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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that overlap in their clinical presentation, pathology and genetic origin. Autoimmune disorders are also overrepresented in both ALS and FTD, but this remains an unexplained epidemiologic observation 1-3 . Expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial ALS and FTD (C9-ALS/FTD), and lead to both repeat-containing RNA and dipeptide accumulation, coupled with decreased C9orf72 protein expression in brain and peripheral blood cells 4-6 . Here we show in mice that loss of C9orf72 from myeloid cells alone is sufficient to recapitulate the age-dependent lymphoid hypertrophy and autoinflammation seen in animals with a complete knockout of C9orf72. Dendritic cells isolated from C9orf72 -/- mice show marked early activation of the type I interferon response, and C9orf72 -/- myeloid cells are selectively hyperresponsive to activators of the stimulator of interferon genes (STING) protein-a key regulator of the innate immune response to cytosolic DNA. Degradation of STING through the autolysosomal pathway is diminished in C9orf72 -/- myeloid cells, and blocking STING suppresses hyperactive type I interferon responses in C9orf72 -/- immune cells as well as splenomegaly and inflammation in C9orf72 -/- mice. Moreover, mice lacking one or both copies of C9orf72 are more susceptible to experimental autoimmune encephalitis, mirroring the susceptibility to autoimmune diseases seen in people with C9-ALS/FTD. Finally, blood-derived macrophages, whole blood and brain tissue from patients with C9-ALS/FTD all show an elevated type I interferon signature compared with samples from people with sporadic ALS/FTD; this increased interferon response can be suppressed with a STING inhibitor. Collectively, our results suggest that patients with C9-ALS/FTD have an altered immunophenotype because their reduced levels of C9orf72 cannot suppress the inflammation mediated by the induction of type I interferons by STING.

Avian pathogenic Escherichia coli (APEC) is a kind of highly pathogenic parenteral bacteria, which adheres to chicken type II pneumocytes through pili, causing inflammatory damage of chicken type II pneumocytes. Without affecting the growth of bacteria, anti-adhesion to achieve anti-inflammatory effect is considered to be a new method for the treatment of multi-drug-resistant bacterial infections. In this study, the anti-APEC activity of schizandrin was studied in vitro. By establishing the model of chicken type II pneumocytes infected with APEC-O78, the adhesion number, the expression of virulence genes, the release of lactate dehydrogenase (LDH), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were detected. The results showed that schizandrin reduced the release of LDH and the adherence of APEC on chicken type II pneumocytes. Moreover, schizandrin markedly decreased the levels of IL-1β, IL-8, IL-6, and TNF-α, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings revealed that schizandrin could reduce the inflammatory injury of chicken type II pneumocytes by reducing the adhesion of APEC-O78 to chicken type II pneumocytes. The results indicate that schizandrin can be a potential agent to treat inflammation caused by avian colibacillosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recent experimental data and clinical, genetic, and transcriptome evidence from patients converge to suggest a key role of interleukin-1β (IL-1β) in the pathogenesis of Kawasaki disease (KD). However, the molecular mechanisms involved in the development of cardiovascular lesions during KD vasculitis are still unknown. Here, we investigated intestinal barrier function in KD vasculitis and observed evidence of intestinal permeability and elevated circulating secretory immunoglobulin A (sIgA) in KD patients, as well as elevated sIgA and IgA deposition in vascular tissues in a mouse model of KD vasculitis. Targeting intestinal permeability corrected gut permeability, prevented IgA deposition and ameliorated cardiovascular pathology in the mouse model. Using genetic and pharmacologic inhibition of IL-1β signaling, we demonstrate that IL-1β lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Targeting mucosal barrier dysfunction and the IL-1β pathway may also be applicable to other IgA-related diseases, including IgA vasculitis and IgA nephropathy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Coxsackievirus group B (CVB) is considered as one of the most common pathogens of human viral myocarditis. CVB-induced myocarditis is mainly characterized by the persistence of the virus infection and immune-mediated inflammatory injury. Costimulatory signals are crucial for the activation of adaptive immunity. Our data reveal that the CVB type 3 (CVB3) infection altered the expression profile of costimulatory molecules in host cells. CVB3 infection caused the decrease of PD-1 ligand expression, partially due to the cleavage of AU-rich element binding protein AUF1 by the viral protease 3C pro , leading to the exacerbated inflammatory injury of the myocardium. Moreover, systemic PD-L1 treatment, which augmented the apoptosis of proliferating lymphocytes, alleviated myocardial inflammatory injury. Our findings suggest that PD1-pathway can be a potential immunologic therapeutic target for CVB-induced myocarditis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Macrophages are the master regulator of the dynamic fibrogenesis-fibrosis resolution paradigm. TNF-like ligand 1 aberrance (TL1A) was found to be able to induce intestinal inflammation and fibrosis. Furthermore, significantly increased TL1A had been detected in liver tissues and mononuclear cells of patients with primary biliary cirrhosis (PBC). This study was to investigate the effect of myeloid cells with constitutive TL1A expression on liver fibrogenesis. We found that TL1A expressions in liver tissues and macrophages were significantly increased in mice with liver fibrosis induced by injection of carbon tetrachloride (CCl 4 ). TL1A overexpression in myeloid cells induced liver function injury, accelerated the necrosis and apoptosis of hepatocytes, recruited macrophages, and promoted activation of hepatic stellate cells (HSCs) and fibrosis. In vitro results of our study showed that TL1A overexpression in macrophages promoted secretion of platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor- α (TNF- α ), and interleukin-1 β (IL-1 β ). Culturing macrophages with TL1A overexpression could accelerate the activation and proliferation of primary HSCs. These results indicated that constitutive TL1A expression in myeloid cells exacerbated liver fibrosis, probably through macrophage recruitment and secretion of proinflammatory and profibrotic cytokines.

