[Schwannoma originating from the branch of the inferior oblique muscle innervated by the oculomotor nerve: a report of two cases].

Patient 1 was a 44-year-old female with a progressively enlarging orbital mass on the right side for 2 years, while patient 2 was a 25-year-old female who complained of protrusion of the right eye for 2 months. Both patients presented with exophthalmos and a palpable infraorbital mass without vision loss. Magnetic resonance imaging examination showed a well circumscribed circular orbital lesion, with hypointensity on T1 weighted image and heterogeneous hyperintensity on T2 weighted image, which could be significantly enhanced, in either eye. Both eyes were diagnosed as begin orbital tumor and received resection under general anesthesia. Intraoperatively, the distal end of the tumors was found to transmigrate to normal nerves and insert into the inferior oblique muscle. Combined with the pathological diagnosis of schwannoma and postoperative occurrence of mydriasis and inferior oblique muscle paralysis in both patients, it was confirmed that the two lesions were schwannomas originating from the branch of the inferior oblique muscle innervated by the oculomotor nerve.

[Comparative study on metagenomics of esophageal flora in elderly and middle-aged esophageal squamous cell carcinoma patients].

Objective: To explore the flora characteristics and differences of esophageal tissues between elderly esophageal squamous cell carcinoma (ESCC) patients and young and middle-aged ESCC patients, so as to assist in studying the potential biomarkers of elderly ESCC patients. Methods: In this study, a retrospective study was adopted. 72 ESCC patients diagnosed in Taihe Hospital, Shiyan City, Hubei Province from July 2018 to July 2019 were selected, including 49 patients in the elderly group (≥ 60 years old, 40 males and 9 females), 23 patients in the young and middle-aged group (<60 years old, 21 males and 2 females). In the same period, 20 healthy persons without abnormal gastroscopy in endoscopy center were selected as the control group (aged 35-78 years old, median age 57 years old, 16 males and 4 females). The genomic DNA was extracted from the affected esophageal tissues of patients with ESCC and the middle esophageal samples of the control group. The V4 hypervariable region of bacterial 16SrRNA gene sequence was amplified. Illumina HiSeq sequencing technology was adopted. The flora characteristics of elderly, young and middle-aged ESCC patients was compared and analyzed. QIIME and Rstudio software were used to analyze the sequence data, and nonparametric Kruskal-Wallis test or Wilcoxon rank sum test were used for statistical methods. Results: Shannon index [5.17 (4.53, 5.95) vs. 4.79 (3.74, 5.97)], Simpson index [0.94 (0.91, 0.96) vs. 0.92 (0.83, 0.96)] and Chao1 index [343.55 (259.76, 570.59) vs. 329.16 (268.88, 648.00)] were similar in flora of two groups, and there was no significant difference (Z=-0.791, -1.057, -0.380, all P>0.05). There was no significant difference in ß-diversity between the elderly group and the young and middle-aged group (PC1=19.14%, PC2=6.95%, PPC1=0.67, PPC2=0.42). At the phyla level, the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria in the young and middle-aged group, while the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria in the elderly group; the significant difference between the two groups was Fusobacteria (Q=0.596, P<0.05). At the genus level, the top 5 genera in the young and middle-aged group in abundance were as follows: Prevotella, Bacteroides, Streptococcus, Selenomonas and Veillonella. In the elderly group, Prevotella, Bacteroides, Streptococcus, Selenomonas and Haemophilus were the top 5 in abundance, and there were significant difference in Fusobacterium between the two groups (Q=0.938, P<0.05). PICRUSt function prediction showed that the abundance of Aminoacyl.tRNA.biosynthesis, Nucleotide.excision.repair, RNA.polymerase, Ribosome, Clavulanic.acid.biosynthesis, Photosynthesis and Photosynthesis. proteins in the elderly group were lower than those in the young and middle-aged group (all Q=0.734, P<0.05). Conclusion: There is no significant difference in α-diversity and ß-diversity between elderly ESCC patients and young and middle-aged patients, but the abundance of Fusobacterium flora increased.

