Serum Cholesterol Levels Research Articles

Chronic Toxic Effects of Chocolate Brown HT Dye on Hepatorenal Functions In Vivo

Background: Synthetic colors are prevalent in modern food processing, with Chocolate Brown HT (E155) being widely used to meet the demand for chocolate colors. This study examined the long-term health effects of E155 on both male and female subjects. Methods: Six treatment groups received E155 in low to high dosages (200, 400, and 600 mg/kg body weight) for 40 weeks, while control groups consumed a normal diet. After the feeding period, biochemical and histological evaluations were conducted alongside regular physical observations. Results: The female high-dose (FHD) group exhibited the most significant decrease in body weight. Body Mass Index (BMI) dropped notably in females at moderate (FMD) and high doses (FHD). Serum levels of cholesterol, LDL, and triglycerides increased dose-dependently, with males being more susceptible. Elevated SGPT and SGOT levels indicated liver function impairment due to E155. Both genders showed centrilobular necrosis and fibrosis at high doses, with immune cell invasion even at low doses. Serum creatinine levels, especially in males, were significantly elevated. Females experienced severe injuries, including arteriolar hyalinosis at low doses and IgA nephropathy in the FHD group. Conclusion: The findings underscore serious public health concerns regarding the long-term intake of E155, which can cause significant hepatic and renal damage, particularly in females. This highlights the need for regulatory review and potential restrictions on the use of E155 in food products.

Effect of the Combined Treatment of Taoren Chengqi Decoction with Laser Photocoagulation on Diabetic Retinopathy

This study investigates the therapeutic effect of the combined treatment of Taoren Chengqi decoction with laser photocoagulation on DR. In animal experiments, A total of 18 rats were used and randomly divided into blank groups, model groups, and treatment groups. The rats in the model group and treatment group were intraperitoneally injected with 60 mg/kg streptozotocin. Moreover, the TCT group was gavaged with Tao-ren Cheng-qi decoction, while the other groups received an equivalent volume of normal saline once daily for 8 weeks. Fasting blood glucose (FBG) and serum interleukin (IL)-6 and IL-1β were determined. In the clinical trial, a total of 80 patients with DR were divided into a laser group (treated with laser photocoagulation) and a combination group (treated with laser photocoagulation+Taoren Chengqi decoction). The central macular thickness (CMT), best-corrected visual acuity (BCVA), and serum levels of high-density lipoprotein cholesterol, low-density-lipoprotein cholesterol, total cholesterol, triglycerides, glycated hemoglobin, and hypoxia-inducible factor 1α were measured in the patients. In animal experiments, we observe that Tao-ren Cheng-qi decoction can effectively reduce the levels of FBG, IL-6, and IL-1β in rats models with DR. Clinical studies revealed that the combination of Taoren Chengqi decoction with laser photocoagulation reduced the levels of blood glucose and lipid-related indices, and improved the inflammatory state, BCVA, and CMT. Therefore, this study suggests that the combined treatment of laser surgery and Taoren Chengqi decoction can be considered an optimal therapeutic approach for patients with DR.

Association between hypercholesterolemia and isolated and simultaneous consumption of ultra-processed foods in older adults.

Consumption of ultra-processed foods (UPFs) is a risk factor for several cardiovascular diseases and mortality, with potential physiological mechanisms including elevated serum cholesterol levels. To analyze the association between hypercholesterolemia and the isolated and simultaneous consumption of UPFs in older adults. This is a cross-sectional epidemiological study conducted with 1322 Brazilian older adults (mean age of 70.4 years; 55.0% females) from the state of Roraima. The data was obtained from the Department of Epidemiological Surveillance of the State of Roraima. Hypercholesterolemia was diagnosed based on nosology criteria. Food consumption patterns were assessed using a nationally standardized instrument comprising four categories of UPFs. Binary logistic regression models were employed to explore potential associations. The prevalence of hypercholesterolemia was high (54.4%, 95% CI 51.7-56.6). While the simultaneous consumption of all UPFs types was lower (15.2%), over half of the older adults reported consuming at least one type of UPFs (71.8%). Isolated consumption of UPFs was associated with approximately twice the odds of hypercholesterolemia. Older adults who consumed two (OR 1.75, 95% CI 1.26-2.43), three (OR 2.28, 95% CI 1.58-3.29), or all four types of UPF (OR 6.65, 95% CI 4.35-9.44) had a higher likelihood of having hypercholesterolemia. Isolated consumption of UPFs is a risk factor for hypercholesterolemia, which can increase up to sixfold when older adults consume multiple UPFs simultaneously. Prioritizing nutritional education and raising awareness regarding the reduction of UPFs consumption is crucial.

