Mingqian Li

Background: Lumateperone, a novel atypical antipsychotic, has emerged as an illuminating hope for patients with schizophrenia and bipolar disorder. While prior studies have employed spontaneous reporting databases and identified over 100 novel adverse events associated with lumateperone, the differences in these adverse events across subgroups remain unclear. Objective: This study provides a comprehensive evaluation of the adverse event profile of lumateperone using the Food and Drug Administration Adverse Event Reporting System database, focusing on the potential differences in reporting adverse events across subgroups. Methods: Based on the results of clinical characteristics and signal detection, the potential differences in reporting lumateperone-associated adverse events across specific subgroups regarding report year, reporter type, sex, age, outcome, indication, and concomitant drug were analyzed using the reporting odds ratio algorithm and Fisher’s exact test with Bonferroni correction. The observed differences were further validated using sensitivity analyses, stratified analyses, and comparative analyses. Results: This study identified 1762 reports and 5074 adverse events associated with lumateperone. Notably, females had a higher frequency of reporting nervous system disorders. Tardive dyskinesia was more frequently resulted in serious consequences. Moreover, bipolar disorder patients more frequently reported nervous system disorders, while schizophrenia patients more frequently reported psychiatric disorders. Conclusions: This study underscores the need for future confirmatory studies into the potential sex, outcome and indication differences in adverse events associated with lumateperone. The findings should be considered preliminary and require further validation.

Ca²⁺, as critical second messengers in biological processes, plays a pivotal role in the regulation of diverse cellular signaling pathways. The dysregulation of calcium signaling is intricately linked to the progression of various cancers. The capacity of Ca²⁺ to modulate cell death and proliferation, along with its potential for pharmacological manipulation, presents a promising avenue for the development of novel cancer therapeutics. This review provides a comprehensive overview of the classification of Ca²⁺ channels and their mechanisms of action in oncogenesis, explores the application of Ca²⁺ blockers in cancer treatment, and underscores the importance of conducting further clinical trials.

Microsecond pulsed electric field (µsPEF) is a newer treatment modality to replace catheter ablation treatment of Atrial fibrillation (AF) due to its fewer side effects. This study aims to find out experimental parameters that effectively induce cardiomyocyte death and the precise mechanisms for microsecond pulsed electric fields (µsPEFs) ablation of cardiomyocytes. CCK8 and flow apoptosis analysis were employed to examine the effects of different µsPEFs on cardiomyocytes in vitro. The mechanisms by which the µsPEFs ablation works were explored through a combination of transcriptome study, transmission electron microscope (TEM) observation of mitochondria, pathway enrichment analysis, and interaction network analysis. In vivo experiments on mice involving HE, Masson, TUNEL and Immunofluorescence staining examinations were conducted to confirm the in vitro experimental results. When more than 30 pulses were applied, a continuous decline in post-ablation relative cell activity was observed, decreasing from 0.36 at 3 h to 0.13 (p < 0.01) at 48 h. Notably, at a voltage of 1500 V/cm and a pulse count of 50, the apoptosis rate exceeded 95%, coupled with a more stable and consistent cell ablation. Following ablation, a notable upregulation in mitochondria-related transcription levels was observed, accompanied by mitochondrial membrane disruption and an increase in Cytochrome C levels. Within a certain range, an increase in voltage and number of electric pulses corresponded to a greater quantity of cell mortality in the ablation zone. The µsPEFs induced cell injury by impairing mitochondrial function and potentially triggering the mitochondrial apoptosis pathway.

Cancer is one of the leading causes of morbidity and mortality in the global population. The effective management of cancer-associated pain and anesthesia are critical aspects of comprehensive cancer treatment. However, the role and mechanism of anesthesia and analgesia-related drugs in tumors remain controversial. In this study, the efficacy of 16 commonly used analgesics and anesthetics against non-small cell lung cancer (NSCLC) was evaluated. Among the 16 examined injections, butorphanol tartrate injection significantly inhibited the proliferation of NSCLC cells and increased the sensitivity of the EGFR-TKI-resistant H1975 cell line to gefitinib. Benzethonium chloride (BC) is the main active antitumor ingredient of butorphanol tartrate injection. BC may regulate the cell cycle, apoptosis and EMT signaling pathways by modulating the P53 signaling pathway. Our study reveals the therapeutic value of butorphanol tartrate injection and BC in the treatment of NSCLC and provides a theoretical basis for comprehensive therapies for NSCLC.

Introduction Breast cancer (BC) is the most prevalent type of cancer and has the highest mortality among women worldwide. BC patients have a high risk of depression, which has been recognized as an independent factor in the progression of BC. However, the potential mechanism has not been clearly demonstrated. Methods To explore the correlation and mechanism between depression and BC progression, we induced depression and tumor in BC mouse models. Depression was induced via chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS). Amino acid (AA) neurotransmitter-targeted metabonomics and gut microbiota 16S rDNA gene sequencing were employed in the mouse model after evaluation with behavioral tests and pathological analysis. Results The tumors in cancer-depression (CD) mice grew faster than those in cancer (CA) mice, and lung metastasis was observed in CD mice. Metabonomics revealed that the neurotransmitters and plasma AAs in CD mice were dysregulated, namely the tyrosine and tryptophan pathways and monoamine neurotransmitters in the brain. Gut microbiota analysis displayed an increased ratio of Firmicutes/Bacteroides. In detail, the abundance of f_Lachnospiraceae and s_Lachnospiraceae increased, whereas the abundance of o_Bacteroidales and s_Bacteroides_caecimuris decreased. Moreover, the gut microbiota was more closely associated with AA neurotransmitters than with plasma AA. Conclusion Depression promoted the progression of BC by modulating the abundance of s_Lachnospiraceae and s_Bacteroides_caecimuris, which affected the metabolism of monoamine neurotransmitters in the brain and AA in the blood.