Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

The reduced mortality of malignant melanoma at the population level is mainly attributable to treatment advances for the past decade.

BACKGROUND: Cutaneous malignant melanoma (CMM) causes most skin cancer deaths in the United States (US). The mortality has been decreasing in the US population. We hypothesize that this population-level reduction is mainly attributable to the treatment advances, rather than the successful primary and secondary prevention. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we collected the incidence, incidence-based mortality (IBM), and 5-year survival (5-YS) rates of CMM from 1994 to 2019. Trends by stage and sex were examined by joinpoint regression analyses and age-period-cohort analyses. RESULTS: The overall incidence of CMM rose by 1.6% yearly from 1994 to 2006 (95% confidence interval [CI]: 0.9% to 2.2%) and then increased with a numerical trend. And we projected the incidence will continue to increase until 2029. In contrast, the IBM for all CMM has decreased yearly by 2.8% (95% CI: -3.9% to -1.8%) since 2010 after continuously increasing by 3.8% annually (95% CI: 3.2% to 4.4%) from 1996 to 2010. For early-stage (localized and regional) CMM, we found the incidence since 2005 plateaued without further increase, while the incidence for CMM at distant stage continuously increased by 1.4% per year (95% CI: 0.9% to 2.0%). Improvements in 5-YS were observed over the study period for all CMM and were most obvious in distant stage. And significant period effects were noted around the year 2010. CONCLUSION: This study demonstrated improved survival and reduced mortality of CMM at the US population level since 2010, which were consistent with the introduction of novel therapies. Encouraging effects of primary prevention among adolescents in the most recent cohorts were found. However, the plateaued overall incidence and early diagnosis rates indicated that advances in primary and secondary prevention are very much needed to further control the burden of CMM.

Angiotensin II type-2 receptor attenuates liver fibrosis progression by suppressing IRE1α-XBP1 pathway.

The renin-angiotensin system (RAS) has been recognized as a crucial contributor to the development of liver fibrosis, and AT2R, an essential component of RAS, is involved in the progression of liver fibrosis. However, the underlying mechanisms by which AT2R modulates liver fibrosis remain elusive. Here, we report that AT2R was induced to be highly expressed during the progression of liver fibrosis, and the elevated AT2R attenuates liver fibrosis by suppressing IRE1α-XBP1 pathway. In this study, we found that AT2R is not expressed in the no cirrhotic adult liver, but is induced expression during liver fibrosis in both cirrhotic patients and fibrotic mice models. Upregulated AT2R inhibits the activation and proliferation of hepatic stellate cells (HSCs). In addition, our study showed that during liver fibrosis, AT2R deletion increased the dimerization activation of IRE1α and promoted XBP1 splicing, and the spliced XBP1s could promote their transcription by binding to the AT2R promoter and repress the IRE1α-XBP1 axis, forming an AT2R-IRE1α-XBP1 negative feedback loop. Importantly, the combination treatment of an AT2R agonist and an endoplasmic reticulum stress (ER stress) alleviator significantly attenuated liver fibrosis in a mouse model of liver fibrosis. Therefore, we conclude that the AT2R-IRE1α signaling pathway can regulate the progression of liver fibrosis, and AT2R is a new potential therapeutic target for treating liver fibrosis.

Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 µM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

Achieving high carrier separation over Bi4O5I2through Ni doping for improved photocatalytic CO2reduction.

Photocatalytic CO2reduction is considered to be an appealing way of alleviating environmental pollution and energy shortages simultaneously under mild condition. However, the activity is greatly limited by the poor separation of the photogenerated carriers. Ion doping is a feasible strategy to facilitate the charge transfer. In this work, Ni-doped Bi4O5I2photocatalyst is successfully fabricated using a one-pot hydrothermal method. A few doping levels appear in the energy band of Bi4O5I2after Ni doping, which are used as springboards for electrons transition, thus promoting photoexcited electrons and holes separation. As a consequence, a remarkably enhanced yield of CO and CH4(6.2 and 1.9µmol g-1h-1) is obtained over the optimized Bi4O5I2-Ni15, which is approximately 2.1 and 3.8 times superior to pure Bi4O5I2, respectively. This work may serve as a model for the subsequent research of Bi-based photocatalysts to implement high-performance CO2photoreduction.

