High-density Lipid Research Articles

8699 ​​Efficacy of Glucagon-like Peptide-1 Analogs In Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract Disclosure: F.A. Kelly: None. A.D. Lôbo: None. I.P. da Silva: None. J.C. Cardoso: None. M.S. Barros: None. F.D. Pessôa: None. M.G. Leite: None. R.Y. Ura Sudo: None. A.M. De Almeida: None. F.A. Moraes: None. V. Morbach: None. M.C. Souza: None. P.G. Lima: None. M.P. Lima: None. I.B. Andrade: None. M.B. Jardine: None. L.M. Lopes: None. Polycystic ovary syndrome (PCOS) affects one in ten women of reproductive age, painting a complex picture of metabolic dysfunction. Its hallmark triad includes irregular menstrual cycles, androgen excess, and polycystic ovaries. Beyond infertility concerns, PCOS carries a heavy burden of metabolic imbalances, often characterized by insulin resistance, dyslipidemia, and chronic low-grade inflammation. These intertwined factors place women with PCOS at increased risk for type 2 diabetes and cardiovascular disease, posing a significant long-term health challenge. Current first-line treatments like metformin focus mainly on managing insulin resistance and regulating menstrual cycles. However, unmet needs remain in addressing the broader metabolic derangements and preventing associated health complications. In light of this, glucagon-like peptide-1 (GLP-1) analogs have emerged as potential game-changers in the PCOS treatment landscape. Their multifaceted effects on metabolism beyond blood sugar regulation offer a promising avenue for optimizing care and improving long-term health outcomes in women with PCOS. This meta-analysis aims to evaluate the use of GLP-1 analogs on patients with PCOS to reduce body mass index (BMI), glycated hemoglobin (HbA1C), fasting blood glucose (FBG), high density lipid (HDL), low density lipid (LDL) and triglyceride. PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCT) comparing the use of GLP-1 analogs to placebo or other therapies in patients with PCOS. Treatment effects for continuous endpoints were pooled through mean differences (MD) with 95% confidence intervals. Heterogeneity was evaluated with the Cochran Q test, the prediction interval and I² statistics. Statistical analysis was performed in Revman 5.4. The results were reported following the Preferred Reporting Items for Systematic Review (PRISMA) guidelines.A total of 4 RCTs with 228 patients were included, of whom 137 were randomized to GLP-1 therapy, 58 to placebo, and 33 to other treatments. Over a mean follow-up time of 24 weeks, patients submitted to GLP-1 analogs presented significant decreases in HbA1C (MD -1.40%; 95% CI -1.64 to -1.16; p<000001; I²=0% ), FBG (MD -4.40 mg/dL; 95% CI -7.63 to -1.17; p=0.008; I²=0%) and HDL-c (MD -0.82 mg/dL; 95% CI -1.33 to -0.31; p=0.002; I²=3%); and a nonsignificant increase in LDL-c (MD 0.37 mg/dL; 95% CI -1.30 to 2.03; p=0.67; I²=0%); and nonsignificant decrease in BMI (MD -1.28 Kg/m²; 95% CI -3.18 to 0.63; p=0.19; I²=98%), and triglyceride (MD -10.50 mg/dL; 95% CI -22.81 to 1.81; p=0.09; I²=0%).In this meta-analysis of RCTs of patients with PCOS, the use of GLP-1 analogs showed a significant reduction in HbA1C, FBG, and HDL-c. A larger sample size of people are needed for further statistical analyses. Presentation: 6/3/2024

Evaluation of the Hypoglycemic and Hypolipidemic Potential of Extract Fraction of Quercus baloot Griff Seeds in Alloxan-induced Diabetic Mice.

The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes. For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds. The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days. The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27 g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas low-density lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes. In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds.

Clinical and Diagnostic Value of High-Density Lipoprotein-Based Inflammatory Indices and Lipid Ratios in Young Adults with Schizophrenia.

