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1.
BMC Geriatr ; 20(1): 115, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228465

RESUMO

BACKGROUND: Previous studies have just found skeletal muscle mass decline is associated with arterial stiffness, but it is unclear whether muscle strength and physical performance as important compositions of sarcopenia are associated with arterial stiffness. The aim of this study was to investigate the relationship between sarcopenia, the components of sarcopenia and arterial stiffness among elderly in the community. METHODS: This study enrolled 450 elderly people who received general medical examinations in Tianjin First Center Hospital. Each of the subjects was greater than 65 years old, including 266 male and 184 female subjects. Based on the diagnostic criteria for sarcopenia in older people developed by the Asian Working Group for Sarcopenia (AWGS), 89 subjects were separated into the sarcopenia group. The living habits, disease status, general status and laboratory examinations of all subjects were collected. The body composition (including appendicular skeletal muscle mass and visceral fat area (VFA) of each participant) was measured by bioimpedance analysis. HS, usual gait speed (GS), and brachial ankle pulse wave velocity (baPWV) were measured. RESULTS: Sarcopenia subjects had higher baPWV, nutrition risk and lower appendicular skeletal muscle index (ASMI), Handgrip strength (HS), GS, body mass index (BMI), triacylglycerol (TG), serum albumin (ALB) and creatinine (Cr) than did non-sarcopenia subjects; Sarcopenia subjects also had higher visceral fat area (VFA) than did non-sarcopenia subjects (p < 0.05). ASMI and HS were negatively associated with baPWV (t = - 5.807, p = 0.000 and t = - 3.085, p = 0.002), but the relationship between baPWV and GS was not statistically significant (t = - 0.862, p = 0.389) by multivariable linear regression. After adjusting for confounders, a multivariate logistic regression analysis revealed that sarcopenia was related with age, BMI, sports and baPWV in community dwelling elderly. CONCLUSIONS: ASMI and HS were negatively associated with baPWV in community dwelling elderly in China; and baPWV was a risk factor of sarcopenia.

2.
Sci Rep ; 10(1): 608, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953461

RESUMO

Multiple kinases converge on the transcription factor cAMP response element-binding protein (CREB) to enhance the expression of proteins essential for long-term synaptic plasticity and memory. The p90 ribosomal S6 kinase (RSK) is one of these kinases, although its role is poorly understood. The present study exploited the technical advantages of the Aplysia sensorimotor culture system to examine the role of RSK in long-term synaptic facilitation (LTF) and long-term enhancement of neuronal excitability (LTEE), two correlates of long-term memory (LTM). Inhibition of RSK expression or RSK activity both significantly reduced CREB1 phosphorylation, LTF, and LTEE, suggesting RSK is required for learning-related synaptic plasticity and enhancement in neuronal excitability. In addition, knock down of RSK by RNAi in Aplysia sensory neurons impairs LTF, suggesting that this may be a useful single-cell system to study aspects of defective synaptic plasticity in Coffin-Lowry Syndrome (CLS), a cognitive disorder that is caused by mutations in rsk2 and associated with deficits in learning and memory. We found that the impairments in LTF and LTEE can be rescued by a computationally designed spaced training protocol, which was previously demonstrated to augment normal LTF and LTM.

3.
J Invest Dermatol ; 140(2): 348-360.e11, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31421124

RESUMO

Both systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown. Through a series of bioinformatics and functional analyses, we prioritized a potential independent functional single-nucleotide polymorphism (rs13239597) within TNPO3 promoter region, residing in a putative enhancer element and validated that IRF5 is the distal target gene (∼118 kb) of rs13239597, which is a key regulator involved in pathogenic autoantibody dysregulation, increasing risk of both SLE and SSc. We experimentally validated the long-range chromatin interactions between rs13239597 and IRF5 using chromosome conformation capture assay. We further demonstrated that rs13239597-A acted as an allele-specific enhancer regulating IRF5 expression, independently of TNPO3 by using dual-luciferase reporter assays and CRISPR-Cas9. Particularly, the transcription factor EVI1 could preferentially bind to rs13239597-A allele and increase the enhancer activity to regulate IRF5 expression. Taken together, our results uncovered a mechanistic insight of a noncoding functional variant acting as an allele-specific distal enhancer to directly modulate IRF5 expression, which might obligate in understanding of complex genetic architectures of SLE and SSc pathogenesis.

