Serum HDL-C Research Articles

HDL mimetics protect Alzheimer’s patients carrying APOE ε4 from SARS-CoV-2 invasion

Patients with Alzheimer’s disease (AD) inheriting Apolipoprotein (APOE) ε4 are susceptible to COVID-19, but the underlying mechanism of how such a neurodegenerative disease promotes respiratory vulnerability to viral infections remains insufficiently understood. The uncovering of genetic basis of COVID-19 outcome holds the potential to establish disease models for therapeutic development. Here, using human iPSC-derived type II alveolar epithelial cells (hAECII) from AD patients with APOE ε4 and healthy individuals, we showed that AECII of AD had a greater level of SARS-CoV-2 invasion but not replication, along with increased expressions of viral receptor and co-receptors, while reduced pulmonary surfactant proteins. Since low serum HDL-C levels have been implicated in the onset of both AD and COVID-19, we further revealed that HDL mimetics, including 4 F dimeric peptide and its phospholipid conjugate pHDL, were effective in protecting AECII bearing APOE ε4 against SARS-CoV-2 invasion. In AD, concomitant with improved AD pathological phenotypes, HDL mimetics specifically restored the defective basal SP-D, a pulmonary innate immune lipoprotein that targets glycans of the spike protein to neutralize invading viruses. Moreover, HDL mimetics demonstrated strong SP-D-independent virucidal effects, which additionally restricted the entry of coronaviral particles into non-AD AECII models and lungs of human ACE2-transgenic mice in response to Alpha and Omicron variants of SARS-CoV-2. Our work offers critical insights into the respiratory sensitivity of AD patients carrying APOE ε4 to viral infection and repurpose HDL-based therapeutics as potential preventive interventions in respiratory viral pandemics.

Beneficial effects of flavonoids on animal models of atherosclerosis: A systematic review and meta-analysis

Atherosclerosis is the main cause of cardiovascular diseases that seriously endanger human health. The existing treatment drugs are effective, but they have some side effects. Accumulating evidence suggests that flavonoids have attracted wide attention due to their multiple cardioprotective effects and fewer side effects. PubMed, Web of Science database, Embase, and Cochrane Library were searched for studies evaluating the effects of flavonoids against atherosclerosis. 119 studies published from August 1954 to April 2023 were included. Random-effects models were performed for synthesis. Compared with the control group, flavonoids significantly reduced longitudinal and cross-sectional plaque area. The findings indicated that flavonoids significantly reduced the concentrations of serum TC, TG, and LDL-C and increased serum HDL-C concentrations. Besides, flavonoids reduced the levels of circulating pro-inflammatory factors, including TNF-α, IL-1β, and IL-6, and increased the serum IL-10 level. This study provides evidence for the potential cardiovascular benefits of flavonoids.

Rutin ameliorate PFOA induced renal damage by reducing oxidative stress and improving lipid metabolism

Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant that can accumulate in the kidneys and eventually cause kidney damage. Rutin (RUTIN) is a natural flavonoid with multiple biological activities, and its use in against kidney damage has been widely studied in recent years. It is not yet known whether rutin protects against kidney damage caused by PFOA. In this study, 30 ICR mice were randomly divided into three groups: CTRL group, PFOA group and PFOA+RUTIN group. The mice were fed continuously by gavage for 28 days. Renal pathological changes were assessed by HE and PASM staining, and serum renal function and lipid indicators were measured. RNA-seq and enrichment analysis using GO, KEGG and PPI to detect differential expression of genes in treatment groups. Kidney tissue protein expression was determined by Western blot. Research has shown that rutin can improve glomerular and tubular structural damage, and increase serum CREA, HDL-C levels and decrease LDH, LDL-C levels. The expression of AQP1 and ACOT1 was up-regulated after rutin treatment. Transcriptomic analysis indicated that PFOA and rutin affect the transcriptional expression of genes related to lipid metabolism and oxidative stress, and may affected by PI3K-Akt, PPAR, NRF2/KEAP1 signaling pathways. In conclusion, rutin ameliorated renal damage caused by PFOA exposure, and this protective effect may be exerted by ameliorating oxidative stress and regulating lipid metabolism.

Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect

Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome-proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. Methods: One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. Results: Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not significantly change, but M2-BPGi, an index of fibrosis, significantly decreased. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions: As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Huayuwendan decoction ameliorates inflammation via IL-17/NF-κB signaling pathway in diabetic rats

Ethnopharmacological relevanceHuayuwendan decoction (HYWD) is a broad used traditional Chinese medicine and therapeutic effects against type 2 diabetes mellitus (T2DM). The mechanism of HYWD on the treatment of T2DM is still unclear. Aim of the studyFor this reason, this study was performed to uncover the effects and mechanism of action of HYWD on T2DM. Materials and methodsMale Wistar rats were chosen to set up the T2DM model. This study was randomly divided into six groups: CON (control), MOD (model), HYWDL (Huayuwendan decoction Low Dose), HYWDM (Huayuwendan decoction Middle Dose), HYWDH (Huayuwendan decoction High Dose), and MET (Metformin). Body weight gains were estimated. Using H&E staining, pathological alterations was explored. The serums of fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2 h PG) were detected by Roche blood glucose meter. LDL-C and HDL-C were analyzed by automatic biochemical analyzer. Network pharmacology analyzed the active ingredients, drug targets, and key pathways of HYWD in T2DM treatment. The islet function and inflammation related factors were determined by ELISA. NF-κB signaling pathway or IL-17 signaling pathway related proteins were analyzed by Western blotting. IL-17RA were determined by immunohistochemistry analyze. ResultsHYWD inhibited weight gain in T2DM rats. Histopathological results showed that HYWD inhibits liver injury. HYWD suppressed LDL-C and enhanced HDL-C in serum of T2DM rats. HYWD reduce FPG and 2 h PG, inhibit Fins, GSP and IRI, but enhance IAI in serum of T2DM rats. In addition, the network pharmacology results identified 292 chemical compounds in HYWD. 279 candidate targets were recognized, including IL-17A, IL-1β, NFкB, stats, mmp3, and cxcl2. The pathways revealed that the possible target of HYWD related with the regulation of IL-17 signaling pathway and NF-κB pathway. Then in vivo study, HYWD reduced the levels of IL-6, TNF-α, IL-17 and IL-1β in serum and inhibit the protein expression involved in IL-17/NF-κB signaling pathway. ConclusionsThe study demonstrates that HYWD may improve T2DM by repressing with the IL-17/NF-κB signaling pathway, which offer encouraging support for using alternative medicine of type 2 diabetes mellitus.

Effects of Seed of Different Mango Cultivars in Triton X-100 Induced Hyperlipdemic Rats

Hyperlipidemia is the most prevalent indicator for susceptibility to atherosclerotic heart diseases. The present study investigated the hypolipidemic potential of Mangifera haden, Mangifera pirie and combined extracts of Mangifera haden and Mangifera pirie seeds in Triton X-100 induced hyperlipidemic rats. Before the starting of the experiment, the animals were acclimatized to the laboratory conditions for a period of seven days. At the end of the acclimatization period, each rat was weighed and randomly divided into twelve groups of five animals each, comprising of test animals and control groups. Proximate analysis, toxicity studies, lipid profile parameters were determined in the study. The research study took place in the animal house of Biochemistry Department, University of Nigeria, Nsukka from July 2020 to August 2022. Proximate composition of Mangifera haden and Mangifera pirie seed extracts revealed that the (%) values of protein, lipid, crude fibre, ash, moisture, and carbohydrate are (4.82, 17.18, 4.29, 2.77, 8.39, 62.55) and (3.81, 20.20, 3.0, 1.0, 34.0, 37.99) respectively. Mangifera haden and Mangifera pirie were administered at different doses (200 mg, 300 mg, 500 mg) of the extracts per kilogram body weight of the animals while combined extract of Mangifera haden and Mangifera pirie were administered at 300 mg and 500 mg of the extract per kilogram body weight of the animals in Triton –Induced hyperlipidemic rats. Simvastatin and Atorvastatin were used as reference standards. Simvastatin was found to be an effective drug to Atorvastatin in lowering lipid profiles. The statistical analyses were carried out using one way ANOVA followed by Dunnett’s Post Hoc Multiple Comparisons test. Mangifera haden, Mangifera pirie and combined extracts of both species show significant decrease (P = 0.05) in the levels of serum Total Cholesterol, triacylglycerols, VLDL-C, LDL-C, Atherogenic index (A.I) and significant increase (P = 0.05) of serum HDL-C against Triton-Induced hyperlipidemic rats. The result also suggest that at 200 mg/kg Mangifera pirie and 300 mg/kg Mangifera haden body weight concentrations are an excellent lipid lowering agent. Single administration of either Mangifera haden or Mangifera pirie effectively suppressed the Triton-Induced hyperlipidemia in rats than the combined extracts. The organic extracts (Mangifera haden or Mangifera pirie) exhibited quite hypolipidemic potential when compared with one of the reference drugs, Atorvastatin which indicates that the organic extracts could be explored as an alternative therapeutic agent in the treatment of hyperlipidemia.

