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1.
Am J Gastroenterol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38546128

RESUMO

INTRODUCTION: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis. DISCUSSION: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.

2.
Gastric Cancer ; 27(3): 622-634, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38502275

RESUMO

BACKGROUND: Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients. METHODS: Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups. RESULTS: Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group. CONCLUSION: FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.


Assuntos
Linfografia , Neoplasias Gástricas , Humanos , Linfografia/métodos , Excisão de Linfonodo/métodos , Índice de Massa Corporal , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Corantes , Gastrectomia/métodos , Estudos Retrospectivos
3.
Gastric Cancer ; 27(1): 176-186, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872358

RESUMO

BACKGROUND: Previous studies have focused on the non-inferiority of RPG compared with conventional port gastrectomy (CPG); however, we assumed that some candidates might derive more significant benefit from RPG over CPG. METHODS: We retrospectively analyzed the clinicopathological and perioperative parameters of 1442 patients with gastric cancer treated by gastrectomy between 2009 and 2022. The C-reactive protein level on postoperative day 3 (CRPD3) was used as a surrogate parameter for surgical trauma. Patients were grouped according to the extent of gastrectomy [subtotal gastrectomy (STG) or total gastrectomy (TG)] and lymph node dissection (D1+ or D2). The degree of surgical trauma, bowel recovery, and hospital stay between RPG and CPG was compared among those patient groups. RESULTS: Of 1442 patients, 889, 354, 129, and 70 were grouped as STGD1+, STGD2, TGD1+, and TGD2, respectively. Compared with CPG, RPG significantly decreased CRPD3 only among patients in the STGD1+ group (CPG: n = 653, 84.49 mg/L, 95% CI 80.53-88.45 vs. RPG: n = 236, 70.01 mg/L, 95% CI 63.92-76.09, P < 0.001). In addition, the RPG method significantly shortens bowel recovery and hospital stay in the STGD1+ (P < 0.001 and P < 0.001), STGD2 (P < 0.001 and P < 0.001), and TGD1+ (P = 0.026 and P = 0.007), respectively. No difference was observed in the TGD2 group (P = 0.313 and P = 0.740). CONCLUSIONS: The best candidates for RPG are patients who undergo STGD1+, followed by STGD2 and TG D1+, considering the reduction in CRPD3, bowel recovery, and hospital stay.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Gastrectomia/métodos , Resultado do Tratamento
4.
Environ Microbiol ; 24(8): 3612-3624, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35191581

RESUMO

The omics-based studies are important for identifying characteristic proteins in plants to elucidate the mechanism of ACC deaminase producing bacteria-mediated salt tolerance. This study evaluates the changes in the proteome of rice inoculated with ACC deaminase producing bacteria under salt-stress conditions. Salt stress resulted in a significant decrease in photosynthetic pigments, whereas inoculation of Methylobacterium oryzae CBMB20 had significantly increased pigment contents under normal and salt-stress conditions. A total of 76, 51 and 33 differentially abundant proteins (DAPs) were identified in non-inoculated salt-stressed plants, bacteria-inoculated plants under normal and salt stress conditions respectively. The abundances of proteins responsible for ethylene emission and programmed cell death were increased, and that of photosynthesis-related proteins were decreased in non-inoculated plants under salt stress. However, bacteria-inoculated plants had shown higher abundance of antioxidant proteins, RuBisCo and ribosomal proteins that are important for enhancing stress tolerance and improving plant physiological traits. Collectively, salt stress might affect plant physiological traits by impairing photosynthetic machinery and accelerating apoptosis leading to a decline in biomass. However, inoculation of plants with bacteria can assist in enhancing photosynthetic activity, antioxidant activities and ethylene regulation related proteins for attenuating salt-induced apoptosis and sustaining growth and development.


