Plasma LDL Levels Research Articles

Exploring the versatility of miRNA-128: a comprehensive review on its role as a biomarker and therapeutic target in clinical pathways.

MicroRNAs (miRNAs/ miRs) are short, noncoding RNAs, usually consisting of 18 to 24 nucleotides, that control gene expression after the process of transcription and have crucial roles in several clinical processes. This article seeks to provide an in-depth review and evaluation of the many activities of miR-128, accentuating its potential as a versatile biomarker and target for therapy; The circulating miR-128 has garnered interest because of its substantial influence on gene regulation and its simplicity in extraction. Several miRNAs, such as miR-128, have been extracted from circulating blood cells, cerebrospinal fluid, and plasma/serum. The miR-128 molecule can specifically target a diverse range of genes, enabling it to have intricate physiological impacts by concurrently regulating many interrelated pathways. It has a vital function in several biological processes, such as modulating the immune system, regulating brain plasticity, organizing the cytoskeleton, and inducing neuronal death. In addition, miR-128 modulates genes associated with cell proliferation, the cell cycle, apoptosis, plasma LDL levels, and gene expression regulation in cardiac development. The dysregulation of miR-128 expression and activity is associated with the development of immunological responses, changes in neural plasticity, programmed cell death, cholesterol metabolism, and heightened vulnerability to autoimmune illnesses, neuroimmune disorders, cancer, and cardiac problems; The paper highlights the importance of studying the consequences of miR-128 dysregulation in these specific locations. By examining the implications of miRNA-128 dysregulation in these areas, the article underscores its significance in diagnosis and treatment, providing a foundation for research and clinical applications.

PON1 rs662, rs854560 and TRIB1 rs17321515, rs2954029 Gene Polymorphisms Are Associated with Lipid Parameters in Patients with Unstable Angina.

Acute coronary heart disease (CHD) is mainly caused by the rupture of an unstable atherosclerotic plaque. Many different factors can cause stenosis or even occlusion of the coronary artery lumen, such as vasculitis and platelet aggregation. Our study was performed to assess the association between PON1 rs662, rs854560 and TRIB1 rs17321515, rs2954029 polymorphisms and the risk of CHD, as well as the association between studied polymorphisms and selected clinical parameters affecting the risk of developing ischemic heart disease. A total of 232 patients with unstable angina were enrolled in this study. There were no statistically significant differences in the PON1 rs662, rs854560 and TRIB1 rs17321515, rs2954029 polymorphism distributions between the total study and control groups. Total cholesterol plasma levels were significantly higher in patients with the PON1 rs662 TT genotype compared to those with the CC+TC genotypes, as well as in patients with the PON1 rs854560 TT genotype compared to those with the AA+AT genotypes. LDL plasma levels were significantly increased in patients with the PON1 rs854560 TT genotype compared to those with the AA+AT genotypes. Plasma levels of HDL were significantly decreased in patients with the TRIB1 rs17321515 AA+AG genotypes compared to those with the GG genotype, as well as in patients with the TRIB1 rs2954029 AA+AT genotypes compared to those with the TT genotype. Our results suggest that the analysed polymorphisms are not risk factors for unstable angina in the Polish population. However, the results of this study indicate an association between the PON1 rs662, rs854560 and TRIB1 rs17321515, rs2954029 polymorphisms with lipid parameters in patients with coronary artery disease.

Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study.

The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40-60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes.

Leveraging Bidirectional Nature of Allostery To Inhibit Protein-Protein Interactions (PPIs): A Case Study of PCSK9-LDLR Interaction.

