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1.
J Am Chem Soc ; 144(17): 7939-7948, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35470672

RESUMO

Cinnamoyl-containing natural products (CCNPs) are a small class of bacterial metabolites with notable bioactivities. The biosynthesis of cinnamoyl moiety has been proposed to be assembled by an unusual highly reducing (HR) type II polyketide synthases (PKS). However, the biosynthetic route, especially the cyclization step for the benzene ring formation, remains unclear. In this work, we successfully reconstituted the pathway of cinnamoyl moiety in kitacinnamycin biosynthesis through a step-wise approach in vitro and demonstrated that a three-protein complex, Kcn17-Kcn18-Kcn19, can catalyze 6π-electrocyclization followed by dehydrogenation to form the benzene ring. We found that the three-protein homologues were widely distributed among 207 HR type II PKS biosynthetic gene clusters including five known CCNPs. In contrast, in the biosynthesis of youssoufene, a cinnamoyl-containing polyene, we identified that the benzene ring formation was accomplished by a distinct orphan protein. Thus, our work resolved the long-standing mystery in cinnamoyl biosynthesis and revealed two distinct enzymes that can synthesize benzene rings via polyene precursors.


Assuntos
Produtos Biológicos , Policetídeo Sintases , Benzeno , Produtos Biológicos/metabolismo , Ciclização , Família Multigênica , Polienos , Policetídeo Sintases/metabolismo
2.
Anim Biotechnol ; : 1-9, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985384

RESUMO

This study aimed to explore the genetic basis of muscle development in goats. The transcriptome dataset for differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) of goat muscle at different developmental stages were obtained using RNA-Seq. A total of 447,806,481 and 587,559,465 clean reads in the longissimus dorsi muscle of Dazu black goats between 75d embryonic stage and 1d after birth were generated through Illumina paired-end sequencing, and their mapping rates were 89.82 and 90.99%, respectively. Moreover, 4517 DEGs and 648 DELs were identified, and 4784 lncRNA-mRNA targeting relationships were predicted. Gene function annotation results showed that 4101 DEGs were significantly enriched to 1098 GO terms, and 2014 DEGs were significantly enriched to 40 KEGG pathways, including many GO terms and pathways related to muscle development, such as cell differentiation and Wnt signaling pathway. Then, 10 DELs and 20 DEGs were randomly selected for RT-qPCR verification, and the agreement rate between the verification and RNA-Seq results was 90%, indicating the high reliability of the RNA-Seq data analysis. In conclusion, this study obtained several mRNAs and lncRNAs related to the muscle development of Dazu black goats and identified several targeted regulatory pairs of lncRNA-mRNA. This study may serve as a reference to understand the genetic basis and molecular mechanism of muscle development in goats.

3.
Surg Endosc ; 36(3): 1789-1798, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788032

RESUMO

BACKGROUND: Although self-expandable mental stents (SEMS) placement is the standard care for relieving obstructive jaundice caused by unresectable malignant biliary stricture, how to maintain stent potency remains an intractable problem. This study was to evaluate the efficacy and safety of endobiliary radiofrequency ablation (RFA) through percutaneous transhepatic cholangiography (PTC) pathway in treating such patients. METHODS: Consecutive patients who were performed endobiliary RFA as well as SEMS placement because of unresectable malignant obstructive jaundice in single institution in recent 8 years were retrospectively reviewed. As comparison, patients who underwent only percutaneous SEMS placement for unresectable malignant biliary stricture during the contemporary period were reviewed. Stent patency, complications, complications, and overall survival (OS) were investigated and analyzed. RESULTS: One hundred and fifty patients who underwent endobiliary RFA and 127 patients who underwent only stent placement were included in this study. In the study group of endobiliary RFA, 87 patients (58.0%) underwent ablation for 1 time, 49 (32.7%) for 2 times, and 14 (9.3%) for 3 times. Complications related to RFA as well as SEMS placement happened in 113 patients (75.3%), without severe complications that needed emergent surgery or interventional therapy. The median duration of stent patency after ablation was 11.2 month, and the median survival time was 12.3 month. As comparison, difference was found in the number of interventional procedures and stents placed, duration of initial stent patency, and the incidence of moderate bleeding and pain. In the study group, only the type of tumor that caused biliary obstruction (intrahepatic carcinoma vs. extrahepatic carcinoma) was a poor independent factor (P = 0.035) for recurrent biliary obstruction. Repeated interventional therapy and adoption of subsequent therapy were only independent factors for OS. CONCLUSIONS: Endobiliary RFA and SEMS placement is technically safe and feasible for unresectable malignant obstructive jaundice to improve the quality of life and prolong survival.


