Role of bile acids in liver diseases mediated by the gut microbiome.

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host's natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Resveratrol enhances chemosensitivity of renal cell carcinoma to paclitaxel.

By restraining proliferation and promoting apoptosis, resveratrol (RES) has anti-tumor effect in various cancers. Here, we examine whether RES exerts similar effect in drug-resistant renal cell carcinoma (RCC). To this end, Caki-1 cells derived from renal carcinoma are subjected to escalated doses of paclitaxel (PTX) to produce the PTX resistant Caki-1PTX cells. Both Caki-1 and Caki-PTX cells are sensitive to PTX, in a dose dependent manner. RES, dose-dependently, suppresses the expression of survivin, a molecular biomarker of cancer and a member of the inhibitor of apoptosis (IAP) family and its co-administration with PTX inhibits the effect of this drug on cell viability. To decipher whether survivin expressed by cancer cells is involved in rendering cells PTX sensitive, survivin is overexpressed. This dramatically counteracts the effects of RES on cell survival in the presence of PTX. Furthermore, decrease of survivin by inhibition of PI3K/AKT pathway significantly inhibits the effect of PTX in Caki-1PTX cells. These data show that RES increases the sensitivity of PTX resistant renal cells to drug treatment.

Apoptosis repressor with caspase recruitment domain deficiency accelerates ischemia/reperfusion (I/R)-induced acute kidney injury by suppressing inflammation and apoptosis: The role of AKT/mTOR signaling.

Acute kidney injury (AKI) is a significant medical problem worldwide. Ischemia-reperfusion (I/R) injury of the kidney is a major cause of AKI. However, the pathogenesis that contributes to renal I/R injury is still unclear. Apoptosis repressor with caspase recruitment domain (ARC) is abundantly expressed in various tissues, and has been reported to play a strong protective role during pathological processes. Our results indicated that ARC expression was decreased in the reperfused kidneys. ARC deficiency markedly accelerated renal dysfunction, promoted reperfusion-regulated tubular epithelial cell apoptosis, and enhanced the vulnerability of kidney to I/R damage. Furthermore, in the kidney samples of mice underwent renal I/R injury, ARC knockout significantly accelerated the expression levels of inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor a (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IL-2. In addition, renal I/R injury-induced apoptosis was further exacerbated in ARC-deficient mice through promoting the expression of cleaved Caspase-3 and poly (ADP-ribose) polymerase (PARP). From the molecular level, ARC deletion obviously accelerated mitochondrial injury, as evidenced by the further decreased adenosine triphosphate (ATP) levels and mitochondrial potential in hypoxia-reoxygenation (H/R)-treated cells. Moreover, ARC knockout exacerbated AKI through activating phosphorylated protein kinase B (AKT), mammalian target of Rapamycin (mTOR) and p53, whereas reducing phosphorylated glycogen synthase kinase 3ß (GSK3ß). Of note, blocking AKT/mTOR signaling markedly attenuated inflammation, mitochondrial damage and apoptosis stimulated by H/R in ARC knockdown cells. In summary, our results suggested that ARC played a pivotal role in the pathogenesis of AKI induced by renal I/R operation through regulating AKT/mTOR signaling.

Pelvic Exenteration for Recurrent and Persistent Cervical Cancer / 中华医学杂志(英文版)

<p><b>Background</b>Pelvic exenteration (PE) for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution.</p><p><b>Methods</b>From January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcomes in univariate and Cox hazard regression analysis.</p><p><b>Results</b>There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years (range 29-65 years). Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 (55.3%) patients and 15 (39.5%) patients, respectively. Two (5.3%) patients died due to complications related to surgeries within 3 months after PE. The median overall survival (OS) and disease-free survival (DFS) were 28.5 months (range 9-96 months) and 23 months (range 4-96 months), respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors for OS and DFS.</p><p><b>Conclusion</b>In our patients with recurrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes.</p><p><b>Trial Registration</b>ClinicalTrials.gov, NCT03291275; https://clinicaltrials.gov/ct2/show/NCT03291275?term=NCT03291275&rank=1.</p>

