Search

Beta-glucan (BG), a polysaccharide comprised of interfacing glucose monomers joined via beta-glycosidic linkages, can be defined as a type of dietary fiber with high specificity based on its interaction with the gut microbiota. It can induce similar interindividual microbiota responses, thereby having beneficial effects on the human body. In this paper, we review the four main sources of BG (cereals, fungi, algae, and bacteria) and their differences in structure and content. The interaction of BG with gut microbiota and the resulting health effects have been highlighted, including immune enhancement, regulation of serum cholesterol and insulin levels, alleviation of obesity and improvement of cognitive disorders. Finally, the application of BG in food products and its beneficial effects on the gut microbiota of consumers were discussed. Although some of the mechanisms of action remain unclear, revealing the beneficial functions of BG from the perspective of gut microbiota can help provide theoretical support for the development of diets that target the regulation of microbiota. [ABSTRACT FROM AUTHOR]

Aims: The association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis. Methods and results: Wild type (WT), PCSK9−/−, and LDLR−/− C57BL/6 mice were used in this study. Eleven week-old male mice were fed high-fat diet (HFD) for 12 weeks or kept on normal diet until old age (22-months). Cardiac function was assessed by ultrasound, cholesterol was quantified with a colorimetric kit and circulating EVs were measured using flow cytometry. Plaques were analysed post-mortem using Oil-Red-O staining of the aortic arch. EVs were measured from platelet free blood plasma samples of normal and hypercholesterolaemic clinical patients. Based on annexin V and CD63 staining, we found a significant increase in EV levels in LDLR−/− and PCSK9−/− mice after HFD, but CD81 showed no significant change in either group. There was no significant change in plaque formation after HFD. PCSK9−/− mice show a favourable cardiac function after HFD. Blood cholesterol levels progressively increased during HFD, with LDLR−/− mice showing high levels while PCSK9−/− were significantly lowered compared to WT animals. In mice at old age, similar cholesterol levels were observed as in young mice. In old age, LDLR−/− mice showed significantly increased plaques. At old age, ejection fraction was decreased in all groups of mice, as were CD63+ EVs. Similarly to mice, in patients with hypercholesterolaemia, CD63+ EVs were significantly depleted. Conclusions: This research demonstrates an inverse relationship between circulating EVs and cholesterol, making EVs a potential marker for cardiovascular disease (CVD). HFD causes reduced cardiac function, but atherosclerotic development is slowly progressing in hypercholesterolaemic models and only observed with old animals. These results also bring further evidence for the benefit of using of PCSK9 inhibitors as therapeutic agents in CVD. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored how adding paprika extract to the diet of laying hens affects egg quality and their blood health. We tested two types of hens, Rhode Island Red and Silky Fowl, by giving them either their usual feed or the same feed with paprika extract for 28 days. We stored the eggs at two different temperatures to see how the paprika might influence their quality over time. We found that paprika improved the color of the egg yolks and affected the hens' blood cholesterol levels in different ways depending on the breed. For Silky Fowl hens, more paprika led to higher levels of good cholesterol, while this was not the case for Rhode Island Red hens. Overall, our findings suggest that paprika extract can improve egg quality and influence blood cholesterol, but the effects vary between different breeds of hens. This information could help farmers enhance egg production and nutritional value through dietary adjustments. This study aimed to evaluate the effects of paprika extract supplementation on egg storage and blood biochemical parameters in 63-week-old Rhode Island Red (RIR) and Silky Fowl (SF) hens. The hens were divided into three groups: a control group with a basal diet and two groups receiving the basal diet with paprika extract. The trial lasted 28 days, with egg quality (yolk color and albumen pH) assessed after storing eggs at 25 °C for 21 days. A total of 144 eggs were used in 42 treatments (two breeds, three diets, and seven storage periods) with three eggs examined each (four eggs were used on day 0 and five eggs on day 21). Additionally, the yolk carotenoid content, yolk color, and pH of eggs stored at 4 °C and 25 °C were compared. Results showed that yolk color fan score (YCFS) decreased with storage, and SF had a higher albumen pH than RIR, with both breeds exhibiting an increase in pH over time. HDL cholesterol (HDL-C) levels and the HDL-C to total cholesterol ratio were significantly influenced by breed, diet, and their interaction. The HDL-C level in SF was affected linearly and quadratically by diet, while no such trend was observed in RIR. The study concluded that paprika extract affects egg quality and blood lipid profiles differently in different breeds, highlighting breed-specific responses to dietary supplementation. [ABSTRACT FROM AUTHOR]

Xylooligosaccharides (XOS) are considered a potent source of prebiotics for humans. The global prebiotic market is expanding in size, was valued at USD 6.05 billion in 2021, and is expected to grow at a 14.9% compound annual growth rate between 2022 and 2030, indicating a huge demand. These XOS are non‐digestible pentose sugar oligomers comprising mainly xylose. Xylose is naturally present in the lignocellulosic biomass (LCB), fruits and vegetables. Apart from the prebiotic effect, these XOS have been reported to reduce blood cholesterol, possess antioxidant effects, increase calcium absorption, reduce colon cancer risk, and benefit diabetic patients. The primary use of XOS is reported in the feed industry followed by health, medical use, food and drinks. LCB mainly contains glucan, xylan and lignin. After glucan, xylan is the second‐highest available sugar on the globe composed of xylose. Therefore, the xylan fraction of LCB has great significance in producing food, feed and energy. Glucan has been exploited for the commercial production of ethanol, xylitol, furfural, hydroxymethyl furfural and glucose. As of now, xylan has limited applications. Therefore, xylan can be exploited to convert to XOS. The production of XOS from LCB fraction not only helps to produce these at a very low price, but also helps in the reduction of greenhouse gases. Its use in food and drinks is increasing as it can be derived from the abundantly and cheaply available LCB. The article provides a review on the production, purification and characterization of XOS in view of their use as nutraceuticals. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Clinical laboratories face limitations in implementing advanced quality control (QC) methods with existing systems. This study aimed to develop a web-based application to addresses this gap, and improve QC practices. QC Constellation, a web application built using Python 3.11, integrates various statistical QC modules. These include Levey-Jennings charts with Westgard rules, sigma-metric calculations, exponentially weighted moving average (EWMA) and cumulative sum (CUSUM) charts, and method decision charts. Additionally, it offers a risk-based QC section and a patient-based QC module aligning with modern QC practices. The codes and the web application links for QC Constellation were shared at https://github.com/hikmetc/QC%5fConstellation, and http://qcconstellation.com, respectively. Using synthetic data, QC Constellation demonstrated effective implementation of Levey-Jennings charts with user-friendly features like checkboxes for Westgard rules and customizable moving averages graphs. Sigma-metric calculations for hypothetical performance values of serum total cholesterol were successfully performed using allowable total error and maximum allowable measurement uncertainty goals, and displayed on method decision charts. The utility of the risk-based QC module was exemplified by assessing QC plans for serum total cholesterol, showcasing the application's capability in calculating risk-based QC parameters including maximum unreliable final patient results, risk management index, and maximum run size and offering risk-based QC recommendations. Similarly, the patient-based QC and optimization modules were demonstrated using simulated sodium results. In conclusion, QC Constellation emerges as a pivotal tool for laboratory professionals, streamlining the management of quality control and analytical performance monitoring, while enhancing patient safety through optimized QC processes. [ABSTRACT FROM AUTHOR]

. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here, we present 1-year efficacy and safety data of the SOLAR study. Objectives:. To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. Materials and methods. : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). Results. : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. Conclusions. : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objectives of this observational cohort study were to evaluate the associations of rumination time (RT) in the last week of pregnancy with transition cow metabolism, inflammation, health, and subsequent milk production, reproduction, and culling. Pregnant nulliparous (n = 199) and parous (n = 337) cows were enrolled 21 d before expected calving. Rumination time and physical activity were monitored automatically by sensors from d −21 to 15 relative to calving. Blood samples were collected on d −14, −5, 4, 8, and 12 ± 1 relative to calving. Diagnoses of clinical health problems were performed by researchers from calving to 15 DIM. In classification 1, cows were ranked based on average daily RT in the last week of pregnancy and classified into terciles as short RT (SRT), moderate RT (MRT), or long RT (LRT) for association analyses. In classification 2, RT deviation from the parity average was used in a receiver operating characteristic curve to identify the best threshold to predict postpartum clinical disease. Cows were then classified as above the threshold (AT) or below the threshold (BT). Compared with cows with LRT, cows with SRT had greater serum concentrations of nonesterified fatty acids (0.47 vs. 0.40 ± 0.01 mmol/L), BHB (0.58 vs. 0.52 ± 0.01 mmol/L), and haptoglobin (0.22 vs. 0.18 ± 0.008 g/L) throughout the transition period, and reduced concentrations of glucose, cholesterol, albumin, and magnesium in a time-dependent manner. Parous cows with SRT had higher odds of postpartum clinical disease (adjusted odds ratio [AOR] = 3.7; 95% CI: 2.1–6.4), lower odds of pregnancy by 210 DIM (AOR = 0.34; 95% CI = 0.15–0.75), and lower milk production (46.9 vs. 48.6 ± 0.5 kg/d) than parous cows with LRT. Deviation in prepartum RT had good predictive value for clinical disease in parous cows (area under the curve = 0.65; 95% CI = 0.60–0.71) but not in nulliparous (area under the curve = 0.51; 95% CI = 0.42–0.59). Separation of parous cows according to the identified threshold (≤−53 min from the parity average) resulted in differences in serum concentrations of nonesterified fatty acids (AT = 0.31 ± 0.006, BT = 0.38 ± 0.014 mmol/L), BHB (AT = 0.49 ± 0.008, BT = 0.53 ± 0.015 mmol/L), and globulin (AT = 32.3 ± 0.3, BT = 34.8 ± 0.5 g/L) throughout the transition period, as well as in serum cholesterol, urea, magnesium, albumin, and haptoglobin in a time-dependent manner. Below threshold parous cows had higher odds of clinical disease (AOR = 3.7; 95% CI = 2.1–6.4), reduced hazard of pregnancy (adjusted hazard ratio = 0.64, 95% CI: 0.47–0.89), greater hazard of culling (adjusted hazard ratio = 2.1, 95% CI: 1.2–3.6), and lower milk production (46.3 ± 0.7 vs. 48.5 ± 0.3 kg/d). External validation using data from 153 parous cows from a different herd and the established threshold in RT deviation (≤−53 min) resulted in similar predictive value, with the odds of postpartum disease 2.4 times greater in BT than AT (37.5% vs. 20.1%). In conclusion, RT in the week preceding calving was a reasonable predictor of postpartum health and future milk production, reproduction, and culling in parous cows but not in nulliparous cows. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease (PD) involves the progressive loss of dopaminergic neurons and the accumulation of α-synuclein. Elevated cholesterol levels may exacerbate α-synuclein aggregation, potentially contributing to PD. This study investigates the link between lipid profiles and PD severity, as well as cognitive functions in patients, aiming to inform pathogenesis and management strategies. Methods: Data from 250 PD patients and 100 healthy controls were analyzed. Serum cholesterol levels were compared with disease severity using Unified Parkinson's Disease Rating Scale (UPDRS) and modified Hoehn & Yahr Rating Scale (mH&Y). Mini-Mental State Examination (MMSE) assessed cognitive functions. Results: Of the participants, 45.4% were female, 54.6% male, with a mean age of 69.09 ± 11.13 years. Mean UPDRS score was 52.34 ± 26.32, mH&Y was 2.28 ± 0.91. Patients had significantly higher HDL levels (47.92 ± 11.63) than controls (45.40 ± 13.89) (p = 0.024). HDL levels were significantly higher in patients with cognitive impairment than in patients with cognitive normal (p = 0.004). On the contrary, triglyceride levels were significantly lower in those with cognitive impairment compared to those with cognitively normal (p = 0.005). Multivariate logistic regression showed being male associated with 3.796 times higher risk of illness, and HDL is associated with 1.030 times increased illness risk. Conclusion: High HDL levels and male gender particularly increase the risk of Parkinson's disease. Additionally, HDL and triglyceride levels affect the cognition of PD patients. Further studies on the impact of cholesterol metabolism on the pathogenesis of PD could contribute to identifying effective treatment targets. [ABSTRACT FROM AUTHOR]

High levels of fats like triglycerides and cholesterol in the blood can cause cardiovascular diseases, prompting the search for safer, natural treatments. This study investigates the efficacy of Ruta chalepensis ethanol extract in lowering cholesterol levels using a rat model of hyperlipidemia induced by Triton WR-1339. Leaves and flowers of R. chalepensis were extracted with ethanol, and LC-MS analysis revealed high levels of quercetin (9.5%), 2,2-Dimethyl-3-methylidenebicyclo [2.2.1] heptane (8.1%), and other compounds, with monoterpenes being the most common class. Male Wistar rats received doses of the extract at 20 and 40 mg/kg, while fenofibrate (100 mg/kg) was the positive control. After 20 h, plasma lipid levels were significantly affected, showing a 72.1% reduction in total cholesterol for the 40 mg/kg group (p < 0.01) and a 67.6% reduction for the 20 mg/kg group (p < 0.01). High-density lipoprotein cholesterol levels decreased by 68.8% in the 40 mg/kg group (p < 0.01) and 58.6% in the 20 mg/kg group (p < 0.01). Low-density lipoprotein cholesterol saw reductions of 67.3% (p < 0.001) in the 40 mg/kg group and 60.4% (p < 0.01) in the 20 mg/kg group. Triglycerides dropped by 90.6% in the 40 mg/kg group (p < 0.001) and 86.7% in the 20 mg/kg group (p < 0.001). Overall, the results highlighted a stronger anti-hyperlipidemic effect in the 40 mg/kg group across all lipid parameters measured. The extract outperformed fenofibrate, particularly at the higher dose. These results imply that R. chalepensis extract is a promising natural alternative for managing hyperlipidemia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of giant salamander protein peptide (CGS) and its Maillard reaction product (CGSXyU) on lowering blood glucose and lipid levels in type II diabetic mice and enhancing immunomodulatory functions in immunosuppressed mice, and anti-fatigue effects in normal mice. Methods: Mice were randomly assigned to a blank control group, a model control group, a positive control group (200 mg/kg metformin), a low-dose sample group (CGS/CGSXyU-L, 50 mg/kg), and a high-dose sample group (CGS/CGSXyU-H, 200 mg/kg). Following the successful induction of diabetes with 100 mg/kg alloxan, the mice underwent gavage treatment for 3 weeks, after which their fasting blood glucose levels, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Mice were randomly assigned to a blank control group, a model control group, a positive control group (50 mg/kg levamisole), a low-dose sample group (CGS/CGSXyU-L, 50 mg/kg), and a high-dose sample group (CGS/CGSXyU-H, 200 mg/kg). Following successful modeling with 100 mg/kg cyclophosphamide, the mice underwent gavage for three weeks, during which their body weights were recorded, and changes in organ indices and cytokine levels were assessed. Similarly, mice were randomly divided into a blank control group, a positive control group (200 mg/kg taurine), a low-dose sample group (CGS/CGSXyU-L, 50 mg/kg), and a highdose sample group (CGS/CGSXyU-H, 200 mg/kg). They were subjected to gavage for four weeks, after which the mice's weight-bearing swimming time, urea nitrogen levels, creatine kinase activity, serum lactate levels, and antioxidant enzyme activity were measured. Results: The CGS/CGSXyU-L/H treated group of mice exhibited reduced fasting blood glucose concentration, serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), along with elevated high-density lipoprotein cholesterol (HDL-C) levels. CGSXyU-H significantly enhanced the body weight (P<0.05), organ index, and levels of immune cytokines (IL-6, IL-10, TNF-α, IFN-γ) in immunocompromised mice. The CGS/CGSXyU-L/H treatment group demonstrated increased time in weight-bearing swimming, reduced creatine kinase activity and serum lactate levels, the BUN level in the CGS-H and CGSXyU-L/H groups decreased, while the GSH-Px activity significantly increased in the CGSXyU-H group (P<0.05), the SOD activity in the CGS-H and CGSXyU-L/H groups also increased. Conclusion: The protein peptides from Andrias davidianus and their Maillard reaction products regulate blood glucose and lipid metabolism in type II diabetes mice, bolster immune function in immunocompromised mice, and effectively improve the anti-fatigue capacity in normal mice. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis is a widely prevalent cause of pain and disability among older adults. It is an incurable condition, and most treatments are aimed at alleviating symptoms. Aim: This study aimed to investigate the impact of statins on osteoarthritis by using a two-sample Mendelian randomization approach, using genetic variants associated with statin use as instrumental variables. Method: Information on single nucleotide polymorphisms associated with statin medication was obtained from the FinnGen study, and data on osteoarthritis were sourced from the UK Biobank. The inverse variance weighted method was used as the primary analytical approach for the Mendelian randomization analysis. Sensitivity analyses were conducted to evaluate horizontal pleiotropy and heterogeneity. To examine the genetic relationship between statins and osteoarthritis, linkage disequilibrium score regression-based estimates were used. Results: Mendelian randomization analysis indicated a positive effect of statin use on the treatment of osteoarthritis (odds ratio 0.951, 95% confidence interval 0.914–0.99, p < 0.05). This conclusion was supported by various Mendelian randomization methods. Sensitivity analyses revealed no significant directional pleiotropy or influential single nucleotide polymorphisms that could compromise the overall causal inference. Linkage disequilibrium score regression-based estimates suggested a modest genetic correlation between statin use and osteoarthritis (Rg = 0.098, Se = 0.034, p < 0.05), thus reinforcing the robustness of the Mendelian randomization analysis. Conclusion: Statins reduce the risk of osteoarthritis, aligning with the results of observational studies. Further research is essential to validate these results and explore the underlying mechanisms in detail. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG. Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is the serious side effect of doxorubicin treatment. Ceramides are formed from the degradation of sphingolipids in cell membranes and play an important role in signaling and modulating biological processes. There is evidence that omega‐3 fatty acid administration can act on this pathway. To evaluate the role of the ceramide pathway in the pathophysiology of doxorubicin‐induced cardiotoxicity and the effect of omega‐3 fatty acid supplementation in the attenuation of chronic doxorubicin‐induced cardiotoxicity in rats. Sixty male Wistar rats were divided into four groups: Control (C), Doxorubicin (D), Omega‐3 fatty acids (W), and Doxorubicin + Omega‐3 fatty acids (DW). The groups received omega‐3 fatty acids (400 mg/kg/day, via gavage) or water for 6 weeks and doxorubicin (3.5 mg/kg, intraperitoneal) or saline once a week for 4 weeks. Doxorubicin‐treated animals showed increases in left atrium and left ventricle diameters, serum triglycerides and cholesterol, malondialdehyde, and protein carbonylation. We also observed a decrease in left ventricular shortening fraction and nSMase1 expression in the heart. Omega‐3 fatty acid supplementation attenuated the structural and functional alterations caused by doxorubicin and decreased protein carbonylation. In contrast to doxorubicin, omega‐3 fatty acids increased neutral nSMase activity in animals that both received and did not receive doxorubicin but with no effect on nSMase1 protein expression. Omega‐3 fatty acid supplementation attenuated the cardiotoxicity caused by doxorubicin. The ceramide pathway may be involved in the pathophysiology of cardiotoxicity, but it is not the mechanism by which omega‐3 fatty acids attenuated cardiac dysfunction. [ABSTRACT FROM AUTHOR]

