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1.
Artigo em Inglês | MEDLINE | ID: mdl-32748473

RESUMO

Silymarin has been shown to be a multiple-functional plant extract having antioxidant, hepatoprotective, hypolipidemic, antihypertensive, antidiabetic and anti-obesity effects. In recent years, the galactagogue effects of silymarin in animals and humans have also been revealed. This research was conducted to test whether dietary inclusion of silymarin during transition and lactation could impact reproductive performance of sows and to explore the underlying mechanisms. From day 108 of gestation to weaning, sows were randomly assigned to receive dietary treatment of silymarin (40 g/day) or not and were designated as control group (CGP, n = 55) or treatment group (TGP, n = 55). The results showed that piglets' average daily gain and average weaning weight were higher in TGP than CGP sows. In comparison with the CGP sows, the TGP sows had higher serum concentrations of catalase (CAT) on day 18 of lactation and glutathione peroxidase (GSH-Px) on day 7 of lactation. The TGP sows had lower concentration of TNF-α on day 7 of lactation and significantly lower concentration of IL-1ß on day 18 of lactation than CGP sows. There was significantly higher serum concentration of PRL on day 7 of lactation in sows consuming silymarin than sows from the CGP group. On day 18 of lactation, the protein and urea contents in milk were significantly increased while the serum urea concentration was significantly decreased in TGP sows. In summary, our results indicate that silymarin supplementation during transition and lactation can increase circulating concentrations of PRL transiently, reduce oxidative stress, increase feed intake and enhance protein metabolism, thereby significantly increasing milk yield of sows and subsequently improving growth performance of their offsprings.

2.
J Med Virol ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32497323

RESUMO

The ongoing outbreak of a new coronavirus (2019-nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID-19) in humans. SARS-CoV-2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 may use the same host cellular receptor, angiotensin-converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS-CoV-2 S protein is much higher than that of ACE2 binding to the SARS-CoV S protein, explaining why SARS-CoV-2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS-CoV-1 and SARS-CoV-2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS-CoV-2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high-risk factors for developing COVID-19, and the infection of other viruses may increase the risk of SARS-CoV-2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.

3.
J Med Virol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343415

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS-CoV-2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in nonsevere cases.

4.
Aging (Albany NY) ; 12(5): 4445-4462, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155132

RESUMO

Forest musk deer (Moschus berezovskii, FMD) is an endangered artiodactyl species, male FMD produce musk. We have sequenced the whole genome of FMD, completed the genomic assembly and annotation, and performed bioinformatic analyses. Our results showed that microsatellites (SSRs) displayed nonrandomly distribution in genomic regions, and SSR abundances were much higher in the intronic and intergenic regions compared to other genomic regions. Tri- and hexanucleotide perfect (P) SSRs predominated in coding regions (CDSs), whereas, tetra- and pentanucleotide P-SSRs were less abundant. Trifold P-SSRs had more GC-contents in the 5'-untranslated regions (5'UTRs) and CDSs than other genomic regions, whereas mononucleotide P-SSRs had the least GC-contents. The repeat copy numbers (RCN) of the same mono- to hexanucleotide P-SSRs had different distributions in different genomic regions. The RCN of trinucleotide P-SSRs had increased significantly in the CDSs compared to the transposable elements (TEs), intronic and intergenic regions. The analysis of coefficient of variability (CV) of P-SSRs showed that the RCN of mononucleotide P-SSRs had relative higher variation in different genomic regions, followed by the CV pattern of RCN: dinucleotide P-SSRs > trinucleotide P-SSRs > tetranucleotide P-SSRs > pentanucleotide P-SSRs > hexanucleotide P-SSRs. The CV variations of RCN of the same mono- to hexanucleotide P-SSRs were relative higher in the intron and intergenic regions, followed by that in the TEs, and the relative lower was in the 5'UTR, CDSs and 3'UTRs. 58 novel polymorphic SSR loci were detected based on genotyping DNA from 36 captive FMD and 22 SSR markers finally showed polymorphism, stability, and repetition.

5.
Aging (Albany NY) ; 12(3): 2373-2392, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012120

RESUMO

Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdown inhibits HCC cell proliferation, migration, and invasion, whereas its overexpression has an opposite effect. Mechanistically, upregulated UBE2M exerts oncogenic effects by translocation of accumulated ß-catenin from the cytoplasm to the nucleus, thus activating downstream ß-catenin/cyclin D1 signaling. In summary, our study demonstrates a notable role of UBE2M in promoting the growth of HCC, providing a novel strategy for HCC prevention and treatment.

