Adipokines and their role in acute pancreatitis.

Acute pancreatitis (AP) is characterized by an inflammatory response that leads to edema and haemorrhaging of pancreatic tissue. In severe cases, it can even result in the necrosis of pancreatic tissue following activation within the pancreas. Adipokines are biologically active molecules released by adipose tissue that have a wide-ranging impact on health and disease. Adipokines are cytokines produced not only in white adipose tissue but also in the fat surrounding the pancreas, and they play a role in the body's inflammatory response. The presence of increased adipose tissue, often associated with obesity, has been linked to a heightened systemic inflammatory response in cases of AP. According to the literature, there are many adipokines. This article summarizes the role of adipokines in AP. Adipokines could be promising biomarkers for both diagnostic and new therapeutic treatment strategies in AP. However, a deeper knowledge of the signaling pathways of adipokines and their potential therapeutic role in AP is necessary.

Contributing role of metabolic genes APOE, FTO, and LPL in the development of atrial fibrillation: insights from a case-control study.

OBJECTIVE: The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). METHODS: A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. RESULTS: The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. CONCLUSION: The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

Cardiometabolic Risk Factors Related to Atrial Fibrillation and Metabolic Syndrome in the Pakistani Population.

Background and Objectives: This study aimed to examine the relationship between cardiometabolic risk factors and atrial fibrillation (AF) and the simultaneous presence of AF and metabolic syndrome (MetS) in the Pakistani population. Materials and Methods: A total of 690 subjects were enrolled (n = 230 patients with AF, n = 230 patients with AF and MetS, and n = 230 controls). The associations between cardiometabolic parameters and AF with and without MetS were analyzed by univariable and multivariable binary regression analyses. Results: Body mass index (BMI), fasting blood glucose (FBG), and triglycerides (TG) were independently positively correlated, but the glomerular filtration rate (GFR) and sodium were independently negatively correlated with AF. An increase in BMI, FBG, and TG levels by one unit measure increased the probability by 55.1%, 20.6%, and 1.3%, respectively, for the AF occurrence. A decrease in GFR and sodium levels increased the probability by 4.3% and 33.6%, respectively, for the AF occurrence. On the other hand, uric acid was independently negatively correlated, whereas sodium was independently positively correlated, with MetS and AF. A decrease in uric acid levels and an increase in sodium levels by 1 unit measure increased the probability for MetS and AF by 23.2% and 7.5%, respectively. Conclusions: Cost-effective and routinely measured parameters, i.e., BMI, FBG TG, GFR, and sodium levels, can be reliable indicators of AF, whereas serum uric acid and sodium levels are independently associated with AF and MetS in the Pakistani population. Timely recognition and the control of modifiable cardiometabolic risk factors are of great significance in the prevention of AF development.

Dexmedetomidine on the interplay of IL-6 and STAT3 pathways in adrenal gland damage-induced scalding burns in rats.

Scalding burns are a common form of thermal injury that often leads to systemic complications. Pro-inflammatory cytokines like interleukin-6 (IL-6) and the activation of signal transducer and activator of transcription 3 (STAT3) pathways have been linked to the pathophysiology of organ damage caused by burns. This study aimed to investigate the potential therapeutic effects of dexmedetomidine, an α2-adrenergic receptor agonist with anti-inflammatory properties, on the interplay of IL-6 and STAT3 pathways in adrenal gland damage following scalding burns in rats. Twenty-eight rats were divided randomly into four groups. Rats in group 1 (n=7, control) were given only 0.9% intraperitoneal (i.p.) NaCl. Rats in group 2 (n=7, DEX) were exposed to 25°C water for 17 s on day 1 and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days; for rats in group 3 (n=7, Burn), boiling water of 94°C was applied inside for 17 s. Rats in group 4 (n=7, Burn+DEX) were exposed to 94°C water for 17 s and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days. Adrenal gland tissues were histopathological examined, and STAT3, IL-6, and TUNEL staining were performed using immunohistochemically. Our results revealed that scalding burns increased IL-6 and STAT3 expression in the adrenal glands of rats. Histological analysis demonstrated that dexmedetomidine administration ameliorated adrenal gland damage and reduced inflammatory cell infiltration. Our findings suggest that dexmedetomidine protects the adrenal glands in scalding burns. This protection appears to be mediated, at least in part, by its modulation of IL-6 and STAT3 pathways.

Effect of fibromyalgia on demographic, biochemical, metabolic and inflammatory profiles: a single-centre retrospective study.