The antiobesity effects of catechin functional kimchi (CFK) were studied in C57BL/6 mice with high-fat diet (HFD)-induced obesity. We prepared four types of kimchi: commercial kimchi (CK), standard kimchi (SK), green tea functional kimchi (GFK), and CFK. CFK decreased the adipo-/lipogenesis-related genes of CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPARγ), and sterol regulatory element-binding protein-1 (SREBP-1) in the liver and epididymal tissues (p < 0.05). On the other hand, CFK showed the highest lipolysis-related gene expression of hormone-sensitive lipase (HSL) and β-oxidation related gene expression of carnitine palmitoyltransferase 1 (CPT-1). CFK produced the lowest inflammation-related mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) among all groups in the epididymal tissues (p < 0.05). In addition, UPLC–Q-TOF-MS showed that CFK is composed mainly of 39 active compounds, e.g., epigallocatechin gallate (EGCG), catechins, apigenin, myricetin, kaempferitin, rutin, quercetin, and other substances with anti-inflammatory, blood cholesterol reduction, blood sugar reduction, body fat reduction, antioxidant, and anticancer functions. Thus, CFK exhibited an antiobesity effect through its modulation of lipid metabolism and active compounds. [ABSTRACT FROM AUTHOR]

The RNA‐guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12b system represents the third family of CRISPR‐Cas systems that are harnessed for genome editing. However, only a few nucleases have demonstrated activity in human cells, and their in vivo therapeutic potential remains uncertain. In this study, a green fluorescent protein (GFP)‐activation assay is conducted to screen a panel of 15 Cas12b orthologs, and four of them exhibited editing activity in mammalian cells. Particularly noteworthy is the NiCas12b derived from Nitrospira sp., which recognizes a "TTN" protospacer adjacent motif (PAM) and facilitates efficient genome editing in various cell lines. Importantly, NiCas12b also exhibits a high degree of specificity, rendering it suitable for therapeutic applications. As proof of concept, the adeno‐associated virus (AAV) is employed to introduce NiCas12b to target the cholesterol regulatory gene proprotein convertase subtilisin/ kexin type 9 (Pcsk9) in the mouse liver. After 4 weeks of injections, an impressive is observed over 16.0% insertion/deletion (indel) efficiency, resulting in a significant reduction in serum cholesterol levels. NiCas12b provides a novel option for both basic research and clinical applications. [ABSTRACT FROM AUTHOR]

Serum triglyceride concentrations increase in dogs with obesity, which is typically assessed by body condition score (BCS), however little is known about changes that take place in non-obese dogs in overweight condition. Further, the associations of triglyceride levels with other markers of energy homeostasis are poorly characterised in healthy animals. The present study aimed to evaluate associations between both BCS and triglyceride concentrations with other markers of lipid and glucose metabolism in healthy, non-obese dogs, as well as to assess whether these markers change significantly in non-obese dogs with overweight as compared to their lean counterparts. Serum concentrations of cholesterol, free fatty acids, triglycerides, insulin, glucose and fructosamine were measured in 532 healthy, client-owned dogs, assigned either to 'lean' (BCS: 3-5) or 'overweight' (BCS: 6-7) categories. Generalised linear mixed models were used to assess associations between BCS categories, triglyceride concentrations and other variables, correcting for the effect of breed. Compared with lean dogs, overweight dogs had a greater serum cholesterol concentration (95% CI, 5.3-6.2 mmol/L or 205-237 mg/dL versus 5.1-5.4 mmol/L or 198-210 mg/dL, p = 0.0032), insulin concentration (95% CI, 17.5-22.1 µU/ml versus 16.7-18.0 µU/ml, p = 0.0374) and were older (95% CI, 4.0-5.3 versus 3.4-3.7 years, p = 0.0005). Triglyceride concentrations were positively associated with fructosamine (r2 = 0.31, p = 0.0012), cholesterol (r2 = 0.25, p < 0.0001), insulin (r2 = 0.14, p = 0.0030) and glucose (r2 = 0.10, p = 0.0014) concentrations, and negatively associated with free fatty acid concentrations (r2 = 0.11, p < 0.0001). However, there was no association between triglyceride concentrations and age. In conclusion, both BCS and triglyceride concentrations were associated with other markers of glucose and lipid metabolism in non-obese healthy dogs, amongst which those with overweight showed metabolic changes as compared to their lean counterparts. Triglyceride concentrations were associated with an increase in insulin and fructosamine concentrations that might reflect an earlyphase impairment in glucose tolerance which, surprisingly, was concurrent with lower basal free fatty acid concentrations. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To identify the associations between gestational cholesterol levels and the risk of postpartum hypercholesterolemia, and to establish trimester‐specific reference values.Serum lipids at gestational weeks 6–8, 16, 24, and 36, and 42 days postpartum were derived from 905 pregnant women of a prospective cohort. The major outcome was postpartum hypercholesterolemia. Logistic regression and restricted cubic splines were conducted to estimate the associations between cholesterol levels at specific gestational ages and postpartum hypercholesterolemia. Associations of the trend of changes in cholesterol levels during pregnancy with postpartum hypercholesterolemia were evaluated by linear mixed‐effect model and linear or logistic regression. Reference values were computed by the receiver operating characteristic curves.Serum concentrations of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and the ratios of TC/HDL‐C and LDL‐C/HDL‐C all increased during pregnancy and decreased at 42 days postpartum. The elevated levels of TC and LDL‐C, decreased levels of HDL‐C in pregnancy, and their rapid change rates were positively associated with higher risks of postpartum hypercholesterolemia. The established reference values from the first to the third trimester were below 5.47, 6.35, and 7.22 mmol/L for TC; below 2.83, 3.82, and 4.21 mmol/L for LDL‐C; and more than 1.50, 1.55, and 1.50 mmol/L for HDL‐C, respectively.Maternal cholesterol levels and their trend of change during pregnancy were predictors of postpartum hypercholesterolemia. Trimester‐specific reference values were established in a Chinese population. [ABSTRACT FROM AUTHOR]

