Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti-inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.

Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear. This study aimed to develop a pipeline based on bioinformatics and systems biology approaches for identifying potential therapeutic targets involving possible biological mechanisms from SZ patients and healthy volunteers. About 420 overlapping differentially expressed genes (DEGs) from three RNA-seq datasets were identified. Gene ontology (GO), and pathways analysis showed several biological mechanisms enriched by the commonly shared DEGs, including extracellular matrix organization (ECM) organization, collagen fibril organization, integrin signaling pathway, inflammation mediated by chemokines and cytokines signaling pathway, and GABA-B receptor II and IL4 mediated signaling. Besides, 15 hub genes (FN1, COL1A1, COL3A1, COL1A2, COL5A1, COL2A1, COL6A2, COL6A3, MMP2, THBS1, DCN, LUM, HLA-A, HLA-C, and FBN1) were discovered by comprehensive analysis, which was mainly involved in the ECM organization and inflammatory signaling pathway. Furthermore, the miRNA target of the hub genes was analyzed with the random-forest-based approach software miRTarBase. In addition, the transcriptional factors and protein kinases regulating overlapping DEGs in SZ, namely, SUZ12, EZH2, TRIM28, TP53, EGR1, CSNK2A1, GSK3B, CDK1, and MAPK14, were also identified. The results point to a new understanding that the hub genes (fibronectin 1, collagen, matrix metalloproteinase-2, and lumican) in the ECM organization and inflammatory signaling pathways may be involved in the SZ occurrence and pathogenesis.

OBJECTIVE: IBD is a chronic idiopathic gut condition characterised by recurring and remitting inflammation of the colonic mucosal epithelium. Benzimidazole is a prominent and attractive heterocyclic compound with diverse actions. Although seven locations in the benzimidazole nucleus can be changed with a number of chemical entities for biological activity, benzimidazole fused with a phenyl ring has caught our interest.
METHODS: To find and optimize novel 1-H phenyl benzimidazole compounds with favorable physicochemical features and drug-like characteristics for the treatment of IBD, in-silico studies and in-vitro approach were being used to identify and optimize these derivatives as potent inhibitors of IL-23 mediated inflammatory signaling pathway.
RESULTS: All six compounds exhibit favorable drug-like properties with good intestinal absorption properties. Its high affinity for the target JAK and TYK, which is thought to be a key immunological signaling cascade in the pathophysiology of IBD, is revealed by docking studies.
CONCLUSIONS: Because of their effects on decreasing iNOS-derived NO release and IL-23-mediated immune signaling by decreasing COX-2 and LOX activity, it\'s conceivable that the compounds CS3 and CS6 are better options for the treatment of IBD based on in-vitro cell line investigations.

Chitooligosaccharide (COS) is a green and non-toxic cationic carbohydrate that has attracted wide attention in recent years due to its anti-inflammatory activity. However, the anti-inflammatory mechanism of COS remains unclear. In this study, RNA-seq was used to investigate the integrated response of COS to LPS-induced damage in macrophages. The results showed that the experimental group with COS had 2570 genes with significant differences compared to the model group, and that these genes were more enriched in inflammatory and immune pathways. The KEGG results showed that COS induces the pleiotropic modulation of classical inflammatory pathways, such as the Toll-like receptor signaling pathway, NF-κB, MAPK, etc. Based on the RNA-seq data and the RT-qPCR, as well as the WB validation, COS can significantly upregulate the expression of membrane receptors, such as Tlr4, Tlr5, and MR, and significantly inhibits the phosphorylation of several important proteins, such as IκB and JNK. Overall, this study offers deep insights into the anti-inflammatory mechanism and lays the foundation for the early application of COS as an anti-inflammatory drug.

Novel bioactive constituents from natural sources are actively being investigated. The phytochemicals in these phenolic compounds are believed to have a variety of beneficial effects on human health. Several phenolic compounds have been found in plants. The antioxidant potential of phenols has been discussed in numerous studies along with their anti-inflammatory effects on pro-inflammatory cytokine, inducible cyclooxygenase-2, and nitric oxide synthase. Through current study, an attempt is made to outline and highlight a wide variety of inflammation-associated signaling pathways that have been modified by several natural compounds. These signaling pathways include nuclear factor-kappa B (NF-кB), activator protein (AP)-1, protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors, tyrosine phosphatidylinositol 3-kinase (PI3K)/AKT, and the ubiquitin-proteasome system. In light of the influence of natural substances on signaling pathways, their impact on the production of inflammatory mediator is highlighted in this review.

