CONCLUSION: Due to the carnosic acid and trehalose unique properties and its low toxicity, it can be used as an agent in cellular transplantation for reducing oxidative stress and inducing autophagy (Fig. 4, Ref. 37).

Corrigendum to: Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study.

Due to oversight on the part of the authors, the names of two of the co-authors have been incorrectly published in the article entitled, "Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study", 2021, Vol. 21, No. 3, pp. 441-447 [1]. The original article can be found online at: https://doi.org/10.2174/1871530320666200713091827. Original: Amin Bakhtiyari, Karimeh Haghani, Salar Bakhtiyari*, Mohammad A. Zaimy, Nooriali Zahed, Ali Gheysarzadeh, Shahram Darabi, Seidali Nahalkhani, Mansour Amraei and Iraj Alipourfard Corrected: Amin Bakhtiyari, Karimeh Haghani, Salar Bakhtiyari*, Mohammad A. Zaimy, Ali Noori-Zadeh, Ali Gheysarzadeh, Shahram Darabi, Ali Seidkhani-Nahal, Mansour Amraei and Iraj Alipourfard.

Quercetin and its Relative Therapeutic Potential Against COVID-19: A Retrospective Review and Prospective Overview.

COVID-19 is an emerging disease that is a major threat to the global community. The main challenge in this disease is the lack of proper or proven medication. The drugs used to treat this disease are only for symptomatic treatment. Studies of other coronaviruses, such as SARS and MERS, suggest that quercetin has sufficient potential to treat COVID-19. Previous studies have shown that quercetin reduces the entry of the virus into the cell by blocking the ACE2 receptor, as well as reducing the level of interleukin-6 in SARS and MERS patients. Therefore, the aim of this review was to scrutinize the potential of quercetin as a drug in the treatment of COVID-19 from a molecular perspective.

The Key Role of Akt Protein Kinase in Metabolic-Inflammatory Pathways Cross-Talk: TNF-α Down-Regulation and Improving of Insulin Resistance in HepG2 Cell Line.

BACKGROUND: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-α inhibitory effects on key insulin signaling pathway elements remain to be verified in insulinresistant hepatic cells. Thus, TNF-α knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-α effect on probable enhancing of insulin resistance. METHODS: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-α gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis was used to assess the Akt protein phosphorylation status. RESULTS: Palmitate-induced insulin resistance caused TNF-α protein overexpression 1.2-, 2.78, and 2.25- fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-α expression showed around 30% reduction in TNF-α knockdown cells as compared to normal cells. In the TNF-α down-regulated cell, Akt phosphorylation was approximately 62% more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. CONCLUSIONS: The obtained data demonstrated that TNF-α protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipidinduced insulin resistance of the diabetic hepatocytes.

Association between ABCC8 Ala1369Ser Polymorphism (rs757110 T/G) and Type 2 Diabetes Risk in an Iranian Population: A Case-Control Study.

OBJECTIVE: Glucose metabolism increases ATP/ADP ratio within the ß-cells and causes ATP-sensitive K+ (KATP) channel closure and consequently insulin secretion. The enhanced activity of the channel may be a mechanism contributing to the reduced first-phase of insulin secretion observed in T2DM. There is no study to date in the Kurdish ethnic group regarding the relationship between SNP Ala1369Ser (rs757110 T/G) of SUR1 gene and T2DM, and additionally, the results of this association in other populations are inconsistent. Therefore, our aim in this study was to explore the possible association between SNP Ala1369Ser and type 2 diabetes in an Iranian Kurdish ethnic group. METHODS: In this study, we checked out the frequency of alleles and genotypes of SNP Ala1369Ser in T2DM individuals (207 patients; men/women: 106/101) and non-T2DM subjects (201 controls; men/women: 97/104), and their effects on anthropometric, clinical, and biochemical parameters. Genomic DNA was extracted from the leukocytes of blood specimens using a standard method. We amplified the ABCC8 rs757110 polymorphic site (T/G) using a polymerase chain reaction (PCR) method and a designed primer pair. To perform the PCR-RFLP method, the amplicons were subjected to restriction enzymes and the resulting fragments separated by gel electrophoresis. RESULTS: The frequency of the G-allele of Ala1369Ser polymorphism was significantly (0.01) higher in the case group than the control group (19% vs. 9%, respectively). In the dominant model (TT vs. TG+GG), there was a significant relationship between this SNP and an increased risk of T2DM (P = 0.00). T2DM patients with TG+GG genotypes had significantly higher fasting plasma insulin and HOMA-IR than those who had the TT genotype (P = 0.02 and 0.01, respectively). CONCLUSION: Our study is the first study to investigate the association between Ala1369Ser ABCC8 genetic variation and T2DM in the Kurdish population of western Iran. The obtained results clearly show that Ala1369Ser polymorphism of ABCC8 is associated with an increased risk of T2DM in this population.

