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1.
Int J Neurosci ; : 1-8, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189419

RESUMO

OBJECTIVE: To compare the therapeutic efficacy of endovascular interventional embolization and microsurgical clipping in patients with ruptured cerebral aneurysms and investigate their subsequent influence on inflammatory indices, neurological function, prognosis, and recovery. METHODS: The two groups were compared in terms of surgery duration, hospital stay, Hunt-Hess classification, and inflammatory indices before and after the surgery, as well as National Institutes of Health Stroke Scale (NIHSS), Baethel Index (BI), and one-year prognosis of patients affected. RESULTS: The surgery duration and hospital stay of the intervention group were (116.27 ± 12.32) min and (19.82 ± 2.26) d, respectively, and those of the clipping group was (173.87 ± 10.39) min and (24.11 ± 2.33) d, respectively (both p < 0.05). Neither the intervention nor the microscopic approach had a significant impact on the severity of the patients' conditions in terms of Hunt-Hess classification (p > 0.05). In the intervention group, CRP was changed to (5.31 ± 1.22) mg/L and PCT decreased to (1.17 ± 0.39) µg/L after the surgery, while the corresponding values in clipping group were (9.78 ± 2.35) mg/L and (2.75 ± 0.81) µg/L (p > 0.05). After surgery, both groups' NIHSS scores declined dramatically, with the intervention group scoring lower than the microscopy group (6.81 ± 1.22 vs 8.72 ± 1.27) (p < 0.05). CONCLUSION: The findings of this study support the potential advantages of endovascular interventional embolization (coiling) over microsurgical clipping for the management of ruptured cerebral aneurysms. These advantages include shorter surgical duration, reduced hospital stay, lower inflammatory response, improved neurological and functional outcomes, and better long-term prognosis.

2.
Gut ; 72(11): 2051-2067, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37460165

RESUMO

OBJECTIVE: Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information. DESIGN: We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS). RESULTS: We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients. CONCLUSION: We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.

3.
BMC Plant Biol ; 23(1): 226, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37106450

RESUMO

BACKGROUND: Continuous cropping is a significant obstacle to sustainable development in the pea (Pisum sativum L.) industry, but the underlying mechanisms of this remain unclear. In this study, we used 16 S rDNA sequencing, transcriptomics, and metabolomics to analyze the response mechanism of roots and soil bacteria to continuous cropping and the relationship between soil bacteria and root phenotypes of different pea genotypes (Ding wan 10 and Yun wan 8). RESULTS: Continuous cropping inhibited pea growth, with a greater effect on Ding wan 10 than Yun wan 8. Metabolomics showed that the number of differentially accumulated metabolites (DAMs) in pea roots increased with the number of continuous cropping, and more metabolic pathways were involved. Transcriptomics revealed that the number of differentially expressed genes (DEGs) increased with the number of continuous cropping. Continuous cropping altered the expression of genes involved in plant-pathogen interaction, MAPK signal transduction, and lignin synthesis pathways in pea roots, with more DEGs in Ding wan 10 than in Yun wan 8. The up-regulated expression of genes in the ethylene signal transduction pathway was evident in Ding wan 10. Soil bacterial diversity did not change, but the relative abundance of bacteria significantly responded to continuous cropping. Integrative analysis showed that the bacteria with significant relative abundance in the soil were strongly associated with the antioxidant synthesis and linoleic acid metabolism pathway of pea roots under continuous cropping once. Under continuous cropping twice, the bacteria with significant relative abundance changes were strongly associated with cysteine and methionine metabolism, fatty acid metabolism, phenylpropanoid biosynthesis, terpenoid backbone biosynthesis, linoleic acid, and amino sugar and nucleotide sugar metabolism. CONCLUSION: Ding wan 10 was more sensitive to continuous cropping than Yun wan 8. Continuous cropping times and pea genotypes determined the differences in root metabolic pathways. There were common metabolic pathways in the two pea genotypes in response to continuous cropping, and the DEGs and DAMs in these metabolic pathways were strongly associated with the bacteria with significant changes in relative abundance in the soil. This study provides new insights into obstacles to continuous cropping in peas.