OBJECTIVE: To observe the effect of acupuncture on microglia polarization and inflammatory reaction in rats with cerebral ischemia-reperfusion injury (CIRI), so as to explore its mechanisms underlying improvement of CIRI.
METHODS: Thirty male SD rats were randomly divided into sham operation, model, and acupuncture groups, with 10 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h, followed by reperfusion. After modeling, rats in the acupuncture group received manual acupuncture stimulation of \"Dazhui\" (GV14), \"Baihui\"(GV20), \"Shuigou\" (GV26), bilateral \"Zusanli\" (ST36) and \"Fengchi\" (GB20) by twirling the needles rapidly for 10 s/acupoint every 10 min, with the needles retained for 20 min. The treatment was conducted once daily for successive 7 days. The neurological function was evaluated according to Longa\'s method. The state of CIRI was observed after Nissl staining, and the expression levels of Iba-1, iNOS, Arg1, BDNF, GDNF and NeuN in the ischemic cortex tissue were detected by immunofluorescence staining. The contents of TNF-α, IL-6 and IL-10 in the ischemic tissue were assayed by ELISA. The protein expression levels of BDNF, GDNF, TLR4, MyD88 and NF-κB in the ischemic tissues were detected by Western blot.
RESULTS: The neurological deficit score on the 24 h and 7th day was considerably higher in the model group than in the sham operation group (P<0.01), and evidently lower on the 7th day in the acupuncture group than in the model group (P<0.01). The number of NeuN positive cells，the area of immunofluorescence dual labelling of Arg1, BDNF and GDNF positive staining, IL-10 content, BDNF and GDNF protein expressions were significantly decreased (P<0.01), and the immunofluorescence dual labelling area of Iba-1 and iNOS, TNF-α and IL-6 contents, the pretein expression levels of TLR4, MyD88 and NF-κB considerably increased (P<0.01) in the model group relevant to the sham operation group. In contrast to the model group, the acupuncture group had a significant increase in the number of NeuN positive cells, the immunofluorescence dual labelling area of Arg1, BDNF and GDNF positive staining, IL-10 content, and BDNF and GDNF protein expressions (P<0.05, P<0.01), and an evident decrease in Iba-1 and iNOS positive staining, contents of TNF-α and IL-6, and the protein expression levels of TLR4, MyD88 and NF-κB (P<0.01, P<0.05). Nissl staining showed a marked reduction in the number of neurons, the nucleus pyknosis and nissl bodies and loose arrangement of the neuronal cells in the model group, which was relatively milder in the acupuncture group.
CONCLUSIONS: Acupuncture intervention can improve neurological function in CIRI rats, which may be related to its effects in regulating the polarization of microglia, reducing inflammatory reaction and increasing the secretion of neurotrophic factors in the brain, inhibiting TLR4/MyD88/NF-κB signaling pathway.
目的：观察针刺对脑缺血再灌注(I/R)损伤大鼠小胶质细胞极化和炎性反应的影响，探讨其潜在的作用机制。方法：雄性SD大鼠随机分为假手术组、模型组、针刺组，每组10只。采用大脑中动脉栓塞法制备大鼠脑I/R损伤模型。针刺组大鼠在造模后于“大椎”“百会”“水沟”及双侧“足三里”“风池”进行针刺，20 min/次，1次/d，连续7 d。采用神经功能评分法评估各组大鼠神经功能；尼氏染色法观察脑梗死侧皮质区神经元损伤情况；免疫荧光染色法检测缺血侧皮质区神经元特异性核蛋白(NeuN)、离子钙结合蛋白1(Iba-1)、诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)的表达；ELISA法检测缺血脑组织中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6和IL-10的含量；Western blot法检测缺血脑组织中BDNF、GDNF、Toll样受体4(TLR4)、髓样分化因子88(MyD88)和核因子κB(NF-κB)的表达水平。结果：与假手术组比较，模型组大鼠神经功能评分升高(P<0.01)，脑缺血侧皮质区神经元数量及尼氏体减少，NeuN阳性细胞数、Arg1阳性表达减少(P<0.01)，Iba-1、iNOS阳性表达增加(P<0.01)，BDNF、GDNF阳性表达和蛋白表达水平及IL-10含量降低(P<0.01)，TNF-α、IL-6含量升高(P<0.01)，TLR4、MyD88和NF-κB蛋白表达水平升高(P<0.01)。与模型组比较，针刺组大鼠神经功能评分降低(P<0.01)，缺血侧皮质区神经元数量及尼氏体增多，NeuN阳性细胞数、Arg1阳性表达增多(P<0.05)，Iba-1、iNOS阳性表达减少(P<0.01)，BDNF、GDNF阳性表达和蛋白表达水平及IL-10含量升高(P<0.01，P<0.05)，TNF-α、IL-6含量降低(P<0.01)，TLR4、MyD88和NF-κB蛋白表达水平降低(P<0.05，P<0.01)。结论：针刺干预可以通过调节脑I/R后小胶质细胞极化、减轻炎性反应和增加神经营养因子的分泌，对I/R后脑组织起神经保护作用，其机制可能与抑制TLR4/MyD88/NF-κB信号通路有关。.

