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1.
BMC Public Health ; 20(1): 955, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552694

RESUMO

BACKGROUND: Tibet is located in the high-altitude area of Southwest China, where the health level is influenced by specific factors such as the natural environment and living habits. However, there has been little research that has focused on Tibetan health conditions. The two-week prevalence rate is an important indicator of the health level of residents. The purpose of this study was to understand the health status of the residents and the health service needs in Tibet. METHODS: The two-week prevalence rate was calculated using data from a population of 10,493 individuals aged 15 and above that was obtained from the 2018 Sixth National Health Service Survey of Tibet. We initially analysed the types and associated factors of two-week illnesses in Tibetan. The influencing factors for the two-week prevalence rate in Tibet were determined by multivariate logistic regression analysis. Subsequently, we assessed the severity of two-week illnesses by calculating the average days of the duration of the disease, the days of being bedridden and the days of being off work. RESULTS: The two-week illness prevalence rate was 20.1% in Tibet. Digestive system diseases were frequent, and hypertension was the most common disease. According to the multivariate logistic regression analysis, the two-week prevalence rate was associated with gender, age, residence, marital status, and employment status. In addition, the severity of two-week illnesses differed among the residents. CONCLUSION: This study identified that health service needs have increased in Tibet and that the health status of the local residents needs to be improved. Moreover, hypertension has become a major health hazard for the residents and should be considered in the utilization of health services.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32427704

RESUMO

OBJECTIVE: To explore the incidence rate and characteristics of symptomatic venous thromboembolism (VTE) after peripherally inserted central catheters (PICC) placement in children with acute leukemia (AL). METHODS: The authors performed a retrospective study aiming at children admitted to Pediatric Blood Diseases Center with a new diagnosis of AL and received a PICC insertion, collected the clinical materials of all venous thrombosis cases, and analyzed the incidence rate and characteristics in various types of AL. RESULTS: From September 2007 to December 2018, a total of 2423 patients got PICCs at least once, of whom 29 patients experienced thrombosis events and the overall incidence rate of symptomatic VTE after PICC insertion was 1.2%. Deep venous thrombosis accounted for the majority with 75.9%. Seven cases of cerebral venous sinus thrombosis were documented and they all developed in patients with acute lymphoblastic leukemia (ALL). No pulmonary embolism was detected. Patients with acute myeloid leukemia (AML) had an identical risk of thrombosis to patients with acute lymphoblastic leukemia (ALL) (1.7% vs. 1.09%, P>0.05). All thrombi in patients with AML were located on the upper extremity, whereas in the ALL group about half of the thromboembolism developed in other locations. There were no statistical differences between patients in different clinical trials of the ALL group (0.7% vs. 1.6%, P>0.05). CONCLUSIONS: The incidence rates of symptomatic VTE after PICC placement in children with AL in our center were relatively low and acceptable. For patients with AML, PICC placement plays the most important role in venous thrombosis. However, in patients with ALL, the potential risk factors were more complex.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 460-465, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434641

RESUMO

OBJECTIVE: To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation. METHODS: Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed. RESULTS: Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The median age of onset of malignant myeloid transformation was 48 months (ranged 7 months to 14 years). Of the 11 children, 45% had abnormalities in the hematological system alone. Mutations of the SBDS gene were detected in all 11 children, among whom 5 (45%) had c.258+2T>C homozygous mutation and 3 (27%) had c.184A>T+c.258+2T>C compound heterozygous mutation. The new mutations of the SBDS gene, c.634_635insAACATACCTGT+c.637_638delGA and c.8T>C, were rated as "pathogenic" and "possibly pathogenic" respectively. The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100% and 0% respectively (P=0.001). CONCLUSIONS: SDS children may have hematological system symptoms as the only manifestation, which needs to be taken seriously in clinical practice. The type of malignant transformation is associated with prognosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32420669

