Unveiling the Ghrelin and Obestatin Roles in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis Assessing Their Pathogenic Implications and Biomarker Utility.

BACKGROUND: Inflammatory bowel disease (IBD), pathologically known as chronic inflammation of the gastrointestinal tract, is among the diseases with a high burden worldwide. Ghrelin and obestatin, as adipocytokines mainly in adipose tissues, are involved in immune responses and inflammatory pathways. Studies have assessed the circulatory ghrelin levels in patients with IBD. Herein, we aim to pool these studies through systematic review and meta-analysis. METHODS: Four international databases, PubMed, Embase, Scopus, and the Web of Science were systematically searched for studies assessing ghrelin or obestatin levels in patients with IBD (either Crohn's disease [CD] or ulcerative colitis [UC]) in active phase or in remission. Random-effects meta-analysis was conducted in order to calculate the pooled estimate using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Nineteen studies were included in our systematic review, comprising 1064 patients with IBD (476 UC and 588 CD). A meta-analysis of 11 studies for comparison of active and quiescent disease showed that patients with active IBD had significantly higher levels of ghrelin (SMD, 0.70; 95% CI, 0.06 to 1.34; P = .03). However, in separate analyses for UC or CD, no such difference was observed (SMD, 1.30; 95% CI, -0.28 to 2.88, P = .11; and SMD, 0.80; 95% CI, -0.41 to 2.01; P = .20, respectively). No significant difference was also observed in ghrelin levels between patients with active IBD and healthy control subjects. Obestatin levels also were not different between patients with active disease and those in remission (SMD, 0.31; 95% CI, -0.05 to 0.68; P = .09). On the other hand, the obestatin/ghrelin ratio was significantly lower in patients with active IBD (SMD, -1.90; 95% CI, -2.45 to -1.35; P < .01). CONCLUSIONS: Our results demonstrate that IBD patients with active disease have higher levels of ghrelin, which needs to be confirmed in future studies. Also, the obestatin/ghrelin ratio might be a promising biomarker for the assessment of disease activity.

Ghrelin, as an adipokine, can be a potential biomarker for distinguishing active inflammatory bowel disease from disease remission. Obestatin/ghrelin ratio was also significantly lower in patients with active inflammatory bowel disease. These biomarkers should be investigated in future studies.

Safety of sodium-glucose cotransporter 2 inhibitors drugs among heart failure patients: a systematic review and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce morbidity and mortality for heart failure (HF) patients and are recommended as cornerstones for their medical therapy. Utilization in clinical practice remains low for multiple reasons, one of which may be adverse events. We investigated the incidence of these events to see if they are associated with SGLT2i use. A systematic search was performed in databases, including PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and WHO's International Clinical Trials Registry Platform. Relevant randomized controlled trial studies assessing the safety outcomes of SGLT2i in HF patients were included in this study. We conducted the common-effect meta-analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of safety outcomes in SGLT2i compared with placebo. Eighteen studies were included in the meta-analysis composed of 12 925 HF patients taking an SGLT2i and 12 747 taking a placebo. The meta-analysis indicated that the all-cause mortality and serious adverse events (SAEs) were lower in the SGLT2i group (RR, 0.91; 95% CI, 0.85-0.97; P = 0.005, I2 = 0%; and RR, 0.92; 95% CI, 0.90-0.95; P < 0.001, I2 = 43%, respectively). Volume depletion and genitourinary infections were more prevalent in the SGLT2i group (RR, 1.17; 95% CI, 1.06-1.28; P = 0.001, I2 = 0%; and RR, 1.27; 95% CI, 1.13-1.43; P < 0.001, I2 = 17%, respectively). Our meta-analysis demonstrated that using SGLT2is in HF patients was correlated with reduced mortality and SAEs, with a more prominent effect in HF with reduced ejection fraction patients and those taking dapagliflozin.

Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM. METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI). RESULTS: Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively. CONCLUSION: Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.

Insights into the Role of Galectin-3 as a Diagnostic and Prognostic Biomarker of Atrial Fibrillation.

