Reduction In Total Cholesterol Research Articles

Strong effects of the ABCA1 agonist CS6253 on Amyloidβ42/40 ratio and lipoproteins in cynomolgus monkeys

AbstractBackgroundATI has discovered a novel molecule, CS6253, for hereditary Apolipoprotein E4 (ApoE4) associated Alzheimer’s disease (AD), which is highly differentiated from other molecules in development by its focus on cholesterol transport. CS6253 is a 26mer peptide optimized for ATP binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, in the brain a rate‐limiting step in cholesterol transport from cells to ApoE. ABCA1 activity, as well as CS6253 in AD mouse models, is associated with improvement in AD pathology.In preparation for human studies, we investigated the effects of the ABCA1 agonist peptide CS6253 on amyloid‐β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans.MethodsCS6253 peptide was injected intravenously to cynomolgus monkeys at various doses in three different studies, 1) a pharmacokinetics (PK) study, 2) a dose‐range finding (DRF) study, and 3) a 30‐day Good Laboratory Practice (GLP) toxicology study. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion‐mobility analysis, and asymmetric flow field flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed‐effects models.ResultsCS6253 intravenous injection, within minutes, induced an increase in small, plasma high‐density lipoprotein (HDL) particles. Plasma TG, ApoE, and Aβ42/40 ratio were transiently increased following CS‐6253 intravenous injection, and a non‐significant decrease in CSF APP and Aβ42 was observed. CS‐6253 in plasma displaced ApoE from HDL to intermediate‐density‐ and low density‐lipoprotein (IDL/LDL) sized particles paralleled by transient reductions in total cholesterol and HDL‐cholesterol. In contrast to plasma, CS6253 had no effect on the assessed CSF apolipoproteins or lipids.ConclusionsIn cynomolgus monkeys administration of the ABCA1 agonist CS6253 transiently increased plasma ApoE and TGs which was paralleled by plasma Aβ42/40 ratio increase, providing a strong rationale for following these markers in ensuing human studies.

Short- and long-term complications after living donor ileal resection

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.

The glycemic, cholesterol, and weight effects of L-carnitine in diabetes: A systematic review and meta-analysis of randomized controlled trials

IntroductionL-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood. MethodsA systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model. ResultsSeventeen studies involving 1622 patients were included. Reductions in FBG (WMD = -0.46 mmol/L, 95% CI = -0.68 to -0.23 mmol/L), HbA1c (WMD = -0.5%, 95% CI = -0.8 to -0.1%), TC (WMD = -0.29 mmol/L, 95% CI = -0.42 to -0.16 mmol/L), and LDL-C (WMD = -0.23 mmol/L, 95% CI = -0.39 to -0.07 mmol/L) were significant. Effects on HDL-C, TG, weight, or BMI were insignificant. Doses between 1001 to 2000 mg showed greatest benefit (p < 0.02 for all). Discussion/ConclusionL-carnitine plays a potential role as adjunctive therapy in diabetes. Additional research is necessary for patients with higher baseline HbA1c and type 1 diabetes.

Supplementation with the Traditional Thai Polyherbal Medicine NawaTab Ameliorates Lipid Profiles in High-Fat Diet-Induced Hyperlipidemic Rats.

A tablet formulation developed from Nawametho decoction (NawaTab), a traditional Thai herbal mixture described in the Worayokasan scripture, has been used clinically for several years in the management of borderline hyperlipidemic individuals. Nevertheless, scientific evidence supporting its claims has never been identified. This study aimed to describe the antihyperlipidemic properties of NawaTab in a well-described model of high-fat diet (HFD)-induced hyperlipidemic rats. Decoction of Nawametho containing equal quantities of Aegle marmelos (L.), Carthamus tinctorius L., Hibiscus sabdariffa Linn., Phyllanthus emblica L., Piper longum L., Piper nigrum L., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz., and Zingiber officinale Roscoe were prepared. The HFD-fed rats were administered NawaTab for 4 consecutive weeks starting from the ninth week of HFD treatment at a dose of 125 mg/kg (p.o.). Anthropometric parameters, serum lipid profiles, lipase activity, and liver and renal functional markers were measured. Histopathological examination of the liver and any steatosis was carried out at the end of this study. Consecutive treatment with NawaTab (125 mg/kg/day) in HFD-induced hyperlipidemic rats caused a significant reduction in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. However, at the tested dose, NawaTab failed to prevent the onset of hepatic steatosis and adipose tissue accumulation. No adverse events due to the consumption of NawaTab on liver and kidney function markers were noted. These findings are the first suggestive evidence for the lipid-lowering capability of NawaTab. However, to promote the use of this formulation in the management of borderline hyperlipidemic patients, elucidation of the underlying mechanisms of action, quantification of biological markers, and clinical trials of NawaTab are urgently needed.

