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1.
Hematology ; 25(1): 134-138, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32153255

RESUMO

Objective: To study the function of human bone morphogenetic protein-6 (BMP6) and hepcidin in cancer-related anemia.Methods: The levels of Hemoglobin (Hb), serum C-reactive protein (CRP), BMP6, hepcidin and ferritin (SF) were measured in 115 patients with solid tumors, who were divided into elevated CRP group and normal CRP group, and further divided into anemia subgroup and non-anemia subgroup according to the CRP level.Results: The prevalence of anemia was 53.9% in all patients. In the elevated CRP group, the levels of CRP, hepcidin and SF of the anemia subgroup were higher than the non-anemia subgroup (P < 0.05); the BMP6 levels had no difference between the subgroups (P > 0.05). In the normal CRP group, the BMP6 level in the anemia subgroup was higher than the non-anemia subgroup (P < 0.01); the CRP, hepcidin and SF levels showed no difference between the subgroups (P > 0.05). Among the 115 patients, CRP and SF were both positively correlated with hepcidin (P < 0.05), and CRP and hepcidin were negatively correlated with Hb (P < 0.05), while SF had no correlation with Hb (P > 0.05); BMP6 was negatively correlated with Hb (P < 0.05) while had no correlation with CRP, hepcidin and SF (P < 0.05).Conclusions: The occurrence of anemia in patients with elevated CRP is associated with hepcidin over-expression, while in patients with normal CRP is associated with BMP6 over-expression. We speculate BMP6 and hepcidin likely play different roles in the occurrence of cancer-related anemia.

2.
Cancer Lett ; 478: 45-55, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32160976

RESUMO

Multiple myeloma (MM) is an incurable hematological malignancy, for which novel effective therapies are urgently needed. We synthesized a novel phosphoramide compound, DCZ0847, showing a potent anti-myeloma activity both in vitro and in vivo. DCZ0847 showed high cytotoxicity towards primary MM cells but had no effect on normal cells and was well tolerated in vivo. The anti-myeloma activity of DCZ0847 was associated with inhibition of cell proliferation; promotion of cell apoptosis via mitochondrial transmembrane potential collapse and caspase-mediated extrinsic or intrinsic apoptotic pathways; and the induction of G2/M phase arrest via downregulation of CDC25C, CDK1, and cyclin B1. In particular, DCZ0847 induced DNA damage and triggered a DNA-damage response by enhancing the levels of γ-H2A.X, phosphorylated (p)-ATM, p-ATR, p-Chk1, and p-Chk2. Additionally, DCZ0847 was able to overcome the bone marrow stromal cells-induced proliferation of MM cells and blocked JAK2/STAT3 signaling. Importantly, DCZ0847 acted synergistically with bortezomib, with the combination exerting greater cytotoxic effects in vitro and in vivo. Together, our results indicate that DCZ0847, alone or in combination with bortezomib, may represent a potential new therapy for patients with MM.

3.
Neural Plast ; 2020: 5052840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148473

RESUMO

Background: Neuropathic pain after brachial plexus avulsion remained prevalent and intractable currently. However, the neuroimaging study about neural mechanisms or etiology was limited and blurred. Objective: This study is aimed at investigating the effect of electroacupuncture on effective connectivity and neural response in corticolimbic circuitries during implicit processing of nociceptive stimulus in rats with brachial plexus pain. Methods: An fMRI scan was performed in a total of 16 rats with brachial plexus pain, which was equally distributed into the model group and the electroacupuncture group. The analysis of task-dependent data determined pain-related activation in each group. Based on those results, several regions including AMY, S1, and h were recruited as ROI in dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing the propagation of noxious stimuli in regions of interest and horizontal comparison of effective connections between the model and electroacupuncture groups. Results: In both groups, DCM revealed that noxious stimuli were most likely driven by the somatosensory cortex, with bidirectional propagation with the hypothalamus and amygdala and the interactions in them. Also, the 3-month intervention of acupuncture reduced effective connections of h-S1 and AMY-S1. Conclusions: We showed an evidence that a full connection model within the brain network of brachial plexus pain and electroacupuncture intervention reduces effective connectivity from h and AMY to S1. Our study for the first time explored the relationship of involved brain regions with dynamic causal modeling. It provided novel evidence for the feature of the organization of the cortical-limbic network and the alteration caused by acupuncture.