Assuntos
Oryza , Antioxidantes/metabolismo , Carbono-Carbono Liases/genética , Carbono-Carbono Liases/metabolismo , Etilenos/metabolismo , Oryza/microbiologia , Proteômica , Estresse Salino , Estresse Fisiológico
5.
Biochem Biophys Res Commun ; 552: 44-51, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33743348

RESUMO

Hepatocellular carcinoma (HCC) is the fifth common types of cancer with poor prognosis in the world. Honokiol (HNK), a natural biphenyl compound derived from the magnolia plant, has been reported to exert anticancer effects, but its mechanism has not been elucidated exactly. In the present study, HNK treatment significantly suppressed the migration ability of HepG2 and Hep3B human hepatocellular carcinoma. The treatment reduced the expression levels of the genes associated with cell migration, such as S100A4, MMP-2, MMP-9 and Vimentin. Interestingly, treatment with HNK significantly reduced the expression level of Cyclophilin B (CypB) which stimulates cancer cell migration. However, overexpressed CypB abolished HNK-mediated suppression of cell migration, and reversed the apoptotic effects of HNK. Altogether, we concluded that the suppression of migration activities by HNK was through down-regulated CypB in HCC. These finding suggest that HNK may be a promising candidate for HCC treatment via regulation of CypB.


Assuntos
Compostos de Bifenilo/farmacologia , Carcinoma Hepatocelular/genética , Movimento Celular/efeitos dos fármacos , Ciclofilinas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lignanas/farmacologia , Neoplasias Hepáticas/genética , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ciclofilinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
6.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204438

RESUMO

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.


Assuntos
Hepacivirus/fisiologia , Hepatite C/metabolismo , Hepatite C/virologia , Interações Hospedeiro-Patógeno , NF-kappa B/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Replicação Viral , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular , Células Cultivadas , Hepatite C/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Modelos Biológicos , Estrutura Molecular
7.
Small ; 16(35): e2002311, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32743935

RESUMO

Here, a novel, versatile synthetic strategy to fabricate a yolk-shell structured material that can encapsulate virtually any functional noble metal or metal oxide nanocatalysts of any morphology in a free suspension fashion is reported. This strategy also enables encapsulation of more than one type of nanoparticle inside a single shell, including paramagnetic iron oxide used for magnetic separation. The mesoporous organosilica shell provides efficient mass transfer of small target molecules, while serving as a size exclusion barrier for larger interfering molecules. Major structural and functional advantages of this material design are demonstrated by performing three proof-of-concept applications. First, effective encapsulation of plasmonic gold nanospheres for localized photothermal heating and heat-driven reaction inside the shell is shown. Second, hydrogenation catalysis is demonstrated under spatial confinement driven by palladium nanocubes. Finally, the surface-enhanced Raman spectroscopic detection of model pollutant by gold nanorods is presented for highly sensitive environmental sensing with size exclusion.

8.
Int J Mol Sci ; 21(15)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752233

RESUMO

Hepatic hepcidin is a well-known major iron regulator and has been reported to be closely related to hepatitis C virus (HCV) replication. However, pharmacological targeting of the hepcidin in HCV replication has not been reported. A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation. Here, we investigated the therapeutic effect of 4-PBA on hepcidin expression and HCV replication. We used HCV genotype 1b Huh 7.5-Con1 replicon cells and engraftment of NOD/SCID mice as in vitro and in vivo models to test the effect of 4-PBA. It was found that 4-PBA inhibited HCV replication in Huh7.5-Con1 replicon cells in a concentration- and time-dependent manner through the induction of hepcidin expression by epigenetic modification and subsequent upregulation of interferon-α signaling. HCV formed a membranous web composed of double-membrane vesicles and was utilized for RNA replication. Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.


Assuntos
Epigênese Genética/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepcidinas/genética , Fenilbutiratos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/fisiologia , Hepatite C/prevenção & controle , Hepatite C/virologia , Hepcidinas/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , Estrutura Molecular , Fenilbutiratos/química , Bibliotecas de Moléculas Pequenas/química , Replicação Viral/genética
9.
J Cell Physiol ; 234(7): 10345-10359, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30387140

