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author:("Yu, xianfeng")
1.  webSDA: a web server to simulate macromolecular diffusional association 
Nucleic Acids Research  2015;43(Web Server issue):W220-W224.
Macromolecular interactions play a crucial role in biological systems. Simulation of diffusional association (SDA) is a software for carrying out Brownian dynamics simulations that can be used to study the interactions between two or more biological macromolecules. webSDA allows users to run Brownian dynamics simulations with SDA to study bimolecular association and encounter complex formation, to compute association rate constants, and to investigate macromolecular crowding using atomically detailed macromolecular structures. webSDA facilitates and automates the use of the SDA software, and offers user-friendly visualization of results. webSDA currently has three modules: ‘SDA docking’ to generate structures of the diffusional encounter complexes of two macromolecules, ‘SDA association’ to calculate bimolecular diffusional association rate constants, and ‘SDA multiple molecules’ to simulate the diffusive motion of hundreds of macromolecules. webSDA is freely available to all users and there is no login requirement. webSDA is available at
PMCID: PMC4489311  PMID: 25883142
2.  Simvastatin ameliorates low-dose streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model 
The present study aims to study the possible renal protective effect of simvastatin in the development and progression of type 2 diabetic nephropathy. A rat model of T2DN was induced by high-fat diet together with single low-dose of streptozotocin. The diabetic rats were either given treatment or vehicle control for 13 weeks to develop nephropathy. At the end of treatment, parameters of renal function were determined. Kidney samples were collected for histological studies and generated homogenates for biochemical analysis. In T2DN rats, severe hyperglycemia was developed, FBG were markedly elevated. Diabetes induced significant alterations in renal structure, such as severe reduction of glomerular tufts, increase in Bowman’s spaces, thickening of GBM. In addition, and SCr, UAER and BUN are elevated, accompanied with reduction in UCr and CCr, indicating obvious renal failure. On the other hand, endogenous antioxidants SOD, GSH-Px were reduced, whereas MDA was increased. However, treatment of T2DN rats with simvastatin restored renal changes in different aspects. Our results showed that STZ-induced T2DN could be attenuated by simvastatin. The renoprotective effects of simvastatin was indicated by improvements in kidney function parameters, and was attributed by its lipid-lowering effect as well as its anti-oxidative stress, anti-inflammatory properties without having noticeable influence on glycemic control. Simvastatin ameliorates low-dose Streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model.
PMCID: PMC4483801  PMID: 26131264
Simvastatin; oxidative stress; type 2 diabetic nephropathy; rat
3.  Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29 
The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain cancers. In addition to this Cosmc mutation-induced expression, the Tn antigen is also expressed in such cell lines as Jurkat T, LSC and LS174T. Whether the Cosmc mutation is present in the colon cancer cell line HT-29 is still unclear. Here, we isolate HT-29-Tn+ cells from HT-29 cells derived from a female colon cancer patient. These HT-29-Tn+ cells show a loss of the Cosmc gene coding sequence (CDS) leading to an absence of T-synthase activity and Tn antigen expression. Additionally, almost no methylation of Cosmc CpG islands was detected in HT-29-Tn+ as well as in HT-29-Tn- and Tn- tumor cells from male patients. In contrast, the methylation frequency of CpG island of Cosmc in normal female cells was ~50%. Only one active allele of Cosmc existed in HT-29-Tn+ and HT-29-Tn- cells as based upon detection of SNP sites. These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn+ cells can be related to the absence of CDS in Cosmc active alleles, while an inactive allele deletion of Cosmc in HT-29 cells has no influence on Cosmc function.