Differences in the serum lipid profile of goats with varying autonomic nervous system tone

Goat farming is a promising branch of animal husbandry, as statistics show a rapid increase in global demand for goat milk and meat products. To meet market demand, new methodological approaches are needed to improve animal productivity while maintaining the quality of the raw materials. In this context, this study aims to determine the impact of autonomic nervous system tone on lipid metabolism in goats. The study involved Saanen goats, with the experimental groups formed based on the results of variation-pulsometric study and electrocardiography, followed by the determination of autonomic nervous system tone using the Baevsky method. The serum lipid profile of goats was studied using a LabLine-010 spectrophotometer. The following indicators were biochemically analysed in serum samples: content of triacylglycerols, cholesterol, high-density, low-density, and very-low-density lipoproteins, and the atherogenic index was calculated. It was established that the content of triacylglycerols was 23% lower (P< 0.05) in sympathotonic animals and 41% lower (P< 0.001) in vagotonic animals compared to normotonic animals. The level of lowdensity lipoproteins in the blood serum of sympathotonic animals decreased by 40% (P < 0.05), and in vagotonic animals – by 76% (P< 0.01), relative to normotonic animals. The content of highdensity lipoproteins in sympathotonic animals increased by 36% (P<0.001), relative to normotonic animals. The level of cholesterol in the blood serum of goats differed by 16% (P < 0.01) in sympathotonic animals and 15% (P< 0.01) in vagotonic animals compared to normotonic animals. A significant influence of autonomic nervous system tone on the processes of maintaining lipid homeostasis in goats was determined. Taking into account the individual features of the influence of the autonomic nervous system on lipid metabolism when distributing animals will contribute to the effective adjustment of diets. After all, each animal has a different tone of the autonomic nervous system, which significantly affects the features of substance transformation in its body

Molecular docking analysis of Ficus religiosa L. fruit extracts with HMG-COA reductase inhibitors, anti-hyperlipidemic effects of its in Albino wistar rats, triggered by Triton-X 100 and High fat diet

Hyperlipidemia is the major risk factor for coronary artery disease in various patients suffering with cardiovascular disorders. Literature claims that flavonoids and phenolic compounds are able to reduce hyperlipidemia. Aim of the present study is to establish antihyperlipidemic activity of Ficus religiosa L. fruits extract with molecular docking approach and perform in-vivo study.Extraction has performed by Soxhlet apparatus with methanol for 72 h. Further, the extract has subjected to phytochemical tests followed by GC-MS analysis. Molecular docking study has been conducted to screening the compounds in extract which have affinity to HMG-COA reductase (PDB ID: 1HWK) receptor with reference to Atorvastatin. Anti-hyperlipidemic activity of the extract has investigated by studying in vivo effects on Triton-X 100 and High fat diet induced animal model. The animals were divided in 5 groups of 6 each. The extract has administered at a dose of 1000 mg/kg (p.o) and 500 mg/kg (p.o) to both models. Atorvastatin was used as standard.The GC-MS result of Ficus religiosa L. fruits has demonstrated the presence of phenols, flavonoids. Molecular docking study has been performed to identify the anti-oxidant compounds in the extracts. The extract has shown a significant decrease in the levels of Body weight, serum cholesterol, glucose, triglyceride, LDL, VLDL and significant increase in the level of serum HDL. The result of the research has showed that Ficus religiosa L. fruits possess antihyperlipidemic activity in both groups; the results were statistically significant compared to Atorvastatin.

Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes based on AMPK signaling pathway

