A specific serum lipid signature characterises patients with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidaemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterise the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, FC 2.2, p < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, p < 0.0001), and ceramide (FC 2.4, p < 0.0001) levels and bile acid (FC 0.7, p < 0.001), acylcarnitines (FC 0.7, p < 0.001), and cholesterol esters (FC 1.0, p < 0.001) than those of healthy controls, and higher di- (FC 1.1, p < 0.0001; FC 0.9, p < 0.01) and triacylglycerol (FC 6.3, p < 0.0001; FC 3.9, p < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol (TC) and TG values correlated with Cer(d16:1/22:0), Cer(d18:1/20:0), Cer(d18:1/20:0(OH)), Cer(d18:1/22:0), Cer(d18:1/23:0), Cer(d18:1/24:1), Cer(d18:2/22:0), Cer(d18:2/24:1). TC also correlated with Cer(d18:1/24:0), Cer(d18:2/20:0), HexCer(d16:1/22:0), HexCer(d18:1/18:0), and Hex2Cer(d18:1/20:0). TGlevels correlated with Cer(d18:0/24:1). Alanine transaminase values correlated with Cer(d18:0/22:0), insulin with Cer(d18:1/22:1) and Cer(d18:1/24:1), and HDL with hexosylceramide (HexCer)(d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.

Platelets as an inter-player between hyperlipidaemia and atherosclerosis.

Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet-hyperlipidaemia interplay and its impact on atherogenesis. Native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet-specific LDL receptor (LDLR) ApoE-R2', whereas oxLDL binds to the platelet-expressed scavenger receptor CD36, lectin-type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet-released platelet factor 4 and transforming growth factor ß modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet-hyperlipidaemia interplay in atherosclerosis are also discussed.

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

AIM: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. RESULTS: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. CONCLUSIONS: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

The GPR40 novel agonist SZZ15-11 improves non-alcoholic fatty liver disease by activating the AMPK pathway and restores metabolic homeostasis in diet-induced obese mice.

AIM: Non-alcoholic fatty liver is the most common cause of chronic liver disease. GPR40 is a potential therapeutic target for energy metabolic disorders. GPR40 is a potential therapeutic target for energy metabolic disorders. SZZ15-11 is a newly synthesized GPR40 agonist. In this study, we estimate the potency of SZZ15-11 in fatty liver treatment. METHODS: In vivo, diet-induced obese (DIO) mice received SZZ15-11 (50 mg/kg) and TAK875 (50 mg/kg) for 6 weeks. Blood glucose and lipid, hepatocyte lipid and liver morphology were analysed. In vitro, HepG2 cells and GPR40-knockdown HepG2 cells induced with 0.3 mM oleic acid were treated with SZZ15-11. Triglyceride and total cholesterol of cells were measured. At the same time, the AMPK pathway regulating triglycerides and cholesterol esters synthesis was investigated via western blot and quantitative polymerase chain reaction in both liver tissue and HepG2 cells. RESULTS: SZZ15-11 was found to not only attenuate hyperglycaemia and hyperlipidaemia but also ameliorate fatty liver disease in DIO mice. At the same time, SZZ15-11 decreased triglyceride and total cholesterol content in HepG2 cells. Whether examined in the liver of DIO mice or in HepG2 cells, SZZ15-11 upregulated AMPKα phosphorylation and then downregulated the expression of the cholesterogenic key enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and inhibited acetyl-CoA carboxylase activity. Furthermore, SZZ15-11 promotes AMPK activity via [cAMP]i accumulation. CONCLUSION: This study confirmed that SZZ15-11, a novel GPR40 agonist, improves hyperlipidaemia and fatty liver, partially via Gs signalling and the AMPK pathway in hepatocytes.

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study.

BACKGROUND: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. METHODS: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. RESULTS: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. CONCLUSIONS: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

The pharmacokinetics of dabigatran in a rat model of hyperlipidaemia induced by poloxamer 407.

Various pharmacokinetic changes have been reported in experimental hyperlipidemic (HL) animal models. To evaluate whether P-glycoprotein (P-gp) activity was affected in HL rats, we assessed the pharmacokinetics of dabigatran after oral administration of dabigatran etexilate (DABE); this is a dabigatran prodrug and a well-known P-gp substrate.HL and control rats exhibited similar area under the plasma concentration-time curve (AUC), total body clearance (CL), and steady state volume of distribution (Vss) values following intravenous administration of dabigatran (1 mg/kg). This suggested that the distribution and elimination of dabigatran were similar in control and HL rats.The hepatic and intestinal P-gp protein levels did not differ significantly between control and HL rats. The dabigatran AUC and extent of absolute oral bioavailability (F) values were similar in control and HL rats following oral administration of DABE (10 mg/kg as dabigatran). Therefore, there was no apparent change in intestinal P-gp activity in HL rats compared to control rats.This study revealed no significant change in P-gp expression or activity in the intestine or liver of HL rats, and similar pharmacokinetics of dabigatran. Hyperlipidaemia may not directly affect the oral absorption of P-gp substrate drugs.