Assuntos
Pisum sativum , Solo , Pisum sativum/genética , Ácido Linoleico , Microbiologia do Solo , Bactérias , Transcrição Gênica
4.
Physiol Plant ; 175(3): e13950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37291799

RESUMO

Plant acclimation to salt and alkali stress is closely linked to the ability of the antioxidant system to mediate the scavenging of reactive oxygen species (ROS). In this study, we investigated the effects of salt stress and alkali stress on ROS, antioxidant enzymes, transcriptome, and metabolome. The results showed that the levels of superoxide anions, hydrogen peroxide, malondialdehyde, and electrolyte leakage increased under salt and alkali stress, with higher concentrations observed under alkali stress than salt stress. The activities of superoxide dismutase (EC 1.15.1.1), peroxidase (EC 1.11.1.7), catalase (EC 1.11.1.6), ascorbate peroxidase (EC 1.11.1.11), glutathione reductase (EC 1.6.4.2), dehydroascorbate reductase (EC 1.8.5.1), and monodehydroascorbate reductase (EC 1.6.5.4) varied under salt and alkali stress. The transcriptome analysis revealed the induction of signal transduction and metabolic processes and differential expression of genes encoding antioxidant enzymes in response to salt and alkali stress. The metabolome analysis demonstrated increased ascorbic acid and glutathione under salt stress, while most phenolic acids, flavonoids, and alkaloids increased under salt and alkali stress. Integrative analysis of the metabolome and transcriptome data revealed that the flavonoid biosynthesis pathway played a key role in the grapevine's response to salt stress. The total flavonoid content increased under salt and alkali stress, but the accumulation of flavonoids was higher under salt stress than alkali stress. In conclusion, our findings indicate significant differences in the antioxidant defense of grapevines under these two stresses, providing insight into distinct acclimation mechanisms in grapevine under salt and alkali stress.


Assuntos
Antioxidantes , Estresse Oxidativo , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transcriptoma , Superóxido Dismutase/metabolismo , Metaboloma
5.
Environ Toxicol ; 38(4): 962-974, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36655595

RESUMO

Cadmium (Cd), a persistent and harmful heavy metal in the environment, can accumulate in the kidneys and cause nephrotoxicity. Selenium (Se) is a beneficial natural element that alleviates the toxicity of Cd. To ascertain the relationship between the protective mechanism of Se against Cd nephrotoxicity and ferroptosis and pyroptosis, we randomly divided 48 sheep into four groups and treated them with Cd chloride and/or sodium selenite for 50 days. The data confirmed that Cd apparently resulted in impaired kidney histology and function, depletion of GSH and nicotinamide adenine dinucleotide phosphate contents and CAT and SOD activities, elevation of MDA level, as well as the reduction in selenoprotein mRNA (GPX1, GPX4, TXNRD1, SELP) levels and GPX4 protein level and immunofluorescence intensity. Meanwhile, Cd induced ferroptosis by causing iron overload, up-regulating PTGS2, NCOA4, TFR1, and LC3B mRNA levels and PTGS2 and LC3B-II/LC3B-I protein levels, reducing SLC7A11 and FTH1 mRNA and protein levels, and enhancing the immunofluorescence co-localization of FTH1/LC3B. Moreover, it was also found that Cd triggered pyroptosis, which was evidenced by the increase of NLRP3 immunohistochemical positive signal, GSDMD-N immunofluorescence intensity, IL-1ß and IL-18 release and the levels of pyroptosis-related mRNA (NLRP3, ASC, Caspase-1, GSDMD, IL-1ß and IL-18) and proteins (NLRP3, Caspase-1p20, GSDMD-N, IL-1ß and IL-18). Notably, Se increased the expression level of GPX4 and the transcription factors TFAP2c and SP1, and ameliorated Cd-induced changes in aforementioned factors. In conclusion, GPX4 utilization by Se might be required to alleviate Cd-induced ferroptosis and pyroptosis in sheep kidney.


