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Mcl-1 is a member of the Bcl-2 anti-apoptotic protein family with important roles in the development, lifespan and metabolism of lymphocytes, as well as oncogenesis. Mcl-1 displays the shortest half-life of all Bcl-2 family members, with miRNA interference and proteasomal degradation being major pathways for Mcl-1 downregulation. In this study, we have identified a previously undescribed control mechanism active at the RNA level. A divergently transcribed lncRNA LOC107985203 (named here mcl1-AS1) negatively modulated Mcl-1 expression resulting in downregulation of Mcl-1 at both mRNA and protein level in a time-dependent manner. Using reporter assays, we confirmed that the mcl1-AS1 lncRNA promoter was located within Mcl-1 coding region. We next placed mcl1-AS1 under tetracycline-inducible control and demonstrated decreased viability in HEK293 cells upon doxycycline induction. Inhibition of mcl1-AS1 with shRNA reversed drug sensitivity. Bioinformatics surveys predicted direct mcl1-AS1 lncRNA binding to Mcl-1 transcripts, suggesting its mechanism in Mcl-1 expression is at the transcriptional level, consistent with a common role for anti-sense transcripts. The identification of a bi-directional promoter and lncRNA controlling Mcl-1 expression will have implications for controlling Mcl-1 activity in cancer cells, or for the purpose of enhancing the lifespan and quality of anti-cancer T lymphocytes.
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Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Éxons , Células HEK293 , Humanos , Íntrons , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Regiões Promotoras Genéticas , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Objective To compare the differences in the hypertension prevalence among children aged 7-12 in Guangzhou based on different references of hypertension. Methods A total of 7698 children aged 7-12 years old in Guangzhou were recruited by stratified cluster random sampling method. Demographic information such as gender and age was collected by questionnaire. Children’s height, weight, and blood pressure were objectively measured. There were five references for diagnosing children’s hypertension: Mi 2010, Mi 2017, Ma 2017, America 2004, and America 2017 reference. Results Based on the references above, the prevalence of hypertension for children aged 7-12 in Guangzhou reached a very high level. The prevalence of hypertension, high systolic blood pressure (SBP) and high diastolic blood pressure (DBP) based on Mi 2017 reference were all higher than those based on Mi 2010 reference, but both of them were distinctly higher than Ma 2017 reference. Compared with Mi 2010 reference, the agreement of diagnosis of high SBP and high DBP were both higher for Mi 2017 than those for Ma 2017. The agreement of high SBP was higher between Mi 2017 and America 2017 than that between Ma 2017 and America 2017 (Kappa: 0.846 vs. 0.727). Conclusion The prevalence of hypertension in children aged 7-12 in Guangzhou reachs a very high level. The prevalence of hypertension based on Mi 2017 reference is the highest and follows with America 2017 reference, and the agreement between them is excellent. Compared with Mi 2010 or America 2017 reference, the agreement for Ma 2017 is lower than that for Mi 2017 reference, respectively.
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Objective To investigate the association between maternal food group intakes during pregnancy and the risk of infantile eczema in a Chinese population. Methods A prospective birth cohort study was conducted and 523 women were recruited at 20-28 weeks of pregnancy in Guangzhou from 2017 to 2018. A validated 81-item quantitative food frequency questionnaire was used to assess maternal dietary intakes during the past month. Food items were divided into ten food groups according to the Chinese Dietary Guidelines. Offspring were followed up at 6 months by the symptom questionnaire of eczema. Multivariate Logistic regression model was conducted to evaluate the association between maternal food group intakes during pregnancy and the risk of infantile eczema. Results The cumulative incidence of eczema at 6 months was 51.8%. Maternal consumption of poultry was higher in the eczema group (27.62±25.20 g/d) than the control group (22.03±22.63 g/d, P=0.022). Comparing to the lowest quantile (Q1), higher maternal intake of poultry (Q4) and fish (Q3) were significantly associated with an increased risk of infantile eczema (OR=2.71, 95% CI=1.24-4.81; OR=2.38, 95% CI=1.23-4.59, respectively) after multivariate adjustment. Conclusion Higher intakes of poultry or fish during pregnancy were associated with an increased risk of infantile eczema in Chinese population.
