Plasma Low-density Lipoprotein Research Articles

Therapeutic Effects of Statins: Promising drug for Topical and Transdermal Administration.

Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach.

#3006 Therapeutic apheresis in Fabry disease

Abstract Background and Aims Fabry's disease (FD) is a rare lysosomal disorder linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-Gal A). This mutation leads to a defect in the metabolism of glycosphingolipids, causing the progressive accumulation of globotriaacylceramide (GB3) or LysoGB3 in cells, tissues, and organs. In the treatment of FD, we have enzyme replacement therapy (ERT) with Agalsidase-alfa (Replagal®), Agalsidase-beta (Fabrazyme®), and chaperones (Migalastat®). However, there are limitations such as disease progression and morbimortality. Regarding ERT, the development of circulating immunoglobulin G (IgG) antibodies against agalsidase (aGAL) in the long term appears to be associated with a loss of effectiveness. The use of Therapeutic Apheresis (TA), such as plasma exchange therapy (PE) and low-density lipoprotein apheresis (LDL-apheresis), is employed in the treatment of various pathologies due to its ability to eliminate plasma, antibodies, low-density lipoproteins, apolipoproteins, and the adaptability of therapy to the molecule to be removed. The aim was to demonstrate that LDL-apheresis and PE favor Lyso-Gb3 elimination, and PE also eliminates IgG-aGAL as an adjunctive treatment in FD and conducted a proof-of-concept study. Method Two branches of intervention were established, where patients were classified into two groups based on the presence or absence of anti-agalsidase IgG antibodies. If they have the presence of antibodies, they would be eligible for plasma exchanges with two objectives: removing pre-formed antibodies and eliminating Lyso-Gb3. Conversely, in the absence of pre-formed antibodies, LDL-apheresis is performed with the aim of eliminating Lyso-Gb3. The proof-of-concept study was done with two FD patients undergoing ERT were identified, one with IgG-aGAL and the other with very low levels. PE was performed on the first patient, and LDL-apheresis on the second. Lyso-Gb3 levels were titrated in blood before and after LDL-apheresis, and in the washout bag of the column. For antibodies, titration was done in pre and post PE blood and in the extracted plasma from PE. Results After applying TA techniques, we observed that PE reduces IgG-aGAL by 85%, and in the case of LDL-apheresis, there was a 28% reduction in IgG-aGAL. While the ability to eliminate LysoGb3 showed a reduction of 25.5% in PE and 39.7% for LDL-apheresis. To eliminate a potential confounding factor, LysoGb3 determination in albumin was within normal limits. Conclusion With these results, we confirm that PE is more efficient in removing IgG-aGAL but also eliminates LysoGb3, whereas LDL-apheresis is a very effective technique for removing Lyso-Gb3 but also contributes to antibody removal. Based on these findings, we consider TA to be an effective adjunctive tool for FD treatment, even as a standalone treatment. However, these are very preliminary results and should be reproduced with a larger number of patients.

Weight loss, glycolipid profile changes in type 2 diabetes patients after esophagectomy: a propensity score matching analysis

BackgroundType 2 diabetes mellitus (T2DM) is a common co-morbidity in patients who receive esophagectomy and has unfavorable effects on glucose and lipid metabolism in patients. This study examines how weight and glycolipid metabolism change in patients with T2DM following esophagectomy.MethodsThis retrospective, one-center, observational analysis with a propensity score matching analysis (PSM) included 114 patients who underwent esophageal surgery in the Department of Cardiothoracic Surgery, the 900th Hospital of Joint Logistic Support Force from 2017 to 2020, which were separated into T2DM group and Non-T2DM group. Weight, body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured and analyzed before and after the operation.ResultsTwo groups showed similar reductions in weight and BMI after surgery. In the T2DM group, weight decreased from 63.10(10.31) before surgery to 55.10(11.60) kg at 6 months (P < 0.001) with BMI decreasing from 22.67 (2.90) to 19.77 (3.48); While in the Non-T2DM group, weight decreased from 61.42 (8.46) to 53.19 (9.26) kg at 6 months after surgery with BMI decline from 22.49 (2.77) before operation to 19.45 (3.08) at 6 months after surgery. Fasting plasma glucose levels showed a significant decrease (P = 0.035) in the T2DM group at a six-month point of 7.00 (2.21) mmol/L compared to preoperative levels of 7.67 (2.32) mmol/L. HDL levels increased significantly in the Non-T2DM group at six months postoperatively at 1.52 (0.05) with P < 0.001 compared to preoperative levels of 1.22(0.04) mmol/L. TG, LDL, and TC levels decreased significantly in both groups from the preoperative to the 6-month point.ConclusionsEsophagectomy induces weight loss in T2DM and Non-T2DM groups, improves long-term glucose metabolism in the T2DM group, and enhances lipid metabolism in both groups. Further research is needed to understand their mechanisms.