Assuntos
Ferroptose , Selênio , Animais , Ovinos , Cádmio/metabolismo , Selênio/farmacologia , Interleucina-18/metabolismo , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ciclo-Oxigenase 2/metabolismo , Rim/patologia , Caspase 1/metabolismo , RNA Mensageiro/metabolismo
6.
J Appl Biomed ; 21(4): 208-217, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38112460

RESUMO

Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-ß1 expression, which activated its downstream target Smad-2 to activate the TGF-ß1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-ß1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.


Assuntos
Lagomorpha , Fator de Crescimento Transformador beta , Animais , Humanos , Coelhos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1/farmacologia , Hidroxiprolina/farmacologia , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacologia , Transdução de Sinais , Lagomorpha/metabolismo , Colágeno/farmacologia , Anastomose Cirúrgica
7.
Exp Eye Res ; 219: 109058, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35364100

RESUMO

PURPOSE: This study aimed to explore cellular localisation of CD38 in the retina and evaluate the role and potential mechanism of CD38 deficiency in retinal ischaemia/reperfusion (I/R) injury. METHODS: Six-to eight-week-old male CD38 knockout (KO) and wild-type mice in C57BL/6 background were used. Immunostaining was performed to determine the cellular localisation of CD38 in the retina. Haematoxylin and eosin staining and immunostaining of Brn3a were used to evaluate the retinal I/R injury. Western blotting was performed to detect toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-p65, ionised calcium-binding adapter molecule 1, Sirtuin1 (Sirt1), Ac-p65, and pro-inflammatory cytokines protein expression. RESULTS: CD38 was highly expressed in mouse retinal microglia and astrocytes/Müller cells. CD38 deficiency reduced I/R-induced retinal damage and retinal ganglion cell death. Following retinal I/R injury, TLR4, MyD88, nuclear factor-κB p-p65 (NF-κB p-p65), pro-inflammatory cytokines and CD38 protein levels were also upregulated. After I/R injury, retinal inflammation factors IL-1ß, IL-6, and TNF-α mRNA and protein levels were increased. IL-1ß, IL-6, and TNF-α were reduced in CD38 KO mice after I/R injury. Retinal I/R injury induced the activation of microglia, but this effect was also suppressed by KO of CD38. Additionally, retinal I/R induced a significant increase in Ac-p65 protein levels and decrease in Sirt1 protein levels, while this effect was greatly attenuated by KO of CD38. CONCLUSION: CD38 deficiency protects the retina from I/R injury by suppressing microglial activation partly via activating Sirt1-mediated suppression of TLR4/MyD88/NF-κB signalling.


Assuntos
Traumatismo por Reperfusão , Receptor 4 Toll-Like , Animais , Citocinas/metabolismo , Interleucina-6/metabolismo , Isquemia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Retina/metabolismo , Sirtuína 1/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Pharmacol Res ; 165: 105411, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401002

RESUMO

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.


Assuntos
Adenocarcinoma/diagnóstico , Antineoplásicos/uso terapêutico , Misturas Complexas/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/metabolismo , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos , Trametes , Resultado do Tratamento
9.
J Assist Reprod Genet ; 38(10): 2631-2639, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33834328

RESUMO

OBJECTIVE: To study the correlation between SNPs at phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) rs9838117 site, erb-b2 receptor tyrosine kinase 2 (ERBB2) rs1058808 site, and their interactions with environmental factors and the epithelial ovarian cancer (EOC) risk. METHODS: Sanger sequencing was used to analyze the genotypes of PIK3CA rs9838117 and ERBB2 rs1058808 site in 587 patients with epithelial ovarian cancer (EOC). Multi-factor dimensionality reduction (MDR) was applied to analyze the interaction between PIK3CA rs9838117 and ERBB2 rs1058808 site and the clinical data. RESULTS: The risk of EOC in T allele carriers at PIK3CA rs9838117 was 1.95 times (95%CI: 1.55-2.46, P<0.01) that of G allele carriers. The risk of EOC in G allele carriers at ERBB2 rs1058808 was as 0.64 times (95%CI: 0.54-0.75, P <0.01) as the risk for C allele carriers. In the interaction model between clinical data, PIK3CA rs9838117 site and ERBB2 rs1058808 SNP site, EOC risk in high-risk combination was 3.10 times (95%CI: 1.49-6.46, P <0.01) that of low-risk combination. CONCLUSION: The SNPs at PIK3CA rs9838117 and ERBB2 rs1058808 loci were associated with the risk of EOC.


