Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis.

Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM.

Buyang Huanwu Decoction prevents hemorrhagic transformation after delayed t-PA infusion via inhibiting NLRP3 inflammasome/pyroptosis associated with microglial PGC-1α.

Ethnopharmacological Relevance: Delayed tissue-type plasminogen activator (t-PA) thrombolysis, which has a restrictive therapeutic time window within 4.5 h following ischemic stroke (IS), increases the risk of hemorrhagic transformation (HT) and subsequent neurotoxicity. Studies have shown that the NLRP3 inflammasome activation reversely regulated by the PGC-1α leads to microglial polarization and pyroptosis to cause damage to nerve cells and the blood-brain barrier.

The Nuclear Condensates of ESE3/EHF Induce Cellular Senescence without the Associated Inflammatory Secretory Phenotype in Pancreatic Ductal Adenocarcinoma.

Senescent cells are in a stable state of cell cycle arrest, leading to a natural barrier to tumorigenesis. Senescent cells secrete a pool of molecules, including cytokines, chemokines, proteases, and growth factors, termed the senescence-associated secretory phenotype (SASP), paradoxically contributing to pro-tumorigenic processes. However, the mechanism for regulating senescence and SASP in tumor cells remains unclear.

Inhibition of autophagy attenuates cognitive decline and mitochondrial dysfunction in an Alzheimer's disease mouse model with chronic cerebral hypoperfusion.

This study aimed to investigate the impact of chronic cerebral hypoperfusion (CCH) on cognitive function, amyloid-β (Aβ) deposition, cellular autophagy, and mitochondrial dynamics in an Alzheimer's disease (AD) mouse model, and to evaluate the intervention effects of autophagy modulation on these outcomes. Utilizing the APP/PS1 mouse model combined with CCH, we assessed cognitive function, Aβ deposition, and the expression levels of relevant proteins through behavioral tests and immunohistochemical analysis. Our findings revealed pronounced cognitive deficits and increased Aβ deposition in the AD + CCH group mice, along with upregulation of mitochondrial fission proteins (Drp1, Fis1) and downregulation of mitochondrial fusion proteins (Opa1, Mfn1), indicating a shift towards mitochondrial fission and promoting cell apoptosis.

Novel steroidal β-carboline derivatives as promising antibacterial candidates against methicillin-resistant Staphylococcus aureus.

A novel series of steroidal β-carboline quaternary ammonium derivatives (SCQADs) derived from natural cholic acid and its derivatives was designed, synthesized and biologically evaluated against four Gram-positive bacteria for the first time. Most of these derivatives exhibited promising antibacterial activity against the tested strains, particularly, compound 21g displayed strong antibacterial activity against MRSA (MIC = 0.5-1 μg/mL) with low cytotoxicity.