Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine’s adverse metabolic effects—such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy—was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

Imipramine is a tricyclic antidepressant that has been approved for treating depression and anxiety in patients and animals and that has relatively mild side effects. However, the mechanisms of imipramine-associated disruption to metabolism and negative hepatic, renal, and retinal effects are not well defined. In this study, we evaluated C57BL6/J mice subjected to a high-fat diet (HFD) to study imipramine’s influences on obesity, fatty liver scores, glucose homeostasis, hepatic damage, distribution of chromium, and retinal/renal impairments. Obese mice receiving imipramine treatment had higher body, epididymal fat pad, and liver weights; higher serum triglyceride, aspartate and alanine aminotransferase, creatinine, blood urea nitrogen, renal antioxidant enzyme, and hepatic triglyceride levels; higher daily food efficiency; and higher expression levels of a marker of fatty acid regulation in the liver compared with the controls also fed an HFD. Furthermore, the obese mice that received imipramine treatment exhibited insulin resistance, worse glucose intolerance, decreased glucose transporter 4 expression and Akt phosphorylation levels, and increased chromium loss through urine. In addition, the treatment group exhibited considerably greater liver damage and higher fatty liver scores, paralleling the increases in patatin-like phospholipid domain containing protein 3 and the mRNA levels of sterol regulatory element-binding protein 1 and fatty acid-binding protein 4. Retinal injury worsened in imipramine-treated mice; decreases in retinal cell layer organization and retinal thickness and increases in nuclear factor κB and inducible nitric oxide synthase levels were observed. We conclude that administration of imipramine may result in the exacerbation of nonalcoholic fatty liver disease, diabetes, diabetic retinopathy, and kidney injury.

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Structurally composed of a low-density lipoprotein (LDL)-like particle covalently linked to apolipoprotein(a) [apo(a)], Lp(a) exhibits unique atherogenic, thrombogenic, and inflammatory properties, largely due to its role as a carrier of oxidized phospholipids (OxPL). Plasma Lp(a) concentrations are predominantly determined by the number of kringle IV type 2 (KIV-2) repeats in the LPA gene, with minimal influence from lifestyle or environmental factors. Despite substantial evidence linking elevated Lp(a) to cardiovascular risk, clinical testing remains underutilized, especially in East Asian countries. In Taiwan, although population-level Lp(a) concentrations are comparatively low, a significant subset exceeds risk thresholds, with local studies confirming its prognostic value in coronary artery disease and ischemic stroke. Barriers, including limited physician awareness, implementation barriers, and therapeutic nihilism, contribute to its under-recognition. This review highlights the molecular features of Lp(a), its pathogenesis of cardiovascular disorders, epidemiology, and current barriers and future advances in diagnostic testing, with a particular focus on implications for cardiovascular risk management in Taiwan.

Shortened door-to-balloon time (D2B) has been documented to confer cardiovascular benefits for ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). However, prolonged myocardial ischemic duration usually negates the beneficial effects due to delayed symptom-to-door time (S2D). In this study, we sought to investigate the joint effect of S2D-D2B in predicting clinical outcomes. This study retrospectively enrolled 342 consecutive STEMI patients receiving PPCI. The baseline demographic data, clinical features, S2D, D2B, and S2B were compared between survivors and non-survivors. We further analyzed the relationships between mortality rates and S2D/D2B in patients with different age categories. The receiver-operating characteristic curves analysis revealed D2B time 65. Mins, S2D time 125 min, and S2B time 170 min had the greatest predictive power for mortality rate. Patients with D2B < 65min and S2D time <125 min had the lowest mortality rate (1.62%). Whereas, patients with a D2B ≥ 65 min and S2D ≥ 125 min had the highest mortality rate (21%, P = 0.0004). Multiple variate analyses showed that combined D2B ≥ 65 min and S2D ≥ 125 min was an independent predictor for a higher mortality rate (HR 9.44, P = 0.0111). Shorter S2B time was also associated with a lower mortality rate in overall and younger populations. The reductions of both D2B and S2D were associated with improved mortality rates in STEMI patients receiving PPCI, especially in younger populations. The findings call for community and healthcare system efforts to address these critical time intervals to enhance survival rates in STEMI patients.

Background: Reduced-dose prasugrel is widely used in East Asia for acute coronary syndrome (ACS), but real-world data in diverse Asian populations are limited. This study evaluated its effectiveness and safety in Taiwanese patients. Methods: The PROMISE-TW Registry was a multicenter, retrospective study including 1167 patients with ACS or chronic coronary syndrome (CCS) treated with reduced-dose prasugrel (20 mg loading, 3.75 mg maintenance) across 13 hospitals in Taiwan from 2018 to 2022. The primary endpoint was 1-year major adverse cardiovascular events (MACEs: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). Secondary outcomes included composite ischemic events and major bleeding (BARC 3–5). Results: Among enrolled patients (mean age 63.9 years; 81.2% male; 83% ACS), percutaneous coronary intervention was performed in 90.8%. At one year, MACEs occurred in 1.9%, composite ischemic events in 8.2%, and major bleeding in 0.8%. Subgroup analysis identified prior stroke, diabetes, and chronic total occlusion intervention as predictors of bleeding. Male sex, chronic kidney disease, and left circumflex artery intervention predicted higher ischemic risk. Conclusions:Reduced-dose prasugrel provided effective ischemic protection and low bleeding rates in Taiwanese patients, especially those with ACS. These findings support the clinical utility of dose-adjusted prasugrel in East Asian populations and highlight the importance of individualized risk assessment.