The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

Association of vitamin D levels with anthropometric and adiposity indicators across all age groups: a systematic review of epidemiologic studies.

Objectives: It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages. Methods: Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle-Ottawa criteria. Results: Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered. Conclusion: Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

Investigating the effect of combined use of selenium and Myo-inositol supplements on thyroid function and autoimmune characteristics in thyroid disorders: a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review the effect of selenium and inositol combination on thyroid function, autoimmune characteristics in thyroid diseases. RESEARCH DESIGN AND METHODS: To identify eligible studies, a systematic search was conducted in the PubMed/MEDLINE, Science-Direct, CINHAL, EMBASE, SCOPUS, Psychinfo, Cochrane, ProQuest, and Web of Science were searched using the main concepts, and all English-written articles that were published between 2007 and 2022 and had an available full text were examined. RESULTS: The data analysis of this research revealed that after the simultaneous use of selenium and inositol supplements, the level of Triiodothyronine(T3) increased by 0.105 in patients with thyroid disorders although this increase was not significant (P-value: 0.228). The level of Thyroxine (T4) significantly increased by 0.06 (P-value: 0.04). Anti-Thyroid Peroxidase Antibody (TPOAb) titer decreased by 119.36%, which was not significant (P-value: 0.070). Finally, the level of Thyroid-stimulating hormone (TSH) decreased by 1.45%, which was a significant change (P-value: 0.001). CONCLUSION: It was observed that simultaneous use of selenium and inositol supplements did not change the T3 and TPOAb titer levels; however, it leads to a decrease in TSH and increase in T4 levels. Further studies are required due to the limited number of studies.

A narrative review on the role of hesperidin on metabolic parameters, liver enzymes, and inflammatory markers in nonalcoholic fatty liver disease.

Insulin resistance, oxidative stress, hyperlipidemia, and inflammation play main roles in the development of nonalcoholic fatty liver disease (NAFLD). Some studies have reported that hesperidin can reduce hyperglycemia and hyperlipidemia by inhibiting inflammatory pathways. In the current study, our purpose was to evaluate whether it can influence the primary parameters in NAFLD and improve the treatment effectiveness for future trials. Various studies have found that hesperidin involves multiple signaling pathways such as cell proliferation, lipid and glucose metabolism, insulin resistance, oxidative stress, and inflammation, which can potentially affect NAFLD development and prognosis. Recent findings indicate that hesperidin also regulates key enzymes and may affect the severity of liver fibrosis. Hesperidin inhibits reactive oxygen species production that potentially interferes with the activation of transcription factors like nuclear factor-κB. Appropriate adherence to hesperidin may be a promising approach to modulate inflammatory pathways, metabolic indices, hepatic steatosis, and liver injury.

Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies.

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

Impact of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors-γ, α and fibroblast growth factor-21 serum levels in patients with various presentation of metabolic conditions: a GRADE assessed systematic review and dose-response meta-analysis of clinical trials.

There is some debate about the effects of omega-3 fatty acids on the regulation of adipose tissue related genes. This systematic review and meta-analysis aimed to evaluate the effects of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors (PPAR-α and PPAR-γ) and serum fibroblast growth factor-21 (FGF-21) levels in adults with different presentation of metabolic conditions. To identify eligible studies, a systematic search was conducted in the Cochrane Library of clinical trials, Medline, Scopus, ISI Web of Science, and Google Scholar up to April 2022. Eligibility criteria included a clinical trial design, omega-3 fatty acids supplementation in adults, and reporting of at least one of the study outcomes. Effect sizes were synthesized using either fixed or random methods based on the level of heterogeneity. Fifteen studies met the inclusion criteria. Omega-3 fatty acids supplementation significantly increased the PPAR-γ (10 studies) and PPAR-α (2 studies) gene expression compared to the control group (WMD: 0.24; 95% CI: 0.12, 0.35; p < 0.001 and 0.09; 95% CI: 0.04, 0.13; p < 0.001, respectively). Serum FGF-21 (8 studies) levels exhibited no significant change following omega-3 fatty acids supplementation (p = 0.542). However, a dose-response relationship emerged between the dose of omega-3 fatty acids and both PPAR-γ gene expression and serum FGF-21 levels. Overall, this study suggests that omega-3 fatty acids supplementation may have positive effects on the regulation of adipose tissue related genes in patients with various presentation of metabolic condition. Further research is needed to validate these findings and ascertain the effectiveness of this supplementation approach in this population. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, CRD42022338344.

