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1.
PLoS One ; 19(7): e0304442, 2024.
Article in English | MEDLINE | ID: mdl-38985806

ABSTRACT

BACKGROUND: This pilot study aimed to investigate medication nonadherence among Taiwanese patients with diabetes, hypertension, and hyperlipidemia using the Chinese version of the Two-Part Medication Nonadherence Scale (C-TPMNS) and the National Health Insurance (NHI) Medicloud system. The study revealed insights into the factors contributing to nonadherence and the implications for improving patient adherence to medications for chronic conditions. However, the small sample size limits the generalizability of the findings. Additionally, the study identified the need for further research with larger and more diverse samples to validate the preliminary findings. METHODS: The study conducted surveys individuals in central Taiwan who received three-high medications and those who returned expired medications from chain pharmacies. A structured questionnaire including the C-TPMNS was administered, and additional data on medical history and HbA1c, LDL, and blood pressure levels were collected from the NHI Medicloud system. Data analysis was performed using multiple ordered logistic regression and Wald test methods. Setting interpretation cutoff point to determine medication nonadherence. RESULTS: The study found that 25.8% of participants were non-adherent to prescribed medications. Non-adherent individuals had significantly higher systolic blood pressure (SBP ≥ 140 mmHg) than adherent participants. Non-adherence was also associated with factors such as lower education, single status, living alone, abnormal glucose postprandial concentration, and triglyceride levels. The C-TPMNS demonstrated good reliability (Cronbach's alpha = 0.816) and validity (area under the ROC curve = 0.72). CONCLUSION: The study highlighted the complexity of medication nonadherence with diverse determinants and emphasized the importance of tailored interventions. The findings underscored the need for region-specific research to comprehensively address medication nonadherence, especially focusing on adherence to medications for hypertension, hyperlipidemia, and diabetes. The study also identified the need for larger, more diverse studies to validate and expand upon the initial findings and emphasized the importance of pharmacist interventions and patient empowerment in managing chronic conditions and improving overall health outcomes.


Subject(s)
Diabetes Mellitus , Hyperlipidemias , Hypertension , Medication Adherence , Humans , Medication Adherence/statistics & numerical data , Medication Adherence/psychology , Hyperlipidemias/drug therapy , Hypertension/drug therapy , Hypertension/psychology , Pilot Projects , Male , Female , Taiwan , Middle Aged , Diabetes Mellitus/drug therapy , Aged , Surveys and Questionnaires , Adult
2.
PLoS One ; 19(7): e0304516, 2024.
Article in English | MEDLINE | ID: mdl-38950289

ABSTRACT

BACKGROUND: The connection between urinary bisphenol A (BPA) and hyperlipidemia is still unclear, and few studies have evaluated whether urinary BPA affects mortality among individuals with hyperlipidemia. Therefore, we aimed to investigate the link between urinary BPA and hyperlipidemia and assess the impact of urinary BPA on mortality risk in subjects with hyperlipidemia. METHODS: We analyzed data of the National Health and Nutrition Examination Survey from 2003 to 2016. Multivariable logistic analysis was performed to examine the relationship between urinary BPA and hyperlipidemia. Cox regression analysis was carried out to investigate the relationship between urinary BPA and all-cause mortality in subjects with hyperlipidemia. RESULTS: This study included 8,983 participants, of whom 6,317 (70.3%) were diagnosed with hyperlipidemia. The results showed that urinary BPA was higher in participants with hyperlipidemia group than those without hyperlipidemia (3.87 ± 0.32 vs. 2.98 ± 0.14, P = 0.01). Urinary BPA levels were analyzed in tertiles. Compared with tertile 1 of BPA (reference), the odds ratio (95% confidence interval) of hyperlipidemia related to tertile 3 of BPA was 1.28 (1.11-1.48). The hazard ratio for all-cause death associated with the highest versus lowest tertile of urinary BPA was 1.20 (95% confidence interval: 1.01-1.44; P = 0.04) among participants with hyperlipidemia. CONCLUSIONS: The study indicated a positive relationship between urinary BPA and the risk of hyperlipidemia. Urinary BPA was associated with a significantly higher risk of all-cause mortality in adults with hyperlipidemia.