RESUMO

LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that co-operate with 1,25(OH) 2 D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), co-operates with the vitamin D receptor and CCAAT/enhancer binding protein α (CEBPα) to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2 D 3 regulation of CAMP by histone deacetylase inhibitors involves co-operation between acetylation and chromatin remodeling through Brahma-related gene 1 (BRG1; a component of the SWItch/sucrose nonfermentable [SWI/SNF] complex). BRG1 can be an activator or repressor depending on BRG1-associated factors. Protein arginine methyltransferase 5 (PRMT5), a methlytransferase which interacts with BRG1, represses 1,25(OH) 2 D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of the CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression to increase the antibacterial capability of the airway.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Epigênese Genética/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Vitamina D/análogos & derivados , Acetilação , Montagem e Desmontagem da Cromatina/genética , Células Epiteliais , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , Pulmão , Receptores de Calcitriol/genética , Fatores de Transcrição/genética , Transcrição Gênica/genética , Vitamina D/genética , Catelicidinas
10.
Biotechnol Lett ; 41(12): 1451-1458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655924

RESUMO

OBJECTIVES: To explore potential effects of recombinant peptidyl-prolyl isomerase human Cyclophilin A (CypA) in the growth of mouse hair and human hair follicle dermal papilla cells (HDP). RESULTS: The hair growth of 8-weeks C57BL/6 mouse was significantly stimulated by recombinant human CypA protein. CypA also promoted Human Dermal Papilla (HDP) cell growth and induced ß-catenin protein through GSK3ß inhibition. CONCLUSIONS: The molecular chaperone CypA stimulates hair follicle and HDP cells through Wnt/ß-catenin signaling pathway, suggesting that it might be a key molecule for hair loss disorder therapy.


Assuntos
Ciclofilina A/metabolismo , Folículo Piloso/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Proteínas Recombinantes/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Ciclofilina A/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética
11.
Apoptosis ; 23(11-12): 707-709, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30293220

RESUMO

The original version of this article contained a mistake. The bands for HA Tag and t-ERK in Figs. 2d, 2h, 3d are incorrect. The author informs that these errors had no influence in the scientific content of the paper. The corrected figures (Figs. 2 and 3) are given below.

12.
BMC Plant Biol ; 18(1): 109, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871605

RESUMO

BACKGROUND: The interaction between arbuscular mycorrhizal fungi (AMF) and AMF spore associated bacteria (SAB) were previously found to improve mycorrhizal symbiotic efficiency under saline stress, however, the information about the molecular basis of this interaction remain unknown. Therefore, the present study aimed to investigate the response of maize plants to co-inoculation of AMF and SAB under salinity stress. RESULTS: The co-inoculation of AMF and SAB significantly improved plant dry weight, nutrient content of shoot and root tissues under 25 or 50 mM NaCl. Importantly, co-inoculation significantly reduced the accumulation of proline in shoots and Na+ in roots. Co-inoculated maize plants also exhibited high K+/Na+ ratios in roots at 25 mM NaCl concentration. Mycorrhizal colonization significantly positively altered the expression of ZmAKT2, ZmSOS1, and ZmSKOR genes, to maintain K+ and Na+ ion homeostasis. Confocal laser scanning microscope (CLSM) view showed that SAB were able to move and localize into inter- and intracellular spaces of maize roots and were closely associated with the spore outer hyaline layer. CONCLUSION: These new findings indicate that co-inoculation of AMF and SAB effectively alleviates the detrimental effects of salinity through regulation of SOS pathway gene expression and K+/Na+ homeostasis to improve maize plant growth.


Assuntos
Bactérias/metabolismo , Homeostase , Micorrizas/fisiologia , Potássio/metabolismo , Sódio/metabolismo , Zea mays/microbiologia , Parede Celular/metabolismo , Proteínas de Fluorescência Verde , Transporte de Íons , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/fisiologia , Tolerância ao Sal , Plântula/microbiologia , Plântula/fisiologia , Cloreto de Sódio/metabolismo , Esporos Fúngicos , Estresse Fisiológico , Simbiose , Zea mays/fisiologia
13.
BMC Plant Biol ; 18(1): 51, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587643