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood., Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry., Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment., Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.

In previous studies, abdominal obesity has been related to total low-grade inflammation and in some cases has resulted in insulin resistance and other metabolism related disorders such as diabetes. Quercetin is a polyphenol, which is a derivative of plants, and has been shown in vitro as well as in a few animal models to have several potential anti-inflammatory as well as anticarcinogenic applications. The substance has also been shown to aid in the attenuation of lipid peroxidation, platelet aggregation, and capillary permeability. However, further research is called for to gain a better understanding of how quercetin is able to provide these beneficial effects. This manuscript reviewed quercetin's anti-inflammatory properties in relation to obesity and type 2 diabetes., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this article.

Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background Context: Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed., Purpose: To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects., Study Design: In vitro experiments and in vivo analysis in a rodent model., Methods: In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry. In vivo, rats underwent a left-sided laminotomy at L5 to expose the S1 nerve root and were randomized into four different groups according to the intervention at the laminotomy site: collagen sponge only (no BMP-2 or Spp24), BMP-2 in a collagen sponge only, BMP-2 in a collagen sponge+an empty collagen sponge to act as a barrier, and BMP-2 in a collagen sponge+Spp24 in a collagen sponge to act as a barrier. Functional evaluation was done using the Basso, Beattie, and Bresnahan scale and immunohistochemical analyses were performed using calcitonin gene-related peptide and Substance P staining., Results: The neuroinflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuroinflammation in animals treated with BMP-2 and also improved the function after BMP-2 administration., Conclusions: These results confirm that BMP binding proteins have great potential as adjuvant therapies to limit BMP-2 related side-effects in spine surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Estrogen is involved in inflammation/pain of temporomandibular joint (TMJ), but the underlying mechanisms are largely unknown. Cadherin-11 plays an essential role in synovial inflammation. This study examined whether estrogen could potentiate cadherin-11 in synoviocytes and contribute to TMJ inflammatory pain. Female rats were ovariectomized, treated with increasing doses of 17β-estradiol for 10 days, and injected intra-articularly with complete Freund's adjuvant to induce TMJ inflammation. The expression of cadherin-11 in synovial membrane was evaluated. TMJ pain was blocked with intra-articular injection of anti-cadherin-11 antibody and evaluated by head withdrawal threshold. Primary TMJ synoviocytes were treated with estradiol and tumor necrosis factor (TNF)-α or blocked with anti-cadherin-11 antibody to assess the expression of cadherin-11, interleukin (IL)-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). We observed that estradiol potentiated the inflammation-induced expression of cadherin-11 in the synoviocytes of synovial membrane from inflamed TMJ. Estradiol induced cadherin-11 expression in a dose- and time-dependent manner in primary synoviocytes and further potentiated the induction of cadherin-11 by TNF-α in synoviocytes. Furthermore, an estrogen receptor antagonist or a NF-κB inhibitor partially blocked the effects of estradiol on cadherin-11 induction in the synovial membrane. Blocking cadherin-11 partially reversed the TMJ inflammatory pain and estradiol-potentiated proliferation of synovial lining cells accompanied with iNOS expression. In addition, blocking cadherin-11 reversed TNF-α-induced and estradiol-potentiated transcription of IL-6, COX-2, and iNOS in primary synoviocytes. These results suggest that estrogen aggravated TMJ inflammatory pain partially through cadherin-11-mediated release of proinflammatory cytokines and enzymes in the synoviocytes., (Copyright © 2014. Published by Elsevier Ltd.)