Subject(s)
Benzhydryl Compounds , Hyperlipidemias , Nutrition Surveys , Phenols , Humans , Phenols/urine , Benzhydryl Compounds/urine , Benzhydryl Compounds/adverse effects , Hyperlipidemias/urine , Hyperlipidemias/mortality , Male , Female , Middle Aged , Adult , Aged
3.
J Orthop Surg Res ; 19(1): 393, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970109

ABSTRACT

BACKGROUND: To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats. METHODS: We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed. RESULTS: Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group. CONCLUSION: Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.


Subject(s)
Cistanche , Hyperlipidemias , Osteoporosis , Ovariectomy , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Ovariectomy/adverse effects , Female , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/physiology , Phosphatidylinositol 3-Kinases/metabolism , Hyperlipidemias/complications , Hyperlipidemias/metabolism , Osteoporosis/etiology , Osteoporosis/metabolism , Rats , Rats, Sprague-Dawley , Bone Density/drug effects , Random Allocation
4.
Int J Mol Sci ; 25(13)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39000541

ABSTRACT

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Hyperglycemia , Hyperlipidemias , Lipid Metabolism , Liver , Animals , Gastrointestinal Microbiome/drug effects , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Mice , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Lipid Metabolism/drug effects , Hyperglycemia/drug therapy , Hyperglycemia/metabolism , Liver/metabolism , Liver/drug effects , Fungal Polysaccharides/pharmacology , Male , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Glucose/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Termitomyces/metabolism , Blood Glucose/metabolism , Polysaccharides/pharmacology , Mice, Inbred C57BL
5.
Front Immunol ; 15: 1371477, 2024.
Article in English | MEDLINE | ID: mdl-39007149

ABSTRACT

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.


Subject(s)
Diet, High-Fat , Macrophages , Mice, Inbred C57BL , Myocardium , Animals , Diet, High-Fat/adverse effects , Mice , Macrophages/immunology , Macrophages/metabolism , Female , Myocardium/metabolism , Myocardium/immunology , Obesity/immunology , Obesity/metabolism , Hyperlipidemias/immunology , Hyperlipidemias/metabolism
6.
BMC Cardiovasc Disord ; 24(1): 354, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992615

ABSTRACT

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.


Subject(s)
Disease Models, Animal , Inflammasomes , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Mice, Inbred C57BL , Mice, Knockout, ApoE , NLR Family, Pyrin Domain-Containing 3 Protein , Phenanthrenes , Signal Transduction , Syk Kinase , Vasodilation , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Syk Kinase/metabolism , Matrix Metalloproteinase 2/metabolism , Phenanthrenes/pharmacology , Male , Matrix Metalloproteinase 9/metabolism , Vasodilation/drug effects , Hyperlipidemias/drug therapy , Hyperlipidemias/physiopathology , Vasodilator Agents/pharmacology , Phosphorylation , Mice , Aorta/drug effects , Aorta/physiopathology , Aorta/metabolism , Aorta/enzymology , Apolipoproteins E
7.
Sci Rep ; 14(1): 15935, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987566

ABSTRACT

The association between the composite dietary antioxidant index (CDAI) and hyperlipidemia remains unclear. Therefore, this study aimed to investigate the relationship between CDAI and hyperlipidemia. The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) dataset spanning from 2005 to 2020. Based on 24-h dietary recall interviews, the CDAI was calculated using the intake of six dietary antioxidants. Univariate and multivariate logistic regression models were employed to investigate the relationship between CDAI and the occurrence of hyperlipidemia. Additionally, restricted cubic spline (RCS) analysis was utilized to investigate potential non-linear relationships between the CDAI and risk of hyperlipidemia. The final analysis included 30,788 adults in the United States, among whom 25,525 (82.91%) were diagnosed with hyperlipidemia. A significant negative correlation was observed between the CDAI and hyperlipidemia in the unadjusted (Odds ratio [OR] 0.97 [95% CI 0.96, 0.98]) and multi-variable adjusted (OR 0.98 [95% CI 0.97, 0.99]) models. When the CDAI values were analyzed as a categorical variable, individuals in the highest quartile (OR 0.82 [95% CI 0.73, 0.92]) exhibited a nearly one fifth decreased risk of hyperlipidemia compared to those in the lowest quartile. Additionally, RCS analysis revealed a linear relationship between CDAI and hyperlipidemia (P for nonlinearity = 0.124). The results remained consistent across subgroups except for individuals under the age of 60 or those with diabetes mellitus. There was a significant negative correlation between the CDAI and risk of hyperlipidemia, indicating that maintaining an optimal CDAI level could effectively reduce the incidence of hyperlipidemia.