RESUMO

OBJECTIVES: Our aim is to distinguish different trajectories of cognitive change in Chinese geriatric population and identify risk factors for cognitive decline in each subpopulation. METHODS: We obtained data from five waves (2002, 2005, 2008, 2011, 2014) of the Chinese Longitudinal Health Longevity Survey, using the Chinese Mini-Mental State Examination (C-MMSE) as a proxy for cognitive function. We applied growth mixture modeling (GMM) to identify heterogeneous subpopulations and potential risk factors. RESULTS: Our sample included 3859 older adults, 1387 (48.7%) male and 1974 (51.2%) female with age range of 62 to 108 (average of 74.5) at initial survey. Using GMM and best fit statistics, we identified two distinct subgroups in respect to their longitudinal cognitive function: (a) cognitively stable (87.8%) group with 0.49 C-MMSE points decline per 3 years, and (b) cognitively declining (12.2%) group with 6.03 C-MMSE points decline per 3 years. Of note, cognitive activities were protective, and hearing and visual impairments were risk factors in both groups. Diabetes, hypertension, stroke and cardiovascular disease were associated with cognitive decline in the cognitively declining group. Physical activities, and intake of fresh vegetables, fruits, and fish products were protective in the cognitively stable group. CONCLUSIONS: Using GMM, we identified heterogeneity in trajectories of cognitive change in older Chinese people. Moreover, we found risk factors specific to each subgroup, which should be considered in future studies.

5.
ChemMedChem ; 15(12): 1089-1100, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32233075

RESUMO

Gramicidin S (GS), one of the most widely investigated antimicrobial peptides (AMPs), is known for its robust antimicrobial activity. However, it is restricted to topical application due to undesired hemolytic activity. With the aim of obtaining nontoxic GS analogues, we describe herein a molecular approach in which the native GS ß-turn region is replaced by synthetic ß,γ-diamino acids (ß,γ-DiAAs). Four ß,γ-DiAA diastereomers were employed to mimic the ß-turn structure to afford GS analogues GS3-6, which exhibit diminished hemolytic activity. A comparative structural study demonstrates that the (ßR,γS)-DiAA is the most-stable ß-turn mimic. To further improve the therapeutic index (e. g., high antibacterial activity and low hemolytic activity) and to extend the molecular diversity, GS5 and GS6 were used as structural scaffolds to introduce additional hydrophobic or hydrophilic groups. We show that GS6K, GS6F and GS display comparable antibacterial activity, and GS6K and GS6F have significantly decreased toxicity. Moreover, antibacterial mechanism studies suggest that GS6K kills bacteria mainly through the disruption of the membrane.

6.
Nat Commun ; 11(1): 1473, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193380

RESUMO

Caffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. Due to its occasional side effects, reduction of caffeine in a natural way is of great importance and economic significance. Recent studies reveal that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha (Kucha), which involves oxidation at the C8 and methylation at the N9 positions of caffeine. However, the underlying molecular mechanism remains unclear. Here, we identify the theacrine synthase CkTcS from Kucha, which possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation. The crystal structure of the CkTcS complex reveals the key residues that are required for the N9-methylation, providing insights into how caffeine N-methyltransferases in tea plants have evolved to catalyze regioselective N-methylation through fine tuning of their active sites. These results may guide the future development of decaffeinated drinks.

7.
Chemosphere ; 249: 126129, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32062210

RESUMO

A novel coagulant poly-ferric-titanium-silicate-sulfate (PFTS) was synthesized and employed to treat two typical kinds of dye wastewaters-disperse blue and reactive yellow. The results indicated that PFTS with a Si/Fe molar ratio of 0.02 exhibited superior coagulation performance, especially under alkaline condition. The residual turbidity after coagulation by PFTS was only half of that after coagulation by poly-ferric-titanium sulfate (T-PSF). The sludge volume index was also reduced by PFTS compared to T-PSF in reactive dye treatment. Through the structure and morphology investigation of PFTS, it was found that new bonds of Si-O-Fe, Si-O-Ti and Fe-OH (Si-OH) were formed, and multi-branched structures and expanded surface area were generated. Additionally, compared with T-PSF, the floc strength and the floc size were also enhanced by PFTS, which was attributed to the polymerization between polysilicic acid and Fe/Ti which formed multi-branched structures, and finally adsorption and bridging ability of the coagulant was improved. Furthermore, the floc formed in reactive yellow wastewater treatment was larger and looser than that formed in disperse blue wastewater, with poorer strength and recovery ability, which can also interpret the better coagulation efficiency in disperse dye water treatment. From the results of coagulant characterization, zeta potential and flocs properties, it can be inferred that charge neutralization by the positive charged hydrolysate of coagulant was identified as the critical effect in disperse dyes removal, while the sweep and adsorption of metal hydroxyl compound formed during the hydrolysis of coagulants were considered to play a key role in reactive dye removal.


