Chromatin remodeling factor ARID2 suppresses hepatocellular carcinoma metastasis via DNMT1-Snail axis.

Recurrence and metastasis remain the major obstacles to successful treatment of hepatocellular carcinoma (HCC). Chromatin remodeling factor ARID2 is commonly mutated in HCC, indicating its important role in cancer development. However, its role in HCC metastasis is largely elusive. In this study, we find that ARID2 expression is significantly decreased in metastatic HCC tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibits migration and invasion of HCC cells in vitro and metastasis in vivo. Moreover, ARID2 knockout promotes pulmonary metastasis in different HCC mouse models. Mechanistic study reveals that ARID2 represses epithelial-mesenchymal transition (EMT) of HCC cells by recruiting DNMT1 to Snail promoter, which increases promoter methylation and inhibits Snail transcription. In addition, we discover that ARID2 mutants with disrupted C2H2 domain lose the metastasis suppressor function, exhibiting a positive association with HCC metastasis and poor prognosis. In conclusion, our study reveals the metastasis suppressor role as well as the underlying mechanism of ARID2 in HCC and provides a potential therapeutic target for ARID2-deficient HCC.

Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade.

UNLABELLED: Sorafenib is a specific adenosine triphosphate-competitive RAF inhibitor used as a first-line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood. Here, we report that sorafenib treatment can exacerbate disease progression in both patient-derived xenografts and cell line-derived xenografts and that the therapeutic effect of the drug inversely covaries to the ratio of epithelial cell adhesion molecule-positive cells, which may be tumor initiating cells in HCC. The TSC2-AKT cascade mediates this sorafenib resistance. In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of "stemness"-related genes in epithelial cell adhesion molecule-positive cells and enhancement of tumorigenicity. The expression of TSC2 negatively correlated with prognosis in clinical sorafenib therapy. Furthermore, all-trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule-positive cell population enriched by sorafenib, and potentiated the therapeutic effect of sorafenib in the patient-derived xenograft model. CONCLUSION: Our findings suggest that a subtype of HCC is not suitable for sorafenib therapy; this resistance to sorafenib can be predicted by the status of TSC2, and agents inducing differentiation of tumor initiating cells (e.g., all-trans retinoic acid) should improve the prognosis of this subtype of HCC.

ARID2 mitigates hepatic steatosis via promoting the ubiquitination of JAK2.

Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem. However, the complicated pathogenesis of NAFLD contributes to the deficiency of effective clinical treatment. Here, we demonstrated that liver-specific loss of Arid2 induced hepatic steatosis and this progression could be exacerbated by HFD. Mechanistic study revealed that ARID2 repressed JAK2-STAT5-PPARγ signaling pathway by promoting the ubiquitination of JAK2, which was mediated by NEDD4L, a novel E3 ligase for JAK2. ChIP assay revealed that ARID2 recruited CARM1 to increase H3R17me2a level at the NEDD4L promoter and activated the transcription of NEDD4L. Moreover, inhibition of Jak2 by Fedratinib in liver-specific Arid2 knockout mice alleviated HFD-induced hepatic steatosis. Downregulation of ARID2 and the reverse correlation between ARID2 and JAK2 were also observed in clinical samples. Therefore, our study has revealed an important role of ARID2 in the development of NAFLD and provided a potential therapeutic strategy for NAFLD.

PPDPF suppresses the development of hepatocellular carcinoma through TRIM21-mediated ubiquitination of RIPK1.

Pancreatic progenitor cell differentiation and proliferation factor (PPDPF) has been reported to play a role in tumorigenesis. However, its function in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we report that PPDPF is significantly downregulated in HCC and the decreased PPDPF expression indicates poor prognosis. In the dimethylnitrosamine (DEN)-induced HCC mouse model, hepatocyte-specific depletion of Ppdpf promotes hepatocarcinogenesis, and reintroduction of PPDPF into liver-specific Ppdpf knockout (LKO) mice inhibits the accelerated HCC development. Mechanistic study shows that PPDPF regulates nuclear factor κB (NF-κB) signaling through modulation of RIPK1 ubiquitination. PPDPF interacts with RIPK1 and facilitates K63-linked ubiquitination of RIPK1 via recruiting the E3 ligase TRIM21, which catalyzes K63-linked ubiquitination of RIPK1 at K140. In addition, liver-specific overexpression of PPDPF activates NF-κB signaling and attenuates apoptosis and compensatory proliferation in mice, which significantly suppresses HCC development. This work identifies PPDPF as a regulator of NF-κB signaling and provides a potential therapeutic candidate for HCC.

PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic-specific deletion of PPDPF profoundly inhibits tumor development in KRASG12D -driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP-binding sites severely impair the tumor-promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1-PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF-SOS1 axis, and provides a promising therapeutic target for PDAC.

[Effect of manual acupuncture at "Sanyinjiao" (SP6) on spermatogenic cells of mice with oligoasthenospermia induced by microwave radiation].

OBJECTIVE: To observe the effect of acupuncture at "Sanyinjiao" (SP6) on sperm motility, testicular B cell lymphoma/leukelia-2 (Bcl-2), Bcl-2 associated X protein (Bax), and Caspase-3 in mice with oligoasthenospermia induced by microwave radiation, so as to explore its underlying mechanisms in improving oligoasthenospermia. METHODS: Male BALB/C mice were randomly divided into control, model and acupuncture groups(n=6 in each group). The oligoasthenospermia model was established by continuous microwave irradiation with frequency of 2 450 MHz and power density of 40 mW/cm2, 1 h daily for 18 days. At the same time, manual acupuncture was applied to the acupuncture group on bilateral "Sanyinjiao" (SP6) for 30 s, once daily for 18 days. Sperm motility including the percentages of progressive motility (PR), non-progressive motility (NP), and PR + NP sperms was detected by computer-assisted sperm analysis, H.E. staining was used to observe the testicular morphology and Johnson score was calculated, the expression levels of Bcl-2, Bax and Caspase-3 in testis were detected by immunofluorescence. RESULTS: Compared with the control group, the percentages of PR sperms, NP sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly decreased (P<0.05), while the expression levels of Bax and Caspase-3 were increased (P<0.05) in the model group. Compared with the model group, the percentages of PR sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly increased (P<0.05), while the expression levels of Bax and Caspase-3 were decreased (P<0.05) in the acupuncture group. Outcomes of H.E. staining showed that the seminiferous tubules became thinner, spermatogenic cells and sperm decreased or even disappeared, and the supporting cells were partially missing in the model group, which was relatively milder in the acupuncture group. CONCLUSION: Manual acupuncture at SP6 can improve sperm motility in oligoasthenospermia mice induced by microwave radiation, which may be related to its effects in down-regulating the expressions of Bax and Caspase-3, increasing expression of Bcl-2 in the testis.

Targeting USP9X-AMPK Axis in ARID1A-Deficient Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor with high morbidity and mortality. AT-rich interaction domain 1A (ARID1A) accounts for up to 10% of mutations in liver cancer, however, its role in HCC remains controversial, and no targeted therapy has been established. METHODS: The expression of ARID1A in clinical samples was examined by Western blot and immunohistochemical staining. ARID1A was knocked out by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in HCC cell lines, and the effects of glucose deprivation on cell viability, proliferation, and apoptosis were measured. Mass spectrometry analysis was used to find ARID1A-interacting proteins, and the result was verified by co-immunoprecipitation and Glutathione S Transferase (GST) pull-down. The regulation of ARID1A target gene USP9X was investigated by chromatin immunoprecipitation, Glutathione S Transferase (GST) pull-down, luciferase reporter assay, and so forth. Finally, drug treatments were performed to explore the therapeutic potential of the agents targeting ARID1A-deficient HCC in vitro and in vivo. RESULTS: Our study has shown that ARID1A loss protected cells from glucose deprivation-induced cell death. A mechanism study disclosed that AIRD1A recruited histone deacetylase 1 via its C-terminal region DUF3518 to the promoter of USP9X, resulting in down-regulation of USP9X and its target protein kinase AMP-activated catalytic subunit α2 (PRKAA2). ARID1A knockout and a 1989∗ truncation mutant in HCC abolished this effect, increased the levels of H3K9 and H3K27 acetylation at the USP9X promoter, and up-regulated the expression of USP9X and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), which mediated the adaptation of tumor cells to glucose starvation. Compound C dramatically inhibited the growth of ARID1A-deficient tumors and prolongs the survival of tumor-bearing mice. CONCLUSIONS: HCC patients with ARID1A mutation may benefit from synthetic lethal therapy targeting the ubiquitin-specific peptidase 9 X-linked (USP9X)-adenosine 5'-monophosphate-activated protein kinase (AMPK) axis.