The chain-mediating effect of Crp, BMI on the relationship between dietary intake of live microbes and hyperlipidaemia.

BACKGROUND: Inflammation and obesity are the risk factors for hyperlipidaemia. Nonetheless, research regarding the association between dietary live microbes intake and hyperlipidaemia is lacking. Therefore, this study focused on revealing the relationship between them and mediating roles of inflammation and obesity. METHODS: Totally 16,677 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) (1999-2010 and 2015-2020). To explore the correlation between live microbes and hyperlipidaemia as well as blood lipid levels, respectively, multiple logistic regression and linear regression were employed. Furthermore, the mediating roles of body mass index (BMI), C-reactive protein (Crp) and their chain effect were explored through mediating analysis. RESULTS: High dietary live microbes intake was the protective factor for hyperlipidaemia. In addition, high dietary live microbes intake exhibited a positive relationship to the high-density lipoprotein cholesterol (HDL-C) among males (ß = 2.52, 95% CI: 1.29, 3.76, P < 0.0001) and females (ß = 2.22, 95% CI: 1.05, 3.38, P < 0.001), but exhibited a negative correlation with triglyceride (TG) levels in males (ß = -7.37, 95% CI: -13.16, -1.59, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) levels in females (ß = -2.75, 95% CI: -5.28, -0.21, P = 0.02). Crp, BMI and their chain effect mediated the relationship between live microbes with HDL-C levels. Moreover, BMI and the chain effect mediated the relationship between live microbes with LDL-C levels. CONCLUSION: Dietary live microbes intake is related to a lower hyperlipidaemia risk. Crp, BMI and their chain effect make a mediating impact on the relationship.

Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study.

BACKGROUND: Surgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia. METHODS: A retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery. RESULTS: Noteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251). CONCLUSIONS: Oesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.

Awareness of having hypertension, diabetes and dyslipidaemia among US adults: The 2011-2018 NHANES data.

AIM: This study aimed to investigate awareness of having hypertension, diabetes and dyslipidaemia and their associated factors among US adults. METHODS: Data from the National Health and Nutrition Examination Survey, including 21,399 adults aged ⩾20 years (pregnant women excluded) collected between 2011 and 2018, were used. Blood pressure was measured using a Baumanometer calibrated mercury true gravity wall model sphygmomanometer. Serum total cholesterol levels were measured using enzymatic assays. The percentage of haemoglobin A1C (HbA1c), which reflects long-term blood glucose levels, was measured and used to identify diabetes. Participants self-reported whether they were told by a doctor that they have hypertension, dyslipidaemia and diabetes. Awareness was defined as alignment between objective and self-reported measures for having the conditions. Sampling weights and the Taylor series linearisation variance estimation method were used in the analyses. RESULTS: The findings showed that 64.06% of people with hypertension, 54.71% of those with dyslipidaemia and 78.40% of those with diabetes were aware of having the respective condition. Age, sex and health insurance were associated with awareness of having all three conditions, but marital status was not associated with any outcome. Weight status was associated with awareness of having hypertension and dyslipidaemia, whereas ethnicity was associated with awareness of having hypertension and diabetes. Relative family income was only associated with awareness of having hypertension. CONCLUSIONS: Large proportions of US adults with hypertension, dyslipidaemia and diabetes are not aware of having the conditions. Interventions targeting groups at higher risk of being unaware of these conditions are needed.

Analytical method development and validation for simultaneous estimation of Bempedoic acid and Ezetimibe in pure and its pharmaceutical dosage form by RP-HPLC.