Assuntos
Corantes/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Adsorção , Cloretos/química , Eletrólitos , Compostos Férricos , Floculação , Hidrólise , Ferro , Esgotos , Silicatos , Sulfatos , Titânio/química , Águas Residuárias/química , Purificação da Água/métodos
8.
Anal Bioanal Chem ; 412(4): 871-880, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901958

RESUMO

Novel carbon dots (CDs) were synthesized by a one-pot hydrothermal approach using ampicillin as a precursor, and the as-prepared CDs exhibited a high quantum yield (23%). The CDs were found to possess abundant surface functional groups, thus providing good permeability to the cell, and the antibacterial activity of CDs was evaluated. S. aureus and L. monocytogenes were selected as model bacteria, and our results showed that the CDs exhibited antibacterial activity against S. aureus and L. monocytogenes under visible light illumination, even at low concentrations. The antibacterial mechanism is believed to be the production of reactive oxygen species (ROS) from CDs under visible light irradiation, which attacked the bacterial cell membranes, resulting in the death of the bacteria. In addition, because of the multicolor fluorescence properties of CDs, staining of S. aureus and L. monocytogenes obtained multicolor fluorescence images at different excitation wavelengths. Based on these results, CDs are a promising candidate material for biological applications. Graphical abstract.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Carbono/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Ampicilina/análogos & derivados , Ampicilina/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Carbono/química , Humanos , Listeriose/tratamento farmacológico , Nanopartículas/química , Infecções Estafilocócicas/tratamento farmacológico
9.
Int Health ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967316

RESUMO

In the context of a rapidly ageing Chinese population, this study aims to examine trends in the prevalence of cognitive impairment among people ≥65 y of age in China. Our sample is 72 821 adults aged 65-105 y from the seven waves of the Chinese Longitudinal Healthy Longevity Survey, a national mixed longitudinal cohort. The Chinese version of the Mini-Mental State Examination was used to measure CI. Risk factor-adjusted prevalence trend was examined using multilevel regression models. Age-standardized prevalence of cognitive impairment increased from 11.00% in 1998 to 11.84% in 2008 and decreased to 8.88% in 2014. Older age, female gender, less education, rural residence, not married, lack of physical and cognitive activities, suffering from stroke, vision and hearing impairment, and activities of daily living disability were negatively associated with cognitive impairment. Our study suggests a decreasing trend of cognitive impairment prevalence in China. However, whether decreasing prevalence will contribute to a reduced burden of cognitive impairment given the ageing of the population is unknown.

10.
J Photochem Photobiol B ; 202: 111734, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837584

RESUMO

A simple and one-step microwave digestion method was utilized to synthesize the highly photoluminescent glucosamine derived nitrogen and zinc doped carbon dots (N, Zn-CDs) with a bluish-green luminescence property. The synthesized N, Zn-CDs inherited a good photoluminescence property with a quantum yield of 74% and which were characterized by XPS, XRD, TEM, FT-IR, UV-Vis, and fluorescence spectrometry. More importantly, N, Zn-CDs served as a fluorescence sensor for the detection of Fe3+ ions, under optimal conditions, a good linear relationship was established in the concentration range of 0.25-125 µM. Also, the experimental results showed the detection limit of N, Zn-CDs against Fe3+ was 0.15 µM, this could be a promising assay for sensing Fe3+ ions. Also, the role of zinc doping was explored by conducting the detection under similar experimental conditions in the absence of zinc, and reports revealed that the reason for high photoluminescence was due to the zinc doping. Along with the sensing application, our group had investigated the bactericidal property of synthesized N, Zn-CDs against gram-negative (Escherichia coli), and gram-positive pathogens (Staphylococcus aureus). N, Zn-CDs displayed good bactericidal activity against both pathogens under light conditions, but Escherichia coli, even under the dark condition proved its activity. Besides, the morphology of both the strains was displayed before and after the treatment via a scanning electron microscopic images. Also, a plausible mechanism for bactericidal activity was also explained. The reported synthesis method could provide a novel approach for the design of high photoluminescent N, Zn-CDs with good sensing and bactericidal property towards Fe3+ ions, gram-negative and positive bacterial strains.