The association of dietary phytochemical index and nonalcoholic fatty liver disease.

Consumption of phytochemical-rich foods relates to the prevention of chronic diseases. In this study we assessed the dietary phytochemical index (PI) in metabolic parameters, liver enzymes, and severity of fibrosis among nonalcoholic fatty liver disease patients. This cross-sectional study was conducted on 210 patients with NAFLD. Fibrosis-4 index (FLB4), nonalcoholic fatty liver disease fibrosis score (NFS), FBS, lipids profile, AST, ALT, ALP, and GGT were measured. PI was calculated through the information obtained from a validated semi-quantitative food frequency. Multiple regression models were used to estimate mean difference changes in the evaluated variables associated with various dietary PI. Participants' mean ± SD of age and BMI were 39.23 ± 10.52 and 24.40 ± 2.64, respectively. We found that DPI is inversely associated with serum TG, TC, and LDL-C and directly associated with serum HDL-C and a higher score in DPI is associated with lower scores in NFS and FIB-4. Multivariate linear regression showed that there is an inverse association between DPI and AST, ALT, ALP, GGT, NFS, and FIB-4. Higher dietary PI could impact on reduction of NAFLD progression and improvement of metabolic parameters.

Prevalence of overweight and obesity among Iranian population: a systematic review and meta-analysis.

BACKGROUND: Obesity is a major risk factor for chronic diseases. Politicians and practitioners should be aware of the dramatic increase in obesity and its subsequent complications to prevent associated health risks. This systematic review aimed to provide better insight into the prevalence of overweight and obesity in the Iranian population. METHOD: An evaluation was conducted on all published observational studies from both national (SID, Irandoc, Iranmedex) and international (Web of Knowledge, PubMed, Scopus) sources, which reported the prevalence of overweight/obesity among normal population samples, between January 2012 and December 2021. RESULT: A total of 152 eligible studies were included in this meta-analysis. Of the 152 selected studies, 74 reported the prevalence of overweight/obesity in patients aged ≤ 18 years, and 61 studies in adults. In the rest of the articles (17 studies), the results were reported for a combination of these age groups. The prevalence of overweight and obesity in Iran was estimated at 20.1 (95% CI 17.92-22.30) and 13.44 (95% CI 11.76-15.22), respectively. This percentage (95% CI) was 11.71 (10.98-12.46) for overweight and 8.08 (7.02-9.22) for obesity in those aged ≤ 18 years, and 35.26 (32.61-37.99) for overweight and 21.38 (19.61-23.20) for obesity in those aged > 18 years. The overall prevalence of overweight and obesity in the entire population was 35.09% (95% CI 31.31-38.98). CONCLUSION: As obesity is on the rise in Iran, we should seek both weight loss strategies and ways to control comorbidities associated with high BMI.

Association between thyroid function and obesity phenotypes in healthy euthyroid individuals: an investigation based on Tehran Thyroid Study.

AIMS: We investigated whether thyroid function could be associated with obesity phenotypes amongst euthyroid individuals. MATERIALS AND METHODS: A cross-sectional analysis was conducted among healthy, euthyroid subjects. The study participants were chosen from the Tehran Thyroid Study (TTS). We analyzed 2988 euthyroid adults and classified them into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The statistical differences between thyroid hormones between various obesity phenotypes according to age and sex was compared using analysis of covariance (ANCOVA). RESULTS: It was found that MHNW participants had higher levels of FT4 when compared with metabolically healthy or unhealthy obese subjects (P < 0.001), even after adjustment for the confounding variables. No difference was observed in the levels of TSH (P = 0.260) among obesity phenotypes. In the subgroup analysis according to the age, a significant difference was observed in the level of FT4 only in subjects with age < 55 years (P = 0.001). However, analyzing men and women separately did not show a significant difference in the FT4 level among obesity phenotypes (P > 0.05). CONCLUSION: "Metabolically abnormality" was independently related to low normal FT4 levels in overweight/obese euthyroid individuals. There is a need for further research to understand how low FT4 levels are linked to metabolically unhealthy states in euthyroid individuals.

