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1.
Med Sci Monit ; 27: e927624, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33436534

RESUMO

BACKGROUND Traditional Chinese medicine has widely used Bolbostemma paniculatum to treat diseases, including cancer, but its underlying mechanisms remain unclear. The present study aimed to elucidate the potential pharmacological mechanisms of "Tu Bei Mu" (TBM), the Chinese name for Bolbostemmatis Rhizoma, the dry tuber of B. paniculatum, for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS The active components and putative therapeutic targets of TBM were explored using SwissTargetPrediction, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Search Tool for Interactions of Chemicals (STITCH). The HCC-related target database was built using DrugBank, DisGeNet, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). A protein-protein interaction network of the common targets was constructed, based on the matches between TBM potential targets and HCC-related targets, using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the cluster networks were used to elucidate the biological functions of TBM. RESULTS Pharmacological network diagrams of the TBM compound-target network and HCC-related target network were successfully constructed. A total of 22 active components, 191 predicted biological targets of TBM, and 3775 HCC-related targets were identified. Through construction of an HCC-related target database and a protein-protein interaction network of the common targets, TBM was predicted to be effective in treating HCC mainly through the PI3K-Akt, HIF-1, p53, and PPAR signaling pathways. CONCLUSIONS The PI3K/Akt, HIF1, p53, and PPAR pathways may play vital roles in TBM treatment of HCC. Also, the potential anti-cancer effect of TBM on HCC appears to stem from the synergetic effect of multiple targets and mechanisms.

2.
Neuroscience ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33197504

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive memory loss and cognitive dysfunction. Long non-coding RNAs (lncRNAs) have been shown to be among the most promising biomarkers and therapeutic targets of AD. Here, we aimed to investigate whether lncRNA BACE1-AS plays a role in the potential mechanisms of AD. The expression of BACE1-AS, miR-214-3p and ATG5 mRNA was detected using qRT-PCR. The expression of the LC3, P62, ATG5, Bcl-2, p-Tau and cleaved-caspase 3 proteins was examined using western blot analysis. Cell apoptosis, cytotoxicity and ROS levels were estimated using flow cytometry, an LDH kit and a DCFH-DA assay, respectively. The interaction between BACE1-AS or ATG5 and miR-214-3p was validated using a dual-luciferase reporter assay. HE staining and a TUNEL assay were employed to evaluate hippocampal neuronal injury. The BACE1-AS level was found to be upregulated in serum samples of AD patients, brain tissues of AD transgenic (Tg) mice and Aß1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Aß1-42-treated cells. BACE1-AS knockdown alleviated Aß1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Aß1-42 induced cell injury. BACE1-AS indirectly regulated ATG5 expression by binding miR-214-3p. The miR-214-3p inhibitor reversed the protective effects of sh BACE1-AS and sh ATG5 against Aß1-42-induced cell injury. Knockdown of BACE1-AS alleviated neuronal injury by repressing autophagy in vivo. Our findings demonstrate that silencing of BACE1-AS alleviated neuronal injury by regulating autophagy through the miR-214-3p/ATG5 signalling axis in AD.

3.
Chem Biodivers ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33251769

RESUMO

Guchang Zhixie Wan (GZW) is a commonly used Chinese medicine for the treatment of ulcerative colitis (UC). This research explored the potential pharmacological mechanism of GZW in UC. The active ingredients, potential targets and UC-related genes of GZW were retrieved from public databases. The pharmacological mechanisms including key components, potential targets and signal pathways were determined through bioinformatics analysis. The results of this study were verified through virtual molecular docking and cell experiments.  Network analysis revealed that 26 active GZW compounds and 148 potential GZW target proteins were associated with UC. Quercetin, kaempferol and beta-sitosterol were identified as the core active ingredients of GZW. IFNG, IL-1A, IL-1B, JUN, RELA, and STAT1 were indicated as key targets of GZW. These key targets have a strong affinity for quercetin, kaempferol, and beta-sitosterol. GO and KEGG enrichment analysis showed that GZW target proteins are highly enriched in inflammatory, immune, and oxidative stress-related pathways. This study confirmed the therapeutic effect and revealed potential molecular mechanism of GZW on UC. And the protective effects of GZW on inflammatory bowel disease pathway were also revealed through STAT3/NF-kB/IL-6 pathway. The findings of this study enhanced our understanding of GZW in the treatment of UC and provided a feasible method for discovering potential drugs from traditional Chinese medicine formulations.