Assuntos
Carbono/química , Compostos Férricos/análise , Nitrogênio/química , Pontos Quânticos/química , Espectrometria de Fluorescência , Zinco/química , Catálise , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Água Doce/análise , Íons/química , Luz , Limite de Detecção , Micro-Ondas , Pontos Quânticos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
11.
Chemosphere ; 238: 124637, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31470312

RESUMO

The addition of powdered activated carbon (PAC) to remove micropollutants is a commonly used technology to improve drinking water quality. However, the effects of PAC dosing strategy on the coagulation-flocculation process of water treatment have not been well understood, especially for water with low amounts of inorganic particles. Therefore, the current research aimed to comprehensively study the effects of simultaneous addition of PAC and aluminum sulfate (AS) coagulants (denoted as PAC-AS) or adding PAC 2 h before coagulation (denoted as PAC2h-AS) on the coagulation behavior in humic acid (HA) and HA-kaolin water treatment. The results showed that the floc size, growth rate, breakage factor, and fractal dimension were all enhanced by PAC-AS and PAC2h-AS for HA but not for HA-kaolin water treatment. In HA water treatment, PAC-AS reached a larger floc size and faster growth rate, while PAC2h-AS achieved a larger floc breakage factor and fractal dimension value. For PAC2h-AS, the pre-adsorption of HA onto PAC would lower the initial particle concentration and reduce the collision probability during HA water coagulation process; thus, the DOC removal efficiency, floc size, and growth rate of PAC2h-AS were relatively smaller than those of PAC-AS. For the floc strength and floc fractal dimension, the pre-adsorption of HA onto PAC contributed to formation of stronger inter-particle bonds; thus, stronger and more compact flocs were formed by PAC2h-AS compared with those of PAC-AS. The addition of PAC had a smaller impact on the floc properties in HA-kaolin water treatment owing to its higher initial particle concentration.


Assuntos
Carvão Vegetal/farmacologia , Floculação/efeitos dos fármacos , Substâncias Húmicas , Caulim/farmacologia , Purificação da Água/métodos , Adsorção , Compostos de Alúmen , Fractais , Caulim/química , Pós/farmacologia
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(10): 1016-1021, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31642437

RESUMO

OBJECTIVE: To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA. METHODS: Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed. RESULTS: Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A>T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C>T(p.Q59X) was rated as "pathogenic". CONCLUSIONS: ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.


Assuntos
Anemia Sideroblástica , Síndromes Mielodisplásicas , 5-Aminolevulinato Sintetase , Anemia Sideroblástica/genética , Criança , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Proteínas de Transporte da Membrana Mitocondrial , Mutação , Fenótipo
13.
Med Sci Monit ; 25: 6691-6701, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489957

RESUMO

BACKGROUND The small ubiquitin-like modifier 1 (SUMO1) and small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) are long noncoding RNAs (lncRNAs). The prognostic significance of SUMO1 and SUMO1P3 expression in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to use clinical, genetic, and survival data from the Cancer Genome Atlas (TCGA), to analyze the prognostic significance of SUMO1 and SUMO1P3 expression in the two main subtypes of NSCLC, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MATERIAL AND METHODS Data were acquired from TCGA and in silico survival analysis was performed. SUMO1 and SUMO1P3 expression were compared between patients with LUAD and LUSC. Patient outcome was assessed as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Recurrence-free survival (RFS) was defined as the survival time from primary surgery to the time of locoregional or distant recurrence of lung cancer. RESULTS SUMO1P3 was significantly increased in LUSC and LUAD tissues compared with adjacent normal lung tissue and was significantly co-expressed with SUMO1. SUMO1P3 expression was significantly increased in patients with LUAD but not LUSC with reduced RFS after primary or follow-up treatment. Although patients with LUAD who had high SUMO1 or SUMO1P3 expression had reduced RFS compared with low expression groups, univariate and multivariate analysis showed that only SUMO1P3 expression was independently associated reduced RFS (HR, 1.418; 95% CI, 1.041-1.930; p=0.027). CONCLUSIONS SUMO1P3 expression was an independent indicator of reduced RFS in patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Pseudogenes , Proteína SUMO-1/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Proteína SUMO-1/metabolismo , Resultado do Tratamento , Regulação para Cima/genética
14.
Rapid Commun Mass Spectrom ; 33(24): 1877-1883, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31429145