BackgroundWith the increasing awareness of the safety of traditional Chinese medicine and food, as well as in-depth studies on the pharmacological activity and toxicity of Zanthoxylum armatum DC. (ZADC), it has been found that ZADC is hepatotoxic. However, the toxic substance basis and mechanism of action have not been fully elucidated. Hydroxy-α-sanshool (HAS) belongs to an amide compound in the fruits of ZADC, which may be hepatotoxic. However, the specific effects of HAS, including liver toxicity, are unclear. PurposeThe objectives of this research was to determine how HAS affects hepatic lipid metabolism, identify the mechanism underlying the accumulation of liver lipids by HAS, and offer assurances on the safe administration of HAS. MethodsAn in vivo experiment was performed by gavaging C57 BL/6 J mice with various dosages of HAS (5, 10, and 20 mg/kg). Biochemical indexes were measured, and histological analysis was performed to evaluate HAS hepatotoxicity. Hepatic lipid levels were determined using lipid indices and oil red O (ORO) staining. Intracellular lipid content were determined by biochemical analyses and ORO staining after treating HepG2 cells with different concentrations of HAS in vitro. Mitochondrial membrane potential, respiratory chain complex enzymes, and ATP levels were assessed by fluorescence labeling of mitochondria. The levels of proteins involved in lipogenesis and catabolism were determined using Western blotting. ResultsMice in the HAS group had elevated alanine and aspartate aminotransferase blood levels as well as increased liver index compared with the controls. The pathological findings showed hepatocellular necrosis. Serum and liver levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were increased, whereas high-density lipoprotein cholesterol levels decreased. The ORO staining findings demonstrated elevated liver lipid levels. In vitro experiments demonstrated a notable elevation in triglyceride and total cholesterol levels in the HAS group. ATP, respiratory chain complex enzyme gene expression, mitochondrial membrane potential, and mitochondrial number were reduced in the HAS group. The levels of lipid synthesis-associated proteins (ACC, FASN, and SREBP-1c) were increased, and lipid catabolism-associated protein levels (PPARα and CPT1) and the p-AMPK/AMPK ratio were decreased in vivo and in vitro. ConclusionHAS has hepatotoxic effects, which can induce fatty acid synthesis and mitochondrial function damage by inhibiting the AMPK signaling pathway, resulting in aberrant lipid increases.

Gut Microbiota as Therapeutic Targets in Diabetes Management: Opportunities and Challenges

This article delves into the complex interplay between Type 2 Diabetes Mellitus (T2DM), gut microbiota, and dietary strategies for effective diabetes management. T2DM, characterized by insulin resistance and β-cell dysfunction, is influenced by genetic and environmental factors. The gut-brain axis and alterations in incretin functioning contribute to gastrointestinal permeability in T2DM. Plant-based diets offer substantial benefits for managing T2DM by improving emotional well-being, HbA1c levels, weight, and cholesterol. High-fiber diets positively impact gut microbiota, serum metabolism, and emotional health in T2DM individuals. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are emerging as pivotal interventions. Probiotics improve serum fructosamine, HbA1c, and cholesterol levels, while prebiotics like oligofructose-enriched inulin and synbiotics enhance glycemic control and lipid profiles. Insights from microbiome studies in diverse dietary populations provide personalized approaches for diabetes management. Integrating plant-based nutrition, PPSP interventions, and microbiome-focused strategies may offer a comprehensive and effective approach to T2DM management, addressing physiological aspects and empowering individuals in their health journey.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RTÁqPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT fullÁlength transcriptome sequencing. EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to fullÁlength transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

The Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists as Novel Diabetes Drugs Are Mediated via the Suppression of miR-203a-3p and miR-429 Expression.

Coronary artery disease (CAD) is associated with a high fatality rate and a heavy global health care burden. Glucagon-like peptide-1 (GLP-1) exerts positive cardiovascular effects, although the molecular mechanisms are unclear. Therefore, this study aimed to verify whether the cardioprotective effects of GLP-1 are mediated through the regulation of micro-RNA (miRNA) expression. Follow-up assessments were conducted for 116 patients with type 2 diabetes mellitus (T2DM) alone (controls) and 123 patients with both T2DM and CAD. After matching, each group comprised 63 patients, and age, body mass index, and serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), and hemoglobin A1C (HbA1c) were compared. Subsequently, the expression profiles of four circulating miRNAs (miR-203a-3p, miR-429, miR-205-5p, and miR-203b-5p) were assessed via quantitative reverse transcription real-time polymerase chain reaction in the 63 patients with diabetes and CAD between 6 months (baseline) and 12 months after the initiation of GLP-1 receptor (GLP-1R) therapy. As expected, the metabolic factors were significantly improved after 6 months of treatment with GLP-1R compared with pre-treatment values, and the expression levels of two of the miRNAs (miR-203a-3p and miR-429) decreased from baseline levels in those with diabetes and CAD. The results suggest that the cardiovascular benefits induced by GLP-1R are mediated via suppressed expression of two miRNAs: miR-203a-3p and miR-429.

Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.

Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p=0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p=0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Effect of Kankrej Cow Urine Distillate and Panchgavya Supplementation on Growth Performance, Carcass Characteristics and Blood Biochemical Profile of Broiler Chickens

A study was conducted during the month of December, 2023 and January, 2024 to evaluate the effect of cow urine distillate and Panchgavya supplementation on growth performance, nutrient digestibility, carcass characteristics and blood biochemical parameters of broiler chickens. A total of 200 day-old broiler chicks were uniformly distributed into four treatment groups with 50 birds per treatment for a period of 42 days. The dietary treatments were T1: Basal diet, T2: Basal diet+1 ml cow urine distillate (CUD) in drinking water bird-1 day-1, T3: Basal diet+1 ml Panchgavya in drinking water bird-1 day-1 and T4: Basal diet+50 mg of Commercial feed grade antibiotic (Tylosin phosphate) kg-1 of feed. Results revealed that the mean final body weight and body weight gain in broiler chickens were not influenced by the inclusion of CUD and Panchgavya. There was no effect on feed intake, nutrient digestibility, carcass characteristics and blood biochemical parameters due to CUD and Panchgavya supplementation in broiler chickens. The feed conversion ratio was better in Panchgavya and feed antibiotic groups than the control group. The serum cholesterol level was significantly (p<0.05) reduced in Panchgavya and feed antibiotic groups followed by CUD group than the control. It may be concluded that supplementation cow urine distillate and Panchgavya in broiler chickens did not influence growth performance, feed intake, nutrient digestibility, carcass characteristics and blood biochemical parameters. Panchgavya and feed antibiotic supplementation improved feed conversion ratio and reduced serum cholesterol level in broiler chickens.

Відбір пробіотичних мікроорганізмів та їх композицій як основи для лінійки функціональних продуктів харчування з гіпохолестеринемічними властивостями

In modern clinical practice, the main methods for correcting elevated serum cholesterol levels are drugs that block the activity of the enzyme hydroxymethylglutaracyl-CoA-reductase (HMG-CoA-reductase) – statins or drugs that inhibit the absorption of cholesterol and sterols in the intestines ezetimibe. All hypocholesterolemic drugs are rather expensive and have side effects, the main of which is hepatotoxicity. During mono- and combined therapy with HMG-CoA reductase inhibitors and ezetimibe, cases of increased activity of alanine and asparagine transaminases (biochemical indicator of cytolytic syndrome), disorders of the digestive and respiratory systems, the central and peripheral nervous systems, and the sense organs along with weight gain, etc. have been found. Scientific literature has increasingly reported on the ability of lactic acid bacteria to lower serum cholesterol. The ability of certain strains of representatives of the normal microbiota to assimilate and precipitate deconjugated bile acids, as well as to destroy, bind, and assimilate cholesterol, is the basis of their hypocholesterolemic activity (the ability to reduce the level of serum cholesterol). A high level of cholesterol, both in the total blood serum and in low-density lipoproteins, is one of the main risk factors for coronary heart disease, atherosclerosis, cerebrovascular atherosclerosis, hypertension, tumors of the digestive tract, etc. The aim of the study was to establish the hypocholesterolemic activity in vitro and in vivo of previously selected highly effective probiotic strains of lactic- and bifidobacteria for the further creation on their basis of a line of effective functional food with hypocholesterolemic activity for the prevention and concomitant treatment of pathological conditions associated with high cholesterol levels. Methods. Bacterial hypocholesterolemic activity in vitro was determined according to Rudel L.L. and in vivo – on the mice model that was designed by us. Two schemes of the administration of probiotic strains – the prophylactic and therapeutic ones–were developed. Results showed that Lactobacillus acidophilus IMV B-7279 and Bifidobacterium animalis IMV B-7286 strains, as well as the Bifidobacterium animalis IMV B-7286: Bifidobacterium animalis IMV B-7285 (1:1) composition were the most effective probiotics used for treatment of mice with hypercholesterolemia. The cholesterol-lowering activity of all studied probiotic strains and their compositions ranged between 40–78 %. At the same time, it should be noted that the hypocholesterolemic activity of the other studied strains was not lower, and in some cases even higher than that of most of the drugs currently used for cholesterinosis. Conclusions. The obtained results allow us to assert that it is necessary to develop a series of functional foods and probiotics based on the studied strains and their compositions in an encapsulated form, for the prevention and treatment of diseases associated with the negative manifestations of high cholesterol levels.