4.
Asian Pac J Cancer Prev ; 21(10): 2987-2992, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112558

RESUMO

OBJECTIVE: Poly (ADP-ribose) polymerase 1 (PARP1), as a key enzyme in the base excision repair pathway, plays a crucial role in tumorigenesis and progression. This study aimed to assess whether polymorphisms of PARP1 gene could be used as predictive biomarkers for the survival of esophageal squamous cell carcinoma (ESCC) patients from Cixian high-incidence region in northern China. METHODS: In 203 ESCC patients with survival information, PARP1 rs1136410 T/C and rs8679 T/C single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method. All statistical analyses were performed using the SPSS ver. 22.0 software package (SPSS, Chicago, IL, USA). RESULTS: The mean age ± standard deviation of the ESCC patients was 60.4 ± 7.9 years. There was no significant relation of sex, age, smoking status and upper gastrointestinal cancer family history with the survival time of the ESCC patients. The mean survival time of rs1136410 T/T, T/C and C/C genotype carriers were 43.3, 42.3 and 46.6 months, respectively. The rs1136410 was not associated with the survival time of the ESCC patients. For rs8679, the mean survival time of T/T genotype carriers was 43.7 months, which was not significantly different from that of the patients with T/C genotype (42.1 months). CONCLUSION: In Cixian high-incidence region from northern China, rs1136410 and rs8679 SNPs might not be used to predict survival of ESCC patients. There is a need to explore whether other SNPs of PARP1 gene have an effect on prognosis of ESCC patients.

5.
Front Pharmacol ; 11: 01261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123002

RESUMO

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

6.
Front Oncol ; 10: 1450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983975

RESUMO

Background: Adenylyl cyclase type 9 (ADCY9) modulates signal transduction by producing the second messenger cyclic AMP. It has been reported that ADCY9 gene polymorphisms were associated with cancer development. The aim of this study was to investigate whether ADCY9 gene polymorphisms could contribute to the susceptibility of hepatocellular carcinoma (HCC) in the Chinese Han population. Methods: In the present study, five single-nucleotide polymorphisms (SNPs) in ADCY9 were genotyped using Agena MassARRAY platform in 876 subjects from China. Logistic regression was used to assess the effects of SNPs on HCC risk. Associations were also evaluated for HCC risk stratified by age and gender. False discovery rate (FDR) was used to correct multiple testing. Results: After adjusting for age and gender, we found a significant relationship between heterozygous genotypes of rs2531995 and HCC risk (OR = 1.34, 95% CI = 1.01-1.77, p = 0.045). ADCY9 rs2230742 had a strong relationship with lower risk of HCC in allele (p = 0.006), co-dominant (p = 0.023), dominant (p = 0.010), and additive (p = 0.006) models. Stratified analysis showed that rs879620 increased HCC risk and rs2230742 was associated with lower risk of HCC in the individuals aged 55 or younger, rs2531992 significantly decreased HCC risk in the elder group (age > 55). For women, rs2230742 and rs2230741 were significantly associated with HCC risk in multiple models (p < 0.05). FDR analysis showed that rs2230742 could protect individuals from HCC risk in the allele model (FDR-p = 0.030). In addition, haplotype analysis indicated that Crs879620Ars2230742Ars2230741 haplotype was a protective factor for HCC (OR = 0.67, 95% CI = 0.50-0.89, p = 0.007, FDR-p = 0.028). Conclusion: Our findings suggest that ADCY9 gene polymorphisms are associated with HCC risk in the Chinese Han population.

7.
Biosci Rep ; 40(8)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32748943

RESUMO

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways.

8.
Biol Trace Elem Res ; 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32666432

RESUMO

Alzheimer's disease is characterized by the aggregation of amyloid-beta (Aß) peptide into plaques and neurofibrillary tangles. Aß peptide is generated by the cleavage of the ß-amyloid precursor protein (APP) by ß- and γ-secretase. The present study was conducted to investigate the effects of fish oil (or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), selenium, and zinc on learning and memory impairment in an aging mouse model and on APP. We performed the Morris water maze and platform recorder tests on male Kunming mice (10/group) grouped as control and D-galactose-induced aging model mice treated with vehicle, fish oil, fish oil + selenium, fish oil + selenium + zinc, and positive control (red ginseng extract). Fish oil + zinc + selenium for 7 weeks significantly improved learning and memory impairments in aging model animals in the Morris water maze and platform recorder tests, as evidenced by shortened incubation periods and number of errors. In vitro analysis of Aß1-40 content in APP695-transfected CHO cells revealed a decrease after treatment with EPA, DHA, and their combinations with selenium or selenium and zinc. Assaying ß- and γ-secretase activities revealed a decrease in PC12 cells and mouse serum as well as a decrease in ß-site APP-cleaving enzyme 1 and presenilin 1 protein levels in the PC12 cells and mouse serum. Taken together, our results show that fish oil combined with selenium and zinc inhibited APP processing and alleviated learning and memory impairment in a mouse model of aging.

