Tripartite motif-containing protein 31 confers protection against nonalcoholic steatohepatitis by deactivating mitogen-activated protein kinase kinase kinase 7.

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.

The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant defense genes was increased soon after the onset of DM. In addition, ischemia/oxidative stress caused less death in the retinal vasculature of DM versus non-DM mice. Further investigation with T1D mice revealed that protection was transient; it waned as the duration of DM was prolonged. Finally, a loss of protection was associated with the manifestation of both neural and vascular abnormalities that are diagnostic of DR in mice. These observations demonstrate that DM can transiently activate protection from oxidative stress, which is a plausible explanation for the delay in the development of DR from the onset of DM.

State-of-the-art OMICS strategies against toxic effects of heavy metals in plants: A review.

Environmental pollution of heavy metals (HMs), mainly due to anthropogenic activities, has received growing attention in recent decades. HMs, especially the non-essential carcinogenic ones, including chromium (Cr), cadmium (Cd), mercury (Hg), aluminum (Al), lead (Pb), and arsenic (As), have appeared as the most significant air, water, and soil pollutants, which adversely affect the quantity, quality, and security of plant-based food all over the world. Plants exposed to HMs could experience significant decline in growth and yield. To avoid or tolerate the toxic effects of HMs, plants have developed complicated defense mechanisms, including absorption and accumulation of HMs in cell organelles, immobilization by forming complexes with organic chelates, extraction by using numerous transporters, ion channels, signalling cascades, and transcription elements, among others. OMICS strategies have developed significantly to understand the mechanisms of plant transcriptomics, genomics, proteomics, metabolomics, and ionomics to counter HM-mediated stress stimuli. These strategies have been considered to be reliable and feasible for investigating the roles of genomics (genomes), transcriptomic (coding), mRNA transcripts (non-coding), metabolomics (metabolites), and ionomics (metal ions) to enhance stress resistance or tolerance in plants. The recent developments in the mechanistic understandings of the HMs-plant interaction in terms of their absorption, translocation, and toxicity invasions at the molecular and cellular levels, as well as plants' response and adaptation strategies against these stressors, are summarized in the present review. Transcriptomics, genomics, metabolomics, proteomics, and ionomics for plants against HMs toxicities are reviewed, while challenges and future recommendations are also discussed.

Electro-oxidation of Ni (II)-citrate complexes at BDD electrode and simultaneous recovery of metallic nickel by electrodeposition.

The simultaneous electro-oxidation of Ni (II)-citrate and electrodeposition recovery of nickel metal were attempted in a combined electro-oxidation-electrodeposition reactor with a boron-doped diamond (BDD) anode and a polished titanium cathode. Effects of initial nickel citrate concentration, current density, initial pH, electrode spacing, electrolyte type, and initial electrolyte dosage on electrochemical performance were examined. The efficiencies of Ni (II)-citrate removal and nickel metal recovery were determined to be 100% and over 72%, respectively, under the optimized conditions (10 mA/cm2, pH 4.09, 80 mmol/L Na2SO4, initial Ni (II)-citrate concentration of 75 mg/L, electrode spacing of 1 cm, and 180 min of electrolysis). Energy consumption increased with increased current density, and the energy consumption was 0.032 kWh/L at a current density of 10 mA/cm2 (pH 6.58). The deposits at the cathode were characterized by scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). These characterization results indicated that the purity of metallic nickel in cathodic deposition was over 95%. The electrochemical system exhibited a prospective approach to oxidize metal complexes and recover metallic nickel.

The ratio of H/C is a useful parameter to predict adsorption of the herbicide metolachlor to biochars.

Biochar adsorbent was produced by pyrolyzing traditional Chinese medicinal herb residue at 300, 500 and 750 °C (referred to as biochar-300, biochar-500 and biochar-750). Basic physical and chemical analyses, Fourier transform infrared spectroscopy (FT-IR), and thermodynamic analyses were performed to elucidate adsorption and properties of biochar. Biochar adsorption capacity of herbicide metolochlor, as measured by batch-type adsorption experiments by Freundlich constant Kf (mg1-n Ln kg-1), followed the order: biochar-750 > biochar-300 > biochar-500. Thermodynamic analysis suggested that adsorption of metolachlor on biochar was a spontaneous process. The adsorption isotherm for the biochar produced at the highest pyrolysis temperature was characteristic for adsorption process driven by a high surface area of biochar (85.30 m2 g-1), while the adsorption process for the biochar produced at the lowest temperature was controlled by its higher content of organic matter (39.06%) and abundant functional groups. The FT-IR spectra also showed that the biochar prepared at the lowest temperature had the highest number of surface groups. In general, pore-filling induced by the large surface area of the biochar was the dominant adsorption mechanism. When the H/C value was >0.5, the adsorption mechanism of biochar was dominated by surface chemical bond, while pore-filling played a major role when the H/C value was <0.5.

