Inflammation最新文献

Cancer detection is challenging, especially in patients with unspecific cancer symptoms. Biomarkers could identify patients at high risk of cancer. Prior studies indicate that neutrophil extracellular traps (NETs) are associated with cancer, but also with autoimmune and infectious diseases. The objective of this prospective study was to investigate markers associated with NET formation (nucleosomal citrullinated histone 3 [H3Cit-DNA], cell free DNA [cfDNA] and neutrophil elastase [NE]), and c-reactive protein (CRP) in patients with unspecific cancer symptoms, such as fatigue, weight loss or radiological sign of malignancy without an apparent primary tumor, referred to the Diagnostic Center at Danderyd Hospital in Sweden. Blood samples were drawn on admission, before cancer diagnosis. Out of 475 patients, 160 (34%) were diagnosed with cancer, 56 (12%) with autoimmune disease, 32 (7%) with infectious disease, 71 (15%) with other diseases and 156 (33%) received no diagnosis. H3Cit-DNA, cfDNA, NE and CRP were significantly higher in patients with cancer compared to patients without cancer (p < 0.0001, p < 0.0001, p = 0.004, and p = 0.0002 respectively). H3Cit-DNA, but not cfDNA, NE or CRP, was significantly elevated in patients with cancer compared to patients with autoimmune disease (p = 0.0001). H3Cit-DNA, cfDNA, NE or CRP did not differ between cancer and infectious disease. In conclusion, H3Cit-DNA is elevated in patients diagnosed with cancer compared to non-cancer patients with the same symptomatology. Further studies should evaluate if H3Cit-DNA could aid in selecting patients that would benefit the most from a rapid cancer diagnostic work-up.

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1β, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

Autoimmune diseases (AIDs) are immune system disorders where the body exhibits an immune response to its own antigens, causing damage to its own tissues and organs. The pathogenesis of AIDs is incompletely understood. However, recent advances in immune repertoire sequencing (IR-seq) technology have opened-up a new avenue to study the IR. These studies have revealed the prevalence in IR alterations, potentially inducing AIDs by disrupting immune tolerance and thereby contributing to our comprehension of AIDs. IR-seq harbors significant potential for the clinical diagnosis, personalized treatment, and prognosis of AIDs. This article reviews the application and progress of IR-seq in diseases, such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes, to enhance our understanding of the pathogenesis of AIDs and offer valuable references for the diagnosis and treatment of AIDs.

Abstract-This study explored the role of the non-canonical STING-PERK signaling pathway in sepsis-associated acute kidney injury (SA-AKI). Gene expression data from the GEO database and serum STING protein levels in patients with SA-AKI were analyzed. An LPS-induced mouse model and an in vitro model using HK-2 cells were used to investigate the role of STING in SA-AKI. STING expression was suppressed using shRNA silencing technology and the STING inhibitor C176. Kidney function, inflammatory markers, apoptosis, and senescence were measured. The role of the STING-PERK pathway was investigated by silencing PERK in HK-2 cells and administering the PERK inhibitor GSK2606414. STING mRNA expression and serum STING protein levels were significantly higher in patients with SA-AKI. Suppressing STING expression improved kidney function, reduced inflammation, and inhibited apoptosis and senescence. Silencing PERK or administering GSK2606414 suppressed the inflammatory response, cell apoptosis, and senescence, suggesting that PERK is a downstream effector in the STING signaling pathway. The STING-PERK signaling pathway exacerbates cell senescence and apoptosis in SA-AKI. Inhibiting this pathway could provide potential therapeutic targets for SA-AKI treatment.

