isolation-identification-primary-fibroblast-like-synovial-cells-from

Isolation and Identification of Primary Fibroblast-like Synovial Cells from Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial hyperplasia and progressive joint destruction as its ...

Beijing University of Chinese Medicine

China-Japan friendship hospital

In clinical practice, renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), often leading to acute renal failure or end-stage renal disease (ESRD). The current understanding of renal IRI mechanisms remains unclear, and effective therapeutic strategies and clear targets are lacking. Therefore, the need to find explicit and effective ways to reduce renal IRI remains a scientific challenge. The current study explored pyroptosis, a type of inflammation-regulated programmed cell death, and the role of Gasdermins E (GSDME)-mediated pyroptosis, mitochondrial damage, and inflammation in renal IRI. The analysis of human samples showed that the expression levels of GSDME in normal human renal tissues were higher than those of GSDMD. Moreover, our study demonstrated that GSDME played an important role in mediating pyroptosis, inflammation, and mitochondrial damage in renal IRI. Subsequently, GSDME-N accumulated in the mitochondrial membrane, leading to mitochondrial damage and activation of caspase3, which generated a feed-forward loop of self-amplification injury. However, GSDME knockout resulted in the amelioration of renal IRI. Moreover, the current study found that the transcription factor CHOP was activated much earlier in renal IRI. Inhibition of BCL-2 by CHOP leaded to casapse3 activation, resulting in mitochondrial damage and apoptosis; not only that, but CHOP positively regulated GSDME thereby causing pyroptosis. Therefore, this study explored the transcriptional mechanisms of GSDME during IRI development and the important role of CHOP/Caspase3/GSDME mechanistic axis in regulating pyroptosis in renal IRI. This axis might serve as a potential therapeutic target.

CHOP-mediated Gasdermin E expression promotes pyroptosis, inflammation, and mitochondrial damage in renal ischemia-reperfusion injury.

To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca uptake and then concomitantly increased cytosolic Ca levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.

A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans.

Immune checkpoint inhibitor (ICI) plus chemotherapy has become the standard of care for advanced non-small cell lung cancer (NSCLC). Nonetheless, reliable efficacy biomarkers of ICI plus chemotherapy are lacking. In this research, we sought to explore efficacy biomarkers and construct robust prognostic models in NSCLC patients treated with ICI plus chemotherapy.

Neutrophil-to-lymphocyte ratio-based prognostic score can predict outcomes in patients with advanced non-small cell lung cancer treated with immunotherapy plus chemotherapy.

Article	Year
CHOP-mediated Gasdermin E expression promotes pyroptosis, inflammation, and mitochondrial damage in renal ischemia-reperfusion injury. Cell death & disease\| PubMed ID: 38388468	2024
A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans. Cell genomics\| PubMed ID: 40043709	2025
Neutrophil-to-lymphocyte ratio-based prognostic score can predict outcomes in patients with advanced non-small cell lung cancer treated with immunotherapy plus chemotherapy. BMC cancer\| PubMed ID: 40234811	2025

Hao-lu Wu

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