Antifungal agent Terbinafine restrains tumor growth in preclinical models of hepatocellular carcinoma via AMPK-mTOR axis.

The prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory due to limited effective treatment options. In this work, we investigated the therapeutic efficacy of Terbinafine for HCC and the underlying mechanism. The influence of Terbinafine on cell growth, 3D spheroid formation, clonogenic survival, and protein synthesis was investigated in human HCC cell lines. Co-immunoprecipitation, immunofluorescence, and other techniques were employed to explore how Terbinafine exerts its anticancer effect. Subcutaneous tumorigenicity assay, orthotopic and patient-derived xenograft (PDX) HCC models were used to evaluate the anticancer effect of Terbinafine monotherapy and the combinatorial treatment with Terbinafine and sorafenib against HCC. The anticancer activity of Terbinafine was Squalene epoxidase (SQLE)-independent. Instead, Terbinafine robustly suppressed the proliferation of HCC cells by inhibiting mTORC1 signaling via activation of AMPK. Terbinafine alone or in combination with sorafenib delayed tumor progression and markedly prolonged the survival of tumor-bearing mice. The synergy between Terbinafine and sorafenib was due to concomitant inhibition of mTORC1 and induction of severe persistent DNA double-strand breaks (DSBs), which led to the delayed proliferation and accelerated cell death. Terbinafine showed promising anticancer efficacy in preclinical models of HCC and may serve as a potential therapeutic strategy for HCC.

Ochratoxin A Induces Steatosis via PPARγ-CD36 Axis.

Ochratoxin A(OTA) is considered to be one of the most important contaminants of food and feed worldwide. The liver is one of key target organs for OTA to exert its toxic effects. Due to current lifestyle and diet, nonalcoholic fatty liver disease (NAFLD) has been the most common liver disease. To examine the potential effect of OTA on hepatic lipid metabolism and NAFLD, C57BL/6 male mice received 1 mg/kg OTA by gavage daily. Compared with controls, OTA increased lipid deposition and TG accumulation in mouse livers. In vitro OTA treatment also promoted lipid droplets accumulation in primary hepatocytes and HepG2 cells. Mechanistically, OTA prevented PPARγ degradation by reducing the interaction between PPARγ and its E3 ligase SIAH2, which led to activation of PPARγ signaling pathway. Furthermore, downregulation or inhibition of CD36, a known of PPARγ, alleviated OTA-induced lipid droplets deposition and TG accumulation. Therefore, OTA induces hepatic steatosis via PPARγ-CD36 axis, suggesting that OTA has an impact on liver lipid metabolism and may contribute to the development of metabolic diseases.

PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD.

Scinderin suppresses cell proliferation and predicts the poor prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains an intractable disease despite numerous advancements made in the available treatments over recent decades. Therefore, investigation of the underlying pathogenesis of HCC is urgently required. Our previous microarray result showed that SCIN was generally downregulated in 23 paired tumor/normal tissues. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed in the present study in order to detect the expression of scinderin (SCIN). Lentivirus-mediated gene delivery was used in order to produce SCIN-manipulated cell lines. MTT and crystal violet assays were performed in order to investigate cell growth, and fluorescence-activated cell sorting analysis was used in order to determine cell cycle distribution. SCIN was downregulated in HCC samples, and low SCIN expression predicted the poor prognosis of patients with HCC. Notably, SCIN may have the potential to serve as an independent risk factor for overall survival (3-year overall survival rate of 28.6 and 10.3% in high SCIN expression and low SCIN expression groups, respectively) and disease-free survival (3-year recurrence rate of 71.4 and 84.6% in high SCIN expression and low SCIN expression groups, respectively) in HCC. SCIN inhibited HCC cell proliferation both in vitro and in subcutaneous tumor formation assay. Furthermore, SCIN decreased the levels of phosphorylated STAT3, thereby downregulating cyclin A1 levels in HCC cells. The results of the present study demonstrate the tumor suppressive role of SCIN in HCC, providing a candidate strategy to treat this disease.

CHML promotes liver cancer metastasis by facilitating Rab14 recycle.