Hydrogen sulfide protects intestinal mucosa in a neonatal rat model of necrotizing enterocolitis by upregulating the expression of HO-1 / 临床儿科杂志

Objective To explore the protective effects of GYY4137, a new hydrogen sulfide donor, on intestinal mucosa in a neonatal rat model of necrotizing enterocolitis (NEC), and its potential mechanism.Methods Sixty SD rats were randomly assigned into 4 groups: group A (control group), group B (NEC group), group C (NEC with GYY4137 treatment, H2S donor group), and group D (NEC with GYY4137 and Znpptreatment, HO-1 inhibitor group). The SD rat models of NEC were established using simulated milk feeding-hypoxia-cold stress-Lipopolysaccharides. The injury degree of intestinal mucosa was evaluated using HE-staining, and its mechanisms were investigated using biochemical indicators and Western blotting. Results Compared with control group, the pathology score and the total superoxide dismutase (T-SOD) in the NEC group was significantly higher, the concentrations of methane dicarboxylic aldehyde (MDA) and necrosis factor α (TNF-α) were lower(P<0.05). Compared with those in NEC group, the pathology score and the concentration of MDA and TNF-α in the H2S donor group were signiflcantly lower, the T-SOD, and the HO-1 expression was higher. The pathology score and the level of MDA and TNF-α were signiflcantly increased after treated with HO-1 inhibitor Znpp, and T-SOD was signiflcantly decreased.. Conclusions The GYY4137, as a new H2S donor, could attenuate the injury of intestinal mucosa in a neonatal rat model of NEC by upregulating the expression of HO-1.

Effect of Sancaijiangtang on plasma nitric oxide and endothelin-1 levels in patients with type 2 diabetes mellitus and vascular dementia: a single-blind randomized controlled trial.

OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia, and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine. METHODS: In total, 168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study, and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily, while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for 12 weeks. Mini-mental state examinations (Chinese version) and Montreal Cognitive Assessments (Beijing version) were performed, and fasting plasma glucose, fasting insulin, hemoglobin A1c, homeostasis model assessment of insulin resistance, plasma nitric oxide and endothelin-1 levels were measured before and after the treatment. RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treat- ment levels (P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group (P < 0.05). CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore, the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.

Longitudinal evaluation of reparative cartilage after matrix-associated autologous chondrocyte implantation with delayed gadolinium-enhanced MRI of the cartilage / 南方医科大学学报

<p><b>OBJECTIVE</b>To estimate zonal variation of GAG content in reparative cartilage after matrix associated autologous chondrocyte implantation (MACI) using delayed gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC).</p><p><b>METHODS</b>Seven patients (14 cartilage defects) undergoing MACI were recruited for examination with dGEMRIC at 3, 6, and 12 months after the procedure to calculate global and zonal longitudinal relaxivity (Δ R1) of the normal cartilage and reparative cartilage.</p><p><b>RESULTS</b>The mean Δ R1 values of normal cartilage were significantly lower than those of reparative cartilage after MACI. A significant decrease was noted in the mean Δ R1 values from the deep layer to the superficial layer in the reparative cartilage at the 3 examinations. The Δ R1 values of the reparative cartilage showed no significant variation between 3 months and 6 months, but a significant decrease in the Δ R1 values occurred at 12 months.</p><p><b>CONCLUSIONS</b>dGEMRIC is feasible to assess cartilage repair noninvasively following MACI.</p>

HSP70/CD80 DNA vaccine inhibits airway remodeling by regulating the transcription factors T-bet and GATA-3 in a murine model of chronic asthma.

