Baicalein alleviates intrahepatic cholestasis by regulating bile acid metabolism via an FXR-dependent manner.

Cholestasis is characterized by impaired bile secretion and flow, leading to the accumulation of toxic bile acids in the liver, further causing inflammatory reaction, fibrosis, and ultimately liver transplantation. Although first-line clinical agents such as Ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) are available, serious side effects still exist. Therefore, pharmacologic treatment of cholestatic liver disease remains challenging. Here, we used a murine model of cholestasis treated with or without intraperitoneal injection of baicalein and found that baicalein could attenuate 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammatory response, ductular reaction, liver fibrosis, and bile acid metabolism disorders. Furthermore, the therapeutic effect of baicalein was hampered in the presence of Guggulsterone (GS), an Farnesoid X receptor (FXR) antagonist. These results indicated that baicalein alleviated DDC diet-induced cholestatic liver injury in an FXR-dependent manner.

Docosahexaenoic and Eicosapentaenoic Acids Promote the Accumulation of Browning-Related Myokines via Calcium Signaling in Insulin-Resistant Mice.

BACKGROUND: Myokines have a prominent effect on improving insulin resistance (IR) by inducing browning of white adipose tissue (WAT). Although docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) play roles in improving IR and stimulating browning, whether they mediate myokines directly remains unknown. OBJECTIVE: This study aims to investigate the effects of DHA and EPA on browning-related myokines under IR and clarify the mechanism via Ca2+ signaling. METHODS: The expression and secretion levels of myokines in IR mice and IR myotubes were detected after DHA/EPA treatment. The crosstalk between myotubes and adipocytes was evaluated through a method in which IR adipocytes were treated with the culture medium supernatant of myotubes treated with DHA/EPA. The expression of browning markers in the WAT of IR mice and adipocytes was determined. A calcium chelator was used to determine whether DHA and EPA regulate myokine production through a calcium ion-dependent pathway. RESULTS: In vivo experiments: 3:1 and 1:3 DHA/EPA promoted the mRNA levels of Irisin, IL-6, IL-15, and FGF21 in skeletal muscle, stimulated WAT browning, reduced lipid accumulation; 3:1 DHA/EPA upregulated the serum concentration of Irisin; 1:3 DHA/EPA upregulated the serum concentrations of Irisin, IL-6, and FGF21. In vitro experiments: the levels of Irisin and IL-6 in C2C12 myotubes and their medium supernatant were significantly elevated in the 3:1 and 1:3 groups and the upregulation of browning markers and reduction in fat accumulation were observed in adipocytes treated with the medium supernatant of C2C12 myotubes in the 3:1 and 1:3 groups. However, the above phenomena disappeared when Ca2+ signaling was inhibited. CONCLUSIONS: Treatment with DHA and EPA at composition ratios of 3:1 and 1:3 induces browning of WAT in IR mice, which is likely related to the promotion of the accumulation of myokines, especially Irisin and IL-6, via Ca2+ signaling.

The therapeutic potential of exosomes derived from different cell sources in liver diseases.

Exosomes are small nanovesicles with a size of approximately 40-120 nm that are secreted from cells. They are involved in the regulation of cell homeostasis and mediate intercellular communication. In addition, they carry proteins, nucleic acids, and lipids that regulate the biological activity of receptor cells. Recent studies have shown that exosomes perform important functions in liver diseases. This review will focus on liver diseases (drug-induced liver injury, hepatic ischemia-reperfusion injury, liver fibrosis, acute liver failure, and hepatocellular carcinoma) and summarize the therapeutic potential of exosomes from different cell sources in liver disease.

CTRP4 acts as an anti-inflammatory factor in macrophages and protects against endotoxic shock.

Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS-induced endotoxemia and cecal ligation and puncture (CLP)-induced sepsis, we investigated the effects of C1q/TNF-related protein 4(CTRP4) on septic lethality and sepsis-induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4-expressing macrophages as the key cell type inhibiting LPS-induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.

miR-194 inhibits liver cancer stem cell expansion by regulating RAC1 pathway.

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients.

Applied anatomy of small branches of the portal vein in transverse groove of hepatic hilum.