4.
Toxicol Lett ; 321: 146-154, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31836503

RESUMO

BACKGROUND: Exposure to particulate matters (PMs) can lead to an acute exacerbation of allergic airway diseases, increasing the severity of symptoms and mortality. However, little is known about the underlying molecular mechanism. This study aimed to investigate the effects of PMs on acute exacerbation of allergic airway inflammation and seek potential therapeutic targets. METHODS: Non-allergic control and ovalbumin (OVA)-allergic wide-type (WT) and Toll-like receptor 2 knockout (Tlr2-/-) mice were exposed to 100 µg of PM (diameter 5.85 µm) or saline by the oropharyngeal instillation. The responses were examined three days after exposure. In the RAW264.7 macrophage cell line, Tlr2 was knocked down by small-interfering RNA or the NF-κB inhibitor JSH-23 was used, and then the cells were stimulated with PMs for 12 h before comparison of the inflammatory responses. RESULTS: PM exposure led to increased inflammatory cell recruitment and airway intensity of PAS + staining in OVA-allergic WT mice, accompanied with an accumulation of inflammatory cells and elevated inflammatory cytokines, such as IL-6 and IL-18, in the bronchoalveolar lavage fluid (BALF). Furthermore, the protein levels of TLR2 and the NLRP3 inflammasome were elevated concomitantly with the airway inflammation post-OVA/PMs challenge. Tlr2 deficiency effectively inhibited the airway inflammation, including pulmonary inflammatory cell recruitment, mucus secretion, serum OVA-specific immunoglobulin E (IgE), and BALF inflammatory cytokine production. Additionally, the P-induced NLRP3 activation in the RAW 264.7 cell line was diminished by the knockdown of Tlr2 or JSH-23 treatment in vitro. CONCLUSION: Our results indicated that PMs exacerbate the allergic airway inflammation mediated by the TLR2/ NF-κB/NLRP3 signaling pathway. Inhibition of NF-κB seems to be a possible treatment.


Assuntos
Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Material Particulado/toxicidade , Hipersensibilidade Respiratória/induzido quimicamente , Receptor 2 Toll-Like/metabolismo , Alérgenos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Pulmão/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Tamanho da Partícula , Células RAW 264.7 , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/genética
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1933-1937, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839062

RESUMO

OBJECTIVE: To investigate the level of serum microRNA-609 and its clinical prognostic value in patients with thalassemia. METHODS: One hundred and twenty-seven patients with thalassemia treated in our hospital from April 2017 to April 2018 were selected, 100 healthy persons were selected as control group. The changes of miR-609 were analyzed by RT-PCR, the relationship between miR-609 and clinical indicators of thalassemia was analyzed, and the prognostic risk factors of thalassemia were evaluated by multivariate logistic regression analysis. RESULTS: The relative expression level of miR-609 in thalassemia patients was 3.17±0.24, which was significantly higher than that in control group (P<0.05). The levels of ALT, Plt and MCH in patients with high expression of miR-609 were significantly higher than those in patients with low expression of miR-609 (P<0.05). The levels of Hb and sICAM-1 in patients with high expression of miR-609 were significantly lower than those in patients with low expression of miR-609 (P<0.05). There was no correlation between the level of miR-609 and the patient's sex, age and AST (P>0.05). The incidence rate of mild anemia in high expression group was significantly lower than that in low expression group (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of moderate anemia (P>0.05). The number of patients with severe anemia in the miR-609 high expression group was higher than that in miR-609 low expression group (P<0.05). The incidence rate of dizziness, fatigue and fever in patients with miR-609 high expression group was significantly higher than those in patients with miR-609 low expression (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of nausea in patients with thalassemia. ROC curve showed that the AUC value of microRNA-609 was 0.862, the sensitivity was 83.6%, and the specificity was 84.1%, which suggested that miR-609 had a high diagnostic value for thalassemia. Multivariate logistic regression analysis showed that MCH and mir-609 were risk factors for poor prognosis of thalassemia patients. CONCLUSION: The increased level of serum miR-609 in patients with thalassemia is a risk factor for poor prognosis and can be used as a reference index for evaluating the efficacy for patients.


