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关键词： Nanotechnology   HWW   PARP1   IL-17A   Behaviors   Neurotransmitters  

摘要： Hospital wastewater (HWW) poses a serious hazard to human health security concerning its high susceptibility to neurodegeneration. Water sources and ecosystems are exposed to a complicated pollution load from a variety of refractory organics and pharmaceutical active composites. This study evaluates the treated newly developed nanocomposite (NiFe2O4) HWW on the neural injury induced by HWW action in rats. Three groups of male Wistar rats were distributed, with eight rats in each: group I: tap water served as a control;group II: HWW;and group III: nano-HWW. Each group was intragastrical administrated with each type of water (2.5 ml/100 g ***/6 h) for 28 consecutive days. The open field test and Morris Water Maze assessed behavioral activity and spatial learning 2 days before the last day. The research demonstrated that HWW treated with nanocomposite (NiFe2O4) may exert decreased risks of the neural impairment effect of HWW. This improvement was achieved by reducing the neurotoxicity by lowering nitric oxide contents, lipid peroxidation, acetylcholinesterase, interleukin-17A (IL-17A), and poly(ADP-ribose) polymerase1(PARP1) while restoring the antioxidant biomarkers and neurotransmitter levels (beta-endorphin, norepinephrine, dopamine, and serotonin) of the treated groups in the cortex and brainstem and enhancement of the histopathology of the cortex as well. In conclusion, this study introduced a newly developed nanotechnology application for treating HWW to protect from neural injury. The findings of this research have significant value for policymakers, Ministry of Health management, and environmental organizations in their selection of suitable techniques and procedures to optimize hospital wastewater treatment efficiency.

关键词： Gastritis   Gastric cancer   Helicobacter pylori   Non   Helicobacter pylori bacteria   IL-33  

摘要： Gastric cancer, a globally prevalent malignant tumor, is characterized by low early diagnosis rate, high metastasis rate, and poor prognosis, particularly in East Asia, Eastern Europe, and South America. Helicobacter pylori (H. pylori) is recognized as the primary risk factor for gastric cancer. However, the fact that fewer than 3 % of infected individuals develop cancer suggests that other bacteria may also influence gastric carcinogenesis. A diverse community of microorganisms may interact with H. pylori, thereby driving disease progression. Here, the role of the cytokine IL-33, a member of the IL-1 family, is scrutinized. Its production can be induced by H. pylori through the activation of specific signaling pathways, and it contributes to the inflammatory environment by promoting the release of pro-inflammatory cytokines. This article reviews the conflicting evidence regarding IL33's role in the progression from gastritis to gastric cancer and discusses the potential therapeutic implications of targeting the IL-33/ST2 axis, with various antibodies and inhibitors in development or undergoing clinical trials for inflammatory diseases. However, the role of IL-33 in gastric cancer treatment remains to be fully elucidated, with its effects potentially dependent on the cellular context and stage of cancer progression. In summary, this review provides a comprehensive overview of the intricate relationship between gastric microbiota, IL-33, and gastritis - gastric cancer transition, offering insights into potential therapeutic targets and the development of novel treatment strategies.

关键词： Hepatic stellate cells   cancer   AMIGO2   interleukin-8   extracellular vesicles   migration.  

摘要： Background/Aim: Our previous studies have demonstrated that amphoterin-induced gene and open reading frame 2 (AMIGO2) functions as a driver gene for liver metastasis, regulating adhesion between cancer cells and liver endothelial cells. AMIGO2-containing small extracellular vesicles (sEVs) derived from gastric cancer (GC) cells were shown to enhance adhesion to hepatic endothelial cells, contributing to pre-metastatic niche formation. However, their role in promoting cancer cell migration into the liver parenchyma remained unclear. This study investigated whether AMIGO2-containing sEVs activate hepatic stellate cells (HSCs) and promote cancer cell migration. Materials and Methods: AMIGO2-over-expressing and control cell lines (MKN28) were established. sEVs isolated from each cell line were added to human HSCs (TWINT-1). The supernatant collected was added to MKN28 to quantitatively evaluate migration ability and nuclear translocation of NF-kB. A chemokine array identified secreted factors affected by sEV treatment. Results: HSCs were activated by AMIGO2-containing EVs, resulting in increased IL-8 secretion through NF-kB nuclear translocation. This IL-8-rich supernatant significantly enhanced GC cell migration. Neutralizing IL-8 with antibodies suppressed this migration, confirming its pivotal role. Conclusion: AMIGO2-containing sEVs derived from GC cells actively modify the hepatic microenvironment by activating HSCs and inducing IL-8 secretion, which promotes GC cell migration into the liver parenchyma. This process contributes to the formation of a pre-metastatic niche, highlighting AMIGO2-containing sEVs as potential therapeutic targets for preventing liver metastasis.

摘要： Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein >3 mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5 mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dorsomedial prefrontal cortex (dmPFC), ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.