Acoustic Delivery of Plasma Low-Density Lipoprotein into Liver via ApoB100-Targeted Microbubbles Inhibits Atherosclerotic Plaque Growth.

Atherosclerosis is the main risk factor for cardiovascular disease, which accounts for the majority of mortality worldwide. A significantly increased plasma level of low-density lipoprotein cholesterol (LDL-C), surrounded by a monolayer of phospholipids, free cholesterol, and one apolipoprotein B-100 (ApoB-100) in the blood, plays the most significant role in driving the development of atherosclerosis. Commercially available cholesterol-lowering drugs are not sufficient for preventing recurrent cardiovascular events. Developing alternative strategies to decrease the plasma cholesterol levels is desirable. Herein, we develop an approach for reducing LDL-C levels using gas-filled microbubbles (MBs) that were coated with anti-ApoB100 antibodies. These targeted MBApoB100 could selectively capture LDL particles in the bloodstream through forming LDL-MBApoB100 complexes and transport them to the liver for degradation. Further immunofluorescence staining and lipidomic analyses showed that these LDL-MBApoB100 complexes may be taken up by Kupffer cells and delivered to liver cells and bile acids, greatly inhibiting atherosclerotic plaque growth. More importantly, ultrasound irradiation of these LDL-MBApoB100 complexes that accumulated in the liver may induce acoustic cavitation effects, significantly enhancing the delivery of LDL into liver cells and accelerating their degradation. Our study provides a strategy for decreasing LDL-C levels and inhibiting the progression of atherosclerosis.

Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study.

Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships. Through Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables' (IVs) assumptions. Unique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82-0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23-105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52-6.77], p < 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78-20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy. Dyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.

Correction of plasma fat-soluble vitamin levels by blood lipids in elderly patients with coronary heart disease

This study aims to investigate the correlation between plasma fat-soluble vitamin levels and blood lipid in elderly patients with coronary heart disease (CHD). A total of 120 participants were enrolled, including 60 CHD patients and 60 controls without CHD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified plasma levels of vitamins A, D, E, and K. Data analysis was conducted using the statistical analysis system module of MetaboAnalyst 5.0. The CHD group showed significantly higher levels of plasma total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) compared to controls. The CHD group exhibited significantly higher plasma levels of VA and VE, positively correlating with TC, TG, and LDL-C. After adjusted by TG levels, the CHD group had significantly lower plasma levels of VA and VE, negatively correlating with TC, TG, and LDL-C. The CHD group also had significantly lower concentrations of VD3, independent of TG modification, compared to controls. VD3 negatively correlated with TC, TG, and LDL-C. Elderly individuals with CHD display abnormal blood lipid metabolism, and fat-soluble vitamins adjusted by TG levels can more accurately and timely response to implicit fat-soluble vitamins deficiency in CHD patients.

Clustering of health behaviors and their associations with cardiometabolic risk factors among adults at high risk for type 2 diabetes in India: A latent class analysis.

We aimed to identify clusters of health behaviors and study their associations with cardiometabolic risk factors in adults at high risk for type 2 diabetes in India. Baseline data from the Kerala Diabetes Prevention Program (n = 1000; age 30-60 years) were used for this study. Information on physical activity (PA), sedentary behavior, fruit and vegetable intake, sleep, and alcohol and tobacco use was collected using questionnaires. Blood pressure, waist circumference, 2-h plasma glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standardized protocols. Latent class analysis was used to identify clusters of health behaviors, and multilevel mixed-effects linear regression was employed to examine their associations with cardiometabolic risk factors. Two classes were identified, with 87.4% of participants in class 1 and 12.6% in class 2. Participants in both classes had a high probability of not engaging in leisure-time PA (0.80 for class 1; 0.73 for class 2) and consuming <5 servings of fruit and vegetables per day (0.70 for class 1; 0.63 for class 2). However, participants in class 1 had a lower probability of sitting for >=3 h per day (0.26 vs 0.42), tobacco use (0.10 vs 0.75), and alcohol use (0.08 vs 1.00) compared to those in class 2. Class 1 had a significantly lower mean systolic blood pressure (β = -3.70 mm Hg, 95% confidence interval [CI] -7.05, -0.36), diastolic blood pressure (β = -2.45 mm Hg, 95% CI -4.74, -0.16), and triglycerides (β = -0.81 mg/dL, 95% CI -0.75, -0.89). Implementing intervention strategies, tailored to cluster-specific health behaviors, is requiredfor the effective prevention of cardiometabolic disorders among high-risk adults for type 2 diabetes.

