Reduced Serum Cholesterol Research Articles

Effect of Dietary Supplementation of Lactiplantibacillus plantarum N-1 and Its Synergies with Oligomeric Isomaltose on the Growth Performance and Meat Quality in Hu Sheep.

Probiotics have gained tremendous attention as an alternative to antibiotics, while synbiotics may exhibit a greater growth promoting effect than their counterpart probiotics due to the prebiotics' promotion on the growth and reproduction of probiotics. The objective of this study was to investigate the influence of Lactiplantibacillus plantarum N-1 and its synbiotic with oligomeric isomaltose on the growth performance and meat quality of Hu sheep. Hu sheep (0-3 days old) were fed with water, probiotics of N-1, or synbiotics (N-1 and oligomeric isomaltose) daily in three pens for 60 days and regularly evaluated to measure growth performance and collect serum (five lambs per group). Longissimus thoracis (LT) and biceps brachii (BB) muscle tissues were collected for the analysis of pH value, color, texture, nutrients, mineral elements, amino acids, volatile compounds, and antioxidant capacity. The results showed that dietary supplementation of N-1 tended to improve growth performance and meat quality of Hu sheep, while the synergism of N-1 with oligomeric isomaltose significantly improved their growth performance and meat quality (p < 0.05). Both the dietary supplementation of N-1 and synbiotics (p < 0.05) increased the body weight and body size of Hu sheep. Synbiotic treatment reduced serum cholesterol and improved LT fat content by increasing the transcription level of fatty acid synthase to enhance fat deposition in LT, as determined via RT-qPCR analysis. Moreover, synbiotics increased zinc content and improved LT tenderness by decreasing shear force and significantly increased the levels of certain essential (Thr, Phe, and Met) and non-essential (Asp, Ser, and Tyr) amino acids of LT (p < 0.05). Additionally, synbiotics inhibited the production of carbonyl groups and TBARS in LT and thus maintained antioxidant stability. In conclusion, it is recommended that the use of synbiotics in livestock breeding be promoted to improve sheep production and meat quality.

Statins to Prevent Anthracyclines-Induced Cardiotoxicity

While anthracyclines are a class of chemotherapeutic agents that have improved the treatment of a broad spectrum of malignancies, it is one of the most cardiotoxic agents used to treat the tumor. Despite their dose-dependent cardiotoxicity, anthracyclines-based chemotherapy has become the main stay of tumor therapy due to its efficacy. Meanwhile, Statins, widely used in the clinical setting to reduce serum cholesterol levels and to reduce cardiac morbidity and mortality, have pleiotropic biological effects independent of their lipid-lowering effects. Many studies at home and abroad believe that statins can prevent the cardiotoxicity caused by anthracyclines and propose that statins can play beneficial pleiotropic cardiovascular effects through anti-inflammatory and antioxidant mechanisms, thus playing a cardioprotective effect. Illuminating the mechanisms of Anthracyclines-induced cardiotoxicity and Statins associated therapeutic continue to be the main focus in the field of anti-tumor. Therefore, we summarized the current research surrounding the mechanisms of anthracyclines-induced cardiotoxicity and the protective effect of statins on anthracyclines-induced cardiotoxicity and its possible mechanism.

Effects of supplemental dried wild leek (Allium scorodoprasum L. subsp. rotundum) leaves on laying performance, egg quality characteristics, and oxidative stability in laying hens

This study aimed to examine the effect of dietary supplementation of dried wild leek (Allium scorodoprasum L. subsp. rotundum) leaves on laying performance, egg traits, antioxidant status, and oxidative stability in laying hens. For this purpose, a total of 96 Lohmann White laying hens aged 22 weeks allocated into four treatment groups each containing 24 hens. Hens were fed a diet supplemented with 0 (control), 1 (WL1), 2 (WL2), and 3 (WL3) g/kg dried wild leek (DWL) leaves. During the 10-week trial, egg weight was increased and feed efficiency was improved with 2 and 3 g/kg DWL leaves. No significant differences were observed among groups for egg production, feed intake, internal and external egg quality characteristics, and egg yolk cholesterol concentration. Levels of malondialdehyde and total antioxidant-oxidant status of egg yolk were not affected from DWL supplementation. However, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity was increased and oxidative stress index was decreased in egg yolk. Superoxide dismutase enzyme activity was increased in the group of WL3, and total antioxidant status levels were increased in the groups of WL2 and WL3 in serum. DWL supplementation reduced serum cholesterol concentration significantly. No marked changes were observed in other blood parameters. In conclusion, DWL is considered to be high antioxidant supplement due to having high antioxidant capacity and important bioactive compounds. Dietary supplementation of DWL leaves at 3 g/kg could be a viable and beneficial feed additive to improve egg weight and feed efficiency, increase DPPH radical scavenging activity in egg yolk and antioxidant status of hen. Therefore, the usage of DWL leaves in the laying hen diets will be beneficial for egg producers and poultry nutritionists to produce functional eggs having low cholesterol and high antioxidants.

A Comparative Study of Cholesterol Levels in Non-Pregnant Females Taking Ketogenic Versus Low Calorie Diet

Introduction: Over the past few years, the population of Pakistan has become much aware of the need of weight loss and healthy lifestyle. We evaluated the cholesterol profiles to observe how keto diet and low-calorie diet influence the basic lipid profile of females. Aims: The aim of this study was to compare the cholesterol and triglyceride levels in adult non pregnant females taking ketogenic versus low calorie diet for a one month Methodology: The design of this study was a cross sectional study design. This study was conducted in lady reading hospital Peshawar and the duration of this study was from January 2022 to February 2022. 60 non pregnant females of age between 35-45 years with BMI ranging between 30-34.9 were included in the study. 30 were on low calorie diet, 30 were on keto diet. The serum cholesterol and triglyceride levels were calculated on day 1 and day 30 of the study. Results: The serum chloesterol levels were significantly reduced in individuals taking low calorie diet as compared to keto diet over a period of thirty days. After few weeks, anthropometric and body composition measurements revealed a significant reduction significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of body weight. There was a significant, slightly decrease of LBM. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced. Practical Implication: to determine the effects of a ketogenic diet (KD) in women age with a diagnosis of PCOS. We hypothesized that a modified KD (KEMEPHY diet) would lead to an improvement in body weight, plasma cholesterol, triglycerides, hyperinsulinemia, and hormonal outcomes Conclusion: Low calorie diet was significantly better than ketogenic diet in reducing serum cholesterol and triglyceride levels in individuals on a 30-day diet plan of respective type. Our results suggest that a ketogenic diet may be considered as a valuable nonpharmacological treatment for Polycystic ovary syndrome. Longer treatment periods should be tested to verify the effect of a ketogenic diet on the dermatological aspects of Polycystic ovary syndrome. Keywords: Cholesterol, Ketogenic Diet, Serum, Lifestyle, Low Calorie, Nutritionist

Pseurotin A Validation as a Metastatic Castration-Resistant Prostate Cancer Recurrence-Suppressing Lead via PCSK9-LDLR Axis Modulation.

Metastatic castration-resistant prostate cancer (mCRPC) cells can de novo biosynthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 proved to contribute to mCRPC cell motility since PCSK9 knockdown (KD) in mCRPC CWR-R1ca cells led to notable reductions in cell migration and colony formation. Human tissue microarray results proved a higher immunohistoscore in patients ≥ 65 years old, and PCSK9 proved to be expressed higher at an early Gleason score of ≤7. The fermentation product pseurotin A (PS) suppressed PCSK9 expression, protein-protein interactions with LDLR, and breast and prostate cancer recurrences. PS suppressed migration and colony formation of the CWR-R1ca cells. The progression and metastasis of the CWR-R1ca-Luc cells subcutaneously (sc) xenografted into male nude mice fed a high-fat diet (HFD, 11% fat content) showed nearly 2-fold tumor volume, metastasis, serum cholesterol, low-density lipoprotein cholesterol (LDL-C), prostate-specific antigen (PSA), and PCSK9 levels versus mice fed a regular chow diet. Daily oral PS 10 mg/kg treatments prevented the locoregional and distant tumor recurrence of CWR-R1ca-Luc engrafted into nude mice after primary tumor surgical excision. PS-treated mice showed a significant reduction in serum cholesterol, LDL-C, PCSK9, and PSA levels. These results comprehensively validate PS as an mCRPC recurrence-suppressive lead by modulating the PCSK9-LDLR axis.

Intensive cholesterol-lowering treatment reduces synovial inflammation during early collagenase-induced osteoarthritis, but not pathology at end-stage disease in female dyslipidemic E3L.CETP mice

The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterol-lowering therapies in OA development has remained elusive. Recently, we did not observe beneficial effects of intensive cholesterol-lowering treatments on spontaneous OA development in E3L.CETP mice. We postulated that in the presence of local inflammation caused by a joint lesion, cholesterol-lowering therapies may ameliorate OA pathology. Female ApoE3∗Leiden.CETP mice were fed a cholesterol-supplemented Western type diet. After 3 weeks, half of the mice received intensive cholesterol-lowering treatment consisting of atorvastatin and the anti-PCSK9 antibody alirocumab. Three weeks after the start of the treatment, OA was induced via intra-articular injections of collagenase. Serum levels of cholesterol and triglycerides were monitored throughout the study. Knee joints were analyzed for synovial inflammation, cartilage degeneration, subchondral bone sclerosis and ectopic bone formation using histology. Inflammatory cytokines were determined in serum and synovial washouts. Cholesterol-lowering treatment strongly reduced serum cholesterol and triglyceride levels. Mice receiving cholesterol-lowering treatment showed a significant reduction in synovial inflammation (P=0.008, WTD: 95% CI: 1.4- 2.3; WTD+AA: 95% CI: 0.8- 1.5) and synovial lining thickness (WTD: 95% CI: 3.0-4.6, WTD+AA: 95% CI: 2.1-3.2) during early-stage collagenase-induced OA. Serum levels of S100A8/A9, MCP-1 and KC were significantly reduced after cholesterol-lowering treatment (P=0.0005, 95% CI:-46.0 to-12.0; P=2.8×10-10, 95% CI:-398.3 to-152.1; P=2.1×10-9,-66.8 to-30.4, respectively). However, this reduction did not reduce OA pathology, determined by ectopic bone formation, subchondral bone sclerosis and cartilage damage at end-stage disease. This study shows that intensive cholesterol-lowering treatment reduces joint inflammation after induction of collagenase-induced OA, but this did not reduce end stage pathology in female mice.

Effects of roxadustat on anemia, iron metabolism, and lipid metabolism in patients with non-dialysis chronic kidney disease.

We determined the effects of roxadustat on the values of anemia, iron metabolism, renal function, proteinuria, and lipid metabolism and identified the associated factors of the change in hemoglobin levels after roxadustat administration in non-dialysis chronic kidney disease (CKD) patients who were receiving an erythropoietin-stimulating agent (ESA). We conducted retrospective analysis of the changes in hemoglobin, serum ferritin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels; transferrin saturation; the estimated glomerular filtration rate; and the urinary protein/creatinine ratio over 24 weeks after the change from an ESA to roxadustat in 50 patients with non-dialysis CKD and anemia (roxadustat group). Seventy-two patients with non-dialysis CKD and anemia who proceeded ESA therapy were used as the control (ESA) group. We observed no significant between-group differences in clinical parameters at baseline except for the significantly lower hemoglobin concentration and lower proportion of diabetes mellitus in the roxadustat group. The hemoglobin concentration was significantly higher in the roxadustat group after 24 weeks (11.3 ± 1.2 versus 10.3 ± 1.0 g/dL; value of p < 0.05), whereas the transferrin saturation, ferritin concentration, estimated glomerular filtration rate, and urinary protein/creatinine ratio were not different between the two groups. TC (135.9 ± 40.0 versus 165.3 ± 38.4 mg/dL; value of p < 0.05), LDL-C (69.1 ± 28.3 versus 87.2 ± 31.5 mg/dL; value of p < 0.05), HDL-C (41.4 ± 13.5 versus 47.2 ± 15.3 mg/dL; value of p < 0.05), and triglyceride concentrations (101.5 ± 52.7 versus 141.6 ± 91.4 mg/dL, value of p < 0.05) were significantly lower in the roxadustat group compared with the ESA group at 24 weeks. Multiple linear regression analysis showed that the roxadustat dose at baseline (standard coefficient [β] = 0.280, value of p = 0.043) was correlated with the change in the hemoglobin levels during the first 4 weeks of roxadustat treatment, whereas age (β = 0.319, value of p = 0.017) and the roxadustat dose at 24 weeks (β = -0.347, value of p = 0.010) were correlated with the hemoglobin concentration after 24 weeks of roxadustat administration. Roxadustat can improve anemia and reduce serum cholesterol and triglyceride levels in non-dialysis CKD patients after the patients' treatment was switched from an ESA without affecting renal function or proteinuria. These results indicate that roxadustat has superior effects to ESAs regarding anemia and lipid metabolism at the dose selected for the comparison in patients with non-dialysis CKD.

Pros and cons for statins use and risk of Parkinson's disease: An updated perspective.

Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). Statins are the most common lipid-lowering agents used in the management of dyslipidemia and the prevention of primary and secondary cardiovascular diseases (CVD) events. In addition, there is a controversial point regarding the role of serum lipids in the pathogenesis of PD. In this bargain, as statins reduce serum cholesterol so they affect the PD neuropathology in bidirectional ways either protective or harmful. Statins are not used in the management of PD, but they are frequently used in the cardiovascular disorders commonly associated with PD in the elderly population. Therefore, the use of statins in that population may affect PD outcomes. Concerning the potential role of statins on PD neuropathology, there are conflicts and controversies either protective against the development of PD or harmful by increasing the risk for the development of PD. Therefore, this review aimed to clarify the precise role of statins in PD regarding the pros and cons from published studies. Many studies suggest a protective role of statins against PD risk through the modulation of inflammatory and lysosomal signaling pathways. Nevertheless, other observations suggest that statin therapy may increase PD risk by diverse mechanisms including reduction of CoQ10. In conclusion, there are strong controversies regarding the protective role of statins in PD neuropathology. Therefore, retrospective and prospective studies are necessary in this regard.

Effect of dulaglutide injection on weight beyond glycemic control: real-world observational study

Dulaglutide is an effective Glucagon-like Peptide-1 (GLP-1) Receptor Agonist (RA) in optimizing weight and glycemic control in obese patients with Type 2 Diabetes Mellitus (T2DM). The study's objective was the real-world evaluation of the metabolic effect of Dulaglutide on weight and glycemic control in patients with T2DM from Southern Iraq. This study is a six-month observational prospective longitudinal evaluation of 185 obese individuals with T2DM. They were initiated on Dulaglutide as an add-on drug with Oral Antidiabetic (OAD) or insulin therapy. General characteristics of the patients, glycated hemoglobin (HbA1c), blood glucose, lipid profile, and side effects profile were evaluated at the enrollment and the end of the study. The enrolled 185 obese patients with T2DM, had a T2DM duration (2 -14 years) and initial HbA1c range (6 - 19.5%), with different treatment modalities, including insulin, OADs, or both. The study showed a significant reduction in weight, HbA1c, and serum cholesterol, with minimal hypoglycemic events in 5% of patients (n=9). The gastrointestinal side effects were mild to moderate and self-limited in &gt;96% of patients (n=178), while they were so severe in 4% (n=7) and caused discontinuation of Dulaglutide. Therefore, the insulin regimen was either stopped (n=28), changed (n=7), or reduced (n=9). No change on oral medications was performed in 141 patients. In conclusion, Dulaglutide 1.5 mg administered once a week significantly reduced the weight, HbA1c, Self-Monitoring of Blood Glucose (SMBG), and cholesterol levels with minimal hypoglycemic risk.

Pectin Feeding Influences Fecal Bile Acid Excretion, Hepatic Bile Acid and Cholesterol Synthesis and Serum Cholesterol in Rats

This study was designed to investigate the effects of pectin on cholesterol and bile acid metabolism and to elucidate the mechanisms involved in its hypolipidemic effect in rats. The key regulatory enzymes in cholesterol and bile acid metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and cholesterol 7α-hydroxylase, were determined. Circulating, hepatic, and biliary lipid concentrations and fecal bile acid excretion were also measured. Male Wistar rats were fed a fiber-free or a pectin-supplemented (7 g/100 g) diet for 4 wk. Bile flow and the biliary secretion of both bile acids and cholesterol were not significantly different than controls in pectin-fed rats. The addition of pectin to the diet resulted in lower serum and liver cholesterol concentrations (-27 and -17%, respectively). Fecal bile acid excretion (+168%) and the hepatic activity of cholesterol 7α-hydroxylase (+70%) were significantly higher in pectin-fed animals. HMG-CoA reductase activity was also significantly greater (+11%) in the presence of dietary pectin. Results of our study indicate that pectin, by enhancing fecal bile acid excretion, may cause increased hepatic synthesis of bile acids and liver depletion of cholesterol in rats, which results in a higher rate of cholesterol synthesis and reduced serum cholesterol concentrations.

Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene

The positive link between osteoporosis and hypercholesterolemia has been documented, and bone resorption inhibitors, such as nitrogen-containing bisphosphonates (N-BP) and selective estrogen receptor modulators (SERMs), are known to reduce serum cholesterol levels. However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (n = 3986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (n = 1624) as an N-BP and raloxifene (RLX) as an SERM (n = 1623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2 years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of ≥ 140 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL, age group of ≥ 75 years, and T score of BMD ≥ -3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, p = 0.001], 0.25 [95% CI 0.09 0.65, p = 0.005], 0.71 [95% CI 0.56 0.91, p = 0.006], 0.47 [95% CI 0.30 0.75, p = 0.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.

Managing a case of hyperlipidaemia from the homoeopathic perspective: a case report

Hyperlipidaemia is a disorder characterised by elevated levels of lipid in blood and is frequently regarded as one of the main risk factors for atherosclerotic illnesses, including coronary heart disease. The associated risk factors include obesity, sedentary lifestyle, fatty food intake, excessive alcoholism and smoking. Since hyperlipidaemia has few or no significant clinical signs, a lipid panel or lipid profile analysis constitutes as the primary method of diagnosis. A case of 51-year-old male suffering from Hyperlipidaemia for few years, which was temporarily relieved with conventional treatment, has been presented here. Clinically patient reported with pain in calves, burning feet, dyspepsia and occasional arthritic pain. After a thorough clinical evaluation, Lycopodium Clavatum in increasing potency (up to Q5), was prescribed when needed. The outcome assessment was done by using the ‘Modified Naranjo Criteria’. This case report demonstrates improvement of symptoms as well as the reduction of serum cholesterol and triglycerides with individualised homoeopathic treatment.

Functional potential of Aloe vera juice against CCl4 induced hepatotoxicity in animal model

The present study was designed to evaluate functional potential of Aloe vera juice against (CCl4 induced) hepatotoxicity using animal model. Biochemical analyses including liver, renal enzymes, bone biomarkers and lipid profile were conducted after 4 weeks of oral Aloe vera juice administration. Liver enzymes, AST, ALP and total bilirubin were reduced up to 15-7%, 60-32.52% and 29-48%, respectively in Aloe vera juice treated rats i.e., 10 mL/kg and 20 mL/kg doses. Reduction in serum cholesterol (8%), LDL (12%) and triglycerides (15%) were observed. Urea was significantly reduced up to 11% which further reduced up to 30% at higher dose. Increased content of serum proteins (23-50%) and albumin (40-116%) were found at the different doses. Vitamin D was found maximum in G4 i.e., 38.63 mg/dL as compared to lowest i.e., 5.12 mg/dL in G2, similarly improvement in calcium i.e., 11-22% was observed in G3 and G4. The serum oxidative stress markers indicated raised superoxide dismutase (9%), glutathione (15%), catalase (9%) and reduced lipid peroxidation 78% at higher concentration of Aloe vera juice consumption. In addition, histological evaluation also depicted positive impact on hepatic and renal portfolio in all treated rats. All of the findings enlighten the potential of Aloe vera juice as a functional beverage.

Lactiplantibacillus plantarum PGB02 Improved Serum Cholesterol Profile by Tweaking Genes Involved in Cholesterol Homeostasis in Male Swiss Albino Mice.

The effect of Lactiplantibacillus plantarum PGB02 isolated from buttermilk on serum cholesterol profile of normal and hypercholesterolemic mice was evaluated. Further changes in the expression of mice genes were determined. The hypercholesterolemia was induced in experimental mice by feeding high cholesterol and fat diet. Serum cholesterol parameters, physical parameters, cholic acid excretion, and cholesterol metabolism related gene expression analysis was carried out. L. plantarum PGB02 efficiently reduced total cholesterol, triglycerides, and LDL-cholesterol and improved HDL-cholesterol in hypercholesterolaemic mice. Body weight was reduced and fecal cholic acid increased in probiotic treatment groups. Gene expression analysis revealed that L. plantarum PGB02 up-regulated the expression of LDL receptors, CYP7A1, ABCA1, ABCG5, ABCG8, and down-regulated the expression of FXR and NPC1L1 genes. Summarizing the mechanism, L. plantarum PGB02 improved hypercholesterolemia by increasing bile acid synthesis and excretion, reducing exogeneous cholesterol absorption from the intestine, and increased LDL clearance through upregulation of LDL-receptors. The present study has given insight into the mechanism of serum cholesterol reduction by bile salt hydrolase positive L. plantarum PGB02 in mice. L. plantarum PGB02 reduced the serum cholesterol level through increased bile acid synthesis and deconjugation and reduced absorption of cholesterol in the intestine. Isolate PGB02 shown cholesterol removal potential as good as statin.

How statin drugs affect exosomes?

Statins reduce serum cholesterol and isoprenoids by the inhibition of cholesterol synthesis in the mevalonate pathway. Exosomes are extracellular vesicles (30-200 nm) released by all cells that regulate cell-to-cell communication in health and disease by transferring functional proteins, metabolites and nucleic acids to recipient cells. There are many reports that show an effect of statins on exosomes, from their production and release to their content and performance. In this review, we have summarized existing data on the impact of statins on the biosynthesis, secretion, content, uptake and function of exosomes.

AUF-1 knockdown in mice undermines gut microbial butyrate-driven hypocholesterolemia through AUF-1-Dicer-1-mir-122 hierarchy.

Cholesterol homeostasis is a culmination of cellular synthesis, efflux, and catabolism to important physiological entities where short chain fatty acid, butyrate embodied as a key player. This discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance. Hepatic mir-122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of mir-122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model. We synthesized unique self-transfecting GMO (guanidinium-morpholino-oligo) linked PMO (Phosphorodiamidate-Morpholino Oligo)-based antisense cell-penetrating reagent to selectively knock down the key player in butyrate mediated cholesterol regulation. We showed that butyrate treatment caused upregulation of RNA-binding protein, AUF1 resulting in RNase-III nuclease, Dicer1 instability, and significant diminution of mir-122. We proved the importance of AUF1 and sequential downstream players in AUF1-knock-down mice. Injection of GMO-PMO of AUF1 in mouse caused near absence of AUF1 coupled with increased Dicer1 and mir-122, and reduced serum cholesterol regardless of butyrate treatment indicating that butyrate acts through AUF1. The roster of intracellular players was as follows: AUF1-Dicer1-mir-122 for triggering butyrate driven hypocholesterolemia. To our knowledge this is the first report linking AUF-1 with cholesterol biogenesis.

A Comprehensive Study of Gemfibrozil Complexation with β-Cyclodextrins in Aqueous Solution Using Different Analytical Techniques

Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and triglyceride levels. Complexation of GEM with native β-cyclodextrin (β-CD) and with the derivatives hydroxypropyl-β- and randomly methylated β-CD (HPβ-CD and Meβ-CD) was studied in aqueous solution of pH 2.8 and 7.0. The stability constants were determined by spectrofluorimetry, 1H-NMR spectroscopy and solubility assays. Considering the well-known difficulties to obtain similar stability constants by different techniques, the agreement of the values obtained supports the reliability of the results presented. The advantages and drawbacks of each analytical technique for the study of inclusion complexation were discussed as well. In addition, the thermodynamic parameters of complexation, enthalpy (ΔH) and entropy (ΔS), were determined and related to the type of molecular interactions that take place between GEM and the different cyclodextrins. Finally, solid dispersions were prepared by co-evaporation, kneading, vacuum desiccation, and coprecipitation, and complexation was evaluated by X-ray diffraction.

Effects of Different Concentration of Copper on Performance, Immunity and Carcass Traits in Broiler Japanese Quails.

In this study, the effects of dietary copper supplements on broiler Japanese quail growth performance, immune response, blood biochemistry, and carcass quality were examined. Two copper sources (copper sulphate-CuS, and copper methionine-CuM), each at five distinct dietary dosages of 5, 10, 15, 100, and 150mg/kg, were used. A total of 280 (10 × 4 × 7) day-old quail chicks of uniform body weight were randomly distributed into 10 treatments with 4 replicates each and having 7 chicks in each replicate. In comparison to CuS-supplemented diets, CuM-supplemented diets (100mg Cu/kg diet) considerably (P ≤ 0.01) increased body weight gain and improved feed conversion ratio (FCR). In the 150-mg CuM/kg diet, the cell-mediated immune response (foot web index to PHAP) was considerably (P ≤ 0.01) greater. The humoral immune response (HA titre to SRBC) was substantially (P ≤ 0.01) lower with CuS-supplemented meals than with CuM-supplemented diets. When compared to CuS source, the weight of the bursa and spleen from CuM source was considerably (P ≤ 0.01) higher. The 100- and 150-mg CuM/kg diets considerably (P ≤ 0.01) reduced serum cholesterol levels. Thus, it may be concluded that dietary supplementation of copper methionine as a source of Cu @ 100mg Cu/kg diet to broiler Japanese quails was more effective in improving growth performance, immunological response, carcass quality features, and serum cholesterol reduction.

2360. Serum Cholesterol Variability and Mortality in PLWH On Lipid-Lowering Therapy

Abstract Background In people living with HIV (PLWH), consistent use of lipid lowering therapy (LLT) is associated with lower all-cause mortality and use of tenofovir disoproxil fumarate (TDF) with reduced serum cholesterol (C). In the general population, high cholesterol variability (CV) is independently associated with all-cause mortality. We explored the relationship between consistency of LLT/TDF exposure, cholesterol variability, and mortality in PLWH. Methods In a cohort of 15,860 PLWH who achieved undetectable viremia on ART between 2001 and 2011 we used multivariable Cox modeling, stratified by prevalent cardiovascular disease (CVD) to identify predictors of mortality and built multi-level marginal structural models for different LLT/TDF exposure levels based on percentage of days covered (PDC) over the past year, categorizing exposures into low (PDC &amp;lt; 50%), high (50–93%), and consistent (≥94%). The latter two were further subdivided into single and dual exposures for a composite LLT model where we explored effect sizes before and after inclusion of time-updated absolute C values and its 1-year coefficient of variation (CoV). We also examined the relationship between consistency of LLT/TDF use and C variability in a mixed linear model. Results During a median follow-up (f/u) of 4.3 years, there were 2,269 deaths. For 43% of f/u time patients were exposed to TDF, for 13% to non-statin LLT, and for 17% to statins. The hazard ratio (HR) of death for consistent use was 0.38, 95% confidence interval (CI) 0.32–0.45 for TDF, 0.40 (CI:0.28–0.58) for non-statin LLT, and 0.50 (CI:0.40–0.63) for statins (Fig 1). In the composite model, increasing LLT intensity was inversely associated with mortality risk but low C and high CV remained strong independent predictors of death. High HDL C values were protective (Table). The effect sizes for high LLT intensity and high HDL-CV moderately decreased when they were modeled jointly. Compared to unexposed patients, HDL CoV was significantly lower during consistent LLT exposures but higher for patients with low LLT exposure (Fig 2). Conclusion In PLWHA, intensity of LLT exposure is inversely related with all-cause mortality. The highest LLT intensity levels were associated with the lowest HDL-CV. This could serve as a partial explanation for the lower mortality. Disclosures Roger Bedimo, MD, Gilead Sciences: Advisor/Consultant|Janssen: Advisor/Consultant|Merck &amp; Co.: Advisor/Consultant|Merck &amp; Co.: Grant/Research Support|ViiV Healthcare: Advisor/Consultant.

Atorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway

Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin’s protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.