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Introduction: Since 2016, a highly lethal visceral gout induced by infection with the novel goose astrovirus (GoAstV) resulted in an ongoing outbreak in goslings in China, with a mortality rate ranging from 10% to 50%, and causing considerable economic losses in the goose industry. However, the pathogenesis of GoAstV and the molecular mechanism by which kidney lesions are induced by GoAstV infection are unclear. Methods: In the present study, a GEK cell infection model for GoAstV was established, and the apoptosis, inflammatory and innate immune responses induced by GoAstV were investigated in GEK cells. Results: The results shown that the expression of proapoptotic proteins, including Bax, caspase-3, caspase-9 and cytochrome c , increased in the infection group; however, the expression of the antiapoptotic protein Bcl-2 decreased, indicating that apoptosis was induced by GoAstV infection in GEK cells. Besides, the activation of the RIG-I/MDA5 pathway and the downstream upregulation of proinflammatory cytokines, including the adapter proteins MAVS, IRF7 and NF-κB and the proinflammatory cytokines IL-6, IL-8 and TNF-α, were detected in GEK cells infected with GoAstV. In addition, GoAstV infection induces the activation of the NLPR3 pathway and further stimulates the increased production of IL-1β. In summary, the present study revealed that GoAstV infection could induce apoptosis and the activation of the RIG-I/MDA5 and NLRP3 pathways in GEK cells, as well as the massive release of proinflammatory cytokines. Discussion: These results are helpful for elucidating the molecular mechanism of pathological lesions in the kidney in gout goslings infected with GoAstV and the interaction between GoAstV and the innate immune system of the host. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the prognostic value of systematic inflammatory response in patients with lymph node-negative colorectal cancer. Methods: We retrospectively investigated 245 patients with lymph node-negative colorectal cancer who underwent curative resection and evaluated the prognostic impact of systematic inflammatory response, which was represented by neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and C-reactive protein-to-albumin ratio (CAR). Then, the prognostic significance of the systematic inflammatory response on survival was analyzed using the Kaplan-Meier method in patients selected by propensity score matching (PSM) analysis. Results: In the multivariate analysis, CAR ≥ .081 (P = .004) was independent predictors of disease-free survival, while American Society of Anesthesiologists physical status ≥3 (P = .049) and CAR ≥ .081 (P < .001) were independent predictors of overall survival. By PSM analysis, PSM-high-CAR was significantly associated with worse disease-free survival (P = .043) and overall survival (P = .041) in patients with lymph node-negative colorectal cancer. Conclusions: C-reactive protein-to-albumin ratio may be a significant indicator of poor long-term outcomes in patients with lymph node-negative colorectal cancer. [ABSTRACT FROM AUTHOR]

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG. [ABSTRACT FROM AUTHOR]

Summary: The inflammatory response to a truly closed castration procedure in 51 horses using an inguinal approach was quantified by serum amyloid A (SAA) measurements to be on average 94 mg/L on day three after surgery. The average SAA value after field castrations, using a scrotal approach, was reported by four different investigations to be between 480 and 708 mg/L on day three post‐operatively. The discrepancy in SAA levels between these different approaches proved to be significant (p < 0.001), quantifying a substantially lower inflammatory response of the closed inguinal technique over regular field castrations using a scrotal approach. [ABSTRACT FROM AUTHOR]

Background: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. Methods: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. Results: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1β, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. Conclusions: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism. [ABSTRACT FROM AUTHOR]

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury. Various calcium channels are involved in cerebral ischemia/reperfusion injury. Cav3.2 channel is a main subtype of T-type calcium channels. T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. However, the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear. Here, in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons. The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons. We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury. Cav3.2 knockout markedly reduced infarct volume and brain water content, and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury. Additionally, Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress, inflammatory response, and neuronal apoptosis. In the hippocampus of Cav3.2-knockout mice, calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury. These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling. Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), degenerative joint disease, is the most prevalent form of arthritis worldwide. Besides its substantial burden on society, the high OA morbidity greatly diminishes patients' quality of life. According to recent research, patients-derived serum extracellular vesicles (EVs) are critically involved in sustaining the corresponding disease progression. However, limited research has fully explored the specific functions and molecular mechanisms of OA serum-derived EVs in disease progression. Consequently, we aimed to investigate the underlying mechanism of OA rats-derived serum EVs in regulating OA progression. Before constructing the exosome-cell co-culture system, EVs were extracted from OA and control rat serum and co-cultured with bone marrow mesenchymal stem cells (BM-MSCs). Western blotting (WB), RT-qPCR, and enzyme-linked immunosorbent assay (ELISA) results revealed that OA rat serum-derived EVs upregulated cell pyroptosis-related markers, including nod-Like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin D (GSDMD), and cleaved caspase-1. The OA rat-EVs also induced the release of LDH and inflammatory cytokines, including interleukin (IL)-1β, IL-18, IL-6, and TNF-α. Additional experiments revealed that OA rat-EVs delivered miR-133a-3p to BM-MSCs and upregulated miR-133a-3p to degrade sirtuin 1 (SIRT1), and activating the downstream NF-κB signaling pathway. Furthermore, the rescuing experiments confirmed that silencing SIRT1 abrogated the miR-133a-3p-induced protective effects in OA-EVs-treated BM-MSCs. In conclusion, OA rats-derived miR-133a-3p-containing EVs modulated the downstream SIRT1/NF-κB pathway-mediated pyroptotic cell death and inflammation in OA. In other words, this study confirmed the role and underlying mechanisms by which OA-associated serum EVs regulate pyroptosis and inflammation response in OA development. [ABSTRACT FROM AUTHOR]

Common digestive precancerous lesions, including oral potentially malignant disorders (OPMDs), gastric ulcers and colorectal adenoma, harbor high risk of cancerous transformation. Early intervention of these lesions is significant to prevent carcinogenesis and improve patients’ prognosis. Lycopene, a carotenoid predominantly accumulated in tomatoes, is clinically recommended with its cis structure; as lycopene harbors the most potent antioxidative effects among carotenoids, its chemopreventive effects on the premalignant lesions is noted. Despite several reviews have assessed lycopene’s efficacy for OPMDs, emerging studies have reported varying efficacy for digestive precancerous lesion with no comprehensive summary. Therefore, this review initially evaluates the efficacy and underlying mechanisms of lycopene for management of digestive precancerous lesions. According to the included studies, lycopene may show high promise in the management of digestive precancerous lesions, such as relieving mouth opening and burning sensation of oral submucous fibrosis (OSF), presenting potentially equivalent efficacy on managing oral lichen planus (OLP) as steroids and alleviating gastrointestinal precancers’ symptoms, meanwhile lowering colon cancer risk. Moreover, its mechanisms for managing digestive precancerous lesions are concretely summarized, including anti-oxidative stress effects, anti-inflammatory response and regulation of cell proliferation and apoptosis, especially its modifications on TLR4/TRIF/NF-κB signaling pathway and p53-dependent cell cycle control and apoptosis. More studies are warranted to confirm its long-term efficacy and preventive role against malignant transformation of digestive precancerous lesions as evidence is insufficient. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis is a common chronic inflammation of joints caused by degenerative changes of articular cartilage. More and more studies have shown that mechanical stress is closely related to the development of osteoarthritis. The Hippo pathway is not only involved in the development of tissue cells, but also an effecting factor of mechanical stress, which is involved in the regulation of bone metabolism and cartilage metabolism. OBJECTIVE: Regulation of the Hippo pathway may become one of the new targets for intervention in osteoarthritis. Therefore, this paper reviewed the research on the effect of mechanical stress regulation of the Hippo pathway on osteoarthritis to provide ideas for the pathogenesis of osteoarthritis and provide a new theoretical basis for the treatment of osteoarthritis. METHODS: PubMed, Web of Science, Embase, CNKI, VIP, and WanFang databases were used for a literature search for articles published from inception to 2023 concerning the influence of mechanical stress on osteoarthritis and mechanical stress, Hippo pathway, and osteoarthritis. A total of 75 articles were finally reviewed. RESULTS AND CONCLUSION: (1) Different mechanical stresses may play different roles in cell proliferation, apoptosis and differentiation, osteoarthritis inflammation, and vascular homeostasis in osteoarthritis. (2) Hard extracellular matrix, low cell density, medium shear force, medium tensile force, and compression force can achieve cell proliferation, osteogenic differentiation, and vascular homeostasis, and inhibit inflammatory response by activating YAP/TAZ. (3) Soft extracellular matrix, high cell density, excessive shear force, excessive tensile force, and compressive force inhibit cell proliferation, enhance cartilage differentiation, disrupt vascular homeostasis, and promote inflammation through inactivation of YAP/TAZ, thus promoting the process of osteoarthritis. [ABSTRACT FROM AUTHOR]