This study aimed to assess High-density Lipoprotein (HDL)-based Inflammatory Indices and lipid profile changes in antipsychotic-naive first-episode schizophrenia (AN-FES) patients, chronic schizophrenia (CS) patients, and explore the clinical and predictive value of these parameters for schizophrenia. The study cohort included 52 AN-FES patients, 46 CS patients, and 52 healthy controls (HCs), with an average age of 24 years. Upon admission, patients underwent complete blood count and lipid profile analyses. Various ratios were calculated, including neutrophil-to-HDL (NHR), monocyte-to-HDL (MHR), lymphocyte-to-HDL (LHR), and platelet-to-HDL (PHR), as well as lipid ratios like triglycerides/HDL, non-HDL/HDL, total cholesterol/HDL, and low-density lipoprotein/HDL. For the AN-FES group, these evaluations were repeated after two months of treatment with atypical antipsychotics. Statistical analyses included correlation analysis, Receiver Operating Characteristic (ROC) curve analysis, and univariate and multivariate regression. Compared to HCs, CS patients exhibited significantly higher MHR and NHR values, while AN-FES patients showed elevated levels of PHR, MHR, and NHR. No significant differences were observed in LHR or lipid ratios across the three groups. In the AN-FES cohort, MHR correlated positively with neutrophil counts, and NHR with monocyte counts. Additionally, white blood cell counts were positively associated with both MHR and NHR. Following treatment, NHR levels decreased, whereas TG/HDL ratios increased, with MHR and PHR remaining elevated. ROC analysis highlighted NHR as the most diagnostically valuable parameter (AUC = 0.799), with 86.5% specificity at an optimal cutoff of 3.534, outperforming MHR and PHR. Regression analyses recognized NHR (OR=2.225) as an independent risk factor for schizophrenia, even after adjusting for confounders. HDL-based inflammatory indices, particularly NHR, may serve as valuable diagnostic and prognostic markers in young adults with schizophrenia, even though significant alterations in lipid ratios were not observed in this demographic.

Artemisia vulgaris Extract as a Novel Therapeutic Approach for Reversing Diabetic Cardiomyopathy in a Rat Model.

Diabetic cardiomyopathy, a severe diabetic complication, impairs heart function, leading to heart failure. Treatment that effectively addresses this condition without causing side effects is urgently needed. Current anti-hyperglycemic therapies are expensive, has side effects and do not effectively prevent cardiac remodeling. Therefore, it is important to explore natural products that may have the potential to reverse cardiac remodeling. That is why the aim of the current study was to determine the left ventricular remodeling potential of the methanolic extract of Artemisia vulgaris in a diabetic cardiomyopathy rat model. Following the initial comprehensive phytochemical evaluation of plant phenolic and flavonoid content, which showed strong anti-hyperglycemic and antioxidant activities, an extract of Artemisia vulgaris was administered in an in vivo experiment. Diabetic cardiomyopathy was induced in Wistar albino rats according to previously described protocols in the literature, and the effect of treatment was checked by serum and histopathological analysis after 45 days. Artemisia vulgaris treatment significantly (p ≤ 0.05) reduced fasting blood glucose (108.5 ± 1.75 mg/dL), glycated hemoglobin (4.03 ± 0.12 %), serum glucose (116.66 ± 3.28 mg/dL), insulin (15.66 ± 0.66 ng/mL), total oxidant status (54.66 ± 3.22 µmol H2O2Equiv.L-1), Malondialdehyde (0.20 ± 0.01 mmol/L), total cholesterol (91.16 ± 3.35 mg/dL), triglycerides (130.66 ± 3.15 mg/dL), low-density lipids (36.57 ± 1.02 mg/dL), sodium (140 ± 3.21 mmol/L), calcium (10.44 ± 0.24 mmol/L), creatine kinase MB (1227.5 ± 17.89 IU/L), lactate dehydrogenase (1300 ± 34.64 IU/L), C-reactive protein (30 ± 0.57 pg/mL), tumor necrosis factor-α (58.66 ± 1.76 pg/mL), atrial natriuretic peptide (2.53 ± 0.04 pg/mL), B-type natriuretic peptide (10.66 ± 0.44 pg/mL), aspartate aminotransferase (86.5 ± 4.99 U/L), Alanine Transaminase (55.33 ± 2.90 U/L), urea (25.33 ± 1.15 mg/dL) and creatinine (0.64 ± 0.02 mg/dL) but significantly increased (p ≤ 0.05) total antioxidant capacity (1.73 ± 0.07 mmol Trolox Equil./L), high-density lipids (40 ± 1.59 mg/dL) and potassium (3.82 ± 0.04 mmol/L) levels. ECG and histopathology confirmed the significant improvement in remodeling and the reversal of structural changes in the heart and pancreas. In conclusion, Artemisia vulgaris possesses significant left ventricular remodeling potential in course of diabetes-induced cardiomyopathy.

Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant.

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

EDUKASI HIPERKOLESTEROLEMIA DI POSYANDU LANSIA KEMBANG SEPATU, WILAYAH KERJA PUSKESMAS BANJARBARU SELATAN

Cholesterol is a yellowish fat molecule that resembles wax which is produced by the liver and circulated throughout the body through the blood vessels. Hypercholesterolemia can occur when LDL (Low Density Lipid) levels are higher than HDL (High Density Lipid) levels. This health education activity aims to increase public knowledge and understanding, especially in the South Banjarbaru Community Health Center, regarding hypercholesterolemia including signs and symptoms, how to use drugs, and prevention. The activity includes several stages, namely the presentation of material using the lecture method and leaflet media, question and answer session, pretest and post test. The percentage result of the pretest average score is 51.4286% and the post test average is 97.1429%. This research concludes that there is an increase in community knowledge of the elderly posyandu after being provided with education and exposure to material related to cholesterol.

Feasibility of replacing fish oil with sunflower oil on the growth, body composition, fatty acid profile, antioxidant activity, stress response, and blood biomarkers of Labeo rohita.

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.

Incorporating longitudinal history of risk factors into atherosclerotic cardiovascular disease risk prediction using deep learning

It is increasingly clear that longitudinal risk factor levels and trajectories are related to risk for atherosclerotic cardiovascular disease (ASCVD) above and beyond single measures. Currently used in clinical care, the Pooled Cohort Equations (PCE) are based on regression methods that predict ASCVD risk based on cross-sectional risk factor levels. Deep learning (DL) models have been developed to incorporate longitudinal data for risk prediction but its benefit for ASCVD risk prediction relative to the traditional Pooled Cohort Equations (PCE) remain unknown. Our study included 15,565 participants from four cardiovascular disease cohorts free of baseline ASCVD who were followed for adjudicated ASCVD. Ten-year ASCVD risk was calculated in the training set using our benchmark, the PCE, and a longitudinal DL model, Dynamic-DeepHit. Predictors included those incorporated in the PCE: sex, race, age, total cholesterol, high density lipid cholesterol, systolic and diastolic blood pressure, diabetes, hypertension treatment and smoking. The discrimination and calibration performance of the two models were evaluated in an overall hold-out testing dataset. Of the 15,565 participants in our dataset, 2170 (13.9%) developed ASCVD. The performance of the longitudinal DL model that incorporated 8 years of longitudinal risk factor data improved upon that of the PCE [AUROC: 0.815 (CI 0.782–0.844) vs 0.792 (CI 0.760–0.825)] and the net reclassification index was 0.385. The brier score for the DL model was 0.0514 compared with 0.0542 in the PCE. Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration.

No evidence for a diminished ovarian reserve among patients with hypertensive disorders of pregnancy: a case control study