4.
Phytopathology ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202483

RESUMO

Colletotrichum gloeosporioides is a hemibiotrophic pathogen causing significant losses to economically important crops and forest trees, including Liriodendron. To explore the interaction between C. gloeosporioides and Liriodendron, and identify the candidate genes determining the pathogenesis, we sequenced and assembled the whole genome of C. gloeosporioides Lc1 (CgLc1) using PacBio and Illumina NGS, and performed a comparative genomic analysis between CgLc1 and Cg01, the latter being a described endophytic species of the C. gloeosporioides complex. Gene structure prediction identified 15,744 protein-coding genes and 837 non-coding RNAs. Species-specific genes were characterized using an ortholog analysis, followed by a pathway enrichment analysis which showed that genes specific to CgLc1 were enriched for the arginine biosynthetic process. Furthermore, genome synteny analysis revealed that most of the protein-coding genes fell into collinear blocks. However, two clusters of polyketide synthase genes were identified to be specific for CgLc1, suggesting they might have an important role in virulence control. Transcriptional regulators co-expressed with polyketide synthase genes were detected through a Weighted Correlation Network Analysis. Taken together, this work provides new insight into the virulence- and pathogenesis-associated genes present in C. gloeosporioides and its possible lifestyle.

5.
Nutrients ; 12(3)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121232

RESUMO

BACKGROUND: Iron, zinc and magnesium perform differently in body metabolism but exist in similar food. This study was to evaluate the associations of dietary iron, zinc and magnesium with metabolic syndrome (MetS). METHODS: A sample of a total of 5323 participants from four of China's mega cities was included in the current study. Both a 3-day 24-h dietary recall and household condiment weighing were applied to assess dietary intake, respectively. Hierarchical logistic regression models were used to evaluate the associations of dietary iron, zinc and magnesium with MetS. RESULTS: After adjusting for age, sex, region, years of education, physical activity level, intended physical exercises, smoking status, alcohol use, daily energy intake and mutual adjustment for dietary iron, zinc and magnesium, significant positive trends were found across quartiles of total dietary iron and the risk of MetS, as well as for magnesium and MetS (p value for trends = 0.01 and 0.02, respectively); dietary zinc was inversely associated with MetS risk (p value for trend < 0.01). Magnesium from grains and potato was positively associated with MetS (p value for trend < 0.01). CONCLUSIONS: Dietary iron and magnesium were positively associated with the risk of MetS, while zinc was inversely associated with the risk of MetS, in China's mega cities. The positive association of magnesium with MetS could be a result confounding by other factors correlated with magnesium in grains and potato, which warrants further study.

6.
J Med Genet ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066631

RESUMO

BACKGROUND: Observational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC. OBJECTIVE: We sought to investigate the possible causal effects of established and putative factors on PDAC risk. METHODS: We conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses. RESULTS: We found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10-5). Fasting insulin (OR 2.84, 95% CI 1.23 to 6.56, p=0.01), low-density lipoprotein cholesterol (OR 1.16, 95% CI 1.02 to 1.32, p=0.03) and type 2 diabetes (OR 1.09, 95% CI 1.01 to 1.17, p=0.02) were also causally associated with PDAC risk. BMI showed both direct and fasting insulin-mediated causal effects. CONCLUSION: We found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.

7.
Nanoscale ; 12(8): 4959-4967, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32053129

RESUMO

Organophosphorus pesticides (OPs) are harmful to people's health and d-amino acids (d-AAs) in the human body are closely related to various diseases. So, detection of OPs in foods and d-AAs in serum is important for food safety and clinical diagnosis. Herein, a long-lasting chemiluminescence (CL) imaging sensor was constructed for the detection of OPs and d-AAs. The method was based on N-(4-aminobutyl)-N-ethylisoluminol/Co2+/chitosan (ABEI/Co2+/CS) hydrogels, where metal organic framework materials (MOF-Pt) were selected as catalysts to improve the sensitivity greatly. Under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), H2O2 was produced by using acetylcholine chloride (ACh) as a substrate, which was sensitive to the proposed CL system. OPs inhibited the activity of AChE and decreased the production of H2O2, reducing CL intensity. The linear range of the method for chlorpyrifos was 0.5 ng mL-1-1.0 µg mL-1, with a limit of detection (LOD) of 0.21 ng mL-1. Seventeen kinds of OPs can be visually and simultaneously discerned by the CL imager. On the other hand, d-AAs were catalyzed and oxidized by d-α-amino oxidase (DAAO) to produce H2O2. Thus, d-Ala in serum was used as a model to be detected by the proposed method. The linear range for d-Ala was 1.0 µM-10 mM, with an LOD of 0.12 µM.

