Clinical significance of mucosal suppressors of cytokine signaling 3 expression in ulcerative colitis

AIM:To investigate the clinical significance of mucosal expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3 in human ulcerative colitis (UC). METHODS:Biopsy specimens for histological analysis and mRNA detection were obtained endoscopically from the rectum of 62 patients with UC (36 men; age 13-76 years). The patients were classified endoscopically according to Matts' grade (grade 1 to 4). Expression of SOCS1 and SOCS3 mRNAs was quantified in samples by competitive reverse transcription-polymerase chain reaction (RT-PCR). GAPDH was used as an internal control for efficiency of RT-PCR and amount of RNA. RESULTS:SOCS3 mRNA expression was significantly higher in inflamed mucosa of UC than in inactive mucosa. The level of expression was well correlated with the degree of both endoscopic and histologic inflammation. Interestingly,among the patients in remission,the group with relatively low expression of SOCS3 showed a higher rate of remission maintenance over a 12-mo period. In contrast,SOCS1 mRNA was expressed in both inflamed and non-inflamed colonic mucosa and was not correlated with the activity of colonic mucosa or prognosis. CONCLUSION:These observations suggest that increased expression of mucosal SOCS3,but not of SOCS1,may play a critical role in the development of the colonic inflammation of UC.

The suppressor of cytokine signalling 2(SOCS2),traumatic brain injury and microglial/macrophage regulation

Traumatic brain injury （TBI） results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration of peripheral macrophages, which phagocytose debris and/or secrete a range of cytokines, chemokines and oth- er factors which modify the injured environment to promote or inhibit repair （Schwartz et al., 2013）. The reactive macro- phages/microglia are broadly divided into two categories.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.

Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure

BACKGROUND:Prior experimentation has shown that loss of the tyrosine kinase(TK) signaling domain of the Ron receptor leads to marked hepatocyte protection in a model of lipopolysaccharideinduced acute liver failure(ALF) in D-galactosamine(GalN)sensitized mice.The aim of this study was to identify the role of Ron in the regulation of hepatic gene expression.METHODS:Microarray analyses were performed on liver RNA isolated sequentially from wild-type(WT) and TK-/mice during the progression of ALF.Gene array data were validated using Western and immunohistochemistry analyses as well as with ex vivo culture systems.RESULTS:At baseline,101 genes were differentially expressed between WT and TK-/-livers,which regulate processes involved in hypoxia,proliferation,apoptosis and metabolism.One hour after ALF induction,WT livers exhibited increased cytokine expression compared to TK-/-livers,and after 4 hours,an induction of suppressor of cytokine signaling(SOCS) genes as well as JAK-STAT pathway activation were prominent in TK-/livers compared to controls.CONCLUSION:Our studies suggest a novel hepato-protective mechanism in Ron TK-/-mice wherein increased and sustained SOCS production and JAK-STAT activation in the hepatocyte may inhibit the destructive proinflammatory milieu and promote survival factors which blunt hepatic death and the ensuing development of ALF.

The role of endotoxin,TNF-α,and IL-6 in inducing the state of growth hormone insensitivity

AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.

Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury,both in vivo and in vitro

Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a day.Zea Longa＇s method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.

Long noncoding RNA HAND2-AS1 re duce d the viability of hepatocellular carcinoma via targeting microRNA-300/SOCS5 axis

Background:Hepatocellular carcinoma(HCC)is one of the most prevalent human cancers with high mortality.Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1(HAND2-AS1)is down-regulated in several cancers including HCC,yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood.Methods:The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR.The protein levels of suppressor of cytokine signaling 5(SOCS5),Bcl-2,Bax and cleaved caspase-3 were determined by Western blot.Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay,respectively.Cell apoptosis was detected using flow cytometry.The interactions between HAND2-AS1 and miR-300,miR-300 and SOCS5 were validated using luciferase reporter assay.Results:HAND2-AS1 was down-regulated in HCC tissues and cell lines,and the expression level of HAND2-AS1 was positively correlated to patient survival.HAND2-AS1 over-expression reduced viability and proliferation in HCC cells.Elevated HAND2-AS1 level induced apoptosis in HCC cells,accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level.We also validated that HAND2-AS1 acted as a sponge of miR-300,and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues.Furthermore,we found that SOCS5 was a downstream target of miR-300.In addition,miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation.miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells.Conclusion:lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.

