Inhibition of Metformin Combined with Cisplatin on Proliferation of Human Osteosarcoma MG-63 Cells / 中国生物化学与分子生物学报

In order to study the effect and its potential mechanism of metformin combined with cisplatin treatment on human osteosarcoma MG-63 cells, MG-63 cells were treated with metformin and cisplatin and the cell proliferation and apoptosis were detected using CCK8 and flow cytometry; Cell clone formation experiment was performed to detect clone formation rate in each group; Trans well experiment was used to detect the migration and invasion ability of osteosarcoma MG-63 cells, and qPCR and Western blot were used to detect the expression of RNA and protein of apoptosis-related genes. The results showed that metformin combined with cisplatin inhibited the proliferation of human osteosarcoma MG-63 cells and promoted their apoptosis significantly (P < 0. 01); Metformin combined with cisplatin inhibited the clone formation (P < 0. 01), and the migration and invasion of human osteosarcoma MG-63 cells (P < 0. 01); Furthermore, metformin combined with cisplatin down-regulated the expression of apoptosis-related genes MCl￣1and XIAP (P <0. 01), but up-regulated the expression of apoptosis-related genes CASPASE￣3 and Cyto C (P <0. 01) and migration and invasion related genes MMP￣2 and MMP￣9 (P <0. 01). Our study indicated that metformin combined with cisplatin inhibited proliferation, promoted cell apoptosis through MCl￣1 and XIAP, and inhibited cell migration and invasion by regulating the MMP￣2 and MMP￣9 pathways in human osteosarcoma MG-63 cells.

Exosome-mediated Let-7a inhibits malignant biological behaviors of triple-negative breast cancer cells by down-regulating MYC expression / 中国肿瘤生物治疗杂志

@#Objective: To investigate the role of exosome (EXO) transporting Let-7a to regulate MYC gene in the malignant biological behaviors of triple negative breast cancer (TNBC) cell, and to explore the underlying mechanism. Methods: After the completion of cell culture, the gene and protein expressions of MYC and Let-7a in TNBC MDA-MB-231cells were detected by qPCR and WB, respectively. Recombinant lenti-virus vector carrying Let-7a and Crisper/Cas-9 system with MYC knockdown were transfected into MDA-MB-231 cells; MTT assay, Transwell assay and Scratch healing assay were performed to examine the proliferation, invasion and migration of MDA-MB-231 cells. Luciferase activity assay was performed to validate the binding between MYC and Let-7a. EXO was isolated and identified by transmission electron microscopy and WB assay in wild-type and Let-7a over-expressed MDA-MB-231 cells, respectively. After co-incubation of two types of EXO and MDA-MB-231 cells, the effects of Let-7a on biological behaviors of MDAMB-231 cells via EXO were detected by qPCR, WB, MTT and Transwell etc. Results: Let-7a was negatively correlated with MYC in breast cancer tissues and cell lines (all P<0.05); MYC promoted while Let-7a inhibited the proliferation, migration and invasion of breast cancer cells (all P<0.01); Let-7a silenced MYC by acting on 3'UTR of MYC gene, thereby reducing the expression of MYC protein (P<0.05); Let-7a was enveloped by EXO and transported to cancer cells, there by inhibiting the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: EXO some mediated Let-7a silences MYC gene by acting on its 3'UTR region, thus inhibiting the proliferation, migration and invasion of MDA-MB-231 cells.

Social behavior and group growth of finishing pigs with divergent social breeding values / Comportamiento social y crecimiento grupal de cerdos en etapa de finalización con valores divergentes de crianza sociales / Comportamento social e crescimento grupal de porcos de engorda com valores divergentes de criação social