Does one-anastomosis gastric bypass provide better outcomes than sleeve gastrectomy in patients with BMI greater than 50? A systematic review and meta-analysis.

In patients with BMI greater than 50, sleeve gastrectomy (SG) may not be adequate to treat obesity. To determine whether one-anastomosis gastric bypass (OAGB) can provide better outcomes compared with SG in patients with BMI greater than 50, a systematic review and meta-analysis was conducted, including a total of nine retrospective studies with a total of 2332 participants. There was a significant difference in the percentage of excess weight loss [weighted mean difference (WMD): 8.52; 95% CI: 5.81-11.22; P<0.001) and percentage of total weight loss (WMD: 6.65; 95% CI: 5.05-8.24; P<0.001). No significant differences were seen in operative time (WMD: 1.91; 95% CI: -11.24 to 15.07; P=0.77) and length of stay in hospital (WMD: -0.41; 95% CI: -1.18 to 0.37; P=0.30) between the two groups. There were no significant differences between OAGB with SG in Clavien-Dindo grades I-III [odds ratio (OR): 1.56; 95% CI: 0.80-3.05], or grade IV complications (OR: 0.72; 95% CI: 0.18-2.94). The meta-analysis on remission of type 2 diabetes indicated a comparable effect between SG and OAGB (OR: 0.77; 95% CI: 0.28-2.16). The OAGB group had a significantly higher rate of remission of hypertension compared with the SG group (OR: 1.63; 95% CI: 1.06-2.50). The findings of this meta-analysis suggest that the OAGB accomplished a higher percentage of total weight loss and percentage of excess weight loss at short-term and mid-term follow-up but, there was no major difference between the OAGB and SG operations in terms of perioperative outcomes, complications, and diabetes remission.

Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator.

Several bioinformatics studies have been performed on high-throughput expression data to determine the cellular pathways and hub genes affected by Gastric cancer (GC). However, these studies differ in using a healthy tissue or normal tissue adjacent to the tumour (NAT) as calibrator tissues. This study was designed to find how using healthy or NAT tissues as calibrator tissues could affect pathway enrichment data and hub genes in GC. Two gene expression datasets with NAT tissues (GSE79973 and GSE118916) and one dataset with healthy tissues (GSE54129) were downloaded and processed by the limma package to screen the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis were performed by the Enrichr online tool. Protein-protein interaction network construction, module analysis, and hub genes selection were performed by Cytoscape software, Molecular Complex Detection plugin, and cytoHubba plugin, respectively. The gene expression profiling interactive analysis web server was used to analyse RNA sequencing expression data from The Cancer Genome Atlas Program. The Kaplan-Meier plotter was used to perform survival analysis. Our results showed that some KEGG and GO pathways were shared between studies with NAT and the study with healthy tissues. However, some terms, especially inflammation-related terms, were missed when NAT tissues were used as calibrator tissues. Also, only FN1 and COL1A1 are common hub genes between DEGs of the studies with NAT and healthy tissues. Since hub genes are usually extracted and suggested as candidate targets for GC diagnosis, prognosis, or treatment, selecting healthy or NAT tissues may affect the hub genes selection.

Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

Association between different metabolic phenotypes and the development of hypothyroidism: 9 years follow-up of Tehran thyroid study.

