Hypoxia, hypoxia-inducible factors and inflammatory bowel diseases.

Adequate oxygen supply is essential for maintaining the body's normal physiological function. In chronic inflammatory conditions such as inflammatory bowel disease (IBD), insufficient oxygen reaching the intestine triggers the regulatory system in response to environmental changes. However, the pathogenesis of IBD is still under investigation. Recent research has highlighted the significant role of hypoxia in IBD, particularly the involvement of hypoxia-inducible factors (HIF) and their regulatory mechanisms, making them promising therapeutic targets for IBD. This review will delve into the role of hypoxia, HIF, and the associated hypoxia-inflammatory microenvironment in the context of IBD. Potential interventions for addressing these challenging gastrointestinal inflammatory diseases will also be discussed within this framework.

Comparison of different sources of mesenchymal stem cells: focus on inflammatory bowel disease.

Inflammatory bowel disease (IBD) poses a significant challenge in modern medicine, with conventional treatments limited by efficacy and associated side effects, necessitating innovative therapeutic approaches. Mesenchymal stem cells (MSC) have emerged as promising candidates for IBD treatment due to their immunomodulatory properties and regenerative potential. This thesis aims to explore and compare various sources of MSC and evaluate their efficacy in treating IBD. This study comprehensively analyses MSC derived from multiple sources, including bone marrow, adipose tissue, umbilical cord, and other potential reservoirs. Core elements of this investigation include assessing differences in cell acquisition, immunomodulatory effects, and differentiation capabilities among these MSC sources, as well as comparing their clinical trial outcomes in IBD patients to their therapeutic efficacy in animal models. Through meticulous evaluation and comparative analysis, this thesis aims to elucidate disparities in the efficacy of different MSC sources for IBD treatment, thereby identifying the most promising therapeutic applications. The findings of this study are intended to advance our understanding of MSC biology and offer valuable insights for selecting the most effective MSC sources for personalized IBD therapy. Ultimately, this research endeavor will optimise therapeutic strategies for managing inflammatory bowel disease through the utilization of MSC.

The new insights of hyperbaric oxygen therapy: focus on inflammatory bowel disease.

Inflammatory bowel diseases (IBD), with an increasing incidence, pose a significant health burden. Although there have been significant advances in the treatment of IBD, more progress is still needed. Hyperbaric oxygen therapy (HBOT) has been shown to treat a host of conditions such as carbon monoxide poisoning, decompression sickness, and gas gangrene. In the last few years, there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD. Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress, inhibiting mucosal inflammation, promoting ulcer healing, influencing gut microbes, and reducing the incidence of IBD complications. This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.

Synergism of non-thermal plasma and low concentration RSL3 triggers ferroptosis via promoting xCT lysosomal degradation through ROS/AMPK/mTOR axis in lung cancer cells.

BACKGROUND: Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. METHODS: CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. RESULTS: We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. CONCLUSION: Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application.

Exogenous carbon monoxide promotes GPX4-dependent ferroptosis through ROS/GSK3ß axis in non-small cell lung cancer.

The gas therapy is drawing increasing attention in the treatment of many diseases including cancer. As one of gas signaling molecules, carbon monoxide (CO) has been proved to exert anti-cancer effects via triggering multiple cell death types, such as autophagy, apoptosis and necrosis. Here, we showed that low concentration CO delivered from CO-releasing molecule 3 (CORM-3) effectively induced ferroptosis, known as a novel proinflammatory programmed cell death, in vitro and in vivo. Mechanistically, we found that CO triggered ferroptosis by modulating the ROS/GSK3ß/GPX4 signaling pathway, resulting in the accumulation of lipid hydroperoxides and the occurrence of ferroptosis. We think our findings provide novel insights into the anti-cancer mechanisms of CO, and suggest that CO could potentially be exploited as a novel ferroptosis inducer for cancer treatment in the future.

Blockade of Syk modulates neutrophil immune-responses via the mTOR/RUBCNL-dependent autophagy pathway to alleviate intestinal inflammation in ulcerative colitis.