[The imaging signs and significances of the enlargement of the infraorbital nerve and the frontal nerve in orbital lymphoproliferative diseases].

Objective: To describe imaging signs of infraorbital nerve enlargement (IONE) and frontal nerve enlargement (FNE) in orbital lymphoproliferative diseases (LPDs), and to explore the diagnostic value and differential diagnostic role of the signs. Methods: A retrospective case series study. The data of 222 cases (262 eyes) of LPDs and 95 cases (134 eyes) of inflammatory pseudotumors (IPs) pathologically confirmed by the Peking University People's Hospital and the Third Medical Center of the Chinese PLA General Hospital from January 2013 to December 2018 were analyzed. The LPDs were lymphoma (including atypical lymphoid hyperplasia) in 91 cases (110 eyes) and reactive lymphoid hyperplasia (RLH) in 131 cases (152 eyes). The patients with LPD included 101 males and 121 females, aged (58±17) years, and the patients with IP included 44 males and 51 females, aged (49±21) years. All patients underwent orbital CT or MRI with T1 weighted imaging, T2 weighted imaging and enhanced T1 weighted imaging scanning. Slice thickness was 3 mm. In the coronal CT or MRI, the criterion for determining IONE was the inferior orbital nerve diameter greater than the optic nerve, and the criterion for determining FNE was the forehead nerve diameter equal to or greater than the optic nerve. The pathological types and imaging features of nerve enlargement were recorded. The incidence rates of different pathological types were compared using chi-square test. Results: The enlarged nerves showed homogeneous soft tissue density on CT images, accompanied with enlarged bony infraorbital nerve grooves (foramina). MRI showed moderate signals of T1 and T2 weighted imaging, with clear boundaries and obvious enhancement, which could spread to the pterygopalatine fossa and the cranial cavity. The accompanying images included the enlargement of lacrimal glands or extraocular muscles, intraorbital mass or sinuses opacity. The IONE and/or FNE were found in 12 patients with LPD, but were not found in any patients with IP. The difference was statistically significant (12/222 vs. 0/95, χ²=5.337, P=0.021). Among the cases with nerve enlargement, there were 2 cases of diffuse large B cell lymphoma and 10 cases of RLH (2/91 vs. 10/131, χ²=3.103, P=0.078), as well as 7 cases of IgG4-related ophthalmic disease (IgG4-ROD) and 3 cases of non-IgG4-ROD (7/28 vs. 3/103, χ2=15.232, P=0.000). Conclusions: Lymphoma and RLH can express IONE and/or FNE, in which the IgG4-ROD is the most common and specific type. CT and MRI scans can show enlarged nerves and accompanying signs. Neural thickening can also be applied as a discrimination marker of LPDs and IPs. (Chin J Ophthalmol, 2020, 56: 832-838).

[Application of lymph node labeling with carbon nanoparticles by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy].

Objective: To evaluate the application value of carbon lymph node tracing technique by preoperative endoscopic subserosal injection in laparoscopic radical gastrectomy. Methods: From June 2013 to February 2015, seventy eight patients with gastric cancer were enrolled and randomly divided into trial group and control group. Subserosal injection of carbon nanoparticles around the tumor was performed by preoperative endoscopic subserosal injection one day before the operation in trial group, while the patients routinely underwent laparoscopic gastrectomy in control group. Results of harvested lymph nodes, postoperative complications were compared between the two groups. Carbon nanoparticle-related side effect was also evaluated. Results: The average number of harvested lymph node in trial group was significantly higher than that in control group (35.5±8.5 vs 29.5±6.5, P<0.05). The rate of overall black-dyed harvested lymph node was 74.7% (1 035/1 386) in trial group, the black-dyed lymph node rate in D1 lymph node was 80.1%, which was significantly higher than that in D2 lymph node (69.8%, χ2=19.38, P<0.01). When comparing the lymph node with and without black-dyed in trial group, the rate of metastasis lymph node was significantly higher in lymph node with black-dyed (17.3% vs 4.0%, χ2=38.67, P<0.01). There was no significant difference in postoperative complications rate between two group (trial group 10.2%; control group 12.8%, χ2=0.00, P>0.05), and no carbon nanoparticle-related side effect was observed. Conclusion: Given a higher harvested lymph node number and a similar rate of complications, preoperative endoscopic subserosal injection of carbon nanoparticles was safe and feasible.

