[Research progress on the role of microglia in sepsis-associated encephalopathy].

Sepsis-associated encephalopathy (SAE) refers to diffuse brain dysfunction caused by sepsis, which is characterized by decreased attention, directional impairment, being prone to irritation, and in severe cases the patient will experience drowsiness and coma. The pathogenesis of SAE mainly includes neuroinflammation, damage of blood-brain barrier, cerebral vascular dysfunction, and neurometabolic changes, among which neuroinflammation is the core pathological process. Microglia are considered to be important immune cells of the central nervous system and play an important role in neuroinflammation. This article systematically describes the role of microglia in the development of SAE, and discusses the phenotype and related signaling pathways of microglia, in order to clarify the role of microglia in SAE and provide a theoretical basis for clinical treatment of SAE.

Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

Blocking salt-inducible kinases with YKL-06-061 prevents PTZ-induced seizures in mice.

INTRODUCTION: Epilepsy is one of the most common neurological diseases, while over one third of adults with epilepsy still have inadequate seizure control. Although mutations in salt-inducible kinases (SIKs) have been identified in epileptic encephalopathy, it is not known whether blocking SIKs can prevent pentylenetetrazole (PTZ)-induced seizures. METHODS: We first determined the time course of SIKs (including SIK 1, 2, and 3) in the hippocampus of PTZ treated mice. And then, we evaluated the effects of anti-epilepsy drug valproate acid (VPA) on the expression of SIK 1, 2, and 3 in the hippocampus of PTZ treated mice. Next, we investigated the effect of different dose of SIKs inhibitor YKL-06-061 on the epileptic seizures and neuronal activation by determining the expression of immediate early genes (IEGs) in the PTZ treated mice. RESULTS: We found that PTZ selectively induced enhanced expression of SIK1 in the hippocampus, which was blocked by VPA treatment. Notably, YKL-06-061 decreased seizure activity and prevented neuronal overactivity, as indicated by the reduced expression of IEGs in the hippocampus and prefrontal cortex. CONCLUSION: Our findings provide the first evidence that SIK1 affects gene regulation in neuronal hyperactivity, which is involved in seizure behavior. Targeting SIK1 through the development of selective inhibitors may lead to disease-modifying therapies that reduce epilepsy progression.

Simvastatin nanocrystals-based dissolving microneedles for wound healing.

Currently, one of the main problems encountered in wound healing therapy is related to inefficient drug delivery. However, dissolving microneedles (DMNs) can be administered percutaneously to effectively deliver a drug to a deep wound area. Simvastatin (SIM) can promote wound healing, albeit its insolubility in water limits its application. Here, we designed a DMNs (SIM-NC@DMNs) drug delivery system loaded with SIM nanocrystals (SIM-NC) and evaluated its efficacy in wound healing. Based on our observations, the dissolution performance of insoluble SIM is significantly improved after the preparation of SIM-NC. For example, the saturation solubility of SIM-NC in deionized water and PBS increased by 150.57 times and 320.14 times, respectively. After the SIM-NC@DMNs are deeply inserted into the wound, the needle portion, which is composed of hyaluronic acid (HA), dissolves rapidly, and the SIM-NC loaded on the needle portion is efficiently released into the deep wound area for optimal therapeutic efficacy. The combination of NC and DMNs makes this system further effective for wound healing. Our cumulative work suggests that the newly developed SIM-NC@DMNs possess great potential in accelerating wound healing. By day 12 after treatment, the residual wound area in the Control group was 21.34 %, while the residual wound area in the SIM-NC@DMNs group was only 2.36 %. This result as well as provides certain evidence of its efficacy for wound healing therapy. The SIM-NC@DMNs drug delivery system may become an efficient treatment modality that promotes wound healing, with a promising potential in the field of wound healing research.

IGF2/IGF2R/Sting signaling as a therapeutic target in DSS-induced ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.

Achieving desirable charge transport by porous frame engineering for superior 3D printed rechargeable Ni-Zn alkaline batteries.