ABSTRACT Turmeric improves performance in nonruminants, but results in laying hens are not consistent. This meta‐analysis assessed the performance of laying hens fed turmeric powder (TP)–based diets. Nineteen studies retrieved from Google Scholar, Scopus, ScienceDirect, PubMed, and Web of Science databases were used for the meta‐analysis. The outcome variables analysed were productive indices (feed intake [FI], feed conversion ratio [FCR], hen day production [HDP], egg weight [EW], egg mass [EM]), egg quality (Haugh unit [HU], shell thickness [SHT], shell strength [SHS], yolk cholesterol [YC]), serum biochemical parameters (serum cholesterol [SC], alanine transferase [ALT], and aspartate transferase [AST]), and moderator variables (layer strains, inclusion level, feeding duration, and hen's age). All analyses were performed on OpenMEE software and the R package. A random‐effects model (REM) was used and results were presented as standardised mean difference (SMD) at a 95% confidence interval (CI). The results showed that dietary TP improved FCR (SMD = −0.31; 95% CI: −0.61, −0.01; p = 0.046) and HDP (SMD = 0.49; 95% CI: 0.29, 0.69; p < 0.001), but not EW, EM, HU, SHT, SHS, YC, and serum AST in layers. On the other hand, dietary TP decreased FI (SMD = −0.15; 95% CI: −0.26, −0.05; p = 0.004), SC (SMD = −75.18; 95% CI: −102.55, −47.80; p < 0.001), and ALT (SMD = −3.55; 95% CI: −4.71, −2.40; p < 0.001) in laying hens with proof of significant heterogeneity. However, meta‐regression showed that layer strains and feeding duration accounted for most of the sources of heterogeneity. In conclusion, results suggest that dietary TP increased HDP and reduced FI, FCR, SC, and ALT in laying hens. [ABSTRACT FROM AUTHOR]

Background: The present experiment aimed to evaluate the effects of commercially processed former foodstuffs (cFF) as dietary substitutes of corn, soybean meal and soybean oil on the growth performance, apparent total tract digestibility (ATTD), hematobiochemical profiles, and liver gene abundance in broiler chickens. Two hundred one-day-old male ROSS-308 chicks were assigned to 4 dietary groups (5 replicates of ten birds per replicate) according to their average body weight (BW, 38.0 ± 0.11 g). All groups received a two-phase feeding program: starter, d 1–12 and grower, d 12–33. The control group (cFF0) was fed a standard commercial feed based on corn, soybean meal and soybean oil. The other three groups received diets in which the feed based on corn, soybean meal, and soybean oil was partially replaced with cFF at a substitution level of 6.25% (cFF6.25), 12.5% (cFF12.5) or 25% (cFF25) for the following 33 d. Results: The growth performance data showed no differences in BW or average daily gain among groups, although the average daily feed intake decreased during the grower period (12–33 d) and over entire experimental period (1–33 d) in a linear manner as the cFF inclusion level rose (P = 0.026), positively affecting the gain to feed ratio (P = 0.001). The ATTD of dry matter of the cFF-fed groups were greater with respect to control group and increased throughout the experimental period, whereas the ATTD of ether extract linearly decreased with increasing levels of cFF-fed groups compared with control group and throughout the experimental period (P < 0.05). Additionally, a linear increase in the heterophil to lymphocyte ratio, serum cholesterol, triglycerides and alanine-aminotransferase were observed with increasing dietary levels of cFF (P < 0.05); however, no differences were observed in lipoprotein lipase or sterol regulatory element binding transcription factor gene abundance. Conclusions: The results of this experiment demonstrate that it is possible to incorporate cFF into nutritionally balanced diets for broiler chickens, even up to 25% substitution levels, for up to 33 d without adversely impacting the overall growth performance of male broiler chickens raised under commercial conditions. Further studies are essential to validate the hematological trait findings. [ABSTRACT FROM AUTHOR]

Background: There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson's disease (PD). This study aimed to determine whether MetS increases PD risk. Methods: To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. Results: Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16–1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07–1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02–1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15–1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11–1.26; p = 0.001). Conclusion: MetS can contribute to the incidence of Parkinson's disease, with individual components of MetS demonstrating comparable effects. [ABSTRACT FROM AUTHOR]

Background: The pathogenic causes of primary gout include urate overproduction and/or renal or extra-renal urate underexcretion. The aim of this study was to evaluate the association of gout subtypes with the response to low-purine diet (LPD). Methods: This is a single-center prospective clinical study. Gout patients visiting from 2019 to 2022, from Shandong Gout Clinic Center at the Affiliated Hospital of Qingdao University, China, assigned to three groups according to clinical subtypes, were enrolled and all treated with 2-week low-purine diet. General characteristics, serum uric acid (sUA) and other clinical biochemical variables before and after the diet were evaluated. Results: A total of 626 gout patients (age 41.20 ± 13.41 years, male 98.0%) were included. Of these, 69 (11.0%) were overproduction type, 428 (68.37%) were underexcretion type, and 129 (20.61%) were combined type. Overall, there was a substantial decrease in sUA after a 2-week LPD (p < 0.001). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum triglycerides (TG), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower than those at baseline (p < 0.05). On the other hand, there were significant differences in the reduction of sUA among different types, the rank order being overproduction type (− 88.81 ± 63.01 μmol/L) > combined type (− 65.22 ± 44.13 μmol/L) > underexcretion type (− 57.32 ± 61.19 μmol/L). After adjusting for age, BMI and baseline sUA and eGFR, there were still significant differences in the decline of serum uric acid among different types. Higher baseline sUA (95%CI − 0.285, − 0.191; p < 0.001) and BUN (95%CI − 6.751, − 0.602; p < 0.001) were correlated with greater decrease of sUA. Conclusions: Our findings support the protective role of low-purine diet on sUA levels in gout patients, especially overproduction type. Furthermore, LPD could exert a beneficial effect on gout patients' blood pressure, BMI, blood lipid, BUN and Scr levels. Trial registration Registered with ChiCTR, No. ChiCTR1900022981 at 06/05/2019. [ABSTRACT FROM AUTHOR]

Background: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs. [ABSTRACT FROM AUTHOR]

