This study analyzed safety data for Atorvastatin Calcium Hydrate (ACH) using real‑world adverse event reports from the U.S. FDA Adverse Event Reporting System (FAERS, 2004-2024) and the European Medicines Agency's EudraVigilance (EV, 2002-2024). A total of 104,798 ACH‑related reports were included: 67,498 from FAERS and 37,300 from EV. Four signal detection algorithms (ROR, PRR, BCPNN, MGPS) identified 597 significant positive signals, 356 in FAERS and 241 in EV, covering 27 system organ classes. FAERS signals mainly involved metabolic, cardiac, and nervous system disorders, while EV was dominated by examination abnormalities (66 signals, 27.39%) and musculoskeletal disorders (29 signals, 12.03%). Rhabdomyolysis and drug‑induced liver injury were major designated medical events in both databases. EV also identified liver failure, hepatocellular injury, and death (1,833 cases, 4.91%) as key serious outcomes. Stratified analyses showed elderly patients in FAERS had higher risks of type 2 diabetes and emotional distress. In EV, patients aged ≥65 years accounted for 34.12%, females 49.83% versus males 37.21%, and severe cases reached 94.50%. The study recommends close clinical monitoring for rhabdomyolysis, liver injury, and fatal outcomes, with special attention to liver function and muscle symptoms in elderly, diabetic, emotionally distressed, and female patients.

Cervical cancer treatment is often hindered by the emergence of cisplatin (DDP) resistance. Increasing evidence has indicated that statins possess anti-tumor and chemosensitization potential beyond their lipid-lowering effects. Statin utilization is found to be significantly linked to decreased cervical cancer incidence and mortality. However, whether statins affect chemosensitivity to cisplatin in cisplatin-resistant cervical cancer remains to be clarified. In cervical cancer cisplatin-resistant cell lines (SiHa-DDP and C33a-DDP) constructed from their parental cells, the effects of seven statins (simvastatin, fluvastatin, pitavastatin, lovastatin, atorvastatin, rosuvastatin, and pravastatin) on cell viability in cisplatin-resistant cells and corresponding parental cells were assessed using the CCK-8 assay. Compared with parental counterparts, the IC50 values of seven statin drugs were markedly elevated in cells exhibiting cisplatin resistance. Simvastatin significantly enhanced the efficacy of cisplatin in cisplatin-resistant cervical cancer cells, demonstrating a synergistic anti-cancer effect (CI < 1). Combined therapy using simvastatin and cisplatin inhibited cell viability and migration while promoting cell apoptosis. Mechanistically, simvastatin downregulated protein expressions of caveolin-1 (CAV1), PI3K, and p-AKT. CAV1 knockdown in SiHa-DDP and C33a-DDP cells markedly increased cisplatin sensitivity, confirming its critical role in chemoresistance. Rescue experiments showed that CAV1 overexpression partially counteracted the inhibitory effects of simvastatin. In vivo, compared with monotherapies, simvastatin combined with cisplatin treatment markedly suppressed tumor growth, reduced CAV1 protein expression, decreased the percentage of Ki67-positive cells and promoted apoptosis. In all, simvastatin enhanced cisplatin sensitivity by suppressing the CAV1-mediated PI3K/AKT pathway involvement in the development of cisplatin resistance in cervical cancer cells. These findings reveal a novel mechanism in cervical cancer cells resistant to cisplatin by which simvastatin may serve as a potential adjuvant to improve the therapeutic efficacy of cisplatin-based chemotherapy.

