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1.
J Cheminform ; 15(1): 48, 2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37088813

RESUMO

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.

2.
PeerJ ; 11: e14740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36743960

RESUMO

Hepatitis C remains a major public health problem in the world. The host immune system plays a key role in viral clearance. This study aimed to investigate the connection between retinoic acid-inducible gene I-like (RIG-I-like) receptor gene polymorphism and hepatitis C chronicity in the Chinese Han population. The current study genotyped three SNPs (IFIH1 rs10930046 and DHX58 rs2074158, rs2074160) to assess their association with the chronicity of hepatitis C virus (HCV) infection among 1,590 participants (590 spontaneous HCV clearance cases and 1,000 persistent infection patients). Our research shows that DHX58 rs2074158-G allele (dominant model: adjusted OR = 1.53, 95% CI [1.20-1.95], P = 0.001; additive model: adjusted OR = 1.50, 95% CI [1.27-1.78], P < 0.001) and IFIH1 rs10930046-C allele (additive model: adjusted OR = 1.26, 95% CI [1.07-1.49], P = 0.005) were associated with chronic hepatitis C (CHC). And the risk of CHC increased in people carrying more unfavorable genotypes (rs2074158-AG/GG or rs10930046-CC), with the chronic rates for genotypes number from zero to two in 60.69%, 57.33%, and 85.93%, respectively (adjusted OR = 3.64, 95% CI [2.18-6.08]; P < 0.001). Genetic polymorphism of IFIH1 and DHX58 may be related to CHC in the Chinese Han population. Furthermore, the risk of CHC increases as the number of unfavorable genotypes carried by the HCV-infected person increases. IFIH1 rs10930046, DHX58 rs2074158, age, ALT, and AST levels were all independent predictors of CHC.


Assuntos
Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Helicase IFIH1 Induzida por Interferon/genética , População do Leste Asiático , Hepatite C/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Helicases/genética
3.
Eur J Nucl Med Mol Imaging ; 49(8): 2821-2832, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34860277

RESUMO

PURPOSE: Growing evidence proved the efficacy of multi-parametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided targeted biopsy (TB) in prostate cancer (PCa) diagnosis, but there is no direct comparison between mpMRI-TB and PSMA PET/CT-TB. Gastrin-releasing peptide receptor (GRPR) is highly expressed in PCa, which can compensate for the unstable expression of PSMA in PCa. Therefore, we designed a study to compare the efficiency of mpMRI-TB, dual-tracer (GRPR and PSMA) PET/CT-TB, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer. METHODS: One hundred twelve suspicious PCa patients were enrolled from September 2020 to June 2021. Patients with anyone of positive dual-tracer PET/CT or mpMRI underwent TB, and all enrolled patients underwent systematic biopsy (SB) after TB. The primary outcome was the detection rates of PCa in different biopsy strategies. Secondary outcomes were the performance of three imaging methods, omission diagnostic rates, and upgrading and downgrading of biopsy samples relative to those of prostatectomy specimens in different biopsy strategies. McNemar's tests and Bonferroni correction in multiple comparisons were used to compare the primary and secondary outcomes. RESULTS: In 112 men, clinically significant PCa (grade group[GG] ≥ 2) accounted for 34.82% (39/112), and nonclinically significant PCa (GG = 1) accounted for 4.46% (5/112). 68 Ga-PSMA PET/CT-TB achieved higher PCa detection rate (69.77%) and positive ratio of biopsy cores (0.44) compared with SB (39.29% and 0.12) and mpMRI-TB (36.14% and 0.23), respectively (P < 0.005). Dual-tracer PET/CT screen out patients for avoiding 52.67% (59/112) unnecessary biopsy, whereas dual-tracer PET/CT-TB plus SB achieved high detection rate (77.36%) without misdiagnosis of csPCa. CONCLUSION: Dual-tracer PET/CT might screen patients for avoiding unnecessary biopsy. Dual-tracer PET/CT-TB plus SB might be a more effective and promising strategy for the definite diagnosis of clinically significant PCa than mpMRI-TB.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Biópsia , Radioisótopos de Gálio , Humanos , Biópsia Guiada por Imagem , Masculino , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/patologia , Receptores da Bombesina
4.
China Occupational Medicine ; (6): 652-656, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-976094