Inflammation mediated by activated microglia cells has been shown to contribute to the pathogenesis of Alzheimer disease (AD) [1]. Microglia are the immune cells in the central nervous system, and when activated they secrete the lipid-derived mediator prostaglandin E2 (PGE2), the cytokine interleukin-1beta (IL-1beta), and other inflammatory mediators. Apolipoprotein E isoform 4 (apoE4), coded for by the gene APOE4 (epsilon4), has been shown to correlate with higher risk of onset of AD, as well as with increased severity of other diseases with a neuroinflammatory component. This study investigated isoform-specific effects of apoE on the regulation of PGE2, COX2, and IL-1beta expression. Two physiologically relevant preparations of apoE displayed an isoform-specific effect on inflammation in primary adult microglia cultured from adult rat brain cortex. Specifically, apoE4 alone, but not the more common isoform apoE3, stimulated secretion of PGE2 and IL-1beta. The increase in PGE2 release stimulated by apoE4 was not accompanied by the upregulation of the COX-2 enzyme in microglia.

Receptor interacting protein 2 (RIP2) plays a role in sensing intracellular pathogens, but its function in T cells is unclear. We show that RIP2 deficiency in CD4+ T cells resulted in chronic and severe interleukin-17A-mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper 17 (Th17) cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. While RIP2 deficiency resulted in reduced conventional Th17 cell differentiation, it led to significantly enhanced differentiation of pathogenic (p)Th17 cells, which was dependent on RORα transcription factor and interleukin-1 but independent of nucleotide oligomerization domain (NOD) 1 and 2. Overexpression of RIP2 resulted in suppression of pTh17 cell differentiation, an effect mediated by its CARD domain, and phenocopied by a cell-permeable RIP2 CARD peptide. Our data suggest that RIP2 has a T cell-intrinsic role in determining the balance between homeostatic and pathogenic Th17 cell responses.

Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2−/−, and TLR4−/− mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2−/− mice, but not in TLR4−/− mice, due to differential Treg responses in these genotypes. TLR2−/− mice had reduced numbers of Tregs in the lung during CP infection while TLR4−/− mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

• The role of SPARC family proteins in development and diseases in CNS. • In SPARC family proteins, SPARC activates autophagy and promotes apoptosis. • SPARC family proteins play important roles of angiogenesis in brain. • SPARC family proteins are involved in inflammation in brain. • SPARC regulates glucose and lipid metabolism in the body. SPARC (secreted protein acidic and rich in cysteine) family of proteins is a class of protein involved in tissue development and repair by regulating cell adhesion, proliferation, metastasis, and growth factor signaling to affect the extracellular matrix (ECM) and interactions between cells. Although being highly valued in non-nerve tissues, studies in both cell and animal models have been revealed that SPARC family proteins may also continue to play a vital role in central nervous system (CNS) diseases and development. These SPARC family proteins are widely expressed in the CNS of normal people, and significantly increased in brain tissue following disease or injury, such as SPARC, SPARCL-1, FSTL-1 and testican. In our review, we will pay attention to the functions of SPARC family proteins in autophagy, apoptosis, angiogenesis, adipogenesis, inflammatory response, and cerebral tissue development, injury and repair mainly including but not limited to axon regeneration, formation of glial scar, neural plasticity, regulation of nerve conduction related receptors and rewiring of neural circuitry. [ABSTRACT FROM AUTHOR]

Tumor progression can be affected by various cellular components of tumor cells and/or by tumor microenvironmental factors. The tumor microenvironment comprises a variety of nonmalignant stromal cells and inflammatory cytokines, which are pivotal in tumor promotion and progression. The transforming growth factor-ß (TGF-ß) ligands (TGF-ß1, 2 and 3) are secreted inflammatory cytokines, which are known to be involved in various aspects of tumor development through two transmembrane serine-threonine kinase receptors, TGFßR1 and TGFßR2. TGF-ß promotes or inhibits tumorigenesis depending on the concurrent gene mutations and tissue microenvironment present through the small mothers against decapentaplegic (Smad) and non-Smad pathways. This review aims to provide a comprehensive overview of the role of the TGF-ß pathway in tumor initiation and progression. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke. [ABSTRACT FROM AUTHOR]