Assuntos
Talassemia , Biomarcadores Tumorais , Humanos , MicroRNAs , Prognóstico , Curva ROC , Talassemia/genética
6.
Animals (Basel) ; 9(12)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775331

RESUMO

The heat shock factor 1 (HSF1) gene is a regulator of the heat stress response, maximizing HSP protein expression survival. In this research, we explored the frequency distribution of a missense mutation (NC_037341.1 g.616087A > G, rs135258919) in the HSF1 gene in Chinese cattle with amino acid substitution, valine to alanine. This mutation could be related to the heat tolerance in Bos indicus. A total of 941 individuals representing 35 Chinese native cattle breeds, combining pure taurine (Angus) and indicine cattle, were used to determine the genotypes of the mutation through PCR and partial DNA sequencing. The results showed significant differences in allele frequencies and their genotypes amongst Chinese cattle from different regions. Allele G or indicine-specific allele frequency diminished from south to north China, while allele A (genotype AA) or the taurine-specific allele had a contrary pattern, which agreed with the distribution of taurine and indicine cattle. According to the association analysis, the NC_037341.1 g.616087A > G (rs135258919) of the bovine HSF1 gene, annual temperature (T), relative humidity (RH), and the temperature humidity index (THI) (p < 0.01) were interrelated closely, which indicated that the NC_037341.1 g.616087A > G of the HSF1 gene is associated with heat tolerance in indicine cattle.

7.
Cell Biosci ; 9: 80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583074

RESUMO

Background: Babao Dan (BBD), a traditional Chinese medicine, has been used as a complementary and alternative medicine to treat multifarious liver diseases. In this study, we aimed to observe its protective effect on ethanol-induced liver injury and explore potential mechanisms. Methods: Mice pretreated with BBD (0.125, 0.25 and 0.5 g/kg BW) were administrated by ethanol gavage (5 g/kg BW). Liver injury biomarkers and hepatic redox parameters were evaluated by histopathology as well as serum and hepatic content analysis. AML-12 cell was also utilized to determine the efficacy of BBD against ethanol-induced hepatotoxicity. Results: Drunkenness experiment showed that the latency was significantly increased and the drunken sleep time was decreased in mice pretreated with BBD. We then found that BBD could reduce hepatic lipid peroxidation and steatosis induced by ethanol exposure. BBD could also suppress ethanol-induced depletion of hepatic antioxidant enzyme. Besides that, BBD treatment lessened the induction of hepatic cytochrome P450 2E1, a major contributor to ethanol-mediated oxidative stress, and up-regulated the expression of nuclear factor erythroid 2-related factor 2 and its two transcriptional targets hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit. Furthermore, autophagy induced by BBD contributed to hepatoprotection activity. Conclusions: Our results suggest that BBD can markedly dispel acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy.

8.
Cancer Cell Int ; 19: 243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572060

RESUMO

Background: The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options. Methods: The hypoxic gene signature (HGS) was constructed using transcriptomic data of 309 CRC patients with complete clinical information from the CIT microarray dataset. A total of 1877 CRC patients with complete prognostic information in six independent datasets were divided into a training cohort and two validation cohorts. Univariate and multivariate analyses were conducted to evaluate the prognostic value of HGS. Results: The HGS consisted of 14 genes, and demarcated the CRC patients into the high- and low-risk groups. In all three cohorts, patients in the high-risk group had significantly worse disease free survival (DFS) compared with those in the low risk group (training cohort-HR = 4.35, 95% CI 2.30-8.23, P < 0.001; TCGA cohort-HR = 2.14, 95% CI 1.09-4.21, P = 0.024; meta-validation cohort-HR = 1.91, 95% CI 1.08-3.39, P = 0.024). Compared to Oncotype DX, HGS showed superior predictive outcome in the training cohort (C-index, 0.80 vs 0.65) and the validation cohort (C-index, 0.70 vs 0.61). Pathway analysis of the high- and low-HGS groups showed significant differences in the expression of genes involved in mTROC1, G2-M, mitosis, oxidative phosphorylation, MYC and PI3K-AKT-mTOR pathways (P < 0.005). Conclusion: Hypoxic gene signature is a satisfactory prognostic model for early stage CRC patients, and the exact biological mechanism needs to be validated further.