Assessment of trace metal contamination and ecological risk in the forest ecosystem of dexing mining area in northeast Jiangxi Province, China.

Samples of soil, earthworms, and tree roots from the forest ecosystem in the Dexing Pb/Zn mining area of Jiangxi Province were collected and the status of trace metal pollution analyzed to assess potential ecological risks. Chemometric and geographic information system methods were used to identify and describe the spatial distributions and the main contamination sources of trace metals. The order of potential ecological risks of trace metals in this area are as follows: cadmium (Cd) > arsenic (As) > copper (Cu) > nickel (Ni) > lead (Pb) > chromium (Cr) > zinc (Zn). Elemental spatial distribution maps showed the existence of zones heavily polluted by trace metals around the mining area. Earthworms and roots of three tree species were also heavily contaminated, with concentrations of trace metals in earthworms much higher than in previous studies. The potential ecological risk index and other soil quality indices indicated that soil had moderate to severe contamination and there were high ecological risks, with Cd making the greatest contribution. Multivariate statistical analyses showed that Cd, As, Cu, Pb, and Zn in soil came from a mining activity source, whereas Ni and Cr primarily originated from a natural source.

Trace metal pollution and ecological risk assessment in agricultural soil in Dexing Pb/Zn mining area, China.

Surface agricultural soil samples obtained from Dexing Pb/Zn mining area in Jiangxi province were analyzed for trace metals to assess their pollution status and potential ecological risk. The spatial distributions and the major trace metals pollution sources were described and identified with the combination of chemical measures and geographic information systems technology. The level of pollution in seven metals is decreasing in the following order: zinc (Zn 128.9 mg/kg) > chromium (Cr 64.1 mg/kg) > lead (Pb 58.4 mg/kg) > arsenic (As 45.3 mg/kg) > copper (Cu 41.9 mg/kg) > nickel (Ni 31.3 mg/kg) > cadmium (Cd 1.5 mg/kg). Trace metal spatial distribution maps established by geographic information system techniques displayed two high-pollution zones around mining sites in the study area. Multivariate statistical analyses were also applied, and the results demonstrated that Cd, As, Pb, Cu and Zn in the soils originated from mining activities, whereas Cr and Ni primarily originated from natural sources. The values of pollution index ranged from 4.79 to 71.59, and the values of modified pollution index ranged from 1.98 to 24.69. Moreover, the potential ecological risk values ranged from 264.0 to 3263.5, which indicated considerable ecological risk to very high ecological risk. The potential ecological risk values and other soil contamination indices showed similar patterns that the high-risk areas were around Dexing Pb/Zn mining site. The surface agricultural soil in study area is heavily to extremely polluted , with Cd that made the most dominant contribution.

Production of tartaric acid using immobilized recominant cis-epoxysuccinate hydrolase.

OBJECTIVE: To investigate the expression and immobilization of recombinant cis-epoxysuccinate hydrolase (ESH), and its application in the biological production of L-(+)-tartaric acid. RESULTS: E. coli BL21 (DE3)/pET11a-ESH (His) was engineered to express recombinant ESH. The enzyme had an activity of 262 U mg-1. The recombinant ESH was immobilized on agarose Ni-IDA matrix with metal ion affinity interaction to improve its thermostability and pH stability. The immobilization efficiency and activity yield were 94 and 95%, respectively. The specific catalytic efficiency of immobilized ESH was 104 mg U-1 h-1 during the continuous enzymatic production process. CONCLUSION: ESH with a histidine tag was immobilized and used for the continuous production of L-(+)-tartaric acid.

Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells.

