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1.
Artigo em Inglês | MEDLINE | ID: mdl-34283016

RESUMO

Two halophilic archaeal strains, Gai3-2T and NJ-3-1T, were isolated from salt lake and saline soil samples, respectively, collected in PR China. The 16S rRNA gene sequences of the two strains were 97.5% similar to each other. Strains Gai3-2T and NJ-3-1T had the highest sequence similarities to 'Halobonum tyrrellense' G22 (96.7 and 97.8%, respectively), and displayed similarities of 91.5-93.5% and 92.3-94.7%, respectively, to Halobaculum members. Phylogenetic analysis revealed that the two strains formed different branches and clustered tightly with 'H. tyrrellense' G22 and Halobaculum members. The average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH) and amino acid identity (AAI) values between the two strains were 83.1, 26.9 and 77.9%, respectively, much lower than the threshold values proposed as a species boundary. These values between the two strains and 'H. tyrrellense' G22 (ANI 77.9-78.2%, isDDH 22.5-22.6% and AAI 68.8-69.3%) and Halobaculum members (ANI 77.53-77.63%, isDDH 21.8-22.3% and AAI 68.4-69.4%) were almost identical, and much lower than the recommended threshold values for species delimitation. These results suggested that strains Gai3-2T and NJ-3-1T represent two novel species of Halobaculum. Based on phenotypic, chemotaxonomic and phylogenetic properties, strains Gai3-2T (=CGMCC 1.16080T=JCM 33550T) and NJ-3-1T (=CGMCC 1.16040T=JCM 33552T) represent two novel species of the genus Halobaculum, for which the name Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov. are proposed.


Assuntos
DNA Arqueal/isolamento & purificação , Halobacteriaceae/isolamento & purificação , Lagos/análise , Extratos Vegetais/isolamento & purificação , Solo/química , DNA Arqueal/genética , Halobacteriaceae/genética , Filogenia , Extratos Vegetais/genética , Análise de Sequência de DNA/métodos
2.
BMC Infect Dis ; 20(1): 321, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370734

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.


Assuntos
Antituberculosos/uso terapêutico , Etoposídeo/uso terapêutico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Mycobacterium tuberculosis/isolamento & purificação , Inibidores da Topoisomerase II/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Biópsia , Diagnóstico Precoce , Ferritinas/sangue , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/microbiologia , Masculino , Pancitopenia , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/microbiologia
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 355-360, 2020 Apr.
Artigo em Zh | MEDLINE | ID: mdl-32312375

RESUMO

OBJECTIVE: To study the heritability of obesity in children aged 30-36 months in Xi'an, China, as well as the role of four single nucleotide polymorphisms (SNPs) associated with body mass index in the susceptibility to obesity in children. METHODS: Random sampling was performed to select 1 637 children, aged 30-36 months, from four communities of Xi'an from March 2017 to December 2018. Physical assessment was performed for these children, and a questionnaire survey was conducted for parents. Then the Falconer regression method was used to calculate the heritability of childhood obesity. Venous blood samples were collected from 297 children who underwent biochemical examinations, among whom there were 140 children with obesity/overweight (obesity/overweight group) and 157 with normal body weight (normal body weight group). The MassARRAY RS1000 typing technique was used to detect CDKAL1 gene rs2206734, KLF9 gene rs11142387, PCSK1 gene rs261967, and GP2 gene rs12597579. The distribution of alleles and genotypes was compared between the obesity/overweight and normal body weight groups. An unconditional logistic regression model was used to investigate the benefits of dominant and recessive genetic models. RESULTS: For the 1 637 children, the heritability of obesity from the parents was 83%±8%, and the heritability from mother was slightly higher than that from father (86%±11% vs 78%±12%). There were significant differences in the distribution of rs2206734 alleles and genotypes and rs261967 genotypes between the obesity/overweight and normal body weight groups (P<0.0125). The children carrying T allele at rs2206734 had a significantly higher risk of obesity than those carrying CC (OR=0.24, P<0.0125), and the children carrying GG at rs261967 had a significantly higher risk of obesity than those carrying A allele (OR=4.11, P<0.0125). CONCLUSIONS: Genetic factors play an important role in the pathogenesis of obesity in children, and the SNPs of CDKAL1 rs2206734 and PCSK1 rs261967 are associated with the susceptibility to obesity in children aged 30-36 months in Xi'an.