The protein PCSK9 (proprotein convertase subtilisin/Kexin type 9) negatively regulates the recycling of LDLR (low-density lipoprotein receptor), leading to an elevated plasma level of LDL. Inhibition of PCSK9-LDLR interaction has emerged as a promising therapeutic strategy to manage hypercholesterolemia. However, the large interaction surface area between PCSK9 and LDLR makes it challenging to identify a small molecule competitive inhibitor. An alternative strategy would be to identify distal cryptic sites as targets for allosteric inhibitors that can remotely modulate PCSK9-LDLR interaction. Using several microseconds long molecular dynamics (MD) simulations, we demonstrate that on binding with LDLR, there is a significant conformational change (population shift) in a distal loop (residues 211-222) region of PCSK9. Consistent with the bidirectional nature of allostery, we establish a clear correlation between the loop conformation and the binding affinity with LDLR. Using a thermodynamic argument, we establish that the loop conformations predominantly present in the apo state of PCSK9 would have lower LDLR binding affinity, and they would be potential targets for designing allosteric inhibitors. We elucidate the molecular origin of the allosteric coupling between this loop and the LDLR binding interface in terms of the population shift in a set of salt bridges and hydrogen bonds. Overall, our work provides a general strategy toward identifying allosteric hotspots: compare the conformational ensemble of the receptor between the apo and bound states of the protein and identify distal conformational changes, if any. The inhibitors should be designed to bind and stabilize the apo-specific conformations.

Beneficial Effects of Natural Alkaloids from Berberis glaucocarpa as Antidiabetic Agents: An In Vitro, In Silico, and In Vivo Approach.

Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).

Daily Consumption of Golden Berry (Physalis peruviana) Has Been Shown to Halt the Progression of Insulin Resistance and Obesity in Obese Rats with Metabolic Syndrome.

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.

A high-fat diet induced depression-like phenotype via hypocretin-HCRTR1 mediated inflammation activation.

Background: A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods: Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results: The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions: In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.

Evaluation of the Suitability of Using Anticholesterol Drugs in Cholesterol Patients at Sekip Public Health Centre Palembang

Dyslipidemia is a condition that increases plasma cholesterol, LDL, and triglyceride levels, decreases HDL levels, or causes a combination of abnormalities. In amounts sufficient for what the body needs, cholesterol works to produce hormones, vitamin D, and other components. Cholesterol is produced by the liver and can also be found in animal products. This study aims to determine the profile of treatment and the suitability of the use of anticholesterol drugs in patients with high cholesterol at Sekip Public Health Centre Palembang. This research is non-experimental, using quantitative methods and 40 samples. The demographic results of the total cholesterol levels of patients who experienced a decrease were 100 patients (100%). Demographics of patients by gender: mostly female, as many as 30 patients (75%). Demographics of patients by age: mostly in the age category 56–65 years, as many as 16 patients (40%). Demographics of patients based on comorbidities: the most common was diabetes mellitus, with as many as 12 patients (30%) The highest use of anticholesterol drugs is in the statin group, namely simvastatin (100%). The suitability of the selection of anticholesterol drugs was 100% for 100 patients. The suitability of the selection of the anticholesterol dose in 100 patients (100%)

The Effect of an Innovative Combination of Bergamot Polyphenolic Fraction and Cynara cardunculus L. Extract on Weight Gain Reduction and Fat Browning in Obese Mice.

Obesity is one of the world's most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation may be a crucial strategy for improving WAT inflammation and obesity and accelerating the browning process. The aim of this study was to perform a preclinical "proof of concept" study on Bergacyn®, an innovative formulation originating from a combination of bergamot polyphenolic fraction (BPF) and Cynara cardunculus (CyC), for the treatment of adipose tissue dysfunction. In particular, Bergacyn® supplementation in WD/SW-fed mice at doses of 50 mg/kg given orally for 12 weeks, was able to reduce body weight and total fat mass in the WD/SW mice, in association with an improvement in plasma biochemical parameters, including glycemia, total cholesterol, and LDL levels. In addition, a significant reduction in serum ALT levels was highlighted. The decreased WAT levels corresponded to an increased weight of BAT tissue, which was associated with a downregulation of PPARγ as compared to the vehicle group. Bergacyn® was able to restore PPARγ levels and prevent NF-kB overexpression in the WAT of mice fed a WD/SW diet, suggesting an improved oxidative metabolism and inflammatory status. These results were associated with a significant potentiation of the total antioxidant status in WD/SW mice. Finally, our data show, for the first time, that Bergacyn® supplementation may be a valuable approach to counteract adipose tissue dysfunction and obesity-associated effects on cardiometabolic risk.

