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Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

In recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object: To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods: We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results: In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions: Quercetin's action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (NPs) are used in a wide range of consumer products and in biomedical applications, resulting in an increased production of these materials with potential for exposure, thus causing human health concerns. Although there are many reports on the size-related toxicity of ZnO NPs, the toxicity of different nanoforms of this chemical, toxicity mechanisms, and potency determinants need clarification to support health risk characterization. A set of well-characterized ZnO nanoforms (e.g., uncoated ca. 30, 45, and 53 nm; coated with silicon oil, stearic acid, and (3-aminopropyl) triethoxysilane) were screened for in vitro cytotoxicity in two cell types, human lung epithelial cells (A549), and mouse monocyte/macrophage (J774) cells. ZnO (bulk) and ZnCl2 served as reference particles. Cytotoxicity was examined 24 h post-exposure by measuring CTB (viability), ATP (energy metabolism), and %LDH released (membrane integrity). Cellular oxidative stress (GSH-GSSG) and secreted proteins (targeted multiplex assay) were analyzed. Zinc oxide nanoform type-, dose-, and cell type-specific cytotoxic responses were seen, along with cellular oxidative stress. Cell-secreted protein profiles suggested ZnO NP exposure-related perturbations in signaling pathways relevant to inflammation/cell injury and corresponding biological processes, namely reactive oxygen species generation and apoptosis/necrosis, for some nanoforms, consistent with cellular oxidative stress and ATP status. The size, surface area, agglomeration state and metal contents of these ZnO nanoforms appeared to be physicochemical determinants of particle potencies. These findings warrant further research on high-content "OMICs" to validate and resolve toxicity pathways related to exposure to nanoforms to advance health risk-assessment efforts and to inform on safer materials. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer. It advances quickly and often metastasizes, making the prognosis for patients challenging. This study used weighted gene co-expression network analysis (WGCNA) to study gene expression data of different stages of ccRCC obtained in the GEO database. The analysis identified three significant highly preserved gene modules across the datasets: GSE53757, GSE22541, GSE66272, and GSE73731. Functional annotation and pathway enrichment analysis using DAVID revealed inflammatory pathways (e.g., NF-kB, Hippo, and HIF-1 pathways) that may drive ccRCC development and progression. The study also introduced the involvement of viral infections associated with the disease in the metabolic reprogramming of ccRCC. A drug repurposing analysis was also conducted to identify potential drug candidates for ccRCC using the upregulated and downregulated hub genes. The top candidates are ziprasidone (dopamine and serotonin receptor antagonist) and fentiazac (cyclooxygenase inhibitor). Other drug candidates were also obtained, such as phosphodiesterase/DNA methyltransferase/ATM kinase inhibitors, acetylcholine antagonists, and NAD precursors. Overall, the study's findings suggest that identifying several genes and signaling pathways related to ccRCC may uncover new targets, biomarkers, and even drugs that can be repurposed, which can help develop new and effective treatments for the disease. [ABSTRACT FROM AUTHOR]

Abstract Background Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions Quercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.

"Metaflammation," proposed by Hotamisligil in 2006, refers to a chronic low-grade inflammation triggered by metabolic factors such as excessive nutrition and energy, persisting at subacute levels over an extended period. Immune cells infiltrate the inflammatory site, leading to enhanced expression or activity of various inflammatory molecules and subsequent inflammatory damage. Recent research on metabolic-related fatty liver disease has revealed that modern metaflammation plays a pivotal role in the pathogenesis of NAFLD. The associated inflammatory pathways offer promising prospects for the development of targeted drugs. This article provides an updated review on the advancements in metaflammation within NAFLD. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Gout poses a significant health threat. The use of Lactobacillus from the gut microbiota is one potential remedy. However, the intricate molecular mechanisms governing the impact of Lactobacillus on gout remain largely uncharted. In this study, a strain of Limosilactobacillus reuteri RE225 was separated from the gut of mice and colitis was treated with polypeptide intervention.Limosilactobacillus reuteri RE225 reduced foot tumefaction markedly in mice with gout and extended the pain threshold time in their feet. It also improved the health of gut microbiota. Intervention with L. reuteri RE225 also suppressed the TLR4/MyD88/NF‐κB and nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) pathways in the mice, reduced the levels of pro‐inflammatory cytokines – interleukin 1β (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) – and increased the level of the anti‐inflammatory cytokine interleukin 10 (IL‐10), thereby mitigating inflammation.This study provides a theoretical basis for the comprehensive development of Limosilactobacillus reuteri and new ideas for the non‐pharmacological treatment of gout. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Periodontal disease, a multifactorial inflammatory condition affecting the supporting structures of the teeth, has been increasingly recognized for its association with various systemic diseases. Understanding the molecular comorbidities of periodontal disease is crucial for elucidating shared pathogenic mechanisms and potential therapeutic targets. In this study, we conducted comprehensive literature and biological database mining by utilizing DisGeNET2R for extracting gene–disease associations, Romin for integrating and modeling molecular interaction networks, and Rentrez R libraries for accessing and retrieving relevant information from NCBI databases. This integrative bioinformatics approach enabled us to systematically identify diseases sharing associated genes, proteins, or molecular pathways with periodontitis. Our analysis revealed significant molecular overlaps between periodontal disease and several systemic conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and inflammatory bowel diseases. Shared molecular mechanisms implicated in the pathogenesis of these diseases and periodontitis encompassed dysregulation of inflammatory mediators, immune response pathways, oxidative stress pathways, and alterations in the extracellular matrix. Furthermore, network analysis unveiled the key hub genes and proteins (such as TNF, IL6, PTGS2, IL10, NOS3, IL1B, VEGFA, BCL2, STAT3, LEP and TP53) that play pivotal roles in the crosstalk between periodontal disease and its comorbidities, offering potential targets for therapeutic intervention. Insights gained from this integrative approach shed light on the intricate interplay between periodontal health and systemic well-being, emphasizing the importance of interdisciplinary collaboration in developing personalized treatment strategies for patients with periodontal disease and associated comorbidities. [ABSTRACT FROM AUTHOR]