6.
J Cell Biochem ; 121(4): 2938-2949, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31692072

RESUMO

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.

7.
Eur J Gastroenterol Hepatol ; 32(2): 265-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789948

RESUMO

BACKGROUND: To explore the risk factors and prognostic factors related to the acute-on-chronic liver failure (ACLF) occurrence and adverse outcome after withdrawal of nucleos(t)ide analogs (NAs) in chronic hepatitis B (CHB) patients. METHODS: Hospitalized CHB patients with relapse after NAs withdrawal at our medical center were retrospectively included in the present study from January 2011 to May 2018. Logistic regression, Cox regression analysis, Kaplan-Meier log-rank test, and area under the receiver operating characteristic curves (AUROC) were used. RESULTS: A total of 389 CHB patients (including 46 ACLF patients) were included. Their median age was 48.0 years; 315 patients were male and 74 were female. The age ≥30 years and HBVDNA ≤1000 copies at admission in logistic regression were the independent risk factors for ACLF after NAs withdrawal in CHB patients. In patients who developed ACLF, only the model of end-stage liver disease combining serum natrium concentration (MELD-Na) score and relapse after Lamivudine (LAM) cessation in the Cox multivariate regression analysis were independent predictors for 12-week mortality. The artificial liver support system (ALSS) showed no improvement in the 12-week survival of ACLF patients. We further defined 22.35 as the optimal cutoff value of MELD-Na score to predict 12-week mortality for ACLF patients, with the AUROC of 0.817, a sensitivity of 76.5%, and a specificity of 75.9%. CONCLUSION: The age ≥30 years and HBVDNA ≤1000 copies at admission strongly correlate with occurrence of ACLF, and higher MELD-Na score and relapse after LAM withdrawal are closely related with 12-week mortality among patients with ACLF after NAs withdrawal.

8.
Sci Rep ; 8(1): 14407, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30258087

RESUMO

As the first examination of distribution, guanine-cytosine (GC) pattern, and variation analysis of microsatellites (SSRs) in different genomic regions of six bovid species, SSRs displayed nonrandomly distribution in different regions. SSR abundances are much higher in the introns, transposable elements (TEs), and intergenic regions compared to the 3'-untranslated regions (3'UTRs), 5'UTRs and coding regions. Trinucleotide perfect SSRs (P-SSRs) were the most frequent in the coding regions, whereas, mononucleotide P-SSRs were the most in the introns, 3'UTRs, TEs, and intergenic regions. Trifold P-SSRs had more GC-contents in the 5'UTRs and coding regions than that in the introns, 3'UTRs, TEs, and intergenic regions, whereas mononucleotide P-SSRs had the least GC-contents in all genomic regions. The repeat copy numbers (RCN) of the same mono- to hexanucleotide P-SSRs showed significantly different distributions in different regions (P < 0.01). Except for the coding regions, mononucleotide P-SSRs had the most RCNs, followed by the pattern: di- > tri- > tetra- > penta- > hexanucleotide P-SSRs in the same regions. The analysis of coefficient of variability (CV) of SSRs showed that the CV variations of RCN of the same mono- to hexanucleotide SSRs were relative higher in the intronic and intergenic regions, followed by the CV variation of RCN in the TEs, and the relative lower was in the 5'UTRs, 3'UTRs, and coding regions. Wide SSR analysis of different genomic regions has helped to reveal biological significances of their distributions.


Assuntos
Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Genoma , Íntrons , Repetições de Microssatélites , Ruminantes/genética , Animais
9.
Biomed Pharmacother ; 105: 1147-1154, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30021351

RESUMO

microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.


Assuntos
Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Transdução de Sinais/fisiologia
11.
World J Gastroenterol ; 23(33): 6100-6110, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28970725

RESUMO

AIM: To clarify the mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in gastric cancer (GC) migration and invasion. METHODS: Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve (AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qPCR, western blot and immunohistochemistry were used to evaluate the mRNA and protein expression of E-cadherin. RNA-binding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin. RESULTS: The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues (P < 0.001). Its over-expression was correlated with tumor-node-metastasis (TNM) stage (P = 0.024), tumor invasion (P = 0.018), lymph node metastasis (P = 0.023), and poor prognosis (P < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival (P = 0.033), together with TNM stage (P = 0.002) and lymph node metastasis (P = 0.002). The AUCROC was up to 0.709 (95%CI: 0.623-0.785, P < 0.001). Knockdown of HOTAIR by siRNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines, and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION: HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Caderinas/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Antígenos CD , Biomarcadores Tumorais/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Imunoprecipitação da Cromatina , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Seguimentos , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Regulação para Cima
12.
Oncol Lett ; 14(3): 2703-2708, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28928813

