BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy.
METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters.
RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline.
CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

OBJECTIVE: For many years, statins have been the most commonly used drugs in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and rosuvastatin at different concentrations on hepatocellular carcinoma (HepG2) cells.
METHODS: The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein diacetate (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay.
RESULTS: The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin.
CONCLUSIONS: The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.

OBJECTIVE: Patients with systemic autoimmune myopathies (SAMs) have high prevalence of dyslipidemia and, consequently, possible endothelial dysfunction and vascular stiffness. Our objective was to evaluate the possible benefits on endothelial function and vascular stiffness, as well as adverse effects of atorvastatin in SAMs.
METHODS: A pilot longitudinal, double-blind, randomized, placebo-controlled study was conducted. Twenty-four of 242 patients were randomized at a 2:1 ratio to receive atorvastatin (20 mg/d) or placebo for a period of 12 weeks. Demographic data, comorbidities, and clinical and laboratory parameters, as well as endothelial function and arterial stiffness, were evaluated.
RESULTS: Of the 24 randomized patients, 4 patients were excluded, with remaining 20 patients (14 in the atorvastatin group and 6 in the placebo group). The mean age of the patients was 49.0 years, and 75% of the patients were female. At baseline, the demographic data, disease status, treatment, cardiovascular comorbidities, and risk factors were comparable between the atorvastatin and placebo groups. After 12 weeks of follow-up of atorvastatin therapy, no improvements were observed for endothelial function and arterial stiffness in either group (p > 0.05). As expected, a significant reduction in total and low-density lipoprotein cholesterol levels was observed. During the study, no clinical intercurrences or disease relapses were observed in either group.
CONCLUSIONS: The atorvastatin drug attenuated low-density lipoprotein cholesterol without worsening clinical outcomes in SAMs. No change was observed for endothelial function and arterial stiffness. Additional studies, with long-term follow-up time and different atorvastatin dosage, are needed to corroborate the results of this study.

Persistent organic pollutants (POPs) are linked with insulin resistance and type-2 diabetes (T2D) in the general population. However, their associations with gestational diabetes (GDM) are inconsistent.
We prospectively evaluated the associations of POPs measured in early pregnancy with GDM risk. We also assessed whether pre-pregnancy BMI (ppBMI) and family history of T2D modify this risk.
In NICHD Fetal Growth Study, Singletons, we measured plasma concentration of 76 POPs, including 11 organochlorine pesticides (OCPs), 9 polybrominated diphenylethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 per-and polyfluoroalkyl substances (PFAS) among 2334 healthy non-obese women at 8-13 weeks of gestation. GDM was diagnosed by Carpenter and Coustan criteria. We constructed chemical networks using a weighted-correlation algorithm and examined the associations of individual chemical and chemical networks with GDM using multivariate Poisson regression with robust variance.
Higher concentrations of PCBs with six or more chlorine atoms were associated with increased risk of GDM in the overall cohort (risk ratios [RRs] range: 1.08-1.13 per 1-standard deviation [SD] increment) and among women with a family history of T2D (RRs range: 1.08-1.48 per 1-SD increment) or normal ppBMI (RRs range: 1.08-1.22 per 1-SD increment). Similar associations were observed for the chemical network comprised of PCBs with ≥6 chlorine atoms and the summary measure of total PCBs and non-dioxin like PCBs (138, 153, 170, 180). Furthermore, four PFAS congeners - perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), and perfluorododecanoic acid (PFDoDA) - showed significant positive associations with GDM among women with a family history of T2D (RRs range:1.22-3.18 per 1-SD increment), whereas BDE47 and BDE153 showed significant positive associations among women without a family history of T2D.
Environmentally relevant levels of heavily chlorinated PCBs and some PFAS and PBDEs were positively associated with GDM with suggestive effect modifications by family history of T2D and body adiposity status.

Ganoderic Acids (GAs) are the major medicinal compounds in Ganoderma lucidum used as traditional Chinese medicine since ancient times. Ganoderic acid A (GAA) is the first discovered ganoderic acids reported in the literature, which is also one of most abundant triterpenoids of Ganoderma lucidum. Especially, GAA has been extensively investigated in recent decades for its positive medicinal activities. However, the vibrational properties of GAs have rarely been studied or reported. In this work, we focused on the typical GAA and studied the infrared (IR) and Raman spectra based on both experiments and DFT calculations. As such, we could not only achieve the assignments of the vibrational modes, but also from the IR and Raman spectra, we found that the spectral region from 1500 cm-1 to 1800 cm-1 is particularly useful for distinguishing different types of GAs. In addition, its dehydrogenated derivative ganoderenic acid A (GOA) was also studied, which could be identified due to its spectral feature of strong IR and Raman bands around 1620 cm-1. This work therefore may facilitate the application of IR and Raman spectroscopies in the inspection and quality control of Ganoderma lucidum.

Wnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation of β-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of β-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrödinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of β-catenin and ganoderic acid A with GScore (-9.44), kcal/mol, lipophilic EvdW (-2.86), electro (-0.72), Glide emodel (-50.401), MM-GBSA (-87.441), H bond (-1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner.

The clinical benefits of statins in dialysis patients are unproven. New follow-up data from the 4D Study indicate no clear reduction in cardiovascular events among patients with type-2 diabetes. Assessing outcomes 7.4 years beyond the randomization period (20 mg atorvastatin versus placebo), no differences in a composite cardiovascular outcome were observed and no safety concerns emerged. Current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not need updating based on these new data.

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OBJECTIVE: This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT).
METHODS: A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n = 16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n = 15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l)/22.5) was calculated.
RESULTS: During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group 1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p < 0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% 16.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p < 0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r = 0.37, p = 0.04) in the entire group of patients (n = 31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r = -0.57, p = 0.034).
CONCLUSIONS: In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.