RESUMO

RATIONALE: Herbal dietary supplements (HDSs) adulterated with undeclared synthetic drugs can lead to serious health problems METHODS: A fast-switching positive/negative high-voltage (+/- HV) was developed to apply on electrospray ionization mass spectrometry (ESI-MS) with porous tips for rapid screening of five antirheumatic drugs in antirheumatic HDSs. The fast-switching (switch-time: 100 ms) negative and positive ions were alternately generated to perform full-MS and tandem-MS analysis, providing an effective method for rapid detection of analytes in whichever mode of detection was most suitable (negative or positive ion mode). The use of different tips and solvents was also optimized in this work. RESULTS: The limits of detection of the five antirheumatic drugs were found to be less than 0.1 ng/g (S/N > 3). The reproducibility of the five drugs was measured to be 10.0-23.3% (n = 5). A single sample analysis could be completed within 1 min. Rapid screening of a total of 28 real HDS samples collected from the market was examined by the fast-switching HV substrate-tip ESI-MS method, and the screening result was further validated by conventional liquid chromatography/mass spectrometry. CONCLUSIONS: Overall, our results demonstrated that fast-switching HV substrate-tip ESI-MS is a rapid, reliable, and effective method for simultaneous screening of various analytes in complex samples.


Assuntos
Antirreumáticos/análise , Contaminação de Medicamentos , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Suplementos Nutricionais/análise , Contaminação de Medicamentos/estatística & dados numéricos , Sensibilidade e Especificidade
15.
BMC Med Genet ; 20(1): 130, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345173

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders. The present study aimed to identify the genetic cause of a Chinese Han family with non-syndromic oculocutaneous albinism (OCA). CASE PRESENTATION: Here, we report an 11-month-old male proband from a Chinese Han non-consanguineous family, who presented with milky skin, yellow white hair, nystagmus, astigmatism, and hypermetropia. We performed the targeted next-generation sequencing (NGS) on the proband and identified two novel compound heterozygous variants (c.1865 T > C (p.Leu622Pro) and exons 17-21 deletion) in OCA2 gene associated with OCA type 2 (OCA2, OMIM 203200). Meanwhile, a previously reported heterozygous mutation (c.4805G > A) in MYO7 gene related with Usher syndrome type 1B was found. The online tools SIFT, PolyPhen-2, and Mutation Taster predicted variant c.1865 T > C was probably damaging. The residue p.Leu622 was in a highly conserved region among species by CLUSTALW. Three-dimensional homology model with I-TASSER indicated that p.Leu622Pro variant disturbed the formation of the α-helix, resulting in a random coil structure. The gross deletion (exons 17-21) in OCA2 gene has was not been reported previously. These two novel variants in OCA2 gene were inherited from each parent respectively, after verification by Sanger sequencing and quantitative PCR (qPCR) in the family. CONCLUSIONS: This study indicates the two novel compound heterozygous mutations in OCA2 gene may be responsible for clinical manifestations of OCA2. It expands the mutation spectrum of OCA2 gene and is helpful to screen for large deletions with targeted NGS protocol in monogenic disease. It also assists the genetic counselling, carrier screening and personalized healthcare of the disease.


Assuntos
Albinismo Oculocutâneo/genética , Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Albinismo Oculocutâneo/fisiopatologia , Éxons , Aconselhamento Genético , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Modelos Moleculares , Miosina VIIa , Miosinas/genética , Conformação Proteica , Análise de Sequência de Proteína , Deleção de Sequência
16.
J Endocrinol ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344684

RESUMO

Prenatal ethanol exposure (PEE) adversely affects the offspring reproductive system. We aimed to confirm the susceptibility to premature ovarian insufficiency (POI) in female PEE offspring and elucidate its intrauterine programming mechanism. The pregnant Wistar female rats were intragastrically administered with 4 g/kg×d of ethanol from gestational day (GD) 9 to 20. Offspring reproductive parameters were detected on GD20, postnatal week (PW) 6, and PW12. The PEE foetuses showed a decreased number of oocytes, increased ovarian cell apoptosis, and upregulated expression levels of ovarian insulin-like growth factor 1 (IGF1) signaling pathway and steroidogenic enzymes. The proportion of atretic follicles in adult rats was increased, while the number of anti-Müllerian hormone-positive antral follicles was decreased. The serum oestradiol (E2) levels were decreased, but the follicle stimulation hormone levels were elevated. The ovarian Igf1 signaling pathway was transformed from activation during puberty to relative inhibition in adulthood, and the expression levels of ovarian steroidogenic enzymes were inhibited in adulthood. Furthermore, we treated the human granulosa cell line KGN with different ethanol concentrations (15, 30, 60, 120 mM) and found that the expression of IGF1 signaling pathway components, 3ß-HSD, and P450arom, as well as the production of E2, was increased. After IGF1 siRNA transfection, P450arom expression and E2 production were downregulated. These results suggest that PEE induces POI susceptibility in adult females, which may be caused by over-activation of the foetal ovarian Igf1 signaling pathway and steroidogenesis under PEE, resulting in accelerated early development of folliculogenesis and depletion of primordial follicles.