Summary This narrative review article explores the complex interplay between obesity, osteoarthritis, and their associated inflammatory cascades, offering a deeper understanding of the underlying of mechanisms of inflammation and potential therapeutic interventions targeting both diseases. Through examination of the shared inflammatory pathway of obesity and osteoarthritis, our objective is to directly elucidate the relationship between these two conditions, highlighting the promising role of glucagon‐like peptide‐1 agonists in modulating inflammation and its therapeutic implications for patients with obesity and osteoarthritis. [ABSTRACT FROM AUTHOR]

Neuroinflammation is increasingly recognized as a pivotal factor not only in neurodegenerative diseases such as Alzheimer's and Parkinson's, but also in the pathogenesis of metabolic disorders that influence or exacerbate these conditions. This review explores the intricate relationships between neuroinflammation, metabolic dysregulation and neurodegenerative diseases. We begin by detailing the fundamental mechanisms of neuroinflammation, focusing on the roles of astrocytes and microglia, and the molecular pathways that contribute to inflammatory processes in the CNS. The discussion then shifts to how metabolic abnormalities such as obesity, insulin resistance and dyslipidemia can initiate or perpetuate neuroinflammatory responses. Furthermore, we examine the evidence linking neuroinflammation to various neurodegenerative diseases, delineating how inflammatory processes can exacerbate neurodegeneration through feedback loops that impair neuronal function and survival. We also review clinical and preclinical studies that provide insights into the bi-directional interactions between neurodegeneration and metabolic health. This includes a critical evaluation of current therapeutic strategies targeting neuroinflammation, ranging from conventional anti-inflammatory treatments to innovative approaches aimed at modulating metabolic factors. Lastly, the review identifies promising therapeutic avenues, challenges in current treatment paradigms, and the potential for integrative interventions that address both metabolic and inflammatory components. Our goal is to emphasize the need for comprehensive strategies that consider the complexity of these intertwined systems in the treatment of neurodegenerative and metabolic diseases. [ABSTRACT FROM AUTHOR]

Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients.  Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.

Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact. [ABSTRACT FROM AUTHOR]

Cheonggukjang (CGJ) is a traditional food, made by the fermentation of beans, and it has different recipes for different regions in Korea. However, it has anti-inflammatory, anti-cancer, and anti-obesity effects, and is known to affect changes in the intestinal microbiota. In this study, we investigated the immune-enhancing effects of four type CGJs (one commercial and three transitional CGJs). In the cyclophosphamide (CP)-treated immunosuppressed rat, oral administration of CGJs for 4 weeks was used to investigate weight of body and immune organ, change of microbiota, blood and serum parameters, inflammation pathways (MAPKs and NFκB) and histology of spleen. It showed an immunity-enhancing effect through increase Bacteroidetes in gut, the recovery of complete blood count, levels of cytokines and IgG, activation of inflammatory pathways, and histology of spleen. In conclusion, these results show that the intake of a commercial brand CGJ, and traditional CGJs can maintain or promote the body's immunity.