9.
Medicine (Baltimore) ; 99(23): e20534, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502011

RESUMO

BACKGROUND: We designed this study to assess the effects and safety of Buyang-Huanwu Decoction (BYHWD) for the treatment of patients with acute ischemic stroke (AIS). METHODS: Electronic databases of Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO, Scopus, Allied and Complementary Medicine Database, VIP Database, and China National Knowledge Infrastructure will be comprehensively and systematically searched from initial time of each electronic database to the present without limitations of language and publication status. Randomized controlled trials on BYHWD alone against any other interventions for the treatment of AIS will be included. All process of study selection, data collection, and methodological quality assessment will be independently undertaken by 2 investigators. Cochrane risk of bias tool and RevMan 5.3 software will be utilized for the performance of methodological quality assessment and statistical analysis, respectively. RESULTS: This study will summarize most recent high quality evidence on investigating the effects and safety of BYHWD alone against any other interventions for the treatment of patients with AIS. CONCLUSIONS: The findings of this study will provide helpful evidence for the clinical practice for patients with AIS using BYHWD, as well as the relevant future researches.Study registration number: INPLASY202040169.


Assuntos
Isquemia Encefálica/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Hemorragia Cerebral , Humanos , Metanálise como Assunto , Qualidade de Vida , Recidiva , Projetos de Pesquisa , Acidente Vascular Cerebral/etiologia , Revisões Sistemáticas como Assunto
10.
BMC Med Genet ; 21(1): 134, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560637

RESUMO

BACKGROUND: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk. METHODS: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk. CONCLUSIONS: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Fatores Etários , Estudos de Casos e Controles , Feminino , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais
11.
J Psychosoc Oncol ; 38(5): 557-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32367769

RESUMO

PURPOSE: The cancer caregiving experience is multifaceted and dynamic across different phases of the cancer care continuum. This longitudinal study examined the trajectories of CQOL and caregiver emotional distress across the first year post-diagnosis. METHODS: Participants were 111 caregivers of newly diagnosed patients who completed baseline, 6-month, and 12-month follow-ups. Trajectories of CQOL, CQOL domains, caregiver depression, anxiety, and stress, were estimated using linear and quadratic mixed models. RESULTS: The trajectory of overall CQOL followed an inverse U-shape trend, while caregiver depression, anxiety, and stress remained stable. For CQOL domains, physical/practical needs followed a gradual trend of improvement, while social support followed an inverse U-shape trend; caregiver burden, emotional reactivity, and responsibility/duty remained stable. CONCLUSIONS: The multidimensional needs of caregivers of newly diagnosed patients appeared to follow different trajectories across the first year post-diagnosis. While most CQOL domains remained stable, caregivers may experience adjustment difficulties in terms of relational concerns and social support.

12.
Asian J Psychiatr ; 51: 102019, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32251896

RESUMO

Cognitive impairment in older adults is a major public concern for Singapore's aging population. The study aimed to (1) examine the effects of age, gender, and education on neuropsychological test performance, and (2) establish regression-based norms in the Singapore older adult (≥ 60 years) population. Data on neuropsychological test performance was extracted from the Well-being of the Singapore Elderly (WiSE) study (n = 2033). Participants who met criteria for dementia were excluded. The data included scores from the 10/66 Dementia Research Group neuropsychological test battery measuring verbal fluency, immediate memory recall, delayed memory recall, and global cognitive function. The General Linear Model (GLM) was used to examine the effects of age, gender, and education on neuropsychological test performance. Stratified weighted means and standard deviations by age, gender and education were reported to establish regression-based normative data. Results from GLM showed that older age and having lower education were associated with poorer performance on all four neuropsychological test measures, and females showed better performance on the tests for immediate memory recall and delayed memory recall. The current study provides useful information on cognitive functioning based on the 10/66 neuropsychological test battery in the older adult population in Singapore. This may help to improve neuropsychological assessments for older adults.

