Dietary restriction and fasting alleviate radiation-induced intestinal injury by inhibiting cGAS/STING activation.

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8+ cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses.

Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota.

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.

Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin.

Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-ß1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.

Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis.

Lactoferrin (Lf) has been shown to benefit cognitive function in several animal models. To elucidate the underlying mechanisms, male C57BL/6J mice were randomly divided into the control (CON), Western-style diets (WD), lactoferrin (Lf), and Lf + antibiotics (AB) groups. The Lf group was intragastrically administered with Lf, and the Lf + AB group additionally drank a solution with antibiotics. After 16 weeks of intervention, Lf improved the cognitive function as indicated by behavioral tests. Lf also increased the length and curvature of postsynaptic density and upregulated the related protein expression, suggesting improved hippocampal neurons and synapses. Lf suppressed microglia activation and proliferation as revealed by immunofluorescence analysis. Lf decreased the serum levels of pro-inflammatory cytokines and downregulated their protein expressions in the hippocampus region. Lf also inhibited the activation of NF-κB/NLRP3 inflammasomes in the hippocampus. Meanwhile, Lf upregulated the expression of tight junction proteins, and increased the abundance of Bacteroidetes at phylum and Roseburia at genus, which are beneficial for gut barrier and cognitive function. The antibiotics eliminated the effects of long-term Lf intervention on cognitive impairment in the Lf + AB group, suggesting that gut microbiota participated in Lf action. Short-term Lf intervention (2 weeks) prevented WD-induced gut microbiota alteration without inducing behavioral changes, supporting the timing sequence of gut microbiota to the brain. Thus, Lf intervention alleviated cognitive impairment by inhibiting microglial activation and neuroinflammation through the microbiome-gut-brain axis.

Glomerular filtration rate estimated by differing measures and risk of all-cause mortality among Chinese individuals without or with diabetes: A nationwide prospective study.

BACKGROUND: Whether estimated glomerular filtration rates (eGFRs) by differing biomarkers are differentially associated with mortality or whether the associations differ by diabetes status remains unclear, especially in Chinese population. METHODS: We included 6995 participants without diabetes (mean age: 60.4 years) and 1543 with diabetes (mean age: 61.8 years). Each eGFR measure was divided into normal (≥90 mL/min/1.73 m2 ), modestly declined (60 to <90 mL/min/1.73 m2 ), and chronic kidney disease (CKD) (<60 mL/min/1.73 m2 ) groups. Cox proportional hazards models were used to estimate hazard ratio (HR) of all-cause mortality associated with each eGFR. RESULTS: Over a follow-up of 7 years, 677 and 215 deaths occurred among individuals without or with diabetes, respectively. Among those without diabetes, all measures of modestly declined eGFR were not associated with mortality, whereas CKD defined by eGFR cystatin C (eGFRcys) and eGFR creatinine (eGFRcr)-cys (HRs were 1.71 and 1.55, respectively) but not by eGFRcr were associated with higher risk of mortality. Among diabetes, all measures of modestly declined eGFR (HRs: 1.53, 1.56, and 2.09 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) and CKD (HRs: 2.57, 2.99, and 3.92 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) were associated with higher risk of mortality. Regardless of diabetes status, an addition of eGFRcys or eGFRcr-cys to traditional risk factors lead to a larger improvement in the prediction of all-cause mortality risk than adding eGFRcr. CONCLUSIONS: The association of eGFR with mortality risk appeared to be varied by its measures and by diabetes status among middle-aged and older Chinese, which needs to be considered in clinical practice.

Obesity and cancer: Mouse models used in studies.

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.

Correction to: Amelioration of radiation­induced liver damage by p-coumaric acid in mice.

[This corrects the article DOI: 10.1007/s10068-022-01118-8.].

Treatment of a large area perioral viral herpes infection following noninvasive ventilation: A case report.