[Research advances in the role of CX3CL1 and its receptor in liver diseases].

In recent years, an increasing number of studies have found that the interaction between CX3CL1 and its receptor plays an important role in a series of inflammatory, infectious, and neurological processes and in various cancers. Therefore, its therapeutic targeting represents a promising treatment strategy for diseases. This review summarizes the structure, biological function, and mechanism of signal transduction of CX3CL1 and its receptor, and introduces the research progress in CX3CL1 and its receptor in hepatitis, hepatic fibrosis, cirrhosis, and hepatoma.

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

OBJECTIVE: To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. METHODS: A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. RESULTS: The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. CONCLUSION: The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

CTCF cooperates with noncoding RNA MYCNOS to promote neuroblastoma progression through facilitating MYCN expression.

Previous studies have indicated the important roles of MYCN in tumorigenesis and progression of neuroblastoma (NB), the most common extracranial solid tumor derived from neural crest in childhood. However, the regulatory mechanisms of MYCN expression in NB still remain largely unknown. In this study, through mining public microarray databases and analyzing the cis-regulatory elements and chromatin immunoprecipitation data sets, we identified CCCTC-binding factor (CTCF) as a crucial transcription factor facilitating the MYCN expression in NB. RNA immunoprecipitation, RNA electrophoretic mobility shift assay, RNA pull down and in vitro binding assay indicated the physical interaction between CTCF and MYCN opposite strand (MYCNOS), a natural noncoding RNA surrounding the MYNC promoter. Gain- and loss-of-function studies revealed that MYCNOS facilitated the recruitment of CTCF to its binding sites within the MYCN promoter to induce chromatin remodeling, resulting in enhanced MYCN levels and altered downstream gene expression, in cultured NB cell lines. CTCF cooperated with MYCNOS to suppress the differentiation and promote the growth, invasion and metastasis of NB cells in vitro and in vivo. In clinical NB tissues and cell lines, CTCF and MYCNOS were upregulated and positively correlated with MYCN expression. CTCF was an independent prognostic factor for unfavorable outcome of NB, and patients with high MYCNOS expression had lower survival probability. Taken together, these results demonstrate that CTCF cooperates with noncoding RNA MYCNOS to exhibit oncogenic activity that affects the aggressiveness and progression of NB through transcriptional upregulation of MYCN.

Suppression of Inflammatory Responses by Dihydromyricetin, a Flavonoid from Ampelopsis grossedentata, via Inhibiting the Activation of NF-κB and MAPK Signaling Pathways.

Ampelopsis grossedentata, an indigenous plant in southern China, has been used for treating pharyngitis in traditional Chinese medicine for hundreds of years. In this study, we explored the anti-inflammatory activity of dihydromyricetin (1), its major bioactive component, and the underlying mechanism of this action. We demonstrated that 1 suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) as well as increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lipopolysaccharide (LPS)-treated mice. Moreover, 1 was found to markedly inhibit the production of nitric oxide (NO) and the levels of TNF-α, IL-1ß, and IL-6, whereas it increased the level of IL-10 in LPS-induced RAW 264.7 macrophage cells. Compound 1 also reduced the protein expression of inducible nitric oxide synthase (iNOS), TNF-α, and cyclooxygenase-2 (COX-2) in macrophage cells. Furthermore, 1 suppressed the phosphorylation of NF-kappa B (NF-κB) and IκBα as well as the phosphorylation of p38 and JNK but not ERK1/2 in LPS-stimulated macrophages. Taken together, the present results suggest that 1 exerts its topical anti-inflammatory action through suppressing the activation of NF-κB and the phosphorylation of p38 and JNK. Thus, 1 may be a potentially useful therapeutic agent for inflammatory-related diseases.

MicroRNA-145 inhibits the growth, invasion, metastasis and angiogenesis of neuroblastoma cells through targeting hypoxia-inducible factor 2 alpha.