Metastasis-associated recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC), however, the underlying mechanisms remain largely elusive. In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients. CHML promotes migration, invasion and metastasis of HCC cells, in a Rab14-dependent manner. Mechanism study reveals that CHML facilitates constant recycling of Rab14 by escorting Rab14 to the membrane. Furthermore, we identify several metastasis regulators as cargoes carried by Rab14-positive vesicles, including Mucin13 and CD44, which may contribute to metastasis-promoting effects of CHML. Altogether, our data establish CHML as a potential promoter of HCC metastasis, and the CHML-Rab14 axis may be a promising therapeutic target for HCC.

BMP10 suppresses hepatocellular carcinoma progression via PTPRS-STAT3 axis.

Bone morphogenetic protein 10 (BMP10), one member of the BMP family, is involved in various development events. Dysregulation of BMP10 has been observed in several diseases, including hypertensive cardiac hypertrophy, Hirschsprung disease and blood vessel formation. However, its role in liver cancer remains largely unknown. In this study, we reported that BMP10 was significantly downregulated in HCC at both mRNA and protein level. Decreased BMP10 was associated with bigger tumor size, worse TNM stage, earlier recurrence and poorer survival. BMP10 negatively regulated HCC cell proliferation in vitro and in vivo. Mechanism study revealed that BMP10 suppressed tumor cell growth by inhibiting STAT3 signaling. Interestingly, we found that cytoplasmic BMP10 interacted with both receptor protein tyrosine phosphatase sigma (PTPRS) and STAT3, which facilitated dephosphorylation of STAT3 by PTPRS. Altogether, our study has revealed the clinical significance of BMP10 in HCC, and suppression of HCC cell growth by BMP10 via PTPRS-STAT3 axis, providing a potential therapeutic strategy for targeting STAT3 signaling in HCC.

Liver cancer: WISP3 suppresses hepatocellular carcinoma progression by negative regulation of ß-catenin/TCF/LEF signalling.

OBJECTIVES: Wnt1-inducible signalling pathway protein 3 (WISP3/CCN6) belongs to the CCN (CYR61/CTGF/NOV) family of proteins, dysregulation of this family contributed to the tumorigenicity of various tumours. In this study, we need to explore its role in hepatocellular carcinoma that remains largely elusive. MATERIALS AND METHODS: The expression of WISP3/CCN6 was analysed by qRT-PCR and Western blotting. Effects of WISP3 on proliferation and metastasis of HCC cells were examined, respectively, by MTT assay and Boyden Chamber. Roles of WISP3 on HCC tumour growth and metastatic ability in vivo were detected in nude mice. Related mechanism study was confirmed by immunofluorescence and Western blotting. RESULTS: The expression of WISP3 was significantly downregulated in HCC clinical samples and cell lines, and reversely correlated with the tumour size. Forced expression of WISP3 in HCC cells significantly suppressed cell growth and migration in vitro as well as tumour growth and metastatic seeding in vivo. In contrast, downregulation of WISP3 accelerated cell proliferation and migration, and promoted in vivo metastasis. Further study revealed that WISP3 inhibited the translocation of ß-catenin to the nucleus by activating glycogen synthase kinase-3ß (GSK3ß). Moreover, constitutively active ß-catenin blocked the suppressive effects of WISP3 on HCC. CONCLUSIONS: Our study showed that WISP3 suppressed the progression of HCC by negative regulation of ß-catenin/TCF/LEF signalling, providing WISP3 as a potential therapeutic candidate for HCC.

[Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions Possibly by Down-regulating Serum TNF-α and Anti-cyclic Citrullinated Peptide Antibody Levels in Collagen-induced Arthritis Rats].

OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36) and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor-α (TNF-α) and anti-cyclic citrullinated peptide antibody (ACPA) contents in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis (RA)．. METHODS: Thirty-two male Wistar rats were randomized into control, model, medication (Methotrexate) and fire-needling groups (n＝8 in each). The RA model was established by injecting type Ⅱ chicken collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and Freund's incomplete adjuvant (immunization once more) into the subcutaneous tissues of the right foot bottom, back and tail root of rats. Fire-needling was applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60) alternatively for 3 times in each acupoint, once daily for 10 days. For rats of the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was administrated by gavage, once every 5 days, twice together. The rats' right hind ankle diameter was measured before and after the treatment. The X-ray film of the right ankle was taken, and the contents of serum TNF-α and ACPA were assayed by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-α and ACPA were significantly increased in the model group compared to the control group (P<0.05), and X-ray film showed swollen and deformed tarsus joints, and narrowing of the joint space. After the intervention, the ankle diameter, serum TNF-α and ACPA levels were considerably decreased in both medication and fire-needle groups compared with the model group (P<0.05). Meanwhile, the joint swelling and bone deformity became relatively milder. There were no significant differences between the medication and fire-needling groups in the ankle diameter and the contents of serum TNF-α and ACPA (P>0.05). CONCLUSION: Fire-needling stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the inflammatory reactions of hind-ankle joint in CIA rats, which may be related to its effect in down-regulating ACPA and TNF-α levels.