Rechargeable 3D printed batteries with extraordinary electrochemical potential are typical contenders as one of the promising energy storage systems. Low-cost, high-safety, and excellent rechargeable aqueous alkaline batteries have drawn extensive interest. But their practical applications are severely hampered by poor charge carrier transfer and limited electrochemical activity at high loading. Herein, we report a unique structure-based engineering strategy in 3D porous frames using a feasible 3D printing technique and achieve 3D printed full battery devices with outstanding electrochemical performance. By offering a 3D porous network to provide prominently stereoscopic support and optimize the pore structure of electrodes, the overall charge carrier transport of engineered 3D printed Ni-Zn alkaline batteries (E3DP-NZABs) is greatly enhanced, which is directly demonstrated through a single-wired characterization platform. The obtained E3DP-NZABs deliver a high areal capacity of 0.34 mA h cm-2 at 1.2 mA cm-2, and an outstanding capacity retention of 96.2% after 1500 cycles is also exhibited with an optimal electrode design. Particularly, parameter changes such as a decrease in pore sizes and an increase in 3D network thickness are favorable to resultant electrochemical performance. This work may represent a vital step to promote the practical application progress of alkaline batteries.

FAPbBr3@PbBr(OH) phosphor with high stability for anti-counterfeiting application via water induction.

Organic-inorganic hybrid perovskite nanocrystals have become a very widely used as semiconductor light-emitting materials. However, perovskite nanocrystals face stability challenges, which is a key factor hindering their application. In this paper, by introducing water into the synthesis of formamidinium lead bromide (FAPbBr3) perovskite, ultra-stable FAPbBr3@PbBr(OH) fluorescent material was prepared. The photoluminescence intensity of the material after the addition of water increased 2.9 times compared with that before the addition of water. The excellent green fluorescence emission was still maintained after four cycles of wash-dry treatment. Meanwhile, it also exhibits good ultraviolet and thermal stability. The above enhanced performance of FAPbBr3nanocrystals is attributed the protection of PbBr(OH). In addition, the prepared material can be used in anti-counterfeit patterns. The anti-counterfeit patterns have good color rendering and the luminous color has a high dependence on temperature. Both of these features make it very valuable for various fluorescent anti-counterfeiting labels.

Mechanisms of NAT10 as ac4C writer in diseases.

In the early stage, N4-acetylcytidine (ac4C) was regarded as a conservative nucleoside present on tRNA and rRNA. Recently, studies have shown that ac4C also exists in human and yeast mRNA. N-Acetyltransferase-like protein 10 (NAT10) is the first enzyme to be found to catalyze ac4C production in eukaryotic RNA and has acetyltransferase activity and RNA-binding activity. Here, we first describe the structure and cellular localization of NAT10. Then, we conclude the active roles of NAT10 as the ac4C "writer" in mRNA stability and translation efficiency, oocyte maturation, bone remodeling, and fatty acid metabolism. With respect to disease, we focused on the promoting functions of NAT10 in proliferation, metastasis, and apoptosis in multiple tumors. The immune regulatory role of NAT10 in systemic lupus erythematosus and the maintenance role of NAT10 in virus RNA stability and replication in influenza A virus are also introduced. This review identifies NAT10 as a potential target for diagnosis, therapy, and prognosis in clinical application.

Porous Colorimetric Microneedles for Minimally Invasive Rapid Glucose Sampling and Sensing in Skin Interstitial Fluid.

