MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

[Effect of methylprednisolone on neurological behavior and the BDNF and NMDA receptor expression after traumatic spinal cord injury in rats].

OBJECTIVE: To study the effect of methylprednisolone on spinal cord injury rats' neural behavior and the expression of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartic acid (NMDA). METHODS: To establish rat model of spinal cord injury (SCI), the rats were randomly divided into sham operation group, SCI group and methylprednisolone group (n = 16 in each group). Eight rats were used for the behavioral assessment and BDNF measurement,the other eight animals was for the NMDA receptor test in each group. Within 8 h spinal cord contusion, methylprednisolone (50 mg/kg) was injected for methylprednisolone group, then after that the intramuscular injection of methylprednisolone was per day reduction in 10 mg/kg, till 5 days. By using immunohistochemical staining, the distribution of BDNF in the spinal cord and positive cell localization was observed and the number of positive cells were counted. The NMDA receptor affinity (Kd) and maximum binding amount (Bmax) were measured with [3H] MK-801 radioligand method, and the rat hind limb functional was also evaluated with BBB score analysis. RESULTS: Both the number of BDNF positive cells and the BBB score in methylprednisolone group was significant higher than that of SCI group; While increased receptor affinity (Kd) and decreased Bmax for NMDA receptor in methylprednisolone group was seen less than in SCI group (P < 0.05). CONCLUSION: Methylprednisolone can improve the function of rat hind limb, increase BDNF level and decreased NMDA receptor expression after spinal cord injury.

[Effect of gold belt on the BDNF and NMDA receptor expression and behaviour changes in rats following traumatic spinal cord injury].

OBJECTIVE: To study the effects of gold belt (GB), a Chinese Herbal, on behavioral changes and brain derived neutrophic factor (BDNF) expression and N-methyl-D-aspartic acid (NMDA) receptor level in rats subjected to spinal cord injury (SCI). METHODS: Adult male SD rats were randomly divided into three groups: (1) Sham group; (2) Spinal cord injury group (SCI group); (3) Spinal cord injury followed with gold belt treatment (gold belt 50 mg/(kg x d), intragastric gavage once daily for 7 days) group (GB group). The Basso, Beattie and Bresnahan (BBB) locomotor scale method was performed to evaluate the hindlimb motor function in the days 0, 3, 10 and 28. After 13 days, 8 rats in each group were treated with 1% sodium pentobarbital (30 mg/kg), myoloid tissue in T10 position was taken and stored in liquid nitrogen to detect NMDA receptor affinity and maximum binding amount (Bmax) with radioligand binding assay. After 28 days, rats were sacrificed and the spinal cords were harvested for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of the spinal cord. RESULTS: After spinal cord contusion, GB resulted in a significant increase on the number of BDNF positive neurons compared with traumatic group, and increased BBB score and decreased NMDA receptor were also found in GB group. Whereas decreased BDNF expression, NMDA receptor affininty (Kd) were observed in traumatic injury group. CONCLUSION: The gold belt treatment could effectively improve motor function, increase expression of BDNF, reduce the level of NMDA receptors in SCI rats. These data suggested that the gold belt played a role in the neuroplasticity after spinal cord injury.

Chinese integrative medicine: translation toward person-centered and balanced medicine.

Chinese integrative medicine (CIM) focuses on the integration of conventional medicine (biomedicine) with Chinese medicine (CM). Although the CIM field has witnessed several advancements, the definition and classification of CIM is not quite clear, given that an independent theory system has not yet been established in this field. Therefore, future research and studies should focus on the following objectives: (1) emphasizing CM features, (2) improving CIM positioning, and (3) establishing CIM standards. These concerted efforts will help CIM be at par with international standards and criteria. With the development of CIM, the world will embrace a new medical system providing person-centered treatment with a balanced medicine approach.

[Randomized controlled trial of integrated traditional Chinese and western medicine treatment for posthepatitic cirrhotic ascites: a systematic review].