CXCL13 is a chemokine that plays an important role in the regulation and development of secondary lymphoid organs. CXCL13 is also involved in the regulation of pathological processes, particularly inflammatory responses, of many diseases. The function of CXCL13 varies depending on the condition of the host. In a healthy condition, CXCL13 is mainly secreted by mouse stromal cells or human follicular helper T cells, whereas in diseases conditions, they are produced by human peripheral helper T cells and macrophages in non-lymphoid tissues; this is termed ectopic expression of CXCL13. Ectopic CXCL13 expression is involved in the pathogenesis of various immune-mediated inflammatory diseases as it regulates the migration of B lymphocytes, T lymphocytes, and other immune cells in inflammatory sites as well as influences the expression of inflammatory factors. Additionally, ectopic expression of CXCL13 plays a key role in ectopic lymphoid organ formation. In this review, we focused on the sources of CXCL13 in different conditions and its regulatory mechanisms in immune-mediated inflammatory diseases, providing novel ideas for further research on targeting CXCL13 for the treatment of immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objective: This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD). Methods: We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme‐linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit‐8 (CCK‐8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis‐related factors was detected using western blot (WB) and quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low‐density lipoprotein (ox‐LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1 beta (IL‐1β). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe‐TRPV6 + si‐PKA group. Conclusions: In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and efficacy of selective intraarterial hypothermia combined with mechanical thrombectomy in the treatment of acute cerebral infarction based on microcatheter technology. Methods: A total of 142 patients with anterior circulation large vessel occlusion were randomly assigned to the hypothermic treatment group (test group) and the conventional treatment group (control group). National Institutes of Health Stroke Scale (NIHSS) scores, postoperative infarct volume, the 90-day good prognosis rate (modified Rankin Scale (mRS) score =2 points), and the mortality rate of the two groups were compared and analyzed. Blood specimens were collected from patients before and after treatment. Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), IL-10, and RNA-binding motif protein 3 (RBM3) were measured. Results: The 7-day postoperative cerebral infarct volume [(63.7 ± 22.1) ml vs. (88.5 ± 20.8) ml] and NIHSS scores at postoperative Days 1, 7, and 14 [(6.8 ± 3.8) points vs. (8.2 ± 3.5) points; (2.6 ± 1.6) points vs. (4.0 ± 1.8) points; (2.0 ± 1.2) points vs. (3.5 ± 2.1) points] in the test group were significantly lower than those in the control group. The good prognosis rate at 90 days postoperatively (54.9 vs. 35.2%, P = 0.018) was significantly higher in the test group than in the control group. The 90-day mortality rate was not statistically significant (7.0 vs. 8.5%, P=0.754). Immediately after surgery and 1 day after surgery, SOD, IL-10, and RBM3 levels in the test group were relatively higher than those in the control group, and the differences were statistically significant. Immediately after surgery and 1 day after surgery, MDA and IL-6 levels in the test group were relatively reduced compared with those in the control group, and the differences were statistically significant (P < 0.05). In the test group, RBM3 was positively correlated with SOD and IL-10. Conclusion: Mechanical thrombectomy combined with intraarterial cold saline perfusion is a safe and effectivemeasure for the treatment of acute cerebral infarction. Postoperative NIHSS scores and infarct volumes were significantly improved with this strategy compared with simple mechanical thrombectomy, and the 90-day good prognosis rate was improved. The mechanism by which this treatment exerts its cerebral protective effect may be by inhibiting the transformation of the ischaemic penumbra of the infarct core area, scavenging some oxygen free radicals, reducing inflammatory injury to cells after acute infarction and ischaemia-reperfusion, and promoting RBM3 production in cells. [ABSTRACT FROM AUTHOR]

Background: Insomnia (ISM) is one of the non-traditional drivers of atherosclerosis (AS) and an important risk factor for AS-related cardiovascular disease. Our study aimed to explore the shared pathways and diagnostic biomarkers of ISM-related AS using integrated bioinformatics analysis. Methods: We download the datasets from the Gene Expression Omnibus database and the GeneCards database. Weighted gene co-expression network analysis and gene differential expression analysis were applied to screen the ASrelated gene set. The shared genes of ISM and AS were obtained by intersecting with ISM-related genes. Subsequently, candidate diagnostic biomarkers were identified by constructing protein-protein interaction networks and machine learning algorithms, and a nomogram was constructed. Moreover, to explore potential mechanisms, a comprehensive analysis of shared genes was carried out, including enrichment analysis, protein interactions, immune cell infiltration, and single-cell sequencing analysis. Results: We successfully screened 61 genes shared by ISM and AS, of which 3 genes (IL10RA, CCR1, and SPI1) were identified as diagnostic biomarkers. A nomogram with excellent predictive value was constructed (the area under curve of the model constructed by the biomarkers was 0.931, and the validation set was 0.745). In addition, the shared genes were mainly enriched in immune and inflammatory response regulation pathways. The biomarkers were associated with a variety of immune cells, especially myeloid immune cells. Conclusion: We constructed a diagnostic nomogram based on IL10RA, CCR1, and SPI1 and explored the inflammatory-immune mechanisms, which indicated new insights for early diagnosis and treatment of ISM-related AS. [ABSTRACT FROM AUTHOR]

As an indispensable inflammatory mediator during sepsis, granulocyte colony-stimulating factor (G-CSF) facilitates neutrophil production by activating G-CSFR. However, little is known about the role of intracellular downstream signalling pathways in the induction of inflammation. To explore the functions of molecules in regulating G-CSFR signalling, RNA sequencing and integrated proteomic and phosphoproteomic analyses were conducted to predict the differentially expressed molecules in modulating the inflammatory response after G-CSFR expression was either up- or downregulated, in addition to the confirmation of their biological function by diverse experimental methods. In the integrated bioinformatic analysis, 3190 differentially expressed genes (DEGs) and 1559 differentially expressed proteins (DEPs) were identified in multiple-group comparisons (p < 0.05, FC > ± 1.5) using enrichment analyses, as well as those classic pathways such as the TNF, NFkappaB, IL-17, and TLR signalling pathways. Among them, 201 proteins, especillay intercellular cell adhesion molecule-1 (ICAM1) and PKCa, were identified as potential molecules involved in inflammation according to the protein–protein interaction (PPI) analysis, and the leukocyte transendothelial migration (TEM) pathway was attributed to the intervention of G-CSFR. Compared with the control and TNF-a treatment, the G-CSFR (G-CSFROE)-overexpressing led to an obvious increase in the number of leukocytes with the TEM phenotype. Mechanically, the expression of ICAM1 and PKCa was significantly up- and downregulated by G-CSFROE, which directly led to increased TEM; moreover, PKCa expression was negatively regulated by ICAM1 expression, leading to aberrant leukocyte TEM. Altogether, the ICAM1‒PKCa axis was found a meaningful target in the leukocyte TEM induced by G-CSFR upregulation. [ABSTRACT FROM AUTHOR]

