International Immunopharmacology

Salidroside (SAL) is a natural bioactive compound with anti-oxidative, anti-inflammatory, and neuroprotective properties. In the present study, we generate an experimental design to investigate SAL-mediated protective effect and underlying mechanism on lipopolysaccharide (LPS)-induced neuroinflammation and cognitive impairment in the septic encephalopathy mice model (SEMM). In SEMM, Open-Field Test (OFT) and Novel Object Recognition Test evaluated LPS-induced cognitive impairment, behavioural phenotypes, and memory impairment (NOR)...

Sepsis is a pathological condition that affects the metabolism of administered drugs, leading to changes in the duration and intensity of their intended efficacies. Proinflammatory cytokines downregulate the expression of cytochrome P450s (P450s). The effects of P450 expression under inflammatory conditions have been studied using prophlogistic substances such as lipopolysaccharide; however, few studies have focused on clinical models of sepsis. Here, we show that cecal ligation and puncture (CLP), an approach for the study of human polymicrobial sepsis, leads to the expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNFα) at 24 h after the CLP operation...

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is well known that the formation of positive feedback between synovial hyperplasia and inflammatory infiltration is intimately associated with the occurrence and development of RA. However, the exact mechanisms still remain unknown, making the early diagnosis and therapy of RA difficult. This study was designed to identify prospective diagnostic and therapeutic biomarkers, as well as their-mediated biological mechanisms in RA...

Acquired aplastic anemia (AA) is an autoimmune disease of bone marrow failure mediated by abnormally activated T cells, manifested by severe depletion of hematopoietic stem and progenitor cells (HSPCs) and peripheral blood cells. Due to the limitation of donors for hematopoietic stem cell transplantation, immunosuppressive therapy (IST) is currently an effective first-line treatment. However, a significant proportion of AA patients remain ineligible for IST, relapse, and develop other hematologic malignancies, such as acute myeloid leukemia after IST...

Schizandrin B (SchB) protects against oxidative, inflammatory, and ferroptotic injury. Oxidative stress and inflammation are indispensably involved in nephrolithiasis and ferroptosis also plays an important role in stone formation. It is unclear whether SchB can ameliorate nephrolithiasis; its underlying mechanism is also unknown. First, we employed bioinformatics to investigate the mechanisms of nephrolithiasis. To evaluate the efficacy of SchB, HK-2 cell models of oxalate-induced damage, Erastin-induced ferroptosis, and the Sprague Dawley rat model of Ethylene Glycol-induced nephrolithiasis were established...

Kawasaki disease (KD) is an acute febrile rash illness among children of unknown etiology, with coronary artery injury. The main purpose of this study was to investigate the protective effects of liraglutide on KD, and elucidate the underlying mechanisms. The candida albicans water-soluble fraction (CAWS)-induced coronary arteritis of mouse KD model in vivo and tumor necrosis factor α (TNF-α) induced endothelial cell injury of human umbilical vein endothelial cell (HUVEC) model in vitro were used to explore the anti-inflammation and anti-apoptosis effects of liraglutide on KD...

Immunostimulatory effects of radiotherapy can be synergistically augmented with immune checkpoint blockade to act both on irradiated tumor lesions and distant, non-irradiated tumor sites. Our hypothesis was that low-dose total body irradiation (L-TBI) combined with hypo-fractionated radiotherapy (H-RT) and anti-programmed cell death protein 1 (aPD-1) checkpoint blockade would enhance the systemic immune response. We tested the efficacy of this triple therapy (L-TBI + H-RT + aPD-1) in BALB/c mice with bilateral breast cancer xenografts...

Intrauterine adhesion (IUA) is manifested by endometrial fibrosis and inflammation, which seriously affects female reproductive health. Macrophages are mainly inflammatory cells and have been reported to participate in the fibrosis of IUA. Oroxylin A (OA), a kind of flavonoid compounds, was showed to possess the inhibitory effects on inflammation and fibrosis. However, the role of OA in IUA remains unclear. In the present study, we found that OA effectively alleviated the level of inflammation and uterine fibrosis in IUA mice...

Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival...

Triple-negative breast cancer (TNBC) exhibits high levels of Epithelial-mesenchymal transition (EMT) and Programmed death ligand 1 (PD-L1) expression, which promotes immune escape and metastasis. Brazilein is a natural compound extracted from Caesalpinia sappan L., and has been demonstrated to be an anti-inflammatory anti- proliferative and apoptosis-inducer in various cancer cells. Here, we investigated the effect of brazilein on EMT and PD-L1 expression in breast cancer cells and its related molecular mechanisms using MCF-7 and MDA-MB-231 cells as a model...