A simple, accurate and precise method was developed for the simultaneous estimation of the bempedoic acid and ezetimibe in pure and tablet dosage form. The developed method was validated as per International Conference on Harmonization guidelines. The chromatographic separation was achieved isocratically on a Waters- C18, 250 × 4.6 mm, 5 µm column. Mobile phase containing K2HPO4-methanol in the ratio 60:40 in buffer at pH 4.3 was pumped through column at a flow rate of 1.0 ml/min. The temperature was maintained at 25°C. The optimized wavelength selected was 242 nm. The separation of bempedoic acid and ezetimibe showed retention times of 3.090 and 4.268 min respectively. The RSD values of the bempedoic acid and ezetimibe were 0.34 and 0.08 respectively. The accuracy of method was determined at three levels (50,100 and 150%). The percentage recovery was obtained as 100.0 and 100.0% for bempedoic acid and ezetimibe, respectively. The limits of determination and quantitation obtained from regression equations of bempedoic acid and ezetimibe were 1.065, 3.550 and 0.203, 0.677, respectively. The regression equation of bempedoic acid is y = 20,795x + 24,168, and it is y = 6,885.7x + 11,000 for ezetimibe. The retention times were decreased and the run time was decreased, so that the method developed is simple and economical that can be adopted for regular quality control tests in industry.

Association between Dyslipidaemia and Cognitive Impairment: A Meta-Analysis of Cohort and Case-Control Studies.

BACKGROUND: This study explored the specific relationship between different lipid indicators and cognitive impairment and aimed to provide a reference for implementing targeted lipid regulation measures to prevent and alleviate cognitive impairment. METHODS: We searched three databases (PubMed, Embase, and Web of Science) for literature related to hyperlipidaemia, lipid levels, and cognitive impairment, and used the Newcastle-Ottawa Scale to evaluate the quality of the identified literature. A meta-analysis was performed using RevMan 5.4, and the combined effect size ratio using a random-effects model (odds ratio [OR] and 95% confidence interval [CI]) was used to evaluate the association between dyslipidaemia and cognitive impairment. RESULTS: Among initially identified 2247 papers, we ultimately included 18 studies involving a total of 758,074 patients. The results of the meta-analysis revealed that patients with hyperlipidaemia had a 1.23-fold higher risk of cognitive impairment than those with normal lipid levels (OR = 1.23, 95% CI: 1.04-1.47, p = 0.02). Further subgroup analysis showed that elevated total cholesterol (TC) levels increased the risk of cognitive impairment by 1.59-fold (OR = 1.59, 95% CI: 1.27-2.01, p < 0.0001) and were more significant in older or male patients. Moreover, elevated triglyceride levels were inversely correlated with cognitive disorders, whereas elevated low-density lipoprotein cholesterol levels were unrelated to cognitive impairment risk. CONCLUSIONS: Dyslipidaemia was strongly associated with cognitive impairment, and elevated TC levels were a risk factor for cognitive impairment. Furthermore, the damaging effects of elevated TC levels on cognition were more pronounced in older and male populations.

Dyslipidaemia is associated with Cutibacterium acnes hip and knee prosthetic joint infection.

PURPOSE: Optimization of medical factors including diabetes and obesity is a cornerstone in the prevention of prosthetic joint infection (PJI). Dyslipidaemia is another component of metabolic syndrome which has not been thoroughly investigated as an individual, modifiable risk factor. This study examined the association of dyslipidaemia with PJI caused by the lipophilic microbe Cutibacterium acnes (C. acnes). METHODS: A retrospective chart review examined patients with positive C. acnes culture at hip or knee arthroplasty explantation. A control group with methicillin-sensitive Staphylococcus aureus (MSSA) positive cultures at explantation was matched for age, sex, and surgical site, as well as a second control group with no infection. A total of 80 patients were included, 16 with C. acnes, 32 with MSSA, and 32 with no infection. All patients had a lipid panel performed within one year of surgery. Lipid values and categories were compared using multinomial logistic regressions. RESULTS: High or borderline triglycerides (TG) (relative risk ratio (RRR) = 0.13; P = 0.013) and low high-density lipoprotein (HDL) (RRR = 0.13; P = 0.025) were significantly associated with C. acnes PJI compared to MSSA-PJI. High or borderline TG (RRR = 0.21; P = 0.041) and low HDL (RRR = 0.17; P = 0.043) were also associated with a greater probability of C. acnes infection compared to no infection. CONCLUSIONS: The presence of elevated TG and low HDL were both associated at a statistically significant level with C. acnes hip or knee PJI compared to controls with either MSSA PJI or no infection. This may represent a specific risk factor for C. acnes PJI that is modifiable.

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

BACKGROUND: Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. METHODS: This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. RESULTS: In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia. CONCLUSION: The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

The association of garlic intake and cardiovascular risk factors: A systematic review and meta-analysis.