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, manifest as a result of intricate interactions involving genetic predisposition, environmental factors, intestinal microbiota dynamics, and immune dysregulation, ultimately leading to persistent mucosal inflammation. Addressing this complex pathology requires a nuanced understanding to inform targeted therapeutic strategies. Consequently, our study explored the viability of Aged Garlic Extract (AGE) as an alternative therapeutic regimen for IBD management. Utilizing gas chromatography-mass spectrometry (GC-MS) and scanning electron microscopy (SEM), we characterized AGE, revealing distinctions from Fresh Garlic Extract (FGE), particularly the absence of allicin in AGE and accompanying structural alterations. In In-Vivo experiments employing an IBD rat model, AGE intervention exhibited remarkable antioxidant, antibacterial, and anti-inflammatory properties. Noteworthy outcomes included improved survival rates, mitigation of intestinal damage, restoration of gut microbial diversity, reinforcement of tight junctions, and reversal of mitochondrial dysfunction. Collectively, these effects contributed to the preservation of enterocyte integrity and the attenuation of inflammation. In conclusion, the unique chemical composition of AGE, coupled with its substantial influence on gut microbiota, antioxidant defenses, and inflammatory pathways, positions it as a promising adjunctive therapy for the management of IBD. These observations, synergistically considered with existing research, provide significant insights into the potential utility of AGE in addressing the intricate pathophysiology inherent to IBD. The potential strength of study and rationale of using AGE against IBD includes exploring alternative therapeutic regimens if conventional treatments are associated with side effects, identification of potential hotspots/pathways involved in disease progression and study can provide economically cheaper and naturally occurring alternative to patient community who are struggling to afford expensive medications. These promising findings underscore the necessity for additional investigations to ascertain the feasibility of clinical translation, thereby substantiating the potential therapeutic role of AGE in the management of IBD.

Phytochemicals are compounds found in plants that possess a variety of bioactive properties, including antioxidant and immunomodulatory properties. Recent studies have highlighted the potential of phytochemicals in targeting specific signalling pathways involved in cytokine storm, a life-threatening clinical condition resulting from excessive immune cell activation and oversupply of proinflammatory cytokines. Several studies have documented the immunomodulatory effects of phytochemicals on immune function, including their ability to regulate essential cellular and molecular interactions of immune system cells. This makes them a promising alternative for cytokine storm management, especially when combined with existing chemotherapies. Furthermore, phytochemicals have been found to target multiple signalling pathways, including the TNF-α/NF-κB, IL-1/NF-κB, IFN-γ/JAK/STAT, and IL-6/JAK-STAT. These pathways play critical roles in the development and progression of cytokine storm, and targeting them with phytochemicals represents a promising strategy for controlling cytokine release and the subsequent inflammation. Studies have also investigated certain families of plant-related constituents and their potential immunomodulatory actions. In vivo and in vitro studies have reported the immunomodulatory effects of phytochemicals, which provide viable alternatives in the management of cytokine storm syndrome. The collective data from previous studies suggest that phytochemicals represent a potentially functional source of cytokine storm treatment and promote further exploration of these compounds as immunomodulatory agents for suppressing specific signalling cascade responses. Overall, the previous research findings support the use of phytochemicals as a complementary approach in managing cytokine storm and improving patient outcomes.

Zinc oxide nanoparticles (NPs) are used in a wide range of consumer products and in biomedical applications, resulting in an increased production of these materials with potential for exposure, thus causing human health concerns. Although there are many reports on the size-related toxicity of ZnO NPs, the toxicity of different nanoforms of this chemical, toxicity mechanisms, and potency determinants need clarification to support health risk characterization. A set of well-characterized ZnO nanoforms (e.g., uncoated ca. 30, 45, and 53 nm; coated with silicon oil, stearic acid, and (3-aminopropyl) triethoxysilane) were screened for in vitro cytotoxicity in two cell types, human lung epithelial cells (A549), and mouse monocyte/macrophage (J774) cells. ZnO (bulk) and ZnCl2 served as reference particles. Cytotoxicity was examined 24 h post-exposure by measuring CTB (viability), ATP (energy metabolism), and %LDH released (membrane integrity). Cellular oxidative stress (GSH-GSSG) and secreted proteins (targeted multiplex assay) were analyzed. Zinc oxide nanoform type-, dose-, and cell type-specific cytotoxic responses were seen, along with cellular oxidative stress. Cell-secreted protein profiles suggested ZnO NP exposure-related perturbations in signaling pathways relevant to inflammation/cell injury and corresponding biological processes, namely reactive oxygen species generation and apoptosis/necrosis, for some nanoforms, consistent with cellular oxidative stress and ATP status. The size, surface area, agglomeration state and metal contents of these ZnO nanoforms appeared to be physicochemical determinants of particle potencies. These findings warrant further research on high-content “OMICs” to validate and resolve toxicity pathways related to exposure to nanoforms to advance health risk-assessment efforts and to inform on safer materials.

Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including delusions, hallucinations, disorganized speech and behavior, and cognitive impairment. Recent research has suggested that the immune system dysregulation may play a significant role in the pathogenesis of schizophrenia, and glial cells, such as astroglia and microglia known to be involved in neuroinflammation and immune regulation, have emerged as potential players in this process. The aim of this systematic review is to summarize the glial hallmarks of schizophrenia, choosing as cellular candidate the astroglia and microglia, and focusing also on disease-associated psychological (cognitive and emotional) changes. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Scopus, and Web of Science for articles that investigated the differences in astroglia and microglia in patients with schizophrenia, published in the last 5 years. The present systematic review indicates that changes in the density, morphology, and functioning of astroglia and microglia may be involved in the development of schizophrenia. The glial alterations may contribute to the pathogenesis of schizophrenia by dysregulating neurotransmission and immune responses, worsening cognitive capabilities. The complex interplay of astroglial and microglial activation, genetic/epigenetic variations, and cognitive assessments underscores the intricate relationship between biological mechanisms, symptomatology, and cognitive functioning in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Ischemia/reperfusion injury (IRI) is generally unavoidable following liver transplantation. Here, we investigated the role of protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G) in hepatic IRI. Methods: Hepatic IRI was mimicked by employing a hypoxia/reperfusion (H/R) model in RAW 264.7 cells and a 70% warm ischemia model in C57BL/6 mice, respectively. In vitro, expression changes of tumor necrosis factor-α and interleukin were detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The protein expressions of PPM1G and the stimulator of interferon genes (STING) pathway components were analyzed by western blot. Interaction between PPM1G and STING was verified by coimmunoprecipitation (CO-IP). Immunofluorescence was applied for detection of p-IRF3. Flow cytometry, qRT-PCR and western blot were utilized to analyze markers of macrophage polarization. In vivo, histological analyses of mice liver were carried out by TUNEL and H&E staining. Changes in serum aminotransferases were also detected. Results: Following H/R intervention, a steady decline in PPM1G along with an increase in inflammatory cytokines in vitro was observed. Addition of plasmid with PPM1G sequence limited the release of inflammatory cytokines and downregulated phosphorylation of STING. CO-IP validated the interaction between PPM1G and STING. Furthermore, inhibition of PPM1G with lentivirus enhanced phosphorylation of STING and its downstream components; meanwhile, p65, p38, and Jnk were also surged to phosphorylation. Expression of INOS and CD86 was surged, while CD206, Arg-1, and IL-10 were inhibited. In vivo, PPM1G inhibition further promoted liver damage, hepatocyte apoptosis, and transaminases release. Selective inhibition of STING with C-176 partially reversed the activation of STING pathway and inflammatory cytokines in vitro. M1 markers were also suppressed by C-176. In vivo, C-176 rescued liver damage and transaminase release caused by PPM1G inhibition. Conclusion: PPM1G suppresses hepatic IRI and macrophage M1 phenotype by repressing STING-mediated inflammatory pathways. [ABSTRACT FROM AUTHOR]

Phytochemicals are compounds found in plants that possess a variety of bioactive properties, including antioxidant and immunomodulatory properties. Recent studies have highlighted the potential of phytochemicals in targeting specific signalling pathways involved in cytokine storm, a life-threatening clinical condition resulting from excessive immune cell activation and oversupply of proinflammatory cytokines. Several studies have documented the immunomodulatory effects of phytochemicals on immune function, including their ability to regulate essential cellular and molecular interactions of immune system cells. This makes them a promising alternative for cytokine storm management, especially when combined with existing chemotherapies. Furthermore, phytochemicals have been found to target multiple signalling pathways, including the TNF-α/NF-κB, IL-1/NF-κB, IFN-γ/JAK/STAT, and IL-6/JAK-STAT. These pathways play critical roles in the development and progression of cytokine storm, and targeting them with phytochemicals represents a promising strategy for controlling cytokine release and the subsequent inflammation. Studies have also investigated certain families of plant-related constituents and their potential immunomodulatory actions. In vivo and in vitro studies have reported the immunomodulatory effects of phytochemicals, which provide viable alternatives in the management of cytokine storm syndrome. The collective data from previous studies suggest that phytochemicals represent a potentially functional source of cytokine storm treatment and promote further exploration of these compounds as immunomodulatory agents for suppressing specific signalling cascade responses. Overall, the previous research findings support the use of phytochemicals as a complementary approach in managing cytokine storm and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect them. As carriers of nucleic acids, proteins, lipids, metabolites, and virulence factors, EVs act as delivery vehicles for intercellular communication and quorum sensing. Innate immune cells have the capacity to intercept, internalize, and interpret ‘messages’ contained within these EVs. This review categorizes the ability of EVs secreted by bacterial, parasitic, and fungal pathogens to trigger both pro- and anti-inflammatory innate immune responses in the host. Understanding molecular pathways and inflammatory responses activated in innate immune cells upon pathogen-derived EV stimulation is critical to gain insight into potential therapeutics and combat these infectious diseases.

Chronic inflammation is a hallmark of obesity and is recognized as a cancer risk. While EPA and DHA combat inflammation associated with obesity, their effects on obesity-linked intestinal tumors requires further study. This study used the azoxymethane/dextran sulfate sodium (AOM/DSS) model in mice made obese by a high-fat diet to assess the effects of EPA and DHA on tumorigenesis. The results showed that obesity aggravates colon tumor development in mice, yet both EPA and DHA significantly suppressed tumor formation in the obese murine colon. EPA and DHA altered the intestinal epithelium's fatty acid profile, enhancing its anti-inflammatory properties. Both treatments led to a decrease in the pro-inflammatory Desulfovibrio, while EPA specifically increased probiotic Parasutterella and decreased mucus- destroying Bacteroides. In conclusion, EPA and DHA have inhibitory effects on colon tumor formation in obese mice, primarily by modulating the gut flora and inhibiting inflammation in the colon.

Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact.

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer. It advances quickly and often metastasizes, making the prognosis for patients challenging. This study used weighted gene co-expression network analysis (WGCNA) to study gene expression data of different stages of ccRCC obtained in the GEO database. The analysis identified three significant highly preserved gene modules across the datasets: GSE53757, GSE22541, GSE66272, and GSE73731. Functional annotation and pathway enrichment analysis using DAVID revealed inflammatory pathways (e.g., NF-kB, Hippo, and HIF-1 pathways) that may drive ccRCC development and progression. The study also introduced the involvement of viral infections associated with the disease in the metabolic reprogramming of ccRCC. A drug repurposing analysis was also conducted to identify potential drug candidates for ccRCC using the upregulated and downregulated hub genes. The top candidates are ziprasidone (dopamine and serotonin receptor antagonist) and fentiazac (cyclooxygenase inhibitor). Other drug candidates were also obtained, such as phosphodiesterase/DNA methyltransferase/ATM kinase inhibitors, acetylcholine antagonists, and NAD precursors. Overall, the study’s findings suggest that identifying several genes and signaling pathways related to ccRCC may uncover new targets, biomarkers, and even drugs that can be repurposed, which can help develop new and effective treatments for the disease.

Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including delusions, hallucinations, disorganized speech and behavior, and cognitive impairment. Recent research has suggested that the immune system dysregulation may play a significant role in the pathogenesis of schizophrenia, and glial cells, such as astroglia and microglia known to be involved in neuroinflammation and immune regulation, have emerged as potential players in this process. The aim of this systematic review is to summarize the glial hallmarks of schizophrenia, choosing as cellular candidate the astroglia and microglia, and focusing also on disease-associated psychological (cognitive and emotional) changes. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Scopus, and Web of Science for articles that investigated the differences in astroglia and microglia in patients with schizophrenia, published in the last 5 years. The present systematic review indicates that changes in the density, morphology, and functioning of astroglia and microglia may be involved in the development of schizophrenia. The glial alterations may contribute to the pathogenesis of schizophrenia by dysregulating neurotransmission and immune responses, worsening cognitive capabilities. The complex interplay of astroglial and microglial activation, genetic/epigenetic variations, and cognitive assessments underscores the intricate relationship between biological mechanisms, symptomatology, and cognitive functioning in schizophrenia.

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Different from inflammatory arthritis, where biologicals and targeted synthetic molecules have revolutionized the disease course, no drug has demonstrated a disease modifying activity in osteoarthritis, which remains one of the most common causes of disability and chronic pain worldwide. The pharmacological therapy of osteoarthritis is mainly directed towards symptom and pain relief, and joint replacement is still the only curative strategy. Elucidating the disease pathophysiology is essential to understand which mechanisms can be targeted by innovative therapies. It has extensively been demonstrated that aberrant WNT and IL-1 signaling pathways are responsible for cartilage degeneration, impaired chondrocyte metabolism and differentiation, increased extracellular matrix degradation, and altered subchondral bone homeostasis. Platelet-rich plasma is an autologous blood derivative containing a concentration of platelets that is much higher than the whole blood counterpart and has shown promising results in the treatment of early knee osteoarthritis. Among the proposed mechanisms, the modulation of WNT and IL-1 pathways is of paramount importance and is herein reviewed in light of the proposed regenerative approaches. [ABSTRACT FROM AUTHOR]

Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one's eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs; 3 and 6 PUFAs) are essential for human health because they serve as metabolic precursors of eicosanoids, a class of signaling molecules that are essential for controlling a body's inflammation. Since humans are unable to produce any of the omega-3 or omega-6 PUFAs, they both constitute imperative nutritional ingredients. Long-standing concerns about long-chain omega-3 fatty acids' impact on diabetes management have been supported by experimental investigations that found significant increases in fasting glucose following omega-3 fatty acid supplementation and foods rich in PUFA and omega-3 fatty acid. Cellular explanations to explain the connection between inflammation and IR include mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and oxidative stress. Modifications in the lipid composition of mitochondrial membranes and/or receptor-mediated signaling may be part of the mechanism behind the activation of mitochondrial fusion by fish oil/omega-3 PUFA. The exact molecular processes by which omega-3 PUFAs control mitochondrial activity to defend against IR are still unknown. [ABSTRACT FROM AUTHOR]

The body's normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases. [ABSTRACT FROM AUTHOR]

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis. Methods: The effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-kB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gutmicrobiota inmouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora. Results: The results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-kB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity. Discussion: This study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future. [ABSTRACT FROM AUTHOR]