Atrial fibrillation (AF) is an irregular atrial activity and the most prevalent type of arrhythmia. Although AF is easily diagnosed with an electrocardiogram, there is a keen interest in identifying an easy-to-dose biomarker that can predict the prognosis of AF and its recurrence. Galectin-3 (Gal-3) is a beta-galactoside binding protein from the lectin family with pro-fibrotic and -inflammatory effects and a pivotal role in a variety of biological processes, cell proliferation, and differentiation; therefore, it is implicated in the pathogenesis of many cardiovascular (e.g., heart failure (HF)) and noncardiovascular diseases. However, its specificity and sensitivity as a potential marker in AF patients remain debated and controversial. This article comprehensively reviewed the evidence regarding the interplay between Gal-3 and patients with AF. Clinical implications of measuring Gal-3 in AF patients for diagnosis and prognosis are mentioned. Moreover, the role of Gal-3 as a potential biomarker for the management of AF recurrence is investigated. The association of Gal-3 and AF in special populations (coronary artery disease, HF, metabolic syndrome, chronic kidney disease, and diabetes mellitus) has been explored in this review. Overall, although further studies are needed to enlighten the role of Gal-3 in the diagnosis and treatment of AF, our study demonstrated the high potential of this molecule to be used and focused on by researchers and clinicians.

Endocan in prediabetes, diabetes, and diabetes-related complications: a systematic review and meta-analysis.

BACKGROUND: Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which diabetes can impact patients' lives. Endocan as an inflammatory endothelial biomarker has been shown to increase in several communicable and non-communicable diseases. Herein, we aim to investigate the role of endocan as a biomarker in diabetes as a systematic review and meta-analysis. METHODS: International databases, including PubMed, Web of Science, Scopus, and Embase were searched for relevant studies assessing blood endocan in diabetic patients. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of circulating endocan levels between diabetic patients and non-diabetic controls were conducted through random-effect meta-analysis. RESULTS: Totally, 24 studies were included, assessing 3354 cases with a mean age of 57.4 ± 8.4 years. Meta-analysis indicated that serum endocan levels were significantly higher in diabetic patients in comparison with healthy controls (SMD 1.00, 95% CI 0.81 to 1.19, p-value < 0.01). Moreover, in the analysis of studies with only type-2 diabetes, the same result showing higher endocan was obtained (SMD 1.01, 95% CI 0.78 to 1.24, p-value < 0.01). Higher endocan levels were also reported in chronic diabetes complications such as diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy. CONCLUSION: Based on our study's findings, endocan levels are increased in diabetes, however, further studies are needed for assessing this association. In addition, higher endocan levels were detected in chronic complications of diabetes. This can help researchers and clinicians in recognizing disease endothelial dysfunction and potential complications.

Association between brain-derived neurotrophic factor levels and obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Chronic intermittent hypoxia associated with obstructive sleep apnea (OSA) can affect neurons and glial cells, leading to cell stress and damage, and changes in brain-derived neurotrophic factor (BDNF) levels. This study investigated the relation between BDNF, OSA, and continuous positive airway pressure (CPAP) - the standard of care in patients with OSA. METHODS: Five databases were searched for studies that evaluated BDNF serum and/or plasma levels in patients with OSA and controls or publications assessing the effect of CPAP treatment on BDNF levels. We used standardized mean difference (SMD) with its 95% confidence interval (CI) comparison between patients with OSA and controls. RESULTS: Ten studies were included in our study assessing the relation between BDNF levels, OSA, and CPAP treatment. Five studies of BDNF levels in OSA compared to controls showed no significant difference (SMD = - 0.52, 95% CI [- 1.93; 0.89], p-value = 0.47). No statistically significant difference was found between CPAP treatment in patients with OSA and BDNF levels (SMD = - 0.78, 95% CI [- 1.77; 0.21], p-value = 0.12). CONCLUSION: BDNF peripheral levels are not significantly altered in OSA or by its related treatment, preventing its use as a biomarker.