AbstractRespiratory co-exposure to ambient PM2.5 and electronic cigarettes (e-cigarettes) frequently occurs in public. However, the combined effects on human respiratory health have not been well documented. To discuss potential co-effects and possible biological mechanisms, A549/THP-1 co-cultures and BEAS-2B cells were exposed to unvapedtobacco or mint-flavored e-liquids (0–7.2% v/v), e-cigarette aerosol extract (ECE, 0–50% v/v), PM2.5 (60 μg/mL), or PM2.5 + ECE for 24 h. Cell viability assessments on e-liquids, ECE, PM2.5 + ECE showed that the mint flavor exhibited higher cytotoxicity compared to the tobacco flavor in both A549/THP-1 and BEAS-2B. However, the influence of flavors on ROS levels and mRNA expression of inflammatory markers (IL-6, TNF-α, IL-8, IL-1β) after ECE exposure demonstrated inconsistency in the two cell models. PM2.5 + ECE treatment notably elevated ROS production and inflammation responses compared to ECE alone exposure. Only co-exposure induced a significant increase in nuclear transcription factor-κB p65 (NF-κB p65) and NOD-like receptor 3 (NLRP3) protein expression regardless of flavors. Our results indicate that PM2.5-treated cells exacerbate the adverse effects induced by ECE in both A549/THP-1 and BEAS-2B cells. Flavors in unvaped e-liquids affect cytotoxicity, oxidative stress and inflammation response, but these effects vary depending on the vaping process and the specific cell line. [ABSTRACT FROM AUTHOR]

This study aimed to compare the acute inflammatory response following high-intensity eccentric exercise between resistance-trained young and master athletes with similar performance levels. Resistance-trained young (n=8; 22±2 years) and master (n=8; 52±4 years) male athletes of a similar performance level performed a standardized high-intensity eccentric squat exercise protocol (10 sets of half-squats at 70% of 1-repetition maximum). The serum concentration of 20 biomarkers related to tissue damage, inflammation, remodeling, and repair was measured at baseline, immediately after exercise, and over a 72 h recovery period. Both groups experienced similar muscle damage as evidenced by a comparable increase in creatine kinase activity 24 h after exercise (p<0.001). Interleukin-6 (p=0.009) and growth hormone (p<0.001) increased immediately post-exercise in both groups. Monocyte chemoattractant protein-1 increased immediately post-exercise only in young athletes (p=0.003) and then decreased 24 h later. There were no significant differences for the remaining variables, including cell markers related to neutrophil/macrophage activation or pro/anti-inflammatory cytokines. Resistance-trained young and master athletes, matched for performance level, showed an overall similar inflammatory response to eccentric exercise, possibly reflecting regulatory mechanisms or immunological adaptations to chronic stimulation in master athletes. [ABSTRACT FROM AUTHOR]

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases. [ABSTRACT FROM AUTHOR]

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO2), zinc oxide (ZnO), silica (SiO2), cerium oxide (CeO2), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO2 and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO2. This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks. [ABSTRACT FROM AUTHOR]

This study investigated the effects of substituting inorganic trace minerals (ITM) with advanced chelate technology-based TM (ACTM) in broiler chicken feed on productive performance, metabolic profile, humoral immunity, antioxidant status, and modulation of NF-kB and Nrf2 signaling pathways in mixed Eimeria species exposure. The study involved 480 newly hatched male broiler chickens, which were divided into 5 treatment groups, each with 6 replicate cages and 16 chickens per replicate. The experimental treatments included an uninfected negative control group fed a basal diet with recommended inorganic TM levels (NC), an infected positive control group fed the same diet (PC), a PC group supplemented with salinomycin (SAL), and two PC groups in which the basal diet was replaced with 50% and 100% ACTM instead of inorganic TM (ACTM50 and ACTM100, respectively). All groups, except for the NC group, were orally challenged with mixed Eimeria species oocysts on day 14. According to the results, the PC group showed lower feed intake, breast yield, low-density lipoprotein-cholesterol concentration, lactobacillus spp. counts, and serum IgG levels, but higher jejunal TGF-β expression versus the NC group. The broilers in the NC, SAL, and ACTM100 groups showed higher body weight gain, carcass yield, and TGF-β expression, but lower serum alkaline phosphatase activity, ileal E. coli count, and jejunal expression levels of IL-1β, IL-6, IFN-γ, Nrf2, and SOD1 compared to the PC group, with the NC group having the highest body weight gain and lowest IL-1β and Nrf2 expression levels. Furthermore, the administration of ACTM100 treatment improved feed efficiency, increased serum iron, zinc, manganese, and copper levels, enhanced total antioxidant capacity and different antioxidant enzyme activities, and reduced malondialdehyde concentration. In conclusion, complete replacement of ITM with ACTM effectively protects broilers from Eimeria infection, with similar positive effects to SAL treatment in terms of productive performance and anti-inflammatory responses and better antioxidant responses and mineral availability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells. The Toll-like receptors (TLRs)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway plays an important role in the development of the disease. Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE: To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models, which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS: The literature related to the topic from January 2002 to December 2022 was searched in CNKI, WanFang and PubMed databases. A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION: The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response. The TLRs/ MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells, destroying the integrity of the blood-brain barrier, and promoting the activation of T cells, B cells and microglia. By targeting TLRs, MyD88 and NF-κB molecules, inhibiting the activation or signal transduction of TLRs, MyD88 and NF-κB, and reducing the secretion of pro-inflammatory factors, multiple sclerosis can be treated. Animal studies have shown that active ingredients of traditional Chinese medicines, such as flavonoids and glycosides, and traditional Chinese medicine compound formulas, such as Buyang Huanwu Tang, can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway, which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sepsis complicated by myocardial injury is characterized by a high mortality. Metformin can prevent sepsis-induced myocardial dysfunction byexerting anti-inflammatory effects, improving oxidative stress, and reducing apoptosis. However, it is unclear whether metformin-induced autophagy plays an important role in the protective effect against sepsis-induced myocardial injury. OBJECTIVE: To explore the effect of metformin pretreatment on myocardial injury in septic mice. METHODS: A total of 40 male Kunming mice were randomly divided into sham operation group, model group, metformin group, and metformin+ 3-methyladenine group, with 10 mice in each group. The latter two groups were intraperitoneally injected with metformin for 14 days at a fixed time every day, and the metformin+3-methyladenine group was intraperitoneally injected with 3-methyladenine 1 hour before modeling. Twenty-four hours after the last injection of metformin, cecal ligation and perforation were used to construct a model of myocardial injury in septic mice. The sham operation group was not ligated and perforated. All mice were sacrificed 24 hours after surgery, and blood and myocardial specimens were collected. The levels of inflammatory factors and myocardial injury markers in serum were detected by ELISA. The mRNA expression of autophagy markers LC3B and p62 in myocardial tissue was detected by RT-qPCR. The protein expression of LC3B, Beclin-1, p62, p-AMPK, and AMPK in myocardial tissue was detected by western blot. The pathological changes in myocardial tissue were detected by hematoxylin-eosin staining. RESULTS AND CONCLUSION: Autophagy was inhibited in septic mice with myocardial injury. Compared with the sham operation group, the levels of serum tumor necrosis factor-α, interleukin-1β, interleukin-6, creatine kinase isoenzyme, and troponin T were increased in the model group (P < 0.05), but there was no significant difference in p62, LC3II/LC3I, and p-AMPK/AMPK between the two groups (P > 0.05). Compared with the model group, the levels of tumor necrosis factor-α, interleukin-6, creatine kinase isoenzyme, troponin T, and p62 were decreased in the metformin group (P < 0.05), while LC3II/LC3I, p-AMPK/ AMPK and Beclin-1 level were increased (P < 0.05). Compared with the metformin group, the levels of tumor necrosis factor-α, interleukin-6, creatine kinase isoenzyme, troponin T, and p62 were increased in the metformin+3-methyladenine group (P < 0.05), while LC3II/LC3I and Beclin-1 level were decreased (P < 0.05). Myocardial hematoxylin-eosin staining indicated that myocardial fibers arranged normally in the sham operation group, but disorderedly in the model group, with interstitial edema and a large number of infiltrated inflammatory cells. A small amount of vacuolar changes were observed in the metformin group. The arrangement of myocardial fibers in the metformin+3-methyladenine group was slightly disordered, with more vacuolar changes. To conclude, metformin pretreatment may reduce myocardial injury in septic mice by activating the AMPK signaling pathway and inducing autophagy. [ABSTRACT FROM AUTHOR]