Purpose: The association between metabolic phenotypes and thyroid function has not yet been established; therefore, this study examined whether different metabolic phenotypes are associated with the development of hypothyroidism. Methods: Study participants were selected from the Tehran Thyroid Study (TTS). A total of 3338 euthyroid adults were included and categorized into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The participants were assessed at baseline and during three follow-up studies at three-year intervals. Multiple logistic regression analysis was used to examine the relationship between metabolic phenotypes and the development of hypothyroidism. Results: In the total population, the chi-square test was only significant (P=0.008) in 3rd year with a higher prevalence of hypothyroidism in the MUNW phenotype, followed by MHO, MUO, and MHNW. Moreover, in the 3rd and 9th years of follow-up, hypothyroidism was more prevalent in MUO only in male subjects (P=0.002 and 0.035, respectively). In the unadjusted model, the MHO phenotype increased the odds of hypothyroidism compared with the MHNW phenotype (OR=1.51; 95% CI=1.04, 2.18; P-value=0.031). After adjusting for confounding factors, the odds of hypothyroidism were higher in the MUNW (OR=1.86; 95% CI=1.17, 2.96; P-value=0.008), MHO (OR=1.71; 95% CI=1.09, 2.67; P-value=0.018), and MUO (OR=1.64; 95% CI=1.03, 2.62; P-value=0.036) phenotypes than in the MHNW group. The MUNW phenotype increased the risk of hypothyroidism compared to MHNW, only in males. However, in females, the MHO phenotype increased the risk of hypothyroidism compared to MHNW. Conclusion: Both obesity and metabolic abnormalities are associated with hyperthyroidism. Healthy metabolic and weight maintenance were associated with a lower risk of hypothyroidism in males and females.

Changes in Bone Turnover Markers after Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: a Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was performed to compare the alterations in bone turnover markers between SG and RYGB. A literature search was conducted in PubMed, Medline, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to find the studies. There was significant less increment in osteocalcin [WMD = - 5.98, 95% CI (- 9.30, - 2.47) P < 0.01] and parathyroid hormone (PTH) [WMD = - 9.59, 95% CI (- 15.02, - 4.16) P < 0.01] in the SG group compared to the RYGB group. No significant differences were seen in change of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (PINP), Ca, and 25(OH)-D between SG and RYGB groups. According to our meta-analysis, bone formation markers appear to have more increment following RYGB than SG. This observation is accompanied by a larger increase in PTH after RYGB patients compared to SG patients. PROSPERO: CRD42022308985.

The effect of exercise training on serum concentrations of chemerin in patients with metabolic diseases: a systematic review and meta-analysis.

CONTEXT: Elevated serum concentrations of chemerin is a significant factor in the development of metabolic disorders. OBJECTIVE: This systematic review and meta-analysis evaluated the influence of exercise training on serum concentrations of chemerin in patients with metabolic diseases. METHODS: Thirteen studies including 463 participants were included and analysed using a random-effects model to calculate weighted mean differences with 95% confidence intervals. RESULTS: Results indicated that exercise training significantly decreased serum concentrations of chemerin in patients with metabolic diseases when compared with controls. Subgroup analysis showed that exercise training resulted in decreases in serum concentrations of chemerin in men, however, this was not significant in women. Moreover, subgroup analyses based on the type of exercise did not reveal differential effects on serum concentrations of chemerin. CONCLUSION: Exercise training may produce improvements in serum concentrations of chemerin in patients with metabolic diseases. Further longer-term studies are needed to confirm these findings.

The effects of medical linear accelerator X-rays on human peripheral blood lymphocytes in the presence of glucosamine.

Glucosamine is widely prescribed as a dietary supplement used to treat arthritis. In this study, the radioprotective ability of glucosamine was evaluated against radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Blood samples were collected from five healthy male donors and were divided into four groups. Isolated lymphocytes and blood samples were treated with 10 µM of glucosamine for 2 h before exposure to 2 Gy radiation. The radioprotective potential of glucosamine was assessed by micronucleus assay, reactive oxygen species (ROS) level analysis, and flow cytometry. Irradiation significantly increased the micronuclei frequency as compared to the control group. Contrary to that pretreatment with glucosamine before irradiation significantly reduced the frequency of micronuclei. Furthermore, pretreatment with glucosamine significantly prevented the percentage of apoptotic lymphocytes. Also, glucosamine pretreatment significantly reduced the production of ROS in irradiated lymphocytes. This study shows glucosamine to be a potent radioprotector against radiation that induces DNA damage and apoptosis in human lymphocytes. Several additional in vivo and in vitro studies are needed before glucosamine can be considered as a radioprotective candidate in patients undergoing radiation therapy.

