Sequence-based detection of emerging antigenically novel influenza A viruses.

The detection of evolutionary transitions in influenza A (H3N2) viruses' antigenicity is a major obstacle to effective vaccine design and development. In this study, we describe Novel Influenza Virus A Detector (NIAViD), an unsupervised machine learning tool, adept at identifying these transitions, using the HA1 sequence and associated physico-chemical properties. NIAViD performed with 88.9% (95% CI, 56.5-98.0%) and 72.7% (95% CI, 43.4-90.3%) sensitivity in training and validation, respectively, outperforming the uncalibrated null model-33.3% (95% CI, 12.1-64.6%) and does not require potentially biased, time-consuming and costly laboratory assays. The pivotal role of the Boman's index, indicative of the virus's cell surface binding potential, is underscored, enhancing the precision of detecting antigenic transitions. NIAViD's efficacy is not only in identifying influenza isolates that belong to novel antigenic clusters, but also in pinpointing potential sites driving significant antigenic changes, without the reliance on explicit modelling of haemagglutinin inhibition titres. We believe this approach holds promise to augment existing surveillance networks, offering timely insights for the development of updated, effective influenza vaccines. Consequently, NIAViD, in conjunction with other resources, could be used to support surveillance efforts and inform the development of updated influenza vaccines.

The effect of weight loss therapies on sirtuin 1 regulation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recent evidence shows the role of sirtuin 1(SIRT1), a family of evolutionarily conserved proteins, as a potential therapeutic target in the prevention and treatment of obesity and metabolic diseases. Some evidence shows the moderating effects of weight loss interventions on this factor. However, the findings are contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of weight loss interventions on SIRT 1 modulation. METHODS: For this study, we searched four electronic databases using predefined keywords from inception until March 2024. We includedrandomized controlled trials that evaluated the effect of weight reduction strategies on SIRT1 levels. The random-effects model analysis was used to obtain the pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI). The meta-analysis was conducted using RevMan version 5.3 software and Stata version 12.0. RESULTS: Twelve studies with 627 volunteers were included. The pooled findings showed that weight loss interventions have no significant effect on the modulation of SIRT1 compared to the control group (pooled WMD of 0.58 ng/mL; 95% confidence interval [CI] -0.17 to 1.33; p = 0.130). However, subgroup analysis showed that weight loss interventions significantly modulate SIRT1 at metabolic disease (WMD: 1.2 ng/mL, 95% CI: 0.11 to 2.62, I2 = 82.9%). In addition, subgroup findings indicated health status and body mass index (BMI) as sources of high and potential heterogeneity. CONCLUSIONS: Based on the findings, weight loss therapies in individuals having a metabolic disorder appear to generate a considerable increase in SIRT1 levels.

The relation between MIND diet with odds of attention-deficit/hyperactivity disorder in Iranian children: a case-control study.

This study aims to investigate the association between the MIND index (Mediterranean- Dietary approaches to Stop Hypertension diet Intervention for Neurodegenerative Delay) and attention-deficit hyperactivity disorder (ADHD) in the Iranian children. It builds upon existing research that highlights the role of dietary antioxidants in alleviating psychological disorders, cognitive impairments, and memory deficits. Additionally, previous studies have separately explored the beneficial effects of the Mediterranean and DASH diets on these issues. A case-control study was undertaken in Iran, involving a sample of 360 children and adolescents aged 7-13 years. Participants were divided into two groups, namely the case group (n = 120) and the control group (n = 240), with age and sex being matched between the groups. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) was employed for the diagnosis of ADHD. The MIND diet score was computed using the food intake data acquired from the Food Frequency Questionnaire (FFQ) completed by the subjects. The mean ± SD for the age and BMI of the study population was 8.76 ± 1.64 years and 16.90 ± 3.58 kg/m2, respectively. The mean score of MIND in this study was 27.93. After adjustment for potential confounder in the final model, subjects in highest compared to the lowest quartile of MIND diet score had significantly lower odds of ADHD (OR = 0.59, 95% CI 0.37-0.83; P-trend = 0.019). This study provides valuable evidence suggesting that adherence to the MIND diet is associated with decreased odds of ADHD.