BackgroundExisting evidence suggests a relation between cardiovascular dysfunction and diminished ovarian reserve. While it is known that pre-existent cardiovascular dysfunction is also associated with the development of preeclampsia (PE) during pregnancy, we hypothesize that signs of diminished ovarian reserve may occur more frequently among women with a history of hypertensive disorders of pregnancy (HDP). The aim of our study was therefore to analyse if women with a history of HDP show signs of diminished ovarian reserve, represented by lower anti-Mullarian hormone (AMH) levels, compared to controls. For this retrospective observational case control study, patients included women with a history of HDP, whereas controls constituted of women with a history of an uncomplicated pregnancy. The study was conducted in a tertiary referral centre in which all women underwent a one-time cardiovascular and metabolic assessment. Ovarian reserve and markers of cardiovascular function were evaluated, adjusted for age and body mass index (BMI) using linear regression analyses.Results163 patients and 81 controls were included over a time span of 3 years. No signs of diminished ovarian reserve i.e. lower AMH level were observed in the patient group versus controls. A subgroup analysis even showed higher AMH levels in late onset HDP as compared to controls (2.8 vs. 2.0 µg/L, p = 0.025). As expected, cardiovascular function markers were significantly less favourable in the patient group compared to controls; higher levels of systolic blood pressure (BP) (5%), diastolic BP (4%), triglycerides (29%), glucose (4%) and insulin levels (81%) (all p < 0.05), whereas high density lipid (HDL) cholesterol was 12% lower (NS).ConclusionsDespite unfavourable cardiovascular risk profile, the present study does not substantiate the hypothesis that women with HDP show accelerated ovarian ageing as compared to healthy parous controls. Although HDP patients should be warned about their cardiovascular health, they shouldn’t be concerned about unfavourable ovarian reserve status.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes

BackgroundMaternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy.MethodsA retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age.Results(1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA.ConclusionsWe suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 μM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Reduced toxic effects of nano‑copper sulfate in comparison of bulk CuSO4 on biochemical parameters in the Rohu (Labeo rohita)

Considering the wide application of nanoparticles in various fields of life and growing concern regarding their toxic effects, the present study was designed with the aim to evaluate the potential risks of using copper sulfate nanoparticles (CuSO4-NPs) in comparison to bulk form. Nanoparticles of CuSO4, having mean size of 73 nm were prepared by ball milling method, and fingerlings of Labeo rohita were exposed to two levels, 20 and 100 μg L−1 of CuSO4 in both bulk and nano forms for 28 days and their comparative effects on the metallothioneins (MTs), heat shock proteins 70 (HSP 70), lipid profile, cholesterol (CHOL) and triglyceraldehyde (TG) levels, activities of some metabolic enzymes Alanine transaminase (ALT), Aspartate transaminase (AST) Akaline phosphatase (ALP), and genes expressions of HSP-70, TNF-α and IL1-ß were investigated. CuSO4 showed the concentration and particle type dependent effects. The over expression of HSPs and MTs, significant decreases in CHOL, TG, low density lipid (LDL) levels and ALP activity, while significant increases in high density lipid (HDL)level as well as ALT and AST activities and HSP-70, TNF-α and IL1-β expressions were observed in response to higher concentration of both bulk and nano form of copper sulfate. At lower concentration (20 μg L−1), however, only bulk form showed toxicity. Thus, low concentrations of CuSO4-NPs pose negligible threat to freshwater fish.

Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors

A series of novel indole-thiazolidinedione hybrid analogues (7a to 7 u) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues, 7r was found to be the most active PL inhibitor with an IC50 of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed via fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the in vitro results (Pearson’s r = 0.8355, p < 0.05). A molecular dynamics study (100 ns) indicated that 7r was stable in a dynamic environment. The analogue 7r exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the in-vitro profiles, 7r was selected for the in-vivo pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of 7r on the inhibition of triglyceride absorption. A four-week treatment of 7r in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of 7r in the PL inhibition. Overall, the synthesized analogue 7r exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity. Communicated by Ramaswamy H. Sarma

Protective effect of tretinoin derivative and TXNRD1 protein on streptozotocin induced gestational diabetes via an age-rage signaling-pathway.