Assuntos
Neoplasias dos Ductos Biliares , Ablação por Cateter , Colestase , Icterícia Obstrutiva , Ablação por Radiofrequência , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ablação por Cateter/métodos , Colestase/etiologia , Colestase/cirurgia , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/cirurgia , Qualidade de Vida , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
4.
Healthcare (Basel) ; 9(9)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34574934

RESUMO

Dementia has become a serious global health problem for older people. In the past, primary screening for dementia was carried out by a paper test. These standard traditional tests (e.g., Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE)) have been used for many years. In addition to paper tests, is there another way to let people have better involvement and emotions during the test procedure? With the advancement of technology, the application of virtual reality (VR) and augmented reality (AR) have changed and improved many medical technologies. However, there are few applications of VR and AR in dementia screening. The purpose of this study was to apply VR and AR to construct a pilot tool for virtual scenario initial dementia cognitive screening (VSIDCS) with a cultural exhibition, to achieve better involvement and emotions in participants. There were three operating interfaces designed for the system: a VR screening interface, cognitive board, and AR recognition interface. There were twenty-four middle-aged people (Female 10 and Male 14 between 50 and 65 years of age and with an average age of 58.7 years) selected for the test. The results of the experiments showed that VSIDCS test scores are consistent with those of the MoCA and MMSE. Additionally, VSIDCS can induce better involvement and emotions than the MoCA and MMSE. Participants showed better enthusiasm and more positive experiences during the VSIDCS test.

5.
Yonsei Med J ; 62(10): 918-927, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34558871

RESUMO

PURPOSE: We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. MATERIALS AND METHODS: Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. RESULTS: Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. CONCLUSION: Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Ligadura , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia
6.
Anim Biotechnol ; : 1-8, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289783

RESUMO

This study compared and analyzed the genetic diversity and population structure of exon 2 of the DQB1 gene and 13 autosomal neutral microsatellite markers from 14 Chinese goat breeds to explore the potential evolutionary mechanism of the major histocompatibility complex (MHC). A total of 287 haplotypes were constructed from MHC-DQB1 exon 2 from 14 populations, and 82 nucleotide polymorphic sites (SNPs, 31.78%) and 172 heterozygous individuals (79.12%) were identified. The FST values of the microsatellites and MHC-DQB ranged between 0.01831-0.26907 and 0.00892-0.38871, respectively. Furthermore, 14 goat populations showed rich genetic diversity in the microsatellite loci and MHC-DQB1 exon 2. However, the population structure and phylogenetic relationship represented by the two markers were different. Positive selection and Tajima's D test results showed the occurrence of a diversified selection mechanism, which was primarily based on a positive and balancing selection in goat DQB. This study also found that the DQB sequences of bovines exhibited trans-species polymorphism (TSP) among species and families. In brief, this study indicated that positive and balancing selection played a major role in maintaining the genetic diversity of DQB, and TSP of MHC in bovines was common, which enhanced the understanding of the MHC evolution.

7.
J Cell Mol Med ; 25(12): 5782-5798, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33982381

RESUMO

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.