Effects of Tryptophan Supplementation in Diets with Different Protein Levels on the Production Performance of Broilers.

Tryptophan plays an important role in the pig industry but has the potential to improve performance in the poultry industry. The purpose of this study was to examine the effects of tryptophan supplementation in diets with different protein levels on the feed intake, average daily gain (ADG), and feed conversion ratio (F/G) of broilers. A total of 180 twenty-one-day-old broilers (half male and half female) were weighed and randomly allocated to twelve groups, with six male and six female groups. Each group consisted of 15 broilers. The broilers were fed low- (17.2%), medium- (19.2%), or high- (21.2%) protein diets with or without extra tryptophan (up to 0.25%) during the 28-day experiment. Food intake and body weight were measured weekly during the trial period. Male broilers fed a medium-protein diet containing more tryptophan showed a lower F/G. In the low-protein diet groups, additional tryptophan caused a significant reduction in the feed intake of female broilers during the first two weeks. Moreover, the serum GLP-1, cholesterol, and bile acid levels, as well as the expression of FXR mRNA in the ileum, were significantly increased. Additionally, the FXR mRNA in the hypothalamus and the GCG and GLP-1R mRNAs in the ileum tended to increase in these broilers. In summary, the tryptophan concentration in the diet can influence the feed intake and metabolism of broilers. Under a standard diet, an appropriate amount of tryptophan is beneficial to the F/G of male broilers, while under a low-protein diet, tryptophan supplementation may cause a short-term reduction in the feed intake of female broilers by increasing serum GLP-1 and bile acid signals.

Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes

BackgroundRecently deorphanized G protein-coupled receptor 146 (GPR146) was shown to respond to signal from a newly identified hormone—cholesin—and to play a role in hepatic lipid metabolism. However, the importance of its biological activity in human organism remains elusive, mainly due to the lack of studies on human tissues up to this point. This study aimed to identify the cholesin receptor-associated genes and clinical factors linked with their expression in cardiovascular system and associated adipose tissues.MethodsRight cardiac auricle, aortic wall, saphenous vein, and adipose tissue (periaortic-PAT, epicardial-EAT, thymic-TAT) samples were collected during coronary artery bypass grafting. Clinical records of the study participants were assessed for the presence of diabetes, medications taken and serum cholesterol levels. GPR146 mRNA expression in all gathered tissues was assessed with qPCR, and RNA seqencing was performed in selected tissues of 20 individuals to identify pathways associated with GPR146 expression.ResultsWe included 46 participants [37 male, 23 with type 2 diabetes, median age 68.50 (Q1–Q3: 63.00–72.00) years, BMI 28.39 (26.06–31.49) kg/m2]. GPR146 expression in adipose tissues significantly correlated with BMI, c-peptide, total cholesterol, and LDL concentrations. Selected metabolic pathways were significantly and positively enriched in GPR146-dependent manner. GPR146-coexpressed genes contained key regulators of lipid metabolism involved in such pathways as fatty acid metabolism, tricarboxilic acid cycle and peroxisomal metabolism. Those genes correlated positively with serum concentrations of LDL, HDL, and total cholesterol. SGLT2i treatment was associated with inversion of GPR146-related signature in EAT, suggesting potential impact on cholesin-GPR146 network.ConclusionsGPR146 expression is associated with serum lipids and metabolically-relevant transcriptomic changes in EAT similar to SGLT2i-associated ones.Graphical abstract

Effect of Dietary Addition of Fennel (Foeniculum vulgare) Seed on Growth Performance, Haemato-Biochemical Profile and Faecal Microbiota of Kankrej Calves