Seizure is paroxysmal abnormal electrical discharges in the cerebral cortex. Inflammatory pathways and oxidative stress are involved in the pathophysiology of seizures. Stress can induce an oxidative stress state and increase the production of inflammatory mediators in the brain. We investigated the effects of acute and chronic stresses on the seizure threshold in pentylenetetrazol (PTZ)-induced seizures in mice, considering oxidative stress and inflammatory mediators in the prefrontal cortex. In this study, 30 male Naval Medical Research Institute (NMRI) mice were divided into 3 groups, including acute stress, chronic stress, and control groups. PTZ was used for the induction of seizures. The gene expression of inflammatory markers (IL-1β, TNF-α, NLRP3, and iNOS), malondialdehyde (MDA) level, nitrite level, and total antioxidant capacity (TAC) were assessed in the prefrontal cortex and serum. Our results showed that stress could increase the expression of inflammatory cytokines genes and oxidative stress in the prefrontal cortex of the brain and serum following PTZ-induced seizures, which is associated with increased seizure sensitivity and decreased the seizure threshold. The effects of chronic stress were much more significant than acute stress. We concluded that the effects of chronic stress on seizure sensitivity and enhancement of neuroinflammation and oxidative stress are much greater than acute stress. [ABSTRACT FROM AUTHOR]

The triggers and pathogenesis of axial spondyloarthritis (axSpA) are not yet completely understood. However, therapeutic agents targeting tumor necrosis factor-α and interleukin-17 inflammatory pathways have proven successful in suppressing many of the clinical symptoms and signs of axSpA, giving us an indication of which pathways are responsible for initiating and maintaining the inflammation. The mechanisms that eventuate in syndesmophytes and ankyloses are less clear. This review addresses these two critical pathways of inflammation, discussing their nature and these factors that may activate or enhance the pathways in patients with axSpA. In addition, genetic and other markers important to the inflammatory pathways implicated in axSpA are explored, and prognostic biomarkers are discussed. Treatment options available for the management of axSpA and their associated targets are highlighted.

Different from inflammatory arthritis, where biologicals and targeted synthetic molecules have revolutionized the disease course, no drug has demonstrated a disease modifying activity in osteoarthritis, which remains one of the most common causes of disability and chronic pain worldwide. The pharmacological therapy of osteoarthritis is mainly directed towards symptom and pain relief, and joint replacement is still the only curative strategy. Elucidating the disease pathophysiology is essential to understand which mechanisms can be targeted by innovative therapies. It has extensively been demonstrated that aberrant WNT and IL-1 signaling pathways are responsible for cartilage degeneration, impaired chondrocyte metabolism and differentiation, increased extracellular matrix degradation, and altered subchondral bone homeostasis. Platelet-rich plasma is an autologous blood derivative containing a concentration of platelets that is much higher than the whole blood counterpart and has shown promising results in the treatment of early knee osteoarthritis. Among the proposed mechanisms, the modulation of WNT and IL-1 pathways is of paramount importance and is herein reviewed in light of the proposed regenerative approaches.

Cancer and inflammation interlink with many pathways. Millions of people died because of these two disorders. Major pathways that cause both inflammation and cancer are STAT3, NF‐κB, COX, and histone acetylation. However, these are the target for medicinally potent heterocycles such as pyrimidines, indole, and pyrazole. Many NSAIDs reported in the literature belong to both natural and synthetic molecules. This review encompasses molecular mechanisms for inflammation, NSAIDs derived from natural sources and synthetic methods, and recent reports on heterocycles as potent anti‐inflammatory agents and their significance in cancer treatment. Literature for the study, accomplished from 2019 to 2022. [ABSTRACT FROM AUTHOR]

