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Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP., (© 2024. The Author(s).)

Background: The IL-23/IL-17 axis plays an important role in the immunopathogenesis of periodontal disease. A systematic review was conducted to synthesize all research reporting on the levels of the IL-23/IL-17 axis in gingival crevicular fluid (GCF) from subjects with gingivits, and periodontitis, compared to healthy controls. Methods: The protocol followed the PRISMA, and Cochrane guidelines, and was registered with the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/7495V. A search was conducted in the electronic databases PubMed/MEDLINE, Scopus, Google Schoolar, and Cochrane from November 15th, 2005, to May 10th, 2023. The quality of the studies was assessed using the JBI tool for cross-sectional studies. Results: The search strategy provided a total of 2,098 articles, of which 12 investigations met the inclusion criteria. The total number of patients studied was 537, of which 337 represented the case group (subjects with gingivitis, and chronic periodontitis), and 200 represented the control group (periodontally healthy subjects). The ages of the patients ranged from 20 to 50 years, with a mean (SD) of 36,6 ± 4,2, of which 47% were men, and 53% were women. 75% of the investigations collected GCF samples with absorbent paper strips, and analyzed cytokine IL-17 levels individually. In addition, qualitative analysis revealed that there are differences between IL-23/IL-17 axis levels in subjects with chronic periodontitis, gingivitis and healthy controls. Conclusions: Thus, IL-23/IL-17 axis levels could be used in the future as a diagnostic tool to distinguish between periodontal diseases. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that circRNAs are involved in the pathogenesis of osteoarthritis (OA) by affecting various fundamental cellular characteristics of chondrocytes. The purpose of this paper is to investigate the role and regulatory mechanism of hsa_circ_0020014 (circ_0020014) in chondrocytes of OA. Methods: The inflammatory cytokine interleukin 1 beta (IL-1β) was used to stimulate human chondrocytes. Cell viability, proliferation, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2′-deoxyuridine (EdU), and flow cytometry assays. Several protein levels were determined by western blotting (WB). Levels of inflammatory cytokines and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). Relative expression of circ_0020014 was estimated by real-time polymerase quantitative chain reaction (RT-qPCR). Bioinformatics prediction combined with dual-luciferase reporter, RIP and RNA pull-down assays were done to probe into the regulatory mechanism of circ_0020014. Results: Circ_0020014 was overexpressed in OA patient-derived articular cartilages and IL-1β-stimulated chondrocytes. Silencing of circ_0020014 lighted IL-1β-prompted chondrocyte proliferation repression, apoptosis, inflammation, and oxidative stress. Mechanically, circ_0020014 functioned as a miR-24-3p molecular sponge to regulate cathepsin B (CTSB) expression. Furthermore, miR-24-3p inhibition alleviated circ_0020014 knockdown-mediation repression of IL-1β-urged chondrocyte injury. In addition, CTSB overexpression whittled miR-24-3p upregulation-mediated suppression of IL-1β-urged chondrocyte injury. Conclusion: Our findings demonstrated that the circ_0020014/miR-24-3p/CTSB axis was associated with IL-1β-prompted chondrocyte injury, supporting the involvement of circ_0020014 in the OA pathogenesis. Highlights: A significant upregulation of circ_0020014 was observed in OA patient-derived articular cartilages. Inhibition of circ_0020014 lessened IL-1β-urged chondrocyte injury. Circ_0020014 could interact with miR-24-3p to mediate CTSB expression. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA), characterized by inflammation and articular cartilage degradation, is a prevalent arthritis among geriatric population. This paper was to scrutinize the novel mechanism of long noncoding RNA (lncRNA) NEAT1 in OA etiology. Methods: A total of 10 OA patients and 10 normal individuals was included in this study. Cell model of OA was built in human normal chondrocytes induced by lipopolysaccharide (LPS). An OA Wistar rat model was established through intra-articular injection of L-cysteine and papain mixtures (proportion at 1:2) into the right knee. Quantitative reverse transcription-polymerase chain reaction was employed to ascertain the expression levels of NEAT1, microRNA (miR)-374b-5p and post-GPI attachment to protein 1 (PGAP1), while dual-luciferase reporter experiments were used for the validation of target relationship among them. Cell cycle and apoptosis were calculated by flow cytometry analysis. CCK-8 assay was done to evaluate the proliferative potentials of chondrocytes. The levels of cell cycle-related proteins (Cyclin A1, Cyclin B1 and Cyclin D2) and pro-apoptotic proteins (Caspase3 and Caspase9) were measured by western blotting. Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 levels were determined via ELISA. Hematoxylin & eosin (HE) Staining was used for pathological examination in OA rats. Results: Pronounced downregulation of NEAT1 and PGAP1 and high amounts of miR-374b-5p were identified in OA patients, LPS-induced chondrocytes and OA rats. NEAT1 targeted miR-374b-5p to control PGAP1 expression. Loss of NEAT1 or upregulation of miR-374b-5p dramatically accelerated apoptosis, led to the G1/S arrest and promoted the secretion of inflammatory cytokines in LPS-induced chondrocytes, while ectopic expression of PGAP1 exhibited the opposite influences on chondrocytes. Additionally, we further indicated that upregulation of miR-374b-5p attenuated the effects of PGAP1 overexpression on LPS-induced chondrocytes. Conclusions: Reduced NEAT1 induces the development of OA via miR-374b-5p/PGAP1 pathway. This suggests that the regulatory axis NEAT1/miR-374b-5p/PGAP1 is a novel and prospective target for OA treatment. [ABSTRACT FROM AUTHOR]