Syzygium brachythyrsum (SB) is an ethnic herb widely used by the Dai ethnic minority in Yunnan province of China. Our previous studies have shown that the polyphenol extract of SB (PSB) exhibits antioxidant and anti-inflammatory effects, and inhibits the formation of macrophage-derived foam cells by reducing lipid uptake and inflammation, suppressing reactive oxygen species (ROS), and downregulating the NF-κB and MAPK signaling pathways. This study aims to investigate the effects of PSB on suppressing atherosclerosis in vivo and to explore the underlying mechanisms.A high-fat diet was used to induce the development of atherosclerosis in ApoE-/- mice for 12 weeks. Mice were treated with three doses of PSB and atorvastatin. Morphological characteristics of aorta bulk, aortic root and liver were examined using Oil Red O and H&E staining. ELISA, immunofluorescence and fluorescence staining were used to assess lipid level, pro-inflammatory cytokines, oxidative indexes, ROS levels and CD36 protein expression in the aortic root. In vitro, an ox-LDL-induced THP-1 macrophage-derived foam cell model was established. ROS fluorescence and Western blot analyses were performed to investigate the involvement of the ROS/Keap1/Nrf2 signaling pathway, with or without the Nrf2 inhibitor ML385. The Results suggested that PSB significantly reduced lipid plaques in the aorta, and hepatic lipid accumulation. PSB also improved serum and hepatic lipid profiles and inflammatory levels, alleviated oxidative stress and reduced CD36 expression in vivo. Furthermore PSB inhibited ox-LDL induced foam cell formation, alleviated the stimulation of oxidative stress in THP-1 foam cells by activating the ROS/Keap1/Nrf2 signaling pathway. These effects were blocked by the Nrf2 inhibitor ML385.For the first time, our study revealed the anti-atherosclerotic effects of polyphenol extract of S. brachythyrsum. It offers insight into the potential mechanism by which PSB mitigates the early onset of AS via ROS/Keap1/Nrf2 pathway. In summary, the current study suggests that PSB, as a complementary therapy, may have a beneficial effects on cardiovascular diseases and deserves further investigation.

Macrophage polarization correlates strongly with the progression and prognosis of spinal cord injury (SCI), yet the therapeutic potential of macrophage polarization-related genes (MPRGs) in SCI remains unexplored. This study identified hub genes associated with MPRGs for SCI diagnosis, prognosis, and therapy. Differentially expressed genes (DEGs) between SCI and control groups were intersected with MPRGs to identify six differentially expressed MPRGs (DE-MPRGs). Machine learning algorithms, including LASSO, RF, and XGBoost, selected three hub genes (Soat1, Comt, and Myo1f) with elevated expression in SCI samples. Functional enrichment analysis indicated involvement in immune-related pathways. Immune infiltration analysis revealed differences in 11 immune gene sets between SCI and controls, all positively correlated with the hub genes. In silico drug prediction identified 37 small molecules, including dexamethasone and atorvastatin, as potential modulators of macrophage polarization in SCI. Single-cell RNA sequencing showed significantly higher expression of all hub genes in M2 than in M1 macrophages. RT-qPCR validation confirmed upregulation of the hub genes in SCI models. These results highlight Soat1, Comt, and Myo1f as novel hub genes in SCI, offering insights into macrophage polarization mechanisms and potential therapeutic targets.

Introduction: Oxidative stress and inflammation are major factors linked to obesity and metabolic dysfunction, leading to a significantly higher risk of related diseases. Atorvastatin and liraglutide possess lipid-lowering, antioxidant, and anti-inflammatory effects that could synergistically improve obesity-related perturbations through modulation of the Nrf2/HO-1 signaling pathway. Methodology: We assessed liraglutide's pharmacological potential in extending atorvastatin's benefit on obesity, hyperlipidemia, and fatty liver in rats fed a high-fat diet (HFD) for 12 weeks. We specifically evaluated the effects of liraglutide treatment on atorvastatin-induced anti-inflammatory and antioxidant mechanisms, with a particular focus on Nrf2/HO 1 modulation in adipose and hepatic tissue. In silico analyses, including molecular docking and AlphaFold- Multimer modeling, evaluated the binding affinities of atorvastatin and liraglutide to Nrf2 and HO 1. Results: Compared to ND, the HFD-fed rats had a significantly higher final body weight (362.4 ± 12.7 g vs. 245.6 ± 9.8 g in ND, p < 0.05). There was a marked increase in serum total cholesterol (178.6 ± 9.2 mg/dL vs. 98.3 ± 6.4), fasting glucose (340.1 ± 8.2 mg/dL vs. 82.3 ± 3.1), HbA1c (7.8 ± 0.3 vs. 4.5 ± 0.2), and hepatic COX-2 expression (99.9 ± 6.3 vs 19.6 ± 2.4). The oxidative stress markers were also disturbed, as indicated by SOD (42.5 ± 3.1 vs. 95.2 ± 4.6 U/mg protein), GSH (18.3 ± 1.5 vs. 42.7 ± 2.8 nmol/mg), and p62 (0.005 ± 0.001 vs. 0.125 ± 0.01). Atorvastatin lowered cholesterol (121.2 ± 7.5 mg/dL), COX-2 (61.3 ± 3.3), and body weight (301.7 ± 11.5 g) compared to HFD. Meanwhile, liraglutide caused a greater reduction in body weight (268.5 ± 10.3 g), glucose (112.5 ± 6.7 mg/dL), and COX-2 (42.2 ± 2.9) than atorvastatin. The combination therapy produced the most significant effects, returning body weight (253.6 ± 9.1 g) to baseline, normalizing glucose and lipids, reducing COX-2 to 22.9 ± 2.0, and reactivating the Nrf2/HO-1 pathway, as shown by increased HO-1 expression and the restoration of p62 levels (0.078 ± 0.004). In silico analyses suggest that atorvastatin favorably binds to Nrf2 and HO-1, while liraglutide interacts with structurally relevant interfaces on these proteins, providing a mechanistic basis for their complementary antioxidant and cytoprotective effects. Conclusions: Our findings support targeting the Nrf2/HO-1 signaling pathway as a potential therapy for reversing hyperlipidemia and preventing mediators of inflammation and oxidative stress damage in the liver tissue. The evidence of increased efficacy observed with the combined atorvastatin and liraglutide supports a potential novel understanding of the complementary effects of atorvastatin and liraglutide. This finding requires further investigation to elucidate the combination's therapeutic advantages in treating metabolic disorder scenarios.