The characteristic of ulcerative colitis (UC) is extensive colonic mucosal inflammation. Moringa oleifera (M. oleifera) is a medicine food homology plant, and the polysaccharide from M. oleifera leaves (MOLP) exhibits antioxidant and anti-inflammatory activity. The aim of this study to investigate the potential effect of MOLP on UC in a mouse model as well as the underlying mechanism. Dextran sulfate sodium (DSS) 4% in drinking water was given for 7 days to mice with UC, at the same time, MOLP (25, 50, and 100 mg/kg/day) was intragastric administered once daily during the experiment. Structural analysis revealed that MOLP had an average molecular weight (Mw) of 182,989 kDa and consisted of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galactose uronic acid, glucuronic acid, glucose uronic acid and mannose uronic acid, with a percentage ratio of 1.64, 18.81, 12.04, 25.90, 17.57, 12.01, 3.51, 5.28, 0.55, 1.27, and 1.43%, respectively. In addition, the features of MOLP were identified by Fourier-transform infrared (FT-IR) and spectra, X-ray diffraction (XRD). The results showed that MOLP exhibited protective efficacy against UC by alleviating colonic pathological alterations, decreasing goblet cells, crypt destruction, and infiltration of inflammatory cells caused by DSS. Furthermore, MOLP notably repressed the loss of zonula occludens-1 (ZO-1) and occludin proteins in mucosal layer, as well as up-regulating the mRNA expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-γ (PPAR-γ), whereas down-regulating the activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB) signaling pathway and the production of pro-inflammatory cytokines. Therefore, these results will help understand the protective action procedure of MOLP against UC, thereby providing significance for the development of MOLP.

The innate immune system is the first line of defense for the host against any microbial attack. It can quickly identify microorganisms and produce an immune response, removing pathogenic microorganisms. However, a strong immune response might lead to excessive inflammation and even autoimmune diseases. NLRC3 is an important regulator of innate immune system homeostasis. It is a member of the anti-inflammatory NLR family and can inhibit excessive immune response in the body. In this review, we primarily focused on the current research progress on NLRC3 and its potential application. It can decrease the production of pro-inflammatory cytokines by inhibiting the NF-κB, MAK-ERK, PI3K-mTOR, IL-6/JAK2/STAT3, and cGAS-STING pathways. It also inhibits inflammatory responses by interfering with the assembly and activity of the NLRP3 inflammasome complexes. Additionally, NLRC3 can also reduce the functions of some antigen-presenting cells and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. NLRC3 is closely related to the development of tumors, infectious diseases, autoimmune diseases, and AD. These diseases might be treated effectively by regulating the expression of NLRC3.

Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids in Coptis chinensis Franch. (CCFIAs) exerted a multitude of biological activities such as anti-inflammatory, antioxidant, antibacterial, and immunomodulatory etc, revealing a great potential for calming CS. Therefore, in this timeline review, we report and compare the effects of CCFIAs to attenuate the exacerbation of inflammatory responses by modulating signaling pathways like NF-ĸB, mitogen-activated protein kinase, JAK/STAT, and NLRP3. In addition, we also discuss the role of berberine (BBR) in two different triggers of CS, namely sepsis and viral infections, as well as its clinical applications. These evidence provide a rationale for considering CCFIAs as therapeutic agents against inflammatory CS and this suggestion requires further validation with clinical studies.