PURPOSE: The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum. METHODS: According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as "Short hepatic portal veins (SHPVs)". SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured. RESULTS: There were 181 SHPVs in 30 liver specimens, including 46% (83/181) from the left portal vein, 31% (56/181) from the bifurcation, and 23% (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22% (40/181) supplied for segment IV, 9% (17/181) for segment V, 4% (7/181) for segment VI, 23% (41/181) for segment VII, and 42% (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3-12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm. CONCLUSIONS: SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

"Wrapping the gastroduodenal artery stump" during pancreatoduodenectomy reduced the stump hemorrhage incidence after operation.

OBJECTIVE: After pancreaticoduodenectomy (PD), the postoperative gastroduodenal artery stump (GDAS) hemorrhage is one of the most serious complications. The purpose of this study is to determine whether wrapping the GDAS during PD could decrease the postoperative GDAS hemorrhage incidence. METHODS: A retrospective review involving 280 patients who underwent PD from 2005 to 2012 was performed. Wrapping the GDAS during PD was defined as "Wrapping the GDAS using the teres hepatis ligamentum during PD". A total of 140 patients accepted the "wrapping" procedure (wrapping group). The other 140 patients didn't apply the procedure (non-wrapping group). Age, sex, preoperative data, estimated intraoperative blood loss, postoperative complications, pathologic parameters and hospitalization time were compared between two groups. RESULTS: There were no significant differences in patient characteristics between two groups. After wrapping, the incidence of postoperative GDAS bleeding decreased significantly (1/140 vs. 9/140, P=0.01). The rates of the other complications (such as intra-abdominal infection pancreatic fistula, billiary fistula, gastrointestinal bleeding, et al.) showed no significant differences. CONCLUSIONS: Wrapping the GDAS during PD significantly reduced the postoperative GDAS hemorrhage incidence. And the "wrapping" had no obvious influence on other complications.

Risk factors of intra-abdominal bacterial infection after liver transplantation in patients with hepatocellular carcinoma.

OBJECTIVE: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). METHODS: A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system (SPSS) software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. RESULTS: A series of 13 patients (13/82, 15.9%) had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin (HGB) <90 g/L] and postoperative abdominal hemorrhage (72 hours >400 mL), with the odds ratios at 8.121 (95% CI, 1.417 to 46.550, P=0.019) and 5.911 (95% CI, 1.112 to 31.432, P=0.037). CONCLUSIONS: Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.

Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo.

Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA-MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells.

Different ratios of DHA/EPA reverses insulin resistance by improving adipocyte dysfunction and lipid disorders in HFD-induced IR mice.

Objective: Insulin resistance (IR) is linked to the development of diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVDs). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fish oils (FOs) were used to investigate their potential in high-fat diet (HFD)-induced IR mice under different ratios. Methods: A total of 84 male C57BL/6J (6 weeks old) mice were fed with HFD containing 45% kcal from fat for 16 weeks to establish the IR model. The IR mice were then fed with HFD or HFD + 4% DHA/EPA with different ratios (3 : 1, 1.5 : 1, 1 : 1, 1 : 1.5, 1 : 3, respectively) for another 12 weeks. During the experiment, the CON group (n = 12) was set to feed with a basic diet containing 10% kcal from fat. Results: HFD feeding for 16 weeks reduced insulin sensitivity and accelerated hypertrophy of white adipose tissue (WAT). Different ratios of DHA/EPA except for 1 : 1 decreased the HOMA-IR index, average area of adipocytes, and serum MDA, but increased the protein expression of PI3K. All ratios of DHA/EPA increased the protein expression of IRS-1, GLUT4, and adiponectin. Moreover, dietary DHA/EPA changed serum fatty acid (FA) composition by increasing the serum concentration of n-3 PUFAs. DHA/EPA supplements also improved serum lipid profiles (TG/TC/LDL-c/HDL-c, FFA) and reduced the hepatic steatosis area. Conclusions: The results indicate that an appropriate higher ratio of DHA (1.5 : 1) in DHA/EPA supplementation is recommended for IR prevention.

Early control of short hepatic portal veins in isolated or combined hepatic caudate lobectomy.