Background: Podocyte injury is a common pathologic mechanism in diabetic kidney disease (DKD) and obesity-related glomerulopathy (ORG). Our previous study confirmed that Inonotus obliquus (IO) improved podocyte injury on DKD rats. The current study explored the pharmacological effects, related mechanisms and possible active components of IO on ORG mice. Methods: Firstly, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis (UPLC-Q-TOF-MS) with network pharmacology to construct the human protein-protein interaction mechanism and enrich the pathway, which led to discover the crucial mechanism of IO against ORG. Then, ORG mice were established by high-fat diet and biochemical assays, histopathology, and Western blot were used to explore the effects of IO on obesity and podocyte injury. Finally, network pharmacology-based findings were confirmed by immunohistochemistry. The compositions of IO absorbed in mice plasma were analyzed by UPLC-Q-TOF-MS and molecular docking was used to predict the possible active compounds. Results: The network pharmacology result suggested that IO alleviated the inflammatory response of ORG by modulating TNF signal. The 20-week in vivo experiment confirmed that IO improved glomerular hypertrophy, podocyte injury under electron microscopy, renal nephrin, synaptopodin, TNF-α and IL-6 expressions with Western blotting and immunohistochemical staining. Other indicators of ORG such as body weight, kidney weight, serum total cholesterol, liver triglyceride also improved by IO intervention. The components analysis showed that triterpenoids, including inoterpene F and trametenolic acid, might be the pharmacodynamic basis. Conclusion: The research based on UPLC-Q-TOF-MS analysis, network pharmacology and in vivo experiment suggested that the amelioration of IO on podocyte injury in ORG mice via its modulation on TNF signal. Triterpenoids were predicated as acting components. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) affects up to 10% of adults globally, and its complications can mask the risk of gastrointestinal bleeding or malignancy. Methods: Our study enrolled 633 endoscopic patients stratified according to T2DM presence (4:1 ratio in favor of the control group). Results: T2DM patients referred for endoscopy experienced lower prevalence of epigastric pain and heartburn (OR = 0.637/OR = 0.346, p < 0.05). Often being anemic (OR = 2.23, p < 0.001), they had significantly lower hemoglobin (p = 0.001) and serum iron (p = 0.02), but serum cholesterol was higher in non-diabetics. Ulcers, erosions and mucosal hemorrhages were comparable between groups (p < 0.05), although low-dose aspirin use was more prevalent in diabetics (p = 0.000, OR = 2.34). T2DM was associated with the increased frequency of antro-corporal active gastritis (OR = 1.451/OR 1.501), with smokers presenting a higher frequency of active H. pylori infection (OR = 3.37). T2DM predicted anemia (adjusted OR = 1.70) and the absence of gastroesophageal reflux symptoms (adjusted OR = 0.37), but not active H. pylori gastritis or premalignant lesions. Conclusion: In an endoscopic population, patients with T2DM had lower hemoglobin and serum iron levels. There was an inverse correlation between T2DM and heartburn. H. pylori gastritis and premalignant lesions occurred more frequently in diabetic patients (predominantly pangastritis) before adjusting for age or associated comorbidities, with smoking increasing the risk for active infection. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is an independent risk factor for cardiovascular disease and lowering circulating levels of low-density lipoprotein cholesterol (LDL-C) can prevent and reduce cardiovascular events. MicroRNA-181d (miR-181d) can reduce the levels of triglycerides and cholesterol esters in cells. However, it is not known whether miR-181d-5p can lower levels of circulating LDL-C. Here, we generated two animal models of hypercholesterolemia to analyze the potential relationship between miR-181d-5p and LDL-C. In hypercholesterolemia model mice, adeno-associated virus (AAV)-mediated liver-directed overexpression of miR-181d-5p decreased the serum levels of cholesterol and LDL-C and the levels of cholesterol and triglyceride in the liver compared with control mice. Target Scan 8.0 indicated Proprotein convertase subtilisin/kexin type 9 (PCSK9) to be a possible target gene of miR-181d-5p, which was confirmed by in vitro experiments. miR-181d-5p could directly interact with both the PCSK9 3′-UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, Dil-LDL uptake assays in PCSK9 knockdown Huh7 cells demonstrated that miR- 181d-5p promotion of LDL-C absorption was dependent on PCSK9. Collectively, our findings show that miR-181d-5p targets the PCSK9 3′-UTR to inhibit PCSK9 expression and to reduce serum LDL-C. miR-181d-5p is therefore a new therapeutic target for the development of anti-hypercholesterolemia drugs. [ABSTRACT FROM AUTHOR]

Background: With the ban on the use of antibiotics in poultry nutrition, the opinion of nutritionists turned to their alternatives. Garlic and mushroom are the two important phytobiotic compounds in poultry nutrition. Objectives: This experiment was done to investigate the effect of garlic powder (GP) and mushroom powder (MP) on the growth performance, meat quality, serum lipid profile, and intestinal morphology of broilers. Methods: Five hundred and seventy‐six one‐day‐old male Ross 308 broiler chicks were assigned to eight treatments with six replications based on a completely randomized design in a factorial arrangement of 4*2 with four levels of GP (0.00, 0.50, 1.00, 1.50%) and two levels of MP (0.00, 1.00%). Results: No significant effects of GP and MP on the performance were observed. With increasing levels of GP in the diets, the lightness and redness of breast meat decreased and increased, respectively (p < 0.05). The effect of increasing the amount of GP on the reduction of total cholesterol level was similar in the absence or presence of MP. With increasing levels of GP in the diets, the villus height (VH) and VH to crypt depth ratio (VH: CD) increased. The use of MP in the diets significantly increased VH and VH: CD (p < 0.05). Conclusion: The addition of GP and MP to the broilers' diets did not have any negative effect on the performance. These pharmaceutic herbs improved intestinal morphology. In addition, increasing the level of GP amended the meat color and reduced the level of serum cholesterol. [ABSTRACT FROM AUTHOR]

Background Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. Methods: A total of 394 samples were collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing–Bablok regression and Bland–Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. Results: The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Passing–Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. The resulting positive and negative predicted values were 0.77 and 0.92, respectively, vs. 0.46 and 0.96 from the external formula. Conclusions: Total cholesterol analysis in dried blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection. [ABSTRACT FROM AUTHOR]

This document presents the findings of a study that examined the experiences of older adults with limited English proficiency (LEP) in receiving preventive services and interacting with their healthcare providers. The study found that compared to older adults with English proficiency (EP), those with LEP had similar rates of receiving preventive services but reported poorer experiences with their healthcare providers. However, patients with LEP who had visit accompaniment had better experiences with their providers, including better communication, respect, and time spent with the patient. The study suggests that strategies to facilitate accompaniment, such as after-hours visits, may help improve the experiences of patients with LEP. The study acknowledges limitations, such as the cross-sectional design and self-reported data, and recommends interventions to improve the experiences of patients with LEP, such as interpreter use, AI-assisted translation, and multilingual health information. [Extracted from the article]

Simple Summary: This research examined how light exposure during incubation affects broiler chickens after hatch. Incubating eggs were exposed to different light durations during incubation (from none to all the time). After hatching, chicks' growth, stress levels, health, and immune response were checked. Results show that light during incubation did not affect most of these measures; however, chicks exposed to 20 h of light had heavier hearts. Overall, light during incubation does not seem to have a big impact on post-hatch performance. This study evaluated the subsequent effect of photoperiods during incubation on post-hatch growth and stress response of commercial broiler chickens. A total of 875 Ross 308 broiler breeder (48 weeks of age) eggs were hatched using different durations (0, 4, 8, 12, 16, 20, and 24 h a day) of dichromatic light [green and red (495 to 750 nm); 2700 K; 250 lux; SUNJIE; China] throughout the whole period of incubation. A total of 50 0-day-old hatched straight run broiler chicks from each photoperiod during incubation were used to evaluate subsequent growth performance (feed intake, body weight, and feed conversion ratio); stress parameters (physical asymmetry, tonic immobility, and vocalization,); welfare traits (feather score and gait score); carcass traits (live weight, dressed weight, carcass yield, liver weight, gizzard weight, heart weight, abdominal fat weight, breast weight, and leg weight); and serum chemistry (globulin, total protein, cholesterol, glucose, and uric acid). There were no influences of photoperiod during incubation on post-hatch growth, stress parameters, welfare, and carcass traits. Heart yield was higher in birds incubated under 20 h light than in those from the 16 h light group. Incubation under different lighting durations also altered blood biochemical profile but did not influence serum globulin and cholesterol levels. It was concluded that under experimental conditions, incubation of broiler eggs under different lighting durations did not impact subsequent post-hatch performance (21–35 d). [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with dyslipidemia being a significant risk factor. This meta-analysis provides a comprehensive evaluation of the impact of bovine dairy-derived milk fat globule membrane (MFGM) supplementation on blood lipid profiles in adults. A systematic search was conducted across various databases up until March 2024, resulting in the inclusion of 6 trials with a total of 464 participants. The findings indicated that MFGM phospholipid supplementation may significantly reduce total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. A combined analysis of the effects on TC, LDL, and triglycerides (TG) revealed a significant overall reduction in these markers. However, no significant increase or reduction was observed on high-density lipoprotein (HDL) and TG levels. Overall, MFGM phospholipid intake may significantly decrease the level of TC and LDL, while no significant changes in TG and HDL were observed. These results suggest that MFGM supplementation could be a promising dietary intervention for improving lipid profiles in adults. Nonetheless, further research is warranted to confirm these results and to better understand the potential variability in the impact of MFGM on blood lipid levels. [ABSTRACT FROM AUTHOR]