Abstract Background: Behavioral traits of pigs have been shown to be partly under genetic control, which raises the possibility that behavior might be altered by genetic selection, resulting in pigs with better growth performance. Objective: To evaluate the behavior and growth of finishing pigs and investigate pigs selected for high or low social breeding value (SBV) in relation to social behavior and group growth. Methods: Thirty-five females and 35 boars from five positive and five negative SBV groups of finishing pigs were grown from 30 to 90 kg and housed in 10 test pens (3.0 × 3.3 m, 7 pigs/pen). Pigs were recorded with video technology for nine consecutive hours on days 1, 15, and 30 after mixing. Pigs were weighed at approximately 90 kg body weight and the number of days to reach 90 kg was then calculated. Results: The frequency and duration of behaviors were present in the positive and negative SBV groups after mixing. On day 1 after mixing, agonistic behavior was significantly higher (p=0.027) for the -SBV group compared with the +SBV group. Feeding and feeding-together behaviors were significantly higher (p<0.003) in the +SBV group on days 1 and 30 after mixing. Moreover, growth performance to reach 90 kg body weight was significantly faster (p<0.002) in the +SBV group than in the -SBV group. Conclusion: Social interactions, such as feeding-together behavior, among pen mates might affect their growth rate and feed intake. Selection for SBV could be used as an indirect technique for improving growth performance of pigs.

Resumen Antecedentes: Se ha demostrado que los rasgos conductuales de los cerdos están parcialmente bajo control genético, lo que plantea la posibilidad de que el comportamiento pueda ser alterado vía selección genética y resulte en cerdos con mejores rendimientos de crecimiento. Objetivo: Evaluar el comportamiento y crecimiento de los cerdos en etapa de finalización e investigar cerdos seleccionados por un valor alto o bajo de crianza social (SBV) en relación al comportamiento social y al crecimiento grupal. Métodos: Treinta y cinco hembras y 35 verracos, pertenecientes a cinco grupos positivos y cinco grupos negativos de SBV de cerdos en etapa de finalización, llevados hasta los 90, desde 30 kg de peso, alojados en 10 corrales de prueba (3,0 x 3,3 m, 7 cerdos/corral). Los cerdos fueron observados con la ayuda de tecnología de vídeo por nueve horas consecutivas en los días 1, 15 y 30 luego de ser mezclados. Además, los cerdos se pesaron a los 90 kg de peso aproximadamente y se calculó el número de días para alcanzar dicho peso. Resultados: La frecuencia y duración de los comportamientos de los cerdos en la etapa de finalización se presentaron en los grupos de SBV negativos y positivos luego de ser mezclados. El día 1 luego de la mezcla, el comportamiento agonístico fue significativamente mayor (p=0,027) en el grupo -SBV que en el grupo +SBV. Los comportamientos de consumo de alimento y de consumo en compañía fueron significativamente mayores (p<0,003) en el grupo +SBV en los días 1 y 30 luego de la mezcla. Además, el crecimiento para alcanzar 90 kg de peso corporal fue significativamente más rápido (p=0,002) en el grupo +SBV que el grupo -SBV. Conclusiones: Las interacciones sociales, tales como el comportamiento de consumo de alimento en compañía, entre los compañeros de corral, pueden afectar la tasa de crecimiento y consumo de alimento. La selección por SBV podría usarse como técnica indirecta para mejorar el rendimiento de crecimiento en cerdos.

Resumo Antecedentes: Os traços comportamentais dos porcos demonstraram estar parcialmente sob controle genético, o que aumenta a possibilidade de que o comportamento possa ser alterado pela seleção genética e resulte em porcos com melhor comportamento de crescimento. Objetivo: Avaliar o comportamento e o crescimento dos porcos de engorda e investigar os porcos selecionados para alto ou baixo valor de reprodução social (SBV) em relação ao comportamento social e crescimento do grupo. Métodos: Trinta e cinco fêmeas e 35 machos, pertencentes a cinco grupos de SBV positivos e cinco negativos de porcos de engorda, foram engordados até 90 de 30 kg e alojados em 10 currais de teste (3,0 × 3,3 m, 7 porcos/curral). Os porcos foram observados com o auxílio de tecnologia de vídeo durante nove horas consecutivas nos dias 1, 15 e 30 após a mistura. Além disso, os porcos foram sopesados em aproximadamente 90 kg de peso corporal e o número de dias para atingir 90 kg foi então calculado. Resultados: A frequência e a duração dos comportamentos dos porcos de engorda foram apresentadas com grupos de SBV positivo e negativo após a mistura. No dia 1 após a mistura, o comportamento agonístico foi significativamente maior (p=0,027) no grupo -SBV do que no grupo +SBV. Os comportamentos de alimentação e alimentação conjunta foram significativamente maiores (p<0,003) no grupo +SBV nos dias 1 e 30 após a mistura. Além disso, o comportamento de crescimento do grupo para atingir 90 kg de peso corporal foi significativamente mais rápido (p<0,002) no grupo +SBV do que no grupo -SBV. Conclusão: As interações sociais, como o comportamento de alimentação conjunta, entre companheiros de curral podem afetar a taxa de crescimento e a ingestão alimentar. A seleção para SBV pode ser uma técnica indireta para melhorar o comportamento de crescimento dos porcos.