RESUMO

The overexpression of heat shock protein 70 (HSP70), a major stress-inducible heat shock protein, has been identified to enhance the proliferation, survival, invasion and metastasis of diverse types of human cancer. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. The present study demonstrated that HSP70 expression was higher in tested HCC cell lines, compared with the normal hepatocyte LO2, and the suppression of HSP70 significantly inhibited the proliferation of SMMC-7721 and Hep3B cells. The growth inhibitory effect was mediated by cell cycle arrest at the G1/S phase with reduced cyclin D1 and increased p27Kip1 expression. Furthermore, HSP70 knockdown significantly inhibited the migration and invasion abilities of HCC cells. In conclusion, HSP70 is a key regulator involved in the proliferation, migration and invasion of HCC, and it may be used as a potential therapeutic target for HCC.

13.
Cell Death Dis ; 8(6): e2850, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28569780

RESUMO

Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer's disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal ß-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway.


Assuntos
Precursor de Proteína beta-Amiloide/genética , Isquemia Encefálica/genética , MicroRNAs/genética , Neurônios/metabolismo , Receptores de Morte Celular/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Artérias Carótidas/cirurgia , Caspase 3/genética , Caspase 3/metabolismo , Caspase 6/genética , Caspase 6/metabolismo , Morte Celular , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/cirurgia , Giro Denteado/metabolismo , Giro Denteado/patologia , Regulação da Expressão Gênica , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Neurônios/patologia , Oligorribonucleotídeos Antissenso/genética , Oligorribonucleotídeos Antissenso/metabolismo , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Receptores de Morte Celular/metabolismo , Transdução de Sinais
14.
J Cancer Res Clin Oncol ; 142(11): 2309-17, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27601163

RESUMO

PURPOSE: Aberrant expression of eukaryotic initiation factor 4E (eIF4E) has been observed in human malignancies. However, its role in hepatocellular carcinoma (HCC) remains to be established. The purpose of this study was to detect eIF4E expression and to evaluate its clinical relevance. METHODS: The eIF4E expression was studied in ninety HCC and randomly selected thirty-one non-tumor tissues from the same patient cohort, as well as in normal hepatic and HCC cell lines. The relation between its expression and clinicopathological parameters was also analyzed. RESULTS: eIF4E expression was higher in HCC samples and cell lines compared with that in non-tumor tissues (P < 0.001) and hepatocyte LO2, respectively. eIF4E overexpression was significantly associated with tumor number (P = 0.005) and incomplete encapsulation (P = 0.001). The 5-year overall survival rate and disease-free survival rate for patients with high eIF4E expression were 32.5 and 31.2 %, respectively; and for low eIF4E expression, it was 67.9 and 64.4 %, respectively (P < 0.001). Furthermore, subgroup analysis showed that high eIF4E level predicted poorer overall survival only for incomplete encapsulation (P = 0.001) and cirrhosis (P < 0.001), but not for complete encapsulation (P = 0.804) and non-cirrhosis (P = 0.359). Multivariate analysis revealed that eIF4E overexpression was an independent indicator for both overall survival (hazard ratio, 2.015; P = 0.043) and disease-free survival (hazard ratio, 2.666; P = 0.006). CONCLUSIONS: eIF4E protein might result in the malignant progression of HCC, and its overexpression may be a powerful prognostic biomarker and therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Proteínas de Transporte Nucleocitoplasmático/biossíntese , Prognóstico , Taxa de Sobrevida , Análise Serial de Tecidos , Regulação para Cima
15.
Aging (Albany NY) ; 8(11): 2635-2654, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27644032

RESUMO

As the first systematic examination of simple sequence repeats (SSRs) and guanine-cytosine (GC) distribution in intragenic and intergenic regions of ten primates, our study showed that SSRs and GC displayed nonrandom distribution for both intragenic and intergenic regions, suggesting that they have potential roles in transcriptional or translational regulation. Our results suggest that the majority of SSRs are distributed in non-coding regions, such as the introns, TEs, and intergenic regions. In these primates, trinucleotide perfect (P) SSRs were the most abundant repeats type in the 5'UTRs and CDSs, whereas, mononucleotide P-SSRs were the most in the intron, 3'UTRs, TEs, and intergenic regions. The GC-contents varied greatly among different intragenic and intergenic regions: 5'UTRs > CDSs > 3'UTRs > TEs > introns > intergenic regions, and high GC-content was frequently distributed in exon-rich regions. Our results also showed that in the same intragenic and intergenic regions, the distribution of GC-contents were great similarity in the different primates. Tri- and hexanucleotide P-SSRs had the most GC-contents in the 5'UTRs and CDSs, whereas mononucleotide P-SSRs had the least GC-contents in the six genomic regions of these primates. The most frequent motifs for different length varied obviously with the different genomic regions.


