In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms (SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women\'s Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

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UNASSIGNED: Homozygous familial hypercholesterolemia (HoFH) is characterized by early-onset atherosclerotic cardiovascular disease due to the high low-density lipoprotein cholesterol (LDL-C) burden. Patients with null-null low-density lipoprotein receptor (LDLR) variants respond poorly, if at all, to statins and proprotein convertase subtilisin/kexin type 9 inhibitors, which act by upregulating LDLR expression. The 24-week double-blind treatment period (DBTP) of the phase 3 ELIPSE HoFH (Evinacumab Lipid Studies in Patients with Homozygous Familial hypercholesterolemia; NCT03399786) study demonstrated significant LDL-C reductions in patients with HoFH; LDL-C reductions were also observed in those with null-null LDLR mutations.
UNASSIGNED: The purpose of this study was to evaluate longer-term efficacy and safety of evinacumab in patients with HoFH from the ELIPSE HoFH study.
UNASSIGNED: Patients with HoFH on stable lipid-lowering therapies (LLTs) ± lipoprotein apheresis and screening LDL-C ≥70 mg/dL who completed the DBTP entered the 24-week open-label treatment period (OLTP) and received intravenous evinacumab 15 mg/kg every 4 weeks. OLTP results were summarized descriptively.
UNASSIGNED: A total of 64 patients completed the DBTP and received open-label evinacumab. Despite multiple LLTs, the mean baseline LDL-C at DBTP entry was 250.5 ± 162.3 mg/dL. From baseline to week 48 (end of OLTP), evinacumab reduced mean LDL-C by 46.3% (mean reduction, 134.3 ± 117.3 mg/dL), with similar mean LDL-C reductions for patients with null-null (47.2%) and non-null variants (45.9%). Adverse events occurred in 47 (73.4%) patients; 4 (6.3%) patients experienced adverse events considered evinacumab-related (drug hypersensitivity, infusion-related reaction and asthenia, generalized pruritis, and muscle spasms).
UNASSIGNED: In patients with HoFH, evinacumab demonstrated substantial and sustained LDL-C reduction regardless of LDLR function, and was generally well tolerated.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

UNASSIGNED: This research describes the methodology used for the preparation of selenium nanoparticles from Pseudomonas aeruginosa and their administration to lambs for lipid profile checking, administration of selenium nanoparticles as a medication in lambs results in hypolipidemia.
UNASSIGNED: The study aimed to investigate the potential of selenium nanoparticles in improving lipid profiles in lambs.
UNASSIGNED: Healthy lambs (n = 10) of similar age and weight were selected for the study. The animals were housed in individual pens with free access to water and a standard diet. The lambs were randomly divided into two groups: the control group (n = 5) and the treatment group (n = 5). The control group received a standard diet, while the treatment group received the same diet and oral administrated with selenium nanoparticles at 0.1 mg/kg body weight. The administration was carried out daily for a period of 8 weeks. Blood samples were collected from the jugular vein of each lamb at the beginning of the study (baseline) and at the end of the 2 weeks treatment period. The samples were collected in vacutainer tubes and allowed to clot. Serum was separated by centrifugation at 3,000 rpm for 10 minutes and stored at -80°C for estimation of lipid profile total cholesterol (TC), triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The serum samples were used for the estimation of lipid profile levels using an enzymatic colorimetric method. The absorbance was measured at 540 nm using a spectrophotometer.
UNASSIGNED: The results showed a significant decrease in serum TC, triglyceride, and very-low-density lipoprotein cholesterol levels after selenium nanoparticle supplementation compared to the control group (p < 0.05), the results indicated a significant increase in serum HDL levels after selenium nanoparticle supplementation compared to the control group (p < 0.05). This indicates that selenium nanoparticle supplementation has a beneficial effect on reducing TC levels in lambs.
UNASSIGNED: The conclusion section will summarize the findings of the study and highlight the potential of selenium nanoparticles in improving lipid profiles in lambs. The implications of the study for animal nutrition and health will be discussed, along with the need for further research in this area.