Though monitoring blood glucose (BG) is indispensable for regulating diabetes, the frequent pricking of the finger by the commonly used fingertip blood collection causes discomfort and poses an infection risk. Since glucose levels in skin interstitial fluid (ISF) correlate with blood glucose levels, monitoring glucose in the skin ISF can be a viable alternative. With this rationale, the present study developed a biocompatible porous microneedle capable of rapid sampling, sensing, and glucose analysis in ISF in a minimally invasive manner, which can improve patient compliance and detection efficiency. The microneedles contain glucose oxidase (GOx) and horseradish peroxidase (HRP), and a colorimetric sensing layer containing 3,3',5,5'-tetramethylbenzidine (TMB) is on the back of the microneedles. After penetrating rat skin, porous microneedles harvest ISF rapidly and smoothly via capillary action, triggering the production of hydrogen peroxide (H2O2) from glucose. In the presence of H2O2, HRP reacts with TMB contained in the filter paper on the back of microneedles, causing an easily visible color shift. Further, a smartphone analysis of the images quickly quantifies glucose levels in the 50-400 mg/dL range using the correlation between color intensity and glucose concentration. The developed microneedle-based sensing technique with minimally invasive sampling will have great implications for point-of-care clinical diagnosis and diabetic health management.

Systemic treatment with GnRH agonist produces antidepressant-like effects in LPS induced depression male mouse model.

Gonadotropin-releasing hormone (GnRH) is at the head of the neuroendocrine reproductive axis. However, the non-reproductive functions of GnRH expressed in various tissues, including hippocampus, are still not known. Here, we unveil a previously unknown effect of GnRH, which mediates depression-like behaviors through the modulation of microglia function during immune challenge. Specifically, we found that either systemic treatment with GnRH agonist or over-expression of endogenous hippocampal GnRH via viral tool abolished the depression-like behavior after LPS challenges in mice. And the anti-depressant of GnRH was dependent on the hippocampal GnRHR signaling, since antagonizing GnRHR by drug treatment or by hippocampal GnRHR knockdown could block the antidepressant-effect of GnRH agonist. Interestingly, we found that the peripheral GnRH treatment prevented the microglia activation mediated inflammation in the hippocampus of mice. In light of the research findings presented here, we propose that, at least in the hippocampus, GnRH appears to act on GnRHR to regulate higher order non-reproductive functions associated with the microglia mediated neuroinflammation. These findings also provide insights into the function and cross-talk of GnRH, a known neuropeptide hormone, in neuro-immune response.

5-aminolevulinic acid-loaded dissolving microneedle array for photodynamic therapy of rheumatoid arthritis on rats.

Photodynamic therapy (PDT) is a noninvasive technique that can be used to treat rheumatoid arthritis (RA) by irradiating photosensitizers with specific wavelengths of light to generate reactive oxygen species (ROS), thus leading to targeted cell necrosis. However, efficient delivery of photosensitizers with low side effects is a key issue. We developed a 5-aminolevulinic acid-loaded dissolving microneedle array (5-ALA@DMNA) that can locally and efficiently deliver photosensitizers for RA treatment by PDT. 5-ALA@DMNA was fabricated through a two-step molding process, which was characterized. The effects of 5-ALA-mediated PDT on RA fibroblast-like synoviocytes (RA-FLs) were investigated via in vitro experiments. Adjuvant arthritis rat models were established to evaluate the therapeutic effect of 5-ALA@DMNA-mediated PDT on RA. The results showed that 5-ALA@DMNA could penetrate the skin barrier and efficiently deliver photosensitizers. 5-ALA-mediated PDT can significantly inhibit the migration ability and selectively induce apoptosis of RA-FLs. Moreover, 5-ALA-mediated PDT had a significant therapeutic effect on rats with adjuvant arthritis, which may be related to the upregulation of interleukin (IL)- 4 and IL-10 and downregulation of TNF-α, IL-6, and IL-17. Thus, 5-ALA@DMNA-mediated PDT may be a potential therapy for RA.