RESUMO

@#Objective ( ) To explore the feasibility of using generalized estimating equation GEE to analyze the influencing - ( ) factors of high frequency hearing loss HFHL among noise exposed workers in an air conditioner manufacturing enterprise. Methods - The noise exposed workers in an air conditioner manufacturing industry who had been tested for pure tone hearing threshold twice or more from 2015 to 2019 were selected as the research subjects using the judgment sampling method. Data , , , , , ( ) such as age length of service gender smoking alcohol consumption body mass index BMI and HFHL were collected. The Results influencing factors of HFHL were analyzed using the GEE. The detection rates of HFHL from 2015 to 2019 were , , , , , 22.2% 23.8% 24.2% 24.1% and 20.9% respectively. Among them the detection rate of HFHL in 2019 was lower than that ( P ) , , in 2017 and 2018 all <0.001 . The GEE analysis results showed that the risks of HFHL in 2015 2016 2017 and 2018 were ( P ), higher than that in 2019 all <0.01 regardless of interaction effects and after adjusting for confounding factors such as , [OR( CI)] ( - duration of noise exposure smoking and BMI. The odds ratios and 95% confidence intervals 95% were 1.19 1.07 ), ( - ), ( - ) ( - ), 1.33 1.26 1.13 1.39 1.30 1.18 1.43 and 1.27 1.15 1.39 respectively. The risk of HFHL was higher in males than in (P ), OR( CI) ( - ) , (P ), OR females <0.01 and 95% was 3.78 3.00 4.77 . The older the age the higher the risk of HFHL <0.01 and ( CI) ( - ) Conclusion - 95% was 1.07 1.05 1.09 . The influencing factors of HFHL among noise exposed workers in the air conditioner industry are age and gender. GEE can be used to analyze the factors influencing the longitudinal data of HFHL in workers with noise exposure.

5.
World J Gastrointest Oncol ; 13(11): 1741-1754, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34853647

RESUMO

BACKGROUND: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a potential preneoplastic lesion. AIM: To elucidate the microRNA (miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules (YWXY) in SPEM lesions. METHODS: Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent. YWXY was administered to the mice with induced SPEM by tamoxifen, and the gastric mucosa was harvested on the tenth day of the experiment. Then immunohistochemistry and immunofluorescence were performed to validate the SPEM, lesions and the potential mechanism was investigated. RNA transcripts were detected with reverse transcription-quantitative polymerase chain reaction. RESULTS: The expression of miR-7 was downregulated in the SPEM lesions, and expression of trefoil factor 2 (TFF2) and clusterin was high in the human gastric mucosa. In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67. Simultaneously, YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction, indicating its potential mechanism of targeting miR-7 by mediating TFF2. The expression of vascular endothelial growth factor-ß and gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions, speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-ß and gastric intrinsic factor. CONCLUSION: miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa. YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.

6.
Pathol Oncol Res ; 26(3): 1559-1564, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31482399

RESUMO

Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor associated with aggressive clinical behavior, metastasis and low survival. To date, only 67 cases have been described in the English language literature, and an understanding of the behavior of CCOC has been based on limited case reports. The aim of the research was to further reveal the features of CCOC. We report 5 new cases of CCOC, with a mean age of 52.4 years. The clinical and histopathologic data of the disease obtained from earlier literature (95 cases) and the 5 new cases were analyzed. Data were extracted, including demographics, histopathologic findings, clinical presentation, primary treatment and outcomes. Immunohistochemical results revealed that the cancer is positive for AE1/AE3, EMA and CK19, negative for smooth muscle actin SMA, Vim and S-100. EWSR1 translocation was also observed in the new cases, which may help in the diagnosis of CCOC. Metastases of CCOC were rare, but the local recurrence rate of CCOC rose to 42%. The best treatment for patients with CCOC is wide local excision combined with regional lymph node dissection.


Assuntos
Carcinoma/patologia , Neoplasias Mandibulares/patologia , Tumores Odontogênicos/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
7.
Ultrasound Med Biol ; 46(3): 610-619, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31810804

RESUMO

To assess the practicality of 3-D power Doppler angiography (3-D-CPA) for local drug perfusion dosage guidance of refractory infantile hemangioma (IH) treatment, 47 cases (48 lesions) of refractory IH were selected for local bleomycin infusion (once a month). Ultrasound was performed before treatment and 1 and 2 months after the first treatment. The 3-D volume (V) change of infantile hemangiomas and the ratio of bleomycin injection to 3-D V before treatment were calculated, and statistical analysis was performed. One month after percutaneous local drug perfusion, 37 participants (77.08%) exhibited significant improvement; controlled growth was observed on six lesions (12.5%); and treatment of the remaining 5 lesions (10.42%) failed to suppress growth. The calculated tolerable and effective dose of bleomycin for refractory IH was 0.34 ± 0.03 mL/cm3; the corresponding 3-D V decreased approximately 70.27 ± 6.27%. Three-dimensional CPA can provide abundant information on internal lesions. In particular, 3-D-CPA can quantitatively assess changes in lesion volume and guide the effective and rational use of interventional drugs.