BACKGROUND: Caudate lobectomy has long been considered technically difficult. This study aimed to elaborate the significance of early control of short hepatic portal veins (SHPVs) in isolated hepatic caudate lobectomy or in hepatic caudate lobectomy combined with major partial hepatectomy, and to describe the anatomical characteristics of SHPVs. METHODS: The data of 117 patients who underwent either isolated or combined caudate lobectomy by the same team of surgeons from 2005 to 2009 were retrospectively analyzed. From 2005 to 2007 (group A, n=55), we carried out early control of short hepatic veins (SHVs) only; from 2008 to 2009 (group B, n=62), we carried out early control of both SHVs and SHPVs. The two groups were compared to evaluate which surgical procedure was better. A detailed anatomical study was then carried out on the last 25 consecutive patients in group B to study the number and distribution of SHPVs during surgery. RESULTS: Patients in group B had less intra-operative blood loss, less impairment of liver function, shorter postoperative hospital stay, fewer postoperative complications and required less blood transfusion (P<0.05). The number of SHPVs in the 25 patients was 183, with 7.3+/-2.7 per patient. The diameters of SHPVs were 1 to 4 mm. On average, 3.4 SHPVs/patient came from the left portal vein, 2.2 from the bifurcation, 1.4 from the right portal vein, and 0.3 from the main portal vein. On average, 3.3 SHPVs/patient supplied segment I of the liver, 0.4 for segment II, 2.1 for segment IV, 1.4 for segment V and 0.1 for segment VI. CONCLUSION: Early control of SHPVs in isolated or combined hepatic caudate lobectomy may be a useful method to decrease surgical risk and improve postoperative recovery.

PARK7 deficiency inhibits fatty acid ß-oxidation via PTEN to delay liver regeneration after hepatectomy.

BACKGROUND & AIMS: Transient regeneration-associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid ß-oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism-associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high-fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknown METHODS: Park7 knockout (Park7-/- ), hepatocyte-specific Park7 knockout (Park7△hep ) and hepatocyte-specific Park7-Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx) RESULTS: Increased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx. Park7-/- and Park7△hep mice showed delayed liver regeneration and enhanced TRAS after PHx. PPARa, a key regulator of ß-oxidation, and carnitine palmitoyltransferase 1a (CPT1a), a rate-limiting enzyme of ß-oxidation, had substantially decreased expression in the regenerating liver of Park7△hep mice. Increased phosphatase and tensin homolog (PTEN) expression was observed in the liver of Park7△hep mice, which might contribute to delayed liver regeneration in these mice because genomic depletion or pharmacological inhibition of PTEN restored the delayed liver regeneration by reversing the downregulation of PPARa and CPT1a and in turn accelerating the utilization of TRAS in the regenerating liver of Park7△hep mice CONCLUSION: Park7/Dj1 is a novel regulator of PTEN-dependent fatty acid ß-oxidation, and increasing Park7 expression might be a promising strategy to promote liver regeneration.

Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis.

Energy metabolism reprogramming has been implicated in tumorigenesis and development. Key metabolism enzyme Aldolase A (ALDOA) has been shown to be highly expressed and involved in various kinds of cancers including hepatocellular carcinoma. In this study, we found that ALDOA was highly expressed in clinical intrahepatic cholangiocarcinoma (ICC) tissues, and its high expression was negatively correlated with overall survival (OS) and recurrence-free survival (RFS) in ICC patients. Knockdown of ALDOA expression significantly inhibited the proliferation and migration of ICC both in vitro and in vivo, while highly-expressed ALDOA in ICC cells promoted the proliferation and migration of ICC cells. By applying ALDOA inhibitor and metabolic mass spectrometry tests, we demonstrated that ALDOA modulated the biological characteristics and metabolic level of ICC cells depending on its enzymatic activity. In summary, ALDOA promotes ICC proliferation and migration by enhancing ICC cells glycolysis. Blocking enzymatic activity of ALDOA provides a strategy to inhibit ICC.

Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation.

AIM: to determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population. METHODS: twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib. RESULTS: the median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. CONCLUSION: Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.

Transcriptomic analyses reveal the molecular mechanisms of schisandrin B alleviates CCl4-induced liver fibrosis in rats by RNA-sequencing.

