Dyslipidemia Research Articles

Assessment of Obesity-related Metabolic Conditions: a novel objective scoring system better informs metabolic disease severity

BackgroundReporting of obesity-associated metabolic disease severity and longitudinal response to bariatric surgery is not standardized. We updated our co-morbidity scoring tool to the Assessment of Obesity-related Metabolic Conditions (AOMC) to combine pharmacotherapy and biochemical data to score diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DYS) severity. ObjectivesThe aim of this study is to determine whether the AOMC system more accurately stages metabolic disease severity than a clinically based Assessment of Obesity-Related Comorbidities (AORC) system. SettingUniversity hospital, United States. MethodsA retrospective cohort study of prospectively collected demographic, clinical, and biochemical data was performed on adults evaluated for bariatric surgery over 6years. AORC versus AOMC scores and disease severity were compared using McNemar’s and Wilcoxon’s tests. ResultsOf 1442 patients, AOMC newly diagnosed metabolic disease in more patients than did AORC: DM (73.4% versus 44.5%), HTN (91.7% versus 67.9%), and DYS (63.8% versus 53.4%). Of those on pharmacotherapy, AOMC found fewer patients with adequately controlled disease: DM (39.9% versus 97.7%), HTN (64.7% versus 99.3%), and DYS (51.8% versus 99.0%). For those in whom both scores could be calculated, disease severity was upstaged in most patients: DM (65.9%), HTN (42.9%), and DYS (30.9%). There were also significant shifts toward higher scores for all conditions and severity classifications, with more patients diagnosed with pre–metabolic and severe disease (untreated/uncontrolled). ConclusionsOur study demonstrated that the severity of DM, HTN, and DYS is vastly under-represented by clinical history alone and lacks standardized assessments. Our AOMC tool more accurately describes longitudinal metabolic response to bariatric surgery.

Distinctive characteristics, risk factors, and prevention of premature myocardial infarction: A narrative review.

The proportion of young individuals that present with acute myocardial infarction is a major problem that keeps increasing. The specific characteristics of premature coronary artery disease and its differences between young and older individuals need to be elucidated. Although risk factors are similar in different age categories, there is a great difference in their prevalence. The vast majority of young patients are males and there is a higher prevalence of cigarette smoking, family history of premature coronary artery disease, lipid disorders, and illicit drug use, while the prevalence of hypertension and diabetes mellitus is lower. Young individuals with acute coronary syndrome usually present either with ST-segment elevation or non-ST-segment elevation myocardial infarction. It is not unusual for young patients to present with atypical symptoms to the office of primary care physicians, leading occasionally to incorrect or delayed diagnosis. Therefore, prompt and correct diagnosis is necessary to implement the specific management as quickly as possible. A literature research of studies was conducted for the last 10 years, regarding the risk factors and prevention of premature myocardial infarction. As databases, we used PubMed and peer reviewed journals. The aim of this review is to raise awareness among family medicine and primary care physicians, regarding the clinical presentation of young patients with acute myocardial infarction, to provide optimal medical attention.

Hair treatment products containing pigeon pea oil as chemical properties and anti-oxidant activity