13.
Artif Cells Nanomed Biotechnol ; 48(1): 473-478, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31975615

RESUMO

Schisandrin B (Sch B) and miR-101 family members play critical roles in the pathogenesis of liver fibrosis. However, the relationship between them has not been reported yet. Thus, this study aims to fill this research gap. Results showed that Sch B significantly upregulated the expression of miR-101-5p in HSC-T6 cells. Sch B also increased the expression of miR-101-5p by combined administration of TGF-ß1 and Sch B. Using miR-101-5p inhibitor, we demonstrated that Sch B can target miR-101-5p through the TGF-ß signalling pathway to regulate the proliferation and activation of HSC-T6 cells. A rat model of carbon tetrachloride-induced liver fibrosis was established, and results indicated that Sch B can attenuate liver fibrosis by upregulating the expression of miR-101-5p. In conclusion, Sch B can directly target miR-101 to suppress liver fibrosis. Sch B or miR-101-5p may be used as a therapeutic approach for the prevention and treatment of liver fibrosis.


Assuntos
Intoxicação por Tetracloreto de Carbono , Lignanas/farmacologia , Cirrose Hepática , MicroRNAs/metabolismo , Compostos Policíclicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Animais , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Ciclo-Octanos/farmacologia , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(5): 489-493, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33629564

RESUMO

Objective: To investigate the effects of Sini San prescription(SNS) on the proliferation and apoptosis of HepG2 cells and its molecular mechanism. Methods: The morphological changes of hepatocellular carcinoma HepG2 cells treated by SNS were observed by inverted microscope. MTT assay was used to detect the inhibitory effect of SNS on cell proliferation. Fluorescence staining and flow cytometry were employed to analyze the effect of SNS on apoptosis of HepG2 cells. Rho123 (Rhodamine 123) staining method was performed to detect the changes of mitochondrial membrane potential, and Western blot was used to evaluate the expression of proteins related to apoptosis. Results: The number of hepatocellular carcinoma HepG2 cells were significantly decreased (P<0.01) and cells showed typical apoptotic cell morphology after treated with serum contained SNS. The inhibition rate of HepG2 cells was increased with the increase of concentration of serum contained SNS. The number of cells in G1 phase was significantly increased, while G2 phase was decreased after treated with serum contained SNS(P<0.05).The apoptosis rate and mitochondrial membrane potential of HepG2 cells were significantly increased and decreased after treated with serum contained SNS(P<0.05). The expression levels of Bax, caspase-3,-9 and cyt-c were significantly increased, while the expression of bcl-2 was decreased in HepG2 cells treated with serum contained SNS(P<0.05).Conclusion: Sini San prescription can inhibit the proliferation of HepG2 cells and induce apoptosis by mitochondrial pathway.

15.
Pharmazie ; 74(7): 418-422, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288898

RESUMO

Diacylglycerol kinase zeta (DGKZ) is associated with the pathogenesis of a variety of malignant diseases, but its biological function on acute myeloid leukemia (AML) has not been explored. The aim of this study was to analyze apoptosis induced by knockdown of DGKZ and its mechanism in human acute myeloid leukemia HL-60 cells. qRT-PCR was carried out to detect the expression of DGKZ in HL-60, THP-1, Jurkat, K562, and CD34 cell lines. Additionally the expression of DGKZ in AML cells obtained from patients were detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) assay was used to determine the viability of HL-60 cells DGKZ knocked down. Apoptosis and cell cycle phase of HL-60 cells after DGKZ knockdown were evaluated by flow cytometry. Western blot analysis was performed to investigate expressions of the proteins related to apoptosis and cell cycle. Results showed that expression of DGKZ was significantly higher in HL-60 and AML cells obtained from patients than those of Jurkat, THP-1, K562 and human CD34 cell. Compared with the shCtrl group, DGKZ was markedly knocked down in HL-60 cells transfected with lentivirus encoding shRNA. DGKZ knockdown significantly inhibited the proliferation and induced cycle arrest at the G2/M phase in HL-60 cells. The expressions of MAPK, caspase-3, caspase-8, cytochrome C markedly increased and p-MAPK and survivin decreased in HL-60 cells after DGKZ knockdown. The results suggest that knockdown of DGKZ can induce apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells through the MAPK/survivin/caspase pathway.