BACKGROUND: Alphaherpesvirus belongs to the Herpesviridae family and has large, monopartite double-stranded linear DNA. It mainly infects the skin, mucosa, and nerves, and can affect various hosts, including humans and other animals. Here, we present a case of a patient seen by the gastroenterology department at our hospital who experienced an oral and perioral herpes infection following treatment with a ventilator. The patient was treated with oral and topical antiviral drugs, furacilin, oral and topical antibiotics, local epinephrine injection, topical thrombin powder, and nutritional and supportive care. A wet wound healing approach was also implemented with good response. CASE SUMMARY: A 73-year-old woman presented to the hospital with a chief complaint of "abdominal pain for 3 d with dizziness for 2 d." She was admitted to the intensive care unit for septic shock and spontaneous peritonitis secondary to cirrhosis and was given antiinflammatory and symptomatic supportive treatment. A ventilator was used to assist breathing for acute respiratory distress syndrome, which developed during her admission. A large area of herpes infection appeared in the perioral region 2 d following noninvasive ventilation. The patient was transferred to the gastroenterology department, at which time she had a body temperature of 37.8 C and a respiratory rate of 18/min. The patient's consciousness was intact, and she no longer had abdominal pain or distension, chest tightness, or asthma. At this point, the infected perioral region changed in appearance and was now accompanied by local bleeding with crusting of blood at the wounds. The surface area of the wounds measured approximately 10 cm × 10 cm. A cluster blisters appeared on the patient's right neck, and ulcers developed in her mouth. On a subjective numerical pain scale, the patient reported a pain level of 2. Overall, her diagnoses other than the oral and perioral herpes infection included: (1) Septic shock; (2) spontaneous peritonitis; (3) abdominal infection; (4) decompensated cirrhosis; and (5) hypoproteinemia. Dermatology was consulted regarding the treatment of the patient's wounds; they suggested treatment with oral antiviral drugs, an intramuscular injection of nutritious nerve drugs, and the application of topical penciclovir and mupirocin around the lips. Stomatology was also consulted and suggested the use of nitrocilin in a local wet application around the lips. CONCLUSION: Through multidisciplinary consultation, the patient's oral and perioral herpes infection was successfully treated with the following combined approach: (1) Application of topical antviral and antibiotic treatments; (2) keeping the wound moist with a wet wound healing strategy; (3) systemic use of oral antiviral drugs; and (4) symptomatic and nutritional supportive care. The patient was discharged from the hospital after successful wound healing.

Protective effect and mechanism of lactoferrin combined with hypoxia against high-fat diet induced obesity and non-alcoholic fatty liver disease in mice.

Obesity is a global epidemic, it can induce glucose and lipid metabolism disorder and non-alcoholic fatty liver disease (NAFLD). This study explored a new way to control weight and improve fatty liver, namely, living in hypoxia environment and supplement with lactoferrin (Lf). Sixty male C57BL/6J mice were divided into six groups, namely, control, hypoxia, high-fat diet, hypoxia + high-fat diet, hypoxia + high-fat diet + low dose Lf intervention, and hypoxia + high-fat diet + high-dose Lf intervention. Mice in the hypoxia treatment groups were treated with approximately 11.5 % oxygen for 6 h every day for 8 weeks. Results showed that interventions combining Lf and hypoxia treatments showed better effect against obesity and NAFLD than hypoxia treatment alone. The interventions controlled weight gain in mice, improved glucolipid metabolism in mice. The combination intervention reduced cholesterol absorption by reducing the level of hydrophobic bile acids, and elevating the level of hydrophilic bile acids. Gut microbiota analysis revealed that the combination intervention considerably elevated short chain fatty acids (SCFAs)-producing bacteria level, and reduced the Desulfovibrionaceae_unclassified level. Thus, Lf combined with hypoxia intervention effectively prevents obesity and NAFLD by restoring gut microbiota composition and bile acid profile.

Effect of 3,3'-diselenodipropionic Acid on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

3,3'-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention because of its antioxidant properties and safety. Its protective effect against dextran sodium sulfate (DSS)-induced mouse ulcerative colitis (UC) and the role of T helper 17 (Th17) cell proliferation were investigated. Fifty C57BL/6 male mice were randomly assigned to one of five groups: control (Con), DSePA, DSS, low-dose DSePA (LSe), and high-dose DSePA (HSe). Mice in the DSS, LSe, and HSe groups drank 2% DSS to induce UC, and received normal saline, 1 and 2 mg/mL DSePA solution by intraperitoneal injection, respectively. The DSePA group only received 2 mg/mL DSePA solution. After 5 weeks, DSS challenge induced UC in the mice, which manifested as decreased body weight, shortened colon length, the loss of goblet cells, activated proliferating cells, and multiple signs of intestinal lesions by histological observation, all of which were reversed to varying degrees by DSePA administration. DSS upregulated the colonic protein expression of the macrophage marker F4/80 and proinflammatory cytokines (IL-1ß, IL-6, and TNFα), whereas DSePA administration downregulated the expression of these factors. DSS upregulated the mRNA expression of retinoic acid receptor-related orphan receptor γt (RORγt, mainly expressed in Th17 cells), IL-17A, and IL-17F and the levels of IL-17A and IL-17F in the colon, whereas DSePA administration decreased them. No difference was observed between the Con group and the DSePA group without DSS induction. Thus, DSePA administration ameliorated DSS-induced UC by regulating Th17-cell proliferation and the secretion of proinflammatory cytokines.