The comparing small type (T9) and big type (ICP 7035), which were extracted by hexane maceration, this study looks at the properties of pigeon pea oil in hair treatment products. It finds that the percentage yield of big seed (ICP 7035) oil is higher than that of small seed (T9) oil, at 9.64 ± 0.10 and 9.32 ± 0.08, respectively. A study on the chemical properties of the oil revealed values for saponification, acidity, iodine, and peroxide. In all trials, T9 outperformed ICP 7035 in terms of test results, demonstrating the presence of fatty acids in the molecular components of triglycerides. Compared to ICP 7035, T9 had a lower molecule weight and a lower saturation level, making it less susceptible to oxidative lipid disorder and the tendency to deplete oil. The flavonoid content of T9 is higher than that of ICP 7035, equal to 27.76 ± 0.65 mg GAE g-1 extract and 25.90 ± 0.69 mg GAE g-1 extract, respectively. The flavonoid content of T9 is higher than that of ICP 7035, equal to 20.67 ± 0.58 mg QE g-1 extract and 18.76 ± 0.65 mg QE g-1 extract, respectively. The DPPH test showed that T9 was a stronger antioxidant than ICP 7035, with amounts of 0.26 ± 0.04 mg g-1 of extract and 0.35 ± 0.05 mg g-1, respectively. The development of hair care products revealed that a mixture containing the optimal dosage of T9 effectively ensured smooth hair lines and prevented microorganism contamination in all recipes. GRAPHICAL ABSTRACT HIGHLIGHTS Pigeon Pea Oil in Hair Care Products Comparison of T9 and ICP 7035 oil properties. ICP 7035 yield was higher than T9 yield. Chemical properties of oil included saponification, acidity, iodine, and peroxide. T9 oil had better phenolics, flavonoids, and DPPH values than ICP 7035. T9-rich mixtures in hair care products ensure smooth hair lines and prevent microorganism contamination.

Effects of liver X receptor in O3-induced airway inflammation and remodeling in mice.

The current clinical treatment of chronic obstructive pulmonary disease (COPD) mainly uses drugs to improve symptoms, but these drugs cannot reverse the progression of the disease and the pathological changes in lung tissue. This study aimed to investigate the effects and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in mice. Wild mice and LXR deficient mice were exposed to O3 twice a week for 6 weeks. Some wild mice were intraperitoneally injected with T0901317 (a LXR agonist) before O3 exposure. Wild mice were exposed to ambient air and intraperitoneally injected with normal saline (NS) as control group. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected to evaluate airway inflammation, airway remodeling and lipid disorder. After O3 exposure, LXR deficient mice showed severe airway inflammation and airway remodeling compared with the wild mice. There were a lot of foamy macrophages appeared in BALF of LXR deficient mice. The inflammatory proteins such as myeloid differentiation primary response protein 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) in the lung tissues of LXR deficient mice were significantly increased compared with the wild mice. In wild mice exposed to O3, T0901317 treatment can alleviate airway inflammation, airway remodeling and foamy macrophages in BALF. And MyD88 and IRAK expression in lung tissue were also attenuated by T0901317 treatment. LXRs play protective roles in O3-induced lipid accumulation, airway inflammation and airway remodeling.

Mechanism of folium polygoni cuspidati in liver-yang-hyperactivity hypertension based on network pharmacology, molecular docking and experimental pharmacological validation

Ethnopharmacological relevanceAt present,the global form of hypertension is severe,and liver-yang-hyperactivity hypertension（GYSK hypertension）is the most common type of hypertension.Folium Polygoni Cuspidati（HZY）are mainly used in Yunnan, China,to treat dizziness, headache,and hypertension caused by GYSK,and the content of the active ingredients of HZY and its efficacy varies in different periods.However,the mechanism of action and the effect of harvesting period are not clear. Aim of the studyThe purpose of this research was to investigate the effect of HZY in April and September on GYSK hypertension. Materials and methodsThe model of GYSK hypertension was established with aconite decoction and L-NAME,and the blood pressure,the symptoms of GYSK,the cardiac index and the pathological changes of aorta were observed,to study the effect of HZY in April and September on GYSK hypertension.The chemical composition of HZY was analysed by UPLC-QTOF-MS and its mechanism for the treatment of GYSK hypertension was predicted by network pharmacological studies and experimentally validated using serum metabolomics and Western blot techniques. ResultsApril HZY and September HZY can significantly improve the GYSK symptoms of rats, inhibit the RAAS system, improve oxidative stress and regulate blood lipids so as to play a blood pressure lowering efficacy and have a protective effect on the vascular endothelial cells.UPLC-QTOF-MS yielded 29 components of HZY,and network pharmacology predicted that its mechanism may be related to Lipid and atherosclerosis,PI3K/Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway,etc.Western Blot validation showed that HZY activated PI3K,p-Akt protein expression and inhibited p-erk,p-p38 and TNF-α protein expression.Serum metabolomics suggested that April HZY exerts its efficacy mainly by regulating amino acid metabolism and September HZY mainly by regulating lipid metabolism. ConclusionsIn GYSK hypertensive rats treated for three weeks, both April HZY and September HZY could have antihypertensive effects,but the mechanisms of action were different and similar, both could regulate metabolite disorders of sugars, lipids,amino acids and peptides,and regulate blood pressure through the PI3K/Akt-eNOS and MAPK signalling pathways, with the difference that April HZY had stronger regulatory effects on the metabolism of amino acids.metabolism.

Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

Investigation of Cytotoxicity and Lipid-lowering Effects of Rivea hypocrateriformis Desr. Leaf Extracts on HepG2 Cells: An In Vitro Study

Background and Purpose Chronic diseases, such as cardiovascular disease as well as type 2 diabetes, are associated with hyperlipidemia, characterized by high blood lipid levels. HepG2 cells, a human liver cancer cell line, have become a popular model for evaluating the effectiveness of drugs in treating hyperlipidemia. These cells are preferred due to their ability to mimic liver cell physiology and easy maintenance in culture. Methods In this study, HEP, HEC, HEA, and HEE extracts of Rivea hypocrateriformis were tested on HepG2 cells for cytotoxicity using the MTT assay. The IC50 values of the extracts were determined and compared to analyze their toxicity. Microscopic images of the cell lines were also examined to observe any structural changes induced by the extracts. Results and Conclusion The results showed that both HEC and HEE extracts exhibited significant toxicity on HepG2 cells at the highest concentration of 500 µg/ml. Gradual decreases in concentration led to a gradual rise in % cell viability. The IC50 values of HEC and HEE were calculated to be 61.49 µg/ml and 87.08 µg/ml, respectively, indicating that HEC was slightly more toxic than HEE. According to the results obtained using the vanilla method, HEC and HEE extracts markedly reduced lipid content compared to the oleic acid-induced group. The gene expression regulation of AMPK, FAS, LDL receptor, and HMG-CoA was investigated using the RT-PCR method. The results showed that the extract-treated groups exhibited higher AMPK and LDL receptor gene expression. In contrast, the HEE extract showed higher activity than HEC in suppressing the FAS gene. Overall, the findings suggest that HEC and HEE extracts have potential as anticancer and lipid-lowering agents. Detailed research is needed to understand how the active constituents work.

The Role of Selected lncRNAs in Lipid Metabolism and Cardiovascular Disease Risk.

Lipid disorders increase the risk for the development of cardiometabolic disorders, including type 2 diabetes, atherosclerosis, and cardiovascular disease. Lipids levels, apart from diet, smoking, obesity, alcohol consumption, and lack of exercise, are also influenced by genetic factors. Recent studies suggested the role of long noncoding RNAs (lncRNAs) in the regulation of lipid formation and metabolism. Despite their lack of protein-coding capacity, lncRNAs are crucial regulators of various physiological and pathological processes since they affect the transcription and epigenetic chromatin remodelling. LncRNAs act as molecular signal, scaffold, decoy, enhancer, and guide molecules. This review summarises available data concerning the impact of lncRNAs on lipid levels and metabolism, as well as impact on cardiovascular disease risk. This relationship is significant because altered lipid metabolism is a well-known risk factor for cardiovascular diseases, and lncRNAs may play a crucial regulatory role. Understanding these mechanisms could pave the way for new therapeutic strategies to mitigate cardiovascular disease risk through targeted modulation of lncRNAs. The identification of dysregulated lncRNAs may pose promising candidates for therapeutic interventions, since strategies enabling the restoration of their levels could offer an effective means to impede disease progression without disrupting normal biological functions. LncRNAs may also serve as valuable biomarker candidates for various pathological states, including cardiovascular disease. However, still much remains unknown about the functions of most lncRNAs, thus extensive studies are necessary elucidate their roles in physiology, development, and disease.