Effect of Overweight and Obesity on the Response to Anti-TNF Therapy and Disease Course in Children With IBD.

BACKGROUND: This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD). METHODS: This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included; those who were overweight/obese were compared with children who were well/undernourished. RESULTS: Six hundred thirty-seven children (370 [58%] males; mean age 11.5 ±â€…3.5 years) were included; 140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI ≤1 SD (CG). The mean follow-up time was 141 ±â€…78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction; however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse. CONCLUSIONS: Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

Overweight and obese children with inflammatory bowel disease required more frequent dose escalations, but overall loss of response to anti-TNF therapy was not increased. Furthermore, in the long term, they tend to have a higher risk for relapse.

Pertussis vaccines, epidemiology and evolution.

Pertussis, which is caused by Bordetella pertussis, has plagued humans for at least 800 years, is highly infectious and can be fatal in the unvaccinated, especially very young infants. Although the rollout of whole-cell pertussis (wP) vaccines in the 1940s and 1950s was associated with a drastic drop in incidence, concerns regarding the reactogenicity of wP vaccines led to the development of a new generation of safer, acellular (aP) vaccines that have been adopted mainly in high-income countries. Over the past 20 years, some countries that boast high aP coverage have experienced a resurgence in pertussis, which has led to substantial debate over the basic immunology, epidemiology and evolutionary biology of the bacterium. Controversy surrounds the duration of natural immunity and vaccine-derived immunity, the ability of vaccines to prevent transmission and severe disease, and the impact of evolution on evading vaccine immunity. Resolving these issues is made challenging by incomplete detection of pertussis cases, the absence of a serological marker of immunity, modest sequencing of the bacterial genome and heterogeneity in diagnostic methods of surveillance. In this Review, we lay out the complexities of contemporary pertussis and, where possible, propose a parsimonious explanation for apparently incongruous observations.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

BACKGROUND: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. METHODS: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. RESULTS: We included 101 children with a mean age at diagnosis of 12.8 ±â€…2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. CONCLUSIONS: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Tofacitinib, widely reported in adult ulcerative colitis, has very limited pediatric data. This international collaboration is the largest pediatric study on the efficacy and safety of tofacitinib to date, providing important supportive data to clinicians and regulators.

Direct and macrophage stimulation mediated effects of active, inactive, and cell-free supernatant forms of Akkermansia muciniphila and Faecalibacterium duncaniae on hepcidin gene expression in HepG2 cells.

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression.

Association between Baltic sea diet and healthy Nordic diet index with risk of non-alcoholic fatty liver disease: a case-control study.

Recent evidence shows the beneficial effects of Baltic Sea diet score (BSDS) and healthy Nordic diet index (HNDI) on chronic diseases, however, there is no evidence to investigate them on the risk of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate the associations between BSDS and HNDI with the risk of NAFLD. In this case-control study, 552 people in good health and 340 people with NAFLD over the age of 18 took part. The evaluation of BSDS and HNDI employed a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Binary logistic regression was used to determine how OBS and NAFLD are related. The mean BSDS and HNDI were 16.00 ± 2.49 and 11.99 ± 2.61, respectively. The final model's confounder adjustment revealed that greater HNDI adherence scores gave protection against the occurrence of NAFLD (odds ratio [OR]: 0.42; 95% confidence interval [CI] 0.18-0.98; P for trend = 0.043). In addition, those with the highest BSDS scores had significantly lower risks of developing NAFLD compared to subjects with the lowest scores (OR = 0.48, 95% CI 0.32-0.89; p for trend = 0.003). Our findings showed that following a healthy Nordic diet can significantly prevent the risk of developing NAFLD, and suggest that the highly nutritious components of the Nordic diet are beneficial for the prevention of NAFLD.