PMCID: PMC4440074  PMID: 26045765
Tn antigen; Cosmc; T-synthase; colon cancer; CpG methylation
4.  The prognostic value of miR-34a expression in completely resected gastric cancer: tumor recurrence and overall survival 
The prognosis of gastric cancer is mainly linked to tumor recurrence. MicroRNA-34a (miR-34a) is a direct transcriptional target of p53 and links tumor suppressor function and the oncogenic pathways in some cancers. However, the role of miR-34a in predicting prognosis of gastric cancer has not been fully elucidated. In this study, we aimed to investigate the expression level of miR-34a and its prognostic value in gastric cancer. A total of 137 consecutive gastric cancer patients who underwent gastrectomy with D2 lymph node dissection were included in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-34a expression in gastric cancer tissues and adjacent normal tissues. The results showed that the levels of miR-34a expression were significantly decreased in the tumor tissues compared with the adjacent normal tissues (P<0.001). Low miR-34a expression level was associated with lymph node involvement (P=0.004), advanced TNM stage (P=0.006), poor tumor differentiation (P=0.024), high tumor recurrence rate (P=0.008), and poor five-year survival (P<0.001). The median time to recurrence and median overall survival time were significantly shorter in patients with low miR-34a levels compared with those with high miR-34a levels (P=0.028 and P=0.021, respectively). Furthermore, when analyzed with a multivariate Cox regression model, a low miR-34a level was significantly correlated with high recurrence rate and poor overall survival. Taken together, our results suggest that downregulation of miR-34a in gastric cancer is associated with high recurrence rate and poor overall survival and that miR-34a may be served as a prognostic marker for gastric cancer.
PMCID: PMC4402859  PMID: 25932212
microRNA-34a; gastric cancer; tumor recurrence; overall survival
5.  Inhibiting CB1 receptors improves lipogenesis in an in vitro non-alcoholic fatty liver disease model 
The endocannabinoids system (ECs) mediated mainly by CB1 and CB2 receptors plays an important role in non-alcoholic fatty liver disease by regulating lipid metabolism. This study is to further investigate the expression of CB1 and CB2 in the fat accumulation liver cells and to identify possible underlying mechanism by detecting the key lipogenesis factors.
Sodium oleate and sodium palmitate were added into the HepG2 cell line for forming fat accumulation liver cell. MTT assay was used to test the cell’s cytotoxicity. The accumulation rate of fat in HepG2 cell was analyzed by the fluorescent staining. The mRNA and protein expression levels of CB1, CB2, SREBP-1c, ChREBP, L-PK, ACC1, FAS, LXRs and RXR were detected by RT-PCR and Western blot before and after the use of the antagonist.
The receptors of CB1 were expressed in HepG2 cells with low levels while in HepG2 fatty liver cells with higher levels (p < 0.05). However, after the application of antagonist, the expressions were significantly decreased (p < 0.05). The expressions of SREBP-1c, ChREBP and LXRs were detectable in HepG2 cells and the expressions were increased in HepG2 fatty liver cells (p < 0.05). After using the antagonists, the expressions of SREBP-1c, ChREBP, LXRs, ACC1 and FAS were significantly decreased (p < 0.05). But L-PK and RXR changed little in two groups (p > 0.05).
Results of the present study demonstrated that CB1 receptors had important pathophysiological effects on the formation of fatty liver. CB1 receptors could be regulated by SREBP-1c, ChREBP and LXRs. Therefore, targeting CB1 receptors for the treatment of NAFLD might have a potential application value.
PMCID: PMC4247673  PMID: 25406988
Endocannabinoids (ECs); Lipogenesis; Nonalcoholic fatty liver disease (NAFLD); Receptor cannabinoid (CB1,CB2)
6.  Ginsenoside-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis in rats 
Ginsenoside-Rb3 (G-Rb3) has been previously demonstrated to attenuate myocardial ischemia-reperfusion injury (MIRI). The aim of the present study was to investigate this further and determine whether G-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis. Adult male Sprague Dawley rats were randomly divided into four groups: Sham, MIRI, G-Rb3 treatment (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The drug or placebo treatment was administered to the rats once a day for three consecutive days, and MIRI was then induced by subjecting the rats to left anterior descending coronary artery ligation for 30 min and reperfusion for 2 h. The results showed that G-Rb3 treatment significantly reduced the number of apoptotic cells in the myocardium and the expression of B-cell lymphoma 2-associated X protein, and increased the expression of B-cell lymphoma 2. The activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-MB in the serum were also reduced significantly by the G-Rb3 treatment. These findings suggest that G-Rb3 inhibits apoptosis in the early stage of MIRI, and attenuates MIRI when the reperfusion continues. G-Rb3 was also shown to significantly reduce the level of malondialdehyde and increase the activity of superoxide dismutase in the myocardium, which suggests that attenuating reactive oxygen species accumulation and oxidative stress may be the major mechanism underlying the anti-apoptotic effects of G-Rb3. The release of inflammatory factors was significantly attenuated by G-Rb3, which may also be associated with its anti-apoptotic effects.