Assuntos
Obesidade Infantil , Polimorfismo de Nucleotídeo Único , Índice de Massa Corporal , Pré-Escolar , China , Humanos , Sobrepeso , Fatores de Risco
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 783-788, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-31416503

RESUMO

OBJECTIVE: To investigate the influence of pre-pregnancy parental body mass index (BMI), maternal weight gain during pregnancy, and their interaction on neonatal birth weight. METHODS: A total of 1 127 pregnant women who underwent regular prenatal examinations and full-term singleton delivery in the First Hospital of Xi'an Jiaotong University from January 2017 to October 2018 were enrolled. The data on their pre-pregnancy BMI, maternal weight gain during pregnancy, pre-pregnancy BMI of the husband, and neonatal birth weight were collected. The interaction between pre-pregnancy parental BMI and maternal weight gain during pregnancy was analyzed, and their correlation with neonatal birth weight was analyzed. RESULTS: Among the 1 127 full-term neonates, the detection rates of low birth weight neonates and macrosomia were 2.22% (25/1 127) and 3.82% (43/1 127) respectively. There were significant differences in pre-pregnancy parental BMI and maternal weight gain during pregnancy among the low birth weight, normal birth weight, and macrosomia groups (P<0.05). Neonatal birth weight was positively correlated with pre-pregnancy parental BMI and maternal weight gain during pregnancy (r=0.097-0.322, P<0.05). Low maternal weight before pregnancy increased the risk of low birth weight (RR=4.17, 95%CI: 1.86-9.38), and maternal overweight/obesity before pregnancy (RR=3.59, 95%CI: 1.93-6.67) and excessive weight gain during pregnancy (RR=3.21, 95%CI: 1.39-7.37) increased the risk of macrosomia. No interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy was observed. CONCLUSIONS: Pre-pregnancy parental BMI and maternal weight gain during pregnancy are related to neonatal birth weight, and there is no interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy.


Assuntos
Ganho de Peso na Gestação , Complicações na Gravidez , Peso ao Nascer , Índice de Massa Corporal , Feminino , Humanos , Recém-Nascido , Gravidez , Fatores de Risco , Aumento de Peso
5.
Cell Physiol Biochem ; 45(6): 2329-2337, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29550808

RESUMO

BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry. Western blot analysis was performed to detect the protein expressions of apoptosis-related factors, and core factors in MEK/ERK and mTOR signaling pathways. RESULTS: Toxic effects of sevoflurane on hippocampal neurons were observed, as cell viability was reduced, apoptotic cell rate was increased, Bcl-2 was down-regulated, and Bax, cleaved caspase-3 and -9 were up-regulated after 1% sevoflurane exposure for 16 h. Sevoflurane exhibited a temporarily (less than 16 h) inhibitory effect on MEK/ERK pathway, but has no impact on mTOR pathway. Roflumilast promoted the release of cAMP and down-regulated the protein expression of PDE-4. Roflumilast (1 µM) alone has no impact on viability and apoptosis of hippocampal neurons. However, roflumilast increased cell viability and deceased apoptosis in sevoflurane-injured neurons. Besides, roflumilast could recover sevoflurane-induced deactivation of MEK/ERK pathway. CONCLUSION: To conclude, this study demonstrated a neuroprotective role of roflumilast in sevoflurane-induced nerve damage. Roflumilast promoted hippocampal neurons viability, and reduced apoptosis possibly via modulation of MEK/ERK signaling pathway.


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclopropanos/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Éteres Metílicos/toxicidade , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Wistar , Sevoflurano
6.
Biomed Environ Sci ; 31(4): 322-326, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29773097

RESUMO

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.


Assuntos
Colágeno Tipo XI/genética , Predisposição Genética para Doença , Genótipo , Doença de Kashin-Bek/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , Estudos de Casos e Controles , Humanos
7.
Biomed Environ Sci ; 29(7): 539-43, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27554126

RESUMO

To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high-resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome-wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD.