Recent evidence shows that hypoxia-inducible factor 2 alpha (HIF-2α) may have critical roles in the growth and progression of neuroblastoma (NB) under non-hypoxic conditions. However, the underlying mechanisms and clinical potentials of normoxic HIF-2α expression in NB still remain largely unknown. In this study, HIF-2α immunostaining was identified in 26/42 NB tissues, which was correlated with clinicopathological features. In subtotal 20 NB cases, microRNA-145 (miR-145) was downregulated and inversely correlated with HIF-2α expression. Bioinformatics analysis revealed a putative miR-145 binding site in the 3'-untranslated region (3'-UTR) of HIF-2α messenger RNA (mRNA). Overexpression or knockdown of miR-145 responsively altered both the mRNA and protein levels of HIF-2α and its downstream genes, cyclin D1, matrix metalloproteinase 14 and vascular endothelial growth factor, in normoxically cultured NB cell lines SH-SY5Y and SK-N-SH. In a luciferase reporter system, miR-145 downregulated the luciferase activity of HIF-2α 3'-UTR, and these effects were abolished by a mutation in the putative miR-145-binding site. Overexpression of miR-145 suppressed the growth, invasion, metastasis and angiogenesis of SH-SY5Y and SK-N-SH cells in vitro and in vivo, while restoration of HIF-2α expression rescued the tumor cells from miR-145-mediated defects in these biological features. Furthermore, anti-miR-145 inhibitor rescued the HIF-2α knockdown-mediated repression on the growth, migration, invasion and angiogenesis of NB cells. These data indicate that miR-145 suppresses HIF-2α expression via the binding site in the 3'-UTR under normoxic conditions, thus inhibiting the aggressiveness and angiogenesis of NB.

A comparison of quality of life and satisfaction of women with early-stage breast cancer treated with breast conserving therapy vs. mastectomy in southern China.

BACKGROUND: The purpose of this study was to compare the quality of life (QoL) and overall satisfaction with treatment of women with stage T1-2N0M0 breast cancer treated with breast conserving therapy (BCT) or mastectomy (MAS) in southern China. METHODS: Functional assessment of cancer therapy-breast, traditional Chinese version 4 (FACT-B), was administered to 180 patients with stage T1-2N0M0 breast cancer (82 BCT and 98 MAS) treated between July 2000 and July 2008. RESULTS: The two groups differed in tumor pathology and how axillary lymph nodes were treated (sentinel node biopsy vs. dissection), while other disease and socioeconomic characteristics were similar. The median follow-up after completion of radiotherapy was 60 months in the BCT group, and 65 months in the MAS group. The scores of the physical, functional, and emotional domains and breast-specific concerns of FACT-B were not significantly different between the groups. The social domain score of the BCT group was significantly greater than those of the MAS group. CONCLUSIONS: Patients who underwent BCT did not report better QoL than those who received MAS, but BCT patients experienced easier social adjustment.

Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation.

Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function. Because acetylation and ubiquitination both modify the ɛ-amino group of lysine residues, we investigated whether FOXO3 deacetylation by SIRT1 or SIRT2 facilitates FOXO3 ubiquitination and subsequent proteasomal degradation. We found that SIRT1 and SIRT2 promote FOXO3 poly-ubiquitination and degradation. Proteasome-inhibitor treatment prevented sirtuin-induced FOXO3 degradation, indicating that this process is proteasome dependent. In addition, we demonstrated that E3 ubiquitin ligase subunit Skp2 binds preferentially to deacetylated FOXO3. Overexpression of Skp2 caused poly-ubiquitination of FOXO3 and degradation, whereas knockdown of Skp2 increased the amount of FOXO3 protein. We also present evidence that SCF-Skp2 ubiquitinates FOXO3 directly in vitro. Furthermore, mutating four known acetylated lysine residues (K242, K259, K290 and K569) of FOXO3 into arginines to mimic deacetylated FOXO3 resulted in enhanced Skp2 binding but with inhibition of FOXO3 ubiquitination; this suggests that some or all of these four lysine residues are likely the sites for ubiquitination. In the livers of mice deficient in SIRT1, we detected increased expression of FOXO3, indicating SIRT1 regulates FOXO3 protein levels in vivo. Furthermore, we found that the elevation of SIRT1 and Skp2 expression in malignant PC3 and DU145 prostate cells is responsible for the downregulation of FOXO3 protein levels in these cells. Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation.