PMCID: PMC4218709  PMID: 25371727
ginsenoside-Rb3; myocardium; ischemia-reperfusion injury; apoptosis
7.  Quality of Life in Patients with Irritable Bowel Syndrome (IBS), Assessed Using the IBS–Quality of Life (IBS-QOL) Measure After 4 and 8 Weeks of Treatment with Mebeverine Hydrochloride or Pinaverium Bromide: Results of an International Prospective Observational Cohort Study in Poland, Egypt, Mexico and China 
Clinical Drug Investigation  2014;34(11):783-793.
Background and Objective
Irritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS–Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide.
This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China).
A total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study.
This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.
PMCID: PMC4210642  PMID: 25258162
8.  Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Pana quinquefolium, on permanent focal cerebral ischemic injury in rats 
Oxidative stress is significant in the pathogenesis of cerebral ischemia. Panax quinquefolium 20(S)-protopanaxadiol saponins (PQDS) have been demonstrated to exhibit a variety of biological effects in the cardiovascular system as a result of their antioxidant properties. However, little is known regarding the effect of PQDS on cerebral ischemia. The purpose of this study was to investigate whether PQDS exhibited protective effects against cerebral ischemia. A model of cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Adult male rats were randomly divided into five groups: Sham, MCAO and PQDS treatment groups at doses of 12.5, 25.0 and 50.0 mg/kg. The effects of PQDS on neurological deficits, cerebral infarct area, brain water content, and the malondialdehyde (MDA) and Ca2+ levels and Na+-K+-ATPase and superoxide dismutase (SOD) activities in the brain tissue were analyzed, and the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in the serum were evaluated. Moreover, the expression of Bcl-2 was analyzed using western blotting. Pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly reduced the neurological deficit score, decreased the infarcted area and decreased the brain water content from 83.09 to 80.27% (P<0.05). In addition, PQDS pretreatment decreased the NOS activity and the NO levels in the serum compared with those in the MCAO group. Furthermore, pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly increased the activities of SOD and Na+-K+-ATPase and decreased the levels of Ca2+ and MDA in the brain tissue (P<0.05) compared with those in the MCAO group. Pretreatment with PQDS (25.0 and 50.0 mg/kg) also increased the protein expression level of Bcl-2 compared with that in the MCAO group. The histopathological results demonstrated the protective effect of PQDS on ischemic injury. The results indicated that PQDS has protective effects against ischemic injury in rats. The mechanism may be associated with the inhibition of oxidative stress and apoptosis.
PMCID: PMC3861457  PMID: 24348784
panax quinquefolium 20(S)-protopanaxadiol saponins; cerebral ischemia; antioxidant; Bcl-2
9.  Beneficial effects of 20(S)-protopanaxadiol on antitumor activity and toxicity of cyclophosphamide in tumor-bearing mice 
20(S)-protopanaxadiol (PPD) is an extract of Panax quinquefolius L. The aim of this study was to investigate the effect of PPD on the antitumor activity and toxicity of cyclophosphamide (CTX) in tumor-bearing mice. C57BL/6 mice bearing Lewis lung carcinoma cells were treated with PPD (50 mg/kg) alone, CTX (20 mg/kg) alone or PPD (50 mg/kg) in combination with CTX (20 mg/kg), respectively. The results showed that PPD alone has no significant antitumor activity but synergistically enhanced the antitumor activity of CTX. PPD significantly increased the peripheral white blood cell count, bone marrow cell count, interleukin-2 and interferon-γ in CTX-treated tumor-bearing mice. The lowered levels of spleen index, splenocyte proliferation and natural killer cell activity in tumor-bearing mice following CTX treatment were also increased by PPD administration. PPD may be a beneficial supplement during CTX chemotherapy for enhancing the antitumor efficacy and reducing the toxicity of CTX.
PMCID: PMC3570184  PMID: 23407364
20(S)-protopanaxadiol; cyclophosphamide; white blood cell count; spleen index
10.  Prevalence and factors associated with nonalcoholic fatty liver disease in shanghai work-units 
BMC Gastroenterology  2012;12:123.