Oral cancer is one of the most frequent malignant diseases worldwide, and areca nut is a primary carcinogen causing this cancer in Southeast Asia. Previous studies to examine the effects of this carcinogen often used short-term and high-dose treatment of area nut extract as a research model, which do not recapitulate the conditions of patients with long-term and habitual use of this substance. To approach authentic mechanism of areca nut-induced oral carcinogenesis that occurs in human, we established four isogenic sublines of oral cells which were chronic exposed to areca nut extract. Without eliciting cytotoxicity or senescence, these four sublines cells exhibited significant increase in invasive ability, along with epithelial-mesenchymal transition. These cells also showed resistance to chemotherapeutic drug and irradiation, accompanying with the augmentation of ABCG2 protein efflux and increased ROS clearance. Moreover, these sublines possessed the characteristics of cancer stemness, as demonstrated by enriched CD24-/CD44+ and CD133+ sub-populations, enhanced spheroid cell formation, and induced expressions of pluripotent stemness regulators, including Gp96, Grp78, Slug, Sox9, Snail, and Foxc2. These stemness regulators were further shown up-regulations in oral cancer patients with areca nut-chewing habit, and were statistically correlated with CD44 expression, a stemness marker. In conclusion, our findings suggested that areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells. This study may further contribute to clinical applications in disease prevention, risk assessment or molecular therapeutics on areca nut- associated diseases.

Down-regulation of miR-326 is associated with poor prognosis and promotes growth and metastasis by targeting FSCN1 in gastric cancer.

BACKGROUND: MicroRNAs (miRNAs) have been documented as playing important roles in diverse biological processes including tumorigenesis. However, the function and mechanism of miR-326 in gastric cancer are still unknown. The aim of this study is to identify the role of miR-326 in gastric cancer and clarify the regulation of Fascin1 (FSCN1) by miR-326. METHODS: The expression levels of miR-326 were detected in gastric cancer samples and cell lines by real-time PCR. The clinical and prognostic significance of miR-326 in gastric cancer patients were analyzed. Furthermore, the function of miR-326 on tumor cell growth and mobility were explored through MTT, colony formation, Transwell migration and invasion assays in vitro. A miR-326 target was confirmed using luciferase reporter assays, real-time PCR and Western blot. RESULTS: Our study showed that miR-326 expression was decreased in gastric cancer tissues and cell lines, and low expression of miR-326 was associated to clinical stage, tumor depth, lymph node metastasis and distant metastasis. In survival analysis, low expression of miR-326 was a poor independent prognostic factor for gastric cancer patients. Gain-of-function and loss-of-function studies showed that miR-326 served as a tumor suppressor regulating gastric cancer cells growth, migration and invasion. Furthermore, we identified FSCN1 as the functional target of miR-326 by directly targeting the 3'-UTR of FSCN1. CONCLUSIONS: Our study demonstrated that miR-326 overexpression was a poor prognostic marker for gastric cancer patients, and miR-326 served as a tumor suppressor in gastric cancer via directly regulating FSCN1.

Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review.

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

[Expression of osteopontin splice variant and its clinical significance in gastric cancer].

OBJECTIVE: To investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer. METHODS: The expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: The expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer. CONCLUSIONS: One of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

Chronic toxicity thresholds for sediment-associated Benzo[a]pyrene in the Midge (Chironomus dilutus).

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in aquatic ecosystems and have been shown to be one of the causes of sediment toxicity to benthic invertebrates. Benzo[a]pyrene (BaP) was selected as a representative for the PAH family of compounds for developing chronic sediment toxicity thresholds for Chironomus dilutus. Life-cycle toxicity testing was initiated using newly hatched midge larvae and terminated until hatch of the second generation. Median lethal concentrations were 92.5 ± 19.6 and 56.9 ± 1.76 µg/g organic carbon (OC) after exposing midges to sediment-associated BaP for 20 days (before pupation) and 43 days (end of test), respectively. Sublethal toxicity was described as 5 and 50 % effect concentrations (EC5 and EC50), and these were 6.63 ± 0.82 and 41.1 ± 1.61 µg/g OC for growth reduction at 20 days, respectively. Impairments of emergence and reproduction of C. dilutus were also assessed at the end of the testing, and the EC5 and EC50 values were 3.41 ± 0.53 and 26.9 ± 1.43 µg/g OC for emergence and 2.18 ± 0.34 and 13.4 ± 1.13 µg/g OC for reproduction, respectively. In addition, bioavailability-based chronic toxicity thresholds were also established using Tenax-extractable BaP concentrations. Although more environmentally relevant, data regarding chronic toxicity are less available than those regarding acute toxicity. Therefore, establishing numeric chronic toxicity thresholds for sediment-associated BaP with the consideration of the bioavailability would improve the accuracy of assessing PAH-related sediment toxicity.