Inhibition of forward and reverse transport of Ca2+ via Na+/Ca2+ exchangers (NCX) prevents sperm capacitation

BackgroundWhile calcium is known to play a crucial role in mammalian sperm physiology, how it flows in and out of the male gamete is not completely understood. Herein, we investigated the involvement of Na+/Ca2+ exchangers (NCX) in mammalian sperm capacitation. Using the pig as an animal model, we first confirmed the presence of NCX1 and NCX2 isoforms in the sperm midpiece. Next, we partially or totally blocked Ca2+ outflux (forward transport) via NCX1/NCX2 with different concentrations of SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline; 0, 0.5, 5 and 50 µM) and Ca2+ influx (reverse transport) with SN6 (ethyl 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-1,3-thiazolidine-4-carboxylate; 0, 0.3, 3 or 30 µM). Sperm were incubated under capacitating conditions for 180 min; after 120 min, progesterone was added to induce the acrosome reaction. At 0, 60, 120, 130, and 180 min, sperm motility, membrane lipid disorder, acrosome integrity, mitochondrial membrane potential (MMP), tyrosine phosphorylation of sperm proteins, and intracellular levels of Ca2+, reactive oxygen species (ROS) and superoxides were evaluated.ResultsPartial and complete blockage of Ca2+ outflux and influx via NCX induced a significant reduction of sperm motility after progesterone addition. Early alterations on sperm kinematics were also observed, the effects being more obvious in totally blocked than in partially blocked samples. Decreased sperm motility and kinematics were related to both defective tyrosine phosphorylation and mitochondrial activity, the latter being associated to diminished MMP and ROS levels. As NCX blockage did not affect the lipid disorder of plasma membrane, the impaired acrosome integrity could result from reduced tyrosine phosphorylation.ConclusionsInhibition of outflux and influx of Ca2+ triggered similar effects, thus indicating that both forward and reverse Ca2+ transport through NCX exchangers are essential for sperm capacitation.

Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy.

This study uncovers that despite ursodeoxycholic acid treatment, intrahepatic cholestasis of pregnancy (ICP) is associated with increases in the ratio of cholic acid to chenodeoxycholic acid in both maternal and cord blood, suggesting ongoing dysregulation of bile acid metabolism. The high cholic to chenodeoxycholic acid ratio is correlated with maternal dyslipidemia and high cord blood lipids. These findings may inform more targeted approaches to managing ICP.

Therapeutic mechanism of Cynanchum wilfordii for ulcerative colitis: an analysis using UPLC-QE-MS, network pharmacology and metabolomics

To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis (UC). UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract, and their targets were screened using public databases for construction of the core protein-protein interaction (PPI) network and GO and KEGG enrichment analyses. Forty male C57 mice were randomized into normal control group, model group, mesalazine group and Cynanchum wilfordii group (n=10), and in the latter 3 groups, mouse UC models were established by treatment with 2.5% DSS and the latter 2 groups drug interventions by gavage. The therapeutic effect was evaluated by recording body weight changes and DAI score. Pathological changes of the colon tissue were observed with HE and AB-PAS staining, and JAK2 and STAT3 protein expressions were detected with Western blotting. The metabolites and metabolic pathways were identified by metabonomics analysis. We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts, including 19 steroids. A total of 177 Cynanchum wilfordii targets, 5406 UC genes, and 117 intersection genes were obtained. JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways. Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice (P < 0.05), alleviated intestinal pathologies, and decreased JAK2 and STAT3 protein expressions in the colon tissues. Most of the 83 intersecting differential metabolites between the control, model and Cynanchum wilfordii groups were identified as glycerophospholipids, arachidonic acid, and amino acids involving glycerophospholipid metabolism and other pathways. Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites. Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.