Analysis of Therapeutic Effect and Influencing Factors of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma.

OBJECTIVES: The current study sought to explore the effects of ultrasound (US)-guided radiofrequency ablation (RFA) on papillary thyroid microcarcinoma (PTMC) and influencing factors. METHODS: PTMC patients were assigned to observation (US-guided RFA) and control (surgical operation) groups. A series of operation-related indexes (operation time, intraoperative bleeding, wound closure time, hospital stay, and expenses), visual analogue scale score, lesion size, and thyroid function-related indexes (thyroid-stimulating hormone [TSH], free triiodothyronine*** [FT3], free thyroxine [FT4]), inflammatory factors, and thyroglobulin antibody (TgAb) were assessed and compared. After a 6-month follow-up period, the complications and recurrence were recorded, in addition to analyses of postoperative recurrence cumulative incidence and evaluation of recurrence risk factors. RESULTS: Operation-related indexes of the observation group were relatively decreased compared with the control group. In addition, the lesion volume in the observation group was lower compared to that in the control group at the 6th month after operation, whereas the volume reduction rate was higher. There were no significant differences in regard to thyroid function-related indexes in the observation group before/after operation. After operation, serum TSH levels and inflammatory factors, and TgAb levels were all diminished, while the FT3 and FT4 levels were both elevated in the observation group relative to the control group, and postoperative recurrence cumulative incidence was lower in the observation group. TSH and TgAb were established as the independent risk factors for recurrence after RFA in PTMC patients. CONCLUSIONS: Our findings highlighted that US-guided RFA exhibits better efficacy, safety, and postoperative recovery and lower recurrence risk for PTMC.

Healthy Diet, Polygenic Risk Score, and Upper Gastrointestinal Cancer Risk: A Prospective Study from UK Biobank.

Dietary and genetic factors are considered to be associated with UGI cancer risk. However, examinations of the effect of healthy diet on UGI cancer risk and the extent to which healthy diet modifies the impact of genetic susceptibility on UGI cancer remains limited. Associations were analyzed through Cox regression of the UK Biobank data (n = 415,589). Healthy diet, based on "healthy diet score," was determined according to fruit, vegetables, grains, fish, and meat consumption. We compared adherence to healthy diet and the risk of UGI cancer. We also constructed a UGI polygenic risk score (UGI-PRS) to assess the combined effect of genetic risk and healthy diet. For the results high adherence to healthy diet reduced 24% UGI cancer risk (HR high-quality diet: 0.76 (0.62-0.93), p = 0.009). A combined effect of high genetic risk and unhealthy diet on UGI cancer risk was observed, with HR reaching 1.60 (1.20-2.13, p = 0.001). Among participants with high genetic risk, the absolute five-year incidence risk of UGI cancer was significantly reduced, from 0.16% to 0.10%, by having a healthy diet. In summary, healthy diet decreased UGI cancer risk, and individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy diet.

4-octyl itaconate improves the viability of D66H cells by regulating the KEAP1-NRF2-GCLC/HO-1 pathway.

As a novel nuclear factor E2-related factor 2 (NRF2) activator, the itaconate has shown significant therapeutic potential for oxidative stress diseases. However, its role in Vohwinkel syndrome in relation to the gap junction protein beta 2 (GJB2) mutation is still unclear. This study aimed at investigating the effect of 4-octyl itaconate (OI) on HaCaT and D66H cells and clarify its potential mechanism in vitro. The optimal concentration and treatment time of OI on HaCaT cells and D66H cells were determined by CCK-8 and LDH experiments. The effect of OI on cell proliferation was detected by EdU staining and FACS analysis of PI, while the apoptosis was evaluated by TUNEL staining and FACS analysis of Annexin V. The ROS staining was performed, and the levels of SOD, MDA, GSH and GSH/GSSG were detected to evaluate the effect of OI on oxidative damage induced by D66H-type mutation. CO-IP, Western blot, immunofluorescence and qPCR analyses were employed to detect the activation of KEAP1-NRF2-GCLC/HO-1 pathway by OI. Finally, sh-NRF2 was used to confirm the activation of this pathway by OI. Results showed that OI could improve the cell viability decreased by GJB2 gene mutation by regulating the balance between cell growth and apoptosis induced by oxidative damage. Furthermore, this alleviation process was regulated by the KEAP1-NRF2-HO-1/GCLC pathway. In conclusion, OI could improve the viability of HaCaT and D66H cells via regulating the KEAP1-NRF2-GCLC/HO-1 pathway, which provided a wide spectrum of potential targets for effective therapeutic treatments of Vohwinkel syndrome in the clinic.