Assuntos
Angiografia/métodos , Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Hemangioma/diagnóstico por imagem , Hemangioma/tratamento farmacológico , Imageamento Tridimensional , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/tratamento farmacológico , Ultrassonografia Doppler , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Perfusão/métodos , Estudos Retrospectivos
8.
Yi Chuan ; 41(12): 1110-1118, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857282

RESUMO

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.


Assuntos
Proteínas de Membrana , Músculo Esquelético , Mioblastos , Animais , Diferenciação Celular , Fusão Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Desenvolvimento Muscular , Proteínas Musculares , Músculo Esquelético/citologia , Mioblastos/citologia
10.
Mol Pharm ; 16(1): 393-408, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30475633

RESUMO

Hepatotoxicity is a major cause of drug withdrawal from the market. To reduce the drug attrition induced by hepatotoxicity, an accurate and efficient hepatotoxicity prediction system must be constructed. In the present study, we constructed a three-level hepatotoxicity prediction system based on different levels of adverse hepatic effects (AHEs) combined with machine learning, using (1) an end point, hepatotoxicity; (2) four hepatotoxicity severity degrees; and (3) specific AHEs. After collecting and curing 15 873 compound-AHE pairs associated with 2017 compounds and 403 AHEs, we constructed 27 models with three end point levels with the random forest algorithm, and obtained accuracies ranging from 67.0 to 78.2% and the area under receiver operating characteristic curves (AUCs) of 0.715-0.875. The 27 models were fully integrated into a tiered hepatotoxicity prediction system. The existence of hepatotoxicity existence, severity degree, and potential AHEs for a given compound could be inferred simultaneously and systematically. Thus, the tiered hepatotoxicity prediction system allows researchers to have significant confidence in confirming compound hepatotoxicity, analyzing hepatotoxicity from multiple perspectives, obtaining warnings for the potential hepatotoxicity severity, and even rapidly selecting the proper in vitro experiments for hepatotoxicity verification. We also applied three external sets (11 drugs or candidates that failed in clinical trials or were withdrawn from the market, the PharmGKB (offsides) database, and an herbal hepatotoxicity data set) to test and validate the prediction ability of our system. Furthermore, the hepatotoxicity prediction system was adapted into a flow framework based on the Konstanz Information Miner, which was made available for researchers.


Assuntos
Modelos Teóricos , Algoritmos , Área Sob a Curva , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Fígado/efeitos dos fármacos , Aprendizado de Máquina , Medição de Risco
11.
World J Gastroenterol ; 24(26): 2867-2877, 2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30018481

RESUMO

AIM: To explore the protective effects and underlying mechanisms of total polysaccharides of the Sijunzi decoction (TPSJ) on the epithelial barriers in vitro. METHODS: Caco-2 cell monolayers were treated with or without TPSJ in the presence or absence of TNF-α, and paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate the epithelial barrier function. Immunofluorescence and western blotting were respectively used to evaluate the distribution and expression of the tight junction proteins claudin 1, claudin 2, zo3, and occludin in Caco-2 cells. Western blotting was also used to evaluate the cellular expression of myosin light chain (MLC), phosphorylated MLC (pMLC), MLC kinase (MLCK), and nuclear factor (NF)-κB p65. RESULTS: TPSJ promoted the proliferation of Caco-2 cells and inhibited TNF-α-induced secretion of pro-inflammatory cytokines. Furthermore, TPSJ significantly ameliorated both the reduction of TEER and the increased paracellular permeability observed in tumor necrosis factor (TNF)-α-damaged Caco-2 monolayers. Furthermore, TPSJ remarkably attenuated TNF-α-induced morphological changes, downregulated the expression of claudin 1, claudin 2, zo3, and occludin, and markedly suppressed TNF-α-mediated upregulation of p-MLC and MLCK expression. Finally, TPSJ inhibited the activation and expression of NF-κB p65. CONCLUSION: Our results demonstrate that TPSJ alleviates the TNF-α-induced impairment of the intestinal epithelial cell barrier function by suppressing NF-κB p65-mediated phosphorylation of MLCK and MLC.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Intestinal/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Células CACO-2 , Técnicas de Cultura de Células , Regulação para Baixo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Fosforilação , Polissacarídeos/farmacologia , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Fator de Transcrição RelA/metabolismo , Regulação para Cima
12.
J Int Med Res ; 46(3): 1221-1229, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29322850