In the present study effect of tretinoin derivative was investigated on the pathogenesis of gestational diabetes mellitus (GDM) in mice model in vivo. Diabetes was induced in mice by injecting Streptozotocin (STZ) for 5consecutive days at a dose of 65 mg/kg body weight through the intraperitoneal route. Tretinoin derivative was given to the mice at 0.12 and 0.25 mg/kg doses through gavage in normal saline alternately for one week after STZ injection. The results demonstrated that tretinoin derivative administration to the diabetic mice significantly (P<0.05) alleviated the blood FBG and FINS levels. Administration of tretinoin derivative to the diabetic mice significantly (P<0.05) promoted the blood HDL level and alleviated TC and TG levels. The administration of tretinoin derivative to the diabetic mice significantly (P<0.05) alleviated the CRP, IL-6and TNF-α production in pancreatic tissues. Tretinoin derivative administration to the diabetic mice significantly (P<0.05) elevated the SOD activity, and CAT level and lowered the MDA level in pancreatic tissues. The TXNRD1 expression in diabetic mice was comparable to that in the normal group after administration of tretinoin derivativeat the dose of 0.25 mg/kg dose. In silico data demonstrated that tretinoin derivativeinteracts with TXNRD1 protein with the binding affinity ranging from -10 to 9.4 kcal/ mol. In conclusion, tretinoin derivative administration effectively regulated streptozotocin-induced changes in fasting blood glucose, insulin level, high-density lipid level and triglyceride level in diabetic mice in vivo. The streptozotocin-induced excessive production of C-reactive protein and inflammatory cytokines was also down-regulated in diabetic mice on administration of tretinoin derivative. Therefore, tretinoin derivative can be investigated further as a therapeutic agent for the treatment of gestational diabetes mellitus.

The Relationship of Inflammatory Chemokine, CXCL12, with NT-proBNP: A Marker of Congestive Heart Failure in Rheumatoid Arthritis Patients

Background: Cardiovascular disease (CVD) is the most considerable long-term outcome of rheumatoid arthritis (RA) and the leading cause of premature death in RA patients. The pathogenesis of CVD in RA is largely determined by persistent systemic inflammation and its underlying factors, including chemokines. In this regard, C-X-C motif chemokine ligand 12 (CXCL12) has a crucial role in the CVD and RA pathogenesis. For the first time, plasma CXCL12 was related to conventional CV risk and well-established cardiac biomarkers in RA patients. Methods: This study was conducted on 30 RA patients who have been newly diagnosed, 30 under-treatment RA patients, and 30 healthy subjects. The plasma levels of CXCL12 and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. The high sensitivity C-reactive protein (HS-CRP) concentration was evaluated in plasma samples using the ADVIA 1800 Clinical Chemistry System based on the latex-enhanced immunoturbidimetric assay. The CVD risk was measured by calculating the Framingham risk score (FRS) and systematic coronary risk evaluation (SCORE). Results: The mean FRS and plasma concentration of high-density lipid (HDL), NT-proBNP, and HS-CRP were significantly different between the three groups (P = 0.029, P &lt; 0.001, P = 0.016, P &lt; 0.001, respectively). A significant positive correlation was found between CXCL12 with disease activity score-28 (DAS-28) (P = 0.024, r = 0.293) and NT-proBNP (P &lt; 0.0001, r = 0.570) in the patients’ group. Conclusions: Based on the results, there was a significant relationship between the inflammatory mediator CXCL12 and a well-known cardiac biomarker, NT-proBNP.

Abstract 14621: High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery

Introduction: Cholesterol efflux capacity (CEC) is inversely associated with incident CV events, independent of HDL-C. Obesity is characterized by low HDL-C and impaired HDL function. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), improves CV risk, but we have shown that the impact on CEC may differ by procedure over time post-op. Hypothesis: We hypothesized that RYGB and SG significantly affect HDL protein/lipid cargo and mediate CEC. Methods: We prospectively studied severely obese, nondiabetic women undergoing RYGB (n=31) or SG (n=36) before and at 6 and 12 months after surgery. Statistical analyses included Wilcoxon tests of log fold change in HDL proteins/lipids, hierarchical clustering to identify HDL protein/lipid clusters, and network mediation tests to identify cargo associated with CEC changes. Results: Subjects experienced similar weight loss regardless of procedure (38.0±10.4 kg at 12mo). Concentrations of 40 proteins (11 up, 29 down) and 95 lipids (46 up, 49 down) in HDL changed significantly following bariatric surgery. Proteins and lipids clustered into 9 and 14 groups of similar post-operative trajectories, respectively (Figure A). All clusters, other than 2 lipid clusters, showed similar responses regardless of procedure (Figure B). Despite similarities in cargo, changes in CEC differed depending upon time point and efflux pathway (Figure C). Network mediation analyses suggested that changes in 4 protein and 2 lipid clusters associated with post-operative changes in ABCA1-mediated CEC and changes in 1 lipid cluster associated with changes in non-ABCA1-mediated CEC (Figure D). Conclusions: In conjunction with substantial weight loss, bariatric surgery results in altered HDL protein/lipid cargo and CEC, possibly mediated by distinct HDL cargo. Further study of the mechanisms influencing HDL cargo in obesity and after bariatric surgery may lead to better understanding of CEC and management of CVD.