OBJECTIVE: To research domestic general situation and quality of the clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine. METHODS: Chose CNKI, VIP, Wang fang and CBM as data source and searched the literature of the clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine which published officially from January 1980 to January 2010 and which received a Jaded score of 2 or greater to do a systematic evaluation, including the description of subjects, study design and methods, therapeutic efficacy and statistical methods. RESULTS: 136 articles in all met inclusion criteria and 58 articles which received a Jaded score of 2 or greater did this research. The main problems of domestic posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine in 30 years included: randomized controlled trial design was unreasonable, lack of blinding, lack of standardized criteria, the sample size was small and lack of specific estimation methods, lack of compliance, case off and withdraw, ignoring adverse reaction and the research of life quality. CONCLUSION: The clinical treatment of posthepatitic cirrhotic ascites in Integrated Traditional Chinese and Western Medicine have a "personalized" and "diversity" character and the methods and standards of clinical research need to be improved.

[DUOX2 gene mutation in patients with congenital goiter with hypothyroidism].

OBJECTIVE: To identify DUOX2 gene mutation in patients with congenital goiter with hypothyroidism. METHOD: Five patients who had transit congenital hypothyroidism with goiter were enrolled. The exons of DUOX2 gene were amplified and sequenced. RESULT: A heterozygous missense mutation C1329T in the exon 10 of the DUOX2 gene was found in one patient, predicted to result in a Tryptophan to Arginine substitution at codon 376. However no mutation was detected in the other patients. CONCLUSION: p.Arg376Trp mutation in DUOX2 was found in newborns of congenital hypothyroidism. The alleles frequency of this mutation may contribute to the function loss of congenital hypothyroidism.

Proteomic analysis of chronic restraint stress-induced Gan (肝)-stagnancy syndrome in rats.

OBJECTIVE: To analyze the proteomic characteristics of Gan (肝)-stagnancy syndrome (GSS) by seeking the differential protein in blood and tissues of GSS model rats. METHODS: GSS model rats were established by chronic restraint stress, keeping rats in restrain chamber for 6 h every day for 21 successive days. Their blood and liver samples were collected at the end of experiment for differential protein detection with methods of isoelectrofocusing and polyacrylamide SDS-PAGE, silver staining, and scanning. The gel images were analyzed with Imagemaster 2D Elite software, and the excavated differential protein spots were identified with matrix assistant laser resolving TOF mass spectrometry, Western blot, ELISA, and RT-PCR, respectively. RESULTS: A method for isolating the protein in blood serum and tissues by two-dimensional gel electrophoresis was established and optimized. Six serum proteins and three liver proteins that differentially expressed were identified. The down-regulated differential proteins in serum of GSS model rats were serum albumin precursor, beta 1 globin, antibody against muscle acetylcholine receptor, Ig lambda-2 C region, and transthyretin (TTR), and those in liver tissue were aryl sulfotransferase, enoyl-CoA hydratase, and TTR. TTR down-regulation was found in both serum and liver. Preliminary biological information analysis showed that these differential proteins involved in immune, neuroendocrine, nutrition, and substance metabolism. CONCLUSION: Proteomic analysis of differential proteins showed that TTR, aryl sulfotransferase, and enoyl-CoA hydratase expressions are downregulated in the GSS model rats, suggesting that the susceptibility of cancer could be enhanced by chronic stress.

[Protective effects of Hongbeiyegen against immunological liver injury in mice].

OBJECTIVE: To investigate the protective effects of Hongbeiyegen (HBYG) against immunological liver injury induced by bacille Calmette-Guerin (BCG) and lipopolysaccharide (LPS). METHODS: Immunological liver injury was induced in rats by BCG and LPS injected via the tail vein. The liver index, thymus index and spleen index were calculated and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) and liver homogenate contents of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined. RESULTS: HBYG significantly improved the liver index, thymus index and spleen index, and reduced the serum levels of ALT, AST and NO, and as the liver homogenate contents of TNF-alpha and IL-1beta. CONCLUSION: HBYG offers obvious protective effects against immunological injury liver in mice.