Background: The optimal timing of adjuvant chemotherapy after cytoreductive surgery in epithelial ovarian cancer remains uncertain, and perioperative wound-healing responses may transiently create a pro-tumorigenic and drug-resistant microenvironment. This study aimed to characterize time-dependent wound-induced transcriptomic alterations and to identify pharmacologic agents capable of reversing these responses. Methods: An ID8 murine ovarian cancer model was used to compare no treatment, anesthesia alone, and anesthesia plus surgical wounding mimicking futile laparotomy. Tumors were collected at baseline, 1 day (T1), 1 week (T2), and 2 weeks (T3) after intervention. RNA sequencing was performed, and wound-specific differentially expressed genes (WsDEGs) were defined by excluding anesthesia- and progression-related signatures. Functional enrichment analyses were conducted, followed by transcriptome-based drug repurposing using the REMEDY platform to identify compounds predicted to reverse wound-induced gene expression profiles. Results: Surgical wounding significantly increased tumor burden at T1. Transcriptomic analyses revealed distinct, time-dependent wound-associated programs. At T1, WsDEGs were enriched in inflammatory signaling, coagulation, angiogenesis, and immune cell migration, with Vorinostat and Homoharringtonine identified as top candidates to counteract these signatures. At T2, pathways related to cell survival, adhesion, and morphogenesis predominated, with LY-2090314, Artesunate, and Birinapant emerging as potential modulators. At T3, cell-cycle regulation and lipid metabolic pathways were dominant, and Fulvestrant, Atorvastatin, Imatinib, and ABT-737 were predicted to inhibit these processes. Conclusions: Perioperative surgical wounding induces dynamic, stage-specific transcriptomic programs that may promote ovarian cancer progression and alter drug responsiveness. These findings support time-adapted perioperative pharmacologic strategies to optimize postoperative cancer therapy.