Assuntos
Regiões 3' não Traduzidas , Carcinoma Epitelial do Ovário/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Interação Gene-Ambiente , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Receptor ErbB-2/genética , Adulto , Idoso , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Prognóstico , Fatores de Risco
10.
Microb Pathog ; 147: 104292, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32505653

RESUMO

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection can occur in early childhood, without eradication therapies such infection can persist throughout life and cause many different diseases. This study investigated the metabolic characteristics and explored the underlying mechanism of children with H. pylori infection, and identified potential biomarkers for evaluating the efficacy of H. pylori eradication therapies. METHODS: We performed 1H NMR-based metabonomics coupled with multivariate analysis to investigate the metabolic profiling of serum samples between Children with and without H. pylori infection. In the same manner, we compared the alternations of metabolites in H. pylori-infected children before and after H. pylori eradication therapies. RESULTS: 21 metabolites from serum in H. pylori-infected and H. pylori-uninfected children were identified, which were mainly involved in energy, amino acid, lipid and microbial metabolism. We found that the serum levels of trimethylamine N-oxide and alanine were significantly higher in H. pylori-infected children compared to uninfected sera, whereas lactate was significantly lower. We also found that the levels of trimethylamine N-oxide and creatine in H. pylori-infected children was significantly decreased after H. pylori eradication therapies, whereas lactate and low-density lipoprotein/very low-density lipoprotein was significantly increased. CONCLUSIONS: This is the first study using 1H NMR-based metabolomics approach to explore the effects of H. pylori infection in children. Our results demonstrated that the disturbances of metabolism in energy, amino acids, lipids and microbiota could play an important role in the pathogenesis of gastrointestinal and extragastric diseases caused by H. pylori infection. Trimethylamine N-oxide and lactate might serve as potential serum biomarkers for evaluating the efficacy of H. pylori eradication therapies.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Microbiota , Criança , Pré-Escolar , Humanos , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética
11.
Biotechnol Lett ; 42(8): 1449-1455, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32488443

RESUMO

OBJECTIVES: To evaluate mixotrophic cultivation of microalgae-bacteria consortium in raw wastewater by stepwise addition of fermented effluent containing volatile fatty acids (VFAs). RESULTS: Stepwise increase of VFAs enhanced algal biomass and lipid production, ammonia and phosphate removals. The highest biomass and lipid yield were 1.94 g L-1 and 310 mg L-1 when the addition of fermented effluent containing VFAs increased to 30% (v/v). With the same cultivation conditions, the maximum removals efficiency of ammonia and phosphate were 26.4 and 11.3 mg L-1 d-1. Bacterial diversities increased with the increasing concentration of VFAs and their communities were identified as phyla Actinobacteria, Bacteroidetes, Cyanobacteria and Proteobacteria. CONCLUSIONS: Although bacterial quantities increased with algae growth concurrently, the objective of culturing microalgae-bacteria consortium in raw wastewater without sterilization to produce biomass and lipid yield still can be realized.