Expression of SOCS3 throughout liver regeneration is not regulated by DNA methylation

BACKGROUND:While suppressor of cytokine signaling 3(SOCS3) plays a crucial role in suppressing dysplasia and tumorigenesis,it also offers a typical instance of DNA methylation in the regulation of gene transcription,since the promoter region of the SOCS3 gene is rich in CpG islands(CGIs).During liver regeneration initiated by partial hepatectomy,SOCS3 acts as a suppressor to balance the acute-phase response and terminate the regeneration.This study aimed to determine whether the variation of SOCS3 expression throughout liver regeneration is also regulated by its DNA methylation.METHODS:We established a 70% partial hepatectomy mouse model and the animals were sacrificed at indicated times to assess the SOCS3 expression.We performed bisulfite sequencing PCR and DNA sequencing to investigate the detailed cytosine methylation in the SOCS3 gene.RESULTS:Within the promoter sequence,58 CGIs were identified and 30 were found variously methylated before or after operation;however,methylation remained at a very low level.No evidence indicated that the total methylation level or the methylation of any CpG site regularly changed throughout liver regeneration.CONCLUSION:DNA methylation or demethylation seems to be a relatively stable modification of cytosine,but not a dynamic and reversible process to regulate gene transcription in daily and acute pathophysiological events.

Expression of SOCS-3 and Its Methylation in Renal Cancer

The expression level of suppressor of cytokine signaling-3（SOCS-3） in human renal carcinoma and its methylation state were investigated. Reverse transcription-polymerase chain reaction（RT-PCR）, immuocytochemistry, immunohistochemistry and Western blot were used to detect the expression level of SOCS-3, and the methylation of SOCS gene was investigated by methylation specific PCR in the tissues of 15 cases of renal carcinoma. Compared to those of the normal renal cell line and specimens , the expression level of SOCS-3 in renal carcinoma was significantly lower or can’t be detected（P0.01）. And the methylation of SOCS-3 gene in the tissue of renal carcinoma was significantly higher. The expression of SOCS-3 gene is significantly lower in renal carcinoma and the high methylation of the promoter island of SOCS-3 gene is associated with the lower expression of SOCS-3 gene. It may be one of main mechanisms for the development and progress of renal carcinoma.

Expression of suppressor of cytokine signaling 1 in the peripheral blood of patients with idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis （IPF） is a progressive diffuse parenchymal disease with a poor prognosis.A variety of cytokines and chemokines are involved in its pathophysiology.The aim of this study was to evaluate the clinical features in IPF patients with the expression of suppressor of cytokine signaling 1 （SOCS-1）,which acts as a negative regulator of cytokine signaling.Methods IPF patients （n=20） and healthy controls （n=16） were included in this study.The expression of SOCS-1 was analyzed in peripheral blood mononuclear cells （PBMC） of subjects using RT-PCR.Interleukin 4 （IL-4）,transforming growth factor β1 （TGF-β1） and type Ⅰ collagen expression were also analyzed in each individual using enzyme-linked immunosorbent assay （ELISA）.The clinical characteristics of IPF patients were delineated.These results were analyzed by SPSS13.0 statistics software.Results SOCS-1 mRNA expression was significantly decreased in the PBMC of IPF patients compared with healthy controls; serum levels of IL-4 and TGF-β1 were higher in IPF patients.The patients with lower expression of SOCS-1 developed lower percentage of forced vital capacity （FVC%） and DLCO/VA.A patients＇ SOCS-1 mRNA level was negatively correlated with serum levels of IL-4,and negatively correlated with their high-resolution computed tomography （HRCT） scores.Conclusions SOCS-1 mRNA can be detected in PBMC,and it is down-regulated in IPF patients.The expression of SOCS-1 is associated with the severity of IPF patients＇ symptoms,so it might be the predictor of disease severity.SOCS-1 might play an important role in IPF by reducing the expression of the T helper type 2 （Th2） cell-related cytokine IL-4.

Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis

Objective Rheumatoid arthritis(RA)progression is associated with the balance of T-regulatory(Treg)and T-helper 17(Th17)cells,while the role of microRNAs(miRs)in regulating Treg/Th17 cell balance has not been clarified.This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3(SOCS3)axis in the RA mouse model.Methods A mouse model of collagen-induced arthritis(CIA)was established in male DBA/1J mice.Twenty-two days after CIA induction,the mice received daily treatment with moxibustion for 12 times.Pathological scores were assessed according to the levels of synovial hyperplasia.The expression levels of cytokines interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay.The cluster of differentiation 4(CD4+)splenocytes was analyzed by fluorescence-activated cell sorting.The expression levels of RA-related miRs and target genes were subsequently detected,and the target of miR-221 was confirmed by the dual-luciferase reporter assay.Results It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β,IL-6,TNF-α,IFN-γand IL-17,while upregulated the expression level of IL-10.The Treg/Th17 cell balance was regulated by moxibustion treatment.The expression level of miR-221 was suppressed by moxibustion treatment.Furthermore,SOCS3 was found as the direct target of miR-221,which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.Conclusion Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation

AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS： A rat model of fractionated colorectal γ-irradiation （4-Gy fractions, 3 fractions per week） was designed to investigate the effects of cumulative dose on inflammatory mediators （cytokines and chemo- kines） and immune response （Th1/Th2 profile and immunosuppressive mediator IL-10） during acute （early） response and 6 mo after the end of fractionated irradiation （chronic response）. Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS： Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION： Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway

BACKGROUND:Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis.Our previous study showed that microRNA-761(miR-761)is overexpressed in hepatocellular carcinoma(HCC)tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis.The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated.METHODS:Exosomal miR-761 was detected in six cell lines.Cell counting kit-8(CCK-8)and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells.The luciferase reporter assay was used to analyze miR-761 target genes in normal fi broblasts(NFs).The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in the transformation of cancer-associated fi broblasts(CAFs).RESULTS:In this study,we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment.We found that HCC-derived exosomal miR-761 was taken up by NFs.Moreover,HCC exosomes aff ected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2(SOCS2)and the JAK2/STAT3 signaling pathway.CONCLUSIONS:These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs.Our fi ndings may inspire new strategies for HCC prevention and therapy.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly understood.In this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 hours.An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models.Then,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally administrated.The open field test and tail suspension test were used to test animal behavior.Routine methods were used to detect change in inflammatory cells.Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue.Wet/dry weight ratios were used to measure brain water content.Evans blue leakage was used to determine blood-brain barrier integrity.Enzyme-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain tissue.Western blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and aquaporin-4.Our results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of HACE.These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide(LPS)-induced inflammatory response

Although microRNA-155(miR-155)is considered a pro-inflammatory mediator,cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells.In this study,we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide(LPS)stimulation;223 genes were down-regulated and 85 genes were up-regulated,including suppressor of cytokine signaling 1(SOCS1)and transforming growth factor-β-activated kinase 1-binding protein 2(TAB2),two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4(TLR4)signaling pathway.We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation,and as a proinflammatory mediator by down-regulating SOCS1 in the later stage.Meanwhile,overexpression of TAB23'untranslated region(UTR)in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155,which resulted in an elevated expression level of SOCS1 protein.These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.

Effect of Acupuncture-moxibustion on the Expression of IGF-1 and SOCS2 in Colonic Mucosa of Rats with Ulcerative Colitis

Objective： To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I （IGF-I） and suppressor of cytokine signaling-2 （SOCS2） in colonic mucosa of rat models of ulcerative colitis （UC）, and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods： The rats were randomized into a normal control （NC） group, a model control （MC） group, an herb-partitioned moxibustion （HPM） group and an electroacupuncture （EA） group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat＇s colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results： In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced （P〈0.01）, while the expression of IGF-1 had an increase （P〈0.01）, and the expression of SOCS2 was reduced （P〈0.01）. After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased （P〈0.01）, the expression of IGF-1 decreased （P〈0.01）, and the expression of SOCS2 increased （P〈0.01）. Conclusion： The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.