INTRODUCTION: Airway remodeling is an important pathologic feature of chronic asthma. T-bet and GATA-3, the key transcription factors for differentiation toward Th1 and Th2 cells, play an important role in the pathogenesis of airway inflammation, airway hyperresponsiveness and airway remodeling. Previous studies showed that HSP70/CD80 DNA vaccine can reduce airway hyperresponsiveness and airway inflammation in acute asthmatic mice. The present study was designed to determine the effect of HSP70/CD80 DNA vaccine on airway remodeling through regulating the development of Th1/Th2. MATERIAL AND METHODS: Before being sensitized and challenged by ovalbumin, the BALB/c mice were immunized with DNA vaccine. Lung tissues were assessed by histological examinations. Interferon-γ (IFN-γ)/interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid were determined by ELISA and expressions of IFN-γ, IL-4, T-bet and GATA-3 in spleen were evaluated by real-time polymerase chain reaction. RESULTS: Chronic asthmatic mice had higher airway hyperresponsiveness, a thicker airway wall, more PAS-positive goblet cells, more subepithelial extracellular matrix deposition and more proliferating airway smooth muscle (ASM)-like cells than control mice (p < 0.05). Compared with the chronic asthmatic mice, the treatment with HSP70/CD80 DNA vaccine could reduce airway hyperreactivity, mucus secretion, subepithelial collagen deposition, and smooth muscle cell proliferation (p < 0.05). DNA vaccination also increased levels of IFN-γ/IL-4 in BAL fluid (p < 0.05), and expression of T-bet/GATA-3 in the spleen (p < 0.05). CONCLUSIONS: HSP70/CD80 DNA vaccine can inhibit airway remodeling through regulating the development of Th1/Th2 subsets in asthmatic mice.

Investigation of treatment for cervical intraepithelial neoplasia in women aged 65 years and over / 中华老年医学杂志

Objective To retrospectively analyze the treatment methods of cervical intraepithelial neoplasia (CIN) in women aged 65 years and over.Methods From July 2002 to December 2011,51 postmenopausal women aged 65 years and over with CIN were admitted to our hospital.The diagnosis and treatment were summarized and analyzed,and the CIN related literatures were discussed.Results 31 patients received colposcopy and the colposcopically directed punch biopsy.Squamocolumnar junction (SCJ) was found in 18 patients (58.1％,18/31),and not found in 13 patients (41.9％,13/31).Among the 31 patients,21 patients received conization after biopsy.9 patients were under-diagnosed by biopsy,in which 4 cases (44.4％) SCJ were found and in 5 cases (55.6％)SCJ were not found.In all patients,26 patients received conization and 20 patients received hysterectomy directly.There were 14 patients received hysterectomy after conization.Among 14 patients,the uteruses in 4 patients with conization specimen diagnosed as CIN Ⅱ-Ⅲ and negative margin were 100.0％ (4/4),and the uteruses in 3 patients with conization specimen diagnosed as CINII-Ⅲ and positive margin were 50.0％ (3/6).Conclusions For women aged 65 years and over,it is very important whether SCJ can be seen or not in colpscopy and directed punch biopsy procedure.It is better to do conization if possible.Patients with conization specimen diagnosed CINII-Ⅲ and negative margin needn't subsequent hysterectomy.Patients with positive margin but with bad general conditions or complications can continue to be monitored if they have good follow-up conditions.If patients are diagnosed as carcinoma by conization specimen,total hysterectomy or radical hysterectomy is recommended.

Influences of warming kidney prescription on antiviral therapeutic efficacy and creatine kinase in telbivudine-treated HBeAg-positive chronic hepatitis B patients / 中华肝脏病杂志