Do Genetic Factors Predispose People to COVID-19: A Review Article.

The pandemic of coronavirus disease 2019 (COVID-19) has become a threat to human life and society. Scientists and clinicians are struggling with the intrusive SARS-CoV-2 virus to enhance their knowledge about its pathogenesis and find an effective medicine and vaccine to combat its complications. Till now, they have learned that this SARS-CoV-2 has not infected all people exposed to this virus, and also severe respiratory illnesses have not been observed in all infected patients. Patients over 65 or with underlying diseases are more vulnerable to develop severe disease. Based on this premise, a highly challenging question is why some people are more susceptible to this virus and others are not. The present study was aimed to review the current information, which explains the broad spectrum of COVID-19 presentation. Here, we discussed how genetic background, immune system, underlying disease, smoking status, as well as age, race, and gender affect COVID-19 susceptibility.

The Effect of Stress Management Program on Perceived Stress in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

INTRODUCTION: Stress management plays an important role in improving metabolic control in type 2 diabetes patients. The aim of this study was to find the effect of educational intervention on improving stress management in type 2 diabetic patients in Dezful, Iran. METHODS: In an experimental study, 92 patients with type 2 diabetes who were referred to the Diabetes Clinic of Ganjavian Hospital of Dezful were selected by available sampling method. Then, they were randomly divided into two groups: 46 as intervention and 46 as control. For the intervention group, a stress management training program was designed for one month (8 sessions), while there was no training for the control group. All participants filled the Cohen Perceived Stress Questionnaire (PSQ) in baseline and follow up (3 months) phases. All the data were analyzed using SPSS software by conducting an independent t- test, and paired sample t- test, and Chi-square test at a significant level of 0.05. RESULTS: The mean age of participants was 52.70 ± 10.91 years. Pre-test data revealed that there was no significant difference between the stresses of the two groups (P> 0.05); however, the results of the independent t-test, 3 months after the educational intervention, demonstrated a significant decrease in stress level in the intervention group compared to the control group (P <0.05). CONCLUSION: Based on the findings of this study, it is concluded that the design and implementation of health education interventions can be useful to improve stress management in people with type 2 diabetes.

Insulin-like growth factor binding protein 3 chemosensitizes pancreatic ductal adenocarcinoma through its death receptor.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Gemcitabine and doxorubicin are commonly used as the chemotherapy agents, but most of PDAC tumors eventually acquired resistance to chemotherapy. Accumulating evidence indicates that Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role against tumor growth but its expression has commonly suppressed. The present study was designed to evaluate IGFBP-3 effects in chemotherapy sensitization of PDAC cells. Here, we report that the re-sensitization of chemoresistant PDAC cells was occurred by IGFBP-3 through recruitment of its death receptor (IGFBP-3R). Using gemcitabine, doxorubicin-resistant PDAC cell lines, we found that IGFBP-3 sensitized chemoresistant cells by activating apoptosis (as evaluated by Bax up-regulation, Bcl-2 down-regulation as well as Caspase-3 and Caspase 8 activation). IGFBP-3R was also found to have higher expression level in resistant AsPc-1 and MIA PaCa-2 cells in comparison to parental cells. IGFBP-3R was also highly expressed in PDAC tumor which exposed to chemotherapy in comparison to un-treated PDAC tumors. In addition, we confirmed our finding by using specific siRNA to knocking down of IGFBP-3R which prevents IGFBP-3 Chemosensitization. Taken together, the present study for the first time indicates the clinical relevance for combining IGFBP-3 with chemotherapy to reduce chemoresistance in PDAC.

Evaluating Chondroitin Sulfate and Dermatan Sulfate Expression in Glial Scar to Determine Appropriate Intervention Time in Rats.