Tianhuang formula ameliorates non-alcoholic fatty liver diseases in type 2 diabetic mice through CRLS1-ATF3/ChREBP pathway

ObjectiveTianhuang Formula (THF) is a hospital formula summarized by Professor Jiao Guo's 30 years of clinical experience. Some studies have shown that it can alleviate dyslipidemia in the body. The purpose of this study is to confirm whether THF can improve non-alcoholic fatty liver diseases (NAFLD) in type 2 diabetic mice induced by high-fat diet (HFD)/streptomycin (STZ) and to clarify its potential mechanism. MethodsAfter induction of diabetes, mice were administrated with THF (60 ​mg/kg or 120 ​mg/kg) once daily for 10 weeks. Blood glucose (FBG), glucose tolerance, and insulin resistance (IR) were assayed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Blood lipids, alanine transaminase (ALT), and aspartate transaminases (AST) were detected. Serum fasting insulin (INS) and adiponectin (APN) levels were measured using ELISA. Histological changes in liver and pancreatic islets were observed by H&E staining, followed by Oil Red O staining for liver lipid quantification and periodic acid-Schiff (PAS) staining to detect glycogen accumulation. Western blotting detected the levels of fatty cardiolipin synthase 1 (CRLS1), transcription factor activator 3 (ATF3), and carbohydrate-responsive element binding protein (ChREBP) in the liver. The mRNA transcripts of hepatic inflammatory factors, lipogenesis and lipolysis-related genes, and gluconeogenic enzyme-phosphoenolpyruvate carboxykinase (PEPCK), CRLS1, ATF3, and ChREBP mRNA levels were evaluated by RT-qPCR. ResultsTHF restored impaired glucose tolerance and insulin resistance, respectively. There was an improvement in HFD/STZ-induced liver and islet damage, high serum HDL-C and ANP levels, and a significant decrease in FBG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), FFA, INS, ALT, and AST, and lipid droplet counts in the T2DM mice treated with THF. CREBBP binding protein ATF3 mediated the insulin resistance signaling pathway, which regulated glucose and lipid metabolism in the liver. THF upregulated CRLS1, and ChREBP downregulated the expression of downstream ATF3 in the liver. RT-qPCR analysis also systemically indicated that THF suppressed the pathway and key regulators related to inflammation, lipid accumulation, and gluconeogenesis. ConclusionOur findings demonstrated that THF ameliorated lipid profile and attenuated liver steatosis in T2DM mice through CRLS1-ATF3/ChREBP pathway activation.

The attenuating effects of synbiotic containing Cetobacterium somerae and Astragalus polysaccharide against trichlorfon-induced hepatotoxicity in crucian carp (Carassius carassius)

This study aimed to investigate the hepatotoxic effects of trichlorfon on crucian carp (Carassius carassius) and the attenuating effects of a synbiotic combination of Cetobacterium somerae and Astragalus polysaccharide on hepatotoxicity. Results showed that trichlorfon did indeed induce hepatotoxicity in crucian carp and the synbiotic reversed this hepatotoxicity caused by trichlorfon. The synbiotic increased TC, TG, LDL-C, ALT and AST levels and decreased serum HDL-C levels caused by trichlorfon. H&E and Oil Red O staining demonstrated that the synbiotic ameliorated liver damage and abnormal lipid accumulation. The activity of antioxidant enzymes (T-SOD, CAT, GSH-Px) in the liver was also enhanced by the administration of the synbiotic. The supplementation of the synbiotic also increased the level of short-chain fatty acids in the intestine. In addition, the synbiotic balanced the gut microbial composition, leading to a reduction in the abundance of potentially pathogenic bacteria and an increase in the abundance of bacteria producing short-chain fatty acids. In conclusion, these findings indicate that trichlorfon can induce hepatotoxicity in crucian carp, whereas synbiotics can regulate gut microbiota, promote the growth of beneficial bacteria and increase the production of SCFAs, and alleviate trichlorfon-induced liver injury.