OBJECTIVES: The objective of this study is to ascertain the disparities in demographic features and biochemical profiles between individuals diagnosed with fibromyalgia (FM) and a control group of healthy individuals. METHODS: This retrospective, cross-sectional study compared the demographic, biochemical, metabolic, and inflammatory indexes and rates of 174 FM patients diagnosed using the American College of Rheumatology 2016 diagnostic criteria between January 2023 and January 2024, and 186 healthy control groups. RESULTS: There was no difference between the FM and control groups in terms of alcohol consumption, marital status, or diabetes mellitus. The smoking rate is higher, and the educational level was found to be lower for FM versus the control. There was no significant difference between FM and controls regarding waist-height ratio, triglyceride-glucose index, plasma atherogenic index, vitamin B12, and folate levels. Monocyte HDL ratio, cardiometabolic index, magnesium, HbA1c, and ferritin levels were significantly higher in the control than in FM (p<0.001, p=0.039, p=0.007, p<0.001, p<0.001, respectively). C-reactive protein, erythrocyte sedimentation rate, systemic immune-inflammatory index, neutrophil-lymphocyte rate, platelet lymphocyte rate, and vitamin D levels were found to be higher in FM compared to control (p=0.001, p=0.032, p=0.003, p=0.030, p=0.003, p<0.001, respectively). A weak positive correlation was observed between the fibromyalgia impact questionnaire (FIQ) score and disease duration, as well as between pain degree and ESR, and pain degree and CRP. The study revealed a weak inverse relationship between Widespread Pain Index (WPI) and waist circumference. CONCLUSIONS: This study highlights fthe association f ibromyalgia with elevated inflammatory markers, altered metabolic parameters, and specific demographic characteristics.

Therapeutic Potential of Sodium-glucose Co-transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists for Patients with Acute Coronary Syndrome: A Review of Clinical Evidence.

Atherosclerotic Cardiovascular Disease (ASCVD) is still one of the leading causes of death globally, with Coronary Artery Disease (CAD) being the most prevalent form of ASCVD. Patients with type 2 Diabetes Mellitus (DM) experience an increased risk for ASCVD during the disease course, with CAD being the most common cause of death among affected individuals, resulting in shorter life expectancy and increased morbidity among survivors. Recently, 2 novel classes of anti-diabetic drugs, namely Sodium-Glucose co-Transporter-2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, have shown impressive cardio-renal benefits for patients with type 2 DM, while they might decrease cardio-renal risk even in the absence of baseline DM. However, there is no evidence to date regarding their safety and efficacy in the setting of an acute coronary syndrome (ACS) event, regardless of concomitant DM. This study aims to provide a detailed, updated presentation of currently available clinical evidence concerning the potential role of SGLT-2 inhibitors and GLP-1 receptor agonists in the setting of an ACS, and to highlight whether those drug classes could be utilized as adjuncts to standard-of-care treatment in this specific patient population, along with a presentation of the potential short- and long-term cardiovascular benefits.

Are Oxidative Stress Biomarkers Reliable Part of Multimarker Panel in Female Patients with Type 2 Diabetes Mellitus?

Background: Oxidative stress and inflammation are the key features of metabolic diseases, including type 2 diabetes mellitus (T2D). However, studies that explored redox homeostasis parameters in relation to T2D show discrepant results. Accordingly, we aimed to examine the potential reliability of oxidative stress biomarkers [i.e., determined by malondialdehyde (MDA), advanced oxidation protein products (AOPP) and catalase (CAT)] in addition to traditional cardiometabolic parameters in relation to T2D in female cohort. Methods: A total of 214 women (of them 40.6% T2D) were consecutively recruited in the study. Principal component analysis with varimax rotation was performed to determine the adequate number of factors consisting of anthropometric, traditional cardiometabolic and redox status markers. Results: MDA and AOPP concentrations were lower, but CAT activity was higher in T2D group as compared with controls (P < 0.001, P = 0.002, P < 0.001). Traditional markers related factor (i.e., with positive loading of waist circumference, triglycerides, uric acid, high sensitivity C-reactive protein and negative loadings of high-density lipoprotein cholesterol) was found to be independently related with T2D in multivariate binary regression analysis, whereas oxidative stress related factor (i.e., with positive loading of MDA and AOPP) lost its independent prediction after adjustment for confounding factors (i.e., age, menopausal status, antihypertensive, and hypolipemic therapies). Increased Traditional markers related factor was associated with more than three times higher probability for T2D onset (OR = 3.319, p < 0.001). Conclusion: Oxidative stress biomarkers, i.e., MDA, AOPP, and CAT are not superior over traditional cardiometabolic markers in relation to T2D in female population. Future studies with both gender included are needed to confirm such results.