Anxiety, depression, and stress prevalence among college students during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: Since the end of 2019, the coronavirus disease (COVID-19) outbreak rapidly became a pandemic. The psychological state of people during the COVID-19 pandemic has gained interest. Our aim was to study the prevalence of anxiety, depression, and stress in college students during the COVID-19 pandemic. Methods: A systematic search of Medline, Embase, Web of Science, and the Cochrane Library was conducted up to September 20, 2020. Reviewers independently assessed full-text articles according to predefined criteria. Stata14/SE was used to calculate the prevalence and 95% confidence intervals (CIs) of anxiety, depression, and stress among college students from different countries. A random effects model was adopted. The Egger test was used to determine publication bias. Results: A total of 280 references were retrieved, and 28 papers met our inclusion criteria, for a total of 436,799 college students. Thirteen studies involved non-Chinese college students, and 15 studies involved Chinese college students. The prevalence of anxiety, depression, and stress was 29% (95% CI, 19-25%), 37% (95% CI, 32-42%), and 23% (95% CI, 8-39%), respectively. Conclusion: The COVID-19 pandemic has had a negative psychological effect on college students, and the prevalence of anxiety, depression, and stress among Chinese college students is lower than among non-Chinese college students.

Second primary malignancies in cervical cancer and endometrial cancer survivors: a population-based analysis.

BACKGROUND: We evaluated the relative attribution and interactions of treatment and patient-related risk factors for second primary malignancies (SPMs) in cervical and endometrial cancer survivors. METHODS: Stage I-III cervical and endometrial cancer survivors' data from the Surveillance, Epidemiology, and End Results (SEER) registry between January 1988 and December 2015 were analyzed. The standardized incidence ratio (SIR), excess absolute risk (EAR), and corresponding 95% confidence interval (95% CI) values were calculated. Analyses were classified based on proxies of human papillomavirus (HPV), smoking, hormone, and radiotherapy (RT) status. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer survivors had a higher risk for developing potentially HPV and smoking-related SPMs, especially in the RT group (SIRHPV = 3.7, 95% CI: 2.9-4.6; SIRsmoking = 3.2, 95% CI: 2.8-3.6). Second vaginal cancer patients had the highest SIR (23.8, 95% CI: 14.9-36.0). There were strong synergistic interactions between RT and the proxy of smoking (Pinteraction < 0.001), accounting for 36% of potentially smoking-related SPMs in cervical cancer survivors. CONCLUSIONS: RT, HPV, and smoking promote SPMs in cervical cancer to different extents. The SPM burden in cervical cancer survivors could be mostly attributed to smoking and RT and their interactions.

Development of naringenin-O-alkylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC50 values of 0.91 µM and 0.57 µM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aß1-42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aß1-40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu2+-induced Aß1-42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.

Development of naringenin-O-carbamate derivatives as multi-target-directed liagnds for the treatment of Alzheimer's disease.

In this work, a series of naringenin-O-carbamate derivatives was designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD) through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c showed good antioxidant potency (ORAC = 1.0 eq), and it was a reversible huAChE (IC50 = 9.7 µM) inhibitor. In addition, compound 3c significantly inhibited self-induced Aß1-42 aggregation, and it could activate UPS degradation pathway in HT22 cells and clear the aggregated proteins associated with AD. Moreover, compound 3c was a selective metal chelator, and it significantly inhibited and disaggregated Cu2+-mediated Aß1-42 aggregation. Furthermore, compound 3c displayed remarkable neuroprotective effect and anti-inflammatory property. Interestingly, compound 3c displayed good hepatoprotective effect by its antioxidant activity. More importantly, compound 3c demonstrated favourable blood-brain barrier penetration in vitro and drug-like property. Therefore, compound 3c was a promising multifunctional agent for the treatment of AD.