Assuntos
Modelos Animais de Doenças , Flavanonas/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Sepse/complicações , Animais , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Transdução de Sinais
8.
Anim Biotechnol ; : 1-19, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635178

RESUMO

The genetic diversity and population structures of five Chongqing local chicken populations were investigated using by 24 microsatellite markers. Results revealed that the mean number of alleles (NA) ranged from 7.08 (Daninghe chicken, DN) to 8.46 (Nanchuan chicken, NC). The highest observed heterozygosity (HO) and expected heterozygosity (HE) were observed in DN (HO = 0.7252; HE = 0.7409) and the lowest HO and HE were observed in XS (Xiushan native chicken [XS], HO = 0.5910 and HE = 0.6697). The inbreeding coefficient (FIS) within population ranged from 0.022 (DN) to 0.119 (XS). Among the 24 microsatellite markers, four loci (MCW0111, MCW0016, ADL0278, and MCW0104) deviated from the Hardy-Weinberg equilibrium in all the studied populations. The results of population polygenetic analysis based on Nei's genetic distance and STRUCTURE software showed that the clustering of the five populations was incomplete consistent with geographical distribution. Moreover, a large number of gene flows were widespread among different populations, suggesting that genetic material exchanges occurred due to human activities and migration which was also verified by PCoA. In summary, this study preliminarily showed that Chongqing local chicken populations had rich genetic diversity and remarkable genetic divergence, but still high risk in conversion. These findings would be useful to the management of conservation strategies and the utilization of local chicken populations in further.

9.
J Genet ; 992020.
Artigo em Inglês | MEDLINE | ID: mdl-32661207

RESUMO

Droughtmaster is a tropical breed of beef cattle that can survive in hot climates and easily adapt to torrid environments. These traits are important in livestock breeding. In this study, we genotyped five single-nucleotide polymorphisms (SNPs) of the AHSA2 gene from 190 cattle belonging to three different breeds (Droughtmaster, Angus and Simmental) by using snapshot technology. This work aimed to identify the valuable molecular marker of heat resistance in cattle. Results showed that Droughtmaster exhibited higher expected heterozygosity and polymorphic information content compared with the two other breeds. The AHSA2-1 locus deviated from the Hardy-Weinberg equilibrium in the Droughtmaster breed (P < 0.05). Two SNPs in Droughtmaster diverged significantly from Angus and Simmental. The SNPs were identified as AHSA2-3 and AHSA2-4, which were closely linked to the three breeds based on pair-wise FST. AHSA2-4 involved a missense mutation. In summary, the GG genotypes in AHSA2-3 and AHSA2-4 may be candidate genotypes associated with heat resistance traits and may serve as valuable genetic markers for breeding of heat-tolerant beef cattle in the future.


Assuntos
Marcadores Genéticos , Técnicas de Genotipagem/métodos , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Animais , Cruzamento , Bovinos , Genótipo , Fenótipo , Característica Quantitativa Herdável
10.
BMC Plant Biol ; 20(1): 160, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293269

RESUMO

BACKGROUND: Canker disease caused by Neoscytalidium dimidiatum is a devastating disease resulting in a major loss to the pitaya industry. However, resistance proteins in plants play crucial roles to against pathogen infection. Among resistance proteins, the leucine-rich repeat (LRR) protein is a major family that plays crucial roles in plant growth, development, and biotic and abiotic stress responses, especially in disease defense. RESULTS: In the present study, a transcriptomics analysis identified a total of 272 LRR genes, 233 of which had coding sequences (CDSs), in the plant pitaya (Hylocereus polyrhizus) in response to fungal Neoscytalidium dimidiatum infection. These genes were divided into various subgroups based on specific domains and phylogenetic analysis. Molecular characterization, functional annotation of proteins, and an expression analysis of the LRR genes were conducted. Additionally, four LRR genes (CL445.Contig4_All, Unigene28_All, CL28.Contig2_All, and Unigene2712_All, which were selected because they had the four longest CDSs were further assessed using quantitative reverse transcription PCR (qRT-PCR) at different fungal infection stages in different pitaya species (Hylocereus polyrhizus and Hylocereus undatus), in different pitaya tissues, and after treatment with salicylic acid (SA), methyl jasmonate (MeJA), and abscisic acid (ABA) hormones. The associated protein functions and roles in signaling pathways were identified. CONCLUSIONS: This study provides a comprehensive overview of the HpLRR family genes at transcriptional level in pitaya in response to N. dimidiatum infection, it will be helpful to understand the molecular mechanism of pitaya canker disease, and lay a strong foundation for further research.