Obesity, Diabetes Mellitus, and Metabolic Syndrome: Review in the Era of COVID-19.

Coronavirus disease 2019 (COVID-19), a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now at pandemic levels leading to considerable morbidity and mortality throughout the globe. Patients with obesity, diabetes, and metabolic syndrome (MetS) are mainly susceptible and more probably to get severe side effects when affected by this virus. The pathophysiologic mechanisms for these notions have not been completely known. The pro-inflammatory milieu observed in patients with metabolic disruption could lead to COVID-19-mediated host immune dysregulation, such as immune dysfunction, severe inflammation, microvascular dysfunction, and thrombosis. The present review expresses the current knowledge regarding the influence of obesity, diabetes mellitus, and MetS on COVID-19 infection and severity, and their pathophysiological mechanisms.

The role of endoplasmic reticulum stress in the regulation of long noncoding RNAs in cancer.

Cancer cells must overcome a variety of external and internal stresses to survive and proliferate. These unfavorable conditions include the accumulation of mutations, nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause aggregation of misfolded proteins inside the endoplasmic reticulum. Under these conditions, the cell undergoes endoplasmic reticulum stress (ER-stress), and consequently initiates the unfolded protein response (UPR). Activation of the UPR triggers transcription factors and regulatory factors, including long noncoding RNAs (lncRNAs), which control the gene expression profile to maintain cellular stability and hemostasis. Recent investigations have shown that cancer cells can ensure their survival under adverse conditions by the UPR affecting the expression of lncRNAs. Therefore, understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.

CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells.

Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with BLIMP1-sufficient ex vivo expanded human T cells. Results: BLIMP1-deficiency caused an increase in central memory (CM) T cells and a decrease in effector memory (EM) T cells. There was a decrease in the amount of TIM3 exhaustion marker expression in BLIMP1-deficient T cells; however, there was an increase in PD1 exhaustion marker expression in BLIMP1-deficient T cells compared with BLIMP1-sufficient T cells. Conclusion: Our study provides the first functional evidence of the impact of BLIMP1 on the regulation of human T cell memory and exhaustion phenotype. These findings suggest that BLIMP1 may be a promising target to improve the immune response in adoptive T cell therapy settings.

Effects of sodium-glucose co-transporter-2 inhibitors on anthropometric indices and metabolic markers in overweight/obese individuals without diabetes: a systematic review and meta-analysis.

AIMS: To identify the impact of sodium-glucose co-transporter-2 (SGLT2) inhibitors on anthropometric indices and metabolic markers in individuals without diabetes who are overweight/obese. MATERIALS AND METHODS: Clinical trials investigating the safety and efficacy of SGLT2 inhibitors in overweight or obese adults were sought in PubMed, Scopus, Google Scholar, and EMBASE databases. The overall intervention effect was estimated using a random-effect meta-analysis. Jadad scale was used to assess the risk of bias. The heterogeneity of the studies was assessed using the Cochran's test (Q test) and I2 Index. Analyses of meta-regression were carried out to identify possible sources of heterogeneity among the trials. The analyses were all conducted using Stata, and p < .05 was set as the statistically significant level. RESULTS: Of the five clinical trials that were included in the meta-analysis, five, four, three, and two clinical trials met the eligibility criteria for evaluating the efficacy of SGLT2 inhibitors on the weight, waist circumference (WC) and blood pressure, body mass index (BMI), and lipid and glucose profile, respectively. According to the results, SGLT2 inhibitors lowered BMI (WMD = -0.47 [95% CI: -0.63, -0.31]; p < .001), and WC (WMD = -3.25 [95% CI: -6.36, -0.14]; p = .04), but had no significant influence on blood pressure, lipid, and glucose profile of overweight/obese patients compared to the control groups. CONCLUSION: The SGLT2 inhibitors appear to ameliorate some anthropometric and metabolic markers. There is, however, a limited number of studies, and further research is required for a firm conclusion. REGISTRATION CODE IN PROSPERO: CRD42022306415.