There is a lack of in-depth research on the impacts and changes in chronic psychological stress (CPS) on the cardiovascular system after acute myocardial infarction (AMI). This study aims to explore the comorbid mechanism and dynamic evolution of AMI exposed to CPS. 120 Wistar rats were randomly divided into Sham Operation group, Sham Operation + Chronic Unpredictable Mild Stress (CUMS) group, AMI group and AMI + CUMS group, with each group further divided into subgroups at days 7, 14, and 28. The AMI model was created by ligating the left anterior descending coronary artery, and CUMS model was used to induce CPS in rats. Behavioral changes were assessed through open field tests and sucrose preference tests. Cardiac function and structure were evaluated via echocardiography. The serum levels of TNFα, IL-6, NO, ET, CK-MB, cTNT, and ANP were measured using assay kits. Pathological changes in cardiac and brain tissues were observed under an optical microscope. Comparative analysis across different models revealed that CUMS significantly reduced behavioral activities in rats, with an interaction between CUMS and AMI affecting total distance (P < 0.05). Both CUMS and AMI significantly reduced cardiac function indicators, with their interaction effects on LVEF, LVFS, and CO (P < 0.05). AMI significantly altered cardiac structural parameters, particularly on day 28 (P < 0.05); while the impact of CUMS on cardiac structure was not significant, except for a notable reduction in LVAW/s on day 7 in AMI + CUMS group (P < 0.05). AMI caused significant changes in the serum biomarkers, while CUMS only significantly increased cTnT on day 7, ANP, TNFα, and IL-6 on day 14, and CK-MB on day 28, with their interaction effects on the three myocardial injury markers and TNFα (P < 0.05). Comparative analysis across different time points demonstrated that behavioral activity, cardiac function, CK-MB, cTnT, ANP, TNFα, and ET levels decreased significantly over time in the AMI model rats, while the left ventricular mass increased significantly (P < 0.05). Pathologically, compared with stress or AMI alone, the AMI + CUMS group exhibited more severe myocardia cellular degeneration and inflammatory infiltration, causing larger infract areas in myocardial tissue, as well as cell number decreases and morphological changes in hippocampal tissue. AMI with CPS exacerbates myocardial injury through sustained inflammation and endothelial dysfunction, leading to heart-brain pathology manifestations characterized by decreased cardiac function and hippocampal tissue damage. [ABSTRACT FROM AUTHOR]

Aim: Allergic rhinitis (AR) is an allergic condition characterized by inflammation of the nasal mucosa. Bacterial permeability‐increasing family member A1 (BPIFA1) exhibits anti‐inflammatory properties; however, its impact on AR remains unclear. Aim of this study is to investigate the expression and function of BPIFA1 in AR and its influence on inflammation and immune regulation in a mouse model of AR induced by ovalbumin (OVA). Methods: The expression of BPIFA1 was analyzed using quantitative real‐time PCR (qRT‐PCR) and immunohistochemistry (IHC). Morphological assessments of nasal mucosal tissues were conducted. Levels of inflammatory mediators in nasal lavage fluid (NALF) and serum were quantified using enzyme‐linked immunosorbent assay (ELISA) kits. Protein expressions of BPIFA1, phosphorylated and total p65 (p‐p65/p65), and IκBα were evaluated through Western blot analysis. The total cell counts, including epithelial cells, eosinophils, and lymphocytes in NALF, were determined using a hemocytometer. A mouse model of AR was established by OVA management. Results: BPIFA1 expression was found to be reduced in the nasal mucosa tissues of patients with AR, suggesting a potential role in the disease's progression. We successfully developed a mouse model of AR, where BPIFA1 was similarly downregulated, indicating its possible involvement in modulating the NF‐κB signaling pathway. Overexpression of BPIFA1 in this model attenuated inflammation and allergic responses by inhibiting the NF‐κB pathway. Additionally, overexpression of BPIFA1 promoted the differentiation of regulatory T cells (Treg) and inhibited the differentiation of T helper 17 cells (Th17) in the NALF of AR mice, further demonstrating its regulatory impact on immune responses. The study confirmed that BPIFA1 upregulation reduced the levels of inflammatory cytokines TNF‐α and IL‐6, decreased infiltration of inflammatory cells, and modulated antigen‐specific immunoglobulin levels and histamine in serum. Conclusion: BPIFA1 mitigated both inflammatory and allergic responses in AR mice induced by OVA through the modulation of the NF‐κB signaling pathway and the balance between regulatory T cells (Treg) and T helper 17 cells (Th17). These findings suggest that BPIFA1 could serve as a novel biomarker and therapeutic target for AR, offering potential for the development of targeted treatments to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a form of age-related, non-inflammatory, degenerative joint disease. It is characterized by pain, swelling, and bone hyperplasia; osteoarthritis has a high morbidity and high disability rate, which has a significant impact on the quality of life of patients worldwide. Engaging in sports has been demonstrated to reduce the risk of developing obesity, diabetes mellitus, and other metabolic diseases, additionally, it has been shown to enhance muscle quality, stabilize joints, improve motor coordination abilities, reduce pain, and improve joint function in individuals with osteoarthritis, these findings highlight the potential for sports to play an important role in the management of osteoarthritis. In this review, we presented an overview of the pathogenesis of osteoarthritis, provided a summary of advancements in the utilization of sports in the management of osteoarthritis, and discussed the underlying mechanisms and future application limitations, hoping to provide the foundation for the prevention and treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 can have long-lasting effects, but the effects on blood parameters and inflammation are poorly understood. The aim of this study was to evaluate morphological and inflammatory markers in long-term COVID-19 patients. Aim: To evaluate complete blood count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and morphology in mild versus severe long COVID-19. Material and methods: In total, 39 long COVID-19 patients were stratified into mild (n = 25) and severe (n = 14) groups. Blood counts, NLR, PLR were measured. Cell morphology was analysed. ROC curves were used to determine biomarker thresholds. Survival was assessed using Kaplan-Meier curves. Results and discussion: Severe patients had lower leukocytes but higher neutrophils, indicating greater inflammation. NLR and PLR were significantly increased in severe patients compared to mild patients (NLR 12 vs 8; PLR 140 vs 100). NLR and PLR were higher than in controls, confirming their utility as inflammatory markers. NLR and PLR effectively discriminated between mild and severe disease. High NLR and PLR predicted poorer prognosis. Altered leukocyte morphology such as cytoplasmic vacuolization correlated with severity. Conclusions: NLR and PLR are promising biomarkers for assessing severity of long COVID-19, while morphological changes in blood cells provide additional evidence of inflammation. Further studies in larger populations are warranted. [ABSTRACT FROM AUTHOR]