To study the influences of warming kidney prescription on antiviral therapeutic efficacy and creatine kinase (CK) level in telbivudine-treated HBeAg-positive chronic hepatitis B patients with kidney yang deficiency syndrome. Ninety-six cases were enrolled and randomly divided into two groups (n=48 each): warming kidney prescription treatment or control. Both groups were treated for 52 weeks with telbivudine monotherapy, but the treatment group received additional treatment with the warming kidney prescription. Traditional Chinese medicine (TCM) syndrome score, biochemical response, virological response, serological response, CK level, and adverse reactions were recorded for each group in order to perform comparative analysis of the warming kidney prescription's effects. A total of 84 patients, including 43 cases in the treatment group, completed the study. The warming kidney prescription led to significantly improved total clinical syndrome efficacy, TCM syndrome score, biochemical response, virological response, and HBeAg serological responses, as evidenced by changes for each parameter observed in the treatment group versus the control group (respectively, 88.37% vs. 63.41%, 4.97+/-1.88 vs. 10.13+/-3.72, 95.35% vs. 75.61%, 81.40% vs. 56.10%, 48.84% vs. 26.83% (all, P less than 0.05)). No patient in either group experienced primary treatment failure. Seven cases, all from the control group, experienced virological breakthrough. Elevated CK was observed in both the treatment and control groups, but significantly more patients in the control group experienced this adverse reaction (respectively, 73.17% vs. 44.19%; P less than 0.01). The warming kidney prescription can increase telbivudine antiviral therapeutic efficacy and decrease the telbivudine-induced increase in creatine kinase in HbeAg-positive chronic hepatitis B patients with kidney yang deficiency syndrome.

A prospective cohort study on the influence of high doses of herbs for clearing heat and resolving stasis on survival rates in patients with hepatitis B-related acute-on-chronic liver failure / 中西医结合学报

Hepatitis B-related acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by jaundice, coagulopathy, ascites and hepatic encephalopathy and with a high mortality rate of 65% to 93%. It involves significant ethical issues when a randomized, double-blinded, placebo-controlled clinical study is conducted to such a serious disease. Therefore, a prospective cohort study design was utilized to explore a new treatment modality of applying integrated traditional Chinese and Western medicine.

The effects of HSP70/CD80 DNA vaccine on airway inflammation and hyperresponsiveness of asthmatic mice / 中华微生物学和免疫学杂志

Objective To investigate the effect of HSP70/CD80 DNA vaccine on the airway inflammation and hyperresponsiveness of asthmatic mice. Methods Forty female healthy BALB/c mice were randomly divided into 4 groups; saline group, asthma group, pcDNA3. 1 plasmid control group, and prevention group with HSP70/CD80 DNA vaccine, with 10 mice in each group. The mice were immunized by intramuscular( i. m. ) injection with HSP70/CD80 DNA vaccine before sensitization and challenge with ovalbumin. Then, the murine model of allergic asthma was made with injection of ovalbumin intraperitoneal ( i. p. ) , and inhalation of ovalbumin. Before mice were sanctified, their airway hyperresponsiveness( AHR) was measured. After mice were sanctified, bronchoalveolar lavage fluid( BALF) was obtained and cytokine IL-13 and IFN-γ were measured. And the lung histology and histochemistry were examined. Results Compared with mice in asthma and pcDNA3. 1 group, mice in vaccine group showed significantly reduced airway inflammation (P＜0. 05) and AHR (P＜0. 05). IFN-γ content in BALF were increased in mice from vaccine group compared with the asthma group and the pcDNA3. 1 group ( P ＜0. 05) , and IL-13 content in BALF were decreased. Conclusion HSF70/CD80 DNA vaccine can reduce airway inflammation and hyperresponsiveness in asthmatic mouse and this chimerical plasmid could be a candidate vaccine to prevent asthma.

A new SEIR epidemic model with applications to the theory of eradication and control of diseases, and to the calculation of R0.

We present a novel SEIR (susceptible-exposure-infective-recovered) model that is suitable for modeling the eradication of diseases by mass vaccination or control of diseases by case isolation combined with contact tracing, incorporating the vaccine efficacy or the control efficacy into the model. Moreover, relying on this novel SEIR model and some probabilistic arguments, we have found four formulas that are suitable for estimating the basic reproductive numbers R(0) in terms of the ratio of the mean infectious period to the mean latent period of a disease. The ranges of R(0) for most known diseases, that are calculated by our formulas, coincide very well with the values of R(0) estimated by the usual method of fitting the models to observed data.