Assuntos
Biomassa , Chlorella vulgaris/metabolismo , Ácidos Graxos Voláteis , Lipídeos/análise , Águas Residuárias/microbiologia , Bactérias/metabolismo , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Fermentação , Metabolismo dos Lipídeos , Consórcios Microbianos/fisiologia
12.
Biochem Biophys Res Commun ; 509(2): 329-334, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30579598

RESUMO

Bergapten (BP), derived from Cnidium monnieri (L.) Cusson, is an ingredient widely used in traditional Chinese medicine and has important biological and pharmacological activities. However, the effect of BP on ovariectomy-induced osteoporosis and the underlying mechanism are not entirely clear. In this study, we investigated the effects of BP on ovariectomy-induced osteoporosis and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vivo and in vitro, and explored the underlying mechanism. We found that BP treatment exerted beneficial effects on ovariectomy-induced osteoporosis in vivo. Further, BP attenuated osteoclastogenesis in bone marrow macrophages (BMMs) and RAW264.7 cells without any cytotoxicity. Additionally, BP specifically inhibited RANKL-induced NF-κB and JNK signaling,but did not suppress p38 and ERK. At the mRNA level, BP inhibits the OC-associated transcription factor NFATc1 and c-fos, thereby affecting the expression of OC differentiation-related genes. Moreover, BP disrupted the formation of F-actin rings, which are important for bone-resorbing activity, and impairs OC bone resorption. Therefore, BP may be a useful alternative therapy for post-menopausal osteoporosis.


Assuntos
5-Metoxipsoraleno/farmacologia , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/prevenção & controle , NF-kappa B/genética , Osteogênese/efeitos dos fármacos , Osteoporose/prevenção & controle , Ligante RANK/antagonistas & inibidores , Actinas/genética , Actinas/metabolismo , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Células RAW 264.7 , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Biochem Biophys Res Commun ; 508(3): 902-906, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30538045

RESUMO

The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-RANK regulatory axis is a major regulator of osteoclast differentiation and activation. Icariin, a flavonol glycoside isolated from the Epimedium herb, has been reported to prevents bone loss in ovariectomized mice and inhibits wear particle-induced osteolysis. However, the molecular mechanism through which icariin inhibits RANKL-induced osteoclastogenesis has not been fully understood. Therefore, we aimed to investigate the effects of icariin on RANKL-induced osteoclastogenesis and to elucidate the mechanism underlying this effect. Our results showed that RANKL-induced osteoclastogenesis was inhibited by icariin in bone marrow macrophages (BMMs) and RAW264.7 cells, and that this effect was due to suppression of NF-κB and mitogen-activated protein kinase (MAPK) activation. In addition, icariin inhibited F-actin ring formation and attenuated the bone resorption ability of mature osteoclasts. Collectively, our results indicate that icariin may be a promising potential candidate for the treatment of osteolytic diseases such as osteoporosis. Moreover, our findings lay the foundation for understanding and intervening in osteoclast-related diseases at the molecular level.


Assuntos
Flavonoides/farmacologia , Osteoclastos/fisiologia , Osteogênese/efeitos dos fármacos , Ligante RANK/antagonistas & inibidores , Animais , Bovinos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Células RAW 264.7
14.
Plant Mol Biol ; 96(6): 607-625, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29582247

RESUMO

KEY MESSAGE: Three EDS1 genes were cloned from common wheat and were demonstrated to positively regulate resistance to powdery mildew in wheat. The EDS1 proteins play important roles in plant basal resistance and TIR-NB-LRR protein-triggered resistance in dicots. Until now, there have been very few studies on EDS1 in monocots, and none in wheat. Here, we report on three common wheat orthologous genes of EDS1 family (TaEDS1-5A, 5B and 5D) and their function in powdery mildew resistance. Comparisons of these genes with their orthologs in diploid ancestors revealed that EDS1 is a conserved gene family in Triticeae. The cDNA sequence similarity among the three TaEDS1 genes was greater than 96.5%, and they shared sequence similarities of more than 99.6% with the respective orthologs from diploid ancestors. The phylogenetic analysis revealed that the EDS1 family originated prior to the differentiation of monocots and dicots, and EDS1 members have since undergone clear structural differentiation. The transcriptional levels of TaEDS1 genes in the leaves were obviously higher than those of the other organs, and they were induced by Blumeria graminis f. sp. tritici (Bgt) infection and salicylic acid (SA) treatment. The BSMV-VIGS experiments indicated that knock-down the transcriptional levels of the TaEDS1 genes in a powdery mildew-resistant variety of common wheat compromised resistance. Contrarily, transient overexpression of TaEDS1 genes in a susceptible common wheat variety significantly reduced the haustorium index and attenuated the growth of Bgt. Furthermore, the expression of TaEDS1 genes in the Arabidopsis mutant eds1-1 complemented its susceptible phenotype to powdery mildew. The above evidences strongly suggest that TaEDS1 acts as a positive regulator and confers resistance against powdery mildew in common wheat.