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre‐clinical studies showed benefit with a histone‐neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose‐adjusted, open‐label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady‐state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug‐related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half‐life values ranged from 5 to 7 h. The mean (±SD) terminal half‐life for non‐RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometritis is a prevalent disease in perinatal dairy cows, which leads to compromised reproductive function. Studies have confirmed that A20, also known as TNFAIP3, can regulate inflammatory responses in various cells. However, it remains unclear whether A20 regulates the inflammatory response of bovine endometrial cells and if autophagy plays a role in A20's regulation of inflammatory responses. In this paper, we show that elevated expression of A20 is linked to the progression of endometritis in dairy cows. A20 inhibited the activation of the NF-κB pathway and the mRNA expression levels of proinflammatory cytokines in LPS-induced bovine endometrial epithelial cells. Moreover, it enhanced autophagic activity in the bovine endometrial epithelial cells inhibited by LPS. Our study further showed that A20 mitigated the inflammatory response of bovine endometrial epithelial cells by promoting autophagy. These findings will enhance our understanding of the pathogenesis and provide novel insights for the prevention and treatment of endometritis in dairy cows. Endometritis represents a prevalent condition in perinatal dairy cows. Bovine endometrial epithelial cells (BEECs), as the primary interface between cavity and the external environment, are particularly vulnerable to infection by pathogenic bacteria following parturition. A20 is essential for regulating inflammation and modulating immune responses. Nevertheless, the exact role of A20 in the BEECs in response to inflammatory response is not fully understood. An endometritis model infected by Escherichia coli (E. coli) in vivo and a BEECs inflammation model induced with lipopolysaccharide (LPS) in vitro were built to investigate the function and governing mechanisms of A20 in endometritis. The results showed that infection with E. coli resulted in endometrial damage, inflammatory cell infiltration, and upregulation of inflammatory factors in dairy cows. Furthermore, A20 expression was upregulated in the endometrium of cows with endometritis and in BEECs following LPS stimulation. A20 overexpression attenuated the level of proinflammatory cytokines in LPS-stimulated BEECs; conversely, A20 knockdown lead to an exacerbated response to LPS stimulation. The overexpression of A20 was shown to activate autophagy and suppress the NF-κB signaling pathway in LPS-stimulated BEECs. However, blocking autophagy with chloroquine notably attenuated the anti-inflammatory effect of A20, leading to the activation of the NF-κB signaling pathway. In summary, the study demonstrated that A20's suppression of inflammation in LPS-stimulated BEECs is associated with the activation of autophagy. Therefore, the A20 protein showed potential as a novel treatment focus for managing endometritis in dairy cows. [ABSTRACT FROM AUTHOR]

Background: Postimplantation syndrome (PIS) is a known inflammatory response following endovascular stent placement, yet comparative data between venous and arterial stenting remains limited. This study seeks to evaluate the incidence, characteristics, and clinical implications of PIS across these two distinct vascular territories. Methods: We retrospectively analyzed 191 patients who underwent either venous (n = 36) or arterial (n = 155) stent placement. Data collection encompassed demographic profiles, perioperative laboratory findings, and clinical outcomes. The primary endpoint was the incidence of PIS, defined as the presence of fever (≥38 °C), leukocytosis, and elevated C-reactive protein (CRP) within 30 days postprocedure. Secondary outcomes included length of hospital and ICU stay, incidence of endoleaks, reintervention rates, and 30-day mortality. Comparative statistical analyses were conducted to assess differences between the venous and arterial stent groups. Results: PIS was observed more frequently in arterial stent patients, as evidenced by significantly elevated postoperative white blood cell counts at 24 and 48 h (p = 0.046 and p = 0.014, respectively), along with borderline CRP increases (p = 0.052). Fever occurrence peaked at 72 and 96 h postprocedure, predominantly in the arterial cohort. Furthermore, patients with arterial stents had significantly longer hospital stays (5.59 ± 0.46 days vs. 3.42 ± 0.36 days; p = 0.0018) and a higher rate of 30-day endoleaks (7.1% vs. 0%; p = 0.005). Despite similar mortality and major adverse cardiac event (MACE) rates between groups, arterial stent patients exhibited a greater need for reintervention. While PIS was less common among venous stent recipients, its potential impact on postoperative recovery warrants careful monitoring. Conclusions: Arterial stenting is associated with a higher incidence of PIS and a more pronounced systemic inflammatory response, contributing to longer hospitalization and increased postoperative complications. Although venous stent patients experience PIS less frequently, its occurrence should not be overlooked, as it may influence overall recovery and clinical outcomes. Recognition and management of PIS in both venous and arterial stent patients are critical to improving patient care and optimizing procedural success. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage. [ABSTRACT FROM AUTHOR]

Ovarian puncture has been widely used in assisted reproduction, but there are still gaps about its effects on ovarian morphophysiology, as well as the relationship between inflammation caused by this procedure and the follicular growth and fertility. The aim of this study was to investigate the effects of ovarian puncture on folliculogenesis and fertility. Mice (n = 24) were divided into two groups: (1) SHAM—both ovaries were exposed and repositioned and (2) Punctured—ovaries were exposed, punctured, and repositioned. After 96 h of surgery, ovaries were collected for morphofunctional analysis. New females were used for the superovulation (n = 10) and fertility assays (n = 10). Increased volumetric density of inflammatory cells—p = 0.0005, p = 0.0013; hemorrhagic foci—p < 0.0001; and inflammatory exudate—p < 0.0001 could be noticed on the punctured group, compared to SHAM. The percentage of primordial follicles was lower on the punctured ovaries (p = 0.00294). Ovarian puncture has also induced an increase in the proliferation of granulosa cells of primary (p = 0.0321) and antral follicles (p = 0.0395), and an increased apoptotic index of antral follicles (p = 0.0100). There was no influence on expression of some genes related to inflammation, collagen deposition and folliculogenesis progression. The reproductive aspects (oocyte retrieval and number of fetuses per female) were not altered (p > 0.05). Taken together, our findings strongly suggest that ovarian puncture results in a local inflammation that affects follicular growth and atresia. However, it does not affect female fertility, which strengthens the safety of this procedure. [ABSTRACT FROM AUTHOR]

• Generation of bi- and tri-partite murine iPSC-derived neurospheroids. • Induction of inflammatory stress in bi- and tri-partite neurospheroids. • Single and combined transcriptomic and proteomic analyses. • The presence of microglia exacerbates cellular stress in tri-partite neurospheroids. induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CX 3 CR1eGFP+/- CCR2RFP+/- murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation. First, cytokine analysis demonstrates that both bi-partite and tri-partite NSPHs can be triggered to release IL6 and CXCL10 following three days of stimulation with, respectively, TNFα + IL1β + IFNγ and LPS + IFNγ. Additionally, immunocytochemical analysis for G3BP1 and PABPC1 revealed the development of stress granules in both bi-partite and tri-partite NSPHs after 3 days of stimulation. To further investigate the observed signs of inflammatory response and cellular stress, we performed an untargeted transcriptomic and proteomic analysis of bi- and tri-partite NSPHs under steady-state and inflammatory conditions. Here, using the combined differential gene and protein expression profiles between unstimulated and stimulated NSPHs, Ingenuity Pathway Analysis (IPA) confirms the activation of canonical pathways associated with inflammation and cellular stress in both bi-partite and tri-partite NSPHs. Moreover, our multi-omics analysis suggests a higher level of downstream inflammatory responses, impairment of homeostatic and developmental processes, as well as activation of cell death processes in stimulated tri-partite NSPHs compared to bi-partite NSPHs. Concluding, these results emphasise the advantages of including microglia in NSPH research to study inflammation-induced neurodegeneration in a 3D neural environment. [ABSTRACT FROM AUTHOR]

Calpain and PARP-NF-κB signaling are reported to participate in the ischemic brain injury. In this study, it was investigated whether calpain was contributed to the neurovascular unit (NVU) damage through up-regulating PARP-NF-κB signaling during experimental ischemic stroke. Male Sprague-Dawley rats were suffered from 90 min of middle cerebral artery occlusion, followed by reperfusion. The NVU damage was evaluated by the permeability of blood-brain barrier (BBB), the degradation of proteins in extracellular matrix and tight junctions, and ultrastructural changes. The inflammatory response was determined by the expression of inflammatory genes driven by PARP-NF-κB signaling and the activities of myeloperoxidase (MPO). Treatment with MDL 28,170, a calpain inhibitor, improved neurological functions, reduced TUNEL staining index, lessened brain swelling, and decreased infarct volume in ischemic rats. Moreover, it reduced the BBB permeability, enhanced the levels of laminin, collagen IV and occludin, and attenuated the ultrastructural damage of NVU in penumbra and core after induction of ischemia. Meanwhile, it enhanced the levels of cytosolic IκBα, lessened the levels of nuclear PARP and NF-κB p65, reduced the levels of ICAM-1, TNF-α, IL-1β, MMP-9, and MMP-2,and suppressed the activities of MPO in penumbra and core. These data showed that calpain inhibition suppressed PARP-NF-κB signaling-mediated inflammatory response, reduced NVU damage, and protected brain against ischemic stroke, suggesting the involvement of calpain in the NVU damage through up-regulating PARP-NF-κB signaling during brain ischemia. [ABSTRACT FROM AUTHOR]