Background: Ulcerative colitis (UC) is a progressive chronic inflammatory disorder. Neutrophils play a critical role in regulating intestinal mucosal homeostasis in UC. Spleen tyrosine kinase (Syk) is involved in several inflammatory diseases. Here, we evaluated the effects and underlying mechanisms of Syk on neutrophil immune-responses in UC. Methods: Syk expression in the colonic tissues of patients with UC was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. Colonic biopsies from patients with UC were obtained for single-cell RNA-sequencing. Neutrophils isolated from peripheral blood were pre-treated with R788 (a Syk inhibitor) and gene differences were determined using RNA sequencing. Neutrophil functions were analyzed using qRT-PCR, flow cytometry, and Transwell assay. R788 was administered daily to mice with dextran sulfate sodium (DSS)-induced colitis to verify the effects of Syk on intestinal inflammation. Results: Syk expression was increased in inflamed mucosa and neutrophils of patients with UC and positively correlated with disease activity. Pharmacological inhibition of Syk in neutrophils decreased the production of pro-inflammatory cytokines, chemokines, neutrophil extracellular traps, reactive oxygen species, and myeloperoxidase. Apoptosis and migration of neutrophils were suppressed by Syk blockade. Syk blockade ameliorated mucosal inflammation in DSS-induced murine colitis by inhibiting neutrophil-associated immune responses. Mechanistically, Syk regulated neutrophil immune-responses via the mammalian target of rapamycin kinase/rubicon-like autophagy enhancer-dependent autophagy pathway. Conclusions: Our findings indicate that Syk facilitates specific neutrophil functional responses to mucosal inflammation in UC, and its inhibition ameliorates mucosal inflammation in DSS-induced murine colitis, suggesting its potential as a novel therapeutic target for UC treatment.

Ulcerative Colitis Concomitant with Cytomegalovirus Infection, Bullous Sweet's Syndrome, and Acute Myeloid Leukemia: A Case Report and Literature Review.

Background: Ulcerative colitis (UC) is a chronic, relapsing progressive inflammatory immune disease. There is still no cure for it. Even worse, UC may predispose patients to opportunistic infections, and several extra-intestinal manifestations (EIMs) and comorbidities may antedate, occur with, or postdate the onset of UC, which may increase the mortality risk. But case reports of UC patients simultaneously concomitant with opportunistic infection, EIM, and comorbidity are extremely rare. Case Presentation: We report a case of 51-year-old male patient with incipient UC accompanied by cytomegalovirus (CMV) infection and bullous Sweet's syndrome (bSS, a cutaneous EIM of UC) after treatment with oral mesalazine and prednisolone for 3 weeks. After clearance of the CMV infection by using ganciclovir, the patient was administered two cycles of infliximab to cure UC and bSS; however, he developed acute myeloid leukemia (AML) a month later and died after two cycles of chemotherapy. Conclusion: Based on this rare case of UC concomitant with CMV infection, bSS and AML, we recommend that it is important to distinguish between an acute UC flare and opportunistic infections, especially in patients receiving immunosuppressive therapy, and monitor EIMs and comorbidities timely. Particular attention should be paid to cancer surveillance. Clinicians should be mindful of these facts to adopt optimal therapeutic options to address all aspects of UC. Early initiation of biological therapy may be of benefit to patients with newly diagnosed severe UC.

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases.

BACKGROUND: The high prevalence of chronic inflammatory diseases or autoimmune reactions is a major source of concern and affects the quality of life of patients. Chronic inflammatory or autoimmune diseases are associated with many diseases in humans, including asthma, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and cancer. Splenic tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays an important role in immune receptor signalling in immune and inflammatory responses. METHODS: This is a review article in which we searched for keywords "splenic tyrosine kinase", "inflammation" and "autoimmune diseases" in published literature such as Pubmed and Web of Science to collect relevant information and then conducted a study focusing on the latest findings on the involvement of SYK in chronic inflammatory or autoimmune diseases. RESULTS: This paper reviews the regulation of Fcγ, NF-κB, B cell and T cell-related signalling pathways by SYK, which contributes to disease progression in chronic inflammatory and autoimmune diseases such as airway fibrosis, inflammatory skin disease and inflammatory bowel disease. CONCLUSION: This paper shows that SYK plays an important role in chronic inflammatory and autoimmune diseases. syk targets hematological, autoimmune and other inflammatory diseases and therefore, inhibition of SYK expression or blocking its related pathways may provide new ideas for clinical prevention and treatment of inflammatory or autoimmune diseases.

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma.

Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC). Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC. Single-cell RNA sequencing (scRNA-seq) data from GSE168652 and CESC patients in The Cancer Genome Atlas(TCGA) were systematically analyzed to explore possible molecular mechanisms. Kaplan-Meier evaluated the correlation between LUM (Lumican) and prognostic significance. The expression of LUM protein in biopsy tissues before CCRT was detected by immunohistochemistry in 15 CESC patients. Results: LUM mRNA levels were significantly upregulated in nonresponders of CESC.patients receiving CCRT and positively correlated with poor therapeutic effect. Furthermore, high expression of LUM influenced the immune microenvironment in CESC patient-derived organoids treated with CCRT. LUM overexpression in CESC cells induced resistance to CCRT, potentially via immune landscape modulation. Gene Set Enrichment Analysis (GSEA) revealed that possible mechanisms underlying resistance to CCRT might involve the PARs and IL1 signaling pathway affecting the immune landscape. Conclusions: High LUM expression is correlated with poor efficacy in CESC patients receiving CCRT, possibly through the PARs and IL1 signaling pathway affecting the immune landscape.

PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis.

Neutrophils participate in the pathogenesis of ulcerative colitis (UC) through regulating the intestinal homeostasis. Several inflammatory diseases are reported to be regulated by proline-rich tyrosine kinase 2B (PTK2B). However, the role of PTK2B in regulating the function of neutrophils and the pathogenesis of UC remains unknown. In this study, the mRNA and protein levels of PTK2B in the colonic tissues from UC patients were measured by using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. TAE226, a PTK2B inhibitor, was used to inhibit the activity of PTK2B in neutrophils, and then, the pro-inflammatory factors were analyzed by using qRT-PCR and ELISA. To determine the role of PTK2B in intestinal inflammation, a dextran sulfate sodium (DSS)-induced colitis model was established in PTK2B gene knockout (PTK2B KO) and wild-type (WT) mice. We found that compared with healthy donor controls, the expression level of PTK2B was significantly elevated in inflamed mucosa from UC patients. In addition, expression of PTK2B was positively correlated with the severity of disease. Pharmacological inhibition of PTK2B could markedly reduce the generation of reactive oxygen species (ROS), myeloperoxidase (MPO), and antimicrobial peptides (S100a8 and S100a9) in neutrophils. The vitro study showed that tumor necrosis factor (TNF)-α is involved in promoting the expression of PTK2B in neutrophils. As expected, UC patients treated with infliximab, an anti-TNF-α agent, showed significantly reduced level of PTK2B in neutrophils, as well as in the intestinal mucosa. Of note, compared with DSS-treated WT mice, DSS-treated PTK2B KO mice showed more severe colitis symptoms. Mechanistically, PTK2B could enhance neutrophil migration by regulating CXCR2 and GRK2 expression via the p38 MAPK pathway. Additionally, mice treated with TAE226 exhibited the same effects. In conclusion, PTK2B is involved in the pathogenesis of UC by promoting the migration of neutrophils and inhibiting mucosal inflammation, highlighting PTK2B as a new potential therapeutic target to treat UC.

Loureirin B protects against cerebral ischemia/reperfusion injury through modulating M1/M2 microglial polarization via STAT6 / NF-kappaB signaling pathway.

The latest research indicates that modulating microglial polarization from M1 to M2 phenotype may be a coping therapy for ischemic stroke. The present study thereby evaluated the effects of loureirin B (LB), a monomer compound extracted from Sanguis Draconis flavones (SDF), on cerebral ischemic injury and the potential mechanisms. The middle cerebral artery occlusion (MCAO) model was established in male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo, and BV2 cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that LB significantly reduced infarct volume, neurological deficits and neurobehavioral deficits, apparently improved histopathological changes and neuronal loss in cortex and hippocampus of MCAO/R rats, markedly decreased the proportion of M1 microglia cells and the level of pro-inflammatory cytokines, and increased the proportion of M2 microglia and the level of anti-inflammatory cytokines both in vivo and in vitro. In addition, LB evidently improved the p-STAT6 expression and reduced the NF-κB (p-p65) expression after cerebral I/R injury in vivo and in vitro. IL-4 (a STAT6 agonist) exhibited a similar impact to that of LB, while AS1517499 (a STAT6 inhibitor) significantly reversed the effect of LB on BV-2 cells after OGD/R. These findings point to the protection of LB against cerebral I/R injury by modulating M1/M2 polarization of microglia via the STAT6/NF-κB signaling pathway, hence LB may be a viable treatment option for ischemic stroke.

