Bo Wang

The association between oral microbiome (OM) and myocardial infarction (MI) has become a noteworthy topic in recent years, yet the role played by cathepsin in this association remains unclear. The main objective of this study was to elucidate the role of cathepsin in mediating the effect of OM on MI. The mutual causality among OM, cathepsins, and MI was analyzed using two-sample Mendelian randomization (TSMR), and the mediating role of cathepsins between OM and MI was evaluated using mediation MR analysis. Furthermore, we conducted a meta-analysis to verify the causal relationship between Cathepsin H and MI. Subsequently, we employed summary-data-based MR (SMR) method to examine the potential causal genes and proteins for Cathepsin H and acute myocardial infarction. The meta analysis result indicated that each standard deviation increase in the exposure factor of Cathepsin H was associated with a reduction in the MI risk (OR = 0.9991; 95% CI = 0.9984–0.9998; P = .0089). Our study confirmed that 3 salivary flora, including Lancefieldella_unclassified_mgs_1257 , Fusobacterium_unclassified_mgs_3185, Oribacterium_asaccharolyticum_mgs_3324 , and one tongue dorsal flora, named Saccharimonadaceae_unclassified_mgs_1355 , can regulate the development of MI via Cathepsin H. The results of the SMR analysis indicated a statistically significant negative correlation between the Cathepsin H (CTSH) gene and coronary artery disease ( P -SMR < .05, P -HEIDI > .01). Conversely, a significant positive correlation was observed between the MST1 protein and MI risk ( P -SMR < .05, P -HEIDI > .01). Reverse transcription polymerase chain reaction and ELISA tests on clinical samples showed a significant decrease in Cathepsin H levels – both protein and messenger ribonucleic acid – in the blood of MI patients ( P < .05), while MST1 expression was notably increased ( P < .05). We identified 3 salivary bacteria and one tongue dorsum bacterium that may influence MI development, with Cathepsin H playing a key mediating role. These findings strengthen the evidence linking OM to MI and clarify the role of cathepsins in this relationship. The study highlights how Cathepsin H may mediate the impact of oral flora on MI and proposes new therapeutic directions and targets for MI prevention and treatment.

Castration-resistant prostate cancer (CRPC) represents an advanced stage of prostate cancer progression. Although the combination of androgen deprivation therapy (ADT) with chemotherapy and first generation hormone therapy is initially effective, patients ultimately develop resistance. In recent years, breakthroughs in targeted therapies and immunotherapies, along with the emergence of novel combination strategies, have provided new hope for patients with CRPC. This article systematically reviews the latest advancements in targeted and immunotherapeutic approaches for CRPC, integrating clinical data and mechanistic studies to analyze the efficacy and challenges of novel agents (e.g., second-generation AR inhibitors, PARP inhibitors, PSMA-targeted therapies) and combination regimens. It also provides insights for exploring future optimization directions.

Renal cell carcinoma (RCC), particularly the clear-cell subtype (ccRCC), accounts for 75-85% of kidney cancers and exhibits distinct genetic and biological heterogeneity. While surgical resection remains the mainstay of treatment for localized ccRCC, the persistence of recurrence rates underscores the significant unmet need for effective adjuvant therapies. Recent advancements in immunotherapy and targeted therapies have revolutionized the management of RCC. Immune checkpoint inhibitors have significantly enhanced antitumor immune responses, whereas tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors effectively disrupt angiogenesis and proliferation signaling pathways, respectively. However, non-clear cell RCC subtypes remain understudied due to their rarity and exclusion from major clinical trials. Consequently, this review primarily focuses on ccRCC, aiming to provide a comprehensive and up-to-date overview of the latest advancements in immunotherapy and targeted therapies. By synthesizing current evidence, this review seeks to elucidate the mechanisms of action, clinical efficacy, and limitations of these treatments, while also identifying gaps in knowledge and future research directions. Ultimately, the goal is to offer valuable insights for clinicians and researchers, facilitating the development of optimized, personalized treatment approaches to improve outcomes for ccRCC patients.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.

Background: Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. Methods: Male SD rats aged 3–4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. Results: Compared with the control group, the MVD decreased significantly in the castration group (P < 0.05). When the exogenous E concentration was constant, in general, the MVD of rats in all the groups increased with increasing exogenous DHT concentration. Compared with the castration group, the MVD increased significantly in the E0.05 + DHT0.015 mg/kg, E0.05 + DHT0.05 mg/kg, E0.05 + DHT0.15 mg/kg, E0.05 + DHT0.5 mg/kg, and E0.05 + DHT1.5 mg/kg groups (P < 0.05). In addition, when the exogenous DHT concentration was constant, the MVD increased with increasing exogenous E concentration in all the groups. Among them, compared with the control and castration groups, the MVD increased significantly in the DHT0.15 + E0.015 mg/kg, DHT0.15 + E0.15 mg/kg, and DHT0.15 + E0.5 mg/kg groups (P < 0.05). Conclusions: Androgens play an important role in the regulation of prostatic MVD in SD rats, and a decrease in DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with increasing DHT concentration. In addition, prostatic MVD can be increased gradually with increasing oestrogen concentration.