Assuntos
Ascomicetos , Cactaceae/genética , Cactaceae/microbiologia , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Proteínas/genética , Ácido Abscísico/farmacologia , Acetatos/farmacologia , Cactaceae/efeitos dos fármacos , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Filogenia , Proteínas/classificação , Ácido Salicílico/farmacologia , Estresse Fisiológico
11.
Chem Sci ; 10(18): 4839-4846, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31160959

RESUMO

Cinnamoyl-containing nonribosomal peptides (CCNPs) are a small group of secondary metabolites with potent biological activities produced by actinobacteria. Two remarkable features in the biosynthesis of CCNPs include the nonribosomal peptide synthases (NRPSs) for assembly of the depsipeptide backbone and the type II polyketide synthases (PKSs) for N-terminal cinnamoyl moiety construction. Here, we present a genome mining approach targeting both NRPS and type II PKS for discovery of new CCNPs, which led to the identification of 51 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named kitacinnamycins, one of which showing potent activation ability towards the stimulator of interferon genes (STING) protein, was identified. Bioinformatic, genetic and biochemical analysis revealed the use of the NRPS assembly line to form the macrocyclic peptide backbone, followed by a P450 monooxygenase to generate terminal oxidized groups. A glycosyltransferase with relatively broad substrate specificity transfers sugars to the newly generated OH/COOH group. The protein crystallographic study further provided structural insights into this glycosylation. Our results not only demonstrated the feasibility of genome mining and strain prioritization for the discovery of new bioactive natural products but also disclosed the biosynthetic pathway for kitacinnamycins.

12.
J Nat Prod ; 82(4): 792-797, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30794407

RESUMO

Six novel aromatic polyketide dimers, bialternacins A-F (1-6), were isolated from a plant endophytic Alternaria sp. The structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compounds 1, 2, 5, and 6 were characterized as four pairs of racemic mixtures. Compound (+)-5 was demonstrated to show acetylcholinesterase inhibitory activity with an IC50 value of 15.5 µM. A putative biosynthetic pathway for these compounds was proposed.


Assuntos
Alternaria/química , Policetídeos/isolamento & purificação , Acetilcolinesterase/efeitos dos fármacos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Cristalografia por Raios X , Dimerização , Estrutura Molecular , Folhas de Planta/química , Policetídeos/química , Policetídeos/farmacologia , Análise Espectral/métodos
13.
BMC Genomics ; 20(1): 10, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616517

RESUMO

BACKGROUND: Canker disease caused by Neoscytalidium dimidiatum is the most serious disease that attacks the pitaya industry. One pathogenic fungus, referred to as ND8, was isolated from the wild-type red-fleshed pitaya (Hylocereus polyrhizus) of Hainan Province. In the early stages of this disease, stems show little spots and a loss of green color. These spots then gradually spread until the stems became rotten due to infection by various strains. Canker disease caused by Neoscytalidium dimidiatum poses a significant threat to pitaya commercial plantations with the growth of stems and the yields, quality of pitaya fruits. However, a lack of transcriptomic and genomic information hinders our understanding of the molecular mechanisms underlying the pitaya defense response. RESULTS: We investigated the host responses of red-fleshed pitaya (H. polyrhizus) cultivars against N. dimidiatum using Illumina RNA-Seq technology. Significant expression profiles of 23 defense-related genes were further analyzed by qRT-PCR. The total read length based on RNA-Seq was 25,010,007; mean length was 744, the N50 was 1206, and the guanine-cytosine content was 44.48%. Our investigation evaluated 33,584 unigenes, of which 6209 (18.49%) and 27,375 (81.51%) were contigs and singlets, respectively. These unigenes shared a similarity of 16.62% with Vitis vinifera, 7.48% with Theobroma cacao, 6.6% with Nelumbo nucifera and 5.35% with Jatropha curcas. The assembled unigenes were annotated into non-redundant (NR, 25161 unigenes), Kyoto Encyclopedia of Genes and Genomes (KEGG, 17895 unigenes), Clusters of Orthologous Groups (COG, 10475 unigenes), InterPro (19,045 unigenes), and Swiss-Prot public protein databases (16,458 unigenes). In addition, 24 differentially expressed genes, which were mainly associated with plant pathology pathways, were analyzed in-depth. CONCLUSIONS: This study provides a basis for further in-depth research on the protein function of the annotated unigene assembly with cDNA sequences.