Background: Sepsis poses a serious threat to human life and health, with limited options for current clinical treatments. Acupuncture plays an active role in treating sepsis. However, previous studies have focused on the neuromodulatory effect of acupuncture, neglecting its network modulatory effect. Exosomes, as a new way of intercellular communication, may play an important role in transmitting acupuncture information. This paper explores the possibility of electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs as a potential treatment for sepsis. Methods: The sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS) (12 mg/kg, 24 mg/kg), and EA (continuous wave, 10 Hz, intensity 5) or intraperitoneal injection of Acupuncture Exosomes (Acu-exo) were performed before the model establishment. The therapeutic effect was evaluated by survival rate, ELISA, H&E staining and lung wet/dry weight ration (W/D). In vivo imaging of small animals was used to observe the accumulation of Acu-exo in various organs of sepsis mice. LPS was used to induce macrophages in cell experiments, and the effect of Acu-exo on macrophage inflammatory cytokines was observed. In addition, The miRNA sequencing method was further used to detect the serum exosomes of normal and EA-treated mice, and combined with network biology analysis methods to screen possible key targets. Results: EA and Acu-exo reduced the W/D and lung tissue damage in sepsis mice, down-regulated the expression of serum inflammatory cytokines TNF-α and IL-6, and increased the survival rate of sepsis mice. In vivo imaging of small animals found that Acu-exo were accumulated in the lungs of sepsis mice. Cell experiments proved that Acu-exo down-regulated the expression of inflammatory cytokines TNF-α, IL-6 and IL-1β to alleviate the inflammatory response induced by LPS in macrophages. MiRNA sequencing revealed 53 differentially expressed miRNAs, and network biology analysis revealed the key targets of Acu-exo in sepsis treatment. Conclusion: Electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs may be a potential treatment for sepsis. [ABSTRACT FROM AUTHOR]

Background: Several association studies with small sample sizes of two SNPs in IL28BB (rs12979860 and rs8099917) showed inconsistent results, so in this study, we aim to evaluate the association between the two SNPs and infection susceptibility of Hepatitis B Virus (HBV) in Asian population, especially in Chinese population by meta-analysis. Methods: Search the relevant published papers and perform meta-analysis respectively on IL28B (rs12979860 and rs8099917) in Asian population and Chinese population under an additive genetic model by STATA11.0. Results: The pooled odds ratios (OR) of rs12979860 are 0.79 (95% CI, 0.53-1.18; P = 0.25, I² = 63.2%) and 1.62 (95% CI, 1.04-2.51; P = 0.033, I² = 54.3%) respectively in Asian population and Chinese population analysis. The pooled OR of rs8099917 are 1.05 (95% CI, 0.93-1.19; P = 0.44, I² = 43.3%) and 0.97 (95% CI, 0.84-1.23; P = 0.726, I² = 15.6%) respectively in Asian population and Chinese population analysis. Conclusion: Our study demonstrated that T allele of rs12979680 can increase the risk of HBV infection in Chinese population but not Asian population under an additive genetic model. There is no association between rs8099917 and HBV infection in Chinese population and Asian population. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-35 is a novel anti-inflammatory cytokine that is produced by regulatory T cells. IL-35 mediates immunological functions and plays a protective role in several diseases such as asthma and rheumatoid arthritis. However, the role of IL-35 in gingivitis and periodontitis remains unclear. The aim of this study was to systematically review the literature and collecting the available evidence regarding the role of IL-35 in pathogenesis of periodontal disease. Methods: A systematic search of electronic databases including MEDLINE, Google Scholar, Cochrane Library, Web of Science, and Scopus was conducted in November 2020 to identify studies addressing the Interleukin-35 pathobiology in periodontal disease. The identified studies were subjected to pre-identified inclusion criteria. The retrived papers were assessed by the authours independently and consensus was reached in cases where disagreement occurred. Articles written in languages other than English, case reports, letters to editors, conference abstracts, theses, and dissertations were excluded from the review. Results: A total of 176 possibly relevant articles were identified through the search strategy. Finally, 15 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence.Three subclinical study, ten cross sectional investigation and two randomized clinical trials constituted the final set of studies in this review. At preclinical level, Il-35 showed inhibitory characteristics regarding alveolar bone resorption of animal periodontitis models. The results of observatory human studies confirmed the presence of high levels of IL-35 in saliva, GCF, serum, and gingival biopsies of patients suffering from inflammatory periodontal disease. Moreover, two included clinical trials showed that non-surgical periodontal therapy could downregulate IL-35 production in chronic periodontitis patients. Conclusion: Interleukin-35 has an undeniable role in pathobiology of inflammatory periodontal disease. Further well-controlled studies are needed to better elucidate the functional pattern of IL-35 in pathogeneisis of gingival and periodontal disease. [ABSTRACT FROM AUTHOR]