RESUMO

Objective To investigate the effectiveness of intrapancreatic choledochal cyst excision in treating type I choledochal cyst, and increase understanding of the need for thorough surgical management of the disease. Methods Primary and secondary (including multiple) surgical cases, treated between 2005 and 2015, were retrospectively analysed, and follow-up data of post-treatment effectiveness to date were reviewed. Differences in curative effects were compared between whole and partial excision of the choledochal cyst. Results Out of 350 cases, patients with whole excision of the choledochal cyst ( n = 272) experienced no associated symptoms in the long-term (3/272 [1.1%] experienced stomach ache or fever). Patients with partial resection of the choledochal cyst ( n = 78) developed associated symptoms, including new cyst, calculus of the bile duct (51/78 [65.4%]), and carcinogenesis (11/78 [14.1%]) in the residual intrapancreatic biliary duct. Post-treatment clinical manifestations were significantly different between patients with partial resection versus whole excision of the choledochal cyst ( P<0.05). Conclusion Surgical re-excision should be considered in patients with a residual intrapancreatic portion of the choledochal cyst due to prior incomplete surgery, regardless of clinical symptoms.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares/cirurgia , Calcinose/diagnóstico , Cisto do Colédoco/cirurgia , Cistectomia/métodos , Adolescente , Adulto , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares/patologia , Calcinose/etiologia , Calcinose/patologia , Criança , Cisto do Colédoco/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Recidiva , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
13.
Pain Manag Nurs ; 19(2): 186-194, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29153295

RESUMO

The therapeutic effect of postherpetic neuralgia (PHN) is often disappointing and challenging. The role of intra-cutaneous injection of local anesthetic and steroids in preventing PHN remains unknown. The purpose of this study was to investigate the effect of a single intra-cutaneous injection of ropivacaine plus methylprednisolone on acute thoracic herpes zoster (HZ) pain intensity and duration, eruptive duration, and PHN incidence. A total of 97 patients with acute thoracic HZ diagnosed 1-7 days after the onset of the rash were randomly assigned to receive either 15 mL of 37.5 mg ropivacaine plus 40 mg methylprednisolone (active group, n = 49) or 15 mL of saline (placebo group, n = 48). Over 7 days, all patients received 800 mg of acyclovir 5 times daily and 150 mg pregabalin twice daily. Acetaminophen was used as a rescue analgesia when visual analog scale ≥4. Pain intensity was measured with visual analog scale and the amount of analgesic taken was evaluated at the initial visit and at weeks 1, 4, 12, and 24 after the intra-cutaneous injection. The time of complete resolution of pain, time of healing of skin eruption, and incidence of PHN were reported. The active group displayed a significantly shorter duration of pain (28.4 ±â€¯46.7 vs. 59.2 ±â€¯65.0, respectively; p = .009) and herpetic eruption (22.5 ±â€¯6.8 vs. 32.6 ±â€¯7.6, respectively; p < .001) than the placebo group. A significantly lower incidence of PHN was encountered in the active group after 4 weeks (16.3% vs. 47.9%, respectively; p = .001) and 12 weeks (10.2% vs. 29.2%, respectively; p = .019). Lower incidence of PHN was noticed in the active group after 24 weeks; however, this was not statistically significant (6.1% vs. 18.8%, respectively; p = .059). There was a significant reduction in the average and total doses of pregabalin and acetaminophen in the active group after the injection. No serious side effects were noticed during the study period. Early single intra-cutaneous injection, in combination with antiviral agents and optimal analgesics, in the course of acute thoracic HZ seems to be a simple, well-tolerated, and effective adjuvant treatment modality. It dramatically decreased pain intensity, shortened pain duration, reduced skin eruption, and reduced and may even prevent the development of PHN.