Evaluation of lipoprotein(a) and adiponectin levels in patients with metabolic syndrome for the prediction of CVD risk

Abstract Introduction/Objective Introduction: Metabolic syndrome (MetS) usually intensely forecasts cardiovascular diseases, along with elevating the risk of diabetes mellitus as well as chronic kidney disease. The International Federation for Diabetes (IDF) established in 2006 an accepted metabolic syndrome defined as a “cluster of the most dangerous heart attack and cardiovascular diseases risk factors”. Adiponectin is considered the most crucial factor which plays a serious role in glucose and lipid metabolism. Lipoprotein(a) Lp(a) was considered the single most common independent genetically inherited causal risk factor for cardiovascular diseases (CVD). bolic syndrome patients. Methods/Case Report Objectives: To investigate the correlation between Lipoprotein (a) and adiponectin in metabolic syndrome patients with CVD. Subjects and methods This research was performed at Al-Ahliyya Amman University (AAU) during the period between January 2021 and March 2021. Eighty participants were randomly selected from patients who were recruited from the internal medicine clinics. The participants aged 40 to 60 years were selected after screening for the criteria for diagnosis with MetS. Forty-two of the participants had metabolic syndrome, while the other 38 represented the control group. Adiponectin and Lipoprotein (a) were measured using by ELISA technique. Routine laboratory tests, including a lipid profile, glucose and body mass index (BMI), were measured for all participants. Results (if a Case Study enter NA) Results: Plasma lipoprotein (a), HDL, and LDL levels were significantly higher in MetS patients than in healthy controls p= 0.026, 0.04, and 0.04, respectively. In comparison, no significance was found regarding adiponectin (p = 0.07). Lipoprotein (a) had shown a negative correlation with HDL(r= -0.34), whereas adiponectin was inversely correlated with LDL (r= -0.33) and LDL/HDL ratio (r= -0.34). The multiple linear regression analysis results revealed the predictive potential of Lipoprotein (a), and adiponectin when used in different models for CVD risks using HDL as a risk factor (r = 0.381, p = 0.047). Conclusion The studied metabolic syndrome markers might be essential in detecting cardiovascular events. It can be concluded that Lipoprotein (a) and adiponectin can be used to predict the CVD risks in meta

PCSK9 activation promotes early atherosclerosis in a vascular microphysiological system.

Atherosclerosis is a primary precursor of cardiovascular disease (CVD), the leading cause of death worldwide. While proprotein convertase subtilisin/kexin 9 (PCSK9) contributes to CVD by degrading low-density lipoprotein receptors (LDLR) and altering lipid metabolism, PCSK9 also influences vascular inflammation, further promoting atherosclerosis. Here, we utilized a vascular microphysiological system to test the effect of PCSK9 activation or repression on the initiation of atherosclerosis and to screen the efficacy of a small molecule PCSK9 inhibitor. We have generated PCSK9 over-expressed (P+) or repressed (P-) human induced pluripotent stem cells (iPSCs) and further differentiated them to smooth muscle cells (viSMCs) or endothelial cells (viECs). Tissue-engineered blood vessels (TEBVs) made from P+ viSMCs and viECs resulted in increased monocyte adhesion compared to the wild type (WT) or P- equivalents when treated with enzyme-modified LDL (eLDL) and TNF-α. We also found significant viEC dysfunction, such as increased secretion of VCAM-1, TNF-α, and IL-6, in P+ viECs treated with eLDL and TNF-α. A small molecule compound, NYX-1492, that was originally designed to block PCSK9 binding with the LDLR was tested in TEBVs to determine its effect on lowering PCSK9-induced inflammation. The compound reduced monocyte adhesion in P+ TEBVs with evidence of lowering secretion of VCAM-1 and TNF-α. These results suggest that PCSK9 inhibition may decrease vascular inflammation in addition to lowering plasma LDL levels, enhancing its anti-atherosclerotic effects, particularly in patients with elevated chronic inflammation.