Assuntos
Apoptose/genética , Diacilglicerol Quinase/genética , Leucemia Mieloide Aguda/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Técnicas de Silenciamento de Genes , Células HL-60 , Humanos , Leucemia Mieloide Aguda/patologia , Pontos de Checagem da Fase M do Ciclo Celular/genética , Sistema de Sinalização das MAP Quinases/genética , RNA Interferente Pequeno/genética , Survivina/metabolismo
16.
Front Pharmacol ; 10: 253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936832

RESUMO

The herb Radix Ophiopogonis (RO) has been used effectively to treat nasopharyngeal carcinoma (NPC) as an adjunctive therapy. Due to the complexity of the traditional Chinese herbs, the pharmacological mechanism of RO's action on NPC remains unclear. To address this problem, an integrative approach bridging proteome experiments with bioinformatics prediction was employed. First, differentially expressed protein profile from NPC serum samples was established using isobaric tag for relative and absolute quantification (iTRAQ) coupled 2-D liquid chromatography (LC)-MS/MS analysis. Second, the RO putative targets were predicted using Traditional Chinese Medicines Integrated Database and known therapeutic targets of NPC were collected from Drugbank and OMIM databases. Then, a network between RO putative targets and NPC known therapeutic targets was constructed. Third, based on pathways enrichment analysis, an integrative network was constructed using DAVID and STRING database in order to identify potential candidate targets of RO against NPC. As a result, we identified 13 differentially expressed proteins from clinical experiments compared with the healthy control. And by bioinformatics investigation, 12 putative targets of RO were selected. Upon interactions between experimental and predicted candidate targets, we identified three key candidate targets of RO against NPC: VEGFA, TP53, and HSPA8, by calculating the nodes' topological features. In conclusion, this integrative pharmacology-based analysis revealed the anti-NPC effects of RO might be related to its regulatory impact via the PI3K-AKT signaling pathway, the Wnt signaling pathway, and the cAMP signaling pathway by targeting VEGFA, TP53, and HSPA8. The findings of potential key targets may provide new clues for NPC's treatments with the RO adjunctive therapy.

17.
Psychiatry Clin Neurosci ; 73(7): 416-422, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026106

RESUMO

AIM: Although electroconvulsive therapy (ECT) has been shown to be efficacious for patients with treatment-resistant schizophrenia, there has been limited evidence on the rate of response, cognition, and quality-of-life outcomes. The primary aims of the present study were thus to examine the effectiveness and speed of response to ECT in a naturalistic retrospective cohort in patients with treatment-resistant schizophrenia. METHODS: We performed a retrospective database analysis. The primary effectiveness outcome was defined as an improvement of ≥40% from pretreatment scores based on the Brief Psychiatric Rating Scale (BPRS) Psychotic Symptom subscale. Data were included for analysis for all patients with a primary DSM-5 diagnosis of schizophrenia that was treatment-resistant and who had had an acute course of ECT initiated for the treatment of schizophrenia between 1 July 2016 and 1 December 2016. RESULTS: A total of 50 inpatients were included for analysis. The present study revealed that 50% of patients showed at least a 40% reduction in BPRS Psychotic Symptom subscale scores after completion of ECT and that 16.7% of patients responded after the first three sessions, 39.3% after six sessions, 46.4% after nine sessions, and 50% after 12 sessions. The greatest improvement in BPRS scores was between the third and sixth ECT sessions. BPRS scores, Clinical Global Impression, Montreal Cognitive Assessment, and Global Assessment of Functioning showed significant improvement. There was no significant difference in quality-of-life outcomes. CONCLUSION: Utilizing modern techniques in treatment-resistant schizophrenia, this study demonstrates the real-world effectiveness and rate of response of patients receiving ECT.


Assuntos
Eletroconvulsoterapia , Esquizofrenia/terapia , Resultado do Tratamento , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
Psychiatry Res ; 274: 400-408, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852434

RESUMO

There is limited evidence of a direct comparison of the psychometric performance of generic preference-based measures in patients with mental illness in an Asian patient population. The current study aimed to compare the test-retest reliability, convergent and known-group validity and magnitude of change in scores of the EuroQol Five-Dimension, Health Utility Index Mark 3 (HUI3) and Short-Form Six-Dimension (SF-6D) measures in patients with depression and patients with schizophrenia spectrum disorder. 500 patients were recruited from a tertiary psychiatric institution in Singapore. The Schizophrenia Quality of Life Scale (SQLS), 8-item Patient Health Questionnaire, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Positive and Negative Syndrome Scale were also included. In the schizophrenia sample, the SF-6D was found to have higher test-retest validity, convergent validity with SQLS domain scores, known-group validity and magnitude of change in scores over 6-month follow up than other measures. In the depression sample, the HUI3 was found to have higher test-retest reliability, convergent validity with Q-LES-Q, known group validity and magnitude of change in scores than other measures. Results suggest that the SF-6D and HUI3 to be more suitable as a utility measure for patients with schizophrenia and depression in an Asian patient population.