Assuntos
Analgésicos/farmacologia , Herpes Zoster/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Administração Cutânea , Idoso , Amidas/farmacologia , Amidas/uso terapêutico , Analgésicos/uso terapêutico , Feminino , Humanos , Masculino , Metilprednisolona/farmacologia , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Placebos/farmacologia , Placebos/uso terapêutico , Estudos Prospectivos , Ropivacaina , Esteroides/farmacologia , Esteroides/uso terapêutico , Tórax/anormalidades , Tórax/efeitos dos fármacos , Escala Visual Analógica
14.
Molecules ; 22(9)2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28858253

RESUMO

Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric oxide nanoparticles, gold nanoparticles (Au NPs), and so on. Among them, Au NPs have been considered as the most interesting nanomaterial because of its unique optical, electronic, sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, and tumor therapy in the early detection, diagnosis, and treatment of diseases. This review focuses on some recent advances in the use of Au NPs as drug carriers for the intracellular delivery of therapeutics and as molecular nanoprobes for the detection and monitoring of target molecules.


Assuntos
Portadores de Fármacos/administração & dosagem , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Animais , Portadores de Fármacos/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Sondas Moleculares/administração & dosagem , Sondas Moleculares/química , Imagem Óptica , Coloração e Rotulagem
15.
J Org Chem ; 82(3): 1428-1436, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28090769

RESUMO

A copper-catalyzed tandem arylation-cyclization process to access 1-(arylthio)isoquinolines from isothiocyanates and diaryliodonium salts is described. It is the first general method to construct the potentially useful 1-(arylthio)isoquinoline derivatives. Moreover, 1-(methylthio)isoquinoline derivatives were also achieved successfully with MeOTf instead of diaryliodonium salts under metal-free conditions. Mechanistic studies reveal that these two processes proceed in different routes. This method has been successfully applied to the synthesis of quinazolinone alkaloid rutaecarpine.

16.
Biomed Res Int ; 2016: 9236573, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27872859

RESUMO

Hybrid rice breeding using cytoplasmic male sterility/fertility restoration (CMS/Rf) systems plays an important role in ensuring global food security. Two backcross inbred line (BIL) populations derived from either Xieqingzao B (XB)//XB/Dongxiang wild rice (DWR) (XXD) or XB//DWR/XB (XDX) were used to detect quantitative trait loci (QTLs) for fertility restoration of Dwarf wild abortive- (DA-), Indonesia Paddy- (ID-), and DWR-type CMS in rice. Lines with ID- and DA-type CMS were testcrossed with both the XXD- and XDX-BILs, while the line with DWR-type CMS was testcrossed with the XDX-BILs only. A total of 16 QTLs for fertility restoration of CMS systems were identified, including three for DWR-type CMS, six for DA-type CMS, and seven for ID-type CMS. All of the additive alleles in the QTLs were derived from Oryza rufipogon. Eleven QTLs were clustered in five chromosomal regions, indicating that common Rf loci restored different CMS systems, and the favorable O. rufipogon alleles could be used to develop restorer lines for various CMS types by marker-assisted selection.


Assuntos
Cruzamentos Genéticos , Citoplasma/genética , Endogamia , Oryza/genética , Infertilidade das Plantas/genética , Locos de Características Quantitativas/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Fertilidade , Genética Populacional , Fenótipo
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(10): 1377-1381, 2016 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-27777201

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of intradermal injection of methylene blue for treatment of moderate to severe acute thoracic herpes zoster and prevention of postherpetica neuralgia in elderly patients. METHODS: Sixty-four elderly patients with herpes zoster were randomized to receive a 10-day course of intradermal injection of methylene blue and lidocaine plus oral valaciclovir (group A, 32 cases) and intradermal injection of lidocaine plus oral valaciclovir (group B).Herpes evaluation index, pain rating index, incidence of postherpetic neuralgia, and comprehensive therapeutic effect were compared between the two groups at 11, 30 and 60 days after the treatment. RESULTS: The baseline characteristics were comparable between the two groups (all P>0.05). Compared with that in group B, the time for no new blister formation, blister incrustation and decrustation, and pain relief was significantly shortened in group A (P<0.05) with also obviously lower pain intensity after the treatment. The incidence of postherpetic neuralgia was significantly lower in group A than in group B at 30 days (P<0.05), but not at 60 and 90 days after the treatment. The total clinical response rate was 93.8% in group A, much higher than that in group B (62.5%, P<0.05). CONCLUSION: Intradermal injection of methylene blue can effectively shorten the disease course, reduce the pain intensity and prevent the development of postherpetic neuralgia in elderly patients with herpes zoster.