Subject(s)
Antioxidants , Hyperlipidemias , Nutrition Surveys , Humans , Hyperlipidemias/epidemiology , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , Antioxidants/analysis , United States/epidemiology , Diet , Risk Factors , Aged
8.
PeerJ ; 12: e17583, 2024.
Article in English | MEDLINE | ID: mdl-38948211

ABSTRACT

Background: Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks®-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated. Methods: A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study. Results: The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), p < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure (p < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like Phascolarctobacterium succinatutens, Bifidobacterium angulatum, and Levilactobacillus brevis which might have a beneficial role in the current context and a similar decrease in species like Alistipes finegoldii, and Sutterella faecalis which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Hyperglycemia , Hypertension , Precision Medicine , Humans , Male , Hypertension/diet therapy , Hypertension/microbiology , Female , Middle Aged , Prospective Studies , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/microbiology , Hyperglycemia/diet therapy , Hyperglycemia/microbiology , Precision Medicine/methods , Inflammation/diet therapy , Proof of Concept Study , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Aged , Hyperlipidemias/diet therapy , Hyperlipidemias/blood , Hyperlipidemias/microbiology , Adult , C-Reactive Protein/analysis , C-Reactive Protein/metabolism
9.
Neurology ; 103(1): e209536, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38861692

ABSTRACT

BACKGROUND AND OBJECTIVES: Secondary stroke preventive care includes evaluation and control of vascular risk factors to prevent stroke recurrence. Our objective was to evaluate the quality of ambulatory stroke preventive care and its variation by immigration status in adult stroke survivors in Ontario, Canada. METHODS: We conducted a population-based administrative database-derived retrospective cohort study in Ontario, Canada. Using immigration records, we defined immigrants as those immigrating after 1985 and long-term residents as those arriving before 1985 or those born in Canada. We included community-dwelling stroke survivors 40 years and older with a first-ever stroke between 2011 and 2017. In the year following their stroke, we evaluated the following metrics of stroke prevention: testing for hyperlipidemia and diabetes; among those with the condition, control of diabetes (hemoglobin A1c ≤7%) and hyperlipidemia (low-density lipoprotein <2 mmol/L); medication use to control hypertension, diabetes, and atrial fibrillation; and visit to a family physician and a specialist (neurologist, cardiologist, or geriatrician). We determined age and sex-adjusted absolute prevalence difference (APD) between immigrants and long-term residents for each metric using generalized linear models with binomial distribution and an identity link function. RESULTS: We included 34,947 stroke survivors (median age 70 years, 46.9% women) of whom 12.4% were immigrants. The receipt of each metric ranged from 68% to 90%. Compared with long-term residents, after adjusting for age and sex, immigrants were slightly more likely to receive screening for hyperlipidemia (APD 5.58%; 95% CI 4.18-6.96) and diabetes (5.49%; 3.76-7.23), have visits to family physicians (1.19%; 0.49-1.90), receive a prescription for antihypertensive (3.12%; 1.76-4.49) and antihyperglycemic medications (9.51%; 6.46-12.57), and achieve control of hyperlipidemia (3.82%; 1.01-6.63). By contrast, they were less likely to achieve diabetes control (-4.79%; -7.86 to -1.72) or have visits to a specialist (-1.68%; -3.12 to -0.24). There was minimal variation by region of origin or time since immigration in immigrants. DISCUSSION: Compared with long-term residents, many metrics of secondary stroke preventive care were better in immigrants, albeit with small absolute differences. However, future work is needed to identify and mitigate the factors associated with the suboptimal quality of stroke preventive care for all stroke survivors.