Some features of vitamin D content in arterial hypertension in patients with and without osteoarthritis of the knee joints

The aim of the study was to assess the relationship of serum vitamin D concentration with impaired cardiometabolic profile in hypertension in patients with and without osteoarthritis of the knee joints.Materials and methods. The results of the examination of 196 patients aged 54.06±9.4 years with arterial hypertension (AH) were analyzed, who were divided into groups depending on the presence of osteoarthritis of the knee joints (OA KS): 1st–patients with AH (n=153) and 2nd–patients with AH+OA KS (n=43).All patients were assessed for the level of 25 (OH) D, biochemical parameters of blood plasma (total cholesterol, low and high density lipoproteins, triglycerides, creatinine), cardiac morphometry using ECHOCG.Results. The proportion of people with adequate vitamin D levels was 1.2 times higher among patients with AH+OA CS (32.6 % vs. 26.1 %, p0.05). Additional vitamin D supplementation was significantly more common in the group of patients with AH+OA (0 % vs. 44 %, p&lt;0.001).The subgroup with vitamin D deficiency in patients with hypertension without OA CS had the most unfavorable «cardiometabolic» profile (they had significantly high BMI, total cholesterol, and LVH).Conclusions. In people with arterial hypertension (without OA CS), violations of vitamin D levels (deficiency or insufficiency) are associated with an unfavorable «cardio-metabolic» profile – they need additional testing of vitamin D levels in the blood and correction of the detected violations. The presence of pathology of the musculoskeletal system (OA CS) in patients with arterial hypertension, it had no effect on the level of vitamin D and the frequency of its individual disorders. However, in this cohort of patients (AH+OA), the use of vitamin D supplements was significantly more common (0 % vs. 44 %, p&lt;0.001). The assessment of the effect of vitamin D supplementation on cardiometabolic status deserves further investigation. Patients with arterial hypertension and its combination with comorbid pathology have, on average, vitamin D levels classified as insufficiency.

Oral Supplementation of Ozonated Sunflower Oil Augments Plasma Antioxidant and Anti-Inflammatory Abilities with Enhancement of High-Density Lipoproteins Functionality in Rats.

Research on ozonated sunflower oil (OSO) is mostly restricted to its topical application, whereas the functional and toxicological assessment of oral OSO consumption is yet to be solved. Herein, OSO was orally supplemented in rats to assess the impact on plasma antioxidant status, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Also, the functionality of HDL from the OSO-supplemented rats (OSO-HDL) was tested against carboxymethyllysine (CML)- induced hyperinflammation in embryo and adult zebrafish. The results revealed that four weeks of OSO supplementation (3 g/kg BW/day) had no adverse effect on rats' hematological and blood biochemical profiles. Nonetheless, decreased interleukin (IL)-6, and LDL-C levels, along with enhanced ferric ion reduction ability (FRA) and sulfhydryl content, were observed in the plasma of OSO-supplemented rats compared to the control and sunflower oil (SO) supplemented group. In addition, OSO supplementation stabilized apoA-I/HDL and augmented HDL-allied paraoxonase (PON)-1 activity. The microinjection of OSO-HDL (10 nL, 2 mg/mL) efficiently prevented the CML (500 ng)-induced zebrafish embryo mortality and developmental deformities. Similarly, OSO-HDL thwarted CML-posed neurotoxicity and demonstrated a significant hepatoprotective effect against CML-induced fatty liver changes, hepatic inflammation, oxidative stress, and apoptosis, as well as exhibiting a noticeable influence to revert CML-induced dyslipidemia. Conclusively, OSO supplementation demonstrated no toxic effects on rats, ameliorated plasma antioxidant status, and positively influenced HDL stability and functionality, leading to a protective effect against CML-induced toxicity in zebrafish.

Enhancing prime editor flexibility with coiled-coil heterodimers

BackgroundPrime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency.ResultsHerein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target the Pcsk9 gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol.ConclusionsOur innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.