Catestatin could ameliorate proliferating changes of target organs in spontaneously hypertensive rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Catestatin, a chromogranin A-derived peptide, is a potent antagonist of nicotine-evoked catecholamine release. We know that catecholamine plays an important role in cardiovascular remodeling induced by hypertension, therefore we hypothesized that catestatin would affect target-organ structure during hypertension.</p><p><b>METHODS</b>Twelve spontaneously hypertensive rats (SHRs) were randomized to SHR control group and catestatin group, the normal control group was comprised of six healthy Wistar-Kyoto rats of the same age. Tail-cuff blood pressure and pulse rate were obtained at weeks 1, 4 and 8. At the end of the eight-week period, the heart, abdominal aorta and left kidney were excised and weighed, VG staining was done and the intima-media thickness of vessels and the collagen volume fraction were assessed by an image acquisition and analysis system. The proliferating cell nuclear antigen (PCNA) was observed by immunohistochemistry, and real time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of proliferative genes including cyclin A, ki67 and PCNA in the abdominal aorta.</p><p><b>RESULTS</b>All the parameters in SHR observed in the present study increased significantly compared to Wistar Kyoto rats (P < 0.01). With intervention with catestatin, the systolic blood pressure decreased slightly but it was not significantly different from the SHR control, the cardiac mass index and left ventricular mass index both decreased significant ly, the collagen volume fraction decreased by nearly 30% in the heart, by 25% in vessels and by 10% in the kidney, and the intima-media thickness and expression of proliferative genes, including cyclin A, ki67 and PCNA, in the abdominal aorta also decreased significant ly.</p><p><b>CONCLUSIONS</b>The present study indicated that catestatin could ameliorate proliferating changes of heart, kidney and vessels during hypertension, especially to the deposition of interstitial collagen. Blood pressure was not the main factor to mediate this effect, which suggested that catestatin could become a novel protective factor for hypertensive target organs.</p>

Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype.</p><p><b>METHODS</b>Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms.</p><p><b>RESULTS</b>Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype.</p><p><b>CONCLUSIONS</b>Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.</p>

Imaging of congenital coronary artery anomalies by dual-source computed tomography angiography / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the value of dual-source computed tomography (DSCT) angiography in the examination of congenital coronary artery anomalies.</p><p><b>METHODS</b>We retrospectively examined 2530 patients by DSCT angiography between January 2008 and September 2010. Congenital coronary artery anomalies were shown by maximum intensity projection, curved planar reconstruction, and volume rendering.</p><p><b>RESULTS</b>A total of 284 segments with congenital coronary artery anomalies in 225 patients were displayed. The anomalies included those originated from the main branch of coronary artery (n=121, including 35 segments of right coronary artery with high take-off origin and 24 segments of left coronary artery, 17 segments of right coronary artery dated from left aortic sinus, 4 segments of left coronary artery dated from right aortic sinus, 2 segments of left coronary artery dated from posterior aortic sinus, 2 segments of single coronary artery, and 37 segments of para-coronary artery) , coronary artery dysplasia (n=18) , coronary artery fistula (n=9, including 4 segments of right coronary artery-right ventricle fistula, 2 segments of right coronary artery-pulmonary artery fistula, 2 segments of left coronary artery-left ventricle fistula, and 1 segments of left coronary artery-pulmonary artery fistula) , and myocardial bridge (n=136) . In addition, 818 segments of left sinuatrial nodal artery original anomalies in 1720 patients whose sinuatrial nodal artery were well shown.</p><p><b>CONCLUSION</b>DSCT can be helpful in detecting the anomalies of coronary artery.</p>