Background: Morinda citrifolia (Noni) is a plant that has long been used in various products such as foods and cosmetics. Although noni has been known to have immunostimulatory activity, detailed mechanism at the cellular level has not been fully elucidated yet. In this study, we focused on understanding as to how noni fruit can positively stimulate body's immune responses. Methods: To do this, an ethanol extract of noni fruit (Mc-fEE) was prepared and administered for 30 days to male C57BL/6 mice for in vivo experiment. NK cell activity and cytokine production level from Mc-fEE-treated mice were analyzed by flowcytometry, real-time PCR, and ELISA. Mc-fEE-triggered molecular events were detected from RAW264.7 cells and splenocytes using Western blotting and real-time PCR analyses. Results: The mRNA expression levels of cytokines such as interleukin families, interferon (IFN)-β, and tumor necrosis factor (TNF)-α were increased by Mc-fEE treatment in vitro and in vivo. Western blotting analysis showed that the phosphorylation levels of nuclear factor (NF)-κB and activator protein (AP)-1 subunits these were enhanced in Mc-fEE-treated RAW264.7 cells. In addition, according to in vivo experiments, it was considered that Mc-fEE can increase the population of splenic NK cells and subsequent upregulation of their cytotoxic activity against YAC-1 cells, a T- cell lymphoma. Conclusion: In this paper, we could confirm that Mc-fEE has remarkable immunostimulatory effects by activation and increase of the NK cell population. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. Objective: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. Methods: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. Results: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). Conclusions: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a severe articular cartilage disease whose pathogenesis involves the inflammation of chondrocytes. MicroRNAs (miRNAs) are considered to be effective inflammation regulators. However, the regulatory mechanism of miRNAs in osteoarthritis needs to be further elucidated. In this paper, we aim to investigate the underlying mechanisms by which miR-4303 regulates osteoarthritis. Methods: RT-qPCR is performed to detect the mRNA expression levels of miR-4303, ASPN, PDIA3, PIK3CA, and TRAF3. CCK-8 assay and EdU assay are carried to assess chondrocyte viability. The protein expression levels of ASPN, PCNA, Ki-67, CyclinA1, CyclinB1, CyclinD2, p27, Bax, Bcl-2, cleaved caspase-3, and Cleaved caspase-9 were measured by western blot. FACs is performed to detect the cell cycle and apoptosis of chondrocyte. ELISA is conducted to assess the levels of TNF-β, IL-1β and IL-6 in the supernatant of chondrocytes. The potential binding sites of miR-4303 and ASPN are predicted by the miRDB database and confirmed by the dual-luciferase reporter gene assay. Results: Our findings illustrated that miR-4303 was down-regulated in arthritic tissues and LPS-induced chondrocytes; miR-4303 overexpression rescued the decrease in cell viability, cell cycle arrest and apoptosis induced by LPS. Furthermore, miR-4303 overexpression inhibited the release of inflammatory factors in LPS-induced chondrocytes, miR-4303 relieved chondrocyte inflammation via targeting ASPN. Conclusion: MiR-4303 serves as a prognostic biomarker and relieves chondrocyte inflammation via targeting ASPN. Our findings provide novel prognostic biomarkers in predicting the progression and prognosis of osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Lycium barbarum polysaccharide (LBP), the most abundant functional component of wolfberry, is considered a potent antioxidant and an anti-ageing substance. This review aims to outline the hallmarks of ageing in the pathogenesis of osteoarthritis (OA), followed by the current understanding of the senolytic effect of LBP and its potential use in the prevention and treatment of OA. This will be discussed through the lens of molecular biology and herbal medicine. Methods: A literature search was performed from inception to March 2020 using following keywords: "Lycium barbarum polysaccharide", "DNA damage", antioxidant, anti-apoptosis, anti-inflammation, anti-ageing, osteoarthritis, chondrocytes, fibroblasts, osteoblasts, osteoclasts, and "bone mesenchymal stem cell". The initial search yielded 2287 papers, from which 35 studies were selected for final analysis after screening for topic relevancy by the authors. Results: In literature different in vitro and in vivo ageing models are used to demonstrate LBP's ability to reduce oxidative stress, restore mitochondrial function, mitigate DNA damage, and prevent cellular senescence. All the evidence hints that LBP theoretically attenuates senescent cell accumulation and suppresses the senescence-associated secretory phenotype as observed by the reduction in pro-inflammatory cytokines, like interleukin-1beta, and matrix-degrading enzymes, such as MMP-1 and MMP-13. However, there remains a lack of evidence on the disease-modifying effect of LBP in OA, although its chondroprotective, osteoprotective and anti-inflammatory effects were reported. Conclusion: Our findings strongly support further investigations into the senolytic effect of LBP in the context of age-related OA. [ABSTRACT FROM AUTHOR]

Background: The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease., Methods: A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ 2 test, z test and a multivariate logistic stepwise regression test., Results: We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P <  0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P <  0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis., Conclusions: Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis.

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. [ABSTRACT FROM AUTHOR]

Introduction: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. Methods: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. Results: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. Conclusion: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI. [ABSTRACT FROM AUTHOR]

Background: Oral cancer (OC) is a common malignancy in clinical practice. Saliva testing is a convenient and noninvasive early diagnostic technique for OC. Several salivary cytokines have been identified as potential biomarkers for OC, including IL-8, IL-6, TNF-α, IL-1β, and IL-10. Nonetheless, the optimal cytokine for OC diagnosis remains inconclusive and highly contentious. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved to collect all case–control studies on OC. A meta-analysis was performed to compare the levels of salivary IL-8, IL-6, IL-10, TNF-α, and IL-1β in OC patients and healthy controls. Network meta-analysis (NMA) was carried out to probe into the accuracy of these salivary cytokines in diagnosing OC. Results: This analysis included 40 studies, encompassing 1280 individuals with OC and 1254 healthy controls. Significantly higher levels of salivary IL-8, IL-6, TNF-α, IL-1β, and IL-10 were observed in patients with OC in comparison to healthy controls. The results of NMA showed that TNF-α had the highest diagnostic accuracy for OC, with a sensitivity of 79% and a specificity of 92%, followed by IL-6 (sensitivity: 75%, specificity: 86%) and IL-8 (sensitivity: 80%, specificity: 80%). Conclusion: This study suggests that IL-8, IL-6, IL-10, TNF-α, and IL-1β may be potential diagnostic biomarkers for OC. Among them, TNF-α, IL-6, and IL-8 are highly accurate in the diagnosis of OC. Nevertheless, further studies that eliminate other confounding factors are warranted, and more standardized procedures and large-scale studies are needed to support the clinical use of saliva testing. [ABSTRACT FROM AUTHOR]