Ectopic Thymic Carcinoma Located on The Dorsal Side of The Thyroid Gland.

Migration of the embryonic thymus is thought to be the basis for the formation of ectopic thymic tumors. Thymic ectopy may be a result of the abnormal migration of the third or fourth branchial cleft to the anterior mediastinum during weeks 5-6 of embryonic development. However, ectopic thymic carcinoma has highly nonspecific histologic features and occurs in variable and unpredictable locations making it difficult to diagnose. However, the clinical diagnosis and treatment should not overlook the possibility of ectopic thymic tumors. Here, we report a case of ectopic thymic carcinoma diagnosed as thyroid cancer before surgery occurring in a location consistent with current assumptions. Furthermore, we briefly review the literature on ectopic thymic carcinoma and discuss current diagnostic and treatment approaches.

Osseous Metaplasia and Ectopic Bone Formation in a Patient With Hashimoto's Thyroiditis.

Thyroid nodules are frequently accompanied by degenerative changes, such as hemorrhage, cholesterol crystallization, fibrous tissue deposition, or filling with fat. Although calcification is also a common phenomenon, osteogenesis, characterized by mature bone formation, is very rare. Here, we describe a case of Hashimoto's thyroiditis with osseous metaplasia and ectopic bone formation case and discuss its possible causes.

Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation.

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto's thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto's thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto's thyroiditis.

Lactoferrin Prevents Chronic Alcoholic Injury by Regulating Redox Balance and Lipid Metabolism in Female C57BL/6J Mice.

This study aimed to investigate the preventive effects of lactoferrin (Lf) on chronic alcoholic liver injury (ALI) in female mice. Female C57BL/6J mice were randomly divided into four groups: control group (CON), ethanol administration group (EtOH), low-dose Lf treatment group (LLf), and high-dose Lf group (HLf). In the last three groups, chronic ALI was induced by administering 20% ethanol ad libitum for 12 weeks. Mice in the CON and EtOH groups were fed with AIN-93G diet. Meanwhile, 0.4% and 4% casein in the AIN-93G diet were replaced by Lf as the diets of LLf and HLf groups, respectively. HLf significantly reduced hepatic triglyceride content and improved pathological morphology. HLf could inhibit cytochrome P450 2E1 overexpression and promote alcohol dehydrogenase-1 expression. HLf activated protein kinase B and AMP-activated protein kinase (AMPK), as well as upregulating nuclear-factor-erythroid-2-related factor-2 expression to elevate hepatic antioxidative enzyme activities. AMPK activation also benefited hepatic lipid metabolism. Meanwhile, HLf had no obvious beneficial effects on gut microbiota. In summary, Lf could alleviate chronic ALI in female mice, which was associated with redox balance and lipid metabolism regulation.

Amelioration of radiation-induced liver damage by p-coumaric acid in mice.

Radiation-induced liver damage (RILD) is a spiny problem in radiotherapy or other circumstances that exposure to radiation. The need for radioprotective agent is increasing to protect liver tissue. This study aimed to explore the hepatoprotective effect of p-coumaric acid (CA) against RILD. C57BL/6 male mice were exposed to 4 Gy irradiation and administrated with CA for 4 days starting on the same day of irradiation. Mice were sacrificed to obtain blood and liver tissues on day 3.5 or 14 post irradiation, respectively. The blood and liver tissues were collected. As compared with the only irradiated group, CA supplementation improved liver morphology, decreased serum alanine aminotransferase and aspartate aminotransferase, inhibited BCL2-associated X (BAX) protein expression, and improved the mice hematopoietic function. CA at the dose of 100 mg/kg body weight showed better effect compared to the other doses. Thus, CA might possess potential to protect against RILD.

[Combination of Ecological Ditch and Bioretention Pond to Control Rural Runoff Pollution].