Subject(s)
Ambulatory Care , Emigrants and Immigrants , Secondary Prevention , Stroke , Humans , Ontario/epidemiology , Male , Female , Aged , Stroke/prevention & control , Stroke/epidemiology , Stroke/ethnology , Middle Aged , Secondary Prevention/methods , Retrospective Studies , Ambulatory Care/statistics & numerical data , Emigrants and Immigrants/statistics & numerical data , Aged, 80 and over , Diabetes Mellitus/epidemiology , Adult , Hyperlipidemias/epidemiology , Emigration and Immigration , Cohort Studies
10.
Fa Yi Xue Za Zhi ; 40(2): 172-178, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38847033

ABSTRACT

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.


Subject(s)
Apolipoproteins E , Biomarkers , Disease Models, Animal , Hyperlipidemias , Restraint, Physical , Animals , Hyperlipidemias/metabolism , Hyperlipidemias/complications , Mice , Biomarkers/metabolism , Apolipoproteins E/genetics , Proteomics/methods , Stress, Psychological/complications , MicroRNAs/metabolism , MicroRNAs/genetics , Ferroptosis , Male , Myocardium/metabolism , Myocardium/pathology , Mice, Knockout , Uncoupling Protein 1/metabolism , Computational Biology
11.
Nutrients ; 16(12)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38931308

ABSTRACT

Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in hyperlipidemic rats, taking statins, was observed. (2) Methods: One hundred and twelve white Wistar rats, males and females, were divided into seven: Group I received 20 mg of atorvastatin while groups II and III received a combination of 20 mg of atorvastatin and 100 mg of Sea buckthorn and grape extract. Groups IV and V received 100 mg of Sea buckthorn and grape extract, while groups VI and VII received only high-fat diet (HFD) and normal rodents' fodder. After two and six months, rats were euthanized, and blood was gathered to measure the main paraclinical values and total antioxidant capacity (TAC). Also, the liver and kidney were stored for the organs' cytoarchitecture. For statistics, two-way analysis of variance (ANOVA), was performed. (3) Results: HFD produced hyperlipidemia, accompanied by augmented serum and hepatic oxidative stress markers, in addition to a reduction in antioxidant enzyme activities and glutathione levels. Polyphenolic substances proven efficient against HFD caused oxidative stress. (4) Conclusions: Atorvastatin heightened the histological injuries caused by the fatty diet, but these were diminished by taking atorvastatin in combination with 100 mg/kg of plant extracts.


Subject(s)
Antioxidants , Atorvastatin , Biomarkers , Diet, High-Fat , Hippophae , Hyperlipidemias , Liver , Oxidative Stress , Plant Extracts , Rats, Wistar , Vitis , Animals , Atorvastatin/pharmacology , Oxidative Stress/drug effects , Hyperlipidemias/drug therapy , Male , Hippophae/chemistry , Vitis/chemistry , Plant Extracts/pharmacology , Female , Antioxidants/pharmacology , Diet, High-Fat/adverse effects , Liver/drug effects , Liver/metabolism , Rats , Biomarkers/blood , Kidney/drug effects , Kidney/metabolism , Kidney/pathology
12.
Cell Death Dis ; 15(6): 389, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830896

ABSTRACT

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.


Subject(s)
Cholesterol , NF-E2-Related Factor 2 , Receptors, LDL , Animals , Receptors, LDL/metabolism , Cholesterol/metabolism , NF-E2-Related Factor 2/metabolism , Mice , Mice, Knockout , Mice, Inbred C57BL , Lipid Metabolism , Male , Atherosclerosis/metabolism , Apolipoproteins/metabolism , Apolipoproteins/genetics , Humans , Liver/metabolism , Apolipoproteins E/metabolism , Hyperlipidemias/metabolism
13.
Lipids Health Dis ; 23(1): 164, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831466

ABSTRACT

OBJECTIVE: Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. METHODS: This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. RESULTS: During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. CONCLUSIONS: This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.