Background: Mitochondria play a crucial role in shaping the macrophage inflammatory response during bacterial infections. Spinster homolog 2 (Spns2), responsible for sphingosine-1-phosphate (S1P) secretion, acts as a key regulator of mitochondrial dynamics in macrophages. However, the link between Spns2/S1P signaling and mitochondrial functions remains unclear. Methods: Peritoneal macrophages were isolated from both wild-type and Spns2 knockout rats, followed by non-targeted metabolomics and RNA sequencing analysis to identify the potential mediators through which Spns2/S1P signaling influences the mitochondrial functions in macrophages. Various agonists and antagonists were used to modulate the activation of Spns2/S1P signaling and its downstream pathways, with the underlying mechanisms elucidated through western blotting. Mitochondrial functions were assessed using flow cytometry and oxygen consumption assays, as well as morphological analysis. The impact on inflammatory response was validated through both in vitro and in vivo sepsis models, with the specific role of macrophage-expressed Spns2 in sepsis evaluated using Spns2flox/floxLyz2-Cre mice. Additionally, the regulation of mitochondrial functions by Spns2/S1P signaling was confirmed using THP-1 cells, a human monocyte-derived macrophage model. Results: In this study, we unveil prostaglandin E2 (PGE2) as a pivotal mediator involved in Spns2/S1P-mitochondrial communication. Spns2/S1P signaling suppresses PGE2 production to support malate-aspartate shuttle activity. Conversely, excessive PGE2 resulting from Spns2 deficiency impairs mitochondrial respiration, leading to intracellular lactate accumulation and increased reactive oxygen species (ROS) generation through E-type prostanoid receptor 4 activation. The overactive lactate-ROS axis contributes to the early-phase hyperinflammation during infections. Prolonged exposure to elevated PGE2 due to Spns2 deficiency culminates in subsequent immunosuppression, underscoring the dual roles of PGE2 in inflammation throughout infections. The regulation of PGE2 production by Spns2/S1P signaling appears to depend on the coordinated activation of multiple S1P receptors rather than any single one. Conclusions: These findings emphasize PGE2 as a key effector of Spns2/S1P signaling on mitochondrial dynamics in macrophages, elucidating the mechanisms through which Spns2/S1P signaling balances both early hyperinflammation and subsequent immunosuppression during bacterial infections. [ABSTRACT FROM AUTHOR]

Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti‐inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N‐methyl‐N'‐nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose‐dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA‐seq and western blot revealed that PAL significantly improved IL‐17, TNF, and NF‐kappa B inflammation‐related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL‐17, TNF‐α, and p‐p65 expression. In conclusion, PAL was proposed to mitigate MNNG‐induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG. [ABSTRACT FROM AUTHOR]

Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors. The presence of oral mucosal rupture and ulcerative lesions, which are the defining features of this condition, can significantly affect the quality of life of patients. Additionally, it can interfere with tumor therapy and contribute to an unfavorable prognosis. Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development. Moreover, thalidomide (THD) has been revealed to reduce the incidence and severity of RIOM in patients undergoing chemoradiotherapy for nasopharyngeal carcinoma. However, the mechanism through which THD improves RIOM remains unknown. This study aimed to investigate the role of LZTS3 in RIOM by analyzing various sequencing datasets and conducting knockdown and overexpression experiments. We used small interfering RNA transfection and LZTS3 overexpression, followed by validation through polymerase chain reaction, western blotting, flow cytometry, and enzyme-linked immunosorbent assay. In this study, we identified LZTS3 as a potential target for THD regulation in RIOM. Through a series of experiments, we confirmed that LZTS3 has the ability to inhibit the inflammatory response and apoptosis of cells. In addition, we also found that THD can regulate the expression of LZTS3 by upregulating, thereby affecting inflammatory response and apoptosis. We repeated these results in a live animal model. In summary, THD has the potential to reduce the occurrence of oral mucositis in patients by upregulating LZTS3 levels. These findings provide a promising avenue for future drug research and development to treat RIOM. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of low expression of α-glucosidase (GAA) on morphology, proliferation, inflammatory response, and oxidative stress response of pancreatic β-cells in order to investigate the potential role of GAA in the pathogenesis of diabetes mellitus. Methods The expression of GAA in βTC6 cells was interfered by siRNA1,2,3 and 4, respectively. As a result, the interference effect of siRNA4 was the best, and it was used as the interference sequence in subsequent experiments. βTC6 cells were randomly divided into the siRNA group, negative control group (NC group) and blank control group(Con group), respectively. Cells in the siRNA group were transfected with siRNA4 sequence to reduce the expression of GAA, cells in the negative control group were transfected with siRNANC sequence, and cells in the Con group were not treated. After 24, 48, 72 and 96 h of cell culture, the cell proliferation of each group was detected by CCK-8. They were cultured for 48 h, the number and morphology of cells in each group were observed by inverted microscope, the inflammatory factors IL-6 and IL-1β protein in cells were detected by Western blotting, and the content of reactive oxygen species (ROS) in cells was detected by immunofluorescence. Results Compared with the Con and NC groups, the cells increased, the intercellular space became smaller under the microscope, the OD values of cells increased at 24, 48, 72, and 96 h of culture, and the levels of IL-6 and ROS decreased after 48 h of culture in the siRNA group (all P<0. 01) . No significant differences were found in these indicators between the Con and NC groups(all P>0. 05). Conclusions Low expression of GAA can lead to alterations in cell morphology, enhanced proliferative capacity, and diminished inflammatory and oxidative stress responses of pancreatic β-cells. GAA may participate in the pathogenesis of diabetes by changing the morphology of pancreatic β-cells and enhancing inflammatory and oxidative stress responses. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionThis study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris.This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve.HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator.HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of puerarin (GGS) on lipopolysaccharide (LPS) -induced inflammatory response in human gingival fibroblasts (HGFs) by regulating nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Methods: HGFs cells were cultured in vitro, HGFs cells were divided into blank control (CK) group (0.9% sodium chloride), LPS group (100 nM LPS), LPS+GGS low dose (LPS+GGS-L) group (100 nM LPS+50 μΜ GGS), LPS+GGS high dose (LPS+GGS-H) group (100 nM LPS+100 μΜ GGS), LPS+GGS-H+ML385 (Nrf2/HO-1 signaling pathway inhibitor) group (100 nM LPS+100 μΜ GGS+10 μΜ ML385). The cell proliferation ability was detected by cell counting kit-8 (CCK-8). The levels of interleukin (IL) -6, lactate dehydrogenase (LDH), IL-10 and IL-1ẞ were detected by enzyme-linked immunosorbent assay (ELISA). The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by kits. The apoptosis rate of HGFs was detected by flow cytometry. The formation of cell membrane pores was detected by propidium iodide (PI) staining. The expressions of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2 associated X protein (Bax), NOD-like receptor protein 3 (NLRP3), Nrf2 and HO-1 were detected by Western blot. Results: Compared with CK group, the OD450 (24 and 48 h) value, IL-10 level, GSH-Px and SOD activity, Bcl-2, Nrf2 and HO-1 protein expression of HGFs cells in LPS group were significantly decreased, and the levels of IL-6, LDH, IL-1B, MDA content, apoptosis rate, positive rate of PI staining, Bax and NLRP3 protein expression were significantly increased (P<0.05). Compared with LPS group, the OD450 (24 and 48 h) value, IL-10 level, GSH-Px and SOD activity, Bcl-2, Nrf2 and HO-1 protein expression of HGFs cells in LPS+GGS-L group and LPS+GGS-H group were significantly increased, and the levels of IL-6, LDH, IL-1B, MDA content, apoptosis rate, positive rate of PI staining, Bax and NLRP3 protein expression were significantly decreased (P<0.05). ML385 could reduce the improvement of GGS on LPS-induced inflammatory injury in HGFs cells(P<0.05). Conclusion: GGS may alleviate LPS-induced inflammation and oxidative stress in HGFs cells by activating Nrf2/HO-1 signaling pathway, and reduce cell apoptosis. [ABSTRACT FROM AUTHOR]

