Azithromycin induces liver injury in mice by targeting the AMPK/Nrf2 pathway
Azithromycin is an antibacterial and anti-inflammatory drug widely used for the treatment of various diseases, including those caused by atypical pathogens, bacterial or viral infections, chronic sinusitis, and bronchial asthma, particularly in pediatric patients. However, concerns have emerged regarding its hepatotoxicity and its precise mechanism of action remains unclear.
Galantamine and wedelolactone combined treatment suppresses LPS-induced NLRP3 inflammasome activation in microglial cells
Inflammasome NLR family pyrin domain-containing 3 (NLRP3) is associated with neurological disorders. Neuroinflammation can be suppressed by inhibiting NLRP3 inflammasome activation, decreasing neurodegenerative disorder progression. We devised a therapeutic technique that can reduce neuroinflammation induced by microglial activation, avoiding neurodegeneration. We aimed to investigate the mechanisms underlying the pharmacological effects of galantamine and wedelolactone by evaluating the response of the nuclear factor kappa B (NF-κB) signaling pathway and NLRP3 inflammasome in lipopolysaccharide (LPS)-activated N9 microglia.
Fumaric acid per se and in combination with methotrexate arrests inflammation via moderating inflammatory and oxidative stress biomarkers in arthritic rats
Fumaric acid is a dicarboxylic acid that belongs to the phenolic class enriched in fruits and vegetables that are traditionally used for the treatment of various ailments. The research was planned to find out the anti-inflammatory and anti-arthritic activities of fumaric acid using o and assays. Moreover, safety study was also done. The 0.1 ml complete Freund's adjuvant was injected in left hind paw in all Wistar rats except normal rats at day 1 to induced arthritis. The treatment with fumaric acid at 10, 20, 40, and fumaric acid 40 mg/kg together with methotrexate (MTX) was administered to immunized rats at 8th day oral gavage and continued till 28th day though, MTX was administered as standard control. The fumaric acid notably ( < 0.0001) lessened the paw edema and arthritic scoring, reinstated body and immune organ weight, and oxidation status in treated rats. Fumaric acid notably restored altered C-reactive protein, rheumatoid factor, liver function tests, ESR, WBCs, RBCs and Hb levels in treated rats. The fumaric acid in combination noticeably ( < 0.01-0.0001) suppressed the expression of TNF- α, IL-6, IL-1β, NF-kβ, and COX-2, and over expressed IL-4, and IL-10 in contrast to other treated groups. Fumaric acid had presented a dose-dependent antioxidant, anti-inflammatory and anti-arthritic activities while notable activity exhibited by fumaric acid in combination with MTX. The fumaric acid exhibited non-significant clinical signs of toxicity and mortality in acute toxicity study. The LD50 was more than 2000 mg/kg. Fumaric acid in combination can be used as disease-modifying anti-rheumatic drug but it will need extensive pre-clinical and clinical studies.
Beta-carotene ameliorates diabetic nephropathy in rats: involvement of AMPK/SIRT1/autophagy pathway
This study aimed to demonstrate the protective effect of beta-carotene against STZ-induced DN in rats and explore the possible underlying mechanisms that may have mediated such condition.
Sirtinol, a SIRT1 inhibitor, inhibits the EMT and metastasis of 4T1 breast cancer cells and impacts the tumor microenvironment
The impact of epigenetic drugs on metastasis and the immunological microenvironment is poorly understood. In this study, we looked at how sirtinol, a SIRT1 inhibitor, affected epithelial-mesenchymal transition (EMT), metastasis, and the immune cells.
Monotropein alleviates acute pulmonary embolism in rats by inhibiting the NF-κB pathway
This study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment.
Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in subchondral bone
The aberrant H-type vessel formation was found to be intimately linked to subchondral bone remodeling during osteoarthritis (OA) development. Herein, we investigated the role and mechanism of osteoblast-secreted slit guidance ligand 3 (Slit3) in H-type vessel formation during OA progression.
Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy
One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs).
Prognostic values of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in the early prediction of aluminum phosphide-poisoned patients' outcomes
In Egypt, aluminum phosphide (ALP) is one of the most serious health problems that threaten the health system, with a very high mortality rate that ranges from 30%-100% of cases, according to medical facilities. ALP records suicidal deaths related to the toxin ingestion in Egypt, which accounts for 70% of the deaths. Patients usually deteriorate early; death is expected in the first 48 h. The aim of this study is to investigate the early recorded neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in anticipation of the ALP-intoxicated patients' outcome.
Aloin alleviates corneal injury in alkali burn via inhibiting neutrophil extracellular traps and promoting Nrf2
Ocular chemical burns are a leading cause of blindness. The cornea is injured by alkali-induced oxidative disturbances and an inflammatory response. The aim of this study was to evaluate the protective effects of aloin, an antioxidant, and anti-inflammatory compound, on corneal alkali burn.
Vinpocetine attenuates 5-fluorouracil-induced intestinal injury: role of the Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3 and RIPK1/RIPK3/MLKL signals
5-Fluorouracil (5-FU) is a chemotherapy drug commonly prescribed in cancer management. Unfortunately, intestinal mucositis restricts 5-FU clinical use. Vinpocetine (VNP) is a synthetic alkaloid that is derived from vincamine. Our study was conducted to elucidate the intestinal protective effects of VNP on 5-FU intestinal injury in rats and explore the underlying mechanisms.
Efficacy and safety of combining radiotherapy with immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a real-world study
The significance of local radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC) is well documented. However, the advent of immunotherapy has raised questions regarding the synergistic survival benefits or potential adverse effects.