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<p><b>OBJECTIVE</b>To investigate the characteristics of DUOXA2 gene mutation and the genotype-phenotype relationship in children with congenital hypothyroidism (CH) in Guangzhou, China.</p><p><b>METHODS</b>A total of 20 CH patients with suspected thyroid dyshormonogenesis who had no DUOX2 gene mutation were enrolled. These patients who were born between 2011 and 2012 were screened and diagnosed with CH in the Guangzhou Newborn Screening Center. PCR and direct sequencing were used to analyze DUOXA2 gene mutation.</p><p><b>RESULTS</b>Among the 20 patients, 2 had p.Y246X/p.Y246X homozygous mutation; 4 had monoallelic heterozygous mutation, among whom 2 carried the known pathogenic mutation c.413-414insA, 1 carried p.Y246X, and 1 carried a novel mutation, p.G79R. Reevaluation was performed at the age of 2-3 years, and the results showed that the two patients with p.Y246X/p.Y246X homozygous mutation were manifested as transient and mild permanent CH, respectively. Among the four patients with monoallelic heterozygous mutation, the one who carried p.Y246X mutation was manifested as typical permanent CH, and the other three were manifested as transient CH.</p><p><b>CONCLUSIONS</b>DUOXA2 gene mutation is a common molecular pathogenic basis for CH children with suspected thyroid dyshormonogenesis in Guangzhou, and most of them are manifested as transient CH. There is no association between DUOXA2 genotypes and phenotypes. The novel mutation p.G79R is probably a pathogenic mutation.</p>
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Feminino , Humanos , Recém-Nascido , Masculino , Hipotireoidismo Congênito , Genética , Genótipo , Proteínas de Membrana , Genética , Mutação , FenótipoRESUMO
A novel BODIPY derivative was designed for biomedical applications. Its mono-quaternized structure ensured its water-solubility and suitable amphiphilicity. Showing no singlet oxygen generation to avoid damage to healthy cells, this new derivative proved to be an extremely promising antimicrobial agent, with activity equal or superior to ampicillin against MRS Staphylococcus strains with no short-term resistance issue. Its activity against MSS Staphylococcus strains was largely superior to those of ampicillin and reached the activity of vancomycin against MSS S. epidermidis. This latter result is in particular extremely promising for the treatment of hospital-acquired infections. Also the fluorescence properties of BODIPY allowed imaging of the uptake.
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Antibacterianos/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Staphylococcus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Compostos de Boro/síntese química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Staphylococcus/classificação , Relação Estrutura-AtividadeRESUMO
This article reported the clinical manifestations, steroid profiles and adrenal ultrasound findings in two unrelated Chinese girls with lipoid congenital adrenal hyperplasia (LCAH). Direct DNA sequencing and restriction fragment length polymorphism (RFLP) analysis were used to identify the mutations of steroidogenic acute regulatory protein (StAR) gene. The two patients with 46,XX karyotype, presented hyperpigmentation, growth retardation, and hyponatremia. Steroid profiles analysis revealed elevated plasma adrenocorticotrophic hormone levels, decreased or normal serum cortisol levels and low levels of androgens. Ultrasound examinations revealed that enlarged adrenals in patient 1 and normal adrenals in patient 2. Direct DNA sequencing of StAR gene showed a reported homozygous for c.772C>T(p.Q258X) in patient 1. Compound heterozygous for c.367G>A(p.E123K) and IVS4+2T>A (both novel mutations) were found in patient 2, inherited from her mother and father respectively. The amino acid of mutant position of the novel p.E123K was highly conserved in ten different species and was predicted to have impacts on the structure and function of StAR protein by the PolyPhen-2 prediction software. RFLP analysis revealed three bands (670, 423 and 247 bp) in patient 2 and her father and two bands (423 and 247 bp) in her mother and 50 controls. It is concluded that LCAH should be considered in girls with early onset of adrenal insufficiency and that steroid profiles, karyotype analysis, adrenal ultrasound and StAR gene analysis may be helpful for the definite diagnosis of LCAH.