Ulcerative colitis and thrombocytosis: Case report and literature review.

RATIONALE: Ulcerative colitis (UC) is an autoimmune disease of unknown etiology, sometimes associated with anemia and thrombocytosis. Platelets (PLTs) play a role in amplifying inflammatory and immune responses in chronic inflammation. This study discusses the diagnosis and treatment of a case of UC combined with secondary thrombocytosis and reviews the relevant literature. We report an interaction between thrombocytosis and UC to raise clinicians' awareness of this condition. PATIENT CONCERNS: In the current report, we discuss the case of a 30-year-old female patient who presented with frequent diarrhea and thrombocytosis. DIAGNOSIS: Severe UC combined with intestinal infection was diagnosed based on colonoscopy and intestinal biopsy. The patient had a PLT count >450 × 109/L and was diagnosed with reactive thrombocytosis. INTERVENTIONS AND OUTCOMES: The patient was discharged from the hospital in remission after receiving vedolizumab and anticoagulant treatment. LESSONS: In patients with severe UC with thrombocytosis, clinicians should pay attention to PLTs promoting inflammatory progression, as well as screening for venous thromboembolism risk and prophylactic anti-venous thromboembolism therapy at the time of dosing to avoid adverse effects.

Role of Serum/Glucocorticoid-Regulated Kinase 1 (SGK1) in Immune and Inflammatory Diseases.

Serum/glucocorticoid-regulated kinase 1 (SGK1), a member of the serine/threonine protein kinase gene family, is primarily regulated by serum and glucocorticoids. SGK1 is involved in the development of tumors and fibrotic diseases. However, relatively little research has been conducted on their role in immune and inflammatory diseases. SGK1 may act as a pivotal immune regulatory gene by modulating immune cells (e.g., T cells, macrophages, dendritic cells, and neutrophils) and functions and is involved in the pathogenesis of some immune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis, allergic diseases, sepsis, and major depressive disorder. This review aims to provide an overview of the latest research focusing on the immune and inflammatory regulatory roles of SGK1 and provide new insights into diagnostic and therapeutic approaches for immune and inflammatory diseases.

Downregulation of Nogo-B ameliorates cerebral ischemia/reperfusion injury in mice through regulating microglia polarization via TLR4/NF-kappaB pathway.

Many studies have shown a close association between Nogo-B and inflammation-related diseases. However, uncertainty does exist, regarding Nogo-B function in the pathological progression of cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was utilized in C57BL/6L mice to mimic ischemic stroke in vivo. Using oxygen-glucose deprivation and reoxygenation (ODG/R) model in microglia cells (BV-2) to establish cerebral I/R injury in vitro. Various methods, including Nogo-B siRNA transfection, mNSS and the rotarod test, TTC, HE and Nissl staining, immunofluorescence staining, immunohistochemistry, Western blot, ELISA, TUNEL and qRT-PCR were employed to probe into the effect of Nogo-B downregulation on cerebral I/R injury and the potential mechanisms. A small amount of Nogo-B expression (protein and mRNA) was observed in cortex and hippocampus before ischemia, then Nogo-B expression increased significantly on day 1, reaching the maximum on day 3, remaining stable on day 14 after I/R, and decreasing gradually after 21 days, but it still rose significantly compared with that observed preischemia. Nogo-B down-regulation could markedly reduce the neurological score and infarct volume, improve the histopathological changes and neuronal apoptosis, lower the number of CD86+/Iba1+ cells and the levels of IL-1ß, IL-6, and TNF-α, and raise the density of NeuN fluorescence, the number of CD206+/Iba1+ cells, and the level of IL-4, IL-10 and TGF-ß in brain of MCAO/R mice. Treatment with Nogo-B siRNA or TAK-242 in BV-2 cells could obviously decrease the CD86 fluorescence density and the mRNA expression of IL-1ß, IL-6 and TNF-α, increase CD206 fluorescence density and the mRNA expression of IL-10 after OGD/R injury. In addition, the expression of TLR4, p-IκBα and p-p65 proteins significantly increased in the brain after MCAO/R and BV-2 cells exposed to OGD/R. Treatment with Nogo-B siRNA or TAK-242 prominently reduced the expression of TLR4, p-IκBα and p-p65. Our findings suggest that the down-regulation of Nogo-B exerts protective effect on cerebral I/R injury by modulating the microglia polarization through inhibiting TLR4/NF-κB signaling pathway. Nogo-B may be a potential therapeutic target for ischemic stroke.