Liver fibrosis is a progression of chronic liver disease with lacks effective therapies at present. Schisandrin B (Sch B), a bioactive compound extracted from the traditional Chinese medicine Schisandra chinensis, was reported to benefit liver diseases. This study aimed to investigate the therapeutic effects and molecular mechanisms of Sch B against CCl4-induced liver fibrosis in rats. RNA sequencing and transcriptome analysis were performed collaboratively, including analysis of differential gene expression, gene ontology (GO) analysis, pathway analysis and pathway-act-network analysis. The results demonstrated that Sch B effectively alleviated CCl4-induced liver damage and fibrosis in rats, as evidenced by improved liver function and decreased extracellular matrix deposition. Furthermore, 4440 (1878 up-regulated, 2562 down-regulated) genes in the model group versus (vs) normal group, 4243 (2584 up-regulated, 1659 down-regulated) genes in Sch B-treated group vs model group were identified as differentially expressed genes (DEGs). Subsequently, GO analysis revealed that DEGs were mainly enriched in metabolism, oxidation-reduction, endoplasmic reticulum stress and apoptosis-related biological processes. Pathway analysis suggested that Sch B up-regulated cytochrome P450 drug metabolism, PPAR signaling pathways, and down-regulated glutathione metabolism pathways. In addition, the regulatory patterns of Sch B on key genes and pathways were also confirmed. In conclusion, our study demonstrated Sch B alleviated CCl4-induced liver fibrosis by multiple modulatory mechanisms, which provide new clues for further pharmacological study of Sch B.

CCL20 is overexpressed in hepatocellular carcinoma with bile duct tumor thrombus and correlates negatively with surgical outcome.

There is not yet a consensus regarding prognosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) versus without bile duct tumor thrombus. Chemokine (C-C motif) ligand 20 (CCL20) plays critical roles in the progress of many types of tumor. But the clinicopathological and prognostic value of this marker in HCC with BDTT is unceratin. In this study, we reported that the overall survival (OS) and disease-free survival (DFS) in HCC with BDTT were significantly shorter than in those without BDTT (P<0.05). CCL20 was expressed at a significantly higher level in bile duct tumor thrombus by real-time PCR, western blot, and immunohistochemistry. Patients with high CCL20 expression levels had a poor prognosis. Multivariate survival analysis indicated that CCL20 was an independent prognostic factor for OS. The presence of bile duct tumor thrombus indicateda poor prognosis in HCC patients, but was not a surgical contraindication. CCL20 was associated with tumor progression and high CCL20 expression was correlated with worse surgical outcomes in HCC with BDTT. Inhibition of CCL20 expression might offer novel promising molecular targets for treatment.

Prognostic importance of bile duct invasion in surgical resection with curative intent for hepatocellular carcinoma using PSM analysis.

There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.

Small molecule metabolite biomarkers for hepatocellular carcinoma with bile duct tumor thrombus diagnosis.

Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP, ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are more accurate and less destructive, are urgently needed. In this paper, we analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and EHCC patients and normal people using untargeted GC-MS, and identified 21 metabolites that show different levels among different samples. Using targeted UHPLC-QQQ-MS analysis, we found that several metabolites are significantly changed. ROC curve analysis revealed two metabolites, L-citrulline and D-aspartic acid, as potential biomarkers that can distinguish BDTT from other bile duct diseases.

Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice.

Inflammatory bowel disease (IBD) is an important factor in the induction of colon cancer, but its mechanism is unclear. Colitis and colitis-associated colorectal cancer (CAC) models induced using both dextran sulfate sodium (DSS) and the azoxymethane/DSS protocol were established in wild-type (WT) and CTRP4 transgenic (CTRP4-tg) C57BL6/J mice. Body weight, stool consistency and the presence of blood in the stool were analyzed; tumor quantity, size and histological characteristics were analyzed during the development of CAC. The CTRP4-tg mice exhibited significantly reduced colitis and developed far fewer macroscopic tumors; these tumors were smaller in size, and a majority of the colon tumors in these mice were restricted to the superficial mucosa. Tumors of lower grades were observed in the CTRP4-tg mice. Interleukin-6 was markedly downregulated in the CTRP4-tg mice during CAC tumorigenesis. The phosphorylation of ERK, signal transducer and activator of transcription 3 and Akt in the colon and the proliferation of intestinal epithelial cells were decreased in the CTRP4-tg mice. The injection of recombinant CTRP4 protein significantly reduced the colitis symptoms of the WT mice. CTRP4 plays an important role in inflammation and inflammation-associated colon tumorigenesis, and our research may provide a novel method for the treatment of IBD and CAC.