Background: Having positive psychological well-being has been associated with serum high-density lipoprotein cholesterol (HDLC), but no longitudinal study to date has examined the association between Ikigai and serum HDLC. Therefore, we examined the association between Ikigai and change in serum HDLC over time using a cohort dataset spanning 2010–2018. Methods: The study included 471 men and 776 women aged 40–74 years who underwent a cardiovascular examination in 2010 and were asked their levels of Ikigai. We combined "definitely yes" and "yes" as "with Ikigai" and recorded "a little" as "with a little Ikigai" and "no" as "without Ikigai". We measured serum HDLC using direct methods. The association between Ikigai and serum HDLC levels at baseline, and changes in this relationship during an eight-year period, were analyzed using linear mixed-effect models. Results: At the baseline, relative to those without Ikigai, women with Ikigai had higher serum HDLC (baseline difference in those with a little Ikigai = 7.52 mg/dl, 95% confidence interval [CI]: 1.12 to 13.9 and in those with Ikigai = 8.11 mg/dl, 95% CI: 1.54 to 14.7). The difference in serum HDLC between women with and without Ikigai remained over the eight-year follow-up period. There were no similar Ikigai-associated differences in the serum HDLC of men. Conclusions: Women with Ikigai showed differences in serum HDLC that were observed at baseline and persisted over time. [ABSTRACT FROM AUTHOR]

Background and Objective: Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. Methods: Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. Results: A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (β: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (β: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations. Conclusions: Both the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration. [ABSTRACT FROM AUTHOR]

The aim of this experiment was to study the effects of Flammulina velutipes bran supplementation on the growth performance, serum biochemical indices, immune organ index, and ileum morphology of Sanhuang chickens. A total of 192 one-day-old healthy Sanhuang chickens (half male and half female) with similar body weight were randomly divided into four groups with six replicates per group and eight chickens per replicate. Chickens in the control group were fed a basal diet, and chickens in experimental groups were fed the basal diet supplemented with 2%, 5%, and 7% Flammulina velutipes bran, respectively. The experiment lasted for 48 days. The results showed that the Flammulina velutipes bran had no significant effects on growth performance, spleen index, and ileum morphology of Sanhuang chickens (P>0.05). Compared with the control group, 7% of the Flammulina velutipes bran could increase bursa index of Fabricius (P<0.05), increase the levels of albumin and high density lipoprotein cholesterol in serum (P<0.05), and decrease the levels of low density lipoprotein cholesterol, urea nitrogen, cholesterol and triglyceride (P<0.05). The results show that feeding Flammulina velutipes bran has no effect on growth performance and ileal morphology of Sanhuang chickens, adding 7% Flammulina velutipes bran can improve immune organ index, serum lipid metabolism and protein metabolism. [ABSTRACT FROM AUTHOR]

The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K–L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of dietary supplementation of nanoparticles of Selenium (Nano-Se) on productive performance, nutrient digestibility, carcass criteria, selenium retention, blood biochemistry, and histopathological examination of broiler chicken. A total of 192 1-day-old male broiler chickens (Cobb 500) were randomly assigned to one of four treatment diets, with each diet given to six replicates of eight chicks. The birds were randomly assigned to one of four treatment groups, each of which included Nano-Se at levels of 0, 0.2, 0.3, or 0.4 mg/kg. The feeding experiment lasted 35 days. Nano-Se addition to broiler diets at 0.2 and 0.3 mg/kg enhanced body weight and body weight gain linearly compared to the control diet and 0.4 mg/kg. The apparent digestibility coefficient of ether extracts linearly increased with increasing Nano-Se levels up to 0.4 mg/kg. Increasing Nano-Se decreased serum cholesterol, triglycerides, alanine aminotransaminase, aspartate aminotransaminase, and creatinine in broiler chickens. Also, serum antioxidants showed a significant increase with increasing Nano-Se levels. As Nano-Se levels were supplemented, improvements in cooking loss, water-holding capacity, and antioxidants were observed as compared to the control. Additionally, a noticeable improvement in meat quality was observed regarding the obtained meat characters. It was preferred to use low doses of Nano-Se (0.3 mg/kg), as tissue retention of Se for both meat and liver was more comparable to the control. In conclusion, nutritional supplementation with Nano-Se increased growth performance, nutrient digestibility, selenium retention, meat quality, blood biochemistry, histological indices, and antioxidant activity of broiler chickens. Overall, the best performance of broilers was observed with Nano-Se supplementation at 0.3 mg/kg, highlighting its potential as a novel supplement for broiler diets. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is one of the main causes of death in the world. The increased level of blood cholesterol is significantly correlated to CVD incidents. Statins are a group of drugs that decrease the synthesis of cholesterol in the liver by inhibiting the final enzyme of the pathway named HMG-CoA reductase. Several investigations showed that different patients give different responses to the administration of statin drugs according to their genetic background. In this research study, using Genome-Wide Association Studies (GWAS) data analysis methods, such as the SimpleM statistical approach and genomic connection matrix, we tried to discover the novel candidate SNPs that were involved in response to statin drugs. The investigation was carried out using 3,221 cardiovascular patients' data about genotypes and phenotypes of two important parameters including total cholesterol, and LDL level, in response to statin administration. Functional annotation of nearest genes to candidate SNPs was also carried out by using comprehensive databases and tools such as BioMart-Ensembl, UCSC, NCBI, and WebGestalt software. Our results represented eight novel SNPs (rs10820084, rs4803750, rs10989887, rs1966503, rs17502794, rs10785232, rs484071, rs4785621) significantly associated with statin response in different individual cardiovascular patients for the first time. In addition, the groups of genes that are close to the SNPs were also represented and evaluated in detail. Our results illustrated that some of the genes such as BAAT, BCL3, and CMTM6 have a direct functional impact on cholesterol level or LDL biosynthesis which confirmed the effects of neighbor SNPs on the response to statin drugs. Today, finding the loci, genes, and molecular mechanisms involved in the response to drugs is of great importance in pharmacogenomics and personalized medicine. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the changes in cholesterol levels during medical ovarian suppression. Methods: We reviewed the medical records and blood test results of 187 female patients with breast cancer who underwent gonadotropin-releasing hormone (GnRH)-agonist therapy for > 24 weeks at our hospital between 1 January 2018 and 31 December 2020. The study excluded patients in this cohort who had previously been diagnosed with dyslipidemia, diabetes, or had recently received lipid-lowering agents, resulting in a final sample size of 152 participants. The age at diagnosis and preoperative body mass index (BMI) were included as baseline demographics. A generalized additive mixed model was applied to analyze the relationship between the duration of GnRH-agonist treatment and changes in cholesterol levels. Results: The study participants had a mean age of 42.5 ± 5.2 years and a mean preoperative BMI of 23.0 ± 3.6 kg/m²; the mean GnRHagonist therapy duration was 19.3 months (range: 5.6--37.7 months); and the total cholesterol level before GnRH-agonist treatment was 171 mg/dL that was significantly higher at 181 mg/dL (P = 0.03) during the most recent measurement. The total cholesterol level was unaffected by the GnRH-agonist therapy until 19.3 months after which it significantly increased by 1.28 mg/dL per month (P = 0.011). There was no significant effect of age, preoperative BMI, or the glomerular filtration rate on the total cholesterol levels. Conclusions: Long-term GnRH agonist therapy for > 19 months can cause a significant increase in the serum cholesterol levels. To prevent complications, patients receiving the treatment should be informed and monitored for the possible progression of dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is common in people with NAFLD, although not always overt glucose intolerance. Present study was done to describe the frequency of undiagnosed diabetes mellitus in patients of non alcoholic fatty liver disease at a tertiary care centre. Material & Methods: This was a hospital based observational cross-sectional study conducted in the Department of Medicine, Surgery and Biochemistry at Dr. Vithalrao Vikhe Patil Foundation's Medical College. Patients fulfilling the inclusion criteria were selected. A detailed informed consent was taken from all the participants. Demographic profile recorded and detailed history with examination was done in all the patients as per the proforma attached. Analysis of symptoms was done along with underlying co- morbid conditions and drugs used. Anthropometric data, such as body mass index (BMI) and blood pressure were measured. Results: Mean age of the cases was 53.62±10.69 years. Mean age in males was 55.33±10.19 years while in female it was 51.04±10.92 years. Maximum number of patients was in 5th and 6th decades. Out of 120 total patients, total males were 29 and females were 91. Out of 18 total diabetic patients, 12 were females and 6 were males. Impaired fasting glucose were found in 55(45.83%) of patients. Increased serum Cholesterol level were seen in 56(46.66%) patients. Increased serum triglyceride level was seen in 68(56.67%) patients. Low serum HDL level was seen in 78(65%) patients. Increased serum LDL levels were 37(30.83%) of patients. ALT and AST levels were elevated in 63(52.5%) and 61(50.83%) of patients. Total of 120 cases, 64(53.33%), 52(43.33%) and 4(3.33%) of cases had grade I, II, and III fatty liver respectively. Conclusion: The prevalence of several components of metabolic syndrome is higher in NAFLD patients, according to our findings. [ABSTRACT FROM AUTHOR]