Assuntos
DNA Intergênico , Genoma , Repetições de Microssatélites , Primatas/genética , Animais , Citosina , Guanina
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(1): 24-8, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26955672

RESUMO

OBJECTIVE: To observe the auxiliary efficacy and safety of Hebi Recipe (HR)in treating early rheumatoid arthritis (RA). METHODS: Totally 63 early RA patients with Gan-Pi disharmony were randomly assigned to the treatment group [32 cases, treated by HR (one dose per day, taken in two portions for 24 successive weeks) plus Methotrexate (MTX)] and the control group (31 cases, treated by MTX alone). The dosage of MTX was increased from 7.5 mg to 12.5 mg, once per week, 24 weeks as one course of treatment. Efficacy for Chinese medical syndromes, American College of Rheumatology 20 (ACR20) improvement rate, disease activity score in 28 joints (DAS28), laboratory related indices [ESR, rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP)], and related ultrasonic inspection items (synovium thickness, synovium blood flow classification, effusion of joint), and adverse reactions were observed. RESULTS: The total effective rate (83.9%, 26/31 cases) and ACR20 improvement rate (74.2%, 23/31 cases) were higher in the treatment group than in the control group [60.7% (17/28 cases), 46.4% (13/28 cases); P < 0.05]. Compared with before treatment in the same group, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the two groups after treatment (P < 0.01, P < 0.05). Compared with the control group after treatment, ACR20 improvement rate, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the treatment group (P < 0.01, P < 0.05). Liver dysfunction occurred in 1 case of the treatment group. One leucopenia and 2 liver dysfunction occurred in the control group. CONCLUSION: HR could effectively improve joints and systemic symptoms of early RA patients with Gan-Pi disharmony.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Proteína C-Reativa , Quimioterapia Combinada , Humanos , Metotrexato , Fitoterapia , Fator Reumatoide , Síndrome , Resultado do Tratamento
17.
PLoS One ; 10(7): e0133667, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26196922

RESUMO

Microsatellites or simple sequence repeats (SSRs) have become the most popular source of genetic markers, which are ubiquitously distributed in many eukaryotic and prokaryotic genomes. This is the first study examining and comparing SSRs in completely sequenced genomes of the Bovidae. We analyzed and compared the number of SSRs, relative abundance, relative density, guanine-cytosine (GC) content and proportion of SSRs in six taxonomically different bovid species: Bos taurus, Bubalus bubalis, Bos mutus, Ovis aries, Capra hircus, and Pantholops hodgsonii. Our analysis revealed that, based on our search criteria, the total number of perfect SSRs found ranged from 663,079 to 806,907 and covered from 0.44% to 0.48% of the bovid genomes. Relative abundance and density of SSRs in these Bovinae genomes were non-significantly correlated with genome size (Pearson, r < 0.420, p > 0.05). Perfect mononucleotide SSRs were the most abundant, followed by the pattern: perfect di- > tri- > penta- > tetra- > hexanucleotide SSRs. Generally, the number of SSRs, relative abundance, and relative density of SSRs decreased as the motif repeat length increased in each species of Bovidae. The most GC-content was in trinucleotide SSRs and the least was in the mononucleotide SSRs in the six bovid genomes. The GC-contents of tri- and pentanucleotide SSRs showed a great deal of similarity among different chromosomes of B. taurus, O. aries, and C. hircus. SSR number of all chromosomes in the B. taurus, O.aries, and C. hircus is closely positively correlated with chromosome sequence size (Pearson, r > 0.980, p < 0.01) and significantly negatively correlated with GC-content (Pearson, r < -0.638, p < 0.01). Relative abundance and density of SSRs in all chromosomes of the three species were significantly negatively correlated with GC-content (Pearson, r < -0.333, P < 0.05) but not significantly correlated with chromosome sequence size (Pearson, r < -0.185, P > 0.05). Relative abundances of the same nucleotide SSR type showed great similarity among different chromosomes of B. taurus, O. aries, and C. hircus.