Impact of the COVID-19 pandemic on the outcomes of Indonesian chronic disease management program

&lt;b&gt;Background: &lt;/b&gt;The&lt;i&gt; &lt;/i&gt;Indonesian Government launched chronic disease management program (PROLANIS) with the aim of improving clinical outcomes and preventing disease complications of patients with type 2 diabetes (T2D). During the coronavirus disease 2019 (COVID-19) pandemic, the overwhelmed healthcare system shifted resources away from non-communicable diseases in the attempt to mitigate it. Thus, the implementation of PROLANIS during the COVID-19 pandemic might not be as optimal as before the pandemic era, leading to worse clinical outcomes. This pilot study aims to evaluate the impact of the COVID-19 pandemic on PROLANIS in rural areas by analyzing the changes of metabolic control and renal function parameters.&lt;br /&gt; &lt;b&gt;Methods:&lt;/b&gt; This study used data from three PROLANIS groups report in rural areas in East Java Province, Indonesia. Study population was PROLANIS participants who came for six-month-evaluation in December 2019 (T0), June 2020 (T1), and December 2020 (T2). Evaluated metabolic control parameters were body mass index (BMI), blood pressure, hemoglobin A1C (HbA1C), total cholesterol (TC), high-density lipid, low-density lipid, and triglyceride (TG), whereas evaluated renal function parameters were blood urea nitrogen, serum creatinine, and urinary albumin. Independent t-test and Wilcoxon signed-rank test were used for statistical analyses. p-value &amp;lt;0.05 was considered statistically significant.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Among 52 PROLANIS participants included in the analyses, four metabolic control parameters (BMI, blood pressure, TC, and TG) and all renal function parameters significantly worsened right after the pandemic started but improved 6 months afterwards. Meanwhile, HbA1C continuously worsened throughout the study period, albeit statistically insignificant.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;The metabolic control and renal function parameters in our study population deteriorates especially in the beginning of the COVID-19 pandemic.

Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 × 10–16 and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci.uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.

Microalbuminuria as the Tip of Iceberg in Type 2 Diabetes Mellitus: Prevalence, Risk Factors, and Associated Diabetic Complications.