[Therapeutic effect of Hongbeiyegen on alcohol-induced rat hepatic fibrosis].

OBJECTIVE: To observe the therapeutic effect of Hongbeiyegen [the root of Alchornea trewioides(Benth.) Muell.-Arg.] on alcohol-induced liver fibrosis (AF) in rats and explore its mechanism. METHODS: In rats with AF, the serum levels of transforming growth factor beta1 (TGFbeta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected along with examination of the changes in serum hyaluronic acid (HA), laminin (LN), procolagen type III (PC III), collagen type IV (C IV), glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) levels. RESULTS: Compared with the control group, Hongbeiyegen could significantly reduce the levels of TGFbeta1, TIMP-1, HA, LN, PC III, CIV, ALT and AST in rats with AF. CONCLUSION: Hongbeiyegen can relieve and ameliorate liver fibrosis possibly by inhibiting the expression of TGFbeta1 and TIMP-1.

[Inhibiting effects of root of Mallotus apelta on duck hepatitis B virus].

OBJECTIVE: To evaluate the inhibiting effects of the root of Mallotus apelta (Lour.) Muell.-Arg. on duck hepatitis B virus (D-HBV) in vivo. METHODS: Forty nestling ducks with congenitally infection of D-HBV detected by PCR were randomly divided into five groups: untreated group, lamivudine-treated group, and high-, medium- and low-dose root of Mallotus apelta-treated groups. The ducks in the lamivudine-treated group were fed lamivudine with a dose of 50 mg/kg once. Ducks in the three-dose Mallotus apelta-treated groups were treated with different doses of decoction of this herbal medicine for 21 days respectively. The serum content of D-HBV DNA was determined by quantitative real-time PCR technique before and 7 days after the treatment, and on the 7th, 14th and 21st day of the treatment. Liver biopsy was also executed before and after the treatment to observe the histopathological changes. RESULTS: Lamivudine showed a rapid inhibiting effect on D-HBV DNA, but this effect didn't last long, and the serum level of D-HBV DNA increased again after treatment. The serum level of D-HBV DNA dropped markedly in the high- and medium-dose Mallotus apelta-treated groups on the 14th and 21st day. Low-dose Mallotus apelta revealed no obvious inhibiting effect on D-HBV. After treatment, the inhibiting effect in the root of Mallotus apelta-treated group continued as compared with that in the untreated group. The histopathological changes of liver tissues showed that the inflammation in the high-dose root of Mallotus apelta-treated group was weakened as compared with that in the lamivudine-treated group. CONCLUSION: The root of Mallotus apelta has therapeutic effect on D-HBV. It can restrain the duplication of D-HBV in vivo. Although this effect is weaker than that of lamivudine, it continues longer. Thus this herbal medicine is an effective, safe and economical drug for hepatitis B.

[Experimental study on effect of baoganning on activity of nuclear transcription factor-kappaB in hepatic stellate cells].

OBJECTIVE: To investigate the effect of Baoganning (BGN) on activity of nuclear transcription factor-kappaB (NF-kappaB) in hepatic stellate cells (HSCs) and its relevant mechanisms. METHODS: Normal Wistar rats were medicated with BGN decoction by gavage for 7 days to prepare BGN drug-serum. The effect of BGN drug-serum on HSC-T6 growth was measured by MTT assay; phosphorylation level of NF-kappaB inhibiting factor IkappaB at different time after BGN stimulation was detected by Western blotting analysis; and the binding level of NF-kappaB with DNA was measured 30 min after drug-serum stimulation with gel shift assay. RESULTS: BGN could significantly inhibit the HSC-T6 growth and quickly supress the phosphorylation of IkappaB, with the effect reached its peak at 30 min and restored to baseline level 6 h after stimulation, and reduce the binding capacity of NF-kappaB with DNA. CONCLUSION: BGN can inhibit phosphorylation of IkappaB, restrain the activity of NF-kappaB and change the binding level of NF-kappaB with DNA.