Research progress in effects of pyroptosis on intestinal inflammatory injury. / ç»†èƒžç„¦äº¡åœ¨è‚ é“ç‚Žæ€§æŸä¼¤ä¸­ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Inflammatory injury of the intestine is often accompanied by symptoms such as damage to intestinal mucosa, increased intestinal permeability, and intestinal motility dysfunction. Inflammatory factors spread throughout the body via blood circulation, and can cause multi-organ failure. Pyroptosis is a newly discovered way of programmed cell death, which is mainly characterized by the formation of plasma membrane vesicles, cell swelling until the rupture of the cell membrane, and the release of cell contents, thereby activating a drastic inflammatory response and expanding the inflammatory response cascade. Pyroptosis is widely involved in the occurrence of diseases, and the underlying mechanisms for inflammation are still a hot spot of current research. The caspase-1 mediated canonical inflammasome pathway of pyroptosis and caspase-4/5/8/11-mediated non-canonical inflammasome pathway are closely related to the occurrence and development of intestinal inflammation. Therefore, investigation of the signaling pathways and molecular mechanisms of pyroptosis in intestinal injury in sepsis, inflammatory bowel diseases, infectious enteristic, and intestinal tumor is of great significance for the prevention and treatment of intestinal inflammatory injury.

HC067047 Ameliorates Sepsis-associated Encephalopathy by Suppressing Endoplasmic Reticulum Stress and Oxidative Stress-Induced Pyroptosis in the Hippocampi of Mice.

Sepsis-associated encephalopathy (SAE) is a common neurological complication of sepsis and is characterized by hyperneuroinflammation. NLRP3 inflammasome-mediated pyroptosis can induce an inflammatory cascade response and plays a key role in SAE. TRPV4 is involved in the hyperinflammatory response associated with inflammation; however, whether TRPV4 inhibition might alleviate SAE-related brain damage is still unknown. Therefore, we aimed to investigate the role and mechanism of HC067047, a potent inhibitor of TRPV4, in hyperneuroinflammation and blood-brain barrier (BBB) dysfunction in a lipopolysaccharide (LPS)-induced SAE mouse model. We found that HC067047 administration significantly inhibited the expression of TRPV4 and p-CamkIIα in the hippocampi of SAE mice. Furthermore, HC067047 treatment attenuated LPS-induced endoplasmic reticulum (ER) stress and oxidative stress (OS), thus remarkably preventing NLRP3 inflammasome-mediated pyroptosis, as well as the expression of proinflammatory factors (IL-1ß and IL-18). Additionally, we found that HC067047 selectively prevented pyroptosis in hippocampal cells, mainly the neurons, oligodendrocytes and the resident microglia. The disruption of BBB integrity in SAE mice was also rescued by HC067047 intervention. Thus, we can conclude that the TRPV4 inhibitor HC067047 could protect against hippocampal cell pyroptosis, which might be due to the attenuation of the NLRP3 inflammasome-mediated pyroptosis pathway caused by ER stress and OS. Our findings suggest a potential preventive role for HC067047 in SAE.

IGF2 inhibits hippocampal over-activated microglia and alleviates depression-like behavior in LPS- treated male mice.

Over-activated microglia and inflammatory mediators are found in patients with depression, while manipulation of the microglia function might represent a potential therapeutic strategy. Insulin-like growth factor 2 (IGF2) has been implicated in bacterial infections and autoimmune disorders, but the role of IGF2 on the active phenotype of microglia and neuroinflammation has not been well established. IGF2 influences in modulating microglia responding to neuroinflammation induced by lipopolysaccharide（LPS）challenge will be carefully examined. In the current study, we verified that systemic IGF2 treatment could produce an anti-depression effect in LPS-treated mice. Particularly, we found that systemic IGF2 treatment inhibited microglia over-activation and prevented its transformation to a pro-inflammatory phenotype, thereby protecting hippocampal neurogenesis. Since microglia reactive to neuroinflammation is a common feature of neuropsychiatric disorders, the discoveries from the present study may provide therapeutic innovation for these diseases.

HC067047 as a potent TRPV4 inhibitor repairs endotoxemia colonic injury.