Declining disease burden of HCC in the United States, 1992-2017: A population-based analysis.

BACKGROUND AND AIMS: The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination. APPROACH AND RESULTS: Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence-based mortality (IBM), and 1-year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute's Joinpoint Regression Program. Age-period-cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990-2019) as a likely validation set. Joinpoint and age-period-cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992-2011 and sharply decreased thereafter by -2.3% annually (95% CI: -3.5% to -1.1%). IBM peaked in 2013 (age-standardized mortality rate: 6.98 per 100,000 person-years) in the US population. IBM started to decrease significantly in 2013 by -3.2%/year (95% CI: -5.4% to -1.1% per year) after a continuous increase of 3.5% annually during 1993-2013. Overall, the 1-year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60-69 and born between 1952-1957 were found. CONCLUSIONS: We found significantly decreased overall HCC-specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.

Electrochemical Synthesis of Cyclic Diaryl Phosphinamides via Intramolecular sp2 C-H Phosphinamidation.

We developed an oxidant- and transition-metal-free approach to construct six-membered cyclic phosphinamides via an intramolecular electrochemical C-H phosphinamidation process. With nBu4NBr as the catalyst and electrolyte, cyclic phosphinamides bearing a variety of functional groups (22 examples) were readily accessed under mild conditions. Meanwhile, this protocol provided an alternative route to organic electroluminescent materials and P-N ligands.

Complete pathological response with diabetic ketoacidosis to the combination of sintilimab and anlotinib in an unresectable hepatocellular carcinoma patient: a case report.

Most hepatocellular carcinoma (HCC) patients have dismal prognoses because they are already in the advanced stage at the time of initial diagnosis and are unable to undergo upfront surgery. Recent studies of immune checkpoint inhibitors (ICIs) and antiangiogenic agents (AAAs) have shown encouraging results for unresectable HCC (uHCC). Here, we report a patient with uHCC who was treated with a combination of anlotinib and sintilimab (sintilimab 200 mg, intravenous glucose tolerance test, q21d and anlotinib 12 mg, orally, d1-14, q21d), an analog of the combination of lenvatinib and pembrolizumab with much lower cost. The patient with recurrent uHCC was downstaged to resectable disease by the combination therapy. After eight cycles of treatment with anlotinib and sintilimab, the patient underwent a second operation. The histology of the resected mass revealed a major and almost complete pathological response. However, this patient was diagnosed with type I diabetes mellitus with ketoacidosis after nearly 10 cycles of combination treatment with anlotinib and sintilimab. Active follow-ups revealed no signs of local recurrence or distant failure. In conclusion, this case report demonstrated that the combination of anlotinib and sintilimab, one of the strategies combining ICIs with AAAs, showed promising efficacy in the treatment of uHCC patients.

Design, synthesis and evaluation of cinnamic acid hybrids as multi-target-directed agents for the treatment of Alzheimer's disease.

Herein, combining 1,2,3,4-tetrahydroisoquinoline and benzylpiperidine groups into cinnamic acid derivatives, a series of novel cinnamic acid hybrids was rationally designed, synthesized and evaluated by the multi-target-directed ligands (MTDLs) strategy. Hybrid 4e was the most promising one among these hybrids with a reversible huBuChE inhibitor (IC50 = 2.5 µM) and good MAO-B inhibition activity (IC50 = 1.3 µM) and antioxidant potency (ORAC = 0.4 eq). Moreover, compound 4e significantly inhibited self-mediated Aß1-42 aggregation (65.2% inhibition rate). Compound 4e exhibited remarkable anti-inflammatory propery and neuroprotective effect. Furthermore, compound 4e displayed favourable blood-brain barrier penetration via parallel artificial membrane permeation assay (PAMPA). The obtained results also revealed that compound 4e significantly improved dyskinesia recovery rate and response efficiency on AD model zebrafish. Further, 4e did not show obvious acute toxicity at dose up to 1500 mg/kg in vivo and improved scopolamine-induced memory impairment. Importantly, compound 4e showed good stability in both artificial gastric fluid and artificial intestinal fluid. Therefore, compound 4e presented a promising multi-targeted active molecule for treating AD.