Subject(s)
Blood Urea Nitrogen , Cardiovascular Diseases , Hyperlipidemias , Nutrition Surveys , Humans , Hyperlipidemias/blood , Hyperlipidemias/mortality , Male , Female , Middle Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Proportional Hazards Models , Aged , Adult , Risk Factors
14.
Front Endocrinol (Lausanne) ; 15: 1380163, 2024.
Article in English | MEDLINE | ID: mdl-38846488

ABSTRACT

Background: Although the importance and benefit of heme oxygenase-1 (HO-1) in diabetes rodent models has been known, the contribution of HO-1 in the pre-diabetic patients with hyperlipidemia risk still remains unclear. This cross-sectional study aims to evaluate whether HO-1 is associated with hyperlipidemia in pre-diabetes. Methods: Serum level of HO-1 was detected using commercially available ELISA kit among 1,425 participants aged 49.3-63.9 with pre-diabetes in a multicenter Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) prospective observational study. Levels of total cholesterol (TC) and triglyceride (TG) were measured and used to defined hyperlipidemia. The association between HO-1 and hyperlipidemia was explored in different subgroups. Result: The level of HO-1 in pre-diabetic patients with hyperlipidemia (181.72 ± 309.57 pg/ml) was obviously lower than that in pre-diabetic patients without hyperlipidemia (322.95 ± 456.37 pg/ml). High level of HO-1 [(210.18,1,746.18) pg/ml] was negatively associated with hyperlipidemia (OR, 0.60; 95% CI, 0.37-0.97; p = 0.0367) after we adjusted potential confounding factors. In subgroup analysis, high level of HO-1 was negatively associated with hyperlipidemia in overweight pre-diabetic patients (OR, 0.50; 95% CI, 0.3-0.9; p = 0.034), especially in overweight women (OR, 0.42; 95% CI, 0.21-0.84; p = 0.014). Conclusions: In conclusion, elevated HO-1 level was negatively associated with risk of hyperlipidemia in overweight pre-diabetic patients, especially in female ones. Our findings provide information on the exploratory study of the mechanism of HO-1 in hyperlipidemia, while also suggesting that its mechanism may be influenced by body weight and gender.


Subject(s)
Heme Oxygenase-1 , Hyperlipidemias , Prediabetic State , Humans , Hyperlipidemias/blood , Hyperlipidemias/epidemiology , Female , Male , Cross-Sectional Studies , Middle Aged , Heme Oxygenase-1/blood , Prediabetic State/blood , Prediabetic State/epidemiology , Prospective Studies , Longitudinal Studies , Risk Factors , China/epidemiology
15.
Mo Med ; 121(3): 206-211, 2024.
Article in English | MEDLINE | ID: mdl-38854609

ABSTRACT

The incidence of diabetes and hyperlipidemia are increasing at rapid rates in children. These conditions are associated with increased risk of macrovascular and microvascular complications causing major morbidity and mortality later in life. Early diagnosis and treatment can reduce the lifelong risk of complications from these diseases, exemplifying the importance of screening in the pediatric population. The following article presents a summary of the current guidelines for diabetes and hyperlipidemia screening in pediatric patients.


Subject(s)
Dyslipidemias , Mass Screening , Humans , Child , Dyslipidemias/diagnosis , Mass Screening/methods , Mass Screening/standards , Practice Guidelines as Topic , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Pediatrics/methods , Pediatrics/standards , Hyperlipidemias/diagnosis , Adolescent
16.
BMC Womens Health ; 24(1): 323, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835013

ABSTRACT

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.


Subject(s)
Chorionic Gonadotropin, beta Subunit, Human , Pregnancy Outcome , Pregnancy Trimester, Second , Humans , Pregnancy , Female , Retrospective Studies , Pregnancy Trimester, Second/blood , Adult , Pregnancy Outcome/epidemiology , Chorionic Gonadotropin, beta Subunit, Human/blood , Pregnancy Complications/blood , Pregnancy Complications/epidemiology , China/epidemiology , Pre-Eclampsia/blood , Pre-Eclampsia/epidemiology , Cohort Studies , Polyhydramnios/blood , Polyhydramnios/epidemiology , Chorionic Gonadotropin/blood , Hyperlipidemias/blood , Hyperlipidemias/epidemiology
17.
Trials ; 25(1): 374, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38858768

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. METHODS: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire-metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. DISCUSSION: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. TRIAL REGISTRATION: European Union Clinical Trials Register, EudraCT, 2021-006069-39. Registered on March 13, 2022.