Assuntos
Herpes Zoster/complicações , Azul de Metileno/administração & dosagem , Neuralgia Pós-Herpética/terapia , Aciclovir/administração & dosagem , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Idoso , Humanos , Incidência , Injeções Intradérmicas , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Azul de Metileno/uso terapêutico , Medição da Dor , Valaciclovir , Valina/administração & dosagem , Valina/análogos & derivados , Valina/uso terapêutico
18.
J Hum Genet ; 61(2): 129-35, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26446365

RESUMO

Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). This study investigated the associations of single-nucleotide polymorphisms (SNPs) of VDR with the outcomes of Hepatitis C virus (HCV) infection. Three SNPs (rs2228570, rs757343 and rs739837) were genotyped by TaqMan assay among Chinese population, including 538 HCV spontaneous clearance subjects, 834 persistent infection subjects and 1030 uninfected subjects. Binary logistic analyses were used to control the effects of confounding factors. The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (all PBonferroni<0.05 in dominant/additive model). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in some subgroups. In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (PBonferroni=0.033) and such effect still work in several subgroups in the stratified analysis. Furthermore, haplotype analysis indicated that when compared with the most frequent GC haplotype, the haplotype carrying AA (odds ratio (OR)=0.66, 95% confidence interval (CI)=0.56-0.78) and GA (OR=0.64, 95% CI=0.47-0.85) suggested a protective effect. Our findings indicated that the polymorphisms of VDR are associated with the outcomes of HCV infection among Chinese population.


Assuntos
Hepatite C/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
19.
Biol Trace Elem Res ; 172(1): 193-200, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26660892

RESUMO

It is well known that excess iodide can lead to thyroid colloid retention, a classic characteristic of iodide-induced goiter. However, the mechanism has not been fully unrevealed. Iodide plays an important role in thyroid function at multiple steps of thyroid colloid synthesis and transport among which sodium/iodide symporter (NIS) and pendrin are essential. In our study, we fed female BALB/c mice with different concentrations of high-iodine water including group A (control group, 0 µg/L), group B (1500 µg/L), group C (3000 µg/L), group D (6000 µg/L), and group E (12,000 µg/L). After 7 months of feeding, we found that excess iodide could lead to different degrees of thyroid colloid retention. Besides, NIS and pendrin expression were downregulated in the highest dose group. The thyroid iodide intake function detected by urine iodine assay and thyroidal (125)I experiments showed that the urine level of iodine increased, while the iodine intake rate decreased when the concentration of iodide used in feeding water increased (all p < 0.05 vs. control group). In addition, transmission electron microscopy (TEM) indicated a reduction in the number of intracellular mitochondria of thyroid cells. Based on these findings, we concluded that the occurrence of thyroid colloid retention exacerbated by excess iodide was associated with the suppression of NIS and pendrin expression, providing an additional insight of the potential mechanism of action of excess iodide on thyroid gland.


Assuntos
Proteínas de Transporte de Ânions/antagonistas & inibidores , Iodetos/farmacologia , Simportadores/antagonistas & inibidores , Glândula Tireoide/efeitos dos fármacos , Animais , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Coloides/química , Coloides/metabolismo , Feminino , Iodetos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Transportadores de Sulfato , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia
20.
Yi Chuan ; 37(12): 1175-84, 2015 12.
Artigo em Chinês | MEDLINE | ID: mdl-26704942

RESUMO

Adipose tissues play a critical role in the regulation of energy metabolism and homeostasis, and is also an important endocrine organ. Adipocyte differentiation is a complicated physiological process during which mesenchymal stem cells differentiate into adipocytes. This process is synergistically regulated by a large number of transcription factors, hormones and signaling pathway molecules. As a class of endogenous non-coding RNA (ncRNA), microRNAs (miRNAs) regulate gene expression mainly through post-transcriptional translational repression. In recent years, numerous studies have demonstrated that miRNA could have an impact on adipocyte differentiation and adipogenesis by modulating the expression levels of several adipogenic transcription factors and key signaling molecules. In this review, we summarize the mechanism of miRNA in regulating the differentiation of white/brown/beige adipocytes and the relevant signaling pathways and key factors, in the hope of providing theoretical guidance and new thoughts for treating obesity and other metabolic diseases.


Assuntos
Adipócitos/metabolismo , Adipogenia , Regulação da Expressão Gênica , MicroRNAs/metabolismo , Adipócitos/citologia , Animais , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/síntese química , MicroRNAs/genética , Transdução de Sinais
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