9.
J Natl Compr Canc Netw ; 17(10): 1174-1183, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590148

RESUMO

BACKGROUND: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). METHODS: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. RESULTS: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. CONCLUSIONS: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti-PD-1 therapy in cases of peritoneal or ovarian metastasis.

10.
Math Biosci Eng ; 16(5): 4359-4381, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31499666

RESUMO

The OpenFlow protocol match field capacity is fixed and limited, and packet forwarding in software-defined network lacks valid authentication of data source, integrity verification, and confidentiality protection mechanism. OpenFlow only supports the MPLS label tunnel establishment, and therefore cannot establish a secure tunnel flexibly. In order to solve these problems, we propose P4Sec, a novel software-defined network packet security tunnel forwarding mechanism. As P4 allows the data plane to be reprogrammed to realize the characteristics of packet forwarding, we build a software-defined network security tunnel to prevent data malicious tampering, stealing, forgery and other malicious network behavior, implementing packet routing and forwarding based on gateway identity. Finally, we construct a P4Sec prototype system based on the software switch BMv2, verify the effectiveness of the mechanism through experimental analysis, and evaluate the overhead of the mechanism. The results demonstrate that P4Sec security mechanism ensure the authenticity, integrity, and confidentiality of forwarded data, and realize the secure forwarding requirements of data packets in software-defined network.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31385379

RESUMO

Genetic interaction has been recognized to be an important cause of the missing heritability. The topologically associating domain (TAD) is a self-interacting genomic region, and the DNA sequences within a TAD physically interact with each other more frequently. Sex differences influence cancer susceptibility at the genetic level. Here, we performed both regular and sex-specific genetic interaction analyses within TAD to identify susceptibility genes for lung cancer in 5204 lung cancer patients and 7389 controls. We found that one SNP pair, rs4262299-rs1654701, was associated with lung cancer in women after multiple testing corrections (combined P = 8.52 × 10-9 ). Single-SNP analyses did not detect significant association signals for these two SNPs. Both identified SNPs are located in the intron region of ANGPT1. We further found that 5% of nonsmall cell lung cancer patients have an alteration in ANGPT1, indicated the potential role of ANGPT1 in the neoplastic progression in lung cancer. The expression of ANGPT1 was significantly down-regulated in patients in lung squamous cell carcinoma and lung adenocarcinoma. We checked the interaction effect on the ANGPT1 expression and lung cancer and found that the minor allele "G" of rs1654701 increased ANGPT1 gene expression and decreased lung cancer risk with the increased dosage of "A" of rs4262299, which consistent with the tumor suppressor function of ANGPT1. Survival analyses found that the high expression of ANGPT1 was individually associated with a higher survival probability in lung cancer patients. In summary, our results suggest that ANGPT1 may be a novel tumor suppressor gene for lung cancer.

12.
Future Oncol ; 15(29): 3357-3365, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31411050

RESUMO

Aim: To assess the incidence and predictors of nasopharyngeal carcinoma (NPC)-specific mortality in the first year among NPC patients. Methods: We identified 2714 patients in the SEER program. Results: Of the patients, 151 (5.6%) patients who died as NPC-related disease within 1 year of diagnosis. Specifically, 67.5% of the NPC-related deaths were attributed to keratinizing tumors, while 67.6% were attributed to advanced T stage. Older age, keratinizing squamous tumors and stage T3-4 disease were independent predictors of 1-year NPC-related death. Conclusion: The 1-year mortality rate is low among NPC patients after radiotherapy. Older age, keratinizing tumor and advanced T stage are predictors of high-mortality risk within 1 year in NPC patients.