Background: This study compared the concentrations of interleukin (IL)-6, IL-17, and IL-35 in the gingival crevicular fluid of periodontally healthy participants with individuals who had stage III and IV periodontitis. Methods: In total, 60 participants with stage III grade B-C (n = 12)—stage IV grade C (n = 18) periodontitis and 30 healthy controls were included in this cross-sectional study. Full-mouth clinical periodontal measurements were performed. Concentrations of IL-6, IL-17, and IL-35 were determined using enzyme-linked immunosorbent assays. Parametric/nonparametric methods, Pearson's/Spearman's correlation, and logistic regression methods were used for data analyses. Results: The periodontitis group exhibited significantly higher levels of IL-6, IL-17, and IL-35 compared with the healthy group (p < 0.001). IL-17 levels had a positive correlation with pocket depth (PD) (r = 0.395; p = 0.031) in the periodontitis group. IL-6, IL-17, and IL-35 levels were associated with periodontitis (odds ratio [OR] = 1.344, 95% confidence interval [CI] = 1.159–1.56; OR = 1.063, 95% CI = 1.025–1.102; OR = 1.261, 95% CI = 1.110–1.434, respectively) (p < 0.001, p = 0.001, p < 0.001, respectively). Full-mouth and sampling sites PD and clinical attachment loss (CAL) values were significantly higher in the periodontitis group than in the healthy group (p < 0.001). Conclusions: This study revealed upregulated levels of IL-6, IL-17, and IL-35 in periodontitis patients compared to healthy individuals. IL-17 shows a correlation with increased PD. These findings suggest a potential association between these cytokines and severe and advanced periodontitis. Trial registration: The trial was registered in ClinicalTrials.gov with this identifier NCT05306860 on 24/01/2022. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has recently gained relevance in treating different psychiatric disorders. Limited evidence suggests that the beneficial effects of rTMS on psychopathology could be at least partly mediated through changes in inflammatory response. This systematic review summarizes the literature on whether rTMS can modulate inflammatory markers and thus positively influence the course of psychiatric illnesses. Materials and methods: A systematic review of rTMS and inflammatory markers in psychiatric diseases was conducted according to PRISMA guidelines. Information on the association between rTMS treatment response and changes of inflammatory markers was extracted. The quality of the studies was assessed using the National Heart, Lung, and Blood Institute for human studies and the Systematic Review Center for Laboratory Animal Experimentation for animal studies. Results: This review includes 17 studies (2 animal and 15 human studies) on the relationship between rTMS treatment response and changes of inflammatory markers. Positive changes in microglial activity and anti-inflammatory effects were associated with behavioral improvement in animal models of depression. However, these findings have not been consistently replicated in human studies focusing on treatment-resistant depression. While several studies reported rTMS-induced alterations in peripheral inflammatory markers, only two could demonstrate their association to clinical treatment response. Notably, most studies showed poor or moderate quality in the bias assessment. Conclusions: While certain human studies suggest an association between rTMS-induced anti-inflammatory effects and improvement in psychopathology, heterogeneity, and underpowered analyses constrain the generalizability of these results. The discrepancy between animal and human findings highlights the need for larger, standardized human studies. Trial registration: (PROSPERO Registration: CRD42023492732). [ABSTRACT FROM AUTHOR]

Background: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. Methods: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF):https://doi.org/10.17605/OSF.IO/BS9GM. A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. Results: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). Conclusion: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis. [ABSTRACT FROM AUTHOR]

Aim: This study explores the connection between Behçet's disease (BD), characterized by persistent oral and genital ulcers alongside iritis, and periodontal disease. It examines the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) in gingival crevicular fluid (GCF) and saliva. Methods: Forty Behçet's patients with gingivitis or periodontitis and 47 patients with either gingivitis or periodontitis but without BD were studied. Periodontal status was recorded with standard clinical indexes. GCF and saliva samples were obtained. NO, IL-1β and TNF-α levels were analysed. Current Behçet's symptoms and medications usage were recorded. Results: Mean salivary IL-1β was elevated (p =.045), and mean NO level was decreased in BD patients with gingivitis compared to patients without BD (p =.000). In contrast, mean NO level in crevicular fluid was higher in Behçet's patients with periodontitis than in patients without BD (p =.009). Furthermore, among Behçet's patients, those with vascular involvement had lower salivary NO level compared to patients without vascular involvement (p =.000). Conclusions: Based on our findings, the elevated levels of IL-1β in the saliva of Behçet's patients with gingivitis, along with the decreased NO level, indicate an altered inflammatory response in the oral cavity. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the long-term cost-effectiveness of conventional care (CC) and seven first-line targeted therapies marketed in China for the treatment of patients with ankylosing spondylitis (AS)–namely secukinumab, ixekizumab, infliximab, etanercept, adalimumab and golimumab and tofacitinib–from the perspective of the Chinese health care system. Methods: The York model was structured as a 12-week decision tree leading into two Markov models. This study set 1 year as a recurring cycle and a lifetime timeframe for the model. Primary model outcomes included the costs in Chinese yuan (CNY), health outcomes in quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of ¥89,358 (equal to the per capita gross domestic product in China in 2023) per QALY. Parameters in the York model were captured from network meta-analyses and literature including treatment response, short-term disease progression, patient functioning and long-term structural disease progression. Utilities are dependent on indicators such as the BASDAI score, the BASFI score, gender and age. Drug prices were analysed using the median price of the Chinese market from YAOZH net in the basic analysis. Costs and outcomes were discounted at 5.0%. We performed deterministic and probabilistic sensitivity analyses to investigate the robustness of the results. The prices of original drugs and generic drugs were used in the scenario analysis. Results: Compared with CC, the ICER of golimumab was ¥104,217.4/QALY, which is between 1 and 3 times the GDP per capita, while the ICERs of the other six targeted therapies were less than ¥89,358/QALY. The specific economic rank of the targeted therapy was as follows: secukinumab > ixekizumab > tofacitinib > infliximab > etanercept > adalimumab > golimumab. Treatment response rates such as the BASDAI50, changes in the BASDAI/BASFI scores and the discounting rate were key model drivers. According to the scenario analysis, IL-17 inhibitors were still the most economical intervention when original drugs and generic drugs were used. Conclusion: Targeted therapies are cost-effective treatments for AS. Overall, IL-17 inhibitors were the dominant treatment. The choice of the brand-new prices or generic drug prices can greatly affect economics. [ABSTRACT FROM AUTHOR]