Colonic injury causes severe inflammation during systemic infections in patients with endotoxemia. The prevention of colonic injury could effectively reduce the progression of endotoxemia. We investigated the protective effects and detailed mechanisms of the TRPV4 inhibitor HC067047 in the treatment of colonic injury caused by endotoxemia. An LPS-induced endotoxemia colonic injury model was used to assess the in vivo effects of HC067047. Colon slices were detected by hematoxylin and eosin (HE) staining and immunofluorescence assays. Spectrophotometry was used to determine the levels of MDA, calcium, GSH, and GSSG. Alterations in oxidative stress/mitophagy/inflammatory pyroptosis-related markers were evaluated by Q-PCR and western blot assays. HC067047 reduced the body weight loss and spleen weight index of endotoxemic mice and partly recovered the normal morphology of the colonic mucous layer. As an inhibitor of the calcium permeant cation channel, HC067047 suppressed the phosphorylation of the CAMKIIɑ protein and levels of MDA and calcium, upregulated the ratio of GSH/GSSG, shortened the expression of oxidative stress-related proteins, and enhanced the expression of the anti-oxidative protein CAT in damaged colon tissues. Additionally, HC067047 maintained normal mitochondrial functions in endotoxemia colons by promoting mitochondrial fusion and biosynthesis and suppressing mitochondrial fission and the PINK/Parkin/mitophagy pathway. HC067047 potently blocked inflammatory pyroptosis and protected the colonic tight junction barrier. HC067047 restores endotoxemia colons against oxidative stress, mitophagy, inflammatory pyroptosis, and colonic barrier dysfunction. Hence, HC067047 therapy may be potentially useful in the treatment of colonic injury in endotoxemia.

Caspase-11 contributes to pain hypersensitivity in the later phase of CFA-induced pain of mice.

Chronic pain is a common disease that severely disrupts the quality of life. Persistent neuroinflammation and central sensitization play important roles in its pathogenesis. Caspase-11 is a critical modulator of inflammation of central nervous system. However, its role in chronic pain remains elusive. In this study, chronic pain and acute pain were induced via injecting complete Freund's adjuvant (CFA) and 5 % formalin into the plantar of the right hind paw of wild-type (WT) and Caspase-11 deficient (Caspase-11-/-) mice, respectively. In WT mice, CFA injection significantly decreased the hind paw mechanical pain threshold in Von Frey test on 1-7 days after injection and increased the caspase-11 level of ipsilateral dorsal horn of spinal cord on day 2 and day 5 after injection. Compared to the WT mice, Caspase-11-/- mice showed significantly higher mechanical pain threshold in the later phase of CFA-induced pain, but not in the early phase, and had no significant difference in 5 % formalin induced licking and flinching behavior. In addition, the microglial activation, and the mRNA levels of caspase-1 and IL-18 in the spinal cord of Caspase-11-/- mice restored to baseline on the day 5 after CFA injection, but not in WT mice. Our data indicated that Caspase-11 contributed to persistent inflammation in ipsilateral dorsal horn of spinal cord, and consequently pain hypersensitivity in the later phase of CFA-induced pain.

Hyperactivation of TRPV4 causes the hippocampal pyroptosis pathway and results in cognitive impairment in LPS-treated mice.

Pyroptosis, a newly discovered proinflammatory programmed cell death, is involved in the regulation of cognitive dysfunction, such as Alzheimer's disease. Exploring potential drug targets that prevent pyroptotic procedures might benefit the development of a cure for these diseases. In the present study, we explored whether the transient receptor potential vanilloid 4 (TRPV4) blocker HC067047 and knockdown of TRPV4 in the hippocampus could improve cognitive behavior through the inhibition of pyroptosis in a mouse model developed using systemic administration of lipopolysaccharide (LPS). We found that systemic administration of HC067047 or knockdown of hippocampal TRPV4 prevented the activation of canonical and noncanonical pyroptosis in the hippocampus of LPS-treated mice. Consistent with the inhibition of the hippocampal pyroptosis pathway, a knockdown of hippocampal TRPV4 lowered expression of TNF-α, IL-1ß, IL-18, and IL-6. Furthermore, we verified that the main pyroptosis cell type might be a neuron, indicated by reduced neuronal marker expression. Mechanically, we also found that knockdown of hippocampal TRPV4 might inhibit phosphorylation of CamkⅡα which results in NFκb mediated inflammasome reduction in the hippocampus of LPS-treated mice. More interestingly, mice intraperitoneally injected with HC067047 or the hippocampus injected with TRPV4 shRNA showed improved cognitive behavior, as indicated by the enhanced discrimination ratio in the NORT, NOPT, and SNPT. Collectively, we consider that HC067047 might be a small molecular drug that prevents pyroptosis, and TRPV4 could be an effective therapeutic target for preventing pyroptosis-induced cognitive dysfunction.