INTRODUCTION: The proteoglycans of the extracellular matrix increases in the glial scar during spinal cord injury and significantly affects the inhibition of axonal regeneration. METHODS: The results of injury therapies are limited due to the lack of identifying a timely therapeutic intervention. The present study aimed to investigate the glial scar Chondroitin Sulfate (CS) and Dermatan Sulfate (DS) levels at different post-injury times to determine the appropriate time for therapeutic intervention. RESULTS: By this experimental study, 72 Wistar rats were randomly divided into 12 groups, as follows: control, sham, injured animals at 1, 2, 4, and 8 days, as well as 2, 4, 8, 12, 16, and 20 weeks post-injury. The animals in the injured groups were contused in the T10 segment of the spinal cord. The motor function of animals was assessed using the Basso, Beattie, and Bresnahan (BBB) test. Besides, the histological assessment was performed using Luxol Fast Blue and Bielshovisky Staining. The CS and DS levels of lesions were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. CONCLUSION: The motor function assessment indicated a relative recovery over time. Histological results confirmed some regeneration in the injury site at 20 weeks post-injury. The ELISA results demonstrated a much higher level of DS than that of CS in the glial scar. Considering high levels of DS, compared to CS in the glial scar and its reduction from second weeks after SCI onwards, the second week after SCI seems to be the best time for therapeutic interventions in terms of scar permeability.

TGFαL3-SEB fusion protein as an anticancer against ovarian cancer.

TGFαL3-SEB is a new synthetic fusion protein produced by the combination of the third loop of transforming growth factor with staphylococcal enterotoxin type B. In the current study, the anti-tumor effects of TGFαL3-SEB were evaluated against SKOV3 cells, which highly expressed the epidermal growth factor receptor (EGFR). Our findings showed that incubation of SKOV3 cells with 75, 100 and 150 µg/ml of TGFαL3-SEB significantly reduces the proliferation rate in a concentration-dependent manner (P < 0.05) and its IC50 value was 110 µg/ml. Caspase-3 activity was increased from 100% for control cells to 109, 144, and 169% for 75, 100 and 150 µg/ml of TGFαL3-SEB treatment, respectively. Caspase-9 activity and bax/bcl-2 ratio were also confirmed the apoptosis induction ability of TGFαL3-SEB (P < 0.001). Flow cytometry examination also showed that apoptosis was induced and the number of apoptotic cells was increased from 8.2% in un-treated cells to 20.9, 50, and 90% in response to 75, 100 and 150 µg/ml of TGFαL3-SEB fusion protein in a concentration-dependent manner (P < 0.05). The mRNA expression level of VEGF was also reduced to 0.89, 0.69, and 0.60, respectively in response to 75, 100 and 150 µg/ml of TGFαL3-SEB fusion protein exposure, respectively (P < 0.5). In summary, the findings of our study uncovered that TGFαL3-SEB fusion protein induced apoptosis and reduced angiogenesis in SKOV3 ovarian cancer cells in a concentration-dependent manner. This protein has the potential to act against EGFR expressing malignant cells to serve as a pro-apoptotic and angiogenesis blocker agents; however, further studies are needed to confirm its ability.

Investigating the effect of Crocus sativus L. petal hydroalcoholic extract on inflammatory and enzymatic indices resulting from alcohol use in kidney and liver of male rats.

BACKGROUND: Studies have shown that consumption of high levels of alcohol causes many negative effects on the liver and kidneys where antioxidant ingredients can be a proper solution to reducing the resulting damages. So, the present study investigated the effect of hydroalcoholic extract of Crocus sativus L. (saffron) petal with antioxidant properties on the changes in inflammatory and enzymatic indices resulting from alcohol use in the male rats' kidney and liver. MATERIALS AND METHODS: After preparing the extract, LD50 was determined and high-performance liquid chromatography (HPLC) was employed to specify the type and the rate of the active ingredients of the extract. Then, 36 male Wistar rats were randomly assigned into six groups (n=6). The first group was only administered with normal saline and the second group only received ethyl alcohol 6 mL/kg/day·BW. The third and the fourth groups received ethyl alcohol 6 mL/kg/day·BW plus 167.5 and 335 mg/kg/day·BW saffron petal extract for 8 weeks. The fifth and the sixth groups received ethyl alcohol 6 mL/kg/day·BW for the first 8 weeks and were subsequently gavage fed on saffron extract for 167.5 and 335 mg/kg/day·BW, respectively, during the next 8 weeks. In the beginning and after the termination of the treatment, blood samples were collected from all rats. RESULTS: The LD50 of the extract was about 670 mg/kg. The HPLC results indicated that the extract contains important antioxidant ingredients. At the end of the study, the serum concentration of the inflammatory indices, renal enzymes, and hepatic enzymes experienced a significant reduction in all of the intervened groups compared to the negative control group (minimum significant difference: P<0.05) except for the treatment group 1. CONCLUSION: Based on the current results, the extract has a protective effect in a dosage-dependent way and greater protective roles were documented for higher dosages.