Assuntos
Depressão/diagnóstico , Questionário de Saúde do Paciente/normas , Escalas de Graduação Psiquiátrica/normas , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Idoso , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Singapura , Inquéritos e Questionários
19.
Oncol Res ; 27(6): 673-680, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-30832756

RESUMO

IARS2 encodes mitochondrial isoleucine-tRNA synthetase, which mutation may cause multiple diseases. However, the biological function of IARS2 on acute myeloid leukemia (AML) has not yet been identified. In the present study, qRT-PCR was used to determine the expression of IARS2 in K562, THP1, and HL-60 leukemia cells. Additionally the mRNA levels of IARS2 in CD34 cells and AML cells obtained from patients were detected by qRT-PCR. IARS2-shRNA lentiviral vector was established and used to infect acute myeloid leukemia HL-60 cells. qRT-PCR and Western blot analysis were employed to assess the knockdown effect of IARS2. The proliferation rate and cell cycle phase of HL-60 cells after IARS2 knockdown were evaluated by CCK-8 assay and flow cytometry. The PathScan Antibody Array was used to determine the expression of cell cycle-related proteins in HL-60 cells after IARS2 knockdown. The expression of proliferation-related proteins in HL-60 cells after IARS2 knockdown was determined by Western blot analysis. Results showed that IARS2 expression was stable and much higher in HL-60, THP-1, and K562 leukemia cells and AML cells obtained from patients than that of human CD34 cells. Compared with cells of the shCtrl group, IARS2 was markedly knocked down in cells that were transfected with lentivirus encoding shRNA of IARS2 in HL-60 cells (p < 0.05). IARS2 knockdown significantly inhibited the proliferation and induced cycle arrest at the G1 phase in HL-60 cells. Additionally IARS2 knockdown significantly increased the expression of p53 and p21, and decreased the expression of PCNA and eIF4E in HL-60 cells. In conclusion, IARS2 knockdown can inhibit acute myeloid leukemia HL-60 cell proliferation and cause cell cycle arrest at the G1 phase by regulating the p53/p21/PCNA/eIF4E pathways.


Assuntos
Fator de Iniciação 4E em Eucariotos/metabolismo , Isoleucina-tRNA Ligase/deficiência , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Biomarcadores , Caspases/metabolismo , Ciclo Celular/genética , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Adulto Jovem
20.
Asian J Androl ; 21(3): 300-303, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880687

RESUMO

There is still debate regarding the optimal surgical approach for proximal hypospadias. This retrospective study aims to evaluate the long-term outcomes using transverse preputial island flap urethroplasty. A total of 320 patients were included, with a mean follow-up of 40.2 months (range: 1-156 months). Complications were encountered in 125 patients (39.1%), including fistulas in 53 (16.6%), urethral strictures in 31 (9.7%), and diverticula in 41 (12.8%). The mean timing of presentation with a complication was 15.8 months (median: 1.7, range: 1-145), of which 79.2% were early complications and 20.8% were late complications. In all, 20.8% of the patients with complications presented after ≥1 year, and 12.8% presented after ≥5 years. Univariate analysis revealed that age at the time of surgery, flap length, and location of the urethral meatus were not correlated with complications. A stricture was present in 31.7% (13/41) of those with diverticula (P < 0.001), while late urethral diverticula were accompanied by urethral strictures in 11.1% (1/9) of cases (P = 0.213). These results indicate that transverse preputial island flap urethroplasty still has a high incidence of complications, even when performed by highly experienced physicians. Most complications of hypospadias are diagnosed within 1 year postoperatively, while fistulas and urinary strictures generally occur within 2 months and diverticula tend to be present by 1 year.


Assuntos
Hipospadia/cirurgia , Retalhos Cirúrgicos , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Fatores Etários , Criança , Pré-Escolar , Divertículo/etiologia , Divertículo/terapia , Seguimentos , Humanos , Hipospadia/patologia , Incidência , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Uretra/patologia , Estreitamento Uretral/etiologia , Estreitamento Uretral/terapia
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