Cardioprotective effect of tofisopam against isoprenaline-induced myocardial infarction in rats via modulation of NLRP3\IL-1β\caspase-1 pathway
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Ischemic heart diseases, particularly acute myocardial infarction (MI), represent the most common cause of death. MI is influenced by multiple factors, including the release of inflammatory mediators. A significant percentage of individuals with CVD experience psychological effects, such as anxiety and depression, which are linked to an increased risk of coronary heart disease. Certain anti-anxiety medications have demonstrated immunomodulatory and anti-inflammatory effects. Tofisopam, a 2,3-benzodiazepine with anxiolytic properties, has been shown to exert anti-inflammatory and immunomodulatory effects. The present study investigates the potential of tofisopam as a protective adjuvant against isoprenaline-induced MI in rats and explores the possible underlying mechanisms.
Therapeutic role of physalin A in the pathogenesis of Graves' orbitopathy
Graves' orbitopathy (GO) is an autoimmune condition that causes serious ocular symptoms; its treatment strategies are limited. Physalin A is a phytosterol that has shown various therapeutic properties, including anti-inflammatory and anti-fibrotic effects. In this study, we investigated whether physalin A could inhibit inflammation, fibrosis, hyaluronan (hyaluronic acid) production, and adipogenesis, which are crucial to the pathogenesis of GO.
An integrative lipidomics and transcriptomics study revealing Bavachin and Icariin synergistically induce idiosyncratic liver injury
Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). (PF) and (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood. In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-α-mediated mouse model. Lipidomics and transcriptomics were used to investigate their related mechanism. Liver biochemistry and histopathology analyses revealed that co-exposure to Bav, Ica, and a non-toxic dose of TNF-α prestimulation induced significant liver injury, while Bav and Ica alone did not. Lipidomics identified seven differentially abundant metabolites in the Bav/Ica/TNF-α group compared to the Ica/TNF-α or Bav/TNF-α groups, mainly enriched in alpha-linolenic acid (ALA), arachidonic acid (AA), and linoleic acid (LA) metabolic pathways. Additionally, transcriptomics revealed 49 differentially expressed genes (DEGs) in the Bav/TNF-α vs Bav/Ica/TNF-α and Ica/TNF-α vs Bav/Ica/TNF-α groups, primarily associated with the PI3K/AKT/mTOR signaling pathway and sphingolipid metabolism. Integrative lipidomics and transcriptomics analyses identified significant positive correlations between five differential metabolites (DMs) - PC (O-16:0_14:1), PG (22:1_20:3), PI (16:0_14:1), PS (18:0_19:2), and TG (17:0_18:2_22:5) - and ten DEGs - . Collectively, these results suggest that alterations in intracellular metabolism and gene expression levels may contribute to the synergistic induction of IDILI by the incompatible pair Bav and Ica in the presence of TNF-α.
Intervention of inflammation associated with ankylosing spondylitis by triptolide promotes histone H3 Iys-27 trimethylation
This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS). Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway. We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt ( < 0.05), JAK2 and STAT3 (JAK2: < 0.05; STAT3: < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene. Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.
Immunosuppressive effects of triptolide via interleukin-2/receptor signaling
Triptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression.
Sirt1/Nrf2/TNFα; TLR4/Myd88/NF-κB signaling pathways are involved in mediating hepatoprotective effect of bupropion in rat model of myocardial infarction
The aim of the current study is to identify the possible protective effect of bupropion (BUP) on liver injury in rat model of myocardial infarction (MI). BUP was administered in the presence and absence of MI.
Safety observation of COVID-19 inactivated vaccine in immature mice
To investigate the safety of COVID-19 inactivated vaccine in immature mice.
Factors Inducing Cutaneous Adverse Reactions in Cancer Patients Treated with PD-1 and PD-L1 Inhibitors: A Machine-Learning Algorithm Approach
Immune checkpoint inhibitors (ICIs) show promise in cancer treatment but can lead to immune-related adverse events (irAEs), notably affecting the skin. Understanding the factors behind these skin reactions is crucial for effective management during treatment. Hence, the aim of this study was to uncover associations between patient characteristics and cutaneous adverse reactions among cancer patients undergoing ICI treatment. The study involved 209 cancer patients receiving ICIs. Statistical methods, including the chi-square test, Fisher's exact test, and multivariable logistic regression, were employed to analyze variables such as hypertension, antihistamine use, cancer metastasis, diabetes, and opioid usage. Additionally, machine learning techniques, including logistic regression, elastic net, random forest, and support vector machines (SVM), were utilized to develop predictive models anticipating skin-related adverse events. Results highlighted significant associations between specific patient attributes and the incidence of skin reactions post-ICI treatment. Notably, patients using antihistamines or with cancer metastasis exhibited higher rates of skin adverse reactions, while those with diabetes or using opioids displayed lower incidence rates. Robust performance in forecasting these adverse events was observed, particularly in the predictive models employing logistic regression and elastic net. This pioneering study contributes crucial insights into predictive modeling for ICI-induced skin reactions, emphasizing the importance of personalized treatment strategies. By identifying risk factors and utilizing tailored predictive models, healthcare providers can proactively manage adverse events, optimizing the benefits of ICIs while mitigating potential side effects.
Tanshinone IIA inhibits the apoptosis process of nerve cells by upshifting SIRT1 and FOXO3α protein and regulating anti- oxidative stress molecules and inflammatory factors in cerebral infarction model
As a prevalent cerebrovascular disorder, cerebral infarction (CI) has garnered extensive attention globally due to its high incidence and substantial fatality rate. Ischemia-reperfusion injury (IRI) exacerbates not only neuronal demise but also amplifies neural functional impairment. Tanshinone IIA (Tan IIA) has been identified to confer protection against IRI, yet the precise underlying mechanisms remain elusive. This work aimed to delve into the mechanistic role of Tan IIA in CI, with the goal of furnishing more distinct theoretical substantiation for its clinical application.