Associations of urinary di(2-ethylhexyl) phthalate metabolites with lipid profiles among US general adult population

BackgroundDi(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. MethodsIn this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005–2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. ResultsA total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend <0.05), but there was no notable association with MEHP. RCS demonstrated a linear relationship of DEHP metabolites with HDL-C, TC, TG, and LDL-C (all P for nonlinearity >0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [β = −0.26, 95%CI (−0.43, −0.09), P = 0.002], TC [β = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [β = 2.40, 95%CI (0.85, 3.96), P = 0.003]. ConclusionOur study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

Optimization of the proportions of advantageous components in the hypolipidemic “bioequivalent substance system” of Jiang-Zhi-Ning and its mechanism of action

Context Jiang-Zhi-Ning (JZN), a traditional Chinese medicinal formula, is used to treat hyperlipidemia in clinics. Objective To screen the hypolipidemic “bioequivalent substance system (BSS)” of JZN and elucidate the potential hypolipidemic mechanism. Materials and methods In vitro, the TG content in HepG2 cells was determined after the intervention of the combination of advantageous components (CAC) by uniform design. In vivo, hyperlipidemia models were established by Triton WR-1339 (400 mg/kg; i.p.) in male ICR mice, and corresponding treatments were administered via oral administration once. The mice were divided into 12 groups (n = 5): control, hyperlipidemic model, simvastatin (positive control, 20 mg/kg), gradient doses of JZN granules (2, 4 and 8 g/kg) and the hypolipidemic effective extraction (HEE) of JZN (120, 240 and 480 mg/kg) and CAC groups (20, 40 and 160 mg/kg). Serum TC, TG, LDL-C and HDL-C were performed after 24 h. Transcriptomics and qRT–PCR technology were used to explore the mechanism of the “BSS” of JZN. Results In vitro, the ratio of CAC was determined. CAC could reduce the TG content in HepG2 cells (77.21%). Compared with the model group, the high dose of CAC could markedly decrease the levels of TC (61.86%), TG (105.54%) and LDL-C (39.38%) and increase the level of HDL-C (232.67%). CAC was proved to be the “BSS”. Transcriptomics and qRT–PCR analysis revealed CAC regulated non-alcoholic fatty liver disease, bile secretion, PPAR and adipocytokine signalling pathway. Discussion and conclusions These findings provided new feasible ideas and methods for the elucidation of the pharmacodynamic material basis.

Tartary buckwheat root polysaccharides ameliorate non-alcoholic fatty liver disease via the IL6-SOCS3-SREBP1c pathway.

Our previous study demonstrated that Tartary buckwheat root polysaccharides (TBRP) could reduce insulin resistance in diabetes mellitus by inhibiting SOCS3-stimulated IRS1 protein degradation. However, whether TBRP has the efficiency to treat non-alcoholic fatty liver disease (NAFLD) is still undetermined. This investigation aimed to examine the effects of TBRP on a high-fat diet (HFD)-triggered NAFLD, and elucidate the underlying molecular mechanisms. Briefly, TBRP toxicity in hepatoma (BEL7404) and pancreatic cancer (BxPC3) cells and zebrafish embryos developmental models, were evaluated in-vitro and in-vivo, respectively. TBRP inhibited cellular lipid accumulation by suppressing fat synthesis, furthermore, it improved body weight gain, liver weight, liver-to-body weight ratio, serum lipids triglyceride, total cholesterol, ALT, LDL-C, HDL-C, and AST levels in the NAFLD mice model. Additionally, TBRP treatment also lowered the nitric oxide content. The qPCR assay revealed that mRNA expression of TNF, IL1β, and IL6 was also markedly reduced in TBRP-treated NAFLD mice. The expression of SOCS3, SREBP1c, and STAT3 was elucidated by western blot analysis, which indicated that TBRP markedly decreased the gene expression for de novo fat synthesis by the SOCS3-SREBP1c pathway. These findings reveal that TBRP ameliorates NAFLD via the IL6-SOCS3-SREBP1c signaling pathway and therefore, may represent a promising approach for NAFLD treatment.