OBJECTIVE: We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022...

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo, respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T...

PURPOSE: To screen and identify the mechanism of honokiol on anti-fungi and anti-inflammation in fungal keratitis (FK) through bioinformatic analysis and biological experiments. METHODS: Transcriptome profile demonstrated differential expression genes (DEGs) of Aspergillus fumigatus keratitis between PBS-treated and honokiol-treated groups via bioinformatics analyses. Inflammatory substances were quantified by qRT-PCR, Western blot and ELISA, and macrophage polarization was examined by flow cytometry...

OBJECTIVE: To evaluate the role of aryl hydrocarbon receptor in the pathogenesis of osteoarthritis (OA) and its association with intestinal microbiome-related tryptophan metabolism. METHODS: Cartilage was isolated from OA patients undergoing total knee arthroplasty and analyzed for expression of aryl hydrocarbon receptor (AhR) and cytochrome P450 of family 1, subfamily A, and polypeptide 1 (CyP1A1). To gain mechanistic insights, OA model was induced in Sprague Dawley rats after antibiotic pretreatment combined with a tryptophan-rich diet (or not)...

The present study investigated whether bone marrow-derived mesenchymal stem cells (BMMSCs) facilitate angiogenesis and improve outcomes of pregnancy with obstetric deep venous thrombosis (DVT) and explored the underlying mechanism. A pregnant DVT rat model was established using a "stenosis" method on the lower segment of the inferior vena cava (IVC). The extent of vascularization in thrombosed IVC was examined by immunohistochemistry. In addition, the effect of BMMSCs on DVT pregnancy outcomes was evaluated...

Several researchers have focused on understanding the pathogenesis and treatment strategies for osteoarthritis (OA). Gastrodin (GAS) is a potential anti-inflammatory agent. In this study, we constructed an in vitro OA chondrocyte model by treating chondrocytes with IL-1β. Next, we determined the expression of aging-related markers and mitochondrial functions in chondrocytes treated with GAS. Further, we constructed a "drug-component-target-pathway-disease" interactive network and determined the effect of GAS on the functions and pathways related to OA...

Trigeminal neuralgia (TN) is a complex orofacial neuropathic pain. The crippling condition's underlying mechanism is still not completely understood. The main cause of lightning-like pain in patients with TN may be chronic inflammation that causes nerve demyelination. Nano-silicon (Si) can safely and continuously produce hydrogen in the alkaline environment of the intestine to exert systemic anti-inflammatory effects. Hydrogen has a promising anti-neuroinflammatory impact. The study aimed to determine how intra-intestinal application of a hydrogen-producing Si-based agent affected the demyelination of the trigeminal ganglion in TN rats...

PURPOSE: Identifying of host-directed targets and molecular markers of immune response for tuberculosis (TB) immunotherapy is urgent and meaningful. Previous studies have demonstrated an important role of autophagy in the course and pathophysiology of TB and is associated with the efficacy of TB treatment. However, its role in TB immunotherapy is still incomplete. METHODS: The effect of autophagy on intracellular bacteria load was examined in sulforaphane (SFN)-treated THP-1 cells...

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by clinical heterogeneity, unpredictable progression, and flare ups. Due to the heterogeneous nature of lupus, it has been challenging to identify sensitive and specific biomarkers for its diagnosis and monitoring. Despite the fact that the mechanism of SLE remains unknown, impressive progress has been made over the last decade towards understanding how different immune cells contribute to its pathogenesis. Research suggests that cellular metabolic programs could affect the immune response by regulating the activation, proliferation, and differentiation of innate and adaptive immune cells...

Emerging evidence reveals that single nucleotide polymorphism (SNP) within miRNAs can affect the risk of cardiovascular diseases. However, the role of miRNA SNPs in abdominal aortic aneurysm (AAA) is unclear. This study aimed to determine the association between SNPs in pri-miR-1-3p and AAA risk, as well as its underlying molecular mechanism. SNP genotyping was performed in 335 AAA patients and 335 controls using the KASP method and tissue miR-1-3p expression was measured by qRT-PCR. The biological effects of significant SNP were validated using in vitro studies...