The present study outlines the many risk variables of myocardial infarction (MI) in the patient population. Blood lipid profiles were normolipidemic in the study’s subjects. Myocardial infarction patients and controls were compared concerning their lipid, lipoprotein, and apolipoprotein profiles. Materials & methods: In this study, 84 participants had their blood cholesterol, Apolipoprotein-A, LDL, VLDL, HDL, triacylglycerols, and malondialdehyde studied. Out of the total number of participants, 42 were individuals who had suffered a myocardial infarction (MI). In contrast, the other 42 were controls matched for age and sex. Results: Acute myocardial infarction (MI) patients had significantly elevated levels of total cholesterol and triacylglycerols (TAGs) (p <0.05) despite the presence of low-density lipoprotein (LDL) in their blood. A significant difference was seen between the levels of apolipoprotein-A and low-density lipoprotein in the MI group and those in the control group. Researchers found that those who had a rapid heart attack exhibited significantly higher levels of malondialdehyde (p<0.05). Conclusion: For individuals diagnosed with risk factors, lipid profile monitoring, dietary antioxidant consumption, and measurement of inflammatory markers can all help lower the risk of myocardial infarction (MI). Furthermore, early detection can prevent MI. [ABSTRACT FROM AUTHOR]

Background and Aim: Insulin resistance and type 2 diabetes mellitus are common health issues in obese (OB) cats. In humans, obesity leads to alterations in adipokine and proinflammatory cytokine secretion, causing persistent inflammation. The inflammatory impact of obesity in cats remains unproven. This study investigated associations between obesity and inflammatory and metabolic changes in three groups of client-owned Brazilian domestic shorthair cats: naturally lean, overweight (OW), and OB. Materials and Methods: Cats from the Veterinary Hospital of Professor Sylvio Barbosa e Cardoso (FAVET/UECE) were clinically evaluated. Blood samples were collected for hematological and biochemical profile measurements, and part of the serum was used for measuring adipokine and inflammatory cytokines using sandwich enzyme-linked immunosorbent assay. Results: In both the OW and OB groups, serum cholesterol and insulin concentrations increased, while triglyceride concentrations were notably elevated in the OB group. In the OW and OB groups, serum adiponectin, tumor necrosis factor-α, and interleukin-1β levels were elevated, and leptin levels were significantly higher in the OB group. Conclusion: This study is the first in Brazil to reveal increased serum levels of inflammatory markers in OW and OB client-owned felines. OW cats exhibited higher proinflammatory marker levels, implying obesity-induced inflammation. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to gauge the risk that historically used, and newly produced, PFAS may cause to human health. Numerous studies report toxic effects of PFAS on the human liver as well as increased serum cholesterol levels in adults. A major concern with PFAS, also dubbed "forever chemicals," is that they accumulate in the liver and kidney and persist in serum. The mechanisms responsible for their disposition and excretion in humans are poorly understood. A better understanding of the interaction of PFAS with liver transporters, as it pertains to the disposition of PFAS and other xenobiotics, could provide mechanistic insight into human health effects and guide efforts toward risk assessment of compounds in development. This review summarizes the current state of the literature on the emerging relationships (eg, substrates, inhibitors, modulators of gene expression) between PFAS and specific hepatic transporters. The adaptive and toxicological responses of hepatocytes to PFAS that reveal linkages to pathologies and epidemiological findings are highlighted. The evidence suggests that our understanding of the molecular landscape of PFAS must improve to determine their impact on the expression and function of hepatocyte transporters that play a key role in PFAS or other xenobiotic disposition. From here, we can assess what role these changes may have in documented human health outcomes. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin, and IGF-1, and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first week after birth (mean and SD: 4.4 ± 2.1 d), 1 d before transport (mean and SD: 25.8 ± 7.3 d), and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1, and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized LMM. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin, and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28-d-old calves had higher blood cholesterol (Δ = 0.40 mmol/L) and IGF-1 (Δ = 53.6 ng/mL) concentrations, and evidence of higher insulin (Δ = 12.2 µU/mL) compared with 14-d-old calves. In wk 2 post-transport, 28-d-old calves had higher blood IGF-1 (Δ = 21.1 ng/mL), with evidence of higher insulin (Δ = 12.2 µU/mL) concentrations compared with 14-d-old calves. Cholesterol concentration measured 1 d before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (regression coefficients [β] = 4.8 and 7.7 kg/mmol per liter, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (β = −0.55/mmol/L), with the likelihood of a calf of being treated with antibiotics (β = −0.36/mmol/L) and other medicines (β = −0.45/mmol/L) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both β = −0.01/ng/mL) at the veal farm, and with fecal score recorded in wk 2 post-transport (β = −0.004/ng/mL). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14-d-old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinolone alkaloid present in a wide variety of plants. Other than Type 2 diabetes and hypertension it is also found to have an effect in lowering blood cholesterol levels. However, because of its poor oral bioavailability and substantial first pass hepatic metabolism it is consumed in higher dosage leading to side effects. To reduce dosage and avoid adverse effects, transdermal delivery is investigated using transethosomal gel as a carrier. Transethosomes are ethanolic nanocarriers that are specifically designed for the dermal or transdermal delivery route as it has enhanced permeation of the vesicles. In our study we have successfully investigated the potential use of berberine loaded transethosomal gel (BBR-TE) as a carrier for transdermal delivery. Three-level three-factorial Box Behnken Design was used to optimize BBR-TE (Opt-BBR-TE). The optimized formulation was further evaluated and found to have a particle size of 165.70 nm with entrapment efficiency of 79.60±4.07%. The in vitro drug release study suggested the non-Fickian transport mechanism. The ex vivo skin permeation was found to be 94.35±3.64% when compared to berberine conventional formulation. Berberine has also shown promising antioxidant activity when compared to the standard solution and was entrapped inside TE vesicles in non-crystalline form. The Opt-BBR-TE was converted into gel form. Various parameters of the gel such as pH, Drug Content, Spreadability and extrudability were found to have promising results. Present study data revealed that the developed transethosomal gel formulation was found to be a potentially useful drug carrier for transdermal delivery of berberine. [ABSTRACT FROM AUTHOR]