The experiment was conducted during the month of February and March, 2023 at Livestock Research Station, Kamdhenu University, Sardarkrushinagar, Gujarat, India to evaluate the effect of dietary addition of fennel (Foeniculum vulgare) seed on growth performance, haemato-biochemical profile and faecal microbiota of Kankrej calves. Eighteen Kankrej calves were randomly divided into three treatment groups, viz. Basal diet (control), Basal diet+5 g animal-1 day-1 of fennel seed powder supplementation and Basal diet+10 g animal-1 day-1 of fennel seed powder supplementation for a period of 60 days. Results revealed that there was numerically higher body weight gains were observed in groups fed 5 and 10 g of fennel seed daily than the control, the difference was statistically not significant (p>0.05) among the treatment groups. The mean faecal counts (log10 cfu g-1 in fresh faeces) of lactobacillus were increased, while coliform were reduced in groups fed 5 and 10 g of fennel seed daily as compared to control group. There was no effect (p>0.05) on the haemoglobin, haematocrit, total erythrocytes count and total leucocytes count among the treatment groups. No difference (p>0.05) was found in serum levels of total proteins, albumin, globulin, urea, triglycerides, cholesterol, ALT and AST concentrations among the treatment groups. It may be concluded that dietary fennel seed powder supplementation in calves improved growth performance and had beneficial effect on faecal microbiota with higher faecal lactobacillus count and lower faecal coliform count. Fennel seed supplementation did not affect haemato-biochemical profile of calves.

Special Aspects of Cholesterol Metabolism in Women.

Cardiovascular diseases due to arteriosclerosis are the most common causes of death and disability in both men and women. Hypercholesterolemia, a treatable risk factor, is often detected after a delay in women, and then inadequately treated. It is, therefore, important to know the sex-specific aspects of cholesterol metabolism and to address them specifically. We conducted a selective literature search in PubMed with particular attention to current guidelines. In the population as a whole, the age-associated rise in serum cholesterol levels occurs approximately 10 years later in women than in men. Women are exposed to a higher cholesterol load than men at the beginning of their lives, and especially after menopause. This is correlated with a later, but nonetheless clinically relevant rise in the incidence of myocardial infarction in older women. Because women's LDL cholesterol and lipoprotein(a) levels rise after menopause, their lipid profiles should be re-evaluated at this time. Moreover, conditions that are specific to women such as polycystic ovary syndrome, contraception, and especially the phases of life-such as planning to become pregnant, pregnancy, and breastfeeding-need to be considered for both diagnostic and therapeutic purposes. Sex-specific differences and cholesterolassociated risks are particularly pronounced in women with familial hypercholesterolemia (prevalence 1:250). Lowering high cholesterol levels, especially in postmenopausal women, may prevent the development of cardiovascular diseases.

Downregulation of Setdb2 promotes alternative activation of macrophages via the PI3K/Akt pathway to attenuate NAFLD after sleeve gastrectomy

Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.

Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.

Comprehensive chemical profiling with UHPLC-MS, in-vitro, in-silico, and in-vivo antidiabetic potential of Typha domingensis Pers; A novel source of bioactive compounds

Aim of studyTypha is one of the valuable plant genera in folklore use in diabetes, and it can be a good source of bioactive chemicals. The current project was planned to investigate the pharmaceutical potential of n-butanol fraction of Typha domingensis Pers. (TDBF), a less explored medicinal plant. Materials and methodsThe phytochemical composition of the TDBF was assessed through a comprehensive analysis, encompassing the quantification of total bioactive contents (including total tannins and HPLC-PDA quantification) and a thorough exploration of secondary metabolites through scanning with UHPLC-MS. The pharmacological assessment included the determination of antioxidant activity (Total Antioxidant Capacity and Metal Chelating Assay), hemolytic potential, in-vitro antidiabetic effects (α-glucosidase and α-amylase inhibition, and antiglycation activity), as well as in-vivo antidiabetic activities. Molecular docking and ADMET studies were also performed for UHPLC-MS identified compounds. ResultsThe TDBF showed 134.76 ± 8.23 mg TAE/g total tannin contents. With HPLC-PDA, p-Hydroxy benzoic acid and p-Coumaric acid were quantified. During UHPLC-MS scanning, a total of five bioactive metabolites were identified in the negative mode, while 54 were detected in the positive mode. The in-vivo assessment of antidiabetic activity revealed a notable reduction in blood glucose levels in diabetic rats following treatment with the extract, demonstrating its efficacy compared to the control groups. Furthermore, the extract exhibited a positive impact on renal and liver function, evidenced by lowered levels of serum urea, ALT, ALP, creatinine, and a decrease in serum cholesterol levels. ConclusionThe results of this study showed that Typha domingensis Pers. possesses a variety of bioactive compounds and demonstrates notable potential in regulating diabetes. The study recommends further investigation into isolating these bioactive phytochemicals for their potential therapeutic applications across various diseases.

Unraveling the hepatic stellate cells mediated mechanisms in aging's influence on liver fibrosis

Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-β, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- β and in contrast to Group I. Increased TGF-β and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.