Assuntos
Metilação de DNA , Variação Genética , Estudo de Associação Genômica Ampla , Doença de Kashin-Bek/genética , Adulto , Estudos de Casos e Controles , Análise por Conglomerados , Ilhas de CpG , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos
8.
Pharm Res ; 31(7): 1788-800, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24549817

RESUMO

PURPOSE: To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of constituents. METHODS: We developed a bioactive equivalence oriented feedback screening method and applied it to discover the BECCs from an herbal preparation Cardiotonic Pill (CP). The operations include chemical profiling of CP, followed by an iterative loop of determining, collecting and evaluating candidate BECCs. RESULTS: A combination of 18 compounds was identified as BECCs from CP, which accounts for 15.0% (w/w) of original CP. We have demonstrated that the BECCs were as effective as CP in cell models and in a rat model of myocardial infarction. CONCLUSIONS: This work answers the key question of which are real bioactive components for CP that have been used in clinic for many years, and provides a promising approach for discovering BECCs from herbal medicines. More importantly, the BECCs could be extended to improve quality control of herbal products and inspire an herbal medicines based discovery of combinatorial therapeutics.


Assuntos
Cardiotônicos/química , Cardiotônicos/farmacologia , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Infarto do Miocárdio/tratamento farmacológico , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Animais , Linhagem Celular , Coração/efeitos dos fármacos , Humanos , Masculino , Fitoterapia , Plantas Medicinais/química , Controle de Qualidade , Ratos , Ratos Sprague-Dawley
9.
Expert Rev Hematol ; 17(1-3): 87-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230679

RESUMO

BACKGROUND: This study aimed to explore the effect and mechanism of SCN5A overcoming ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in acute myeloid leukemia (AML) through promoting apoptosis. RESEARCH DESIGN AND METHODS: The tissues derived from AML patients were divided into Sensitive group and Resistance group according to the presence of drug-resistance. Human AML cell line HL-60 and drug-resistant strain HL-60/ADR were divided into HL-60/ADR-vector group, HL-60/ADR-SCN5A group, HL-60-vector group and HL-60-SCN5A group. RT-qPCR was used to detect the mRNA expression level of SCN5A; MTT assay to assess the survival rate and proliferation level of cells; flow cytometry to determine the apoptosis level; and western blot to check the levels of SCN5A, P-glycoprotein (P-gp), MDR protein 1 (MRP1), MDR gene 1 (MDR1), breast cancer resistance protein (BCRP), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) proteins in cells. RESULTS: SCN5A expressed lowly in drug-resistant AML tissues and cells. Up-regulation of SCN5A inhibited MDR in HL-60 cells, enhanced the chemosensitivity of HL-60/ADR, and increased the apoptosis levels of HL-60 and HL-60/ADR cells. However, over-expression of SCN5A inhibited the expression of MDR-related proteins. CONCLUSIONS: SCN5A may overcome ABC transporter-mediated MDR in AML through enhancing the apoptosis and inhibiting the expression of MDR proteins.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Leucemia Mieloide Aguda , Humanos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/genética , Resistência a Múltiplos Medicamentos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética
10.
Chin J Integr Med ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37930511

RESUMO

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

11.
J Nat Prod ; 75(12): 2076-81, 2012 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-23186307

RESUMO

A phytochemical investigation of Chromolaena odorata resulted in the isolation of five new compounds, 5aα,6,9,9aß,10-pentahydro-10ß-hydroxy-7-methylanthra[1,2-d][1,3]dioxol-5-one (1), 1,2-methylenedioxy-6-methylanthraquinone (2), 3-hydroxy-1,2,4-trimethoxy-6-methylanthraquinone (3), 3-hydroxy-1,2-dimethoxy-6-methylanthraquinone (4), and 7-methoxy-7-epi-medioresinol (5), together with 12 known compounds, odoratin (6), 3ß-acetyloleanolic acid (7), ursolic acid (8), ombuin (9), 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (10), (-)-pinoresinol (11), austrocortinin (12), tianshic acid (13), cleomiscosin D (14), (-)-medioresinol (15), (-)-syringaresinol (16), and cleomiscosin A (17). All the compounds were evaluated for their PPARγ transactivation activity, and compound 6 showed moderate activity with an EC(50) value of 3.10 µM.