Assuntos
Caryophyllales/genética , Anotação de Sequência Molecular , Doenças das Plantas/genética , Transcriptoma/genética , Ascomicetos/genética , Ascomicetos/patogenicidade , Caryophyllales/microbiologia , Bases de Dados de Proteínas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Plantas/microbiologia , RNA/genética
14.
J Am Chem Soc ; 140(34): 10909-10914, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30067334

RESUMO

Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final α-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant. The X-ray crystal structures of ChaP and two homologues, docking studies, and site-directed mutagenesis provided insights into the molecular basis of the oxidative rearrangement that involves two successive C-C bond cleavage steps followed by lactonization. ChaP is the first example of a dioxygenase that requires a flavin-activated oxygen as a substrate despite lacking flavin binding sites, and represents a new class in the vicinal oxygen chelate enzyme superfamily.


Assuntos
Antineoplásicos/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Dioxigenases/química , Dioxigenases/metabolismo , Antineoplásicos/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Benzopiranos/química , Domínio Catalítico , Cristalografia por Raios X , Dioxigenases/genética , Dioxigenases/isolamento & purificação , Glicosídeos/biossíntese , Glicosídeos/química , Modelos Químicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Família Multigênica , Mutagênese Sítio-Dirigida , Mutação , Oxirredução , Ligação Proteica , Streptomyces/enzimologia , Streptomyces/genética
15.
Mar Drugs ; 15(8)2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28767052

RESUMO

Two new alkaloids, strepchazolins A (1) and B (2), together with a previously reported compound, streptazolin (3), were isolated from a marine actinomycete, Streptomyces chartreusis NA02069, collected in the Coast of Hainan Island, China. The structures of new compounds were determined by extensive NMR, mass spectroscopic and X-ray crystallographic analysis, as well as modified Mosher's method. Compound 1 showed weak anti-Bacillus subtilis activity with the MIC value of 64.0 µM, and weak inhibitory activity against acetylcholinesterase (AChE) in vitro with IC50 value of 50.6 µM, while its diastereoisomer, Compound 2, is almost inactive.


Assuntos
Alcaloides/isolamento & purificação , Antibacterianos/isolamento & purificação , Streptomyces/química , Acetilcolinesterase/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , China , Inibidores da Colinesterase/farmacologia , Cristalografia por Raios X , Concentração Inibidora 50 , Biologia Marinha , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Piperidinas/química , Piperidinas/isolamento & purificação , Estereoisomerismo
16.
Clin Lab ; 62(3): 365-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27156325