Assuntos
Resistência à Doença/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Triticum/genética , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Ascomicetos/fisiologia , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Teste de Complementação Genética , Mutação , Filogenia , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Folhas de Planta/microbiologia , Proteínas de Plantas/classificação , Isoformas de Proteínas/genética , Homologia de Sequência de Aminoácidos , Triticum/microbiologia
15.
Biochem Biophys Res Commun ; 503(3): 2075-2082, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30107914

RESUMO

Adiponectin (APN) has been shown to play a key role in regulating bone mineral density (BMD). Nevertheless, the effects of APN on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation and mechanism of regulation are not entirely clear. The study, therefore, aimed to evaluate the effect of APN on osteoclastogenesis. Our results showed that APN inhibits osteoclastogenesis and resorption function in vitro by suppressing nuclear factor-κB (NF-κB) and p38 signaling pathways, which is essential for osteoclast formation. Moreover, APN blocked the formation of F-actin rings and attenuated osteoclast-mediated bone resorptive function. Therefore, we concluded that APN may provide a potential treatment for osteoclast-related diseases, such as osteoporosis.


Assuntos
Adiponectina/farmacologia , NF-kappa B/antagonistas & inibidores , Osteogênese/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Adiponectina/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Células RAW 264.7 , Receptor Ativador de Fator Nuclear kappa-B/antagonistas & inibidores , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Int J Ind Ergon ; 62: 27-41, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30514986

RESUMO

To control vibration-induced white finger among workers performing the fine grinding of golf club heads, the aims of this study are to clarify the major vibration sources in the grinding process, to identify and understand the basic characteristics of the club head vibration, and to propose potential approaches for reducing the vibration exposure. The vibrations on two typical club heads and two belt grinding machines were measured at a workplace. A simulated test station was also constructed and used to help examine some influencing factors of the club head vibration. This study found that the club head vibration was the combination of the vibration transmitted from the grinding machines and that generated in the grinding process. As a result, any factor that affects the machine vibration, the grinding vibration, and/or the dynamic response of the club head can influence the vibration exposure of the fingers or hands holding the club head in the grinding process. The significant influencing factors identified in the study include testing subject, grinding machine, machine operation speed, drive wheel condition, club head model, mechanical constraints imposed on the club head during the grinding, and machine foot pad. These findings suggest that the vibration exposure can be controlled by reducing the grinding machine vibration, changing the workpiece dynamic properties, and mitigating the vibration transmission in its pathway. Many potential methods for the control are proposed and discussed. RELEVANCE TO INDUSTRY: Vibrations on handheld workpieces can be effectively transmitted to the hands, especially the fingers. As a result, a major component of the hand-arm vibration syndrome - vibration-induced white finger - has been observed among some workers performing the grinding and/or polishing tasks of the handheld workpieces such as golf club heads. The results of this study can be used to develop more effective methods and technologies to control the vibration exposure of these workers. This may help effectively control this occupational disease.