Subject(s)
Diabetes Mellitus, Type 2 , Fatty Liver , Hyperlipidemias , Multicenter Studies as Topic , Obesity , Quality of Life , Randomized Controlled Trials as Topic , Humans , Diabetes Mellitus, Type 2/complications , Double-Blind Method , Obesity/complications , Hyperlipidemias/complications , Treatment Outcome , Phospholipids , Clinical Trials, Phase IV as Topic , Male , Adult , Female , Middle Aged
18.
Pharmacol Res ; 205: 107232, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38825157

ABSTRACT

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).


Subject(s)
Gastrointestinal Microbiome , Hyperlipidemias , Humans , Gastrointestinal Microbiome/drug effects , Double-Blind Method , Male , Middle Aged , Hyperlipidemias/drug therapy , Hyperlipidemias/blood , Hyperlipidemias/microbiology , Female , Adult , Lipids/blood , Resistant Starch , Starch , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/pharmacology , Aged
19.
Bioinformatics ; 40(Supplement_1): i199-i207, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940159

ABSTRACT

MOTIVATION: The emergence of COVID-19 (C19) created incredible worldwide challenges but offers unique opportunities to understand the physiology of its risk factors and their interactions with complex disease conditions, such as metabolic syndrome. To address the challenges of discovering clinically relevant interactions, we employed a unique approach for epidemiological analysis powered by redescription-based topological data analysis (RTDA). RESULTS: Here, RTDA was applied to Explorys data to discover associations among severe C19 and metabolic syndrome. This approach was able to further explore the probative value of drug prescriptions to capture the involvement of RAAS and hypertension with C19, as well as modification of risk factor impact by hyperlipidemia (HL) on severe C19. RTDA found higher-order relationships between RAAS pathway and severe C19 along with demographic variables of age, gender, and comorbidities such as obesity, statin prescriptions, HL, chronic kidney failure, and disproportionately affecting Black individuals. RTDA combined with CuNA (cumulant-based network analysis) yielded a higher-order interaction network derived from cumulants that furthered supported the central role that RAAS plays. TDA techniques can provide a novel outlook beyond typical logistic regressions in epidemiology. From an observational cohort of electronic medical records, it can find out how RAAS drugs interact with comorbidities, such as hypertension and HL, of patients with severe bouts of C19. Where single variable association tests with outcome can struggle, TDA's higher-order interaction network between different variables enables the discovery of the comorbidities of a disease such as C19 work in concert. AVAILABILITY AND IMPLEMENTATION: Code for performing TDA/RTDA is available in https://github.com/IBM/Matilda and code for CuNA can be found in https://github.com/BiomedSciAI/Geno4SD/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
COVID-19 , Hyperlipidemias , Metabolic Syndrome , Renin-Angiotensin System , SARS-CoV-2 , Humans , Metabolic Syndrome/epidemiology , COVID-19/epidemiology , Hyperlipidemias/epidemiology , Male , Female , Middle Aged , Aged , Comorbidity , Hypertension/epidemiology , Risk Factors
20.
J Ethnopharmacol ; 333: 118438, 2024 Oct 28.
Article in English | MEDLINE | ID: mdl-38848972

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.


Subject(s)
Gastrointestinal Microbiome , Hyperlipidemias , Molecular Docking Simulation , Tea , Animals , Hyperlipidemias/drug therapy , Gastrointestinal Microbiome/drug effects , Male , Mice , Tea/chemistry , Computational Biology , Network Pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Mice, Inbred C57BL , Lipid Metabolism/drug effects , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/isolation & purification , Hypolipidemic Agents/therapeutic use , Disease Models, Animal , Metabolomics , Multiomics
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