RESUMO

BACKGROUND: Inherent characteristics and changes in the physiology of rice as it attains salt tolerance affect the colonizing bacterial endophytic communities of the rice seeds. These transmissible endophytes also serve as a source of the plant's microbial community and concurrently respond to the host and environmental conditions. This study explores the influence of the rice host as well as the impact of soil salinity on the community structure and diversity of seed bacterial endophytes of rice with varying tolerance to salt stress. Endophytic bacterial diversity was studied through culture-dependent technique and Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis. RESULTS: Results revealed considerably diverse communities of bacterial endophytes in the interior of rice seeds. The overall endophytic bacterial communities of the indica rice seeds based on 16S rRNA analysis of clones and isolates are dominated by phylum Proteobacteria followed by Actinobacteria and Firmicutes. Community profiles show common ribotypes found in all cultivars of the indica subspecies representing potential core microbiota belonging to Curtobacterium, Flavobacterium, Enterobacter, Xanthomonas, Herbaspirillum, Microbacterium and Stenotrophomonas. Clustering analysis shows that the host genotype mainly influences the seed endophytic community of the different rice cultivars. Under salt stress conditions, endophytic communities of the salt-sensitive and salt-tolerant rice cultivars shift their dominance to bacterial groups belonging to Flavobacterium, Pantoea, Enterobacter, Microbacterium, Kosakonia and Curtobacterium. CONCLUSION: The endophytic communities of rice indica seeds are shaped by the hosts' genotype, their physiological adaptation to salt stress and phylogenetic relatedness. Under salt stress conditions, a few groups of bacterial communities become prominent causing a shift in bacterial diversity and dominance.


Assuntos
Oryza/efeitos dos fármacos , Oryza/microbiologia , Sementes/efeitos dos fármacos , Sementes/microbiologia , Actinobacteria/genética , Actinobacteria/fisiologia , Endófitos/classificação , Endófitos/genética , Endófitos/fisiologia , Firmicutes/genética , Firmicutes/fisiologia , Genótipo , Oryza/genética , Filogenia , Polimorfismo de Fragmento de Restrição/genética , Proteobactérias/genética , Proteobactérias/fisiologia , RNA Ribossômico 16S/genética , Sementes/genética
14.
BMC Microbiol ; 17(1): 209, 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29073903

RESUMO

BACKGROUND: Rice (Oryza sativa L. ssp. indica) seeds as plant microbiome present both an opportunity and a challenge to colonizing bacterial community living in close association with plants. Nevertheless, the roles and activities of bacterial endophytes remain largely unexplored and insights into plant-microbe interaction are compounded by its complexity. In this study, putative functions or physiological properties associated with bacterial endophytic nature were assessed. Also, endophytic roles in plant growth and germination that may allow them to be selectively chosen by plants were also studied. RESULTS: The cultivable seed endophytes were dominated by Proteobacteria particularly class Gammaproteobacteria. Highly identical type strains were isolated from the seed endosphere regardless of the rice host's physiological tolerance to salinity. Among the type strains, Flavobacterium sp., Microbacterium sp. and Xanthomonas sp. were isolated from the salt-sensitive and salt-tolerant cultivars. PCA-Biplot ordination also showed that specific type strains isolated from different rice cultivars have distinguishing similar characteristics. Flavobacterium sp. strains are phosphate solubilizers and indole-3-acetic acid producers with high tolerance to salinity and osmotic stress. Pseudomonas strains are characterized as high siderophore producers while Microbacterium sp. and Xanthomonas sp. strains have very high pectinase and cellulase activity. Among the physiological traits of the seed endophytes, bacterial pectinase and cellulase activity are positively correlated as well as salt and osmotic tolerance. Overall characterization shows that majority of the isolates could survive in 4-8% salt concentration as well as in 0.6 M and 1.2 M sucrose solution. The activities of catalase, pectinase and cellulase were also observed in almost all of the isolates indicating the importance of these characteristics for survival and colonization into the seed endosphere. Seed bacterial endophytes also showed promising plant growth promoting activities including hormone modulation, nitrogen fixation, siderophore production and phosphate solubilization. CONCLUSION: Though many of the isolates possess similar PGP and endophytic physiological traits, this study shows some prominent and distinguishing traits among bacterial groups indicating key determinants for their success as endophytes in the rice seed endosphere. Rice seeds are also inhabited by bacterial endophytes that promote growth during early seedling development.