Assuntos
Antraquinonas/isolamento & purificação , Chromolaena/química , Dioxóis/isolamento & purificação , Dioxóis/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , PPAR gama/agonistas , Antraquinonas/química , Antraquinonas/farmacologia , Dioxóis/química , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Furanos/química , Furanos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Humanos , Lignanas/química , Luciferases/metabolismo , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Estereoisomerismo
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 42(1): 29-31, 40, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21355295

RESUMO

OBJECTIVE: To analyze the differences of genetic polymorphism of 14 STR loci on chromosome 2 between KBD patients and controls living in and outside of KBD catchment areas. METHODS: Blood samples anticoagulated with EDTA were collected from 135 unrelated individuals of Han population in Shaanxi Province, which included 45 samples from KBD patients, 45 from normal residents living in the KBD catchment areas, and 45 from normal residents outside of the KBD catchment areas. The DNA was extracted from the blood samples for PCR amplification of relevant fragments. The amplified products were analyzed using the ABI 3730 Genetic Analyzer. RESULTS: The allele numbers for 14 STR loci (D2S286, D2S165, D2S160, D2S2211, D2S367, D2S125, D2S206, D2S117, D2S142, D2S2333, D2S126, D2S325, D2S364, D2S337) in the KBD patients were 8, 11, 7, 7, 9, 10, 11, 11, 8, 10, 11, 10, 6 and 9, respectively. Different allele numbers for 14 STR loci were found in the normal residents in the KBD catchment areas (7, 10, 6, 7, 7, 8, 10, 10, 8, 8, 11, 8, 7 and 7) and those outside of the KBD catchment areas (8, 11, 7, 7, 10, 9, 11, 11, 7, 9, 11, 7, 8 and 7). There were significant differences in the allele frequencies in the D2S165 and D2S2333 locus between the KBD patients and the normal residents living in and outside of the KBD catchment areas (P > 0.05). Significant difference in the allele frequencies in the D2S160 loci was found between the KBD patients and the normal residents living in the KBD catchment areas (P = 0.046). Significant difference in the allele frequencies in the D2S364 loci was found among the three groups of participants (P = 0.046). CONCLUSION: The allele distribution patterns of the D2S165 and D2S2333 locus in KBD patients are different from normal people.


Assuntos
Cromossomos Humanos Par 2/genética , Doença de Kashin-Bek/genética , Repetições de Microssatélites/genética , Polimorfismo Genético , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Loci Gênicos , Genótipo , Humanos
13.
World J Stem Cells ; 13(4): 317-330, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33959221

RESUMO

BACKGROUND: As human placenta-derived mesenchymal stem cells (hP-MSCs) exist in a physiologically hypoxic microenvironment, various studies have focused on the influence of hypoxia. However, the underlying mechanisms remain to be further explored. AIM: The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of hP-MSCs. METHODS: A hypoxic cell incubator (2.5% O2) was used to mimic a hypoxic microenvironment. Cell counting kit-8 and 5-ethynyl-20-deoxyuridine incorporation assays were used to assay the proliferation of hP-MSCs. The cell cycle was profiled by flow cytometry. Transcriptome profiling of hP-MSCs under hypoxia was performed by RNA sequencing. CD99 mRNA expression was assayed by reverse transcription-polymerase chain reaction. Small interfering RNA-mediated hypoxia-inducible factor 1α (HIF-1α) or CD99 knockdown of hP-MSCs, luciferase reporter assays, and the ERK1/2 signaling inhibitor PD98059 were used in the mechanistic analysis. Protein expression was assayed by western blotting; immunofluorescence assays were conducted to evaluate changes in expression levels. RESULTS: Hypoxia enhanced hP-MSC proliferation, increased the expression of cyclin E1, cyclin-dependent kinase 2, and cyclin A2, and decreased the expression of p21. Under hypoxia, CD99 expression was increased by HIF-1α. CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell proliferation. CONCLUSION: Hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34335838

RESUMO

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

15.
Can J Microbiol ; 55(5): 599-604, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19483788

RESUMO

A high phytase-producing strain of Aspergillus niger N-3 was identified by screening 104 microbial strains. The gene for A. niger N-3 was cloned and expressed in Pichia pastoris. The coding region without the introns and putative signal sequence was comprised of 1347 nucleotides. It encoded a polypeptide of 448 amino acids, exhibiting high amino acid sequence homologies (94.87%) with the typical phytase of A. niger NRRL 3135. The molecular mass of the recombinant phytase as determined by SDS-PAGE was 60-70 kDa, with maximum activity at approximately 55 degrees C (after incubation at 10 min). The phytase retained about 45% of its enzymatic activity under heat treatment at 90 degrees C for 5 min. It showed a greater affinity for sodium phytate than for p-nitrophenyl phosphate. Dual optima pH (2.0 and 5.5) was gained. The activity at pH 2.0 was about 30% higher than at pH 5.5, which was more suitable to the circumstance of the stomachs of monogastric animals. The extent of glycosylation influenced the characterization of phytase. The deglycosylated phytase showed pH optima at 3.5 and 5.5, and the molecular mass had dropped to 50 kDa.