13.
J Clin Lab Anal ; 33(9): e22990, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402485

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the leading contributors to cancer-related deaths worldwide. The objective of the current study is to identify a multidimensional transcriptome prognostic signature by combining protein-coding gene (PCG) with long non-coding RNA (lncRNA) for patients with LUAD. METHODS: We obtained LUAD PCG and lncRNA expression profile data from three datasets in the Gene Expression Omnibus database and conducted survival analyzes for these individuals. RESULTS: We established a predictive model comprising the three PCGs (NHLRC2, PLIN5, GNAI3), and one lncRNA (AC087521.1). This model segregated patients with LUAD into low- and high-risk groups based on significant differences in survival in the training dataset (GSE31210, n = 226, log-rank test P < .001). Risk stratification of the model was subsequently validated in other two test datasets (GSE37745, n = 106, log-rank test P < .001; GSE30219, n = 85, log-rank test P = .006). Time-dependent receiver operating characteristic (timeROC) curve analysis demonstrated that the model correlated strongly with disease progression and outperformed pathological stage in terms of prognostic ability. Cox proportional hazards regression analysis revealed that the signature could serve as an independent predictor of clinical outcomes in patients with LUAD. CONCLUSIONS: We describe a novel multidimensional transcriptome signature that can predict survival probabilities in patients with LUAD.

14.
Animals (Basel) ; 9(6)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248194

RESUMO

Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4, also known as GCN2), which pertains to the family of serine-threonine kinase, is involved in oxidative stress and DNA damage repair. A missense single-nucleotide polymorphism (SNP) (NC_037337.1 g.35615224 T > G) in exon 6 of the EIF2AK4 gene which encodes a p.Ile205Ser substitution was observed in the Bovine Genome Variation Database and Selective Signatures (BGVD). The purpose of the current study is to determine the allelic frequency distribution of the locus and analyze its association with thermal tolerance in Chinese indigenous cattle. In our study, the allelic frequency distribution of the missense mutation (NC_037337.1 g.35615224 T > G) in Chinese cattle was analyzed by sequencing 1105 individuals of 37 breeds including 35 Chinese indigenous cattle breeds and two exotic breeds. In particular, association analysis was carried out between the genotypes and three environmental parameters including annual mean temperature (T), relative humidity (RH), and temperature-humidity index (THI). The frequency of the mutant allele G (NC_037337.1 g.35615224 T > G) gradually decreased from the southern cattle groups to the northern cattle groups, whereas the frequency of the wild-type allele T showed an opposite pattern, consistent with the distribution of indicine and taurine cattle in China. In accordance with the association analysis, genotypes were significantly associated with T (P < 0.01), RH (P < 0.01), and THI (P < 0.01), suggesting that the cattle with genotype GG were found in regions with higher T, RH, and THI. Thus, our results suggest that the mutation (NC_037337.1 g.35615224 T > G) of the EIF2AK4 gene is associated with thermal tolerance traits in Chinese cattle.

15.
Mol Med Rep ; 20(1): 455-462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180535

RESUMO

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were evaluated by ELISA. The expressions of IκBα and NF­κB p65 were examined by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL­6, TNF­α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF­κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS­induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Licopeno/uso terapêutico , Quinolizinas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Sinergismo Farmacológico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
16.
Front Oncol ; 9: 255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024855

