Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases.

Extracellular vesicles (EVs) have been proven to play a significant immunoregulatory role in many chronic diseases, such as cancer and immune disorders. Among them, EVs derived from NK cells are an essential component of the immune cell functions. These EVs have been demonstrated to carry a variety of toxic proteins and nucleic acids derived from NK cells and play a therapeutic role in diseases like malignancies, liver fibrosis, and lung injury.

A Dual PI3K/HDAC Inhibitor Induces Immunogenic Ferroptosis to Potentiate Cancer Immune Checkpoint Therapy.

The capacity of targeted anticancer agents to exert immunomodulatory effects provides a strong rationale to develop novel agents suitable for combinatorial regimens with immunotherapy to improve clinical outcomes. In this study, we developed a dual-targeting PI3K and HDAC inhibitor BEBT-908 that potently inhibits tumor cell growth and potentiates anti-PD1 therapy in mice by inducing immunogenic ferroptosis in cancer cells. Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling.

The effect of population size for pathogen transmission on prediction of COVID-19 spread.

Extreme public health interventions play a critical role in mitigating the local and global prevalence and pandemic potential. Here, we use population size for pathogen transmission to measure the intensity of public health interventions, which is a key characteristic variable for nowcasting and forecasting of COVID-19. By formulating a hidden Markov dynamic system and using nonlinear filtering theory, we have developed a stochastic epidemic dynamic model under public health interventions.

BEBT-109, a pan-mutant-selective EGFR inhibitor with potent antitumor activity in EGFR-mutant non-small cell lung cancer.

EGFR mutation-positive NSCLC tumors are highly heterogeneous, therefore, exploring an agent simultaneously targeting multiple EGFR mutations may be valuable for clinical practice. Compared with osimertinib, BEBT-109 shows more sensitive and extensive antitumor activity in EGFR mutant NSCLC, while sparing wild-type EGFR cell lines. Meanwhile, unlike the metabolite of osimertinib AZ5104, the main metabolites of BEBT-109 are found lacking in activity against wild-type EGFR cell lines.

EndophilinA2 protects against angiotensin II-induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes.

Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs).

Apigenin C-glycosides of Microcos paniculata protects lipopolysaccharide induced apoptosis and inflammation in acute lung injury through TLR4 signaling pathway.

Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening conditions with high morbility and mortality, underscoring the urgent need for novel treatments. Leaves of the medicinal herb Microcos paniculata have been traditionally used for treating upper airway infections, by virtue of its content of flavonoids such as apigenin C-glycosides (ACGs). C-glycosides have been shown to exert strong anti-inflammatory properties, although their mechanism of action remains unknown.

Autophagy is involved in the protective effect of endophilin A2 on HO-induced apoptosis in H9C2 cardiomyocytes.

Apoptosis plays a critical role in normal embryonic development and tissue homeostasis regulation. EndophilinA2 (EndoA2) is widely reported to regulate endocytosis. Additionally, EndoA2 has been demonstrated to be involved in tumor metastasis, neuroregulation and vascular function.