Assuntos
6-Fitase/genética , 6-Fitase/metabolismo , Aspergillus niger/enzimologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Microbiologia Industrial , 6-Fitase/química , Sequência de Aminoácidos , Animais , Aspergillus niger/genética , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Estabilidade Enzimática , Proteínas Fúngicas/química , Expressão Gênica , Temperatura Alta , Concentração de Íons de Hidrogênio , Íntrons , Dados de Sequência Molecular , Peso Molecular , Nitrofenóis/metabolismo , Compostos Organofosforados/metabolismo , Ácido Fítico/metabolismo , Pichia/genética , Sinais Direcionadores de Proteínas , Homologia de Sequência de Aminoácidos , Especificidade por Substrato
16.
Zhongguo Gu Shang ; 32(5): 462-468, 2019 May 25.
Artigo em Zh | MEDLINE | ID: mdl-31248244

RESUMO

OBJECTIVE: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA. METHODS: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment. RESULTS: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group(P<0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group(P>0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group(P<0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference(P>0.05); there was significant difference between needle knife group and model group(P<0.05); there was no significant difference between electro-acupuncture group and needle-knife group(P>0.05). In gait change, there was significant difference between model group and electro-acupuncture group(P<0.05); there was no significant difference between needle-knife group and model group(P>0.05). In joint activity, there was significant difference between electro-acupuncture group and model group(P<0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group(P<0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group(P>0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly(P<0.01), the ultimate load of the electro-acupuncture group decreased(P>0.05), and the ultimate load of the needle-knife group increased(P>0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly(P<0.05), and the ultimate load of the needle-knife group increased significantly (P<0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased(P>0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly(P<0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased(P>0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased(P>0.05), and the maximum displacement of the needle-knife group increased significantly(P<0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased(P>0.05). There was no significant difference in stiffness among groups(P>0.05). CONCLUSIONS: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA.


Assuntos
Eletroacupuntura , Osteoartrite do Joelho , Animais , Humanos , Articulação do Joelho , Masculino , Músculo Quadríceps , Coelhos , Ratos , Tendões
17.
Future Med Chem ; 11(21): 2821-2830, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510797

RESUMO

Background: Gefitinib and sorafenib have been proved effective for the treatment of cancers in clinical practice for years. Materials & methods: We intended to integrate the structural features of gefitinib and sorafenib and construct structurally unique 7-aromatic ureido-4-anilinoquinazolines. Results: Most of the targets exhibited promising antitumor activities. 8u showed excellent antitumor activities against the three tested cell lines (IC50, 0.81-2.49 µM). The enzymatic, apoptosis assay of 8u were also performed to study their preliminary action of mechanism. Conclusion: 8u deserve further research as antitumor agents.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Quinazolinas/química , Quinazolinas/farmacologia , Ureia/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Quinazolinas/síntese química
18.
Gynecol Obstet Invest ; 65(2): 128-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17957100

RESUMO

OBJECTIVE: Qinba Mountain area of Shanxi Province, China, is one of the poorest, culturally backward regions in China with a high incidence of mental retardation. To investigate whether cytomegalovirus (CMV) plays a role in the high incidence of mental retardation in this region, we studied the incidence of CMV infection during pregnancy and possible risk factors associated with CMV infection. METHODS: 386 consecutive pregnant women in Qinba Mountain area were monitored for the level of a CMV-specific IgM antibody. Polymerase chain reaction was used to detect CMV in breast milk obtained within 2 weeks postpartum and urine samples of newborn infants born to actively CMV-infected mothers. Serum levels of TNF-alpha, IL-6, zinc, copper, iron and selenium were analyzed in CMV-infected pregnant women. RESULTS: The incidence of CMV-active infection during pregnancy, intrauterine transmission and excretion in breast milk were 15.03, 33.33, and 39.58%, respectively. Active CMV infection during pregnancy was correlated with maternal age, education and economic status, parity, and history of obstetric complications. Those women who had active CMV infection, intrauterine transmission, or CMV excretion in milk showed higher values of TNF-alpha and IL-6, lower values of zinc as compared with health age-matched controls (p < 0.05). No differences were identified between studied cases and controls in the level of copper, iron, and selenium (p > 0.05). CONCLUSION: The incidence of CMV-active infection during pregnancy was high in Qinba Mountain area of Shanxi Province. Zinc deficiency may be a risk factor for the development of CMV infection. TNF-alpha and IL-6 may be involved in the pathophysiologic process.