Association of low HDL-c levels with severe symptoms and poor clinical prognosis in patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel bunyavirus, characterized by high fever, thrombocytopenia, and multiple organ damage. Disturbances in lipid metabolism often occur during viral infections, but the changes and clinical significance of lipid profiles in SFTS patients remain unclear. This study aimed to investigate the alterations in lipid profiles and their clinical significance in SFTS patients. A total of 157 SFTS patients and 157 healthy controls were enrolled in this study. Serum lipid levels were collected and analyzed among different groups and prognosis categories. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of lipid levels in distinguishing between severe and mild cases, as well as surviving and non-surviving patients. Pearson correlation analysis was used to examine the associations between lipid levels and clinical laboratory parameters. SFTS patients exhibited significantly lower levels of HDL-c, LDL-c, cholesterol, APoAI, and ApoB compared to healthy controls, while triglyceride levels were significantly higher. Serum HDL-c and ApoAI demonstrated good performance as indicators for distinguishing between survivors and non-survivors (AUC of 0.87 and 0.85, respectively). Multivariate regression analysis indicated that HDL-c independently acts as a protective factor in patients with SFTS. HDL-c levels showed decline in non-survivors but recovered in survivors. Moreover, HDL-c exhibited significant correlations with various clinical laboratory parameters (IL-6, CRP, AST, TT, APTT, PLT, ALB, and CD4). This study identified abnormalities in serum lipid metabolism among SFTS patients. HDL-c and ApoAI levels hold potential as biomarkers for distinguishing survivors from non-survivors. Additionally, HDL-c and ApoAI may serve as therapeutic targets for the management of SFTS patients.

The Correlation Between Lipid Profile and Proteinuria In Adult Nephrotic Syndrome Patients in Bangladeshi Population

The nephrotic syndrome is a constellation of abnormalities that includes massive proteinuria, hypoalbuminemia and edema. Dyslipidemia is an important secondary biochemical abnormalities in nephrotic syndrome due to proteinuria and hypoalbuminemia. Dyslipidemia in nephrotic syndrome involved in the cardiovascular risk and also accelerates the progression of glomerular dysfunction. This study was conducted to evaluate the relationship between dyslipidemia and proteinuria in adult nephrotic syndrome patients. A total of 50 (fifty) diagnosed adult nephrotic syndrome patients from the Dept of Nephrology, Dhaka Medical College, Dhaka with age range from 20-50 years of both sexes were enrolled as study subjects. To evaluate the correlation between serum TC, TAG, HDL-C and LDL-C with 24 hour urinary total protein. This case control study was carried out in the Department of Biochemistry, Dhaka Medical College, Dhaka, during the period of July 2013 to June 2014. With baseline information, lipid profile and 24 hour urinary total protein of study subjects were estimated. Mean values of the variables were determined. Correlation between variables were determined by Pearson's correlation test by using SPSS for windows version 20.0. For all the statistical analysis p&lt;0.05 was considered as significant. Mean(±SD) values of serum total cholesterol (Tchol), TAG, HDL-C and LDL-C in adult nephrotic syndrome patients were 288.23±35.67 mg/dl, 174.53±18.86 mg/dl, 23.71±4.58 mg/dl and 231.16±34.28 mg/dl respectively. Mean value of 24 hour urinary total protein in study subjects was 5.65±0.54 gm/d. Positive correlation was found between 24 hour urinary total protein and Tchol (r=0.476, p&lt;0.05), TAG (r=0.354, p&lt;0.05), LDL-C (r=0.444, p&lt;0.05) and positive correlation was found between 24 hour urinary total protein and HDL-C (r=0.028 p&gt;0.05). Dyslipidemia in adult nephrotic syndrome possesses a significant relationship with proteinuria which could predispose them to develop coronary artery disease.&#x0D; Bangladesh J Med Biochem 2018; 11(2): 24-33

TO DETERMINE THE LEVELS OF GOOD CHOLESTEROL-HDL IN THE PATIENTS HAVING ISCHEMIC STROKE AND DISEASE OUTCOME IN NEXT 2 WEEKS