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BACKGROUND: The final decision to fast or not fast for routine lipid profile examination in a standard, healthy population is unclear. Whereas the United States and European protocols state that fasting for regular lipid analysis is unnecessary, the North American and Chinese guidelines still recommend fasting before routine lipid testing.
OBJECTIVE: This study aimed to unravel the contradiction between the different protocols of lipid profile testing worldwide and clarify the effect of diet on lipid profile testing only in a regular, healthy population.
METHODS: A literature search was conducted through May 2024. The analyses included studies performed from the date 2000 until now because the contradiction of guidelines for lipid profile testing appeared for the first time in this period. A planned internal validity evaluation was performed using the National Institute of Health (NIH) quality measurement tools for observational cohort, case‒control, controlled interventional, and cross-sectional studies. The data were synthesized according to RevMan 5.3.
RESULTS: Eight studies with a total of 244,665 participants were included. The standardized mean difference in cholesterol in six studies showed significant differences in overall effect among fasting and nonfasting states (P < 0.00001), as did high-density lipoprotein cholesterol (P < 0.00001). At the same time, with respect to triglycerides and low-density lipoprotein cholesterol, there were notable variations in the overall effect between the fasted and nonfasted states (P < 0.00001 and P ≤ 0.001, respectively).
CONCLUSIONS: This meta-analysis concluded that fasting for lipid profile testing is preferred as a conservative model to reduce variability and increase consistency in patients\' metabolic status when sampling for lipid testing.

BACKGROUND: Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear.
METHODS: Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results.
RESULTS: Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1_20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2_0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships.
CONCLUSIONS: Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application.

Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011-2014 and 2019-2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.

No single enteric CH4 mitigating strategy has been consistently effective or is readily applicable to ruminants in grassland systems. When CH4 mitigating strategies are effective under grazing conditions, mitigation is mild to moderate at best. A study was conducted to evaluate the potential of combining two CH4 mitigation strategies deemed feasible to apply in grazing dairy cows, the methanogenesis inhibitor 3-nitrooxypropanol additive (3-NOP) and cottonseed supplementation (CTS), seeking to enhance their individual CH4 mitigating potential. Forty-eight dairy cows were evaluated in a continuous grazing study and supplemented with either a starch-based concentrate (STA) or one that contained cottonseeds (1.75 kg DM/d; CTS), and with either 19 g/d of 10% 3-NOP (Bovaer®) or the additive\'s carrier (placebo), in a 2 × 2 factorial arrangement of treatments. Treatments were supplied mixed with a concentrate supplement (5 kg/d as fed) and offered in two equal rations at milking. Methane emissions were measured on weeks 4 and 8 using the sulphur hexafluoride tracer gas technique over a 5-d period. The 3-NOP and CTS treatments tended to interact on absolute CH4 such that 3-NOP decreased CH4 by 13.4% with STA, but there was no mitigation with 3-NOP and CTS. Treatment interactions were also obtained for CH4 yield, where 3-NOP tended to decrease CH4 when supplied with STA, and tended to increase it with CTS. The increase in CH4 yield with the CTS diet was driven by a numerical decrease in DM intake. Methane intensity was not affected by the 3-NOP or CTS treatments. Total volatile fatty acids in ruminal fluid were not affected by 3-NOP supplementation, but a reduction in acetate and an increase in propionate proportion occurred, resulting in decreased acetate: propionate. The 3-NOP additive decreased grass intake; however, energy-corrected milk yield and milk composition were largely unaffected. Milk urea increased with 3-NOP supplementation. Combining twice daily supplementation of 3-NOP and CTS did not enhance their CH4 mitigation potential when fed to grazing dairy cows. The relatively low inhibition of CH4 production by 3-NOP compared to studies with total mixed rations may result from the mode of delivery (pulse dosed twice daily) and time gap caused by experimental handling and moving of animals to pasture after 3-NOP supplementation in the milking parlour, which could have impaired the synchrony between the additive presence in the rumen and grass intake in paddocks.