Background: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. Methods: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P <.05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P <.01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck. Zeng-Sheng-Ping, composed of Sophora tonkinensis Gagnep., Bistorta officinalis Delarbre, Sonchus arvensis L., Prunella vulgaris L., Dioscorea bulbifera L., and Dictamnus dasycarpus Turcz., was regarded as an anti-cancer drug with significant clinical efficacy, but was discontinued due to liver toxicity. Our research group developed a modified Zeng-Sheng-Ping (ZSP-M) based on original Zeng-Sheng-Ping that exhibited high efficiency and low toxicity in preliminary investigations, although its pharmacodynamic mechanism is still unclear. Here, we aimed to elucidate the pharmacodynamic material basis of ZSP-M and investigate its chemopreventive effect on OSCC by modulating tumor associated macrophages (TAMs). Methods: Components of ZSP-M were characterized using ultra-performance liquid chromatography-mass spectrometry. Chemopreventive effect induced by ZSP-M against experimental oral cancer was investigated using the 4-nitroquinoline N-oxide precancerous lesion mouse model. RNA sequencing analysis was used to gain a global transcriptional view of the effect of ZSP-M treatment. A cell co-culture model was used to study the targeted effect of ZSP-M on TAMs and the biological properties of OSCC cells and to detect changes in TAM phenotypes. The binding of ZSP-M active compounds to TNF alpha induced protein 6 (TNFAIP6) protein was analyzed by molecular docking and dynamic simulation. Results: Forty main components of ZSP-M were identified, the most abundant of which were flavonoids. ZSP-M inhibited the degree of epithelial dysplasia in precancerous lesions by inhibiting the expression of the TNFAIP6 and CD163 proteins in the precancerous lesions of the tongue. ZSP-M inhibited proliferation, colony formation, migration and invasion of SCC7 cells by targeting TAMs. ZSP-M reduced the expression of CD163+ cells, inhibited the expression of TNFAIP6 protein, Arg1 mRNA and Il10 mRNA in TAMs, and reduced IL-10 cytokine release in the co-culture environment. This effect was maintained after the addition of recombinant TNFAIP6 protein. Computer simulations showed that trifolirhizin and maackiain are well-connected to TNFAIP6. Conclusions: ZSP-M counteracts the immunosuppressive action of TAMs by specific targeting of TNFAIP6, thereby exerting chemopreventive activity of OSCC. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. Methods: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. Results: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. Conclusions: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF. [ABSTRACT FROM AUTHOR]

In the past few decades, there has been a notable rise in the occurrence of several types of candidiasis. Candida albicans is the most common cause of superficial fungal infections in humans. In this study, plumieride, one of the major iridoids from Plumeria obtusa L. leaves, was isolated and investigated for its potential against Candida albicans (CA)-induced dermatitis in mice. qRT-PCR was done to assess the impact of plumieride on the expression of the major virulence genes of CA. Five groups (n = 7) of adult male BALB/c mice were categorized into: group I: non-infected mice; group II: mice infected intradermally with 107–108 CFU/mL of CA; group III: CA-infected mice treated with standard fluconazole (50 mg/kg bwt.); group IV and V: CA-infected mice treated with plumieride (25- and 50 mg/kg. bwt., respectively). All the treatments were subcutaneously injected once a day for 3 days. Skin samples were collected on the 4th day post-inoculation to perform pathological, microbial, and molecular studies. The results of the in vitro study proved that plumieride has better antifungal activity than fluconazole, manifested by a wider zone of inhibition and a lower MIC. Plumieride also downregulated the expression of CA virulence genes (ALS1, Plb1, and Hyr1). CA-infected mice showed extensive dermatitis, confirmed by strong iNOS, TNF-α, IL-1β, and NF-κB genes or immune expressions. Whereas the treatment of CA-infected mice with plumieride significantly reduced the microscopic skin lesions and modulated the expression of all measured proinflammatory cytokines and inflammatory markers in a dose-dependent manner. Plumieride interfered with the expression of C. albicans virulence factors and modulated the inflammatory response in the skin of mice infected with CA. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IDD) is an increasingly important cause of low back pain (LBP) that results in substantial health and economic burdens. Inflammatory pathway activation and the production of reactive oxygen species (ROS) play vital roles in the progression of IDD. Several studies have suggested that phillyrin has a protective role and inhibits inflammation and the production of ROS. However, the role of phillyrin in IDD has not been confirmed. Purpose: The purpose of this study was to investigate the role of phillyrin in IDD and its mechanisms. Study design: To establish IDD models in vivo, ex-vivo, and in vitro to verify the function of phillyrin in IDD. Method: The effects of phillyrin on extracellular matrix (ECM) degeneration, inflammation, and oxidation in nucleus pulposus (NP) cells were assessed using immunoblotting and immunofluorescence analysis. Additionally, the impact of phillyrin administration on acupuncture-mediated intervertebral disc degeneration (IDD) in rats was evaluated using various techniques such as MRI, HE staining, S-O staining, and immunohistochemistry (IHC). Result: Pretreatment with phillyrin significantly inhibited the IL-1β-mediated reduction in the degeneration of ECM and apoptosis by alleviating activation of the NF-κB inflammatory pathway and the generation of ROS. In addition, in vivo and ex-vivo experiments verified the protective effect of phillyrin against IDD. Conclusion: Phillyrin can attenuate the progression of IDD by reducing ROS production and activating inflammatory pathways. [ABSTRACT FROM AUTHOR]