MIG1 Glucose Repression in Metabolic Processes of Saccharomyces cerevisiae: Genetics to Metabolic Engineering.

BACKGROUND: Although Saccharomyces cerevisiae has several industrial applications, there are still fundamental problems associated with sequential use of carbon sources. As such, glucose repression effect can direct metabolism of yeast to preferably anaerobic conditions. This leads to higher ethanol production and less efficient production of recombinant products. The general glucose repression system is constituted by MIG1, TUP1 and SSN6 factors. The role of MIG1 is known in glucose repression but the evaluation of effects on aerobic/anaerobic metabolism by deletion of MIG1 and constructing an optimal strain brand remains unclear and an objective to be explored. METHODS: To find the impact of MIG1 in induction of glucose-repression, the Mig1 disruptant strain (ΔMIG1) was produced for comparing with its congenic wild-type strain (2805). The analysis approached for changes in the rate of glucose consumption, biomass yield, cell protein contents, ethanol and intermediate metabolites production. The MIG1 disruptant strain exhibited 25% glucose utilization, 12% biomass growth rate and 22% protein content over the wild type. The shift to respiratory pathway has been demonstrated by 122.86 and 40% increase of glycerol and pyruvate production, respectively as oxidative metabolites, while the reduction of fermentative metabolites such as acetate 35.48 and ethanol 24%. RESULTS: Results suggest that ΔMIG1 compared to the wild-type strain can significantly present less effects of glucose repression. CONCLUSION: The constructed strain has more efficient growth in aerobic cultivations and it can be a potential host for biotechnological recombinant yields and industrial interests.

The Phosphorylation of IRS1S307 and AktS473 Molecules in Insulin-Resistant C2C12 Cells Induced with Palmitate Is Influenced by Epigallocatechin Gallate from Green Tea.

In the current investigation, the effect of epigallocatechin gallate (EGCG) on the phosphorylation of IRS1S307 and AktS473 molecules in insulin-resistant C2C12 muscle cells induced with palmitate was studied and compared with the effect of the antidiabetic drug, rosiglitazone. C2C12 myoblasts were cultured in Dulbecco's modified Eagle's medium and differentiated into myotubes using horse serum and the creatine kinase test was used to confirm their differentiation. The treatment of C2C12 myotubes was carried out with palmitate, where albumin was used as the conjugator. The Western blot technique was used to check the useful phosphorylation of IRS1S307 and AktS473 in C2C12 myotubes, in the presence or absence of palmitate. There was a significant (p < 0.00) and linear increase in the activity of creatine kinase over time (0 to 96 h after differentiation) with everyday myoblast formation. While neither EGCG nor rosiglitazone showed a significant (p > 0.05) effect on palmitate content during 96 h of incubation of IRS1S307 , EGCG alone or combined with rosiglitazone increased the phosphorylation of AktS473 , leading to the increase of glucose uptake into C2C12 cells. Thus, it can be concluded that EGCG alone or in combination with rosiglitazone may show some therapeutic effects for the prevention or treatment of Type 2 diabetes owing to its substantial effect on increasing the phosphorylation of AktS473 and the subsequent glucose uptake into the cells.

Leptin, adiponectin, and resistin blood adipokine levels in migraineurs: Systematic reviews and meta-analyses.

INTRODUCTION: Migraine comorbidity with obesity is not new and studies have focused on how adipose tissue-derived substances such as adipokines might be involved in the migraine pathophysiology. Quantification of the nature and magnitude of the association between each adipokine including leptin, adiponectin and resistin with migraine pathophysiology is the objective of the current study. METHODS: Using systematic reviews and meta-analyses and standardized mean difference as effect size, the levels of three adipokines, leptin, adiponectin and resistin, have been investigated in migraineur subjects in the case-control studies. RESULTS: Using random-effects models, the final analyses demonstrated the standardized mean differences of leptin, adiponectin and resistin as 0.534 (95% confidence interval, 0.169-0.898), 0.439 (95% confidence interval, 0.132-0.746) and 0.194 (95% confidence interval, -0.158-0.546), respectively. The p-value for test of significance for each pooled standardized mean difference was examined by the z-test and calculated as 0.004, 0.005 and 0.281 for leptin, adiponectin and resistin (clearly considered as statistically significant, significant and non-significant), respectively. CONCLUSION: Based on the findings, the blood levels of leptin and adiponectin, but not resistin, of the migraineurs are associated with disease pathogenesis.