An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice.

Diabetic retinopathy (DR) is a complex and progressive ocular disease characterized by two distinct phases in its pathogenesis. The first phase involves the loss of protection from diabetes-induced damage to the retina, while the second phase centers on the accumulation of this damage. Traditional assays primarily focus on evaluating capillary degeneration, which is indicative of the severity of damage, essentially addressing the second phase of DR. However, they only indirectly provide insights into whether the protective mechanisms of the retinal vasculature have been compromised. To address this limitation, a novel approach was developed to directly assess the retina's protective mechanisms - specifically, its resilience against diabetes-induced insults like oxidative stress and cytokines. This protection assay, although initially designed for diabetic retinopathy, holds the potential for broader applications in both physiological and pathological contexts. In summary, understanding the pathogenesis of diabetic retinopathy involves recognizing the dual phases of protection loss and damage accumulation, with this innovative protection assay offering a valuable tool for research and potentially extending to other medical conditions.

Resilience to diabetic retinopathy.

Chronic elevation of blood glucose at first causes relatively minor changes to the neural and vascular components of the retina. As the duration of hyperglycemia persists, the nature and extent of damage increases and becomes readily detectable. While this second, overt manifestation of diabetic retinopathy (DR) has been studied extensively, what prevents maximal damage from the very start of hyperglycemia remains largely unexplored. Recent studies indicate that diabetes (DM) engages mitochondria-based defense during the retinopathy-resistant phase, and thereby enables the retina to remain healthy in the face of hyperglycemia. Such resilience is transient, and its deterioration results in progressive accumulation of retinal damage. The concepts that co-emerge with these discoveries set the stage for novel intellectual and therapeutic opportunities within the DR field. Identification of biomarkers and mediators of protection from DM-mediated damage will enable development of resilience-based therapies that will indefinitely delay the onset of DR.

Biomarkers of heart failure: advances in omics studies.

Heart failure is a complex syndrome characterized by progressive circulatory dysfunction, manifesting clinically as pulmonary and systemic venous congestion, alongside inadequate tissue perfusion. The early identification of HF, particularly at the mild and moderate stages (stages B and C), presents a clinical challenge due to the overlap of signs, symptoms, and natriuretic peptide levels with other cardiorespiratory pathologies. Nonetheless, early detection coupled with timely pharmacological intervention is imperative for enhancing patient outcomes. Advances in high-throughput omics technologies have enabled researchers to analyze patient-derived biofluids and tissues, discovering biomarkers that are sensitive and specific for HF diagnosis. Due to the diversity of HF etiology, it is insufficient to study the diagnostic data of early HF using a single omics technology. This study reviewed the latest progress in genomics, transcriptomics, proteomics, and metabolomics for the identification of HF biomarkers, offering novel insights into the early clinical diagnosis of HF. However, the validity of biomarkers depends on the disease status, intervention time, genetic diversity and comorbidities of the subjects. Moreover, biomarkers lack generalizability in different clinical settings. Hence, it is imperative to conduct multi-center, large-scale and standardized clinical trials to enhance the diagnostic accuracy and utility of HF biomarkers.

Multidimensional sleep health and diabetic retinopathy: Systematic review and meta-analysis.

Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for diabetes and poor glycemic control. Recent studies have suggested associations between poor sleep health/OSA and DR. Furthermore, there have been suggestions of melatonin dysregulation in the context of DR. We conducted a systematic review and meta-analysis exploring the associations between multidimensional sleep health (duration, satisfaction, efficiency, timing/regularity and alertness), OSA and melatonin with DR. Forty-two studies were included. Long, but not short sleep, was significantly associated with DR, OR 1.41 (95%CI 1.21, 1.64). Poor sleep satisfaction was also significantly associated with DR, OR 2.04 (1.41, 2.94). Sleep efficiency and alertness were not associated with DR, while the evidence on timing/regularity was scant. Having OSA was significantly associated with having DR, OR 1.34 (1.07, 1.69). Further, those with DR had significantly lower melatonin/melatonin metabolite levels than those without DR, standardized mean difference -0.94 (-1.44, -0.44). We explored whether treating OSA with continuous positive airway pressure (CPAP) led to improvement in DR (five studies). The results were mixed among studies, but potential benefits were observed in some. This review highlights the association between poor multidimensional sleep health and DR.