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the 'inflammasome', and is required to cleave pro-IL-1&bgr; to bioactive IL-1&bgr;. Here we demonstrate for the first time a critical requirement for IL-1&bgr; in response to CP infection. Caspase- 1-/-mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-12/2 mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1&bgr; rescues CP infected Caspase-1-/-mice from mortality, indicating that IL-1&bgr; secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1&bgr; secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation. [ABSTRACT FROM AUTHOR]

Although bioactive sphingolipids have been shown to regulate cardiometabolic homeostasis and inflammatory signaling pathways in rodents, population-based longitudinal studies of relationships between sphingolipids and onset of metabolic syndrome (MetS) are sparse. We aimed to determine associations of circulating sphingolipids with inflammatory markers, adipokines, and incidence of MetS. Among 1242 Chinese people aged 50–70 years who completed the 6-year resurvey, 76 baseline plasma sphingolipids were quantified by high-throughput liquid chromatography-tandem mass spectrometry. There were 431 incident MetS cases at 6-year revisit. After multivariable adjustment including lifestyle characteristics and BMI, 21 sphingolipids mainly from ceramide and hydroxysphingomyelin subclasses were significantly associated with incident MetS. Meanwhile, the baseline ceramide score was positively associated (RRQ4 versus Q1 = 1.31; 95% CI 1.05, 1.63; ptrend = 0.010) and the hydroxysphingomyelin score was inversely associated (RRQ4 versus Q1 = 0.60; 95% CI 0.45, 0.79; ptrend < 0.001) with incident MetS. When further controlling for clinical lipids, both associations were attenuated but remained significant. Comparing extreme quartiles, RRs (95% CIs) of MetS risk were 1.34 (95% CI 1.06, 1.70; ptrend = 0.010) for ceramide score and 0.71 (95% CI 0.51, 0.97; ptrend = 0.018) for hydroxysphingomyelin score, respectively. Furthermore, a stronger association between ceramide score and incidence of MetS was evidenced in those having higher inflammation levels (RRQ4 versus Q1 1.57; 95% CI 1.16, 2.12; pinteraction = 0.004). Our data suggested that elevated ceramide concentrations were associated with a higher MetS risk, whereas raised hydroxysphingomyelin levels were associated with a lower MetS risk beyond traditional clinical lipids. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IVDD) constitutes a crucial pathological foundation for spinal degenerative diseases (SDD) and stands as a primary contributor to both low back pain (LBP) and disability. The progression of IVDD is linked to structural and functional alterations in tissues, where an imbalance in the inflammatory microenvironment can induce extracellular matrix (ECM) degradation, senescence, and apoptosis. This imbalance is a key pathomechanism in the disease's development, gaining considerable attention in recent years. This study aims to conduct a bibliometric analysis of publications pertaining to the inflammatory mechanisms of IVDD to quantitatively assess current research hotspots and directions. In this study, we queried the Web of Science Core Collection (WOSCC) database covering the period from January 1, 2001, to November 7, 2023. Content in this area was analyzed and visualized using software such as Citespace, Vosviewer, and the bibliometrix package. Findings indicate a consistent annual increase in the number of publications, highlighting the widespread attention garnered by research on the inflammatory mechanisms of IVDD. In terms of journal research, Spine emerged with the highest number of publications, along with significantly elevated total citations and average citations compared to other journals. Regarding country analysis, China led in the number of publications, while the USA claimed the highest number of citations and total link strength. Institutional analysis revealed Sun Yat-sen University as having the highest number of publications and total link strength, with Thomas Jefferson University securing the highest total citations. Author analysis identified Ohtori, S. with the highest number of publications, Risbud, M.V. with the highest number of citations, and Inoue, G. with the highest total link strength, all of whom have made significant contributions to the field's development. Citation and co-citation analyses indicated that highly cited documents primarily focused on classical studies exploring inflammatory mechanisms in IVDD pathogenesis. Keyword analysis showcased the ongoing research hotspot as the further investigation of mechanisms and treatment studies. Recent years have seen a shift towards exploring pyroptosis, necrotic apoptosis, autophagy, ferroptosis, oxidative stress, and bacterial infection, among other mechanisms. In terms of treatment, alongside traditional monomer, drug, and compound therapies for IVDD, research is increasingly concentrating on stem cell therapy, exosomes, hydrogels, and scaffolds. This bibliometric analysis of research on inflammatory mechanisms in IVDD provides insights into the current status, hotspots, and potential future trends. These findings can serve as a valuable reference and guide for researchers in the field. • This study is the first to explore the hotspots and future trends in the study of inflammatory mechanisms in IVDD through bibliometric methods. • The ongoing research hotspot as the further investigation of mechanisms and treatment studies. [ABSTRACT FROM AUTHOR]

