OBJECTIVETo investigate the effect of 4' -hydroxywogonin on proliferation and apoptosis of human acute lymphoblastic leukemia SUP-B15 and Jurkat cells, and to analyze its possible mechanism.

METHODSSUP-B15 and Jurkat cells were cultivated in vitro and treated with different concentrations of 4' -hydroxywogonin, the inhibitory effect of 4' -hydroxywogonin on the proliferation of SUP-B15 and Jurkat cells was detected by CCK-8 method; the cell apoptosis was examined by the flow cytometry with Annexin V-APC/7-AAD donble staining; the expression of C-MYC, BCL-2 and cleaved caspase 3 in SUP-B15 and Jurkat cells were measured with Western blot.

RESULTS4' -hydroxywogonin inhibited the proliferation of SUP-B15 and Jurkat cells in a dose-dependent manner (r=0.78, r=0.89), with ICvalue of (6.32± 0.53) µg/ml in SUP-B15 cells and (12.04± 0.42) µg/ml in Jurkat cells at 24 h. The early apoptotic rate of cell was also enhanced with the increase of 4' -hydroxywogonin concentrations. The results of Western blot showed that 4' -hydroxywogonin could down-regulate the expression of proliferation-related molecule C-MYC(P<0.01) and apoptosis-related molecule BCL-2(P<0.01), the expression of apoptosis-related molecule cleaved caspase 3 was up-regulate(P<0.01).

CONCLUSION4' -hydroxywogonin shows the effects of anti-tumor by inducing cell apoptosis and inhibiting cell proliferation, its molecular mechanism maybe relate with down-regulation of C-MYC and BCL-2 expression and up-regulation of the cleaved caspase 3 expression.

BACKGROUNDNucleolin (NCL) is the most abundant RNA-binding protein in the cell nucleolus and plays an important role in chromatin stability, ribosome assembly, ribosomal RNA maturation, ribosomal DNA transcription, nucleocytoplasmic transport, and regulation of RNA stability and translation efficiency. In addition to its anti-apoptotic properties, the underlying mechanisms associated with NCL-related roles in different cellular processes remain unclear. In this study, the effect of NCL on microRNA (miRNA) expression was evaluated by generating transgenic mice with myocardial overexpression of NCL and by analyzing microarrays of mature and precursor miRNAs from mice.

METHODSUsing microinjection of alpha-MyHc clone 26-NCL plasmids, we generated transgenic mice with myocardial overexpression of NCL firstly, and then mature and precursor miRNAs expression profiles were analyzed in NCL transgenic mice (n = 3) and wild-type (WT) mice (n = 3) by miRNA microarrays. Statistical Package for the Social Sciences version 16.0 software (SPSS, Inc., Chicago, IL, USA) was used to perform Student's t-test, and statistical significance was determined at P < 0.05.

RESULTSSeveral miRNAs were found to be differentially expressed, of which 11 were upregulated and 4 were downregulated in transgenic mice with myocardial overexpression of NCL compared to those in WT mice. Several differentially expressed miRNAs were subsequently confirmed and quantified by real-time quantitative reverse transcription-polymerase chain reaction. Bioinformatics analysis was used for the prediction of miRNA targets. Furthermore, in vitro experiments showed that NCL regulated miR-21 expression following hydrogen peroxide preconditioning.

CONCLUSIONSMyocardial-protection mechanisms exerted by NCL might be mediated by the miRNAs identified in this study.

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
Animals ; Apoptosis ; Cause of Death ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Repression, Psychology ; RNA, Small Interfering

The Wnt signaling pathway and its key component β-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, β-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of β-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of β-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of β-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.
beta Catenin ; Biomarkers ; Blotting, Western ; Cyclin D1 ; Cytoplasm ; Diagnosis ; Down-Regulation ; Immunochemistry* ; Lymphoid Enhancer-Binding Factor 1 ; Mammals ; Mammary Glands, Human ; Polymerase Chain Reaction* ; Up-Regulation ; Wnt Signaling Pathway

OBJECTIVETo evaluate the colorectal cancer (CRC) prevention effect of metformin in comparison with that of other T2DM medications from a Markov model perspective.

METHODSLiterature concerning CRC morbidity of T2DM patients with metformin or other diabetes medications treatment was reviewed in PubMed and Cochrane Library database from September 2010 to December 2016.

INCLUSION CRITERIA(1)enrolled population was adult patients with T2DM but without CRC; (2) any of the parameters applied in our model was reported; (3) randomized clinical trials (RCTs), quasi-randomized trials, prospective or retrospective cohort studies. With CRC morbidity as endpoint, parameters were extracted to construct Markov model to assess CRC morbidity and cumulative tumor-free survival in each group over 11 years' follow-up period. Finally, Monte Carlo analysis was performed to evaluate the influence of parameter instability on the model.

RESULTSSeven literatures were recruited and 10 000 patients were virtually allocated for each arm. In contrast with non-metformin group, T2DM patients treated with metformin had a lower rate of CRC(1.670% vs. 2.146%, P=0.016). Moreover, cumulative tumor-free survival of metformin group was, slightly but significantly, better than that of non-metformin group (10.908 years vs. 10.882 years, P=0.000).

CONCLUSIONST2DM patients treated with metformin have a lower morbidity of CRC and a better cumulative tumor-free survival than those of non-metformin group. Large scale RCTs are needed to illustrate the role of metformin in the prevention of CRC.

BACKGROUNDScreening on multidrug-resistant tuberculosis (MDR-TB) has been limited to the serious TB subpopulations excluding the new TB patients. This study aimed to examine MDR-TB burden among the new TB patients.

METHODSWe conducted a study in Zhejiang Province during 2009-2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients. The number, prevalence, and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.

RESULTSA total of 200 and 791 MDR-TB cases were, respectively, identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013. The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time, but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.

CONCLUSIONSThe study indicated that MDR-TB burden among new TB patients was high, thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.

BACKGROUNDThe emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.

METHODSThis prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.

RESULTSThe median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.

CONCLUSIONSSubstantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

OBJECTIVETo report on the first case with chromosome 14q12 triplication involving the FOXG1 gene.

METHODSThe clinical, radiological and array-based comparative genomic hybridization (aCGH) data of a patient was analyzed, in addition with a literature review.

RESULTSThe 9-year-old girl has suffered from severe psychomotor delay, infantile spasms, severe mental retardation, absent language, autistic spectrum disorders, impaired ambulation, poor functional hand use and microcephaly, which were considered as manifestation of FOXG1 related diseases. Magnetic resonance imaging has documented heterotopic gray matter changes. aCGH showed a 1.9 Mb triplication in the 14q12 region, which involved the FOXG1 and a predicted gene 14orf23.

CONCLUSIONFor patients with early-onset severe psychomotor retardation, epilepsy, microcephaly, severe cognitive impairment and encephalodysplasia, analysis of copy number variations and mutations of the FOXG1 gene is crucial for the diagnosis.

Autism Spectrum Disorder ; genetics ; Child ; Chromosomes, Human, Pair 14 ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Female ; Forkhead Transcription Factors ; genetics ; Humans ; Intellectual Disability ; genetics ; Magnetic Resonance Imaging ; Microcephaly ; genetics ; Nerve Tissue Proteins ; genetics