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Asians. However, data on prevalence and factors associated with NAFLD in Asians are lacking. The aim of this study is to investigate the prevalence of NAFLD in Shanghai employees to assess the relationship between NAFLD and age, gender, metabolic risk factors in this studied population.
We selected 7152 employees of Shanghai work-units. Each of them underwent detailed medical history-taking, physical examination, laboratory assessments and abdominal ultrasonography. The diagnosis of NAFLD was done according to established criteria. Receiver operating characteristics (ROC) curves were applied to detect areas under the ROC curves for each index. Nominal logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD.
About 38.17% employees had NAFLD, more in men than in women. The prevalence of NAFLD increased with increasing age. In both genders, the prevalence of metabolic factors was higher in the NAFLD group. Body max index, waist circumference, weight-to-height ratio, blood pressure, blood glucose, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein and uric acid were found to have a diagnostic value for NAFLD. Body max index is a better index for diagnosing NAFLD. Uric acid is a new diagnosing index not inferior to lipid metabolic factors. Metabolic factors can increase the risk of NAFLD up to 1.5 ~ 3.8 times.
Older age, male gender, metabolic factors such as obesity, abdominal obesity, dyslipidemia, hypertension or type 2 diabetes are risk factors for NAFLD. Prevalence of NAFLD in Shanghai employees is high. Prevention is extremely important. Those achieve the critical point should have early intervention.
PMCID: PMC3499402  PMID: 22978800
Prevalence; Risk factors; Nonalcoholic fatty liver
11.  Coffee consumption and risk of cancers: a meta-analysis of cohort studies 
BMC Cancer  2011;11:96.
Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence.
We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to frequency of coffee intake. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with 1 cup/day increment of coffee consumption.
59 studies, consisting of 40 independent cohorts, met the inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR of cancer was 0.87 (95% CI, 0.82-0.92) for regular coffee drinkers, 0.89 (0.84-0.93) for low to moderate coffee drinkers, and 0.82 (0.74-0.89) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers (RR, 0.97; 95% CI, 0.96-0.98). In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers.
Findings from this meta-analysis suggest that coffee consumption may reduce the total cancer incidence and it also has an inverse association with some type of cancers.
PMCID: PMC3066123  PMID: 21406107
12.  FAT10/Diubiquitin-Like Protein-Deficient Mice Exhibit Minimal Phenotypic Differences 
Molecular and Cellular Biology  2006;26(13):5180-5189.
The FAT10 gene encodes a diubiquitin-like protein containing two tandem head-to-tail ubiquitin-like domains. There is a high degree of similarity between murine and human FAT10 sequences at both the mRNA and protein levels. In various cell lines, FAT10 expression was shown to be induced by gamma interferon or by tumor necrosis factor alpha. In addition, FAT10 expression was found to be up-regulated in some Epstein-Barr virus-infected B-cell lines, in activated dendritic cells, and in several epithelial tumors. However, forced expression of FAT10 in cultured cells was also found to produce apoptotic cell death. Overall, these findings suggest that FAT10 may modulate cellular growth or cellular viability. Here we describe the steps to generate, by genetic targeting, a FAT10 gene knockout mouse model. The FAT10 knockout homozygous mice are viable and fertile. No gross lesions or obvious histological differences were found in these mutated mice. Examination of lymphocyte populations from spleen, thymus, and bone marrow did not reveal any abnormalities. However, flow cytometry analysis demonstrated that the lymphocytes of FAT10 knockout mice were, on average, more prone to spontaneous apoptotic death. Physiologically, these mice demonstrated a high level of sensitivity toward endotoxin challenge. These findings indicate that FAT10 may function as a survival factor.
PMCID: PMC1489174  PMID: 16782901
13.  Gating Kinetics of the α1i T-Type Calcium Channel 
The Journal of General Physiology  2001;118(5):457-470.
The α1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (α1G and α1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat α1I stably expressed in HEK293 cells. We found several kinetic differences between α1G and α1I, including some properties that at first appear qualitatively different. Notably, α1I tail currents require two or even three exponentials, whereas α1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for α1I, even for relatively strong depolarizations. Despite these differences, gating of α1I can be described by the same kinetic scheme used for α1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5–12-fold slower for α1I, but the microscopic rate for channel closing is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.
PMCID: PMC2233834  PMID: 11696605
inactivation; activation; T-current; LVA channel; kinetic models

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