The effects of bupropion alone and combined with naltrexone on weight loss: a systematic review and meta-regression analysis of randomized controlled trials.

BACKGROUND: The global prevalence of obesity and overweight is a significant concern in the field of public health. However, addressing and combating these conditions pose considerable challenges. Numerous interventional studies have been conducted to assess the possible impact of bupropion on weight reduction. The primary objective of this study was to conduct a comprehensive investigation into the effects of bupropiona alone and in combination with naltrexone on weight, body mass index (BMI), and waist circumferences (WC). METHODS: A systematic search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled trials that examined the impact of bupropion, either as a standalone intervention or in combination with naltrexone, on weight loss outcomes. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals. RESULTS: Twenty five studies with 22,165 participants' were included in this article. The pooled findings showed that bupropion administration has an effect on lowering weight (WMD: -3.67 kg, 95% CI: -4.43 to -2.93) and WC (WMD: -2.98 cm, 95% CI -3.78 to -2.19) in compared with control groups. The analysis also showed that the effects of the present intervention on weight and WC during the intervention are > 26 weeks and ≤ 26 weeks compared to the other group, respectively. In addition, changes in weight loss and WC after receiving bupropion together with naltrexone were more compared to bupropion alone. CONCLUSIONS: In conclusion, the addition of combination therapies like bupropion and naltrexone to lifestyle modifications including diet would cause significant weight loss.

The effects of weight loss interventions on children and adolescents with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non-alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD. Methods: Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis. Results: Eighteen eligible clinical trials were included in this systematic review and meta-analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose (p = 0.007), insulin (p = 0.002), homeostatic model assessment-insulin resistance (HOMA-IR) (p = 0.003), weight (p = 0.025), body mass index (BMI) (p = 0.003), BMI z-score (p < 0.001), waist circumference (WC) (p = 0.013), triglyceride (TG) (p = 0.001), and aspartate transaminase (AST) (p = 0.027). However, no significant changes were found in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine transaminase (ALT), and hepatic steatosis grades (all p > 0.05) following weight loss interventions. Conclusions: Weight loss interventions had significant effects on NAFLD-related parameters including glucose, insulin, HOMA-IR, weight, BMI, BMI z-score, WC, TG, and AST.

Genomic testing identifies monogenic causes in patients with very early-onset inflammatory bowel disease: a multicenter survey in an Iranian cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis.

INTRODUCTION: There is a proven role for hepcidin and the composition of gut microbiota and its derivatives in the pathophysiology of liver fibrosis. AREA COVERED: This review focuses on the literature search regarding the effect of hepcidin and gut microbiota on regulating liver physiology. We presented the regulating mechanisms of hepcidin expression and discussed the possible interaction between gut microbiota and hepcidin regulation. Furthermore, we investigated the importance of the hepcidin gene in biological processes and bacterial interactions using bioinformatics analysis. EXPERT OPINION: One of the main features of liver fibrosis is iron accumulation in hepatic cells, including hepatocytes. This accumulation can induce an oxidative stress response, inflammation, and activation of hepatic stellate cells. Hepcidin is a crucial regulator of iron by targeting ferroportin expressed on hepatocytes, macrophages, and enterocytes. Various stimuli, such as iron load and inflammatory signals, control hepcidin regulation. Furthermore, a bidirectional relationship exists between iron and the composition and metabolic activity of gut microbiota. We explored the potential of gut microbiota to influence hepcidin expression and potentially manage liver fibrosis, as the regulation of iron metabolism plays a crucial role in this context.