Background/Objective: Immunoglobulin G (IgG) N-glycosylation is an important regulator of immune function and systemic inflammation and has been associated with cardiometabolic diseases. However, little is known about how IgG glycosylation changes during the course of acute coronary syndrome (ACS) and whether these alterations relate to lipid-lowering response after the initiation of statin therapy. The primary aim of this study was to investigate IgG N-glycosylation following ACS and evaluate its association with response to atorvastatin therapy defined as baseline LDL cholesterol reduction of ≥50%. Methods: In this prospective cohort study, 79 statin-naïve patients hospitalized for the first episode of ACS and treated with atorvastatin 80 mg daily after percutaneous coronary intervention were followed longitudinally. Plasma samples were collected at admission (acute phase), discharge (subacute phase), and follow-up (chronic phase). A control group of 21 individuals received atorvastatin for primary prevention. IgG was isolated from plasma, and N-glycans were released, fluorescently labeled with 2-aminobenzamide, and analyzed using hydrophilic interaction-based ultra-high-performance liquid chromatography with fluorescence detection. Derived glycan traits were calculated, including agalactosylated (G0), monogalactosylated (G1), digalactosylated (G2), core fucosylated (F), bisected (B), and sialylated (S) glycans. Results: No significant differences in derived IgG glycan traits were observed between ACS patients and controls at baseline or follow-up. Within the ACS group, a longitudinal analysis revealed significant increases in G0 and F and a decrease in G2 between the acute and chronic phases. A total of 65% of patients achieved ≥50% reduction in LDL cholesterol (LDL-C), whereas only 22% reached the guideline-recommended LDL-C target of <1.4 mmol/L. Patients achieving ≥50% LDL-C reduction exhibited consistently higher G0 and lower G2 and S across disease phases. In a subgroup of patients with baseline LDL-C >3.9 mmol/L, those who failed to achieve ≥50% LDL-C reduction had significantly lower G0 and higher S across all time points. Conclusions: Specific glycan traits are associated with the degree of LDL-C reduction achieved during statin therapy, particularly in patients with high baseline LDL-C. These findings suggest that IgG glycosylation patterns may reflect biological phenotypes associated with differential lipid-lowering responsiveness after ACS.

Chemotherapy- and/or radiotherapy-induced oral mucositis (CRIOM) is a common complication in patients with head and neck cancer, driven largely by excessive proinflammatory cytokine signalling and treatment-associated bacterial dysbiosis. This narrative review synthesizes current mechanistic evidence and summarizes emerging therapeutic strategies targeting these pathways. Research indicates that elevated levels of IL-1β, IL-6, TNF, iNOS, and nitric oxide amplify tissue injury and ulceration, while disruption of oral and gut microbial communities, characterized by loss of beneficial commensals and enrichment of pathogenic taxa, further exacerbates mucosal inflammation. Anti-inflammatory agents, including pentoxifylline, atorvastatin, trans-caryophyllene, azilsartan, recombinant human IL-11, and low-level laser therapy have been shown in preclinical models to reduce cytokine levels and promote mucosal healing. Similarly, microbiome-targeted approaches, such as oral microbiota transplantation and multi-strain probiotic formulations, have demonstrated potential in restoring microbial balance and attenuating CRIOM severity, with current evidence including both preclinical and clinical studies. Overall, current findings highlight cytokine toxicity and dysbiosis as synergistic drivers of CRIOM and support anti-inflammatory and microbiome-modulating strategies as promising adjunctive approaches; however, further well-designed clinical studies are required to validate their efficacy and guide clinical translation.

Terminalia chebula fruit is a medicinal plant high in bioactive compounds that have potential therapeutic benefits. The current study targeted to determine the phytochemical profiles and hypolipidemic effects of aqueous and methanol-based extracts of Terminalia chebula fruits in high-fat diets that made hyperlipidemic Wistar rats. According to qualitative phytochemical examination, the aqueous extract contained phenols, flavonoids, tannins and saponins, whereas the methanol extract contained alkaloids, tannins, and flavonoids, Induction of hyperlipidemia significantly raised total serum cholesterol, triglycerides, LDL, and VLDL levels in the group with high-fat diet when compared to the normal control. Treatment with the methanol extract of Terminalia chebula (200 mg/kg) resulted in significant decreases (P<0.05) in blood total cholesterol (26.6%), triglycerides (17.3%), LDL cholesterol (43.8%), and VLDL cholesterol (17.3%) compared to hyperlipidemic control group. Similarly, the aqueous extract significantly decreased total cholesterol (15.8%), triglycerides (12.8%), LDL cholesterol (28.2%), and VLDL cholesterol (12.8%) (P<0.05). Atorvastatin treatment resulted in a significant improvement in lipid parameters and acted as a positive control. No substantial increase in HDL cholesterol levels was seen in the extract-treated groups. In conclusion, Terminalia chebula fruit extracts had considerable hypolipidemic action, with the methanol extract exceeding the aqueous extract. These effects could be attributable to the presence of polyphenols and flavonoids, which supports Terminalia chebula's potential use as a natural treatment for hyperlipidemia control.