Assuntos
Bactérias/isolamento & purificação , Endófitos/isolamento & purificação , Endófitos/fisiologia , Oryza/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sementes/microbiologia , Bactérias/classificação , Bactérias/enzimologia , Impressões Digitais de DNA , DNA Bacteriano/genética , Endófitos/classificação , Endófitos/enzimologia , Variação Genética , Germinação , Microbiota , Oryza/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Salinidade , Plântula/crescimento & desenvolvimento , Plântula/microbiologia
15.
Biochem Biophys Res Commun ; 478(3): 1396-402, 2016 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-27569281

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. PD involves a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyidine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) inhibit the complex I of the mitochondrial electron transport chain, and have been widely used to construct PD models. Cyclophilin B (CypB) is an endoplasmic reticulum protein that binds to cyclosporine A as a cyclophilin family member. CypB has peptidyl-prolyl cis-trans isomerase (PPIase) activity. We investigated the protective effects of overexpressed CypB on MPP+-induced neurocytotoxicity in SH-SY5Y human neuroblastoma cells. Overexpressed CypB decreased MPP(+)-induced oxidative stress through the modulation of antioxidant enzymes including manganese superoxide dismutase and catalase, and prevented neurocytotoxicity via mitogen-activated protein kinase, especially the c-Jun N-terminal kinase pathway. In addition, CypB inhibited the activation of MPP(+)-induced the pro-apoptotic molecules poly (ADP-ribose) polymerase, Bax, and Bcl-2, and attenuated MPP(+)-induced mitochondrial dysfunction. The data suggest that overexpressed CypB protects neuronal cells from MPP+-induced dopaminergic neuronal cell death.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Ciclofilinas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuroblastoma/patologia , Fármacos Neuroprotetores/metabolismo , Neurotoxinas/toxicidade , Morte Celular , Linhagem Celular Tumoral , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos
16.
Am J Respir Crit Care Med ; 191(11): 1273-86, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25853696

RESUMO

RATIONALE: Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown. OBJECTIVES: To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism. METHODS: Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling. MEASUREMENTS AND MAIN RESULTS: In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated stabilization of endothelial surface caveolin-1. CONCLUSIONS: Elafin reverses obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1-dependent amplification of BMPR2 signaling.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/efeitos dos fármacos , Caveolina 1/efeitos dos fármacos , Elafina/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Inibidores de Proteases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Elastase Pancreática/efeitos dos fármacos , Ratos
17.
Mol Plant Microbe Interact ; 28(10): 1073-81, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26075827

RESUMO

Studies on chilling stress damage and its mitigation through microorganisms in members of family Solanaceae is limited, despite their economic importance. We studied chilling stress alleviation in tomato plants colonized by psychrotolerant bacterial strains Pseudomonas vancouverensis OB155-gfp and P. frederiksbergensis OS261-gfp. Log phase cultures of bacterial strains were coated on surface-sterilized seeds (bacterization) before sowing and nonbacterized (control) seeds were coated with sterile bacterial growth medium. All plants were grown at temperatures of 30 and 25°C and at the end of 4 weeks, chilling treatment (12 and 10°C) was imposed for 1 week on half of the bacterized and control plants. Under normal conditions (30 and 25°C), no significant difference was observed in antioxidant activity, proline accumulation, and expression of cold acclimation genes in tomato leaf tissues of both control and bacterized plants. However, plants exposed to temperatures of 12 and 10°C were found to decrease in robustness and nutrient uptake, accompanied by increased membrane damage. Chilling resistance in bacterized plants was evident from reduced membrane damage and reactive oxygen species levels, improved antioxidant activity in leaf tissues, and high expression of cold acclimation genes LeCBF1 and LeCBF3 compared with control plants. Confocal microscopy confirmed effective colonization and intercellular localization of cold-adapted bacterial strains OB155-gfp and OS261-gfp.