Epicatechin and β-glucan from whole highland barley grain ameliorates hyperlipidemia associated with attenuating intestinal barrier dysfunction and modulating gut microbiota in high-fat-diet-fed mice

Hyperlipidemia is associated with intestinal barrier dysfunction and gut microbiota dysbiosis. Here, we aimed at investigating whether epicatechin (EC) and β-glucan (BG) from whole highland barley grain alleviated hyperlipidemia associated with ameliorating intestinal barrier dysfunction and modulating gut microbiota dysbiosis in high-fat-diet-induced mice. It was observed that EC and BG significantly improved serum lipid disorders and up-regulated expression of PPARα protein and genes. Supplementation of EC and BG attenuated intestinal barrier dysfunction via promoting goblet cells proliferation and tight junctions. Supplementation of EC and BG prevented high fat diet-induced gut microbiota dysbiosis via modulating the relative abundance of Ruminococcaceae, Lactobacillus, Desulfovibrio, Lactococcus, Allobaculum and Akkermansia, and the improving of short chain fatty acid contents. Notably, combination of EC and BG showed synergistic effect on activating PPARα expression, improving colonic physical barrier dysfunction and the relative abundance of Lactobacillus and Desulfovibrio, which may help explain the effect of whole grain highland barley on alleviating hyperlipidemia.

Association Between Remnant Cholesterol and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis.

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.

Efficacy and Safety of Bempedoic Acid in Lipid Disorder Therapy: A Review of Clinical Trials

LDL levels are a key risk factor for atherosclerotic cardiovascular disease. Bempediic acid is an innovative hypolipemic drug, particularly useful for patients intolerant of statins. The article focuses on analyzing the results of clinical trials on the mechanisms of action, efficacy and safety of bempediic acid used both as monotherapy and in combination with other hypolipemic drugs. Scientific evidence based on the CLEAR: Tranquility, Harmony, Serenity, Wisdom, Outcomes study, among others, is presented. Its significant effects on lowering LDL-C, non-HDL-C, and hsCRP levels are highlighted, with important implications for the prevention and treatment of cardiovascular disease. It also outlines how bempedic acid is included in current Polish guidelines for the treatment of lipid disorders. The paper also points to new areas of research, including potential applications of bempediic acid in specific patient groups, such as pregnant women. In addition, the article addresses issues related to the long-term use and safety of bempediic acid, particularly in the context of reducing cardiovascular risk and lowering blood lipid levels, which is crucial for patients with statin intolerance.

Baicalin ameliorates heat stress-induced hepatic injury and intestinal microecology dysbiosis in late gestational mice

Heat stress (HS) disrupts intestinal microbiota, glycolipid metabolism, and hepatic mitochondrial function in late gestational mice. Baicalin (BAI), a Chinese herbal medicine known for its heat-clearing and anti-inflammatory properties, has shown promise in modulating intestinal microecology and mitigating inflammation in various organs. This study investigates whether baicalin attenuates HS-induced intestinal microbial dysbiosis and liver damage in pregnant mice during late gestation. Twenty-four pregnant mice were randomly assigned to four groups, including thermoneutral (TN) (24 ± 1 ℃), HS (35 ± 1 ℃), HS+BAI200 (oral gavaged with 200 mg/kg BW of BAI), and HS+BAI400 (oral gavaged with 400 mg/kg BW of BAI). 400 mg/kg BAI treatment markedly decreased the rectal temperature and increased fetal weight in HS pregnant mice. Furthermore, 400 mg/kg BAI administration effectively ameliorated HS-induced hepatic damage and lipid disorders, reducing HSP70, AST, and ALT levels while increasing TG concentration. Notably, it activated a network of genes involved in lipid synthesis, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and oxidation, such as peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmityl transferase 1 beta (CPT1β). Moreover, BAI intervention restored the intestinal morphology and barrier function, evidenced by increased intestinal villus height, the ratio of villus height to crypt depth, and colonic goblet cells numbers. 400 mg/kg of BAI treatment up-regulated the expression of tight junction proteins, such as claudin-1 and Zonula Occludens-1 (ZO-1), in the jejunum and ileum, counteracting HS-induced downregulation. High-throughput sequencing showed that BAI treatment altered cecal microbial composition, increasing the relative abundance of beneficial Bacteroidota and decreasing Deferribacterota, Turicibacter, and Akkermansia. Spearman’s correlation analysis highlighted significant correlations between differential cecal microbiota and physiological indexes. In conclusion, BAI administration alleviated adverse impacts in heat-exposed mice during late gestation, improving maternal physiological parameters, and ameliorating hepatic damage with altered cecal microbial composition. The findings suggest that BAI may regulate the gut-liver axis by modulating intestinal morphology, microecology, and hepatic function.