Does Pitavastatin Therapy for Patients with Type 2 Diabetes and Dyslipidemia Affect Serum Adiponectin Levels and Insulin Sensitivity?

(1) Background: We aimed to demonstrate the effects of pitvastatin therapy on the serum levels of total adiponectin and high-molecular-weight (HMW) adiponectin in type 2 diabetes and the correlation with insulin sensitivity. (2) Methods: This study was designed as an open-labelled randomized trial. Patients with diabetes who were prescribed pitavastatin therapy were enrolled and randomized to either treatment with 2 mg of pitavastatin once daily (n = 44) (PITA group) or diet and exercise only, except their antidiabetic medications (n = 49), for 24 weeks. (3) Results: In lipid profiles, the reduction in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was significantly increased in the PITA group (TC; 207.5 ± 20 vs. 195.5 ± 30.0 ng/dL, p &lt; 0.001, LDL-C; 132.0 ± 15.8 vs. 123.1 ± 25.7 mg/dL, p &lt; 0.001). Adiponectin and HMW adiponectin were elevated in the PITA group, compared to the control group without significance. The PITA group showed a lower level of HOMA-IR and HOMA-β levels. However, there was no significance (HOMA-IR; p = 0.5921 -at 12 weeks and p = 0.3645 at 24 weeks; HOMA-β; p = 0.8915 at 12 weeks and p = 0.7313 in 6 months). (4) Conclusions: The present study did not show a significant change in serum adiponectin or HMW adiponectin from baseline in serum adiponectin following pitavastatin therapy. Although statin has been considered as a risk for dysglycemia, pitavastatin did not affect insulin sensitivity.

Washed microbiota transplantation improves patients with metabolic syndrome in South China.

Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.

Effect of a Novel Sugar Blend on Weight and Cardiometabolic Health among Healthy Indian Adults: A Randomized, Open-Label Study.

Obesity is one of the major factors contributing to noncommunicable diseases (NCDs), which is associated with a high intake of a sugar-rich diet. Sugar blend (a novel combination of sugar and stevia) has half the calories of sugar with the same sweetness at recommended use and offers better compliance. A randomized controlled trial was conducted to evaluate the efficacy and safety of this sugar blend in normal to mildly overweight subjects with a body mass index (BMI) of 23-26 kg/m. Sixty subjects were categorized into Group A: Sugar group (n = 30), and Group B: Sugar blend group (n = 30). The primary outcomes evaluated were weight, waist circumference, hip circumference, waist/hip ratio, BMI, and the secondary outcomes evaluated were lipid profile, random blood sugar, and HbA1c. All these parameters were assessed at baseline, 30 days, 60 days, and 90 days. Group B showed a significantly higher weight loss (p = 0.013) at 90 days compared with Group A. A significant reduction in waist circumference (p &lt; 0.0001) by 4.4 cm was noted at 90 days, in addition to reduction in total cholesterol (p &lt; 0.0001), triglyceride (p = 0.006), LDL cholesterol (p = 0.0490), and VLDL cholesterol (p = 0.006) in Group B compared with the baseline. The study revealed that the sugar blend is an effective formulation in reducing weight, anthropometric factors, and other related metabolic parameters. It has been proven to be well tolerated and promotes weight loss when used in conjunction with a daily balanced diet and exercise plan.