Ultrasound-Treated and Thermal-Pasteurized Hawthorn Vinegar: Antioxidant and Lipid Profiles in Rats.

The hawthorn fruit, a member of the Rosaceae family, is a medicinal plant with numerous therapeutic properties. It has a wide range of variants, with Crataegus tanacetifolia being the most widely recognized species in the world. The hawthorn fruit has various biological activities, including anti-inflammatory, antibacterial, antioxidant, immune-modulating, and anti-carcinogenic properties. This study focused on improving the antioxidant activity of hawthorn vinegar via different methods. We also aimed to investigate the influence of its hepatic antioxidant abilities on health and extend the shelf life of the vinegar. In the study, the vinegar was produced from the hawthorn fruit, and thermal pasteurization and ultrasound techniques were applied. A total of 56 female adult Wistar-Albino rats were allocated into seven groups and administered hawthorn fruit vinegar via oral gavage on a daily basis. The experimental groups included rats treated with pasteurized vinegar (HVP), ultrasound-treated rats (HVU), and an untreated group that received regular vinegar (HVN) at two different dosage levels (0.5 and 1 mL/kg). The SOD, MDA, and CAT antioxidant levels were measured using the ELISA method in plasma and liver tissue samples. The total plasma cholesterol, triglyceride, HDL, LDL, AST, and ALT values were quantified using commercially available kits. The levels of SOD and CAT in the plasma and liver were found to be significantly higher in the HVU1 group compared to all other groups. Furthermore, the HVU1 cohort exhibited the highest HDL value in plasma. The plasma LDL levels were comparably low in both the thermal-pasteurized and ultrasound-treated groups. There were significant expressions of both CAT and SOD in the liver tissues of the HVU groups (analyzed immunohistochemically). These results indicated that hawthorn vinegar administration with 1 mL/kg in group HVU1 could significantly enhance antioxidant capacity in the liver and, consequently, overall health. It can be suggested that the possible therapeutic effects of hawthorn vinegar may boost its antioxidant capabilities and contribute to an overall improvement in quality of life.

CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients.

Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.

Phytochemical screening and evaluation of glucose-6-phosphate dehydrogenase activity of fermented honey-garlic in hypothyroidism rats

Introduction: Hypercholesterolemia is an indicator of atherosclerosis in blood vessels and is currently a top priority in overcoming health problems, especially non-communicable diseases in developed and developing countries. Thyroid hormones regulate various metabolic processes in the body including synthesis, mobilization, and lipid degradation. A lack of thyroid hormone in the body or called hypothyroidism will decrease the number of LDL receptors in the liver. This causes an increase in plasma LDL levels which also increases total cholesterol levels. Despite the lack of study, Fermented Honey-Garlic (FHG) is now widely developed for its high antioxidant activity. This study aims to determine the content of bioactive compounds in FHG by qualitative secondary metabolite testing and GC-MS analysis and to evaluate the activity of the enzyme glucose-6-phosphate dehydrogenase (G6PD) in rats with hypothyroidism. Method: Rats were grouped into 6 groups: positive control group induced by propylthiouracil (PTU) with a dose of 20 mg/day, negative control treated with distilled water, treatment group with a dose of FHG 0.2 g/kg BW (P1), treatment group with a dose of FHG 0.5 g/kg BW (P2), treatment group with a dose of FHG 1 g/kg BW (P3) and standard drug Simvastatin group with the dose 0,18 mg/day/200 g BW. Results: Results showed that FHG contained flavonoid compounds, alkaloids, tannins, and saponins, and statistical results showed that the significance value for G6PD activity was 0.014 (P&lt;0.05). Conclusion: Therefore, it can be concluded that FHG administration yields a significant effect on G6PD levels.

Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise.

Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise. A total of 24 male Wistar rats were divided into control, cyclosporine (30mg/kg BW), and cyclosporine-exercise groups. After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group. TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.

Effects of the 2019 guideline-update on lipid therapy in patients with acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): 2 Ludwig Boltzmann Institute for Cardiovascular Research. Background The European Society of Cardiology regularly updates its clinical practice guidelines. However, it is not well established whether guideline-changes have significant effects on actual clinical practice. Therefore, we retrospectively analyzed lipid therapy at discharge after acute coronary syndrome (ACS) in a one-year period until 3 months before and a one-year period starting 6 months after publication of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias, respectively. Methods and Results In total we included 702 patients that were discharged alive after treatment for ACS. 360 patients were treated in the period before and 342 were treated in the period after guideline change. 67.7 % of patients were male and 59.1% were treated for ST-elevation myocardial infarction (STEMI). After guideline change the proportion of patients that were discharged on high dose statin was significantly higher as compared to the period before the new guidelines were published (89.2 % vs 79.2 %; p=0.001). Ezetimibe was prescribed more often after the new guidelines (15.0 % vs 3.0 %; p&amp;lt;0.00001). Whereas proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were not prescribed at discharge in the earlier period, five patients were discharged on PCSK9i in the later period. The higher proportion of ezetimibe use and the introduction of PCSK9i resulted in an increased number of patients on high intensity treatment (high dose statin or moderate dose plus ezetimibe or PCSK9i: 92.4 % vs. 79.7 %; p&amp;lt;0.0001) in the period after the new guidelines. In 32.3 % of patients, cholesterol levels were available for the time period between one month and one year after discharge. Median on treatment LDL was significantly higher in the period before (64.4 IQR 47.4 – 94.2 mg/dL) than after the publication of the 2019 guidelines (46.2 IQR 33.8 – 61.8 mg/dl; p&amp;lt;0.00001). Conclusions The update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias was associated with a significant improve in the proportion of high dose statin and ezetimibe treatment in patients after ACS resulting in a significant lower LDL plasma level in a subgroup of patients. The change of these guidelines rapidly translated into clinical practice resulting in improved risk factor control in high-risk patients.

The Relationship of Body Fat Ratio to Anthropometric and Metabolic Parameters in Normal Weight and Overweight Women; The Concept of Normal Weight Obesity

Aim: We aimed to underline the importance of “normal weight obesity concept”, prevent the overlooking of Normal Weight Obesity patients, administrate their treatments and explain them the risks regarding their future lives along with making emphasis on the necessity of change in polyclinical practices about the subject. Methods: We selected 200 female patients that were either normal or overweighted for this study. Patients have been divided into 4 groups with respect to their body mass index and body fat percent values. Differences of bioelectrical impedance analysis measurements between the groups, relation of the anthropometric and metabolic parameters and those parameters’ inner correlations have been inspected. Results: Serum levels of fasting plasma glucose, insulin, HOMA-IR, total cholesterol, LDL, triglyceride and TSH were higher in “Normal Weight Obesity” subjects than “Normal Weight Lean” subjects. The mean LDL levels were found to be higher in the Normal Weight Obesity group compared to the other groups and it was found to be statistically significant. Body fat percent was positively correlated to insulin, HOMA-IR, visceral fat rating, waist – hip circumferences, waist to height – hip to height ratios. Conclusion: The importance of measurement of body fat percent and not to overlook the Normal Weight Obesity patients should be emphasized once more. Therefore, in the primary care, during public screening and polyclinical assessment states, patients should be checked for obesity with not only measuring their weights and heights, but also detection of their detailed body composition. Keywords: obesity, body fat distribution, waist to height ratio

Correlation study on the relationship between dyslipidemia and carotid intima-media thickness in patients with diabetes mellitus.