Ldl-stimulated microglial activation exacerbates ischemic white matter damage

The role of microglia in triggering the blood–brain barrier (BBB) impairment and white matter damage after chronic cerebral hypoperfusion is unclear. Here we demonstrated that the vessel-adjacent microglia were specifically activated by the leakage of plasma low-density lipoprotein (LDL), which led to BBB breakdown and ischemic demyelination. Interestingly, we found that LDL stimulation enhanced microglial phagocytosis, causing excessive engulfment of myelin debris and resulting in an overwhelming lipid burden in microglia. Surprisingly, these lipid-laden microglia exhibited a suppressed profile of inflammatory response and compromised pro-regenerative properties. Microglia-specific knockdown of LDLR or systematic medication lowering circulating LDL-C showed protective effects against ischemic demyelination. Overall, our findings demonstrated that LDL-stimulated vessel-adjacent microglia possess a disease-specific molecular signature, characterized by suppressed regenerative properties, which is associated with the propagation of demyelination during ischemic white matter damage.

Leaf extracts of Euclea natalensis A.D.C ameliorate biochemical abnormalities in high-fat-low streptozotocin-induced diabetic rats through modulation of the AMPK-GLUT4 pathway

ABSTRACT Euclea natalensis is a commonly used plant in traditional African medicine for treating several diseases, including diabetes. The objective of the present study was to evaluate the antidiabetic effects of the leaf extracts of Euclea natalensis and elucidate some of its mechanisms of action. High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley rats were orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights, and food and water intake were measured every seven days for 21 days. Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined. The 200 mg/kg bw of methanol extracts significantly reduced fasting plasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity and hepatic glycogen synthesis, decreased hepatic glucose output, and increased the activities of antioxidant enzymes in diabetic animals after 21 days of treatment. The methanol extract also significantly upregulated the relative expression of GLUT 4 protein via the promoted expression of skeletal muscle and hepatic AMPK. Histological investigation showed ameliorated pancreatic degeneration and expedited regeneration of islets of Langerhans in diabetic rats treated with the methanol extract compared with the dichloromethane extract. The findings demonstrated that Euclea natalensis has beneficial effects on the biochemical and cell abnormalities of type 2 diabetes, partly via the modulation of the AMPK – GLUT 4 pathway.

Applications of Strain-Specific Probiotics in the Management of Cardiovascular Diseases: A Systemic Review.

Cardiovascular diseases (CVDs) are a leading cause of global mortality and novel approaches for prevention and management are needed. The human gastrointestinal tract hosts a diverse microbiota that iscrucial in maintaining metabolic homeostasis. The formulation of effective probiotics, alone or in combination, has been under discussion due to their impact on cardiovascular and metabolic diseases. Probiotics have been shown to impact cardiovascular health positively. An imbalance in the presence of Firmicutes and Bacteroidetes has been linked to the progression of CVDs due to their impact on bile acid and cholesterol metabolism. The probiotics primarily help in the reduction of plasma low-density lipoprotein levels and attenuation of the proinflammatory markers. These beneficial microorganisms contribute to lowering cholesterol levels and produce essential short-chain fatty acids. The impact of lipid-regulating probiotic strains on human health is quite significant. However, only a few have been tested for potential beneficial efficacy, and ambiguity exists regarding strain dosages, interactions with confounding factors, and potential adverse effects. Hence, more comprehensive studies and randomized trials are needed to understand the mechanisms of probiotics on CVDs and to ensure human health. This review assesses the evidence and highlights the roles of strain-specific probiotics in the management of CVDs.

Recapitulating familial hypercholesterolemia in a mouse model by knock-in patient-specific LDLR mutation.

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.

Xylooligosaccharide supplementation in rice protein concentrate based diets: A comprehensive analysis of performance and health of Labeo rohita.

The primary aim of this study was to examine the impact of xylooligosaccharide (XOS) in rice protein concentrate (RPC) based diets on the growth performance, body composition, digestive enzymes, intestinal morphology and blood biochemistry of Labeo rohita fingerlings. Four different XOS levels (0%, 0.5%, 1% and 2%) were used at each RPC (75% and 100%) level. Twenty-five fish per tank with an average initial weight of 25 ± 0.05 g were randomly assigned (Randomised complete block design) to each of the 8 groups in triplicate aquaria (36 × 16 × 12″) and then fed with respective diets @ 3% body weight for 90 days. The results showed significant improvements in growth performance, such as increased weight gain %, specific growth rate, and protein efficiency ratio and improved feed conversion ratio in 1% XOS supplemented diet at 75% RPC. A significant decrease in serum alkaline phosphatase activity (ALP) and plasma melanodialdehyde (MDA) were observed at 1% XOS level in 75% RPC based diets, respectively. Meanwhile, the lowest total cholesterol and highest lysozyme activity were observed in 1% XOS supplemented diet at 75% RPC levels. Moreover, the serum (alanine aminotransferase and aspartate transaminase) and plasma (superoxide dismutase, triglyceride, high density and low density lipoprotein) activities showed nonsignificant effects among the treatments. Furthermore, the digestive enzymes (protease & lipase) and intestinal morphology were significantly influenced at 1% XOS in the 75% RPC-based diet. Polynomial regression analysis showed that 1.25% XOS is the optimum requirement for the growth of rohu fingerlings when fed at 75% RPC based diets. Overall, it was concluded that the 75% RPC diet was efficiently replaced by fishmeal along with 1% XOS addition in L. rohita fingerlings without any negative effect on growth performance and intestinal health.