Lipoprotein (a) and the Occurrence of Lipid Disorders and Other Cardiovascular Risk Factors in Patients without Diagnosed Cardiovascular Disease.

Background: Elevated lipoprotein (a) [Lp(a)] concentrations are linked mainly to genetic factors. The relationship between Lp(a) and other lipid disorders or cardiovascular (CV) risk factors has been less investigated. The aim of this study was to assess the occurrence of lipid disorders and other CV risk factors according to Lp(a) concentrations. Methods: A cross-sectional analysis of 200 primary-care patients who had not been diagnosed with CV disease was conducted. The following risk factors were assessed: older age, history of hypertension, diabetes mellitus or dyslipidemia, smoking, lack of physical activity, body mass index (BMI), and waist circumference. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and small, dense LDL (sdLDL-C). Patients were divided into two groups based on their Lp(a) concentrations: <30 mg/dL and ≥30 mg/dL. Results: In 70% of patients, the Lp(a) concentration was <30 mg/dL. The concentrations of lipid parameters did not differ between the groups. The rate of patients with sdLDL-C >1.0 mmol/L was higher in the low-Lp(a) group (10.0 vs. 1.7%, p = 0.04), with no significant differences regarding the other analyzed lipid disorders (p > 0.05). Both in the low- and high-Lp(a) group, most patients had two other abnormal lipid factors (45.0% and 60.0%, respectively). The distribution of impaired lipid parameters (p = 0.41) and other CV risk factors (p = 0.16) was similar in both groups. There was a lower rate of patients >60 years old (15.0% vs. 32.9%, p = 0.01) and with a BMI ≥ 25 kg/m2 (46.7% vs. 63.6%, p = 0.026) in the high-Lp(a) group, and previously diagnosed hyperlipidemia was more prevalent in this group (65.0% vs. 47.1%, p = 0.02). The occurrence of other cardiovascular risk factors did not differ significantly between the Lp(a) groups (p > 0.05). In the high-Lp(a) group, the highest proportion (25.0%) had two CV risk factors, and in the low-Lp(a) group, 31.4% had four CV risk factors. Conclusions: An elevated Lp(a) concentration is not related to the number of conventional CV risk factors or other impairment major lipid parameters.

Evaluation of Medication Adherence Among Prevalent Users in Hypertension, Dyslipidemia, and Diabetes Using Health Insurance Claims: A Population-Based Cohort Study in Japan.

Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

Integrated untargeted and targeted lipidomics discovers LPE 16:0 as a protector against respiratory syncytial virus infection

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections, imposing a substantial burden on healthcare systems globally. While lipid disorders have been observed in the lungs of infants and young children with RSV pneumonia, the specific characterization of these lipids and their roles in the development and progression of RSV pneumonia remain largely unexplored. To address this tissue, we established a non-targeted high-resolution lipidomics platform using UHPLC-Q-Exactive-MS to analyze lipid profiles in bronchoalveolar lavage fluid (BALF) obtained from mice infected with RSV. Through the lipidomics analysis, a total of 72 lipids species were identified, with 40 lipids were significantly changed. Notably, the primary changes were observed in ether phospholipids and lysophospholipids. Furthermore, a targeted lipidomics analysis utilizing UHPLC-QQQ-MS/MS was developed to specifically assess the levels of lysophospholipids, including lysophosphocholine 16:0 (LPC 16:0), lysophosphoethanolamine 16:0 (LPE 16:0) and lysophosphoglycerol 16:0 (LPG 16:0), in RSV-infected mice compared to control mice. Animal experiments revealed that LPE 16:0, rather than LPC 16:0 or LPG 16:0, provided protection against RSV-induced weight loss, reduced lung viral load, regulated immune cells and mitigated lung injury in mice afflicted with RSV pneumonia. In summary, our findings suggested that the host responses to RSV infection pathology are closely with various lipid metabolic. Additionally, our results elucidated novel biological functions of LPE 16:0 and offering new avenues for drug development against RSV pneumonia.