Evaluation on HBeAg conversion time when treating chronic hepatitis B patients with combination of lamivudine and traditional Chinese medicine / 中华流行病学杂志

Objective To evaluate the effect of the combined use of traditional Chinese medicine and lamivudine(LMD) in treating chronic hepatitis B patients, and to follow the serological response for six months or longer. Methods CNKI, Wanfang data, VIP data, CBMdisk, MEDLINE,EMBASE,BIOSIS and Cochrane Central Register of Controlled Trials database and literature were searched, to include randomized controlled trails (RCT) that used LMD alone or combined with traditional Chinese medicine. RevMan 4.2 was used for data analysis. Results The Meta analysis of 7 trails demonstrated that the HBeAg conversion rate in treatment group was higher than those from the control group, and the differences were statistically significant at 6, 9, 12 months. Conclusion Data demonstrated that early intervention of traditional Chinese medicine might increase the HBeAg conversion rate but conclusion needs to be more specific to the types of trials.

Observation on the therapeutic effect of Shenfu injection on the patients of hepatic cirrhosis with seroperitoneum(yang def iciency of spleen and kidney) / 中华中医药杂志

Objective:To explore yhe therapeutic effect of Shenfu injection on patients of hepatic cirrhosis with seroperitoneum(yang de ciency of spleen and kidey synndrome).Methods:The 84 patients were divided into treatment group and control group,the patients in treatment group were treated with western medicine and Shenfu injection,only western medicine were used in control group,they were all treated for twenty-eight days.Results:The curative e ect,extinction time of seroperitoneum,amelioration of hepatic function and blood routine of the treatment group were better than those of control group.And there were statistical signi canc between two groups(P

Study on the effect of cockroach extract on animals with hepatic injury and its antiviral action in vitro / 国际中医中药杂志

Objective To study the effect of extract of cockroach on animals with acute hepatic injury and its antiviral action in vitro. Methods The animal models with hepar injury were established by CCl4, bcg vaccine and lipopolysaccharide (LPS) . And the activities of ALT and AST in serum were measured. Serum of ducks was separated after cockroach extract was administrated. The serum was added to the culture fluid of HBV-DNA transfected hepatic cancer cells-HepG2. Results After the cockroach extract was administrated, the activities of ALT and AST in mouse serum were reduced. Both the therapeutic indexes of cockroach extract and lamivudine were larger than 2. Conclusions Cockroach extract can improve the liver function of animals with acute hepatic injury, and inhibit the secretion of ALT and AST in serum.

Screening and their anti-tumor activity of antisense oligodeoxynucleotides targeting KDR mRNA in breast cancer MCF-7 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To screen the antisense oligodeoxynucleotides (asONs) which could hybridize with KDR (kinase insert domain-containing receptor) mRNA in an effective and specific way and to explore their anti-tumor effects on breast cancer MCF-7 cell line in vitro.</p><p><b>METHODS</b>The asONs were firstly selected using oligodeoxynucleotides library hybridization or computer prediction, then their hybridization ability with KDR mRNA was further tested with oligonucleotide microarray. The asONs with strong hybridization intensity were selected. Their inhibitory effects on MCF-7 cells proliferation and KDR expression were assayed by MTT, RT-PCR and Western blotting assay, respectively.</p><p><b>RESULTS</b>In 13 asONs selected with oligodeoxynucleotides library hybridization, 8 (8/13, 61.5%) showed strong hybridization signals, while such was only 1 in 17 asONs designed by computer prediction. 9 asONs with strong hybridization intensity were selected and synthesized with phosphorothioated modification. All these asONs inhibited the MCF-7 cells proliferation in a dose-dependent manner, in which asON4 and asON7 screened by oligodeoxynucleotides library in combination with oligonucleotide microarray were the most effective, with inhibitory rates of 51.6% and 62.2% at 0.8 micromol/L, respectively. The KDR expression at mRNA and protein levels was reduced by both the two asONs, in a dose-dependent manner.</p><p><b>CONCLUSION</b>asONs screened by oligodeoxynucleotides library hybridization are well consistent with that chosen with oligonucleotide microarray. The combination of oligodeoxynucleotides library with oligonucleotide microarray is an effective approach of asONs screening. The asONs targeting KDR mRNA showed prominent anti-tumor activity on breast cancer MCF-7 cells.</p>