摘要： Preclinical studies have shown that interleukin (IL)-1 beta blockade can modulate the tumor microenvironment (TME) to activate antitumor immunity and, in combination with immune checkpoint inhibitors (ICIs), prevent cancer growth. Our study investigates if immune biomarkers in the TME affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with the IL-1 beta inhibitor canakinumab plus an ICI-based therapy and describes canakinumab effects on the TMEs in these patients. Exploratory analyses were conducted in two prospective trials evaluating canakinumab combined with pembrolizumab-based regimens in patients with NSCLC: CANOPY-1 (first-line setting) and CANOPY-N (neoadjuvant setting). Immunohistochemistry (IHC) and transcriptomic analyses were performed on baseline tumor samples from CANOPY-1, and IHC and multiplex immunofluorescence analyses were performed on baseline and posttreatment tumor samples from CANOPY-N. Associations with clinical outcomes were evaluated. In CANOPY-1, in patients with low levels of T-cell infiltration in the tumor, the addition of canakinumab to a pembrolizumab-based regimen was associated with progression-free and overall survival improvements. Low levels of T-cell infiltration were associated with an immunosuppressive gene expression phenotype, supporting the role of low T-cell infiltration as a surrogate of an overall immunosuppressive TME. In CANOPY-N, a reduction in immunosuppressive cells in the TME was observed following canakinumab and pembrolizumab treatment. Our exploratory biomarker analyses from the CANOPY-1 and CANOPY-N trials suggest that IL-1 beta blockade may shift the TME toward an immune-activated status and that patients with immunosuppressive TME features could benefit from the addition of canakinumab to an ICI-based ***: Patients with NSCLC with immunosuppressive tumor features and low T-cell infiltration derive less benefit from ICI-based treatment. Biomarker analyses presented he

关键词： DQB1*03:01:60   DQB1*03:526   DQB1*06:03:50   new HLA allele   NGS  

摘要： Three novel HLA alleles HLA-DQB1*03:01:60, -DQB1*03:526, and -DQB1*06:03:50 alleles detected during routine next generation sequencing.

关键词： HIF   hypoxia   IL-13   IL-33   LPS   mast cell  

摘要： Lipopolysaccharide (LPS) is an exacerbating factor for allergic airway inflammation at least partly due to the activation of mast cells (MCs). LPS stimulates MCs to express both pro-inflammatory and type 2 cytokines, among which interleukin (IL)-13 is essential for the generation of allergic diseases. LPS also induces the expression of "alarmins" such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) from various cell types including epithelial cells, and increased serum IL-33 levels were reported to correlate with disease severity of asthma. MCs reside in peripheral tissues where the oxygen concentration is significantly lower than that in the air and further decreased by inflammation and bronchoconstriction in asthma. However, the effects of hypoxia on LPS-induced cytokine expression in MCs have not been fully elucidated. Here we show that LPS induces Il4, Il6, Il13, Il33, Tnf, and Tslp mRNAs in MCs. Notably, hypoxia robustly enhanced expressions of Il13 and Il33, but not the other cytokines in LPS-stimulated MCs. We also found that this promotive effect is dependent on the presence of hypoxia-inducible factor (HIF) 1 alpha protein. Our study will provide new insight on the role of MCs in the LPS-associated pathogenesis of allergic diseases.

关键词： Ankylosing spondylitis   Axial spondyloarthritis   Sacroiliac joints   Low back pain   HLA B27   MHC  

摘要： The history of (axial) spondyloarthritis has started several centuries ago. Since the end of the 19th century major achievements have been made. This historical review tries to show how closely the advances in clinical medicine in rheumatology have been related to advances made in basic sciences.

关键词： female reproductive health   inflammatory bio markers   polycystic ovary syndrome (pcos)   systematic review and meta analysis   women’s health  

摘要： Chronic low-grade inflammation plays a crucial role in the pathophysiology of polycystic ovary syndrome (PCOS). This systematic review aims to synthesize the recent evidence on key inflammatory markers in PCOS and the role of IL-6. A comprehensive literature search was conducted using the PubMed, Web of Science, Cochrane Library, and Google Scholar databases. Studies published between 2014 and 2024 were screened based on predefined eligibility criteria. Both observational and interventional studies that reported levels of inflammatory markers in patients with polycystic ovary syndrome (PCOS) were included. Data were systematically extracted, and the quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies, the Cochrane Risk of Bias tool for randomized controlled trials (RCTs), and the ROBINS-1 tool for non-randomized controlled trials. A statistical synthesis of IL-6 levels was performed for the meta-analysis using a random-effects model in R. A total of 44 studies met the inclusion criteria for qualitative analysis and identified 94 biomarkers. The most commonly used biomarkers across the majority of studies, listed in descending order, are as follows: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), CRP, adiponectin, IL-18, vascular endothelial growth factor (VEGF), IL-8, IL-1β, sex hormone binding globulin (SHBG), leptin, and vascular cell adhesion protein 1 (VCAM-1). Additionally, four case-control studies conducted in four countries (Taiwan, Russia, Spain, and Turkey) were included in the quantitative analysis, which involved 689 participants (PCOS group: n = 365; Control group: n = 324). The pooled mean difference (MD), calculated using the random-effects model, was 0.72 (0.47; 0.98) (p < 0.0001), indicating a significant increase in IL-6 levels among PCOS patients compared to the control group. The funnel plot exhibited slight asymmetry, suggesting publication