To investigate the correlation between dyslipidemia and carotid intima-media thickness (IMT) in patients with diabetes mellitus. A descriptive research design was adopted in this study. One hundred and twenty patients with Type-2 diabetes mellitus who were admitted to the physical examination center of The Fourth Hospital of Hebei Medical University from June 2020 to June 2021 for physical examination were recruited to the experimental group. The 120 patients were divided into three groups according to carotid IMT: normal group, thickened group, and plaque group. Forty healthy people who underwent a physical examination during the same period were recruited as the control group. The differences in IMT in various parts of the experimental group and the control group and the differences in blood lipid indexes were compared and analyzed. In addition, the correlation between mean IMT of bilateral common carotid arteries and blood lipid levels in normal, thickened and plaque groups was compared and analyzed. The intima-media thicknesses of the internal carotid artery and bilateral common carotid arteries of the patients in the experimental group were significantly thicker than those in the healthy control group, the levels of TC, TG and LDL were higher than those in the control group, while the level of HDL was lower than that in the control group, with a statistically significant difference (p=0.00). The levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and LDL were positively correlated with the mean IMT of bilateral common carotid arteries (p<0.05), while the level of HDL was negatively correlated with the mean IMT of bilateral common carotid arteries (p<0.05). Dyslipidemia and glucose metabolism in patients with Type-2 diabetes mellitus have a close bearing on carotid IMT. Clinically, patients with Type-2 diabetes mellitus can be judged by monitoring carotid IMT for dyslipidemia, atherosclerosis and other related complications.

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

Clostridium butyricum alleviates LPS-induced acute immune stress in goats by regulating bacterial communities and blood metabolites.

The mitigation and prevention of acute immune stress are essential for livestock production. Clostridium butyricum (C. butyricum) has shown positive effects in stabilizing intestinal microbiota disorders, improving immune function and inhibiting disease development, but its effects on ruminants are unclear. Therefore, the current trial hypothesized that C. butyricum could improve goats' immune function and antioxidant capacity by regulating bacterial communities and blood metabolism and effectively alleviating the acute immune stress induced by Lipopolysaccharides (LPS). Sixteen healthy goats were fed C. butyricum for 70 days, and the goats were challenged with LPS on day 71. Blood and feces were collected at 0h and 6h after the challenge to evaluate the effects of C. butyricum on their intestinal microbiota, immune function, antioxidant function, and plasma metabolites. The results showed that C. butyricum had no significant effect on plasma biochemical parameters at the beginning of the LPS challenge. However, supplementation with C. butyricum increased plasma levels of IgA, IgG, T-SOD, and T-AOC (P < 0.05), but TNF-α, IL-6, and MDA were decreased (P < 0.05). In contrast, IL-10 showed an increasing trend (P < 0.10). Rectal microbiota analysis showed that C. butyricum significantly increased the relative abundance of Epsilonbacteraeota at the phylum level of goats; at the genus level, the relative abundances of Campylobacter and Anaerorhabdus]_furcosa_group were also significantly increased (P < 0.05). Christensenellaceae_R-7_group as the dominant microbiota also showed a significant increase in their abundance values, while Clostridium and Lachnospiraceae_UCG-001 were significantly lower (P < 0.05). When the LPS challenge continued up to 6h, dietary supplementation with C. butyricum still resulted in significantly higher plasma concentrations of IgA, IL-10, and T-SOD in goats than in the control group, reducing TNF-α levels (P < 0.05). In addition, plasma levels of T-CHOL and LDL were significantly reduced, and the expression of d-proline was significantly upregulated according to metabolomic analysis (P < 0.05). In conclusion, dietary supplementation with C. butyricum helped optimize the expression of bacterial communities and plasma metabolites to enhance the ability of goats to alleviate acute immune stress.