atorvastatin strontium (Newvast)

Novel zirconium-based supramolecular organic frameworks/fullerene@strontium-based MOFs composite for highly sensitive electrochemical sensing of ciprofloxacin.

Xie Yu Y, Jiao Hui H, Meng Jingwen J, Liu Lijun L et al.

A novel ternary composite of zirconium-based supramolecular organic framework/fullerene@strontium-based metal-organic framework (Zr-SOF/C60@Sr-MOF) was synthesized and adopted as an electrode modifier to construct a high-sensitivity electrochemical sensor for ciprofloxacin (CIP) determination. The composition and morphology of the material were confirmed by SEM, TEM, XPS, XRD and FT-IR. Cyclic Voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to evaluate the electron-transfer properties and interfacial behavior of the modified electrodes, and square wave voltammetry (SWV) was employed for the sensitive and quantitative detection of the target analyte. The results reveal that the composite inherits the abundant porous structure of Zr-SOF, the expansive specific surface area of Sr-MOF and excellent electron transfer capability of fullerene. The sensor enables accurate CIP detection in the linear range 5.0 nM-1000 µM, with a detection limit of 7.0 nM (S/N = 3), along with satisfactory selectivity, reproducibility and long-term stability. Practical application was validated in lake water, tap water and milk samples, yielding recoveries of 95.3%-101.63%. This work provides new insights into SOF/MOF-based electrochemical sensing and establishes an efficient strategy for rapid on-site detection of CIP antibiotics in environmental and food matrices.

Pharmacogenomic landscape in Thailand: Array-based profiling and EMR-linked medication exposure.

Pasookhush Phongthana P, Suta Sophida S, Pumeiam Sureeporn S, Mongkolsucharitkul Pichanun P et al.

Pharmacogenomic (PGx) data in Thailand remain limited, and genetics-only surveys rarely quantify "realized actionability"-the overlap between actionable PGx phenotypes and real-world medication exposure. We profiled 4,662 Thai adults using SNP-array data and a pre-specified PGx panel (11 genes; 26 markers) with a hybrid required/optional calling policy for diplotype/phenotype assignment. CPIC level A/B gene-drug relationships were linked to hospital electronic medical record (EMR) prescription/dispensation data to quantify drug-specific realized actionability. Overall callability across gene-results was 98.62%, exceeding 99% for most genes and lower for CYP2C19 (95.99%) and NUDT15 (90.28%). Across nine phenotype-coded genes, 95.99% carried ≥1 CPIC-actionable result (median 2; IQR 2-3). Actionable prevalence among callable individuals was highest for CYP3A5 (58.54%) and CYP2C19 (56.67%), followed by ABCG2 (45.10%) and UGT1A1 (27.37%). EMR linkage identified 1,529 (32.58%) participants exposed to ≥1 study medication; omeprazole (n = 658) and statins were most common (atorvastatin n = 606; simvastatin n = 603). Among users, actionable phenotypes were frequent for CYP2C19-omeprazole (55.02%) and SLCO1B1-statins (21.95-23.05%). In conclusion, an Asian-optimized SNP array supports scalable PGx phenotyping in Thai adults. EMR linkage quantifies realized actionability and highlights high-yield targets (CYP2C19-proton pump inhibitors; SLCO1B1-statins) for pre-emptive implementation.

[Mechanism study of Zhizi Dahuang Decoction in treating atherosclerosis based on network pharmacology, molecular docking, and experimental validation].

Ruan Li-Hua LH, Xu Yi-Jia YJ, He Yao Y, Li Jin-Tao JT et al.

This paper investigated the effects and mechanisms of Zhizi Dahuang Decoction(ZZDHT) in treating atherosclerosis(AS) through a comprehensive approach combining network pharmacology, molecular docking, and in vivo experiments. Active components and target sites of ZZDHT were identified and screened using TCMSP, SwissTargetPrediction, and SEA databases. AS-related target sites were obtained from GeneCards, OMIM, and TTD databases. Network pharmacology was employed to predict the core chemical constituents, core target sites, and potential mechanisms of ZZDHT in treating AS. Molecular docking was employed to evaluate their binding activity between the core components and targets. Core chemical components identified in ZZDHT included quercetin,(+)-dehydrodiconiferyl alcohol, luteolin, and 3',4',5,7-tetramethoxyflavone. KEGG enrichment pathways primarily encompass core targets such as Toll-like receptor 4(TLR4), nuclear factor-κB(NF-κB), interleukin(IL)-6, IL-1β, and tumor necrosis factor(TNF). Molecular docking revealeda strong affinity between the core chemical components and these core targets. Forty male apolipoprotein E knockout(ApoE~(-/-)) mice were randomly assigned to a model group(MOD), low-dose ZZDHT group(ZZDH-L, 2.21 g·kg~(-1)), medium-dose ZZDHT group(ZZDH-M, 4.42 g·kg~(-1)), high-dose ZZDHT group(ZZDH-H, 8.84 g·kg~(-1)), and atorvastatin calcium group(ATO, 0.01 g·kg~(-1)). Additionally, C57BL/6J male mice served as the control group(CON), with 8 mice per group. CON was fed a normal diet, while the other groups were fed a high-fat diet to build an AS mouse model. All groups received corresponding drugs via oral gavage, and the CON and MOD administered an equal volume of 0.9% sodium chloride solution for 8 consecutive weeks. Experimental results showed that compared with MOD, ZZDHT intervention significantly inhibited aortic plaque formation in ApoE~(-/-) mice, reduced inflammatory infiltration at plaque sites, downregulated serum IL-6, IL-1β, and TNF-α levels while increasing IL-10 levels, thereby reshaping inflammatory homeostasis. Simultaneously, it regulated blood lipids by lowering serum total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) levels and increasing high-density lipoprotein cholesterol(HDL-C). qRT-PCR and Western blot confirmed that after treatment, the mRNA content of inducible nitric oxide synthase(iNOS) in aortic tissue decreased significantly, and the mRNA and protein expression of TLR4, myeloid differentiation primary response gene 88(MyD88), and NF-κB were all significantly reduced. Based on network pharmacology and experimental validation, ZZDHT may exert therapeutic effects on AS by modulating the TLR4/NF-κB signaling pathway to inhibit inflammatory responses, regulate blood lipids, reduce plaque lipid deposition, and enhance plaque stability.

Case Report - Anti-HMGCR-Associated Immune-Mediated Necrotizing Myopathy and Interstitial Lung Disease With Long-Term Use of Ezetimibe and Low-Dose Atorvastatin.

Finsterer Josef J