Roles of complement system in psychiatric disorders. / è¡¥ä½“ç³»ç»Ÿåœ¨ç²¾ç¥žç±»ç–¾ç— ä¸­çš„ä½œç”¨.

The complement system is an important part of the innate immune system, including more than 50 secretory proteins and membrane-bound proteins, and it contributes to the clearance of apoptotic cells and invading pathogens to limit inflammatory immune responses and maintaining brain homeostasis. Complement activity is strictly regulated to protect cells from random attacks or to prevent the deposition of complement proteins in physiological cases. However, overactivation or abnormal regulation of the complement cascade in the brain can lead to neuronal damage and brain dysfunction. Recent studies have pointed out that changes in complement molecules exist in patients with psychiatric diseases and play an important role in the occurrence and development of diseases by regulating the function of neurons and glial cells. Therefore, summarizing the latest research progress of complement system in psychiatric diseases such as schizophrenia, autism spectrum disorder, major depression, bipolar disorder and anxiety disorder can provide new ideas for preventing and controlling psychiatric diseases caused by abnormal activation of complement system.

Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders.

Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib (PLX3397) and social isolation. Herein, we adopted PLX3397 to investigate the role of microglia in the modulation of social isolation. Our results found that social isolation during adolescence caused depressive-like, but not anxiety-like behavior in mice in adulthood, with enhanced expression of the microglial marker Iba1 in the hippocampus. In addition, treatment with PLX3397 reduced the expression of the microglial marker Iba1, decreased the mRNA expression of IL-1ß, increased the mRNA expression of Arg1, elevated the protein levels of DCX and GluR1 and restored the dendritic spine branches and density, ultimately mitigating depressive-like behavior in mice. These findings suggest that inhibition of microglia in the hippocampus could ameliorate mood disorders in mice, providing a new perspective for the treatment of psychiatric disorders such as depression.

Betaine Ameliorates Acute Sever Ulcerative Colitis by Inhibiting Oxidative Stress Induced Inflammatory Pyroptosis.

SCOPE: Betaine rich in beet is used as an important source of human nutrition. Here this study aims to explore whether betaine supplementation can protect against acute sever ulcerative colitis (ASUC) and the underlying mechanism METHODS AND RESULTS: ASUC model is induced by dextran sulfate sodium (DSS), and effects of betaine as a methyl donor on ASUC are evaluated. Betaine mitigates the changes, for example, elevated DAI, weight loss, spleen enlargement, colon shortening, and disordered colonic mucosa. The protective effects of betaine on colonic barrier integrity in ASUC are then verified through examining tight junction proteins by western blot and immunofluorescence. Spectrophotometry method and western blot confirm that betaine can decrease levels of oxidative markers (MDA, MPO, NOS, and COX2), and promote expressions of antioxidant proteins (GSH, NRF2, CAT, and SOD1). Further, betaine prevents colonic inflammatory pyroptosis by blocking expressions of NLRP3 inflammasome complex (NLRP3, ASC, and cleaved-caspase 1), N terminal-GSDMD, and release of relevant inflammatory factors. CONCLUSION: Betaine inhibits colonic oxidative stress induced inflammatory pyroptosis to alleviate ASUC, which shows therapeutic potential against colitis and other acute inflammatory disorder.