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development. [ABSTRACT FROM AUTHOR]

SAPHO syndrome is a complex inflammatory disorder affecting the skin and bones, characterized by osteomyelitis, acne, and pustulosis. Cytokines play a pivotal role in the pathogenesis of SAPHO syndrome, especially in inflammatory responses and immune regulation. This article reviews the cytokines involved in the pathogenesis of SAPHO syndrome, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-10, and transforming growth factor-β (TGF-β), and discusses their potential as intervention points for treatment. These findings elucidate the intricate immune regulatory network of SAPHO syndrome and provide a theoretical foundation for the development of new targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

The excessive inflammation caused by the prolonged activation of Toll-like receptor 4 (TLR4) and its downstream signaling pathways leads to sepsis. CD14-mediated endocytosis of TLR4 is the key step to control the amount of TLR4 on cell membrane and the activity of downstream pathways. The actin cytoskeleton is necessary for receptor-mediated endocytosis, but its role in TLR4 endocytosis remains elusive. Here we show that Tropomodulin 1 (Tmod1), an actin capping protein, inhibited lipopolysaccharide (LPS)-induced TLR4 endocytosis and intracellular trafficking in macrophages. Thus it resulted in increased surface TLR4 and the upregulation of myeloid differentiation factor 88 (MyD88)-dependent pathway and the downregulation of TIR domain-containing adaptor-inducing interferon-β (TRIF)-dependent pathway, leading to the enhanced secretion of inflammatory cytokines, such as TNF-α and IL-6, and the reduced secretion of cytokines, such as IFN-β. Macrophages deficient with Tmod1 relieved the inflammatory response in LPS-induced acute lung injury mouse model. Mechanistically, Tmod1 negatively regulated LPS-induced TLR4 endocytosis and inflammatory response through modulating the activity of CD14/Syk/PLCγ2/IP3/Ca2+ signaling pathway, the reorganization of actin cytoskeleton, and the membrane tension. Therefore, Tmod1 is a key regulator of inflammatory response and immune functions in macrophages and may be a potential target for the treatment of excessive inflammation and sepsis. [ABSTRACT FROM AUTHOR]

Background: Our previous research showed that Porphyromonas gingivalis (P. gingivalis) infection can activate the inflammatory signaling pathway and promotes the malignancy development of esophageal squamous cell carcinoma (ESCC). However, the prognostic significance of inflammatory response-related genes (IRRGs) in P. gingivalis -infected ESCC requires further elucidation. Hence, our study constructed a prognostic signature based on P. gingivalis and IRRGs to forecast the survival of patients with ESCC, which may provide insight into new treatment options for ESCC patients. Methods: Differentially expressed genes (DEGs) were identified in P.gingivalis -infected and P.gingivalis -uninfected ESCC cell by RNA sequencing. A risk model was constructed and validated using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database by using univariate Cox regression analysis, LASSO, and the multivariate Cox regression analysis. Kaplan-Meier analysis was carried out to compare the overall survival (OS) between high-risk and low-risk groups. Single-sample gene set enrichment analysis was used to analyze the immune cell infiltration. The Genomics of Drug Sensitivity in Cancer database was used to predict drug sensitivity. Results: There were 365 DEGs between the P.gingivalis -infected and P.gingivalis -uninfected groups. Four genes including DKK1, ESRRB, EREG, and RELN were identified to construct the prognostic risk model (P =.012, C-index = 0.73). In both the training and validation sets, patients had a considerably shorter OS in the high-risk group than those in the low-risk group (P <.05). A nomogram was established using the risk score, gender, and N stage which could effectively forecast the prognosis of patients (P =.016, C-index = 0.66). The high-risk group displayed lower immune infiltrating cells, such as activated dendritic cells, type 2 T helper cells, and neutrophils (P <.05). A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. Conclusion: We demonstrated the potential of a novel signature constructed from 4 P. gingivalis -related IRRGs for prognostic prediction in ESCC patients. [ABSTRACT FROM AUTHOR]

• Tirofiban attenuates brain infarct volume after acute ischemic stroke. • Tirofiban reduces apoptosis oxidative stress after acute ischemic stroke. • Tirofiban regulates the microglia and reduces inflammatory factors. Growing evidence suggests that neuroinflammation is a critical driver of the development, worsening, and cell death observed in acute ischemic stroke (AIS). While prior research has demonstrated that tirofiban enhances functional recovery in AIS patients by suppressing platelet aggregation, its impact and underlying mechanisms in AIS-related neuroinflammation remain elusive. The current study established an AIS mouse model employing photochemical techniques and assessed neurological function and brain infarct size using the modified neurological severity scale (mNSS) and 2,3,5-Triphenyltetrazolium chloride (TTC) staining, respectively. Tirofiban significantly reduced the volume of cerebral infarction in AIS mice, accompanied by an enhancement in their neurological functions. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays along with experiments assessing oxidative stress showed that tirofiban mitigated oxidative damage and apoptosis in the ischemic penumbra post-AIS. Additionally, DNA microarray analysis revealed alterations in gene expression patterns in the ischemic penumbra after tirofiban treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most gene-level downregulated signaling pathways were closely related to the inflammatory response. Moreover, the protein microarray analysis revealed that tirofiban diminished the expression levels of inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha, in the ischemic penumbra. Additionally, immunofluorescence staining showed that tirofiban regulated inflammatory responses by altering the state and phenotype of microglia. In conclusion, this study suggests that tirofiban reduces inflammatory response by regulating microglial state and phenotype and lowering the levels of inflammatory factors, providing neuroprotection in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of silencing miR-126 on proliferation, apoptosis, and inflammatory response of osteoarticular chondrocytes and their mechanism. Methods Human osteoarticular chondrocytes HC-a were cultured in vitro. HC-a cells in the third generation, which were in the logarithmic growth phase and had good growth status, were randomly divided into the control group, IL-1β group, IL-1β + miR-NC group, and IL-1β + miR-126 inhibitor group, respectively. Cells in the IL-1β + miR-NC group and IL-1β + miR-126 inhibitor group were transfected with miR-NC and miR-126 inhibitor, respectively. Except for the control group, the other three groups were treated with 10 ng/mL IL-1β induction to construct the cell models of osteoarthritis (OA) . The cells of each group were collected, and the expression of miR-126 was detected by RT-qPCR, cell proliferation activity was detected by CCK-8, apoptosis rate was detected by flow cytometry, and inflammatory factors TNF-α, IL-6 and IFN-γ in the culture supernatant were detected by ELISA. The expression levels of SIRT1 and Caspase-3 proteins were detected by Western blotting. Results Compared with the control group, the relative expression of miR-126 increased, the cell proliferation activity decreased, apoptosis rate increased, the levels of TNF-α, IL-6 and IFN-γ in culture supernatance increased, the relative expression of SIRT1 protein decreased, and the relative expression of Caspase-3 protein increased in the IL-1β group (all P<0. 05) . Compared with the IL-1β + miR-NC group, the relative expression decreased, cell proliferation activity increased, apoptosis rate decreased, the levels of TNF-α, IL-6 and IFN-γ in culture supernatant decreased, the relative expression of SIRT1 protein increased, and the relative expression of Caspase-3 protein decreased in the miR-126 inhibitor group (all P<0. 05) . There were no significant differences in the above indexes between IL-1β group and IL-1β + miR-NC group (all P>0. 05) . Conclusion Silencing miR-126 can promote the proliferation of OA cells and inhibit apoptosis and inflammation, which may be related to the regulation of SIRT1 protein expression. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsDiscussionOne-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear.We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1.Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1’s anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways.RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications. [ABSTRACT FROM AUTHOR]