To know about the levels of good cholesterol-HDL in ischemic stroke patients and disease outcomes in the next 2 weeks. This study was carried out from July 2021 to Jan 2022 at the Department of Medicine Divisional Teaching Hospital Mir Pur Azad Jammu and Kashmir. Inclusion criteria were any patient aged between &gt; 20 years old, both males and females admitted with sudden onset of focal neurological deficit. They diagnosed the CT brain as an ischemic stroke less than 24 hours old.HDL-C levels immediately after admission before starting aspirin and statins. The patient’s functional outcome was assessed by using the ADL scale at 2 weeks. The data collected was evaluated on SPSS. A total of 150 patients were included in the study. The mean age of patients was 60.16 + 1.35 years. There were 85 (68%) males and 40 (32%) females. One hundred-five patients (84%) had serum HDL-C levels less than the appropriate range, and 20 (16%) had serum HDL-C levels within the appropriate range. Patients with high HDL-C levels show statistically significant better functional outcomes (p-value 0.001). We conclude that high serum HDL-C levels are strongly associated with better functional outcomes 2 weeks after stroke, and patients with high HDL-C levels are at reduced risk of developing stroke.

Effects of dietary lipid levels on lipid accumulation and health status of adult Onychostomamacrolepis

The effects of different dietary lipid levels on lipid accumulation, inflammatory response, serum bio-chemical index and histological features of intestine and hepatopancreas of O.macrolepis was experimentally evaluated in an eight-weeks study. Fish (initial weight 50.11 ± 2.86 g) were fed with five iso-nitrogenous diets (around 390 g/kg protein) varying with lipid level (5%, 7%, 9%, 11%, 13%, being LL5, LL7, LL9, LL11, and LL13 respectively) in triplicates. Results showed that the content of crude lipid in carcass and hepatopancreas were not affected by dietary lipid levels (P > 0.05). Serum ALT, TP, HDL-c and MDA, etc., were not significantly affected by diets (P > 0.05), while serum total antioxidant capacity in LL9 and LL11 groups were significantly higher than the other groups (P < 0.05). Histological features of hepatopancreas and intestine showed no significant difference among the five diets (P > 0.05), while the height of intestine villus showed the higher trend in LL9 compared with other groups. The relative expression of lipid metabolism related genes (ppar α, cpt-1α, fas, and hsl) and immune response related genes (tlr 22, nrf 2, tnfα, and il-γ) in the hepatopancreas of fish fed diets differing in their crude lipid levels were not significantly different (P > 0.05). The results suggested that a proper dietary lipid level of 9%–11% could maintain higher antioxidant and health status of adult O.macrolepis.

Fumigaclavine C ameliorates liver steatosis by attenuating hepatic de novo lipogenesis via modulation of the RhoA/ROCK signaling pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated.MethodsThe pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis. ResultsFC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate.ConclusionsThese findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.

Integrating network analysis and pharmacokinetics to investigate the mechanisms of Danzhi Tiaozhi Decoction in metabolic-associated fatty liver disease (MAFLD)

Ethnopharmacological relevanceBased on ancient classics, Danzhi Tiaozhi Decoction has been successfully used to treat nonalcoholic fatty liver disease for decades. However, its therapeutic mechanisms remain unclear. Aim of the studyThis study aimed to investigate the effects of Danzhi Tiaozhi Decoction (DZTZD) on metabolic-associated fatty liver disease (MAFLD). Materials and methodsFirst, we identified the active ingredients of DZTZD and their potential targets in the Traditional Chinese Medicine System Pharmacology database. Using the overlapped genes, we selected the key MAFLD-associated genes, then conducted GO and KEGG pathway enrichment analyses. Furthermore, DZTZD was administered orally to rats, and their serum and liver tissues were examined for absorbed compounds using pharmacochemistry. UPLC-Q-Exactive Orbitrap/MS was used to determine the main compounds. Then, we validated the binding association of the key targets with their active compounds with AutoDock Tools and other software. Finally, the predicted hub targets were experimentally validated. ResultsWe found 254 active compounds in DZTZD corresponding to 208 targets. Sixteen key genes were identified, and the enrichment analysis revealed multiple signaling pathways, including the AGE-RAGE pathway in diabetic complications and the lipid and atherosclerosis signaling pathway. Next, 160 absorbed components and metabolites were characterized in vivo, and 53 absorbed components and metabolites were characterized in liver tissue. Thirteen parent compounds were identified, including coptisine, quercetin, luteolin, and aloe-emodin. The molecular docking data demonstrated the strongest binding between the active compounds and the core proteins. Moreover, the animal experiments showed that DZTZD decreased body weight, liver weight, lipid accumulation, and ALT, AST, CRP, FFA, IL-6, PEPCK, G6P, TG, TC, and LDL-c serum levels, and increased serum HDL-c levels compared to high-fat induced rats. Besides, the RT-PCR and Western blot showed that DZTZD inhibited the SREBP1c and FAS and increased hyperlipidemia-induced CPT-1A levels. In the high-fat group, JNK phosphorylation increased, and AKT protein phosphorylation decreased, while DZTZD reversed these effects. ConclusionBased on the pharmacological network analysis, pharmacochemistry, and experimental validation, DZTZD can potentially improve MAFLD via the JNK/AKT pathway.