Assuntos
Aclimatação , Antioxidantes/metabolismo , Interações Hospedeiro-Patógeno , Pseudomonas/fisiologia , Solanum lycopersicum/fisiologia , Biomassa , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Genes Reporter , Solanum lycopersicum/citologia , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Folhas de Planta/citologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/metabolismo
18.
Biochem Biophys Res Commun ; 464(1): 112-7, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26095851

RESUMO

Cyclophilin A (CypA), a member of the immunophilin family, is predominantly localized in the cytoplasm. The peptidylprolyl isomerase (PPIase) activity of CypA has been demonstrated to be involved in diverse cellular processes, including intracellular protein trafficking, mitochondrial function, pre-mRNA processing, and maintenance of multiprotein complex stability. In this study, we have demonstrated that CypA regulates apoptosis signaling-regulating kinase 1 (ASK1) through its direct binding. ASK1 is a member of MAPK kinase kinase (MAP3K) family, and selectively activates both JNK and p38 MAPK pathways. Here, we also report that CypA negatively regulates phosphorylation of ASK1 at Ser966, and that CypA reduces ASK1 and its downstream kinases of the JNK and p38 signaling. ASK1 is known to induce caspase-3 activation and apoptosis, and CypA inhibited ASK1-mediated apoptosis by decrease in caspase-3 activity under cellular stress conditions. Overall, we conclude that CypA negatively regulates ASK1 functions by its physical interaction with ASK1.


Assuntos
Ciclofilina A/metabolismo , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Sítios de Ligação , Caspase 3/genética , Caspase 3/metabolismo , Ciclofilina A/antagonistas & inibidores , Ciclofilina A/genética , Regulação da Expressão Gênica , Células HEK293 , Humanos , Peróxido de Hidrogênio/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase Quinase 5/genética , Estresse Oxidativo , Fosforilação/efeitos dos fármacos , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/genética
19.
Animals (Basel) ; 14(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38672301

RESUMO

Tick-borne diseases result from human-ixodid tick encounters, making it crucial to understand host-ixodid tick interactions and host-dependent distribution for epidemiology and prevention. This study examines water deer patterns and ixodid tick interactions in designated croplands of South Korea over two years, finding that the highest deer presence occurred in July and the lowest in May, during crop harvesting. Four tick species were identified, with Haemaphysalis longicornis being predominant (92.2%). Tick life stage analysis revealed peak nymphs and adults in July and larvae in October. Nymph abundance correlated positively with nearby water deer. MaxEnt biodiversity prediction results indicated wider water deer distribution in summer, reflecting their tendency to use multiple croplands. Areas with nymphs and adults aligned with predicted deer presence in summer, while larval areas aligned in autumn. Increased agroforestry expanded water deer habitats, enhancing tick dispersion. Prevention involved minimizing human-deer encounters by strategic land use in tick-prone areas. This comprehensive study provides insights into preventing severe fever with thrombocytopenia syndrome in agricultural workers, emphasizing the need for targeted interventions based on host behavior and tick life stages in different seasons.

20.
Animals (Basel) ; 14(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38254354

RESUMO

The Korean water deer (WD), a predominant wildlife species in South Korea, is listed as vulnerable by the IUCN Red List. Despite belonging to the same family, Cervidae, WD show significantly fewer adult ixodid tick infestations compared to roe deer (RD). Ticks, which cannot fly, engage in questing behavior in natural environments to latch onto hosts. They detect signals like body temperature and host skin chemicals to navigate through the hair coat to the preferred epidermis. In light of this, we performed an extensive comparative study of the skin tissue and hair characteristics of both deer species, focusing on elements contributing to the reduced tick bite incidence in WD. Remarkably, WD exhibited more prominent blood vessels, sebaceous glands, and sweat glands, which are crucial for skin barrier functions (p < 0.005). Moreover, WD had irregular scale patterns on their hair cuticles and possessed hair that was significantly stiffer and 2.83 times thicker than that of RD (p < 0.001). These characteristics potentially impede ticks from reaching the epidermis hair in WD and RD in the context of tick bite prevention. Further investigations in this area could enhance our understanding of tick-host dynamics and contribute to developing preventive measures against tick-borne diseases in other deer species.

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