CD73 blockade alleviates intestinal inflammatory responses by regulating macrophage differentiation in ulcerative colitis.

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by excessive and persistent inflammation. Intestinal macrophages play a considerable role in regulating inflammatory immune reactions in the gut mucosa. It has previously been reported that CD73 is related to the pathogenesis of inflammatory or immune-related diseases; however, the roles of CD73 in UC remain unclear. In this study, CD73 expression in the inflamed mucosa of patients with UC was examined using reverse transcription-quantitative PCR (RT-qPCR), western blotting, and immunohistochemistry. Adenosine 5'-(α, ß-methylene) diphosphate (APCP) was used to block the expression of CD73. Furthermore, the mRNA levels of proinflammatory mediators associated with macrophages following the blocking of CD73 were examined using RT-qPCR. Finally, the regulatory function of CD73 in intestinal inflammation was assessed by administering APCP in a mouse model of dextran sulfate sodium salt (DSS)-induced colitis. Notably, it was found that CD73 expression was significantly increased in the colonic mucosal tissues of patients with UC. Blockade of CD73 inhibited the expression of pro-inflammatory cytokines but promoted the production of anti-inflammatory cytokines in macrophages, while its promotion of M2 macrophage polarization was also verified. In vivo, CD73 blockade markedly alleviated DSS-induced colitis in mice, as characterized by reduced weight loss, reduction in the incidence of diarrhea, and reduced amount of bloody stool. Mechanistically, it was shown that CD73 regulated macrophage differentiation via the NF-κB and ERK signaling pathways. In conclusion, the findings of the present study indicate that CD73 may have a potential impact on the pathogenesis of UC by modulating the immune response of macrophage differentiation; thus, providing a novel pathway for modulating mucosal inflammation in UC.

Targeted pharmacokinetics and bioinformatics screening strategy reveals JAK2 as the main target for Xin-Ji-Er-Kang in treatment of MIR injury.

BACKGROUND AND PURPOSE: Xin-Ji-Er-Kang (XJEK) is traditional Chinese formula presented excellent protective effects on several heart diseases, but the potential components and targets are still unclear. The aim of this study is to elucidate the effective components of XJEK and reveal its potential mechanism of cardioprotective effect in myocardial ischemia-reperfusion (MIR) injury. EXPERIMENTAL APPROACH: Firstly, the key compounds in XJEK, plasma and heart tissue were analyzed by high resolution mass spectrometry. Bioinformatics studies were also involved to disclose the potential targets and the binding sites for the key compounds. Secondly, to study the protective effect of XJEK on MIR injury and related mechanism, mice subjected to MIR surgery and gavage administered with XJEK for 6 weeks. Cardiac function parameters and apoptosis level of cardiac tissue were assessed. The potential mechanism was further verified by knock down of target protein in vitro. RESULTS: Pharmacokinetics studies showed that Sophora flavescens alkaloids, primarily composed with matrine, are the key component of XJEK. And, through bioinformatic analysis, we speculated JAK2 could be the potential target for XJEK, and could form stable hydrogen bonds with matrine. Administration of XJEK and matrine significantly improved heart function and reduced apoptosis of cardiomyocytes by increasing the phosphorylation of JAK2 and STAT3. The anti-apoptosis effect of XJEK and matrine was also observed on AC16 cells, and could be reversed by co-treatment with JAK2 inhibitor AG490 or knock-down of JAK2. CONCLUSION: XJEK exerts cardioprotective effect on MIR injury, which may be associated with the activation of JAK2/STAT3 signaling pathway.

Xin-Ji-Er-Kang Alleviates Isoproterenol-Induced Myocardial Hypertrophy in Mice through the Nrf2/HO-1 Signaling Pathway.