Dextran sulfate bulk and surface-modified microfiltration membrane for simultaneous blood plasma harvesting and low-density lipoprotein removal during plasmapheresis

Plasmapheresis is currently used for the harvesting of blood plasma in medical labs and plasma donation centers. This is a fast, single-step membrane process for both collection of blood plasma and simultaneous blood cell isolation. This paper presents the development of a novel membrane that can be used to simultaneously harvest blood plasma and isolate low-density lipoprotein (LDL), known as bad cholesterol, from the blood. To achieve this goal, dual surface and bulk modification by dextran sulfate (DS) was performed on a polyethersulfone (PES) membrane containing single wall carbon nanotubes (SWCNT). DS is an anionic ligand that repels negatively charged substances like red blood cells (RBCs) and adsorbs positively charged substances like Apo B100; the apoprotein of LDL. Scanning Electron Microscope (SEM), Energy Dispersive X-Ray (EDX), and Fourier Transform Infrared (FTIR) spectroscopy analyses provided evidence of the grafting of DS on single wall carbon nanotubes (DS-SWCNT). Surface studies including water contact angle, zeta potential analysis, surface morphology, Attenuated Total Reflectance-FTIR (ATR-FTIR), and EDX, confirmed the presence of DS on the PES membrane surface. The SEM cross-section results showed the formation of a two-zone morphology with an open structure on the upside and a dense structure on the downside that provide optimal conditions for efficient separation of blood cells. The complete blood count (CBC) and biochemistry analyses revealed dual bulk and surface-modified membrane, and a specific sample (DM2) showed the best performance for blood cells and LDL separation. The maximum separation of blood cells was 87% RBC, 98% white blood cells (WBCs), and 83% platelets (PLTs). Moreover, DM2 exhibited a sieving ratio for LDL of 0.33. Blood compatibility analyses confirmed that DM2 and other related samples had low hemolysis and prolonged coagulation times.

Demographic, biochemical, clinical,and cognitivesymptomdifferences between smokersandnon-smokersin Chineseoldermale patients with chronic schizophrenia.

Several studies have suggested that smoking may impair cognitive function and worsen psychiatric symptoms in people with schizophrenia, but the results have not been consistent. There have been few studies to date that have examined the effects of smoking in older men with chronic schizophrenia. The participants in our study consisted of 167 order Chinese males with chronic schizophrenia and 359 normal control subjects. We split them into smoking and non-smoking groups based on whether or not they smoked. Second, we compared their differences in terms of general demographic characteristics (such as age, education, body mass index, age of illness onset, and course of disease), disease information (such as hypertension, diabetes, and hyperlipidemia), lifestyle factors (such as physical exercise and lunch break), blood biochemical indicators (such as albumin, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting blood glucose), and medication usage (such as clozapine, olanzapine, risperidone, and chlorpromazine). Lastly, a neuropsychologicaltestbattery was used to assess their psychiatric and cognitive symptoms, for example, the Montreal Cognitive Assessment (MoCA) was used to assess their overall cognitive functioning. Their depressive symptoms were assessed by the geriatric depression scale (GDS). Activities of daily living (ADL) were used to assess their ability to lead a daily life, while the positive and negative syndrome scales (PANSS) were used to assess their psychiatric symptoms. Smokers who develop schizophrenia at older ages had a higher body mass index than non-smokers. We also found that plasma albumin, triglycerides, low-density lipoprotein, and fasting blood glucose concentrations were significantly higher in smokers. In contrast, smokers with schizophrenia also had lower PANSS total scores, negative symptom scores, and general psychopathology scores. A forward stepwise binary logistics regression analysis demonstrated a significant association between negative symptom scores and smoking status (B = 0.112, p < 0.001, OR = 1.119, 95% confidence interval: 1.059-1.181). Correlation analysis was carried out and it was found that the amount of cigarette consumption per day had a negative correlation with plasma albumin level(r = -0.290, p = 0.004). However, no such association was found in normal controls. Elderly Chinese men with schizophrenia have a higher percentage of smokers, and although smoking can reduce their plasma albumin levels, it does contribute to the prevention of negative symptoms.