RESUMO

Objectives: We used radiomic analysis to establish a radiomic signature based on preoperative contrast enhanced computed tomography (CT) and explore its effectiveness as a novel recurrence risk prognostic marker for advanced high-grade serous ovarian cancer (HGSOC). Methods: This study had a retrospective multicenter (two hospitals in China) design and a radiomic analysis was performed using contrast enhanced CT in advanced HGSOC (FIGO stage III or IV) patients. We used a minimum 18-month follow-up period for all patients (median 38.8 months, range 18.8-81.8 months). All patients were divided into three cohorts according to the timing of their surgery and hospital stay: training cohort (TC) and internal validation cohort (IVC) were from one hospital, and independent external validation cohort (IEVC) was from another hospital. A total of 620 3-D radiomic features were extracted and a Lasso-Cox regression was used for feature dimension reduction and determination of radiomic signature. Finally, we combined the radiomic signature with seven common clinical variables to develop a novel nomogram using a multivariable Cox proportional hazards model. Results: A final 142 advanced HGSOC patients were enrolled. Patients were successfully divided into two groups with statistically significant differences based on radiomic signature, consisting of four radiomic features (log-rank test P = 0.001, <0.001, <0.001 for TC, IVC, and IEVC, respectively). The discrimination accuracies of radiomic signature for predicting recurrence risk within 18 months were 82.4% (95% CI, 77.8-87.0%), 77.3% (95% CI, 74.4-80.2%), and 79.7% (95% CI, 73.8-85.6%) for TC, IVC, and IEVC, respectively. Further, the discrimination accuracies of radiomic signature for predicting recurrence risk within 3 years were 83.4% (95% CI, 77.3-89.6%), 82.0% (95% CI, 78.9-85.1%), and 70.0% (95% CI, 63.6-76.4%) for TC, IVC, and IEVC, respectively. Finally, the accuracy of radiomic nomogram for predicting 18-month and 3-year recurrence risks were 84.1% (95% CI, 80.5-87.7%) and 88.9% (95% CI, 85.8-92.5%), respectively. Conclusions: Radiomic signature and radiomic nomogram may be low-cost, non-invasive means for successfully predicting risk for postoperative advanced HGSOC recurrence before or during the perioperative period. Radiomic signature is a potential prognostic marker that may allow for individualized evaluation of patients with advanced HGSOC.

17.
IUBMB Life ; 71(7): 1021-1029, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31018046

RESUMO

Melatonin is one of the main hormones that regulate biological rhythms and have immunomodulation, anti-inflammatory, and antioxidation functions. In this study, we aimed to explore the effect of melatonin on the autophagy, apoptosis, and inflammatory reaction of macrophages (RAW264.7 cells) stimulated by nanosilica. SiO2 (100 mg/mL, 10-20 nm) was used to stimulate RAW264.7 cells at different time points (0, 2, 4, 8, 12, and 24 hr). Melatonin (200 µM) was added to SiO2 -stimulated macrophages at 12 hr. Beclin-1, LC3, Bax, Bcl-2, and Caspase-3 were examined with western blotting. Flow cytometry was used to detect apoptosis. The levels of TNF-α, IL-1ß, and IL-18 were detected by ELISA. The level of TNF-α in the supernatant of SiO2 -stimulated cells gradually increased with time but decreased following melatonin administration. In contrast, the expression of IL-1ß and IL-18 increased after melatonin treatment. LC3 and Bax signaling pathways were activated in SiO2 -stimulated RAW264.7 cells, showing elevated expression of LC3 and reduced expression of Bax in the melatonin-treated cells. GFP-LC3 puncta were significantly increased in SiO2 -stimulated RAW264.7 cells and decreased in melatonin-treated cells. The apoptotic rate in SiO2 -stimulated RAW264.7 cells increased with time and decreased after melatonin treatment, and the number of phagosomes increased with the stimulation of nanosilica and the treatment of melatonin. Melatonin might promote autophagy and inhibit apoptosis as well as inflammatory responses of RAW264.7 cells stimulated by nanosilica. © 2019 IUBMB Life, 2019.

18.
Carbohydr Polym ; 213: 247-256, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879666

RESUMO

An active polysaccharide (LPD2) was isolated from longan pulp by comparing the effects of polysaccharides on the phagocytosis of macrophages. LPD2 was composed of arabinose, mannose, glucose, and galactose in a molar ratio of 0.25:0.49:1:0.5 with average molecular weight of 9.64 × 106 Da. The main linkages of the sugar residues of LPD2 were (1→4)-ß-Glc and (1→6)-ß-Man. LPD2 significantly enhanced the lymphocytes proliferation, phagocytosis and NO and IL-6 secretion by macrophage. The anti-TLR2 and anti-TLR4 mAbs markedly suppressed LPD2-mediated NO and IL-6 production. Furthermore, anti-TLR4 or anti-TLR2 plus anti-TLR4 treatment significantly decreased LPD2-induced increase of MyD88, IRAK4, TRAF6 and INOS mRNA expression. Moreover, western blotting analysis showed that LPD2 enhanced the expression of target proteins in MyD88/IRAK4-TRAF6- INOS pathways. These results suggested that LPD2 induced macrophage activation partly via the TLR2- and TLR4-mediated MyD88/IRAK4-TRAF6 signaling pathways. Knowing the structural features and activities of active polysaccharide of longan gives the insights into longan polysaccharide application as an immunomodulatory agent.