RESUMO

BACKGROUND: It was necessary to assess the relationship between Yes-associated protein (YAP) and some clinical features of hepatocellular carcinoma (HCC), especially hepatitis B virus (HBV) correlation factors as they relate to tumorigenesis. METHODS: A tissue microarray including 84 HCC samples was retrospectively analyzed by immunohistochemistry. RESULTS: This study showed that YAP expression was associated with HCC differentiation and the patient age at diagnosis of HCC. The mean age at diagnosis of YAP(+) HCC patients was 46.19 ± 9.45 years old, which is youn- ger than 51.40 ± 12.51 years old found for YAP(-) HCC patients (< 0.048). There was no significant correlation between YAP expression and HBV correlation factors (HBsAg, HBV DNA, and the duration of hepatitis B infec- tion). CONCLUSIONS: YAP(+) HCC patients had a younger mean age at diagnosis and more poor-differentiation charac- teristics of HCC. However, there were no independent HBV correlation factors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/análise , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Fosfoproteínas/análise , Adulto , Fatores Etários , Idoso , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/patologia , Diferenciação Celular , DNA Viral/análise , Feminino , Antígenos de Superfície da Hepatite B/análise , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição
17.
Mol Med Rep ; 11(6): 4101-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25625370

RESUMO

The pathogenesis of hepatocellular carcinoma (HCC) is thought to involve the interaction of numerous genes. Identification of these genes and proteins which regulate liver carcinogenesis is critical for the exploration of novel targeted therapies. Yes­associated protein (YAP) and large tumor suppressor 1 (LATS1) are associated with HCC cells. LATS1 is an upstream inhibitory factor of YAP in the Hippo pathway. The aim of the present study was to measure the expression of LATS1 in Yap­downregulated cancer cells. Immunohistochemistry was used to determine YAP and LATS1 levels in HCC tissue samples. High YAP­expressing cell lines were selected from two human hepatocellular carcinoma cells with different metastatic potential. In addition, changes in cell growth rates and LATS1 expression in human HCC 97H cells, in which YAP had been knocked down using RNA interference (RNAi). The proliferation of cells was evaluated using an MTS assay and changes in the progression of cell division were assessed through cell cycle analysis. Western blot analysis was then used to determine YAP and LATS1 expression levels in 97H cells. The results of the present study demonstrated that overexpression of YAP was negatively correlated with LATS1 expression in HCC cells (P=0.016). Knockdown of YAP using lentivirus­small hairpin (sh)RNA significantly inhibited 97H cell growth; in addition, the downregulation of YAP protein levels (33.4%) was accompanied by downregulation of LATS1 protein levels (68.5%). In conclusion, these results demonstrated that as an inhibitor of YAP, LATS1 was decreased via downregulation of YAP using RNAi. This therefore indicated that the change in YAP levels in HCC cells may regulate LATS1 in a feedback manner.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Neoplasias Hepáticas/patologia , Fígado/patologia , Fosfoproteínas/genética , Interferência de RNA , Proteínas Adaptadoras de Transdução de Sinal/análise , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/genética , Fosfoproteínas/análise , Fatores de Transcrição
18.
Clin Exp Med ; 15(4): 477-82, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25284078

RESUMO

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Several recent studies have provided evidence that rs401681 polymorphisms in intronic region of cleft lip and palate trans-membrane 1-like (CLPTM1L) gene sequence are associated with pancreatic cancer (PC) development, but a comprehensive synopsis is not available. We performed a meta-analysis of 6 case-control studies that included 8,253 pancreatic cancer cases and 37,646 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, this meta-analysis showed that rs401681 allele T was associated with a significantly increased PC risk (OR = 1.17, 95 % CI = 1.12-1.22, P heterpgeneity = 0.596 and I (2) = 0). Similarly, in the subgroup analysis by ethnicity, a significantly increased risk was found among Asians (OR = 1.15, 95 % CI = 1.07-1.24, P heterpgeneity = 0.297 and I (2) = 8.0 %) and among Caucasian (OR = 1.13, 95 % CI = 1.02-1.26, P heterpgeneity = 0.385 and I (2) = 0). No publication bias was found in the present study. This meta-analysis suggests that T allele of CLPTM1L-telomerase reverse transcriptase rs401681 polymorphism is associated with an increased PC risk, especially among Chinese. Further large and well-designed studies are needed to confirm this association.