Differences among Lactiplantibacillus plantarum strains isolated from different fermented foods in their potential cholesterol-lowering properties

Elevated levels of plasma low-density lipoprotein (LDL) cholesterol have been associated with incident atherosclerotic cardiovascular disease. Animal studies and clinical trials have demonstrated that several Lactiplantibacillus plantarum strains are effective in reducing plasma LDL cholesterol levels. However, it is unclear whether the habitats from which Lactiplantibacillus plantarum strains are isolated have an impact on their potential cholesterol-lowering properties. In this study, 107 Lactiplantibacillus plantarum strains isolated from three habitats (20 isolated from fermented dairy products, 23 from fermented grape must, and 64 from fermented vegetables) were compared for their potential cholesterol-lowering properties on an origin scale. These properties included acid resistance, bile tolerance, surface hydrophobicity, and bile acid deconjugation. The results showed that the fermented dairy products-derived strains were the most bile-tolerant and hydrophobic, the fermented grape must-derived strains were the most effective at hydrolyzing conjugated bile acids, and the fermented vegetables-derived strains were the most acid-resistant. Bile salt hydrolase (BSH) genes were detected in 97.2% of the total strains and 100% of the fermented dairy products-derived strains by standard PCR with agarose gel electrophoresis detection. In the 104 bsh genes-containing strains, 92.3% had detectable BSH activity (n = 96). These BSH-positive strains exhibited a greater substrate preference for glycine-conjugated bile acids than taurine-conjugated bile acids. Overall, the fermented dairy products-derived strains appeared to have greater cholesterol-lowering potential than those isolated from the other two habitats. This study provided valuable information regarding where to obtain Lactiplantibacillus plantarum strains with greater cholesterol-lowering potential.

Nomogram for predicting the risk of nonalcoholic fatty liver disease in older adults in Qingdao, China: A cross-sectional study.

To explore the risk factors for non-alcoholic fatty liver disease (NAFLD) and to establish a non-invasive tool for the screening of NAFLD in an older adult population. A total of 131,161 participants were included in this cross-sectional study. Participants were randomly divided into training and validation sets (7:3). The least absolute shrinkage and selection operator method was used to screen risk factors. Multivariate logistic regression was employed to develop a nomogram, which was made available online. Receiver operating characteristic curve analysis, calibration plots, and decision curve analysis were used to validate the discrimination, calibration, and clinical practicability of the nomogram. Sex and age subgroup analyses were conducted to further validate the reliability of the model. Nine variables were identified for inclusion in the nomogram (age, sex, waist circumference, body mass index, exercise frequency, systolic blood pressure, fasting plasma glucose, alanine aminotransferase, and low-density lipoprotein cholesterol). The area under the receiver operating characteristic curve values were 0.793 and 0.790 for the training set and the validation set, respectively. The calibration plots and decision curve analyses showed good calibration and clinical utility. Subgroup analyses demonstrated consistent discriminatory ability in different sex and age subgroups. This study established and validated a new nomogram model for evaluating the risk of NAFLD among older adults. The nomogram had good discriminatory performance and is a non-invasive and convenient tool for the screening of NAFLD in older adults.

Research Progress in the Clinical Treatment of Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease with severe disorders of lipid metabolism. It is mainly marked by increasing levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), xanthoma, corneal arch, and early-onset coronary heart disease (CHD). The prevalence of FH is high, and it is dangerous and clinically underdiagnosed. The clinical treatment for FH includes both pharmacological and non-pharmacological treatment, of which non-pharmacological treatment mainly includes therapeutic lifestyle change and dietary therapy, LDL apheresis, liver transplantation and gene therapy. In recent years, many novel drugs have been developed to treat FH more effectively. In addition, the continuous maturity of non-pharmacological treatment techniques has also brought more hope for the treatment of FH. This paper analyzes the pathogenic mechanism and the progress in clinical treatment of FH. Furthermore, it also summarizes the mechanism and structure-activity relationship of FH therapeutic drugs that have been marketed. In a word, this article provides a reference value for the research and development of FH therapeutic drugs.