Garlic is a common cooking ingredient and used in traditional medicine in Asian countries. There is a growing attention on garlic due to its preventive characteristics in cardiovascular diseases (CVDs). Many studies have reviewed the association between garlic intake and CVDs; however, no consistent conclusions have been drawn. New clinical trials have also been conducted and could contribute to more solid statements. In order to systematically review the reliability of previous studies regarding the implication of garlic in the management of CVDs, we performed in-depth meta-analysis using the most up-to-date randomized clinical trials (RCTs) data with more systematic controls. According to the 22 studies included, the effects of garlic intake on lowering total cholesterol (TC) and low-density lipoprotein (LDL) are more noticeable with lower dosage and longer duration, especially in patients with CVDs. In addition, subgroup analysis indicated that appropriate diet intervention could be an important control factor that should be taken into consideration in any future study designs.

Terminalia catappa attenuates phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

AIM: This study investigated the haematinic, antihyperlipidaemic, hepato-renal protective effects of Terminalia catappa aqueous leaf extract on male Wistar rats exposed to phenylhydrazine toxicity. METHODS: Animals were exposed to phenylhydrazine (PHZ) 50 mg/kg intraperitoneal for two consecutive days thereafter, treated with T. catappa extract (100 mg/kg and 200 mg/kg) orally for 21 days. After the experimentation, animals were sedated with ketamine (70 mg/kg) and euthanized by cervical dislodgement. Blood and organs were collected for haematology and biochemical studies following standard laboratory methods. RESULTS: Our study showed that T. catappa significantly increased erythrocytes, haemoglobin, haematocrit and high density lipoprotein as well as down-regulating leukocytes, thrombocytes, ALP AST, ALT creatinine, urea, total cholesterol as well as low density lipoprotein. The liver, kidney and spleen antioxidant defence were also up-regulated against the adverse effect caused by phenylhydrazine exposure. CONCLUSION: Terminalia catappa attenuated Phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

Duyun compound green tea extracts regulate bile acid metabolism on mice induced by high-fat diet.

Duyun compound green tea (DCGT) is a healthy beverage with lipid-lowering effect commonly consumed by local people, but its mechanism is not very clear. We evaluated the effect of DCGT treatment on bile acids (BA) metabolism of mice with high-fat diet (HFD) - induced hyperlipidaemia by biochemical indexes and metabolomics and preliminarily determined the potential biomarkers and metabolic pathways of hyperlipidaemia mice treated with DCGT as well as investigated its lipid-lowering mechanism. The results showed that DCGT treatment could reduce HFD - induced gain in weight and improve dyslipidaemia. In addition, a total of ten types of BA were detected, of which seven changed BA metabolites were observed in HFD group mice. After DCGT treatment, glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic acid were significantly down-regulated, while hyodeoxycholic acid, deoxycholic acid and chenodeoxycholic acid were markedly up-regulated. These results demonstrated that DCGT treatment was able to make the BA metabolites in the liver of hyperlipidaemia mice normal and alleviate hyperlipidaemia by regulating the metabolites such as glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic, as well as the BA metabolic pathway and cholesterol metabolic pathway involved.

Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats.

Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.Cmax, tmax, and AUC0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t1/2, AUC0-t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology.In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.

Correlation between dietary inflammation and mortality among hyperlipidemics.

BACKGROUND AND OBJECTIVE: Although the the Dietary Inflammatory Index (DII) serves to be one of the reliable indicator for hyperlipidaemia, there is still uncertainty about its relationship to prognosis in the hyperlipidaemic population. In current study, the DII levels were analyzed in relation to the mortality risk among among the hyperlipidaemic individuals with the aim of determining any prospective correlation. METHODS: 14,460 subjects with hyperlipidaemia from the 10-year (2001-2010) National Health and Nutrition Examination Survey (NHANES) were chosen for this study. The endpoint event for follow-up was all-cause mortality, and subjects were tracked for up to December 31, 2019, or death, whichever occurred first. The tertiles of the DII levels were utilized for categorizing the study population into three groups. Survival curves, Cox proportional hazards regression models, restricted cubic spline (RCS), subgroup and interaction analyses, and sensitivity analyses were employed sequentially for the purpose of evaluating the association of the DII with mortality. RESULTS: 3170 (21.92%) all-cause deaths were recorded during an average 148-month follow-up period. Kaplan-Meier survival curves indicated that the survival rate of participants divided into the low DII group was substantially improved compared to that of those in the higher DII group (log-rank P < 0.001). After controlling for confounders, higher levels of DII were observed to be meaningfully linked to an elevated risk of death, no matter whether DII was specified for the continuous (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.04-1.08) or the categorical variable (HR: 1.22; 95% CI: 1.11-1.33). The DII and mortality displayed a linear association, according to the RCS. Stratified and sensitivity analyses reinforced the proof that these findings were reliable. CONCLUSION: Among patients with hyperlipidaemia, the risk of death was positively and linearly linked with DII levels.