КАРДИОМЕТАБОЛИЧЕСКИЙ ПРОФИЛЬ С УЧЕТОМ СТАДИРОВАНИЯ ПО CMDS У ЛИЦ МОЛОДОГО ВОЗРАСТА

Abstract. Introduction. The burden of cardiovascular disease, diabetes mellitus, and the associated mortality remains high. One classification system that predicts the development of cardiovascular events and type 2 diabetes mellitus is Cardiometabolic Disease Staging (CMDS). The study of new cardiometabolic profile parameters is relevant in the context of their association with residual cardiovascular risk. The aim of the study was to evaluate the cardiometabolic profile, including extended parameters, in young adults, while taking into account the CMDS. Materials and Methods. 185 male and female subjects aged 35.0 [30.0–39.0] years were examined. The participants were divided into groups according to the CMDS classification: Stage 0, metabolically healthy; Stage 1 (low risk), one or two risk factors (RFs) other than prediabetes; Stage 2 (intermediate risk), presence of ≥3 risk factors or prediabetes; Stage 3 (high risk), presence of ≥3 risk factors and prediabetes. The study examined visceral adiposity index, visceral fat level, insulin resistance, leptinemia, hyperuricemia, glomerular filtration rate, C–reactive protein, and N–terminal brain natriuretic peptide concentrations. The data were processed in SPSS Statistics 26. Results and Discussion. The cardiometabolic profile demonstrated unfavorable alterations with the progression of CMDS stages. Across the spectrum from CMDS 0 to CMDS 3, we observed a significant rise in the prevalence of abdominal obesity (0% to 100%, p&lt;0,001), body mass index ≥25 kg/m2 (16.2% to 100%, p&lt;0.001), and excess visceral fat level (0% to 23.8%, p&lt;0.001). Simultaneously, the prevalence of hypercholesterolemia demonstrated a significant rise (24.3% to 52.4%, p=0.025), as did elevated low–density lipoprotein cholesterol (32.4% to 76.1%, p=0.014), insulin resistance (2.7% to 66.7%, p&lt;0.001), leptinemia (45.9% to 90.5%, p=0.009), C–reactive protein (2.7% to 57.1%, p&lt;0.001) and hyperuricemia (16.2% to 61.9%, p&lt;0.001). The median values of these parameters also increased. Conclusions. Our data confirm the simultaneous increase in both the quantity and intensity of risk factors, manifestations of adiposopathy associated with increasing residual cardiovascular risk. Our results substantiate the feasibility of using the CMDS classification at the stage of primary prevention of cardiometabolic diseases to identify groups with the most significant metabolism disorders of lipid, carbohydrate and purine metabolism in young adults.

Lipidomics reveals the serum profiles of pediatric allergic rhinitis and its severity.

Allergic rhinitis (AR) is a prevalent upper airway chronic inflammatory disease in children worldwide. The role of bioactive lipids in the regulation of AR has been recognized, but the underlying serum lipidomic basis of its pathology remains unclear. We utilized ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometry (MS) to investigate the serum lipidomic profiles of children with AR. The lipidomic analysis identified 42 lipids that were differentially expressed (p< 0.05, fold change > 2) between the AR (n= 75) and normal control groups (n= 44). Specifically, the serum levels of diacylglycerol (DG), triacylglycerol (TG), fatty acid (FA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, phosphatidyl-ethanolamine, and cardiolipins were significantly higher in the AR group. The diagnostic potential of the identified lipids was further evaluated using receiver operating characteristic curve analysis. The analysis revealed that five lipids, including FA 30:7, LPC O-18:1, LPC 18:0, LPC 16:0, and DG 34:0, had area under the curve values greater than 0.9 (p< 0.05). Furthermore, serum levels of IgE and IL-33, markers of AR severity, were found to have a significant positive correlation (p< 0.05) with DGs, LPCs, TGs, and FAs in AR patients. This study revealed the lipid disorders associated with AR and its severity, providing new insights into the pathological process of AR.