The diagram illustrates the interactions of ROS/RNS with inflammatory molecules and the application of Omics for studying such interactions, and discovering Chinese Medicine compounds and formulae. During the cerebral ischemia-reperfusion injury, the central nervous system interacts with and peripheral system. ROS/RNS interacts with inflammatory cells and factors for mediating ischemic stroke injury. Chinse medicine compounds and TCM formulae can target those interactions for neuroprotection. Omics techniques serve as useful tools for understanding the interaction of ROS/RNS with inflammation, and investigating the mechanisms of Chinse medicine compounds and formulae for treating stroke. Reactive oxygen species (ROS); Reactive nitrogen species (RNS); Advanced glycation end products (RAGE); Toll-like receptor 2/4 (TLR2/4); poly (ADP-ribose) polymerase (PARP); TCM, Traditional Chinese Medicine. • Interactions of oxidative/nitrosative stress, neuroimmune and inflammatory responses in ischemic brain injury. • Omics and systematic biology approach reveal network regulations related to oxidative stress and inflammation in the pathology of stroke. • Active compounds from medicinal herbs with the bioactivity of anti-oxidative stress and anti-inflammation for reducing ischemic brain injury. • Omics approach for exploring the molecular mechanisms and active compounds of Traditional Chinese Medicine for neuroprotection. Oxidative/nitrosative stress and neuroinflammation are critical pathological processes in cerebral ischemia-reperfusion injury, and their intimate interactions mediate neuronal damage, blood-brain barrier (BBB) damage and hemorrhagic transformation (HT) during ischemic stroke. We review current progress towards understanding the interactions of oxidative/nitrosative stress and inflammatory responses in ischemic brain injury. The interactions between reactive oxygen species (ROS)/reactive nitrogen species (RNS) and innate immune receptors such as TLR2/4, NOD-like receptor, RAGE, and scavenger receptors are crucial pathological mechanisms that amplify brain damage during cerebral ischemic injury. Furthermore, we review the current progress of omics and systematic biology approaches for studying complex network regulations related to oxidative/nitrosative stress and inflammation in the pathology of ischemic stroke. Targeting oxidative/nitrosative stress and neuroinflammation could be a promising therapeutic strategy for ischemic stroke treatment. We then review recent advances in discovering compounds from medicinal herbs with the bioactivities of simultaneously regulating oxidative/nitrosative stress and pro-inflammatory molecules for minimizing ischemic brain injury. These compounds include sesamin, baicalin, salvianolic acid A, 6-paradol, silymarin, apocynin, 3H-1,2-Dithiole-3-thione, (−)-epicatechin, rutin, Dl-3 -N- butylphthalide, and naringin. We finally summarize recent developments of the omics and systematic biology approaches for exploring the molecular mechanisms and active compounds of Traditional Chinese Medicine (TCM) formulae with the properties of antioxidant and anti-inflammation for neuroprotection. The comprehensive omics and systematic biology approaches provide powerful tools for exploring therapeutic principles of TCM formulae and developing precision medicine for stroke treatment. [ABSTRACT FROM AUTHOR]

Avian pathogenic Escherichia coli (APEC) can cause serious pathological changes and inflammation in chickens. Schizandrin has anti-inflammatory activity and can prevent damage to various tissues and organs. The purpose of this study was to investigate the protective effect of schizandrin on APEC-induced lung lesions in chickens and explore the potential mechanism of schizandrin protection. The schizandrin (50, 100, and 200 mg/kg) was intragastrically administered for 3 days. APEC was administered using intraperitoneal (i.p.) injection to induce lung lesions. Then, chickens were sacrificed by CO 2 inhalation 24 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings showed that schizandrin markedly inhibited pathological changes, pulmonary edema, MPO activity and MDA content. Moreover, schizandrin markedly reduced the levels of TNF-α, IL-1β, IL-6 and IL-8 in lung tissue. Importantly, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings reveal that schizandrin displays anti-oxidant and anti-inflammatory activity against APEC-induced lung lesions in chickens, paving the way for rational use of schizandrin as a protective agent against lung-related inflammatory disease. • The protective effect of schizandrin on APEC-induced lung lesions in chickens was studied. • Schizandrin reduced the pathological changes and pulmonary edema of lung tissue induced by APEC-O78. • Schizandrin markedly inhibited MPO activity and MDA content in lung tissue. • Schizandrin markedly decreased the production of IL-1β, TNF-α, IL-6, and IL-8 in lung tissue. • The protective effect of schizandrin on APEC-induced lung lesions was related to NF-κB pathways and MAPK pathways. [ABSTRACT FROM AUTHOR]