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CXCL16 knockout inhibit asthma airway inflammation by suppressing H2-DM molecular mediated antigen presentation

The inflammatory microenvironment influences dendritic cell-mediated antigen presentation to regulate asthma Th2 inflammation. The scavenger receptor is expressed on DCs and regulates antigen presentation and T priming. However, whether the transmembrane scavenger receptor (SR-PSOX/CXCL16) regulates the phenotype and antigen presentation function of DCs remains unclear. We found that CXCL16 is mainly expressed on DCs in the lung tissues of asthma patients and asthma mice. CXCL16 knockout led to the suppression of airway inflammation, mucus overproduction, and airway hyperresponsiveness in Aspergillus-induced asthma. In addition, the adoptive transfer of Aspergillus-pulsed DCs shows the CXCL16+ DCs exerted a promoting role in airway inflammation, the CXCL16 DCs inhibit airway inflammation. Additionally, RNA sequencing and flow cytometry data revealed that CXCL16 knockout inhibits airway inflammation by suppressing the antigen processing and presentation function of DCs, which was mediated by MHC II chaperone H2-DM. Furthermore, we found CXCL16 knockout suppressed dendritic cells differentiated forward to cDC2b subtype which is mainly charged with antigen presentation to T cell. In conclusion, we found that CXCL16 downregulated the capacity of DC antigen processing and presentation to suppress airway inflammation by reducing H2-DM expression which mediated DC differentiation. The study suggested that inhibition of CXCL16 can be a potential therapy for asthma.

Discovery of new AMR drugs targeting modulators of antimicrobial activity using in vivo silkworm screening systems

Global concerns about drug-resistant bacteria have underscored the need for new antimicrobial drugs. Emerging strategies in drug discovery include considering the third factors that influence drug activity. These factors include host-derived elements, adjuvants, and drug combinations, which are crucial in regulating antimicrobial efficacy. Traditional in vivo assessments have relied on animal models to study drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). Alternative models, such as silkworms, are being explored to overcome the ethical and financial barriers associated with mammalian models. The silkworm has been proven effective in evaluating ADMET and in highlighting the therapeutic potential enhanced by third factors. Host factors (either mammalian or non-mammalian) enhance the antimicrobial activity of antimicrobial agents such as lysocin E. Additionally, using d-cycloserine to potentiate vancomycin has successfully combated vancomycin-resistant infections in silkworms. Leveraging silkworms in drug discovery could establish a novel screening method incorporating interactions with third factors, whether host related or non-host-related, thus promising new pathways for identifying antimicrobial drugs with unique mechanisms of action.

Metabolite-driven mechanisms reveal chemical ecology of Lehmann Lovegrass (Eragrostis lehmanniana) invasion in North American semi-arid ecosystems

Invasive plants threaten global ecosystems, yet traditional analyses of functional traits cannot fully explain their dominance over co-occurring natives. Metabolomics offers insights into plant invasions, but single-technique studies often miss critical biochemical mechanisms. We employ a multimodal metabolomics approach (¹H NMR, LC MS/MS, FT-ICR-MS, and MALDI-MSI) to investigate the biochemical basis of Lehmann lovegrass (Eragrostis lehmanniana) invasion in semi-arid North America, comparing it with a co-occurring native grass, Arizona cottontop (Digitaria californica). Our analysis reveals three metabolomic traits of Lehmann lovegrass compared to Arizona cottontop: Enhanced nitrogen allocation in shoots, reduced defensive metabolites in root layers; and increased root exudate modulation under stress conditions. These traits suggest Lehmann lovegrass succeeds through adaptation to increasing aridity rather than direct competition, demonstrating adaptation to nutrient-poor environments and high phenotypic plasticity in response to increasing aridity. This integrated metabolomic approach provides new mechanistic insights into invasion ecology and plant adaptation under environmental change.

Cannabinoid-2 receptor depletion promotes non-alcoholic fatty liver disease in mice via disturbing gut microbiota and tryptophan metabolism

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a spectrum of liver damage starting with liver steatosis and lipid disorders presented as the hallmark. Cannabinoid-2 receptor (CB2R) is the receptor of endocannabinoids mainly expressed in immune cells. Our preliminary study revealed the preventative role of CB2R in liver injury related to lipid metabolism. In this study, we aimed to explore the role of CB2R in NAFLD and the underlying mechanism related to microbial community. High-fat diet-induced NAFLD model was established in mice. We found that hepatic CB2R expression was significantly reduced in NAFLD mice and CB2R–/– mice fed with normal chow. Interestingly, cohousing with or transplanted with microbiota from WT mice, or treatment with an antibiotic cocktail ameliorated the NAFLD phenotype of CB2R–/– mice. The gut dysbiosis in CB2R–/– mice including increased Actinobacteriota and decreased Bacteroidota was similar to that of NAFLD patients and NAFLD mice. Microbial functional analysis and metabolomics profiling revealed obviously disturbed tryptophan metabolism in NAFLD patients and NAFLD mice, which were also seen in CB2R–/– mice. Correlation network showed that the disordered tryptophan metabolites such as indolelactic acid (ILA) and xanthurenic acid in CB2R-/- mice were mediated by gut dysbiosis and related to NAFLD severity indicators. In vitro and in vivo validation experiments showed that the enriched tryptophan metabolites ILA aggravated NAFLD phenotypes. These results demonstrate the involvement of CB2R in NAFLD, which is related to gut microbiota-mediated tryptophan metabolites. Our findings highlight CB2R and the associated microbes and tryptophan metabolites as promising targets for the treatment of NAFLD.

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