Assuntos
Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Sapindaceae/química , Animais , Configuração de Carboidratos , Frutas/química , Imunomodulação/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7
19.
Insect Biochem Mol Biol ; 108: 9-15, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30857830

RESUMO

In moth species that utilize alkenyl sex pheromones, the epoxidation of alkenes confers further diversity on the chemical structures of pheromone components. Hc_epo1 (CYP341B14), the first pheromone gland (PG)-specific epoxidase identified from the fall webworm Hyphantria cunea (Erebidae), specifically epoxidizes the Z9 double bond in the triene precursor, (3Z,6Z,9Z)-3,6,9-henicosatriene (Z3,Z6,Z9-21:H). In the present study, we identified a novel PG-specific epoxidase, As_epo1, from the Japanese giant looper Ascotis selenaria (Geometridae), which secretes cis-3,4-epoxy-(6Z,9Z)-6,9-nonadecadiene (epo3,Z6,Z9-19:H) as the main sex pheromone component. A functional assay using the Sf9 insect cell line-baculovirus expression system showed that As_epo1 specifically epoxidizes the Z3 double bond in the pheromone precursor triene, (3Z,6Z,9Z)-3,6,9-nonadecatriene (Z3,Z6,Z9-19:H). As_epo1 also Z3-specifically epoxidized a triene with a longer carbon chain, Z3,Z6,Z9-21:H, which does not occur in this species. A phylogenetic analysis indicated that As_epo1 belonged to the CYP340 family, not the CYP341 family to which Hc_epo1 belongs. These results suggest that moth PG-specific epoxidases with divergent regio-specificities have evolved independently.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Mariposas/enzimologia , Atrativos Sexuais/metabolismo , Animais , Baculoviridae , Feminino , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Mariposas/classificação , Mariposas/metabolismo , Oxirredutases/metabolismo , Filogenia , Atrativos Sexuais/biossíntese , Atrativos Sexuais/química , Células Sf9 , Spodoptera
20.
Insect Biochem Mol Biol ; 107: 46-52, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30742902

RESUMO

Epoxidation of alkenes derived from essential fatty acids is a key step in the biosynthesis of sex pheromones in moth species that utilize alkenyl sex pheromones. The position of the epoxy ring in the pheromone molecule differs depending on the species, thereby conferring diversities on sex pheromones. To date, only one pheromone gland (PG)-specific epoxidase, Hc_epo1 (CYP341B14), has been reported. Hc_epo1, which was identified from an arctiid moth Hyphantria cunea, catalyzes the epoxidation of a double bond at position 9 of the triene, Z3,Z6,Z9-21:H. In the present study, we investigated the PG-specific epoxidase from another arctiid, the mulberry tiger moth Lemyra imparilis, in order to verify whether cytochrome P450 in the CYP341B subfamily, to which Hc_epo1 belongs to, is responsible for the epoxidation of pheromone precursors at position 9 in moths other than H. cunea. A fragment of the Hc_epo1 homolog was amplified from cDNA prepared from the PG of L. imparilis by PCR with degenerate primers. The deduced amino acid sequence of the subsequently cloned homolog, Li_epo1, showed 88.5% identity to Hc_epo1. A functional assay using the Sf9 insect cell line-baculovirus expression system showed that Li_epo1 exhibited epoxidase activity with high selectivity to the double bond at position 9 of two trienes, Z3,Z6,Z9-21:H and Z3,Z6,Z9-23:H, precursors of epoxy diene sex pheromone components in L. imparilis.


Assuntos
Proteínas de Insetos/genética , Mariposas/genética , Oxirredutases/genética , Animais , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Oxirredutases/química , Oxirredutases/metabolismo , Homologia de Sequência de Aminoácidos
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