Ecological ditches and bioretention ponds have received widespread attention and application due to their runoff pollution control capabilities and ecological benefits. However, a single ecological ditch or bioretention pond often has problems, such as unstable nitrogen and phosphorus removal and substrate clogging in rural runoff pollution control. Thus, we connected the two facilities in a series to construct a combined system, using the ecological ditch to pretreat, therefore reducing the pollution load of the bioretention pond and mitigating substrate clogging. At the same time, the submerged area was set and an external natural carrier carbon source was added in the bioretention pond to improve the nitrogen removal. The effects of the carrier carbon source, rainfall intensity, and alternating wet and dry conditions on the control of rural runoff pollution by the combined system were explored. The results showed that adding straw and sawdust as carrier carbon sources could increase the TN removal of the bioretention pond by 19.9% and 20.4%, respectively. When the simulated rainfall intensity increased from light rain to heavy rain, the removal efficiencies of COD, NH4+-N, TN, and TP in the combined system with external carbon source decreased by 17.0%, 16.8%, 20.4%, and 17.2% on average, respectively. The contribution of the ecological ditch to the removal of the four pollutants decreased by 16.3%, 13.0%, 24.2%, and 22.1% on average. Alternating dry and wet operation can improve the pollutant removal. Compared with continuous inflow, the average TN removal of the sawdust group increased by 12.3% after three weeks of drought. The results of microbial community analysis showed that the α-diversity of the bioretention pond in the sawdust group and the straw group was higher than that in control group. The abundance of Thiobacillus was significantly higher in the submerged area of bioretention ponds with carbon sources than that in the control group. These research results are expected to provide technical support for the practical application of the combined system.

Bio-electrocatalytic degradation of tetracycline by stainless-steel mesh based molybdenum carbide electrode.

In order to treat antibiotic wastewater with high efficiency and low energy consumption, this study proposed the coupling of electrocatalytic degradation and biodegradation, and explored a new modified electrocatalytic material in the coupling system. The stainless-steel mesh based molybdenum carbide (SS-Mo2C) was prepared by a low-cost impregnation method and showed superior electrocatalytic degradation ability for tetracycline (TC) when used as the anode in the electrocatalytic system. The degradation rate of TC with SS-Mo2C anode was 17 times higher than that of stainless-steel (SS) anode, and TC removal efficiency was 77% higher than that of SS anode. The electrocatalytic system prior to the biological reactor was proven to be the optimal coupling method. The external coupling system achieved a significantly higher TC removal (87.0%) than that of the internal coupling system (65.3%) and SS-Mo2C showed an excellent repeatable and stable performance. The fewer and smaller molecular weight intermediates products were observed in bio-electrocatalytic system, especially in the external coupling system. Alpha diversity analysis further confirmed that bio-electrocatalytic system increased the diversity of the microbial community. The stainless-steel mesh based molybdenum carbide (SS-Mo2C), which was prepared by a simple and low-cost impregnation method, significantly improved the electrocatalytic activity of anode, thus contributing to tetracycline removal in the bio-electrocatalytic system, especially in the external coupling system.

Protective effects of epigallocatechin-3-o-gallate combined with organic selenium against transforming growth factor-beta 1-induced fibrosis in LX-2 cells.

In this study, we investigated the protective effects and possible mechanism of epigallocatechin-3-o-gallate (EGCG) combined with organic selenium in transforming growth factor (TGF)-ß1-activated LX-2 cells. After 12 h of starvation, LX-2 cells were treated with 10 ng/ml of recombinant TGF-ß1 and different concentrations of EGCG, L-selenomethionine (L-SeMet), or L-selenomethylcysteine (L-SeMC) for 24 h. We found that 100 and 200 µM EGCG combined with 1 mM L-SeMet or L-SeMC showed a synergistic effect in decreasing the survival rate of activated LX-2 cells. In addition, the combination of 100 mM EGCG and 1 mM L-SeMet or L-SeMC promoted the apoptosis of activated LX-2 cells. Compared with the EGCG treatment group, the combination intervention group had significantly suppressed levels of hepatic stellate cell activation markers including alpha-smooth muscle actin, collagen type I alpha 1, collagen type III alpha 1, 5-hydroxytryptophan (5-HT), and 5-HT receptors 2A and 2B. Moreover, interleukin-10 levels were decreased, while TGF-ß1 levels were increased after TGF-ß1 activation in LX-2 culture medium, whereas the combin1ation intervention reversed this phenomenon. The combination treatment had a more pronounced effect than any single treatment at the same dose. These results demonstrated that the combination of EGCG and organic selenium synergistically improves the TGF-ß1-induced fibrosis of LX-2 cells to some extent by promoting apoptosis and inhibiting cell activation. PRACTICAL APPLICATIONS: Here, we found that the effects of epigallocatechin-3-o-gallate (EGCG) + L-selenomethionine or L-selenomethylcysteine were more pronounced than those of EGCG alone. Future studies should investigate the protective effects of green tea and selenium-enriched green tea against hepatic fibrosis and explore the differences in their molecular mechanisms. The results of this study will be helpful for the development and utilization of selenium-enriched tea for food processing and health supplement production.