Assuntos
Bovinos/genética , Genoma , Repetições de Microssatélites , Animais , Composição de Bases , Bovinos/classificação , Estudo de Associação Genômica Ampla , Polimorfismo Genético
18.
J Neurochem ; 134(6): 1139-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26118667

RESUMO

Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the down-regulation of microRNA-195 (miR-195) promotes amyloidogenesis via regulation of amyloid precursor protein and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post-transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR-195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi. Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR-195 over-expression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR-195 inhibition. A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3'UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down-regulation of miR-195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down-regulation of miR-195 led to increased vulnerability via the regulation of multiple targets. Schematic diagram of miR-195 mediated Aß aggregation and tau hyperphosphorylation in chronic brain hypoperfusion (CBH). First, CBH results in the elevation of nuclear factor-κB (NF-κB), which binds with the promoter sequences of miR-195 and negatively regulates the expression of miR-195. Second, down-regulated miR-195 induces up-regulation of APP and BACE1 and leads to an increase in Aß levels. Third, some of the elevated Aß then enter the intracellular space and activate calpain, which promotes the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IκB; IκB is an inhibitor of NF-κB, which activates NF-κB. Cdk5/p25 directly phosphorylates Tau. Fourth, down-regulated miR-195 induces an up-regulation of p35, which provides the active substrates of p25. Our findings demonstrated that the down-regulation of miR-195 plays a key role in the increased vulnerability to dementia via the regulation of multiple targets following CBH.


Assuntos
Doença de Alzheimer/metabolismo , Isquemia Encefálica/metabolismo , Quinase 5 Dependente de Ciclina/metabolismo , MicroRNAs/metabolismo , Proteínas tau/metabolismo , Animais , Western Blotting , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Isquemia Encefálica/complicações , Doença Crônica , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(1): 282-6, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25993865

RESUMO

In the process of modern drug research, the new methods and technologies which can detect drug molecules' chemical composition, structure and interaction with biomolecules are always the key scientific problems people care about. Spectra (including IR, UV and NMR) are the most common analytical methods, of which NMR can obtain detailed parameter about the nucleus of organic molecules through researching the laws of nuclear transition in the impact of surrounding chemical environment. The parameter contains rich information about the chemical composition, structure and interaction with other molecules of organic molecules. In many complex environments, such as liquid, solid or gas state, even biological in situ environment, NMR can provide molecules' chemical composition, atomic-resolution three-dimensional structure, information of interaction with each other and dynamic process, especially the information about drug interacting with biomacromolecules. In recent years, the applications of nuclear magnetic resonance spectrum in drug research and development are more and more widespread. This paper reviewed its recent progress in structure and dynamic of targeted biological macromolecules, drug design and screening and drug metabolism in drug research and development. In the first part, we gave a brief introduction of nuclear magnetic resonance technology and its applications in drug research. In the second part, we explained the basic principles briefly and summarized progress in methods and techniques for drug research. In the third part, we discussed applications of nuclear magnetic resonance ir structure and dynamic of targeted biological macromolecules, drug design and screening and drug metabolism in detail. The conclusions were stated in the last part.


Assuntos
Química Farmacêutica/métodos , Espectroscopia de Ressonância Magnética , Preparações Farmacêuticas/análise
20.
Indian J Biochem Biophys ; 51(3): 201-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25204081

RESUMO

3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) plays an important role in catalyzing the first committed step of isoprenoids biosynthesis in mevalonic acid (MVA) pathway. Here, we cloned a full-length transcript of Paris fargesii Franch. The full-length cDNA of P. fargesii HMGR (Pf-HMGR, GenBank accession no. JX508638) was 1,973 bp and contained a 1,728 bp ORF encoding 576 amino acids. Sequence analysis revealed that the deduced Pf-HMGR had high similarity with HMGRs from other plants, including Ricinus communis (77%), Litchi chinensis (76%), Michelia chapensis (75%) and Panax quinquefolius (72%). It had a calculated molecular mass of about 62.13 kDa and an isoelectric point (pI) of 8.47. It contained two transmembrane domains, two putative HMGR binding sites and two NADP(H)-binding sites. The predicted 3-D structure revealed that Pf-HMGR had a similar spatial structure with other plant HMGRs. Three catalytic regions, including L-domain, N-domain and S-domain were detected by structural modeling of HMGR. Tissue expression analysis revealed that Pf-HMGR was strongly expressed in roots and stems than in leaves. Taken together, our data laid a foundation for further investigation of HMGR's functions and regulatory mechanisms in plants.


Assuntos
Hidroximetilglutaril-CoA Redutases/genética , Liliaceae/enzimologia , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Biologia Computacional , Hidroximetilglutaril-CoA Redutases/química , Hidroximetilglutaril-CoA Redutases/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , RNA Mensageiro/genética , RNA de Plantas/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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