Problem: Diagnosis of female genital tuberculosis (FGTB) remains elusive due to the paucibacillary nature of the disease. We evaluated if analysis of inflammatory pathways of endometrial tissue could establish a better diagnosis of FGTB. Method of Study: One hundred and four infertile women suspected of having GTB or having been treated for GTB in the past, underwent endometrial biopsies for diagnosis and Gene Inflammatory Pathways analysis at our center between 2018–2020. Diagnosis of FGTB was based on acid‐fast bacilli culture, immunocytochemistry, nested‐polymerase chain reaction, histopathological examination, TB GeneXpert, or combinations thereof. Gene expression profiles were also analyzed. Results: Based on diagnostic tests of 104 women, 44 (42%) were considered TB‐positive, 35 (34%) TB‐negative, and 25 (24%) TB‐negative after TB treatment in the past. Inflammatory pathways were significantly upregulated in TB‐positive women versus TB‐negative (41% vs. 6%; p =.0005), and in women who were TB‐negative after TB treatment in the past versus TB‐negative (never treated for TB in the past) (38% vs. 6%; p =.0037). Two‐hundred seventy‐one genes were upregulated, and 61 genes were downregulated in TB‐positive women versus those who were TB‐negative. Differentially expressed genes were mapped to various interlinked inflammatory signaling pathways, including mitogen‐activated protein kinase (MAPK), Natural Killer (NK) cells, nuclear factor kappa‐B (NF‐kB), tumor necrosis factor (TNF), and Toll‐like receptors (TLR) signaling. Conclusions: Inflammatory pathways and gene expression profiles add to the diagnostic tools to identify TB‐positive women at an early stage. The results from this study are still experimental and large multi‐centric studies are suggested before their recommendation in routine clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exosomes derived from mesenchymal stem cells can inhibit neuroinflammation and some damage after intracerebral hemorrhage. There are few studies on the mechanism of neuroprotective effect of exosomes derived from mesenchymal stem cells on hippocampal neurons after intracerebral hemorrhage through heme oxygenase-1. OBJECTIVE: To explore the protection and mechanism of exosomes derived from umbilical cord mesenchymal stem cells on hippocampal neurons after intracerebral hemorrhage. METHODS: (1) A mouse model of intracerebral hemorrhage was established using autologous blood infusion, and then exosomes derived from umbilical cord mesenchymal stem cells were injected into the tail vein at 8 hours after intracerebral hemorrhage. Western blot assay was used to verify the expression of heme oxygenase 1, high mobility group box B1 and Toll-like receptor 4 at 24 hours, 4 and 30 days after intracerebral hemorrhage. (2) In vitro, the mouse hippocampal neuron cell (HT22 cell) intracerebral hemorrhage model was established by hemin stimulation, and cells were pretreated with exosomes derived from umbilical cord mesenchymal stem cells for 12 hours before modeling, and then the HT22 cells were stimulated by hemin for 6 hours. Heme oxygenase 1 expression was detected by western blot assay. (3) HT22 cells were transfected with lentivirus to reduce the expression of heme oxygenase 1, and then pretreated with exosomes derived from umbilical cord mesenchymal stem cells for 12 hours, stimulated with hemin for 6 hours. The expression of heme oxygenase 1 was detected by western blot assay. RESULTS AND CONCLUSION: (1) At 24 hours, 4 and 30 days after intracerebral hemorrhage, the expression of heme oxygenase 1 in the hippocampus on the injured side was significantly increased (all P < 0.05). Compared with the sham-operated group, the protein expression levels of heme oxygenase 1, high mobility group box B1 and Toll-like receptor 4 were significantly increased in the mice of the cerebral hemorrhage group on day 4 after cerebral hemorrhage (all P < 0.05). Compared with the intracerebral hemorrhage group, the protein expression levels of heme oxygenase 1, high mobility group box B1 and Tolllike receptor 4 in the intracerebral hemorrhage + exosome group were significantly decreased (all P < 0.05). (2) In the in vitro cerebral hemorrhage model, compared with the control group, the expression of heme oxygenase 1 protein in HT22 cells was significantly increased in the hemin+PBS group. Compared with the hemin+PBS group, the heme oxygenase 1 protein expression was significantly decreased in HT22 cells in the hemin+exosome group (all P < 0.05). (3) After lentiviral transfection of HT22 cells to knock down the expression of heme oxygenase 1, there was no significant difference in the protein expression of heme oxygenase 1 between the knockdown heme oxygenase 1+hemin+PBS group and the knockdown heme oxygenase 1+hemin+exosome group. (4) The results showed that exosomes derived from umbilical cord mesenchymal stem cells had a neuroprotective effect on injured hippocampal neurons after intracerebral hemorrhage. The mechanism may be related to the regulation of high mobility group box B1 and Toll-like receptor 4-related inflammatory pathways through heme oxygenase 1. [ABSTRACT FROM AUTHOR]

The intervention effects of delivery systems on the digestion and adsorption profiles and, thus, the pharmacological effects of bioactive compounds represent an intriguing scientific hypothesis that can be proven with research case studies. Delivery systems with tailor-made structures fabricating from the same building materials offer a new research strategy for deciphering the modulating effects of the digestive fate on the therapeutic efficacy of encapsulated bioactive compounds. Herein, we developed capsaicin-loaded core-shell nanoparticles (Cap NPs), microparticles (Cap MPs) and nano-in-micro particles (Cap NPs in MPs) and investigated their regulatory effects on the digestive fate and colitis-alleviating mechanisms of capsaicin. Results suggested that the small intestine dominant absorption of Cap NPs differed significantly with the colorectal dominated accumulation of Cap MPs and Cap NPs in MPs in terms of the colitis alleviating mechanisms. Cap NPs alleviated colitis mainly through promoting the colonization of short-chain fatty acid-producing bacteria, maintaining intestinal barrier homeostasis and partially inhibiting the activation of the NF-κB pro-inflammatory pathway. Whereas, better dietary intervention effects were achieved from Cap NPs in MPs via promoting the proliferation of mucus-related bacteria and enhanced triggering efficiency on the TRPV1-mucus-microbiotas cyclic cascade. This work confirmed that rationally designed biomaterial-based delivery vehicles can flexibly interfere with the therapeutic mechanisms of encapsulated cargos, representing a new horizon in the field of precise nutrition. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010–2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions. [ABSTRACT FROM AUTHOR]

In recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma.