Assuntos
Anticorpos Antivirais/sangue , Citocinas/sangue , Infecções por Citomegalovirus/epidemiologia , Leite Humano/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Oligoelementos/sangue , Adulto , China/epidemiologia , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/transmissão , Feminino , Humanos , Imunoglobulina M/sangue , Incidência , Recém-Nascido/urina , Transmissão Vertical de Doenças Infecciosas , Deficiência Intelectual/virologia , Interleucina-6/sangue , Masculino , Reação em Cadeia da Polimerase/métodos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue , Zinco/deficiência
19.
Yi Chuan ; 30(7): 885-92, 2008 Jul.
Artigo em Zh | MEDLINE | ID: mdl-18779132

RESUMO

On the basis of known partial coding DNA sequence (GenBank accession No. AF413111), we tried to clone the full mRNA of rabbit BMP7 gene by sub-cloning and RACE methods. Then after, bioinformatic analysis on the acquired sequences were conducted. The sequencing results showed that the all cloned sequences could be assembled into a 1 654 bp long DNA fragment, which contained the near full coding cDNA for the propetide, full coding cDNA for the mature protein, and full length of 3'UTR of rabbit BMP7. The newly cloned sequences extended the 5'and 3'ends of known partial DNA sequence by 395 bp and 628 bp, respectively. Sequence comparisons revealed that the full length of coding cDNA of rabbit BMP7 was 91.89% and 89.32% identical to that of human and mouse, while the deduced amino acids was 96.51% and 96.01% identical, respectively. The 3'UTR of rabbit BMP7 was 446 bp in length, 57.38% and 45.57% identical to that of human or mouse, respectively. In addition, there were two closely arranged AATAAA sites in the 3'UTR of rabbit BMP7 gene, as well as in human BMP7. The deduced mature protein of rabbit BMP7 had the seven conservative cysteines and a TGF-b family signature, which were the characters of all BMPs. Our results suggested that the main part of rabbit BMP7 had been successively cloned. The alternation of polyadenization sites in the 3'UTR of rabbit BMP7 maybe related to the posttranscriptional regulation of the gene.


Assuntos
Proteína Morfogenética Óssea 7/genética , Coelhos/genética , Regiões 3' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteína Morfogenética Óssea 7/química , Clonagem Molecular , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 33(7): 587-91, 2008 Jul.
Artigo em Zh | MEDLINE | ID: mdl-18667770

RESUMO

OBJECTIVE: To investigate the genetic polymorphism of 15 short tandem repeat(STR)loci on chromosome 2 and chromosome 11 in Shaanxi Han people in China. METHODS: Fluorescence-based gene scan technique was used to examine the genetic polymorphism of 15 STR loci in 175 unrelated individuals from Chinese Han population in Shannxi province. RESULTS: The number of alleles D2S335, D2S396, D2S338, D2S2382, D2S305, D2S151, D2S2368, D2S391,D11S912, D11S4090, D11S4147, D11S4190, D11S4149, D11S4126, and D11S4094 was 11,11,11,10,8,8,9,12 ,7,11,8,10,5,5, and 6. The distribution of allele frequencies of the 15 STR was consistent with Hard-Weinberg equilibrium (P > 0.05). Heterozygosity (H) value was 0.4216 to approximately 0.8517, the average power of discrimination (DP) was 0.6568 to approximately 0.9598, polymorphism information content (PIC) was 0.4078 to approximately 0.8366, and probability of paternity exclusion (EPP) was 0.3135 to approximately 0.8537. CONCLUSION: The 15 STR loci have relatively high genetic polymorphism in Shaanxi Han population, which provides the genetic structure of Chinese Han groups, and is also useful in anthropology and forensic science.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 2/genética , Frequência do Gene , Repetições de Microssatélites/genética , Polimorfismo Genético , Adulto , China/etnologia , Feminino , Humanos , Masculino
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