It has recently become more recognized that renal diseases in adults can originate from adverse intrauterine (maternal) environmental exposures. Previously, we found that prenatal lipopolysaccharide (LPS) exposure can result in chronic renal inflammation, which leads to renal damage in older offspring rats. To test whether prenatal inflammatory exposure predisposes offspring to renal damage, a mouse model of oral adenine consumption-induced chronic kidney disease (CKD) was applied to offspring from prenatal LPS-treated mothers (offspring-pLPS) and age-matched control offspring of prenatal saline-treated mothers (offspring-pSaline). We found that offspring-pLPS mice presented with more severe renal collagen deposition and renal dysfunction after 4 weeks of adenine consumption than sex- and treatment-matched offspring-pSaline controls. To illustrate the underlying molecular mechanism, we subjected offspring-pLPS and offspring-pSaline kidneys to genome-wide transcriptomic analysis. Bioinformatic analysis of the sequencing data, together with further experimental confirmation, revealed a strong activation of the PERK-eIF2α-ATF4-mediated unfolded protein response (UPR) in offspring-pLPS kidneys, which likely contributed to the CKD predisposition seen in offspring-pLPS mice. More importantly, the specific eIF2α-ATF4 signaling inhibitor ISIRB was able to prevent adenine-induced CKD in the offspring-pLPS mice. Our findings suggest that the eIF2α-ATF4-mediated UPR, but not PERK, is likely the major disease-causing pathway in prenatal inflammatory exposure-induced CKD predisposition. Our study also suggests that targeting this signaling pathway is a potentially promising approach for CKD treatment.

Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1β (IL-1β), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1β/IL-18 signaling cascade.

Autoimmune diseases are typically characterized by aberrant activation of immune system that leads to excessive inflammatory reactions and tissue damage. Nevertheless, precise targeted and efficient therapies are limited. Thus, studies into novel therapeutic targets for the management of autoimmune diseases are urgently needed. Radical S-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG) renowned for the antiviral properties of the protein it encodes, named viperin. An increasing number of studies have underscored the new roles of RSAD2/viperin in immunomodulation and mitochondrial metabolism. Previous studies have shown that there is a complex interplay between RSAD2/vipeirn and mitochondria and that binding of the iron-sulfur (Fe-S) cluster is necessary for the involvement of viperin in mitochondrial metabolism. Viperin influences the proliferation and development of immune cells as well as inflammation via different signaling pathways. However, the function of RSAD2/viperin varies in different studies and a comprehensive overview of this emerging theme is lacking. This review will describe the characteristics of RSAD2/viperin, decipher its function in immunometabolic processes, and clarify the crosstalk between RSAD2/viperin and mitochondria. Furthermore, we emphasize the crucial roles of RSAD2 in autoimmune diseases and its potential application value.

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.

Multiple sclerosis (MS) is a neurodegenerative condition that results in axonal and permanent damage to the central nervous system, necessitating healing owing to autoimmune reactions and persistent neuroinflammation. Antioxidant and anti-inflammatory drugs are essential for the management of oxidative stress and neuroinflammation. Additionally, multivitamin supplementation, particularly vitamin B12 (cobalamin), may be beneficial for neuronal protection. Although there is no documented connection between vitamin B12 deficiency and MS, researchers have explored its potential as a metabolic cause. This review highlights the therapeutic benefits of cobalamin (Cbl) in patients with MS.

Deciphering the complex and redundant process of acute inflammation remains challenging. The failure of numerous clinical trials assessing anti-inflammation agents which had promising preclinical effects inevitably questions the validity of current animal models of inflammation. This study aimed to better understand the process of immune inflammatory response and to select more suitable models to evaluate the effect of potential anti-inflammatory drugs. Zymosan and λ-carrageenan are the most used representatives of particulate and soluble irritants that trigger acute inflammation in the air pouch inflammation model. When zymosan was used, the number of exudate cells first increased at 4 h-8 h, followed by a drop at 12 h-24 h. While, the changes in number of leukocytes in peripheral blood and proportion of neutrophils in bone marrow have the opposite trend. Meanwhile, neutrophils released neutrophil extracellular traps (NETs) to clean zymosan particles. In contrast, the cell migration response to carrageenan increased during 4 h to 24 h, no obvious NETs were observed, and the number of leukocytes in peripheral blood increased and the proportion of neutrophils in bone marrow decreased slightly. This study indicated that although both zymosan and carrageenan are sterile irritants, the characteristics of the inflammatory response induced by each other were different. In the acute phase of inflammation, zymosan-stimulated neutrophils were mobilized, recruited, and engulfed, and then died by NETs. Carrageenan stimulated the production of cytokines/chemokines by neutrophils or macrophages, but did not lead to an obvious death by releasing NETs.