Background: To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV). Methods: The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves. Results: There was no difference between group A1 and group A2, group B1 and group B2 in terms of age, gender, duration of hospitalisation and fever. The levels of calcitoninogen(PCT), lactate dehydrogenase concentration(LDH), interleukin(IL)-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ in group A were higher than group B. The severe group (A1, B1) was significantly higher than the mild group (A2, B2) in terms of D-dimer, CRP, PCT, LDH, IL-6, IL-8, IL-10, IL-17a and number of patients with pleural effusion, solid lung changes. Among the individual indexes of D-dimer, CRP, N%,LDH, and PCT, the AUC of the combined test was 0.977, which was higher than that of the individual indicators. Among IL-6, IL-8, IL-10, and IL-17a, the AUC of the combined assay was 0.802, which was higher than that of the individual indicators. Conclusion: MP combined with ADV infection was associated with increased expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, IFN-γ, and LDH. IL-6, IL-8, IL-10, IL-17a, LDH, PCT, CRP, and D-dimer could be used as predictors of SMPP and the combined test can improve the diagnostic value. [ABSTRACT FROM AUTHOR]

Background: Several association studies with small sample sizes of two SNPs in IL28BB (rs12979860 and rs8099917) showed inconsistent results, so in this study, we aim to evaluate the association between the two SNPs and infection susceptibility of Hepatitis B Virus (HBV) in Asian population, especially in Chinese population by meta-analysis., Methods: Search the relevant published papers and perform meta-analysis respectively on IL28B (rs12979860 and rs8099917) in Asian population and Chinese population under an additive genetic model by STATA11.0., Results: The pooled odds ratios (OR) of rs12979860 are 0.79 (95% CI, 0.53-1.18; P = 0.25, I(2) = 63.2%) and 1.62 (95% CI, 1.04-2.51; P = 0.033, I(2) = 54.3%) respectively in Asian population and Chinese population analysis. The pooled OR of rs8099917 are 1.05 (95% CI, 0.93-1.19; P = 0.44, I(2) = 43.3%) and 0.97 (95% CI, 0.84-1.23; P = 0.726, I(2) = 15.6%) respectively in Asian population and Chinese population analysis., Conclusion: Our study demonstrated that T allele of rs12979680 can increase the risk of HBV infection in Chinese population but not Asian population under an additive genetic model. There is no association between rs8099917 and HBV infection in Chinese population and Asian population.

Background: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. Methods: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. Results: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. Conclusion: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth. Methods: Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model. Results: OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (KD = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo. Conclusion: This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effect of the use of different NaOCl concentrations (1%, 2.5%, and 5.25%) during root canal treatment of molar teeth with symptomatic irreversible pulpitis on the change of the IL-8 level in gingival crevicular fluid (GFC). Methods: GCF sampling was performed on experimental tooth with irreversible pulpitis before and after treatment and also contralateral healthy tooth of 54 patients. The patients were divided into three groups according to concentration of NaOCl solution (n = 18); 1%, 2.5%, and 5.25% NaOCl solution. GCF sampling from experimental teeth was repeated one week after root canal treatment. Statistical analysis was performed using Mann-Whitney U, Wilcoxon test, one-way ANOVA and Pearson correlation analysis. Results: There was a significant correlation between IL-8 levels in GCF samples taken from teeth with pulpitis before treatment and from healthy contralateral teeth (p =.000). Furthermore, the pretreatment IL-8 level was significantly higher than the posttreatment IL-8 level(p <.05). The effect of the NaOCl concentration on the change in IL-8 level betweeen pre and post treatment was not found statistically significant (p >.05). Conclusions: The use of NaOCl during root canal treatment can effectively reduce the levels of IL-8 in GCF and improve clinical outcomes. Trial registration: This study was registred in the Institutional Review Board and the Ethics Committee of the University (No:11) on 15/12/2021. [ABSTRACT FROM AUTHOR]

Background: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. Methods: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. Results: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007–1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005–1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147–1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139–1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. Conclusion: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association. [ABSTRACT FROM AUTHOR]

Background and aims: Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study. Methods: Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms. Results: Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin − 1β (IL-1β)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue. Conclusion: Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. Methods: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. Results: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. Conclusions: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage. [ABSTRACT FROM AUTHOR]

Background: Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals. Methods: A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1β, TNF-α, MMP3, and MMP13. Results: 56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions. Conclusions: Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis. Systematic review registration: PROSPERO identifier: CRD42023377228. [ABSTRACT FROM AUTHOR]