Cluster analysis of patient characteristics, treatment modalities, renal impairments, and inflammatory markers in diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is caused by an interplay of various factors where chronic hyperglycemia and inflammation have central role in its onset and progression. Identifying patient groups with increased inflammation in order to provide more personalized approach has become crucial. We hypothesized that grouping patients into clusters according to their clinical characteristics could identify distinct unique profiles that were previously invisible to the clinical eye. A cross-sectional record-based study was performed at the Primary Health Care Center Podgorica, Montenegro, on 424 T2DM patients aged between 30 and 85. Using hierarchical clustering patients were grouped into four distinct clusters based on 12 clinical variables, including glycemic and other relevant metabolic indicators. Inflammation was assessed through neutrophil-to-lymphocyte (NLR) and platelet to lymphocyte ratio (PLR). Cluster 3 which featured the oldest patients with the longest T2DM duration, highest hypertension rate, poor glycemic control and significant GFR impairment had the highest levels of inflammatory markers. Cluster 4 which featured the youngest patients, with the best glycemic control, the highest GFR had the lowest prevalence of coronary disease, but not the lowest levels of inflammatory markers. Identifying these clusters offers physicians opportunity for more personalized T2DM management, potentially mitigating its associated complications.

Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease.

Inflammatory cytokines have been implicated as crucial contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD). The exact mechanisms by which interleukins (ILs) contribute to NAFLD may vary, and ongoing research is aimed at understanding the specific roles of different ILs in the pathogenesis of this condition. In addition, variations in environmental factors and genetics in each individual can influence the onset and/or progression of NAFLD. The lack of clinical studies related to the potential therapeutic properties of IL-1 inhibitors currently does not allow us to conclude their validity as a therapeutic option, although preclinical studies show promising results. Further studies are needed to elucidate their beneficial properties in NAFLD treatment.

Oxidative stress and metabolic biomarkers in patients with Psoriasis.

Background: Psoriasis is an autoinflammatory disease that affects not only skin but multiple organs thus being associated with many comorbidities. Oxidative stress and inflammation play the major role in the pathogenesis of this disease. Studies that examined by-products of oxidative stress in psoriasis show discrepant results. Hence, we aimed to examine the oxidative stress, inflammation and metabolic markers and to explore their potential relationship with disease severity in patients with psoriasis. Methods: This case-control study comprised of 35 patients with psoriasis and 35 age, sex and body mass index-matched healthy controls. Metabolic and oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), and catalase (CAT)] were measured. The principal component analysis (PCA) was employed to reduce the number of measured variables into smaller number of factors. PCA factors were subsequently used in logistic regression analysis for severe psoriasis prediction.

Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS: Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS: A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION: The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.

The Association between Coagulation and Atrial Fibrillation.

The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.

Role of Cardiac Biomarkers in Hepatic Disorders: A Literature Review.

Various studies have reported the association between cardiac markers and hepatic disorders. The main objective of this review article was to elucidate the significance of important cardiac indicators such as ischemia-modified albumin, cardiac troponin, cardiac natriuretic peptides, creatine kinase, creatine kinase-MB, lactate dehydrogenase, heart-type fatty acid-binding protein, osteopontin, soluble suppression of tumorigenicity 2, C-reactive protein, and lipoprotein(a) in the development of hepatic disorders. In addition, it highlighted recent notable discoveries and accomplishments in this field and identified areas requiring further investigation, ongoing discussions, and potential avenues for future research. Early identification and control of these cardiac markers might be helpful to control the prevalence of hepatic disorders associated with cardiovascular diseases.

Interleukins: pathophysiological role in acute pancreatitis.

Acute pancreatitis (AP) is a common inflammatory state characterized by a clinical course that can lead to serious local and extrapancreatic organ malfunction and failure. Interleukins (ILs) are biologically active glycoproteins primarily produced by macrophages and lymphocytes. According to the literature, there are many ILs. However, this article represents a summary of the role of ILs in AP, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, and IL-20. The ways to modulate IL activity to reduce inflammation and improve outcomes in individuals with this condition are under investigation. Drugs that target specific ILs might be developed to mitigate the effects of AP.

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis.

AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.

Contributing role of metabolic genes APOE, FTO, and LPL in the development of atrial fibrillation: insights from a case-control study

SUMMARY OBJECTIVE: The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). METHODS: A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. RESULTS: The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. CONCLUSION: The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.