Clinical analysis of primary malignant melanoma of the cervix / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of primary cervical malignant melanoma, and its prognosis.</p><p><b>METHODS</b>The clinical and pathological data of four patients with primary malignant melanoma of the cervix were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody to melanoma (HMB-45) were measured in all cases by immunohistochemical method. All four patients received radical hysterectomy. Three of them received chemotherapy preoperation or postoperation, and one of them received biotherapy with interferon-gamma and interleukin-2 at the same time. All the cases were followed up.</p><p><b>RESULTS</b>The average age of four patients was 45 years. Clinical symptoms presented with irregular vaginal bleeding, postcoital bleeding, or increase of vaginal discharge. Gynecologic examination showed polypus papilla cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All the four cases were pathologically diagnosed with cervical malignant melanoma. S-100 and HMB-45 were positive in all patients. Two patients died at 6 and 41 months postoperation, respectively. The other two patients survived for 3.5 and 7 years postoperation, respectively.</p><p><b>CONCLUSIONS</b>S-100 protein and HMB-45 play very important roles in the diagnosis of primary malignant melanoma of cervix. Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole carboxamide and biological therapies may improve the prognosis of the primary malignant melanoma of cervix if the disease could be diagnosed in an early stage.</p>

The anti-cancer effect of siRNA targeting human telomerase reverse transcriptase in SMMC-7721 cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the anti-cancer effects of siRNAs targeting hTERT in SMMC-7721 cells.</p><p><b>METHODS</b>Two siRNAs targeting hTERT mRNA were designed and synthesized by T7 transcription system in vitro. MMT, RT-PCR and Western blot were applied to evaluate effects on inhibiting cell growth, hTERT mRNA and protein expression in SMMC-7721 cells.</p><p><b>RESULTS</b>siRNAs decreased cell proliferation in a dose-dependent manner. At a concentration of 100 nmol/L, siRNAs exhibited obvious effects on inhibiting hTERT mRNA and protein expression in SMMC-7721 cells.</p><p><b>CONCLUSION</b>siRNAs targeting hTERT have significant inhibitory effects on hTERT gene expression in SMMC-7721 cells. siRNA has the possibility to become a new anti-cancer agent</p>

Prolongation of functional life-span of neutrophils by recombinant verotoxin 2 / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Verotoxin-producing Escherichia coli (VTEC) strains of serotype O157 : H7 have been implicated in a wide spectrum of diseases, including blood diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). To further explore the pathological role of verotoxin (VT) in HUS and other VTEC associated diseases, we investigated the effects of recombinant verotoxin 2 (rVT2) on the biological activity of neutrophils.</p><p><b>METHODS</b>The technique of flow cytometry, a fluorescent probe 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF/AM), and the assay of reduced cytochrome c to detect superoxide production were used in this study.</p><p><b>RESULTS</b>gammaVT2 significantly inhibited spontaneous apoptosis in neutrophils. Neutrophils with prolonged survival due to gammaVT2 maintained various biological functions, such as the expression of adhesion molecules (shading CD62L and raising CD11b/CD18), adherence to human umbilical vein endothelial cells (HUVECs), and generation of superoxide (O(2)(-)).</p><p><b>CONCLUSION</b>Prolongation of the functional life-span of neutrophils by gammaVT2 may accelerate inflammatory responses at sites of inflammation. This may play a crucial role in neutrophil-mediated tissue injury in HUS and other VTEC-associated diseases.</p>