Background: Antidiabetic therapies are effective, but could indirectly modify the inflammatory response in the ocular microenvironment; therefore, a study was developed to evaluate the inflammatory cytokine profile in the vitreous humor of diabetic patients with retinopathy under treatment with antidiabetic drugs. Methods: Observational, comparative, retrospective, cross-sectional study. Interleukins 1β, 6, 8, 10, and tumor necrosis factor-alpha (TNFα) were evaluated in the vitreous humor obtained from patients with type 2 diabetes mellitus, proliferative diabetic retinopathy, and concomitant retinal detachment or vitreous hemorrhage, and who were already on antidiabetic treatment with insulin or metformin + glibenclamide. The quantification analysis of each cytokine was performed by the cytometric bead array (CBA) technique; medians and interquartile ranges were obtained, and the results were compared between groups using the Mann-Whitney U test, where a p-value < 0.05 was considered significant. Results: Thirty-eight samples; quantification of TNFα concentrations was higher in the group of patients administered insulin, while interleukin-8 was lower; in the metformin + glibenclamide combination therapy group, it occurred inversely. In the stratified analysis, the highest concentrations of interleukin-8 and TNFα occurred in patients with vitreous hemorrhage; however, the only statistical difference existed in patients with retinal detachment, whose TNFα concentration in the combined therapy group was the lowest value found (53.50 (33.03–86.66), p = 0.03). Interleukins 1β, 6, and 10 were not detected. Conclusion: Interleukin-8 and TNFα concentrations are opposite between treatment groups; this change is more accentuated in patients with proliferative diabetic retinopathy and vitreous hemorrhage, where the highest concentrations of both cytokines are found, although only TNFα have statistical difference. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation. Methods: Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. Results: Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis. Conclusions: Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis. [ABSTRACT FROM AUTHOR]

Introduction Many trauma patients die from hemorrhagic shock in the military and civilian settings. Although two-thirds of hemorrhagic shock victims die of reasons other than exsanguination, such as the consequent cytokine storm, anti-inflammatory therapies failed to be utilized. Apoptotic cell–based treatments enhance innate ability to exert systemic immunomodulation as demonstrated in several clinical applications and hence might present a novel approach in hemorrhagic shock treatment. Materials and Methods Twenty-two rats underwent a pressure-controlled hemorrhagic shock model and followed up for 24 hours. An infusion of apoptotic cells (Allocetra-OTS, Enlivex Therapeutics Ltd, Nes Ziona, Israel) was administered to the treatment group. Hemodynamics, blood counts, biochemistry findings, and cytokine profile were compared to a saline-resuscitated control group. Results The treatment group's mean arterial pressure decreased from 94.8 mmHg to 28.2 mmHg, resulting in an 8.13 mg/dL increase in lactate and a 1.9 g/L decrease in hemoglobin, similar to the control group. White blood cells and platelets decreased more profoundly in the treatment group. A similar cytokine profile after 24 hours was markedly attenuated in the treatment group 2 hours after bleeding. Levels of pro-inflammatory cytokines such as interleukin (IL)-1a (28.4 pg/mL vs. 179.1 pg/mL), IL-1b (47.4 pg/mL vs. 103.9 pg/mL), IL-6 (526.2 pg/mL vs. 3492 pg/mL), interferon γ (11.4 pg/mL vs. 427.9 pg/mL), and tumor necrosis factor α (19.0 pg/mL vs. 31.7 pg/mL) were profoundly lower in the treatment group. Conclusion In a pressure-control hemorrhagic shock model in rats, apoptotic cell infusion showed preliminary signs of a uniform attenuated cytokine response. Apoptotic cell–based therapies might serve as a novel immunomodulatory therapy for hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial function is significantly impaired in patients with SLE compared to healthy controls. Elevated activation of the mammalian target of rapamycin complex 1 (mTORC1) is reported in humans and mice with SLE. However, it is unclear if elevated mTORC1 in SLE contributes to impaired mitophagy and endothelial dysfunction. Therefore, we tested the hypothesis that inhibiting mTORC1 with rapamycin would increase mitophagy and attenuate endothelial dysfunction and inflammatory responses in SLE. Methods: Nine-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned into rapamycin treatment (lpr_ Rapamycin and MpJ_Rapamycin) or control (lpr_Control and MpJ&lowbar;Control) groups. Rapamycin was injected i.p. 3 days per week for 8 weeks. After 8 weeks, endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP) were measured in thoracic aortas using a wire myograph. Results: MTORC1 activity was increased in aorta from lpr mice as demonstrated by increased phosphorylation of s6rp and p70s6k and significantly inhibited by rapamycin (s6rp, p < 0.0001, p70s6k, p = 0.04, respectively). Maximal responses to Ach were significantly impaired in lpr_Control (51.7% ± 6.6%) compared to MpJ_Control (86.7% ± 3.6%) (p < 0.0001). Rapamycin prevented endothelial dysfunction in the thoracic aorta from lupus mice (lpr_Rapamycin) (79.6% ± 4.2%) compared to lpr_Control (p = 0.002). Maximal responses to SNP were not different across groups. Phosphorylation of endothelial nitric oxide synthase also was 42% lower in lpr_Control than MpJ_Control and 46% higher in lpr_ Rapamycin than lpr_Control. The inflammatory marker, vascular cell adhesion protein 1 (Vcam 1), was elevated in aorta from lupus mice compared with healthy mice (p = 0.001), and significantly reduced with Rapamycin treatment (p = 0.0021). Mitophagy markers were higher in lupus mice and reduced by rapamycin treatment, suggesting altered mitophagy in lpr mice. Conclusion: Collectively, these results demonstrate the beneficial effects of inhibiting mTORC1 on endothelial function in SLE mice and suggest inflammation and altered mitophagy contribute to endothelial dysfunction in SLE. [ABSTRACT FROM AUTHOR]

Background/aim: Necrotizing enterocolitis (NEC) is a serious condition that predominantly affects premature infants and involves an aberrant immune response and inflammatory cytokine release resulting in intestinal epithelial damage. The current study investigated the immunoregulatory effects of vitamin D3 on the maturation and activation of dendritic cells (DCs) and the antiinflammatory impact on the intestines in a neonatal rat model of NEC. Materials and methods: Inflammatory damage to intestinal tissue was assessed via morphological changes and apoptosis and DC expression of costimulatory molecules, inflammatory factors, and immunoregulatory factors by immunohistochemical staining, quantitative real-time PCR, and immunofluorescence. The fluorescein isothiocyanate-ovalbumin (FITC-OVA) uptake assay was used to analyze DC endocytosis. Results: Vitamin D3 administration attenuated intestinal damage and apoptosis, inhibiting CD86 and increasing CD80 expression. Lipopolysaccharide (LPS)-challenged DC2.4 cells in vitro showed upregulated CD86, tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase 1 (IDO-1) expression, which were all reduced by vitamin D3, except for IDO-1. LPS inhibited CD80 expression, which was restored by vitamin D3 treatment, and endocytic capacity was improved. Vitamin D3 ameliorated intestinal damage in neonatal rats with NEC and exerted antiinflammatory and immunomodulatory effects on DCs. Conclusion: Vitamin D3 has potential as a supplementary treatment for NEC patients. [ABSTRACT FROM AUTHOR]