Objective: Lumbar spine and pelvic fractures(LPF) are combined with peripheral ligament injuries(PLI), frequently. It has been reported that the site of fracture injury is usually paralleled by the secretion of inflammatory proteins. This study aimed to investigate the causal relationship between 91 circulating inflammatory proteins and LPF and PLI by using a Two-sample Mendelian randomization (MR) analysis. Methods: Single nucleotide polymorphisms (SNPs) associated with 91 circulating inflammatory proteins, as exposures were selected from a large genome-wide association study (GWAS). The genetic variant data for LPF and PLI as outcomes from the FinnGen consortium. The inverse-variance-weighted (IVW) method was utilized as the main analysis for exposures and outcomes. In addition, the final results were reinforced by the methods of MR Egger, weighted median, simple mode, and weighted mode. The sensitivity analyses were used to validate the robustness of results and ensure the absence of heterogeneity and horizontal pleiotropy. MR-Steiger was used to assess whether the causal direction was correct to avoid reverse causality. Results: This study has shown that Beta-nerve growth factor(Beta-NGF) and Interferon gamma(IFN-gamma) are both involved in the occurrence of LPF and PLI, and they are reducing the risk of occurrence(OR:0.800, 95%CI: 0.650–0.983; OR:0.723, 95%CI:0.568–0.920 and OR:0.812, 95%CI:0.703–0.937; OR:0.828, 95%CI:0.700–0.980). Similarly, Axin-1 and Sulfotransferase 1A1 (SULT-1A1) were causally associated with LPF(OR:0.687, 95%CI:0.501–0.942 and OR:1.178,95%CI:1.010–1.373). Furthermore, Interleukin-4(IL-4), Macrophage inflammatory protein 1a(MIP-1a), and STAM binding protein(STAM-BP) were causally associated with PLI(OR:1.236, 95% CI: 1.058–1.443; OR:1.107, 95% CI: 1.008–1.214 and OR:0.759, 95% CI: 0.617–0.933). The influence of heterogeneity and horizontal pleiotropy were further excluded by sensitivity analysis. Conclusion: This study provides new insights into the relationship between circulating inflammatory proteins and LPF and PLI, and may provide new clues for predicting this risk. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms. Methods: The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1β, TNFα and IL6 were measured by qRT‒PCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRT‒PCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo. Results: TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons. Conclusion: TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis. [ABSTRACT FROM AUTHOR]

The interleukin-4 (IL-4) signalling cascade has been identified as a pathway potentially important in the development of asthma. Genetic variants within this signalling pathway might contribute to the risk of developing asthma in a given individual. A number of polymorphisms have been described within the IL-4 receptor α (IL-4Rα) gene. In addition polymorphism occurs in the promoter for the IL-4 gene itself. This commentary accompanies a paper by C Ober et al describing the contribution of IL-4Rα polymorphism to susceptibility to asthma and atopy in the Hutterite population and other outbred populations collected during the collaborative studies on the genetics of asthma (CSGA) programme. [ABSTRACT FROM AUTHOR]

Objective: Lumbar disc herniation (LDH) is a common spinal surgical disease. Low back and leg pain caused by LDH is the main factor leading to functional disability, which has caused a serious burden to patients and society. Osteoking can delay the progression of osteoporosis and osteoarthritis, and even has a significant effect on the prevention of deep vein thrombosis after fracture surgery. In recent years, it has been gradually used in the treatment of LDH and has received significant results. However, the underlying mechanism remains unclear. The aim of this study was to predict the mechanism of Osteoking in the treatment of LDH through network pharmacology and verify it by molecular docking method. Methods: The TCMSP database was used to collect the relevant active components and targets of Osteoking, while the GeneCards, OMIM and DisGeNET databases were utilized to collect the relevant disease targets of LDH. The Venny 2.1.0 software was employed to obtain the intersecting gene targets of Osteoking and LDH. PPI network construction and core target selection were performed using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of the relevant targets. Finally, molecular docking was conducted using AutoDock software. Results: The study identified 116 potential targets and 26 core targets for the treatment of LDH with Osteoking. Pathways in cancer, Alzheimer's disease, microRNAs in cancer and the IL-17 signalling pathway were among the main involved signalling pathways. Molecular docking results demonstrated that the key targets AKT1, IL-6, ALB, TNF and IL-1β exhibited relatively stable binding activities with the main active components of Osteoking. Conclusions: Osteoking can alleviate the symptoms of lumbar disc herniation through the modulation of multiple targets and signalling pathways. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) is one of the most common health care-acquired infections. The dramatic increase in antimicrobial resistance of C. difficile isolates has led to growing demand to seek new alternative medicines against CDI. Achillea millefolium L. extracts exhibit strong biological activity to be considered as potential therapeutic agents. In this work, the inhibitory effects of A. millefolium, its decoction (DEC) and ethanol (ETOH) extracts, were investigated on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S) induced inflammation and apoptosis. Methods: Phytochemical analysis of extracts was performed by HPLC and GC analysis. The antimicrobial properties of extracts were evaluated against C. difficile RT001. Cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of extracts and Tox-S were examined by MTT assay and microscopy, respectively. Anti-inflammatory and anti-apoptotic effects of extracts were assessed in Tox-S stimulated Caco-2 cells by RT-qPCR. Results: Analysis of the phytochemical profile of extracts revealed that the main component identified in both extracts was chlorogenic acid. Both extracts displayed significant antimicrobial activity against C. difficile RT001. Moreover, both extracts at concentration 50 µg/mL had no significant effect on cell viability compared to untreated cells. Pre-treatment of cells with extracts (50 µg/mL) significantly reduced the percentage of Vero cells rounding induced by Tox-S. Also, both pre-treatment and co-treatment of Tox-S stimulated Caco-2 cells with extracts significantly downregulated the gene expression level of IL-8, IL-1β, TNF-α, TGF-β, iNOS, Bax, caspase-9 and caspase-3 and upregulated the expression level of Bcl-2. Conclusion: The results of the present study for the first time demonstrate the antimicrobial activity and protective effects of A. millefolium extracts on inflammatory response and apoptosis induced by Tox-S from C. difficile RT001 clinical strain in vitro. Further research is needed to evaluate the potential application of A. millefolium extracts as supplementary medicine for CDI prevention and treatment in clinical setting. [ABSTRACT FROM AUTHOR]