Background: Children who have chronic kidney disease (CKD) or end-stage renal disease (ESRD) often present with a range of concurrent medical conditions, one of which is dyslipidemia. This work aimed to detect the frequency of dyslipidemia among children with ESRD at Zagazig university hospitals. Methods: This cross-sectional observational study included (61 children patients) aged from 4 to 17 years old, who had ESRD (CKD grade V) with estimated glomerular filtration rate less than 15 ml/min/1.73m2 by modified Schwartz equation and on regular hemodialysis. A comprehensive history taking, thorough physical examination, and laboratory tests, including regular labs and the lipid profile, were conducted for all patients. Results: High percentage of examined children had high lipid profile (29.5 %) of the populations, The prevalence of abnormally high levels of total serum cholesterol, triglycerides, and low-density were found to be 29.5%, 75.4% and 16.4% respectively. Triglycerides, VLDL-C, and HDL levels were found to be higher during maintenance hemodialysis. No significant correlation was found between duration of hemodialysis, urea, and creatinine, with Cholesterol, triglyceride, high density lipoprotein (HDL), low density lipoprotein, and very low-density lipoprotein, except for a significant positive correlation between phosphate (Po4) and high density lipoprotein (HDL) (P =0.022). Conclusion: The prevalence of dyslipidemia was found to be high among HD patients in Zagazig university hospitals. Comparisons of lipid parameters with CVD risk stratifications need further studies to prove the benefits of these scores in CVD prediction among the dialysis population. [ABSTRACT FROM AUTHOR]

A simple and facile hydrothermal method was developed for the synthesis of gold nanoparticles (AuNPs) adorned with two-dimensional (2D) heme-like Fe(III)-tetra(4-carboxyphenyl)-porphine (TCPP-Fe) metal-organic framework (MOF) nanocomposite. Notably, the synthesized hybrid nanomaterial (AuNPs/TCPP-Fe hybrid nanosheets) exhibited excellent peroxidase (POD)-like nanoenzymes activity and Raman activity under ultrasound (US) and near-infrared (NIR) irradiation at physiological pH conditions. A cascade colorimetric-SERS dual-mode method was developed for sensitive and rapid cholesterol determination based on the excellent POD-like properties and surface-enhanced Raman spectroscopy (SERS) activity of AuNPs/TCPP-Fe nanoenzymes. The TCPP-Fe nanoenzymes combined with cholesterol oxidase catalyze a cascade reaction to convert cholesterol to H2O2, which then oxidizes colorless, low Raman-activity 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue, high-Raman-activity oxidation product (ox-TMB). The cholesterol in human serum of colorimetric-SERS was successfully assayed with good recovery from 97.8 to 103.7%. The study paves a new method for designing a nanocomposite-based SERS for biochemistry analysis. [ABSTRACT FROM AUTHOR]

Cholesterol is required to maintain the functional integrity of cellular membrane systems and signalling pathways, but its supply must be closely and dynamically regulated because excess cholesterol is toxic. Sterol regulatory element-binding protein 2 (SREBP2) and the ER-resident protein HMG-CoA reductase (HMGCR) are key regulators of cholesterol biosynthesis. Here, we assessed the mechanistic aspects of their regulation in hepatic cells. Unexpectedly, we found that the transcriptionally active fragment of SREBP2 (N-SREBP2) was produced constitutively. Moreover, in the absence of an exogenous cholesterol supply, nuclear N-SREBP2 became resistant to proteasome-mediated degradation. This resistance was paired with increased occupancy at the HMGCR promoter and HMGCR expression. Inhibiting nuclear N-SREBP2 degradation did not increase HMGCR RNA levels; this increase required cholesterol depletion. Our findings, combined with previous physiological and biophysical investigations, suggest a new model of SREBP2-mediated regulation of cholesterol biosynthesis in the organ that handles large and rapid fluctuations in the dietary supply of this key lipid. Specifically, in the nucleus, cholesterol and the ubiquitin–proteasome system provide a short-loop system that modulates the rate of cholesterol biosynthesis via regulation of nuclear N-SREBP2 turnover and HMGCR expression. Our findings have important implications for maintaining cellular cholesterol homeostasis and lowering blood cholesterol via the SREBP2-HMGCR axis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cho- lesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr -- enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours. [ABSTRACT FROM AUTHOR]

Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination. Aim:. The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout. Materials and methods:. The study involved 286 male patients with gout, age 51.2 [42.8; 59.4] years (ys), disease duration 6.2 [3.8; 12.1] ys. All patients underwent standard clinical examination screening traditional risk factors (TRFs) of CVDs. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results:. CHD was found in 111 out of the 286 pts (38.8%), MI had a history in 29.7%. Compared to individuals with CHD, participants without CHD were older (56.7[52.1; 61.1] vs 46.2[40.6; 53.4] ys), had longer duration of gout (9.3[4.7; 15.1] vs 5.6[3.3; 9.7] ys) (for all p < 0.05). Abdominal obesity (OR, 3.6; 95% CI, 1.2–10.9), family history of CHD (OR, 2.2; 95% CI, 1.3–3.7), disease duration of gout more 10 ys (OR, 2.8; 95% CI, 1.6–4.7), age of gout onset < 35 ys (OR, 5.5; 95% CI, 2.6–11.7), intraosseous tophi (OR, 3.03; 95% CI, 1.8–5.01), nephrolithiasis (OR, 1.7; 95% CI, 1.04–3.04), renal failure (OR, 5.6; 95% CI, 2.7–11.4), serum total cholesterol (TC), (OR, 1.6; 95% CI, 1.0–2.8), serum creatinine (OR, 2.5; 95% CI, 1.2–5.1), increased the risk for CHD in patients with a gout. Conclusions:. The prevalence of CHD was 38.8% among individuals with gout (one-third of patients had a history of MI 29.7%). Our study showed that both TRFs of CVD and the severity of gout and a history of renal failure contribute to the development of CHD in patients with gout. [ABSTRACT FROM AUTHOR]

Serum biochemical indicators serve as vital proxies that reflect the physiological state and functions of different organs. The genetic parameters and molecular mechanisms underlying serum biochemical indicators of sheep (Ovis aries) have not been well understood. Therefore, the aim of the present study was to identify the genetic architecture and genomic loci underlying ten serum biochemical indicators in sheep, including alanine transaminase, aspartate transferase, lactate dehydrogenase, cholesterol, glucose, phosphorus, calcium, creatinine, urea and total protein levels. We implemented genetic parameter estimations and GWASs for each trait in 422 Akkaraman lambs. Overall, low to moderate heritability estimates were found in the range of 0.14–0.55. Additionally, low to high genetic correlations were observed among traits. In total, 23 SNP loci were associated with serum biochemical indicators leading to 19 genes. These were SPTA1, MGST2, CACUL1, IGFBP7, PARD3, PHB1, SLC15A5, TRIM35, RGS6, NUP93, CNTNAP2, SLC7A11, B3GALT5, DPP10, HST2ST1, NRP1, LRP1B, MAP3K9 and ENSOARG00020040484.1, as well as LOC101103187, LOC101117162, LOC105611309 and LOC101118029. To our knowledge, these data provide the first associations between SPTA1 and serum cholesterol and between ENSOARG00020040484.1 and serum glucose. The current findings provide a comprehensive inventory of the relationships between serum biochemical parameters, genetic variants and disease-relevant characteristics. This information may facilitate the identification of therapeutic targets and fluid biomarkers and establish a strong framework for comprehending the pathobiology of complex diseases as well as providing targets for sheep genetic improvement programs. [ABSTRACT FROM AUTHOR]

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