17.
Gastroenterology ; 147(5): 1031-42, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25127680

RESUMO

BACKGROUND & AIMS: The anti-cancer effects of vegetables and fruit have been investigated extensively, but the association between vegetable and fruit consumption and risk of hepatocellular carcinoma (HCC) has not been quantified. We performed a meta-analysis of observational studies to clarify the association. METHODS: We identified eligible studies, published from 1956 through May 31, 2014, by searching PubMed, Web of Science, and EMBASE. Random-effects models were used to calculate summary relative risks (RRs) and dose-response analyses were conducted to quantify associations. Heterogeneity among studies was evaluated using Cochran's Q and I(2) statistics. RESULTS: A total of 19 studies involving 1,290,045 participants and 3912 cases of HCC were included in the meta-analysis. The summary RR for HCC was 0.72 for individuals with high intake vs low intake of vegetables (95% confidence interval [CI]: 0.63-0.83) and 0.92 with a daily increase in vegetable intake (100 g/d) (95% CI: 0.88-0.95). Subgroup analyses showed that this inverse association did not change regardless of history of hepatitis, alcohol drinking, smoking, or energy intake. The summary RR for HCC among individuals with high vs low intake of fruit was 0.93 (95% CI: 0.80-1.09), and 0.99 with a daily increase in fruit intake (100 g/d) (95% CI: 0.94-1.05). CONCLUSIONS: Based on a meta-analysis, increased intake of vegetables, but not fruit, is associated with lower risk for HCC. The risk of HCC decreases by 8% for every 100 g/d increase in vegetable intake. The findings should be confirmed by future studies with validated questionnaires and strict control of confounders.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Dieta/efeitos adversos , Frutas , Neoplasias Hepáticas/prevenção & controle , Verduras , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Comportamento Alimentar , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Estudos Observacionais como Assunto , Razão de Chances , Fatores de Proteção , Medição de Risco , Fatores de Risco
18.
Mediators Inflamm ; 2015: 854670, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26578822

RESUMO

OBJECTIVES: The prognostic value of inflammatory index in esophageal cancer (EC) was not established. In the present study, we initially used a nomogram to predict prognostic value of red cell distribution width (RDW) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 277 ESCC patients were included in this retrospective study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). A nomogram was established to predict the prognosis for CSS. RESULTS: The mean value of RDW was 14.5 ± 2.3%. The patients were then divided into two groups: RDW ≥ 14.5% and RDW < 14.5%. Patients with RDW < 14.5% had a significantly better 5-year CSS than patients with RDW ≥ 14.5% (43.9% versus 23.3%, P < 0.001). RDW was an independent prognostic factor in patients with ESCC (P = 0.036). A nomogram could be more accurate for CSS. Harrell's c-index for CSS prediction was 0.68. CONCLUSION: RDW was a potential prognostic biomarker in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC.


Assuntos
Carcinoma de Células Escamosas/sangue , Índices de Eritrócitos , Neoplasias Esofágicas/sangue , Intervalo Livre de Doença , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
19.
Int J Mol Sci ; 16(7): 16347-77, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26193268

RESUMO

Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway.


Assuntos
Pepinos-do-Mar/genética , Transcriptoma , Vibrio/patogenicidade , Animais , Resistência à Doença/genética , Loci Gênicos , Sistema de Sinalização das MAP Quinases , Polimorfismo de Nucleotídeo Único , Pepinos-do-Mar/imunologia , Pepinos-do-Mar/microbiologia
20.
J Res Med Sci ; 19(10): 1012-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25538788

RESUMO

To review cases of simultaneous radical cystectomy and colorectal cancer (CRC) resection for synchronous carcinoma of bladder and colorectum. Between May 1997 and September 2010, five patients were diagnosed with synchronous bladder cancer and CRCs. The primary colorectal tumors included three sigmoid cancers, one ascending colon cancer and one rectal cancer. All patients underwent simultaneous radical cystectomy and CRC resection. Pathologic types were confirmed by the biopsies of cystoscopy and colonoscopy. All patients were performed synchronous radical cystectomy and CRC resection. Four of them received adjuvant chemotherapies for CRC. Two of them died of liver metastasis 32.8 months and 13 months after surgery. Although patients with synchronous carcinoma of bladder and colorectum are rare, the Urologist should be alerted to this possibility when evaluating patients for the initially presenting symptoms and/or detected tumors. The simultaneous surgery is technically feasible for the selected patients.

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