Sodium nitrate protects against metabolic syndrome by sialin-mediated macrophage rebalance

Oral NaNO₃ alleviates #MetabolicSyndrome through the sialin-mediated pathway to rebalance macrophage homeostasis by inhibiting #Cathepsin L via the Rel/#Nrf2 axis, highlighting it as a potent therapeutic to mitigate #MASLD & #Type2Diabetes.

#OpenAccess: doi.org/10.1038/s413...

Human CTSZ variants are associated with TB severity, and CTSZ is present at the host-pathogen interface within human pulmonary Mtb granulomas. Top left: A manually annotated UMAP generated by unsupervised clustering of data from single-cell mRNA-Seq of human biopsy tissue, containing Mtb granulomas from three patients with TB. Top right: Analysis of normalized expression values reveals that CTSZ is specifically induced in granuloma macrophages, particularly in lipid-associated macrophages. Bottom: Brightfield (BF) images and immunofluorescent staining of CTSZ and CD68 within a granuloma biopsy from an individual with pulmonary TB. Goat (Gt) and mouse (Ms) IgG isotype control staining is depicted in the top row. DAPI staining indicates cell nuclei. Scale bar is 60 µM in length.

#Tuberculosis severity varies widely between people; why is this? This study uses the #CollaborativeCross mouse panel to identify the protease #cathepsin Z (CTSZ) as a conserved regulator of #TB outcomes via its influence on CXCL1 in mice & in humans @plosbiology.org 🧪 plos.io/4phwRA8

Human CTSZ variants are associated with TB severity, and CTSZ is present at the host-pathogen interface within human pulmonary Mtb granulomas. Top left: A manually annotated UMAP generated by unsupervised clustering of data from single-cell mRNA-Seq of human biopsy tissue, containing Mtb granulomas from three patients with TB. Top right: Analysis of normalized expression values reveals that CTSZ is specifically induced in granuloma macrophages, particularly in lipid-associated macrophages. Bottom: Brightfield (BF) images and immunofluorescent staining of CTSZ and CD68 within a granuloma biopsy from an individual with pulmonary TB. Goat (Gt) and mouse (Ms) IgG isotype control staining is depicted in the top row. DAPI staining indicates cell nuclei. Scale bar is 60 µM in length.

#Tuberculosis severity varies widely between people; why is this? This study uses the #CollaborativeCross mouse panel to identify the protease #cathepsin Z (CTSZ) as a conserved regulator of #TB outcomes via its influence on CXCL1 in mice & in humans @plosbiology.org 🧪 plos.io/4phwRA8

Human CTSZ variants are associated with TB severity, and CTSZ is present at the host-pathogen interface within human pulmonary Mtb granulomas. Top left: A manually annotated UMAP generated by unsupervised clustering of data from single-cell mRNA-Seq of human biopsy tissue, containing Mtb granulomas from three patients with TB. Top right: Analysis of normalized expression values reveals that CTSZ is specifically induced in granuloma macrophages, particularly in lipid-associated macrophages. Bottom: Brightfield (BF) images and immunofluorescent staining of CTSZ and CD68 within a granuloma biopsy from an individual with pulmonary TB. Goat (Gt) and mouse (Ms) IgG isotype control staining is depicted in the top row. DAPI staining indicates cell nuclei. Scale bar is 60 µM in length.

#Tuberculosis severity varies widely between people; why is this? This study uses the #CollaborativeCross mouse panel to identify the protease #cathepsin Z (CTSZ) as a conserved regulator of #TB outcomes via its influence on CXCL1 in mice & in humans @plosbiology.org 🧪 plos.io/4phwRA8

Cathepsin L plays a crucial role in the diversity and functionality of T cells An international team led by Ludger Klein has provided important insights into the maturation of T cells in the thymus, which is a central process in the development of a functioning immune system.

📣 New in @natimmunol.nature.com:
#Cathepsin L plays a crucial role in the diversity and functionality of #CD4 #Tcells

➡️ www.med.lmu.de/bmc/en/news/...

#cortical #epithelial #cells #receptor #thymus #immune #immunology #MHC #major #histocompatibility #complex #cysteine #protease

📷 J.Greune

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19 Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve...

#MedSky🧪 #IDSky
Does #olgotrelvir ( an oral #antiviral with dual mechanisms of action targeting severe #COVID main protease (i.e. #Mpro) & human #cathepsin L. It has potential to serve as a single-agent treatment For #COVID19
evidence.nejm.org/doi/full/10.... ) work against #SARSCoV2 ?

Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhibition of the Cathepsin B1 Protease Target and Binding Mode Analysis Schistosomiasis, caused by a parasitic blood fluke of the genus Schistosoma, is a global health problem for which new chemotherapeutic options are needed. We explored the scaffold of gallinamide A, a natural peptidic metabolite of marine cyanobacteria that has previously been shown to inhibit cathepsin L-type proteases. We screened a library of 19 synthetic gallinamide A analogs and identified nanomolar inhibitors of the cathepsin B-type protease SmCB1, which is a drug target for the treatment of schistosomiasis mansoni. Against cultured S. mansoni schistosomula and adult worms, many of the gallinamides generated a range of deleterious phenotypic responses. Imaging with a fluorescent-activity-based probe derived from gallinamide A demonstrated that SmCB1 is the primary target for gallinamides in the parasite. Furthermore, we solved the high-resolution crystal structures of SmCB1 in complex with gallinamide A and its two analogs and describe the acrylamide covalent warhead and binding mode in the active site. Quantum chemical calculations evaluated the contribution of individual positions in the peptidomimetic scaffold to the inhibition of the target and demonstrated the importance of the P1′ and P2 positions. Our study introduces gallinamides as a powerful chemotype that can be exploited for the development of novel antischistosomal chemotherapeutics.

#medchem #schistosoma #cathepsin

Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhib. of the Cathepsin B1 Protease Target and Binding Mode Anal. (Mareš) - ACS Infect Dis: doi.org/10.1021/acsi...

@iocbprague.bsky.social