Cilia loss sensitizes cells to transformation by activating the mevalonate pathway.

Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through ß catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by ß-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by KrasG12D , which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.

[Effect of Moxibustion on Serum IL-17 and TNF-α Levels in Collagen-induced Arthritis Rats].

OBJECTIVE: To observe the influence of moxibustion on serum interleukin -17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis. METHODS: A total of 40 male Wistar rats were used in the present study, and 8 rats were randomly selected as a normal control group. The other 32 rats were modeled. The primary immunity emulsion was made with mixed Type Ⅱ chicken collagen and complete Freund's adjuvant, and 0.3 mL emulsion (containing 0.3 mg collagen) was injected equally into left pelma, tail root and the back. Seven days after the primary immune, the same procedure was conducted to induce the secondary immunity, and the emulsion was made with mixed Type Ⅱ chicken collagen and incomplete Freund's adjuvant. The whole course of mo-deling lasted 21 days. And then 24 CIA rats were randomly divided into model group, medication group and moxibustion group (n=8 in each group). For those of the moxibustion group, suspended moxibustion with 20 mm distance above "Zusanli"(ST 36)and "Kunlun" (BL 60) was performed for 20 min/acupoint, once daily, alternately on left and right hind limbs for 10 consecutive days. For those of the medication group, gavage of methotrexate (0.1 mg/100 g) was administrated once every 5 days, and totally two times. Left ankle joint diameter and body weight were detected, and X-ray of left tarsus was observed in each group before and after modeling or after treatment. Serum levels of IL-17 and TNF-α were determined by ELISA kits. RESULTS: After modeling, the left ankle diameter and serum concentrations of IL-17 and TNF-α increased (P<0.05), and the body weight decreased (P<0.05) in the model group compared to the control group, combined with the tarsus soft tissue swelling, joint space narrowing, bone destruction seen from the tarsal X-ray. After intervention, the ankle diameter, the serum IL-17 and TNF-α levels decreased (P<0.05), and the body weight increased (P<0.05) in both medication and moxibustion groups compared to the model group; meanwhile the tarsus soft tissue swelling and the bone deformity turned to be improved. There were no significant differences between the medication group and the moxibustion group in above mentioned indexes (P>0.05). CONCLUSIONS: Moxi-bustion is effective in CIA rats, and the mechanism may be related to the reduction of serum IL-17 and TNF-α levels.

[Effect of Electroacupuncture on Serum TNF-α, IL-1ß and Intercellular adhesion molecule 1 Levels in Rheumatoid Arthritis Rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) on serum TNF-α, IL-1ß and Intercellular adhesion molecule 1 (ICAM-1) levels in rheumatoid arthritis (RA) rats so as to explore its mechanism in relieving RA. METHODS: Eight Wistar rats were used as the normal control group in this study. The RA model was established by injecting mixture solution of incomplete Freund's adjuvant and type II chicken collagen into the left paw. The 24 successful RA rats were randomly divided into model, medication (Prednisolone) and EA groups (n = 8 in each group). EA(2 Hz /100 Hz,1-2 mA)was applied to "Zusanli"(ST 36) and "Kunlun" (BL 60) for 30 min, once daily for 10 days. For rats of the medication group, Prednisolone acetate (0. 1 mL/10 g) was intragastric infused daily. The rats' left ankle diameter was measured before and after the treatment, and the contents of serum TNF-α, IL-1ß and ICAM-1 were assayed by ELISA. RESULTS: In comparison with the normal control group, the rats' ankle diameter, serum TNF-α, IL-1ß and ICAM-1 contents were remarkably increased in the model group (P < 0.05); while compared with the model group, the increased ankle diameter, and serum TNF-α, IL-1ß and ICAM-1 contents were obviously reversed in both medication and EA groups ( P < 0.05), without significant differences between the medication and EA groups (P > 0.05). CONCLUSION: EA intervention is effective in relieving RA rats' inflammatory reactions by down-regulating the levels of serum TNF-α, IL-1ß and ICAM-1.