To date, various derivatives of thiazolidinone in a variety of cell lines have been investigated. The present study aimed to evaluate the toxicity and inhibitory effects of a thiazolidinone derivative called 5-(2,4-bis-4-ethoxy-phenyl azo)-3-hydroxy-benzylidine)-2,4-thiazolidinone (TZD-OCH2CH3) on the expression of NF-кB in LPS-induced RAW264.7 macrophage cell lines. Different concentrations of the MTT assay(0-120 μg/mL) were performed to estimate the biological rate of the cells. The half-maximal inhibitory concentration (IC50) of TZD-OCH2CH3-treated RAW264.7 cells was found to be 115 μg/mL. To determine the inhibitory effect of the synthesized compound on the expression changes of NF-кB, the RAW264.7cells were initially induced with LPS and then treated by 15, 30 and 60 μg/mL of TZD-OCH2CH3. Realtime PCR results confirmed a strong inhibitory effect of TZD-OCH2CH3 on the expression of NF-кB inLPS-induced RAW264.7 cells (IC50 = 48 μg/mL). Overall, these findings suggested that the derivative TZDOCH2CH3 had a significant anti-inflammatory effect.

BackgroundTranscriptome-wide analysis of peripheral blood in post-traumatic stress disorder (PTSD) indicates widespread changes in immune-related pathways and function. Ferroptosis, an iron-dependent regulated cell death, is closely related to oxidative stress. However, little is known as to whether ferroptosis plays a role in PTSD.MethodsWe conducted a comprehensive analysis of combined data from six independent peripheral blood transcriptional studies in the Gene Expression Omnibus (GEO) database, covering PTSD and control individuals. Differentially expressed genes (DEGs) were extracted by comparing PTSD patients with control individuals, from which 29 ferroptosis-related genes (FRGs) were cross-matched and obtained. The weighted gene co-expression network analysis (WGCNA), the Extreme Gradient Boosting (XGBoost) model with Bayesian Optimization, and the least absolute shrinkage and selection operator (LASSO) Cox regression were utilized to construct a PTSD prediction model. Single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT revealed the disturbed immunologic state in PTSD high-risk patients.ResultsThree crucial FRGs (ACSL4, ACO1, and GSS) were identified and used to establish a predictive model of PTSD. The receiver operating characteristic (ROC) curve verifies its risk prediction ability. Remarkably, ssGSEA and CIBERSORT demonstrated changes in cellular immunity and antigen presentation depending on the FRGs model.ConclusionThese findings collectively provide evidence that ferroptosis may change immune status in PTSD and be related to the occurrence of PTSD, which may help delineate mechanisms and discover treatment biomarkers for PTSD.

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs.

The 2019 coronavirus disease (COVID‐19) pandemic has become a global crisis. In the immunopathogenesis of COVID‐19, SARS‐CoV‐2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID‐19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS‐CoV‐2 is important in providing otential therapeutic targets and treatment strategies against COVID‐19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID‐19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID‐19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID‐19. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is an autoimmune disease characterized by chronic symmetric synovial inflammation and erosive bone destruction. Mitochondria are the main site of cellular energy supply and play a key role in the process of energy metabolism. They possess certain self-regulatory and repair capabilities. Mitochondria maintain relative stability in number, morphology, and spatial structure through biological processes, such as biogenesis, fission, fusion, and autophagy, which are collectively called mitochondrial homeostasis. An imbalance in the mitochondrial homeostatic environment will affect immune cell energy metabolism, synovial cell proliferation, apoptosis, and inflammatory signaling. These biological processes are involved in the onset and development of rheumatoid arthritis. In this review, we found that in rheumatoid arthritis, abnormal mitochondrial homeostasis can mediate various immune cell metabolic disorders, and the reprogramming of immune cell metabolism is closely related to their inflammatory activation. In turn, mitochondrial damage and homeostatic imbalance can lead to mtDNA leakage and increased mtROS production. mtDNA and mtROS are active substances mediating multiple inflammatory pathways. Several rheumatoid arthritis therapeutic agents regulate mitochondrial homeostasis and repair mitochondrial damage. Therefore, modulation of mitochondrial homeostasis would be one of the most attractive targets for the treatment of rheumatoid arthritis.

Abstract The 2019 coronavirus disease (COVID‐19) pandemic has become a global crisis. In the immunopathogenesis of COVID‐19, SARS‐CoV‐2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID‐19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS‐CoV‐2 is important in providing otential therapeutic targets and treatment strategies against COVID‐19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID‐19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID‐19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID‐19.

The body’s normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases.