Since COVID-19 pandemic, the protection of lung health against infection with various pathogens has been emphasized. Acute lung injury (ALI) is a severe respiratory disease that causes sudden loss of lung function via pathogenic invasion. Although diverse anti-inflammatory materials have been investigated, the preventive efficacy remains limited. The purpose of this study is to investigate the preventive effects of Melicope pahangenesis T. G. Hartley extract (MPE) on lipopolysaccharide (LPS)-induced ALI. In vivo, oral MPE administration inhibits LPS-induced intestinal thickening, hyperplasia, mucus production, alveolar macrophage recruitment, and IL-1β expression in bronchoalveolar lavage fluid. The production of IL-6 and expression of iNOS and COX-2 were strongly suppressed. In mechanism studies, MPE inhibited phosphorylation of p65, IκB kinase, p38, and JNK1/2 and nuclear translocation of p65. Furthermore, MPE reduced reactive oxygen species and induced radical scavenging activities. Taken together, MPE consistently exerted anti-inflammatory effects in vitro and in vivo.

Synthesis and evaluation of methoxyquinazoline sulfonamide derivatives as bifunctional molecular targeting tumor related inflammation and anti-EGFR triple-mutation.

Chronic diabetic wounds represent a major global health challenge due to their persistent and difficult-to-heal nature, imposing substantial burdens on patients. Moist exposed burn ointment (MEBO), a traditional Chinese medicine preparation, has shown therapeutic potential in treating diabetic wounds; however, its underlying mechanisms remain to be fully elucidated. In this study, MEBO and recombinant bovine basic fibroblast growth factor (rb-bFGF), used as a positive control, were applied to diabetic rat wound models. Wound pathology, ultrastructures, and protein expression profiles were subsequently evaluated. The results demonstrated that MEBO reduced the expression of the inflammatory factors iNOS and IL-6, thereby alleviating inflammatory cell infiltration, while simultaneously increasing the expression of IL-10 and Arg1. Furthermore, MEBO enhanced the expression of ADAM-10 and p-AKT, promoting cell regeneration and increasing collagen deposition. It also elevated Beclin1 expression while reducing GRP78 and CTSK levels, suggesting improved subcellular structural integrity through the regulation of autophagy-related pathways. Notably, MEBO modulated angiogenesis via CD31 expression, thereby accelerating the wound healing process. In conclusion, MEBO significantly promotes wound healing in diabetic rats by regulating inflammatory responses, enhancing cell regeneration, regulating autophagy, facilitating collagen deposition, and promoting angiogenesis.

Inorganic arsenic and its methylated metabolites induce pulmonary immunosuppression via the p62-Keap1-Nrf2 positive feedback loop-mediated M2 macrophage polarization.

Glutathione-conjugated gold nanoparticles mitigate amyloid-beta-induced neuroinflammation and tauopathy through inhibition of NF-κB, the NLRP3 inflammasome axis in 3D human neural stem cell models.

The Scutellaria baicalensis-Coptis chinensis herb pair ameliorates ulcerative colitis via integrated modulation of the aryl hydrocarbon receptor/NLRP3 inflammasome axis with tryptophan metabolites.

Recombinant IL-38 Alleviates Temporomandibular Joint Synovial Inflammation via IL-1R1-NF-κB-IL1β Pathway.

UPLC-PDA-MS guided isolation of lindenane sesquiterpene oligomers with anti-neuroinflammatory activity from two rare Chloranthus species.

The effects of endometrial injury on endometrial receptivity in recurrent implantation failure.

Hexane extract of Pittosporopsis kerrii Craib mitigates LPS-driven inflammatory responses via JAK/STAT1 pathway inhibition in RAW 264.7 macrophages.

Engineering fluorescent iNOS-Inhibitory covalent organic frameworks: Fewer doses than fluticasone propionate for house dust mite-induced allergic rhinitis treatment.

This study investigated the effects of genistein-3'-sodium sulfonate (GSS) on chronic cerebral hypoperfusion (CCH) and the involvement of Takeda G-protein-coupled receptor 5 (TGR5) (also known as GPBAR1 (G protein-coupled bile acid receptor 1)) in its mechanism of action. In a mouse model of CCH, induced by bilateral common carotid artery stenosis (BCCAS), GSS treatment was combined with stereotaxic injection of TGR5 siRNA or expression vectors. Anxiety and depressive behaviors were evaluated using the elevated plus maze, light-dark box, tail suspension, and forced swim tests. Histological changes and blood-brain barrier (BBB) integrity were assessed by hematoxylin and eosin and Evans blue staining. Furthermore, an in vitro low-glucose hypoxia (LGH) microglia activation model was used. Protein and mRNA levels of TGR5, tight junction proteins, microglial markers, inflammatory molecules and caspase-3 were measured by western blotting and qRT-PCR. GSS treatment or TGR5 overexpression reversed the LGH-induced decrease in BV2 cell viability, whereas TGR5 knockdown had the opposite effect. In CCH mice, GSS or TGR5 overexpression improved behavior, alleviated histopathology, reduced injury scores and preserved BBB integrity. Along with these changes, TGR5, ZO-1, claudin-5, and CD206 increased, while the expression of IBA-1, iNOS, CD40, CD68, NF-κB p65, IL-1β, and caspase-3 decreased at protein and mRNA levels. In addition, TGR5 silencing promoted the effects of BCCAS and LGH. Overexpressing TGR5 promoted the effects of GSS, while TGR5 silencing partly abrogated these effects. These findings indicate that GSS can inhibit microglial mobilization and neuroinflammation by activating TGR5, offering a potential targeted therapy for cerebral ischemia and mitigating behavioral changes in CCH through TGR5 regulation.

Coccidiosis, a parasitic disease in animals, is often treated with coccidiostats, but their excessive use has led to drug resistance, reducing treatment efficacy. This study sought to investigate the in vitro and in vivo anticoccidial capacity of zinc oxide nanoparticles using Coriandrum sativum extract (CSE-ZnONPs) against Eimeria papillata. CSE-ZnONPs were synthesized and characterized via transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). E. papillata oocysts were treated in vitro with decreasing selected concentrations from CSE-ZnONPs (100 - 0.5mg/ml K2Cr2O7) of CSE-ZnONPs for 96h as part of a sporulation inhibition assay. For In vivo, five groups (G) of mice were utilized: G1: control group (Non-Infected), G2: received CSE-ZnONPs, G3: infection group with 10³ sporulated oocysts (Infected). G4: infected and treated with CSE-ZnONPs at a dosage of 50mg/kg b.w. (Infected + CSE-ZnONPs). G5: infected and treated with amprolium at a dosage of 120mg/kg b.w. (Infected + Amp). The treatments were persisted for five days. In vitro results indicated that CSE-ZnONPs markedly decreased sporulation rates and caused morphological damage in E. papillata oocysts. The in vivo oral administration of CSE-ZnONPs to infected mice considerably reduced the numbers of jejunal endogenous stages and notably decreased their morphometric dimensions. Immunohistochemistry demonstrated a downregulation of Cluster of Differentiation 4 (CD4) and Inducible Nitric Oxide Synthase (iNOS) expression, whereas biochemical antioxidant studies indicated reduced nitric oxide and malondialdehyde levels, alongside elevated superoxide dismutase and catalase activity. ELISA verified reduced serum concentrations of interferon-γ, tumor necrosis factor-α, interleukin-10, and iNOS in the treated mice. CSE-ZnONPs possess a promising potent in vitro sporulation inhibition and in vivo anticoccidial, antioxidant, anti-inflammatory and immuno-therapeutic properties against E. papillata.

Laggeranines FI, four undescribed sesquiterpenoids from Laggera pterodonta and their inhibitory effects on NO production in RAW 264.7 macrophages.

In vivo evaluation of the neuroprotective effects of melittin on doxorubicin-induced acute and chronic neurotoxicity in mice.

Molecular mechanism of Circ_PRKDC regulating macrophage polarization in wound healing.

BackgroundMajor histocompatibility complex class I (MHC)-I loss is a prevalent mechanism for immune evasion and resistance to immunotherapy. However, how MHC-I loss shapes the tumor microenvironment and influences immune cell interactions, ultimately affecting tumor growth, remains largely unknown.MethodsWe established B2m knockout (MHC-I-deficient) tumor cells using CRISPR/Cas9 and evaluated their growth in subcutaneous and orthotopic mouse models. Immune profiling was performed using flow cytometry and single-cell RNA sequencing. Antibody-mediated cell depletion was used to assess the functional contributions of specific immune subsets. Chemokine expression was analyzed by bulk RNA sequencing, quantitative PCR, ELISA and western blotting, and its functional relevance was determined using knockout or overexpression in tumor cells implanted in vivo. Signaling pathways were interrogated using pharmacological inhibition, RNA interference and western blotting.ResultsMHC-I loss promoted tumor growth in MC38, AKR, and LLC1 models, but unexpectedly suppressed Hepa1-6 and orthotopic MYC;Trp53−/− hepatocarcinoma growth. This differential effect correlated with changes in immune infiltrates. CD4+ T cells, natural killer (NK) cells, and macrophages were required for suppression of MHC-I-deficient Hepa1-6 tumors. CD4+ T cells were essential for recruiting NK cells and monocytes/macrophages and for inducing their tumoricidal phenotypes, including iNOS (inducible nitric oxide synthase) expression in macrophages. The differential infiltration of CD4+ T cells was driven by opposite regulation of CXCL16 on B2m knockout: upregulation in Hepa1-6 cells and downregulation in other models. CXCL16 exerted potent antitumor effects by recruiting CD4+ T cells. Mechanistically, B2M loss regulated CXCL16 via suppression of Akt in MC38 and AKR cells, but via activation of NF-κB in Hepa1-6 cells.ConclusionCXCL16-driven CD4+ T cells are central regulators of antitumor immunity against MHC-I-deficient tumors. The context-dependent regulation of CXCL16 by MHC-I loss determines the immune landscape and tumor outcome, highlighting a potential therapeutic avenue for targeting MHC-I-deficient cancers.

Enhancing memory T cell responses through Soluble Leishmania antigen and natural adjuvants against Leishmania donovani in murine model.

The accumulation of unfolded and misfolded proteins within the endoplasmic reticulum (ER) causes ER stress, leading to various physiological and pathological conditions. The cell activates unfolded protein response (UPR), an adaptive mechanism, to maintain the ER proteostasis. Neuronal ER stress can contribute to various neurodegenerative diseases. This study aims to investigate the effect of tunicamycin-induced ER stress on neuronal inflammation and the molecular mechanism involved. To study the ER stress-associated neuronal inflammation in vitro, we used tunicamycin-induced SH-SY5Y cell lines as the model system. PCR, ELISA, and immunoblot analysis were used to study mRNA and protein expressions. Reactive oxygen species (ROS) production was determined by flow cytometry, and cell viability was determined by MTT assay. Tunicamycin upregulated the mRNA expression of ER stress markers like PERK, ATF4, CHOP, IRE1, XBP1, ATF6 and BiP/GRP78. ER stress induction upregulated the secretion and expression of TNF-α as evidenced by ELISA, PCR and immunoblot analysis. The protein expression of iNOS, COX-2 and total ROS and mitochondrial ROS production were upregulated by tunicamycin in SH-SY5Y cells. Immunoblot analysis suggested that tunicamycin increased the acetylation of NF-κB p65 and downregulates the production of class III histone deacetylase SIRT1 in SH-SY5Y cells. Experiment using resveratrol confirmed the role of SIRT1 in the acetylation of NF-κB p65. Our results suggest that tunicamycin-induced ER stress upregulated neuronal inflammation through ROS-NF-κB- SIRT1 pathway, and targeting this pathway may provide greater therapeutic potential for managing neuronal inflammation associated with neurodegenerative diseases.

Discovering novel bioactive compounds is a fundamental goal in scientific research. To this end, our study employed a predicted data mining approach (PDMA) to efficiently screen for biotransformable precursors capable of yielding new bioactive derivatives. Using the PDMA strategy, we identified p-hydroxyphenethyl anisate (HP) as a substrate and employed Bacillus megaterium tyrosinase (BmTYR) to catalyze the hydroxylation of HP. The results demonstrated that HP was successfully converted into a novel ortho-dihydroxyphenyl compound, 3',4'-dihydroxyphenethyl anisate. This biotransformation yielded a product with significantly enhanced therapeutic potential. Notably, the product showed a potent 11-fold increase in anti-inflammatory activity compared to the precursor. Mechanistically, 3',4'-dihydroxyphenethyl anisate effectively mitigated the hyperimmune response in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the gene expression of pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin-1 beta, interleukin 6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2. Notably, Western blot analysis confirmed that this inhibitory effect was sustained at the protein level, where 3',4'-dihydroxyphenethyl anisate induced a significant downregulation of iNOS expression. Furthermore, the hydroxylated product showed preliminary antioxidant capacity (absent in the parent compound) and observable anti-melanoma activity. This study validates PDMA as an effective strategy for generating novel and high-value bioactive molecules via biotransformation. Our newly produced catechol is a promising candidate for future pharmacological applications.