17.
J Asian Nat Prod Res ; : 1-8, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31163996

RESUMO

Zeaxanthin dipalmitate (3) and two zeaxanthin dipalmitate derivatives, including one new compound (1), were obtained from wolfberry [the fruit of Lycium barbarum L. (Solanaceae)]. Their structures were unambiguously elucidated by spectroscopic analyses. Compound 2 is isolated from the genus Lycium for the first time, and its 1D/2D NMR data are firstly reported. All the compounds belong to carotenoids which are a kind of major bioactive constituents in wolfberry and are also responsible for wolfberry's red color.

18.
Phytochemistry ; 164: 60-66, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096077

RESUMO

Fifteen phenylpropanoid glycosides, including six undescribed compounds were isolated from the fruit of Lycium barbarum L. (Solanaceae) (goji or wolfberry). Their structures were identified by detailed spectroscopic analyses. Seven known compounds were firstly isolated from the genus Lycium, in which the 1D and 2D NMR data of one compound were reported for the first time. Notably, two undescribed compounds were a pair of rare tautomeric glycoside anomers characterized by the presence of free anomeric hydroxy. Antioxidant and hypoglycemic activities of all these compounds were assessed using DPPH radical scavenging, oxygen radical absorbance capacity (ORAC), and α-glucosidase inhibitory assays, respectively. These compounds showed different levels of oxygen radical absorbance capacity, and some isolates exhibited potent antioxidant activity with greater ORAC values than the positive control (EGCG).


Assuntos
Antioxidantes/farmacologia , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Lycium/química , Fenilpropionatos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Conformação Molecular , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Picratos/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
19.
J Med Chem ; 62(17): 7603-7617, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30938996

RESUMO

Gramicidin S (GS), one of the oldest commercially used peptide antibiotics, is known for its robust antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Although it was discovered well over 70 years ago, its clinical potential was limited to topical applications because of its high hemolytic activity. To overcome this side effect, significant efforts have been invested in the chase for GS analogues with high therapeutic index (e.g., high antimicrobial activity and low hemolytic activity) in the past decades. In this Perspective, the structural properties and biological profiles (including the recently discovered activities) of representative GS analogues designed by different approaches are described and analyzed. We also present how the general structure-activity relationships were established and how they could help in the design of more efficient GS analogues.

20.
Food Chem Toxicol ; 128: 256-266, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959089

RESUMO

Prenatal nicotine exposure (PNE) could induce ovarian dysplasia in offspring. This study aimed to confirm its intrauterine origin and explore a programming mechanism of ovarian dysplasia caused by PNE. Pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg.d) from gestation day (GD) 9 to GD20. Serum of female offspring was obtained for hormone assays and ovarian tissues were collected. The results showed that PNE impaired ovarian development, and inhibited estradiol production and cytochrome P450 aromatase (P450arom) expression before and after birth. Moreover, the nicotinic acetylcholine receptors (nAChRs) expression was increased in utero, while histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac levels in the P450arom promoter region were decreased persistently in PNE group before and after birth. In vitro, nicotine decreased P450arom expression and estradiol production in human granulosa cell line KGN. Furthermore, nicotine treatment up-regulated nAChRα6 and α9 expression and down-regulated the H3K9ac and H3K27ac levels of the P450arom promoter region. Non-specific nAChRs inhibitor vecuronium bromide reversed these effects. These results suggest that PNE could induce ovarian dysplasia and inhibit estradiol synthesis in the female offspring rats, which was related to the decreased H3K9ac and H3K27ac levels in the promotor region of the P450arom via the nAChRs.


Assuntos
Aromatase/genética , Estradiol/biossíntese , Células da Granulosa/efeitos dos fármacos , Histonas/metabolismo , Exposição Materna , Nicotina/toxicidade , Ovário/enzimologia , Regiões Promotoras Genéticas , Acetilação , Animais , Feminino , Células da Granulosa/metabolismo , Humanos , Ovário/metabolismo , Gravidez , Ratos , Ratos Wistar , Receptores Nicotínicos/metabolismo
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