Tumor necrosis factor-α 238 G/A polymorphism and gastric cancer risk: a meta-analysis.

Though many studies were performed to assess the association between tumor necrosis factor-α (TNF-α) 238 G/A polymorphism and gastric cancer risk, there were no conclusive findings. A meta-analysis of previous published studies was performed to get a comprehensive assessment of the association between TNF-α 238 G/A polymorphisms and gastric cancer. The pooled odds ratios (ORs) and 95% confidence intervals (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 7,795 participants were finally included into this meta-analysis. Overall, there was an obvious association between TNF-α 238 G/A polymorphism and increased risk of gastric cancer (A vs. G: OR = 1.32, 95% CI 1.02-1.72, P = 0.036; GA vs. GG: OR = 1.32, 95% CI 1.01-1.72, P = 0.042; and AA/GA vs. GG: OR = 1.34, 95% CI 1.02-1.76, P = 0.036). Subgroup analysis by ethnicity showed the statistically significant association between TNF-α 238 G/A polymorphism and gastric cancer was limited to Asian populations (A vs. G: OR = 1.59, 95% CI 1.29-1.97, P < 0.001; GA vs. GG: OR = 1.63, 95% CI 1.29-2.04, P < 0.001; and AA/GA vs. GG: OR = 1.64, 95%CI 1.31-2.05, P < 0.001), and there was no obvious association in Caucasians. In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of gastric cancer, especially in Asians.

Case report: Hematoporphyrin injection (HpD) photodynamic therapy for the treatment of groin extramammary Paget's disease in an elderly male patient.

Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) is a modality for cancer treatment, particularly suitable for challenging sites or elderly patients who can benefit from its minimally invasive and selective nature. We report a case of groin extramammary Paget's disease (EMPD) in a male patient with a lesion located in the right mons pubis. The patient was deemed unsuitable for surgical treatment due to his advanced age, underlying health conditions, extensive rash area, and the specific location of the groin lesion. He opted for hematoporphyrin photodynamic therapy instead of traditional wide local excision. The tumors were successfully treated, with no recurrence observed during the follow-up period. We suggest that hematoporphyrin photodynamic therapy may be an effective alternative to conventional surgery for the treatment of extramammary Paget's disease.

Tripartite motif containing 59 mediates protective anti-oxidative effects in intestinal injury through Nrf2 signaling.

Elevated evidence has reported the important role of oxidative stress injury and inflammatory response in the progression of colitis. Tumor Suppressor TSBF1, TRIM59, is a ubiquitin E3 ligase and mediates immune response. However, the underlying molecular function of TRIM59 on regulation of colitis is still not understood. In the current study, we identify the TRIM59 as a critical and novel endogenous suppressor of kelch-like ECH-associated protein 1 (KEAP1), and we also determine that TRIM59 is a KEAP1-interacting partner protein that catalyses its ubiquitination and degradation in intestinal epithelial cells (IEC). Moreover, IEC-specific loss of the Trim59 disrupts colon metabolic homeostasis, accompanied by intestinal oxidative stress injury, elevated endogenous reactive oxygen species (ROS) production and pro-inflammatory cytokines release, significantly promotes acute or chronic colitis progression. Conversely, transgenic mice with Trim59 overexpression by adeno-associated virus (AAV)-induced Trim59 gene therapeutics mitigates colitis in acute or chronic colitis rodent models and in vitro experiments. Mechanistically, in response to onset of colitis, TRIM59 directly interacts with KEAP1 and promotes ubiquitin-proteasome degradation, thus results in NRF2 activation and its downstream cascade anti-oxidative stress-related pathway activation, which facilitates anti-oxidant defense and reduces tissue damage. All the findings elucidated the potential role of TRIM59 in colitis progression by mediating KEAP1 deactivation and degradation, and could be considered as a therapeutic target for the treatment of such disease.