Xin-Ji-Er-Kang (XJEK) inhibited cardiovascular remodeling in hypertensive mice in our previous studies. We hypothesized that XJEK may prevent isoproterenol (ISO)-induced myocardial hypertrophy (MH) in mice by ameliorating oxidative stress (OS) through a mechanism that may be related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathways. Forty SPF male Kunming mice were randomized into 5 groups (n = 8 mice per group): control group, MH group, MH + different doses of XJEK (7.5 g/kg/day and 10 g/kg/day), and MH + metoprolol (60 mg/kg/day). On the eighth day after drug treatment, electrocardiogram (ECG) and echocardiography were performed, the mice were sacrificed, and blood and heart tissues were collected for further analysis. XJEK administration markedly ameliorated cardiovascular remodeling (CR), as manifested by a decreased HW/BW ratio and CSA and less collagen deposition after MH. XJEK administration also improved MH, as evidenced by decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC) levels. XJEK also suppressed the decreased superoxide dismutase (SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) levels in serum of mice with MH. XJEK-induced oxidative stress may be related to potentiating Nrf2 nuclear translocation and HO-1 expression compared with the MH groups. XJEK ameliorates MH by activating the Nrf2/HO-1 signaling pathway, suggesting that XJEK is a potential treatment for MH.

The role of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in immune diseases.

The long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) has been shown to be involved in the pathogenesis of several diseases. Herein, we discuss recent developments and insights into NEAT1 and its contribution to a variety of immune disorders. Our evaluations revealed that NEAT1's function in immune diseases seems to be focused on the modulation of paraspeckle expression and it is primarily associated with the nuclear retention of its mRNA. NEAT1 is also involved in the sequestration of paraspeckle proteins and in affecting the transcriptional expression of specific immune regulators. The expression of NEAT1 may be aberrantly upregulated in several immune pathologies, indicating that it could serve as a potential prognostic biomarker in these conditions. We summarized describing the expression changes and the role of NEAT1 in several immune diseases. We also described the mechanism of its regulation of the immune cell differentiation and function of NEAT1 in different disease.

Critical roles of RGS16 in the mucosal inflammation of ulcerative colitis.

BACKGROUND: Ulcerative colitis is a chronic and progressive inflammatory disorder. The regulator of the G-protein signaling (RGS) is involved in the pathogenesis of several immune system disorders. RGS16, a member of the RGS protein superfamily, has been shown to play critical roles in several immune system-related diseases. However, the roles of RGS16 in ulcerative colitis remain to be elucidated. METHODS: We analyzed the expression of RGS16 in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of ulcerative colitis patients using quantitative reverse transcription-PCR, western blotting and immunohistochemistry. We performed Spearman's correlation to analyze the correlation between RGS16 expression and the ulcerative colitis endoscopic index of severity (UCEIS), Mayo index, erythrocyte sedimentation rate (ESR) and serum tumor necrosis factor alpha (TNF-a) and IL-17A levels. Further, PBMCs were stimulated with inflammatory cytokines in vitro . RESULTS: RGS16 expression significantly increased in the colonic mucosa and PBMCs from patients with ulcerative colitis and significantly correlated with the Mayo index, UCEIS, ESR and serum TNF-α and IL-17A levels. TNF-α upregulated RGS16 expression in PBMCs in a dose- and time-dependent manner via the nuclear factor kappa beta (NF-kB) signaling pathway. Moreover, anti-TNF treatment with infliximab significantly decreased RGS16 expression in PBMCs and intestinal mucosa of patients with ulcerative colitis. CONCLUSION: Our study revealed a novel mechanism by which RGS16 expression in ulcerative colitis is positively correlated with disease activity. Thus, RGS16 might serve as a potential therapeutic marker for the treatment of ulcerative colitis.

Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction.

BACKGROUND: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. METHODS: A MI model of Kun-ming mice induced by left anterior descending coronary artery ligation was utilized to study the potential therapeutic effects of calcitriol on MI. AC16 human cardiomyocyte-like cells treated with TNF-α were used for exploring the mechanisms that underlie the cardioprotective effects of calcitriol. RESULTS: We observed that calcitriol reversed adverse cardiovascular function and cardiac remodeling in post-MI mice. Mechanistically, calcitriol suppressed MI-induced cardiac inflammation, ameliorated cardiomyocyte death, and promoted cardiomyocyte proliferation. Specifically, calcitriol exerted these cellular effects by upregulating Vitamin D receptor (VDR). Increased VDR directly interacted with p65 and retained p65 in cytoplasm, thereby dampening NF-κB signaling and suppressing inflammation. Moreover, up-regulated VDR was translocated into nuclei where it directly bound to IL-10 gene promoters to activate IL-10 gene transcription, further inhibiting inflammation. CONCLUSION: We provide new insights into the cellular and molecular mechanisms underlying the cardioprotective effects of calcitriol, and we present comprehensive evidence to support the preventive and therapeutic effects of calcitriol on MI.