Abstract 13054: The Novel Galnac-Conjugated Rnai Trigger Downregulates Apoc3 and Triglyceride Levels in Humanized Liver Mouse Model

Background: Hypertriglyceridemia is a critical risk factor for coronary artery disease. Apolipoprotein C-III (APOC3), produced by liver hepatocytes, regulates triglyceride (TG) levels. We studied effect of novel GalNAc-conjugated APOC3 targeting RNAi trigger (STP125G) on APOC3 and TG levels in humanized liver mouse model. Methods: In dose response study, female uPA-SCID mice (n=4 mice/group), group 1 received PBS control, group 2 received 10mg/kg and group 3 received 30mg/kg STP125G, subcutaneously on day 0. Liver biopsies, plasma and serum samples were collected at week 2. In duration response study, male uPA-SCID mice (n=4 mice/group/timepoint), group 1 received PBS control and group 2 received 10mg/kg STP125G, subcutaneously on day 0. Liver biopsies, plasma and serum samples were collected for each group at weeks 2, 4, 8 and 12. Human APOC3 mRNA (qPCR) and protein (ELISA) levels were measured in liver biopsies and plasma samples, respectively. TGs and total cholesterol (TC) levels were measured in serum samples. Results: In dose response study, animals reported significant suppression of mRNA and reduction of plasma protein levels in 10mg/kg (88% and 91%, respectively) and 30mg/kg (92% and 98%, respectively) dose groups as compared to control group ( p &lt;0.001). Animals also reported significant reductions in TGs and TC levels at 10mg/kg (25% and 33%, respectively) and 30mg/kg (43% and 44%, respectively) dose groups as compared to control group ( p &lt;0.05). In duration response study, treated animals reported significant suppression of mRNA levels at week 2 (83%), week 4 (85%) and week 8 (48%) as compared to control group ( p &lt;0.0001). Treated animals reported significant reduction in plasma protein levels at week 2 (82%; p &lt;0.0001), week 4 (89%; p &lt;0.0001) and week 8 (70%; p =0.0005) as compared to control group. At week 4, treated animals reported significant reduction in TGs (53%; p=0.0079) and TC (36%; p=0.0072). Conclusions: The studies demonstrated that a single administration of STP125G, in a humanized liver mouse model, results in significant suppression of human APOC3 mRNA and plasma protein levels that lasts for up to 8 weeks. It also suggests treatment with STP125G results in lowering of triglycerides and total cholesterol in the treated animals.

Abstract 9558: Twenty Five-Year Trends of Serum Cholesterol Levels and Incidence of Atrial Fibrillation: The Kuakini Honolulu Heart Program

Introduction: Several studies have indicated high cholesterol is paradoxically associated with low prevalence of atrial fibrillation (AF). However, the etiology is uncertain. One potential explanation might be the different trends in serum total cholesterol (TC) between AF and non-AF groups. Hypothesis: There are different 25-year trends in TC levels in older men with vs. without incident AF during the 25-year period. Methods: We used data from the Kuakini Honolulu Heart Program, a longitudinal cohort study since 1965. Participants were 3,741 Japanese-American men living in Hawaii who participated in the 4th exam cycle. TC level was repeatedly measured at baseline (mid-life, ages 45-68 years) and after 25 years (late-life, ages 71-93 years). The amount of TC reduction between mid- and late-life was categorized into quartiles. AF was diagnosed by 12-lead ECG at mid- and late-life. We excluded participants who were diagnosed with AF at mid-life (prevalent cases). Results: AF incidence was 4.4% over 25 years. Mid-life TC levels were similar between those with incident AF vs. those without (218.6±36.0mg/dl vs 218.6±35.4mg/dl, p=0.91). However, in those with incident AF, the drop in TC levels between mid- and late-life was significantly larger than in those without AF (-39.4±35.8mg/dl vs -27.9±38.0mg/dl, p&lt;0.001) (Fig1). Moreover, after multivariable adjustment, there was a biological gradient between AF incidence and reduction of TC levels over 25 years (P for tend p&lt;0.001). As a result, the group with incident AF showed significantly lower late-life TC levels compared with the non-AF group (179.7±32.9mg/dl vs 190.3±33.0mg/dl, p&lt;0.001) at late-life (Fig1). Conclusions: Incident AF over 25 years was associated with a greater decrease in serum TC levels between mid- and late-life. The paradoxical associations between AF prevalence and low TC levels might be explained by the different trends in drop from mid- to late-life TC between those with vs. without incident AF.

Physicochemical properties of dietary fiber of bergamot and its effect on diabetic mice.

Bergamot (Citrus medica L. var. sarcodactylis) contains different bioactive compounds, and their effects remain unclear. Therefore, the structural and bio-function of bergamot dietary fiber were investigated. A sequential extraction procedure was utilized to obtain soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) from bergamot. The main monosaccharide in SDF and IDF is arabinose. SDF had a porous structure, which enhanced the water and oil holding capacity, as well as the cholesterol and glucose adsorption capacity, which was superior to that of IDF. In db/db diabetic mice, SDF and IDF regulated glucose tolerance and controlled blood glucose levels. Reduction of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol in SDF and IDF could be observed. In summary, SDF and IDF from bergamot effectively promoted health in patients with diabetes.

Growth, plasma biochemistry and immune-related gene expression of European sea bass (Dicentrarchus labrax) fed bioactive peptides from farmed salmon by-products

The effect of bioactive peptides (BPs) derived from farmed Atlantic salmon (Salmo salar) by-products on growth, blood biochemistry and immune response was tested in European sea bass (Dicentrarchus labrax). Three diets with different levels of BPs (0% BP0, 5% BP5, 10% BP10) in substitution for fish meal (FM) were administered to triplicate fish groups over 58 days. At the end of the trial, fish were subjected to suboptimal environmental conditions (high water temperature, low oxygen) for 7 days. No significant differences (p > 0.05) were observed in final body weight, specific growth rate, feed intake, and feed conversion while lipid efficiency was higher (p < 0.05) in BP10. At the end of the growth trial, plasma profile remarked previous studies on this species; however cholesterol was higher in BP5 while glucose decreased with increasing BP content. In addition, a reduction in plasma total protein, cholesterol, high-density lipoprotein and triglycerides after environmental stressful conditions was observed only in BP5 supporting a better lipid utilization for energy purposes as a strategy to counteract high energy demand periods. The immune gene analysis showed in BP5 a reduction of the pro-inflammatory interleukin 1β (IL-1β), IL-8, and a significant increase in the expression of the anti-inflammatory interleukin-10; on the contrary, BP10 led to an increase in the expression of IL-1β, and IL-8. In conclusion, data suggest that BPs from salmon by-products have a promising implication as circular and functional ingredients for European sea bass diets. In addition to being a valid alternative ingredient to fishmeal in terms of acceptability and growth, it could enhance physiological mechanisms related to lipid metabolism and immune response.

Knockdown of Bcl-3 alleviates psoriasis and dyslipidemia comorbidity by regulating Akt pathway.

Psoriasis is considered as an inflammatory skin disease accompanied by dyslipidemia comorbidity. B-cell leukemia-3 (Bcl-3) belongs to IκB (inhibitor of nuclear factor kappa B [NF-κB]) family, and regulates inflammatory response through associating with NF-κB. The role of Bcl-3 in psoriasis was investigated in this study. Apolipoprotein E (ApoE)-deficient mice were treated with imiquimod to induce psoriasis and dyslipidemia. Mice were injected intradermally in the back with lentiviral particles encoding Bcl-3 small hairpin RNA (shRNA). Hematoxylin and eosin were used to detect pathological characteristics. The blood lipid levels were determined by automatic biochemical analyzer, and inflammation was assessed by enzyme-linked-immunosorbent serologic assay and real-time quantitative reverse transcription polymerase chain reaction. Bcl-3 was elevated in imiquimod-induced ApoE-deficient mice. Injection with lentiviral particles encoding Bcl-3 shRNA reduced Psoriasis area and severity index (PASI) score in ApoE-deficient psoriatic mice. Knockdown of Bcl-3 also ameliorated imiquimod-induced psoriasiform skin lesions in ApoE-deficient mice. Moreover, loss of Bcl-3 enhanced expression of loricrin, an epidermal barrier protein, reduced expression of proliferating cell nuclear antigen (PCNA) and lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1) in imiquimod-induced ApoE-deficient mice. The enhanced levels of blood lipid in ApoE-deficient mice were attenuated by silencing of Bcl-3 with increase of high-density lipoprotein, and reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Knockdown of Bcl-3 attenuated imiquimod-induced decrease of transforming growth factor beta (TGF-β), and increase of Interleukin (IL)-17A, IL-23, IL-6, and tumor necrosis factor-α (TNF-α) in ApoE-deficient mice. Protein expression of phospho-Akt (p-Akt) and p-GSK3β in ApoE-deficient psoriatic mice was decreased by silencing of Bcl-3. Loss of Bcl-3 exerted anti-inflammatory effect on psoriasis and dyslipidemia comorbidity through inactivation of Akt/GSK3β pathway.

Clove bud (Syzygium aromaticum L.) polyphenol helps to mitigate metabolic syndrome by establishing intracellular redox homeostasis and glucose metabolism: A randomized, double-blinded, active-controlled comparative study

• Influence of Clovinol verses synthetic Glutathione (s-GSH) in metabolic syndrome. • Clovinol enhanced Nrf2 and plasma GSH levels by 6-fold compared to s-GSH. • Clovinol helps balanced intracellular redox homeostasis. • Clovinol modulated glucose and lipid metabolism. • Clovinol may help balanced immunity. Present randomised double-blinded comparative study investigated the influence of clove buds ( Syzygium aromaticum ) polyphenol extract (Clovinol) in comparison with synthetic glutathione (s-GSH) (250 mg/day for 84 days) on healthy adults (N = 70) characterised with metabolic syndrome (MetS). Outcome measures included plasma concentration of endogenous antioxidants, inflammatory markers, blood sugar and lipid metabolism markers, in addition to haematological and biochemical parameters of safety. Clovinol enhanced the plasma concentration of GSH by 6-fold and offered statistically significant enhancement in Nrf2, antioxidant enzymes and in GSH/GSSG ratio. Treatment with Clovinol also improved FBS, PPG, HbA1c, HOMA-IR and insulin levels indicating modulation of insulin resistance. Moreover, Clovinol caused significant reduction in total cholesterol, triglycerides, LDL and increased HDL, while s-GSH showed no significant effect on blood glucose and lipid metabolism. Clovinol did not show any significant side effects or toxic deviations in haematological and biochemical parameters, but significantly increased the total leukocyte and reduced neutrophil/lymphocyte ratio and inflammatory markers (IL-1β and TNF-α).

Wasabi (Eutrema japonicum) Reduces Obesity and Blood Pressure in Diet-Induced Metabolic Syndrome in Rats.

6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) has several biological functions. The present study aimed to evaluate the composition of hydroponically grown Tasmanian wasabi (Eutrema japonicum (Miq.) Koidz.) for 6-MSITC in all plant tissues and investigate the influence of wasabi (rhizome and stem blend) in high-carbohydrate, high-fat (H) diet-fed rats. Male Wistar rats were fed either a corn starch (C) or H diet. After the initial 8 weeks, half of the animals on the C and H diets were given 5% (w/w) wasabi powder in their respective diets for an 8-week duration (CW and HW). The control animals received diets without supplementation throughout the 16-week experiment. Our findings demonstrated that wasabi grown under hydroponic conditions contained 6-MSITC in all parts of the plant such as the stem, leaf and flower, as well as the commonly used rhizome, albeit at lower concentrations. Rats treated with wasabi showed reductions in body weight (H, 460.0 ± 9.5; HW, 416.0 ± 3.6 g), fat mass (H, 178 ± 14; HW, 120 ± 23 g), plasma triglycerides (H, 1.7 ± 0.3; HW, 0.9 ± 0.3 mmol/L) and total cholesterol (H, 1.5 ± 0.1; HW, 1.0 ± 0.04 mmol/L), and the plasma activities of aspartate transaminase. Systolic blood pressure and the area under the curve of blood glucose concentration were decreased by wasabi treatment. Thus, wasabi may be a novel alternative treatment to assist in the management of obesity and related metabolic disorders.

The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Cardiovascular diseases (CVD) are the leading causes of death worldwide. Dyslipidemia is a cardiometabolic risk factor of CVD, yet it can be modifiable. Walnuts have been suggested as a dietary intervention to improve the lipid profile. Therefore, we reviewed the literature to assess the evidence linking walnut intake to the improvement of blood lipids, including total cholesterol (TC), low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein (HDL-C) cholesterol, and triglycerides (TG). PubMed and Embase databases were searched from 2010 up to March 2022. We limited our search to randomized controlled trials conducted on humans and published in English during the specified period. Cochrane's risk of bias tool for interventional studies was used. A random-effects model was used for the meta-analysis, and weighted mean differences were obtained (WMD) Thirteen trials from the U.S., Europe, and Asia were included. Walnut intake was associated with significant reductions in TC (WMD: -8.58 mg/dL), LDL-C (WMD: -5.68 mg/dL), and TG (WMD: -10.94 mg/dL). Walnut consumption was not associated with HDL-C. Subgroup analysis showed that overweight/obese and those with comorbidities had more lipid improvement. A longer trial duration did result in further improvements. However, our results may be prone to bias due to extraneous confounding factors. Additionally, levels of heterogeneity were considerable for some outcomes of interest. Results from this meta-analysis provide evidence for the health benefits of walnuts on blood lipids. Walnuts possibly reduce the risk of CVD; thus, they can be successfully added to a dietary pattern to enhance health benefits.

Cardiovascular Disease Risk in a Cohort of Virologically Suppressed People Living with HIV Switching to Doravirine: Preliminary Data from the Real Life.

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.

Characterization of ultrasonically extracted flaxseed polysaccharide gum and assessing its lipid-lowering potential in a rat model.

Flaxseed polysaccharide gum (FPG) was extracted through the ultrasound-assisted process using water as a solvent with a yield ranging from 8.05 ± 0.32% to 12.23 ± 0.45% by changing different extraction variables. The extracted FPG was analyzed for its functional groups and antioxidant potential. The maximum DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity (≈100%) of FPG was noted at concentrations beyond ≈10mg·ml-1. The maximum inhibition percentage through ABTS (2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid) (72.4% ± 1.9%) was noted at 40 mg·ml-1, which was observed to be less when compared to DPPH at the same concentration. The total antioxidant potential of the FPG solution at a concentration of 10mg·ml-1 was equivalent to 461 mg ascorbic acid, which tends to increase with concentration at a much lower scope. The in vivo trial suggested that the least weight gain was noted in experimental groups G2 and Gh2. A significant reduction in total cholesterol was noticed in G1 (-14.14%) and G2 (-17.72%) and in Gh1 (-22.02%) and Gh2 (-34.68%) after 60 days of the trial compared to the baseline values. The maximum reduction in total triglyceride was observed in Gh2 (-25.06%) and Gh1 (-22.01%) after 60 days of the trial. It was an increasing trend in high-density lipoprotein cholesterol (HDL-c) in different experimental groups G2 (10.51%) than G1 (5.35%) and Gh2 (48.96%) and Gh1 (31.11%), respectively, after 60 days of study interval. Reduction of -5.05% and - 9.45% was observed in G1 and G2, while similar results were observed in Gh1 and Gh2. Conclusively, results suggested a possible protective role of FPG against hyperlipidemia.

Effect of Omega-3 Drug and Virgin Coconut Oil in Histopathological and Molecular Changes in Liver of Experimentally Obese Pregnant Albino Rats

The study aimed to evaluate the role of omega-3 and coconut oil in the histological changes caused by obesity in the liver of pregnant obese female rats and to evaluate the molecular change by estimating the gene expression of the insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein (IGFBP-1) genes. The study used 50 albino female rats aging (90-110) and weighting (185-200gr). The experiment included two stages. First stage was to induce obesity by adding (45% fat) to the standard diet, except for the control group. In the second stage, female rats were left to mate and were divided into 5 groups (10 for each group) as follows: G1 was the Control group that remained on a standard diet, G2 was fed a high-fat diet only, G3 was orally dosed with Omega-3 (260 g/kg), G4 was orally dosed with coconut oil (200 mg/kg), G5 was orally dosed with both Omega 3 and coconut oil with the same doses. Animals were sacrificed on the 18th day of pregnancy. Histological examination of the G2 liver showed severe steatosis in hepatocytes, cellular swelling, and congestion in the central portal vein; lipid profile results showed a reduction in total Cholesterol, triglycerides, and LDL-C in the blood serum of groups treated with both omega3 and Coconut oil. Liver in the group treated with Omega 3 alone or with coconut oil showed the normal histological features of the liver tissue. The liver of the G4 group, treated with coconut oil, showed slight cloudy degeneration of some hepatocytes with individual necrosis of some of the others and congestion in the portal vein. Groups treated with omega-3 and coconut oil separately or together showed an increase in the gene expression of IGF-1 and IGFBP-1.

A nano-enabled biotinylated anti-LDL theranostic system to modulate systemic LDL cholesterol

Cardiovascular diseases (CVDs) remain one of the leading causes of death with an estimated 17.9 million lives lost each year. Circulating high levels of low-density lipoproteins (LDL), are susceptible to various modifications such as oxidation and glycosylation (diabetics). This leads to development of atherosclerosis, which can impair quality of life and death. There is a growing need for detection and subsequent treatment of high LDL cholesterol, which could be achieved through design of a system for detection of LDL with subsequent drug release for disease management. Fenofibrate-loaded solid lipid nanoparticles (SLNs) were synthesized and coated with anti-oxidized LDL antibodies to form anti-LDL SLN. The nanoparticles were delivered via an osmotic pump delivery device implanted on the jugular vein of Large White pigs as an anti-LDL theranostic system, referred to as an Intra-Vascular Implantable Sensor and Drug Delivery Device (IVISDDD), for modulation of systemic LDL cholesterol levels. Modulatory fenofibrate release was observed from the IVISDDD following in vivo analysis in response to anti-LDL SLN-LDL complex uptake and degradation. This notably contributed to a 29.9% reduction in total cholesterol via a 37.4% reduction in LDL levels, and an increase in HDL levels. The observed effect on cholesterol levels indicated that the device could be employed for detection of circulating biomarkers and delivery of lipophilic drugs in CVDs.

Statin therapy in children with familial hypercholesterolemia: a meta-analysis

Abstract Background Familial hypercholesterolemia (FH) is a genetic disorder that may develop serious vascular damage leading to a high risk of the development of premature of cardiovascular disease (CVD). Purpose The aim of this meta-analysis was to evaluate the efficacy of statins on lipid profile in children patients with diagnosed FH. Methods We systematically searched selected electronic databases from inception until 15th March 2022. Main endpoints were lipid profile: total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and apolipoprotein B (Apo-B), lipoprotein(a) (Lp(a)). Random effects mean reduction were used to evaluate the efficacy of statins. Results Eight randomized controlled trial (RCTs) with a total of 1025 children patients with FH (statins n=529) were included in the meta-analysis. At mean follow-up was 10.4 months. We showed that in the group of children treated with statins, compared to control, higher mean TC reduction −1.95 mmol/L (−75 mg/dL) [95% CI, −1.36 to −2.54; p&amp;lt;0.001], TG reduction −0.13 mmol/L (−11.5 mg/dL) [−0.04 to −0.23; p&amp;lt;0.001], and LDL-C reduction −1.94 mmol/L (−75 mg/dL) [−1.43 to −2.45; p&amp;lt;0.001] were observed with significantly higher increase of the mean HDL-C, 0.37 mmol/L (14.3 mg/dL) [0.04 to 0.69; p=0.03] (Figure 1). In addition, the statins significantly reduced Apo-B [−0.50 g/L; p&amp;lt;0.001] and did not significantly affect Lp(a) [0.13 mg/dL; p=0.87] in statins group (Figure 2). Conclusions The results of our meta-analysis clearly showed that children treated with statin therapy had significantly improved lipid profile with lack of effect on Lp(a). This data might help to improve statin therapy in FH children, which is highly underused worldwide. Funding Acknowledgement Type of funding sources: None.