Background Microalbuminuria (MA) is an important clinical marker for the early detection of kidney damage in patients with type 2 diabetes (T2DM). Urine albumin-to-creatinine ratio (ACR), also known as urine microalbumin, is a sign of diabetic nephropathy (DN), which is a prevalent complication of diabetes and can result in end-stage renal disease (ESRD) if not managed. The prevalence of MA in T2DM has been steadily increasing worldwide, making it a significant public health concern. The goal of this study was to estimate the prevalence of MA and its relationship to hypertension and other diabetic complications among people with T2DM. Methodology This descriptive cross-sectional study was conducted from February 5, 2022, to February 10, 2023, to analyse data from T2DM patients who visited the outpatient diabetic clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 640 patients, aged 35-60 years, who had been diagnosed with T2DM for at least five years and fulfilled the inclusion criteria. Data on demographic and clinical characteristics, blood pressure (BP) measurements, and laboratory investigations were collected. MA was assessed based on the ACR in a spot urine sample of more than 30 mg/l. Blood pressure greater than 140/90 or already taking anti-hypertensives was taken to constitute hypertension. Factors associated with MA like hypertension, gender, mode of diabetes treatment, duration of diabetes, glycosylated haemoglobin (HbA1c), dyslipidemia, and other diabetic complications such as retinopathy and neuropathy were also recorded. Results The prevalence of MA in this study of T2DM patients study was 39.1%. The mean age of the participants with MA was 53.9 with a standard deviation (SD) of 6.1 years, and the mean duration of diabetes was 10.1 years (SD 6.2 years); 101 (33.4%) males (n=302) and 103 (30.5%) females (n=338) had MA. There was a statistically significant correlation between MA > 30mg/d and hypertension (p = <0.001), diabetes duration since diagnosis (p=0.04), HbA1C level (p = <0.001), dyslipidemia (p=0.001), therapy type (p = <0.001), triglyceridemia (p = 0.03), history of diabetes retinopathy (p= <0.002), and peripheral neuropathy (p= <0.001). However, there was no statistically significant correlation between MA and age (p = 0.56), female gender (p = 0.08), low- and high-density lipids, or statin use (p = 0.06). Conclusion The prevalence of microalbuminuria among T2DM patients is significantly high (39.1%) and is positively correlated with various factors such as male gender, hypertension, suboptimal control of diabetes mellitus, high HbA1c levels, longer disease duration, dyslipidemia with high triglycerides,treatment modalities of T2DM, and other diabetic complications like neuropathy and retinopathy. As diabetes is very prevalent in our country, the number of patients with diabetic kidney disease will rise significantly in the near future, leading to ESRD and other diabetic complications, and immediate intervention is needed to prevent this. Further research is warranted to explore potential interventions and evaluate their impact on patient outcomes.

Prevalence and clinical characteristics of low skeletal muscle index among adults visiting a health promotion center: Cross-sectional study.

Sarcopenia causes a variety of functional impairments and is associated with all-cause mortality, but once it occurs, it is difficult to treat and reverse. However, the prevalence of sarcopenia in healthy people has never been investigated due to the low awareness of sarcopenia in healthy people. This cross-sectional study was conducted in a single health promotion center from the January 1st 2020 to the December 31st 2021. Adults aged 18 years and older with an Inbody as part of their health checkup were included, and all data was collected from the EMR. Obesity was defined as a body mass index (BMI) of 23 (kg/m2) or more by Korean standards, and low skeletal muscle mass was defined as a skeletal muscle index (SMI) of <0.789 for men and <0.512 for women. 60.5% of the total participants (n = 5993) had low skeletal muscle mass. The low SMI group had lower BMI, waist circumference, and abdominal skinfold than the normal SMI group (low SMI group vs normal SMI: BMI; 25.47 ± 2.96 vs 22.98 ± 3.05, P < .001, waist circumference; 90.31 ± 8.80 cm vs 82.69 ± 9.71 cm, P < .001, abdominal skinfold; 18.78 ± 2.44 mm vs 15.99 ± 2.12 mm, P < .001). The body fat percentage was higher in the low SMI group than in the normal SMI group 25.30 ± 6.23% versus 29.82 ± 7.07%, P < .001. Triglyceride and uric acid levels were low in the low SMI group (TG; 147.69 ± 97.27 vs 115.86 ± 68.31, P < .001, uric acid level; 6.30 ± 1.38 vs 5.23 ± 1.30, P < .001) and high-density lipid (HDL) was high (HDL; 53.17 ± 11.41 vs 59.89 ± 14.72, P < .001). The odds ratio of low SMI prevalence for age, sex, BMI, fat body percent, and triglycerides relative to normal SMI was 1.05 (P = .031), 0.14 (P < .001), 0.12 (P < .001), 2.05 (P < .001), and 0.99 (P = .003), respectively. Of those who visited the Health Promotion Center, more than 60% had low SMI identified through Inbody. Low BMI and high body fat percentage increase the risk of low SMI. Compared to normal and low SMI based on obesity, Sex, height, BW, abdominal skinfold, and waist circumflex showed significant P values in both groups. The factors related to low SMI were TG, HDL, and uric acid levels.