The Metabolic and Analytical Changes of Healthy Volunteers upon Intake of Portuguese Extra Virgin Olive Oil: A Comparison Study between Pre- and Post-Intervention.

(1) Background: Extra virgin olive oil (EVOO) is studied mostly for its health benefits in preventing non-communicable chronic diseases, particularly within a Mediterranean dietary pattern. However, few studies have addressed the effect of EVOO in healthy individuals, prior to an established disease. This study aims to evaluate the impact of Northern Portuguese polyphenol-rich EVOO (NPPR-EVOO) consumption on various important clinical parameters in healthy adult volunteers. (2) Methods: This quasi-experimental intervention study assessed the impact of NPPR-EVOO for a period of 100 days. Serum total cholesterol, HbA1c, HDL-c, LDL-c, and CRP, and anthropometric measures-waist and hip perimeters, hand grip strength, and body fat-were assessed and food logs were analyzed. (3) Results: Serum HbA1c (5.12 ± 0.32%; 4.93 ± 0.24, p = 0.000) and LDL-c (96.50 ± 28.57 mg/dL; 87.41 ± 31.38 mg/dL, p = 0.017) significantly decreased following NPPR-EVOO. Also, daily energy significantly increased, but no changes in other dietary parameters, or anthropometry, were seen. Adherence to the Mediterranean diet did not explain the differences found in individuals regarding serum lipid profile and HbA1c, reinforcing the role of EVOO's effect. (4) Conclusions: NPPR-EVOO lowered the serum levels of LDL cholesterol and HbA1c, providing clues on the effect of EVOO-putative health benefits. These results pave the way for a deeper exploration of EVOO as a functional food.

Interbreed differences in the cholesterol profile in cattle in Western Siberia

The authors studied the leading indicators of the cholesterol profile of high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C) and total cholesterol (TC) in Black-and-White, Red Steppe and Holstein breeds of the second or third lactation, bred in large livestock farms—complexes on the territory of Western Siberia. Metabolism and concentration of lipid complexes of cholesterol status play a cardinal role in the homeostasis of cellular metabolic processes. The critical role of serum lipoproteins in cholesterol metabolism is well recognised, as is their role as predictors of cardiovascular disease. At the same time, the atherogenic effect of LRN-C is associated with the transfer of fatty acids, which act as energy substrates for ATP synthesis. Anti-atherogenic properties characterise HDL-C and have an antioxidant and anti-inflammatory effect. The concentration of HDL-C - was determined by the precipitation method of phosphotungstic acid with magnesium chloride; the level of LDL-C - by the enzymatic colourimetric direct method, total cholesterol - by the process of enzymatic hydrolysis and oxidation of CHOD-PAP using reagent kits “HDL-Cholesterol-Novo”, “LDLCholesterol-Novo-A”, “Cholesterol-Novo” (“Vector-Best, Russia. The content of OH and LDL-C in the blood serum of cows at the age of the second or third lactation bred in Western Siberia is higher than the generally accepted standard values, which reflects a different degree of adaptation to climatic conditions. Ranked series of breeds (p &lt; 0.05) according to LDL-C: black-and-white → Holstein → red steppe, medians were 4.91; 2.77 and 2.24 mmol/l, respectively. Differences between the indicators of HDL-C and LDL-C in Black-and-White, Red Steppe and Holstein cows were established, which indicates the genetic determination of the level of lipoproteins in the blood serum. The strength of the influence of the cow breed factor on the level of HDL-C in blood serum was 29%, LDL-C - 17%.

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.