LINC00641 Inhibits the Development of Cutaneous Squamous Cell Carcinoma By Downregulating miR-424 in A431 Cells.

Background: Cutaneous squamous cell carcinoma (CSCC) is the most deadly disease among nonmelanoma skin cancers. LINC00641 plays a role in various cancers, but its role in CSCC has not been reported so far. Methods and Materials: The expression of LINC00641 and miR-424 in cells was detected by RT-qPCR. CCK-8 and colony formation assay were used to detect the proliferation of cells. Western blot was used to detect the expression levels of proliferation-, invasion-, and migration-related proteins. Wound Healing and Transwell experiments detected the ability of cell invasion and migration. In animal experiments, a tumor-bearing model was established in nude mice, and tumor volume was measured and photographed. The expression levels of proliferation-, invasion-, and migration-related proteins were detected by western blot. Results: The expression of LINC00641 was significantly decreased in CSCC cell lines. The overexpression of LINC00641 at the cellular level inhibited the proliferation and migration of CSCC cell line A431 by downregulating the expression of miR-424. The overexpression of LINC00641 in animals inhibited the tumor volume of nude mice by downregulating the expression of miR-424 to inhibit the expression of proliferation- and migration-related proteins. Conclusion: LINC00641 inhibits the development of CSCC by downregulating miR-424.

Development of genistein-O-alkylamines derivatives as multifunctional agents for the treatment of Alzheimer's disease.

The multi-target-directed ligands have been regarded as the promising multifunctional agents for the treatment of Alzheimer's disease (AD). Based on our previous work, a series of genistein-O-alkylamines derivatives was developed to further explore the structure-activity-relationship. The results showed that compound 7d indicated reversible and highly selective hAChE inhibitory activity with IC50 value of 0.53 µM. Compound 7d also displayed good antioxidant activity (ORAC = 1.1 eq.), promising neuroprotective effect and selective metal chelation property. Moreover, compound 7d significantly inhibited self-induced, hAChE-induced and Cu2+-induced Aß aggregation with 39.8%, 42.1% and 74.1%, respectively, and disaggregated Cu2+-induced Aß1-42 aggregation (67.3%). In addition, compound 7d was a potential autophagy inducer and improved the levels of GPX4 protein. Furthermore, compound 7d presented good blood-brain-barrier permeability in vitro. More importantly, compound 7d did not show any acute toxicity at doses of up to 1000 mg/kg and presented good precognitive effect on scopolamine-induced memory impairment. Therefore, compound 7d was a promising multifunctional agent for the development of anti-AD drugs.

Inhibition of C3a/C3aR Axis in Diverse Stages of Ulcerative Colitis Affected the Prognosis of UC by Modulating the Pyroptosis and Expression of Caspase-11.

Ulcerative colitis (UC) is a serious digestive system disease. Furthermore, the activation of C3a/C3aR axis promoted the expression of caspase-11. And higher levels of caspase-11 could induce the pyroptosis and inflammation of cells. However, some studies suggested that caspase-11 could promote and suppress the inflammation during the development of UC. In addition, whether C3a/C3aR axis could affect the development of UC by modulating the expression of caspase-11 is unclear. We established the UC rat model in this study. Next, the C3aR inhibitor was used to treat these rats at diverse stages of UC. Next, the HE staining was performed to detect the intestinal damage. ELISA was performed to reveal the expression of IL-6 and TNF-α in different stages of UC. Western blotting was used to detect the expression of caspase-11 and C3aR in different stages of UC. Stimulation of C3aR inhibitor in early stage of UC promoted the expression of C3aR and caspase-11 in later stage of UC. Treatment of C3aR inhibitor in later stage of UC inhibited the expression of C3aR and caspase-11 in later stage of UC. Furthermore, application of C3aR inhibitor in early stage of UC aggravates the damage of colon tissue and enhanced the secretion of TNF-α and IL-6 in the later stage of UC. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and suppressed the production of TNF-α and IL-6 in the later stage of UC. Application of C3aR inhibitor in early stage of UC induced the poor prognosis of UC by upregulating the expression of caspase-11. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and lead to the favorable prognosis of UC by inhibiting the expression of caspase-11.