Novel MYBPC3 mutations in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients.</p><p><b>CONCLUSION</b>MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.</p>

Plasma hydrogen sulfide and homocysteine levels in hypertensive patients with different blood pressure levels and complications / 中华心血管病杂志

<p><b>OBJECTIVE</b>The present study was designed to observe the plasma concentrations of hydrogen sulfide (H(2)S) and homocysteine (HCY) in hypertensive patients with different blood pressure levels and complications.</p><p><b>METHODS</b>A total of 165 outpatients with essential hypertension were involved in this study (84 males, 81 females, mean age 59.81 +/- 10.60 years old). There were 28 new-onset untreated, 137 ever-treated patients. Among ever-treated patients, blood pressure was normal in 38, grade 1 hypertension in 43, grade 2 and 3 hypertension in 56 patients. Thirty-two patients were accompanied with coronary heart disease (CAD), and 42 patients were accompanied with stroke. A total of 32 age- and sex-matched healthy controls (18 males) were also recruited. Plasma H(2)S and HCY concentrations were determined in all patients and controls.</p><p><b>RESULTS</b>(1) Plasma H(2)S levels were significantly lower (P < 0.05) and HCY levels were significantly higher (P < 0.01) in ever-treated hypertensive patients compared with controls. (2) Plasma HCY levels were significantly higher in patients with hypertension history > 6 months and complicated with CAD compared to patients without CAD. (3) Plasma H(2)S concentrations in patients with stroke history > 5 years were significantly lower than that in patients without stroke (P < 0.01). Plasma HCY concentrations were increased in proportion to stroke history. (4) In ever-treated hypertensive patients, plasma H(2)S concentrations in patients with grade 2 and 3 hypertension were significantly lower (P < 0.05) and HCY levels significantly higher (P < 0.01) than that in patients with well-controlled blood pressure.</p><p><b>CONCLUSION</b>Hyperhomocysteinemia and the novel signaling gasotransmitter H(2)S might play important roles in the pathogenesis and development of hypertension.</p>

Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with anterior myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVES</b>To investigate the efficacy of intracoronary transfer of autologous bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction (MI) on left ventricular function and myocardial perfusion.</p><p><b>METHODS</b>Thirty-five patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled study (20 patients in cell transplantation group; 15 patients in control group). All patients were treated by standard drug therapy and percutaneous coronary intervention (PCI). Baseline and 3 months follow-up evaluations included complete clinical and laboratory examinations, six minutes walk test, echocardiography, Dual-isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) and cardiac magnetic resonance imaging (MRI).</p><p><b>RESULTS</b>Baseline parameters were similar between the two groups. NYHA classification and six minutes walk test at 3 months follow-up were also similar between the two groups. However, left ventricular ejection fraction (LVEF) determined by echocardiography and DISA-SPECT was significantly higher; regional wall motion measured by echocardiography and cardiac MRI, myocardial viability and myocardial perfusion in the infarct zone assessed by DISA-SPECT were all significantly improved than before transplantation and than that in control group at 3 months follow-up.</p><p><b>CONCLUSIONS</b>Our results indicate that intracoronary transplantation of ABMMNCs could improve the left ventricular systolic function and beneficially affect myocardial perfusion up to 3 months post transplantation in patients with myocardial infarction.</p>

Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.</p><p><b>RESULTS</b>Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.</p><p><b>CONCLUSIONS</b>Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.</p>

The relationship between function and thrombosis formation of left atrium appendage assessed by transesophageal echocardiography in patients with nonvalvular atrial fibrillation / 中华全科医师杂志

Objective To explore the relationship between size,shape and function of the left atrium appendage (LAA) and its thrombosis in patients with atrial fibrillation (AF) by transesophageal echocardiography (TEE) to provide evidence for clinical risk assessment,prognosis evaluation and treatment guidance.Method Length,diameter,end-diastolic volume (EDV) and ejection velocity (PEV) of LAA were measured in 41 patients with AF,and thrombus in LAA was detected by TEE.Results Thrombus in LAA was detected in seven of 41 patients of AF (17%).No significant difference in size and EDV was found between the patients with and without thrombus,but there was significant difference in PEV between them (P