The efficacy of low glycemic index diet on seizure frequency in pediatric patients with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Despite extensive research examining the effect of a low glycemic index (LGI) diet on the frequency of seizures in patients with epilepsy, the findings are inconclusive. Hence, we performed a systematic review and meta-analysis in order to clarify the potential effect of a low glycemic index (LGI) diet on the frequency of seizures in children. METHODS: A systematic review and meta-analysis written in accordance with the PRISMA checklist was realized using a comprehensive systematic search in four electronic databases until October 2023 without time or language restrictions. A random effects model was employed to combine the data. The main outcomes were analyzed using weight mean difference (WMD) and 95 % confidence interval (95 % CI). In total, 13 studies met the eligible criteria and were included. RESULTS: The publications included in this study were published between 2005 and 2021. The duration of the interventions in the studies included in this analysis ranged from 6 to 58 weeks. Our findings indicated that the pooled efficacy rate for < 50 %, ≥ 50 %, > 90 % seizure reduction in patients with epilepsy receiving a low glycemic index diet was 39 % (95 % CI: 26, 52), 34 % (95 % CI: 23, 45), and 19 % (95 % CI: 13, 25), respectively. It seems that the efficacy of this ketogenic diet in reducing seizures is greater during a shorter intervention period than 12 weeks. CONCLUSION: This systematic review and meta-analysis suggests that the low glycemia index diet can be beneficial as a treatment for epilepsy in pediatric patients.

The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is one of the most important diseases which controlling its related risk factors, such as metabolic and inflammatory biomarkers, is necessary because of the increased mortality risk of that. The aim of our meta-analysis is to reveal the general effect of vitamin K supplementation on its related risk factors. Original databases were searched using standard keywords to identify all randomized clinical trials (RCTs) investigating the effects of vitamin K on CVD. Pooled weighted mean difference (WMD) and 95 % confidence intervals (95 % CI) were achieved by random-model effect analysis for the best estimation of outcomes. The statistical heterogeneity was determined using the Cochran's Q test and I2 statistics. Seventeen studies were included in this systematic review and meta-analysis. The pooled findings showed that vitamin K supplementation can reduce homeostatic model assessment insulin resistance (HOMA-IR) (WMD: -0⋅24, 95 % CI: -0⋅49, -0⋅02, P = 0⋅047) significantly compared to the placebo group. However, no significant effect was observed on other outcomes. Subgroup analysis showed a significant effect of vitamin K2 supplementation compared to vitamin K1 supplementation on HOMA-IR. However, no significant effect was observed on other variables. Also, subgroup analysis showed no potential effect of vitamin K supplementation on any outcome and omitting any articles did not affect the final results. We demonstrated that supplementation with vitamin K has no effect on anthropometrics indexes, CRP, glucose metabolism, and lipid profile factors except HOMA-IR.

Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study.

A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta-analysis weighted mean RR: 0.71, 95% CI: 0.38-1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization's short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations.

The effect of metformin on adipokines levels: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Considering the role of adipokine on diseases related to metabolic syndrome and even chronic diseases, it seems necessary to investigate effective interventions on these factors. This study aimed to comprehensively investigate the effects of metformin on adipokines. METHODS: A comprehensive search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled studies that have examined the impact of metformin on adipokines, specifically leptin, adiponectin, and resistin. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals. RESULTS: Forty-nine studies were included in this article. The pooled findings showed that that the administration of metformin significantly decreases leptin (WMD: -3.06 ng/ml, 95 % CI: -3.81, -2.30, P < 0.001) and resistin (WMD: -1.27 µg/mL, 95 % CI: -2.22, -0.31, P = 0.009) levels in different populations compared to the control group. However, no significant effect of this antidiabetic drug on adiponectin levels was reported. The results obtained from the subgroup results in the present study also showed that metformin in people with a BMI greater than 30 kg/m2 compared to a BMI ≤ 30 kg/m2 causes a significant decrease in leptin levels and an increase in adiponectin levels. Also, metformin in lower doses (≤1500 mg/day) and younger people (<30 years) causes a significant increase in adiponectin levels. CONCLUSIONS: In general, considering the role of adipokines on metabolic disease and even chronic disease, this drug can be used as a potentially useful drug, especially in obese people, to improve these factors.