Prevalence and clinical risk prediction of hypertriglyceridaemia in a community cohort.

BACKGROUND: Hypertriglyceridaemia (HTG; defined as ≥1.7 mmol/L) has a prevalence of 18-33% with significant inter-regional variation. Despite meta-analysis demonstrating its association with increased risk of cardiovascular disease, only 40% of HTG is identified in the community resulting in underutilisation of lipid-lowering therapy and specialist clinics. An increase in awareness of its clinical risk factors is needed to improve the identification and management of HTG to prevent cardiovascular risk. AIMS: To evaluate the prevalence, distribution and clinical predictors of HTG ≥1.7 mmol/L in a representative community group. METHODS: Data were obtained from the Hunter Community Study (HCS), a longitudinal cohort of community-dwelling men and women aged 55-85 years residing in Newcastle, New South Wales. Fasting triglycerides were identified based on the availability of fasting blood glucose level and categorised according to normal (<1.7 mmol/L), mild (1.7 to <2.3 mmol/L) and moderate-severe HTG (≥2.3 mmol/L). Clinical predictors of HTG were assessed using linear and logistic regression models. RESULTS: Of 2536 triglyceride levels, 2216 (87%) were in a fasting state and included in the study. Three hundred and two (13.6%) participants had mild HTG and 221 (10.0%) participants had moderate-severe HTG. Significant clinical predictors of HTG included male gender, increasing body mass index, current smoking, decreasing daily step counts, increasing fasting glucose and higher thyroid-stimulating hormone. Alcohol intake and blood pressure were not significant in either adjusted regression model. CONCLUSIONS: HTG ≥1.7 mmol/L is common, affecting 24% of the HCS. Clinical predictors identify modifiable risk factors for cardiovascular risk management. Clinician education to promote awareness is required to improve patient outcomes.

Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidaemic rat.

AIM: The aim of the study was to explore the involvement of oxidative stress (OS) in the hepatic inflammation induced by apical periodontitis (AP). Periapical, systemic and hepatic reaction to AP under hyperlipidaemia was also investigated. METHODOLOGY: A total of 16 male Sprague-Dawley rats were fed with a hyperlipidaemic diet (HD) whereas another 16 rats with a normal diet (ND). After 9 weeks, the first molars of the right maxilla and mandible of 8 HD and 8 ND rats were exposed to induce AP (ND, ND + AP, HD and HD + AP group). After 5 weeks, rats were euthanized, the haematological tissue was collected directly from the heart, and serum levels of inflammatory cytokines were measured. Liver tissue was analysed by haematoxylin-eosin and Masson staining, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect mRNA expression of inflammatory cytokines. Serum, periapical, and hepatic OS parameters including total oxidant status (TOS), total antioxidant capacity (TAOC) and oxidative stress index (OSI) were measured by enzyme-linked immunosorbent assay (ELISA). The area of AP lesion in the right maxilla or mandible was radiographically assessed. Student's t-test was performed on the periapical data. A one-way analysis of variance and the Kruskal-Wallis test were analysed for others. RESULTS: The HD + AP group had a larger AP lesion in the maxilla, compared with the ND + AP group (p < .05). The ND + AP group presented higher serum interleukin (IL)-18, IL-1ß, TOS, OSI levels, lower serum TOAC levels, higher hepatic tumour necrosis factor (TNF)-α mRNA expression and higher hepatic TOS, and OSI levels, compared with the ND group (p < .05). The HD + AP group had lower serum IL-4 level, higher serum IL-1ß level, and higher hepatic IL-6 and transforming growth factor (TGF) -ß1 mRNA expression, compared with the HD group (p < .05). CONCLUSIONS: Apical periodontitis could activate systemic and liver inflammation by promoting serum IL-18, 1L-1ß, TOS and OSI expression, enhancing hepatic TOS and OSI expression and inhibiting serum TOAC expression. AP under hyperlipidaemia led to more profound periapical bone destruction in the maxilla and elicit systemic and liver inflammatory responses through elevating serum levels of IL-1ß, descending serum IL-4 level and improving hepatic IL-6 and TGF-ß1 expression.