Objective: We investigated the impact of the long noncoding RNA LINC00958 on cellular activity and oxidative stress in osteoarthritis (OA). Methods: We performed bioinformatics analysis via StarBase and luciferase reporter assays to predict and validate the interactions between LINC00958 and miR-214-3p and between miR-214-3p and FOXM1. The expression levels of LINC00958, miR-214-3p, and FOXM1 were measured by qRT-PCR and western blotting. To assess effects on CHON-001 cells, we performed MTT proliferation assays, evaluated cytotoxicity with a lactate dehydrogenase (LDH) assay, and examined apoptosis through flow cytometry. Additionally, we measured the levels of apoptosis-related proteins, including BAX and BCL2, using western blotting. The secretion of inflammatory cytokines (IL-6, IL-8, and TNF-α) was measured using ELISA. Results: Our findings confirmed that LINC00958 is a direct target of miR-214-3p. LINC00958 expression was upregulated but miR-214-3p expression was downregulated in both OA cells and IL-1β-stimulated CHON-001 cells compared to the corresponding control cells. Remarkably, miR-214-3p expression was further reduced after miR-214-3p inhibitor treatment but increased following LINC00958-siRNA stimulation. Silencing LINC00958 significantly decreased its expression, and this effect was reversed by miR-214-3p inhibitor treatment. Notably, LINC00958-siRNA transfection alleviated the IL-1β-induced inflammatory response, as evidenced by the increased cell viability, reduced LDH release, suppression of apoptosis, downregulated BAX expression, and elevated BCL2 levels. Moreover, LINC00958 silencing led to reduced secretion of inflammatory factors from IL-1β-stimulated CHON-001 cells. The opposite results were observed in the miR-214-3p inhibitor-transfected groups. Furthermore, in CHON-001 cells, miR-214-3p directly targeted FOXM1 and negatively regulated its expression. Conclusion: Our findings suggest that downregulating LINC00958 mitigates IL-1β-induced injury in CHON-001 cells through the miR-214-3p/FOXM1 axis. These results imply that LINC00958 plays a role in OA development and may be a valuable therapeutic target for OA. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the exact mechanism and targets of SZYQD in asthma treatment have not been fully elucidated. Methods: A network pharmacological approach was used to predict the active components, targets, and signalling pathways of SZYQD in asthma, including potential target prediction, protein‒protein interaction (PPI) network construction and analysis, and Gene Ont (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The active ingredients were identified from the SZYQD, and were molecular docked according to the results of network pharmacology. A mouse model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS) was constructed to evaluate the therapeutic effect of SZYQD. Furthermore, the effects of SZYQD and its active ingredients were tested in vitro for regulating inflammation and MUC5AC expression (two main pathophysiologic abnormalities of asthma) in macrophages and airway epithelial cells by using Real-time PCR and western blotting. Results: A total of 28 active ingredients and 111 HUB genes were screened in the relevant databases, including three key ingredients (luteolin, β-carotene, and Sinapine) and nine core target genes (JUN, CTNNB1, IL10, TP53, AKT1, STAT3, TNF, IL6 and EGFR). KEGG and GO analysis indicated that the potential anti-asthmatic mechanisms of SZYQD were related to PI3K-Akt signalling pathway and response to lipopolysaccharide, etc. In the in vivo asthmatic model, our findings demonstrated that SZYQD exerted a protective effect against asthmatic mice induced by OVA and LPS through the inhibition of inflammation and mucus overproduction. Consistently, cell experiments showed that the SZYQD extract or the key active ingredients luteolin significantly decreased lipopolysaccharide (LPS)-induced IL-6 expression and activation of the NF-κB pathway in macrophages. In addition, SZYQD extract or luteolin inhibited activation of the AKT pathway and expression of MUC5AC induced by EGF in airway epithelial cells. Conclusion: The anti-asthmatic mechanism of SZYQD might be associated with inhibiting inflammation and airway mucus hypersecretion by regulating the NF-κB and AKT signalling pathways as predicted by network pharmacology, which provides more evidence for the application of SZYQD in asthma treatment. [ABSTRACT FROM AUTHOR]

Background: Pulp inflammation is complex interactions between different types of cells and cytokines. To mimic the interactions of different types of cells in inflamed dental pulp tissues, dental pulp cells (DPCs) were cocultured with different ratios of macrophages (THP-1) or LPS treatment. Methods: DPCs were cocultured with various ratios of THP-1, then photographed cell morphology and determined cell viability by MTT assay at preset times. Total RNA was also extracted to measure the inflammation marker-IL-6 and IL-8 expressions by RT-Q-PCR. The DPCs and THP-1 were treated with 0.01 – 1μg/ml lipopolysaccharide (LPS) and extract RNA at preset times, and detected IL-6 and IL-8 expression. DPCs were cocultured with various ratios of THP-1 with 0.1 μg/mL LPS, and detected IL-6 and IL-8 expression after 24 and 48 h. The data were analyzed by unpaired t-test or Mann-Whitney test. Differences were considered statistically significant when p < 0.05. Results: THP-1 and DPCs coculture models did not suppress the viability of DPCs and THP-1. Cocultured with various ratios of THP-1 could increase IL-6 and IL-8 expressions of DPCs (p = 0.0056 - p < 0.0001). The expressions of IL-6 and IL-8 were stronger in higher ratio groups (p = 0.0062 - p < 0.0001). LPS treatment also induced IL-6 and IL-8 expressions of DPCs and THP-1 (p = 0.0179 – p < 0.0001 and p = 0.0189 – p < 0.0001, separately). Under the presence of 0.1 μg/mL LPS, DPCs cocultured with THP-1 for 24 h also enhanced IL-6 and IL-8 expression (p = 0.0022). After cocultured with a higher ratio of THP-1 for 48 h, IL-6 and IL-8 expressions were even stronger in the presence of LPS (p = 0.0260). Conclusions: Coculturing dental pulp cells and macrophages under LPS treatment aggravate the inflammatory process. The responses of our models were more severe than traditional inflamed dental models and better represented what happened in the real dental pulp. Utilizing our models to explore the repair and regeneration in endodontics will be future goals. [ABSTRACT FROM AUTHOR]