Assuntos
Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Frequência do Gene , Humanos , Medição de Risco
19.
Hepatobiliary Pancreat Dis Int ; 13(2): 173-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24686544

RESUMO

BACKGROUND: Angiographic embolization (AE) as an adjunct non-operative treatment of intrahepatic arterial bleeding has been widely used. The present study aimed to evaluate the efficacy of selective AE in patients with hepatic trauma. METHODS: Seventy patients with intrahepatic arterial bleeding after blunt abdominal trauma who had undergone selective AE in 10 years at this institution were retrospectively reviewed. The criteria for selective AE included active extravasation on contrast-enhanced CT, an episode of hypotension or a decrease in hemoglobin level during the non-operative treatment. The data of the patients included demographics, grade of liver injuries, mechanism of blunt abdominal trauma, associated intra-abdominal injuries, indications for AE, angiographic findings, type of AE, and AE-related hepatobiliary complications. RESULTS: In the 70 patients, 32 (45.71%) had high-grade liver injuries. Extravazation during the early arterial phase mainly involved the right hepatic segments. Thirteen (18.57%) patients underwent embolization of intrahepatic branches and the extrahepatic trunk and these patients all developed AE-related hepatobiliary complications. In 19 patients with AE-related complications, 14 received minimally invasive treatment and recovered without severe sequelae. CONCLUSIONS: AE is an adjunct treatment for liver injuries. Selective and/or super-selective AE should be advocated to decrease the incidence and severity of AE-related hepatobiliary complications.


Assuntos
Traumatismos Abdominais/terapia , Embolização Terapêutica , Hemorragia/terapia , Artéria Hepática/diagnóstico por imagem , Radiografia Intervencionista , Lesões do Sistema Vascular/terapia , Ferimentos não Penetrantes/terapia , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/fisiopatologia , Adolescente , Adulto , China , Embolização Terapêutica/efeitos adversos , Feminino , Hemodinâmica , Hemorragia/diagnóstico por imagem , Hemorragia/fisiopatologia , Artéria Hepática/lesões , Artéria Hepática/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/fisiopatologia , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/fisiopatologia , Adulto Jovem
20.
Prz Gastroenterol ; 9(6): 348-53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25653730

RESUMO

INTRODUCTION: Function dyspepsia (FD) may cause patients to suffer from anxiety and depression, and psychosocial disorders would have a significant effect on FD symptoms. AIM: To examine the prevalence of anxiety and depression among function dyspepsia (FD) patients and to identify social factors of anxiety-depression among FD patients. MATERIAL AND METHODS: Patients with FD, who fulfilled the Rome III criteria, were enrolled. All patients were administered a validated Chinese version of the self-rating scale (SDS) and self-rating anxiety scale (SAS), and investigated regarding the patients' social factors. RESULTS: A total of 907 patients were enrolled, including 516 (56.89%) FD patients within anxiety-depression status; SDS mean scores were 51.57 ±8.22; SAS mean scores were 51.04 ±7.53; 52.28% were male and 64.25% were female (χ(2) = 262.54, p < 0.01); 56.16% were aged 18-29 years, 54.15% were aged 30-39 years, 54.77% were aged 40-49 years, 62.02% were aged 50-59 years, 69.23% were aged above 60 years (χ(2) = 18.14, p < 0.01); 67.44% were the retirees; 63.31% were manual workers; 55.10% were soldiers; 43.57% were mental workers; 38.89% were students (χ(2) = 716.53, p < 0.01); 64.20% had junior high school degree or below; 57.36% had high school degrees; 42.03% had college degrees; 44.44% had master's or above degrees (χ(2) = 27.21, p < 0.05); 38.10% were in good health condition; 61.90% were in poor health condition (χ(2) = 7.94, p < 0.01); 20.31% had correlative family history; and 79.69% had no correlative family history (χ(2) = 2.23, p > 0.05). CONCLUSIONS: The FD patients have higher rates of anxiety and depression. Gender, age, occupation, education level, and health condition have a significant effect on anxiety and depression status. Female gender, advanced age, high-stress occupation, lower education level, and poor health condition all are risk factors. Family history has no relationship with anxiety and depression among FD patients.

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