Lymphatic sparing versus lymphatic non-sparing laparoscopic varicocelectomy in children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to explore the true efficacy and potential advantages of lymphatic sparing laparoscopic varicocelectomy (LSV) over lymphatic non-sparing laparoscopic varicocelectomy (LNSV) in children and adolescents. METHODS: A search was made for studies published up until 31 August 2010 using the terms "lymphatic sparing varicocelectomy", "laparoscopy", "adolescent" and "children" in the Medline, Embase, Ovid, Web of Science, and Cochrane databases. Randomized controlled trials (RCTs) and observational clinical studies (OCSs) comparing LSV and LNSV were included. A systematic review and meta-analysis was performed using odds ratios (ORs) for dichotomous variables. RESULTS: Out of 127 studies, 2 RCTs and 4 OCSs were eligible for inclusion, comprising 489 cases of LSV and 307 cases of LNSV. The hydrocele rates after LSV were significantly lower than after LNSV (OR = 0.19; 95% confidence interval [CI] = 0.10 to 0.36; p < 0.00001). However, no significant difference was observed between LSV and LNSV with regard to recurrence (OR = 0.65; 95% CI = 0.32-1.33; p = 0.24) or catch-up growth (OR = 2.14; 95% CI =0.97-4.72; p = 0.06). CONCLUSION: LSV is valuable in reducing the incidence of postoperative hydrocele, with similar recurrence and catch-up growth rates as LNSV. A series of RCTs are warranted to explore the efficacy of LSV in the management of varicocele in children and adolescents.

Investigation of porcine endogenous retrovirus in the conservation population of Ningxiang pig.

Porcine endogenous retrovirus (PERV) varies between pig breeds. Screening and analysis of PERV in putative pig breeds may provide basic parameters to evaluate the biological safety of xenotransplantation from pigs to humans. In this study, PERV was investigated among the conservation population of the Ningxiang pig. The result revealed that the genotype of PERV distribution was subtype A, 100%; subtype B, 100%; and subtype C, 100%. The env sequences of PERV-A and -B showed 11 clones detected by KpnI and MboI digestion, indicating that there existed multiple variants of PERV-A and -B in the Ningxiang pig. Reverse transcriptase polymerase chain reaction results showed that PERV had transcriptional activity in these individuals. In addition, PERV A/C recombinant was detected in most individuals of Ningxiang pig. Because PERV A/C recombinants increase the potential infectious risk, the breed may not be a proper donor for xenotransplantation.

Regulation of adiponectin in adipocytes upon exposure to HIV-1.

OBJECTIVES: Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. METHODS: Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. RESULTS: Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. CONCLUSIONS: We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients.

Folic acid supplements during pregnancy and risk of miscarriage.

BACKGROUND: Although taking supplements that contain 400 microg of folic acid before and during early pregnancy reduces a woman's risk for having a baby with a neural-tube defect (NTD), the effects of such supplements on other pregnancy outcomes remain unclear. We examined whether the use of such supplements affects the occurrence of miscarriage. METHODS: Participants were women in China who had taken part in a recent folic acid campaign to prevent NTDs and who had registered in this campaign before they became pregnant for the first time. We examined the risk for miscarriage among women who had confirmed pregnancies and who had or had not taken pills containing only 400 microg of folic acid before and during early pregnancy. RESULTS: The overall rate of miscarriage was 9.1% (2155/23806). The rates of miscarriage among women who had and had not taken folic acid pills before and during the first trimester were 9.0% and 9.3%, respectively (risk ratio 0.97 [95% CI 0.84-1.12]). The distributions of gestational age at pregnancy diagnosis and at miscarriage were similar for both groups of women. INTERPRETATION: In this population-based study of a cohort of women whose use of folic acid supplements while pregnant had been previously documented and who had been pregnant for the first time, we found no evidence that daily consumption of 400 microg of folic acid before and during early pregnancy influenced their risk for miscarriage.

Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists.

Elevated levels of the hormone resistin, which is secreted by fat cells, are proposed to cause insulin resistance and to serve as a link between obesity and type 2 diabetes. In this report we show that resistin expression is significantly decreased in the white adipose tissue of several different models of obesity including the ob/ob, db/db, tub/tub, and KKA(y) mice compared with their lean counterparts. Furthermore, in response to several different classes of antidiabetic peroxisome proliferator-activated receptor gamma agonists, adipose tissue resistin expression is increased in both ob/ob mice and Zucker diabetic fatty rats. These data demonstrate that experimental obesity in rodents is associated with severely defective resistin expression, and decreases in resistin expression are not required for the antidiabetic actions of peroxisome proliferator-activated receptor gamma agonists.

Apoptosis inducing effects of arsenic trioxide on human bladder cancer cell line BIU-87.

OBJECTIVE: To explore the apoptosis inducing effects of arsenic trioxide (As2O3) on human bladder cancer cells and elucidate possible mechanisms. METHODS: After treatment with As2O3, the growth inhibition rates of human bladder cancer cell line BIU-87 were studied by MTT and cell counts methods. DNA synthesis rates were detected by 3H-TdR assay. The morphological changes of cancer cells were observed by light and electronic microscopy and cell apoptosis rates were detected by TdT-mediated dUTP nick end labeling (TUNEL). bcl-2 gene expression of BIU-87 cells was observed by strept avidin-biotin complex (SABC) immunohistochemical method. RESULTS: As2O3 could effectively inhibit the growth of BIU-87 (P < 0.05), which were time and concentration dependent. The inhibition rate of 4.0 mumol/L As2O3 for DNA synthesis of cancer cells was 55.64% (P < 0.01). Partial cancer cells presented the characteristic morphological changes of apoptosis which depended on the time of exposure to drug (P < 0.05). bcl-2 expression of BIU-87 cells was decreased significantly (P < 0.05). CONCLUSION: As2O3 can significantly induce apoptosis in bladder cancer cells by down-regulating the expression of the bcl-2 gene and inhibiting DNA synthesis. This provides a potentially effective method for prevention and cure of human bladder cancer.

The blocking effect of BmP02, one novel short-chain scorpion peptide on transient outward K(+) channel of adult rat ventricular myocyte.

Two components F-2-7-4 and F-2-7-5, each composed of 28 amino acid residues, were purified from the venom of Buthus martensi Karsch by an opportune procedure with cation-exchange column chromatography and repeated HPLC. Both components were totally accounted to about 0. 88% dry weight of the crude venom. The molecular weights of both components were determined to be 2950 and 2935 by mass spectrometry, which were fully coincidence with that of the known novel short-chain peptides BmP02 and BmP03, respectively [Romi-Lebrun R, Martin-Eauclaire M-F, Escoubas P, Wu FQ, Lebrun B, Hisada M, Nakajima T. Characterization of four toxins from Buthus martensi scorpion venom, which act on apamin-sensitive Ca(2+)-activated K(+) channels. Eur J Biochem 1997;145:457-464]. In addition, the sequence of component F-2-7-4 was analyzed to be the same as that of BmP02. The components F-2-7-4 and F-2-7-5 purified in this study were, thus, finally distinguished to be BmP02 and BmP03 from the same venom. Using whole cell patch-clamp recording, it was found that BmP02 diminished the current of transient outward K(+) channel in adult rat ventricular myocyte in a concentration-dependent manner. The inhibitory effect was reversible. Dynamic studies showed that the activation, inactivation and recovery processes of the transient outward K(+) channel were not changed significantly after applying of BmP02. In addition, when BmP02 was applied to guinea pig ventricular myocyte, both delayed and inward rectified K(+) currents showed no change compared with the control. The results suggest strongly that BmP02 or -like peptides from scorpion venom may provide a useful probe for the studying of transient outward K(+) channel in rat ventricular myocyte.