8.
Mol Pharm ; 17(2): 683-694, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31913047

RESUMO

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents was assessed on the basis of cytotoxicity, endosomal escape promotion, and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 106 to 109 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP-treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

9.
J Infect Public Health ; 13(1): 34-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31235340

RESUMO

BACKGROUND: Norovirus (NoV) is recognized as a leading global cause of viral acute gastroenteritis (AGE). To better understand the prevalence and genotypic patterns of NoV infection in Southeast China, we conducted a retrospective study of diarrheal syndrome surveillance of NoV and analyzed the epidemiological characteristics of AGE cases and phylogenetic evolution of NoV strains. METHODS: 1464 AGE patients in two diarrhea surveillance sentinel hospitals were sampled during 2016 and 2017. NoV Positive samples were genotyped by ORF1/ORF2 overlapping regional gene sequencing. Sequences analyses of the NoV genotypes were confirmed by online NoV Genotyping Tool and the phylogenetic analysis was constructed by MEGA 7.0. RESULTS: 139 (9.49%) of the AGE specimens were NoV positive. The GII strain was the main geno-group in NoV infected patients. At least 12 NoV genotypes and seven recombinant strains were detected. Major NoV genotypic transformations were GII.Pe/GII.4, GII.P17/GII.17 and GII.Pe/GII.17 in 2016 to GII.P16/GII.2, GII.P17/GII.17 and GII.Pe/GII.4 in 2017. Phylogenetic analysis showed that GII.P16/GII.2 recombinant strains clustered with those detected in the USA, Russia and Japan in 2016. CONCLUSION: We characterized the molecular epidemiology of NoV infection in AGE patients during 2016-2017. The main three NoV GII genotypes circulating in the population of Taizhou were GII.P17/GII.17, GII.Pe/GII.4 and GII.P16/GII.2.The GII.P16/GII.2 genotype has become the predominant strain since first quarter 2017. Monitoring of the NoV genotypic shift is important for the prevention and control of AGE.

10.
Clin Exp Pharmacol Physiol ; 47(4): 591-598, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31868938

RESUMO

Increasing evidence suggests that general control nonderepressible 2 (GCN2) is a critical regulator of oxidative stress and cell apoptosis in response to various stimuli. However, the role of GCN2 in diabetic retinopathy remains unclear. The aim of the present study was to investigate the effects of GCN2 on oxidative stress and apoptosis in ARPE-19 cells exposed to high glucose. The results showed that GCN2 was highly expressed in high glucose-induced ARPE-19 cells. Moreover, knockdown of GCN2 greatly improved ARPE-19 cell viability in response to high glucose. In addition, GCN2 knockdown significantly suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) activity in high glucose-stimulated ARPE-19 cells. Furthermore, GCN2 knockdown reduced cell apoptosis and enhanced the activation of nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway in high glucose-stimulated ARPE-19 cells. However, knockdown of Nrf2 reversed the effects of GCN2 on oxidative stress and cell apoptosis. Taken together, our findings suggest that knockdown of GCN2 inhibits high glucose-induced oxidative stress and apoptosis in ARPE-19 cells through activation of the Nrf2/HO-1 pathway.

11.
BMC Geriatr ; 19(1): 327, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796000

RESUMO

BACKGROUND: Anemia and frailty contribute to poor health outcomes in older adults; however, most current research in lower income countries has concentrated on anemia or frailty alone rather than in combination. The aim of the present study was to investigate the association between anemia and frailty in community-dwelling adults aged 50 years and older in China. METHODS: The study population was sourced from the 2007/10 SAGE China Wave 1. Anemia was defined as hemoglobin less than 13 g/dL for men and less than 12 g/dL for women. A Frailty Index (FI) was compiled to assess frailty. The association between anemia and frailty was evaluated using a 2-level hierarchical logistic model. RESULTS: The prevalence of anemia was 31.0% (95%CI: 28.4, 33.8%) and frailty 14.7% (95%CI: 13.5, 16.0%). In the univariate regression model, presence of anemia was significantly associated with frailty (OR = 1.62, 95% CI: 1.39, 1.90) and the effect remained consistent after adjusting for various potential confounding factors including age, gender, residence, education, household wealth, fruit and vegetable intake, tobacco use, alcohol comsumption and physical activity (adjusted OR = 1.31, 95% CI:1.09, 1.57). Each 1 g/dL increase in hemoglobin concentration was associated with 4% decrease in the odds of frailty after adjusting for several confounding variables (adjusted OR = 0.96, 95% CI: 0.93, 0.99). CONCLUSION: Anemia and low hemoglobin concentrations were significantly associated with frailty. Therefore, health care professionals caring for older adults should increase screening, assessment of causes and treatment of anemia as one method of avoiding, delaying or even reversing frailty.

12.
Transplantation ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31815909

RESUMO

BACKGROUND: Living donor liver transplantation (LDLT) in children has achieved promising outcomes during the past few decades.{B, 2014 #448;A, 2007 #644} However, it still poses various challenges. This study aimed to analyze perioperative risk factors for postoperative death in pediatric LDLT. METHODS: We retrospectively analyzed medical records of pediatric patients who underwent LDLT surgery from January 1, 2014 to December 31, 2016 in our hospital. Predictors of mortality following LDLT were analyzed in 430 children. Cox regression and Kaplan-Meier curve analysis were used for covariates selection. A nomogram was developed to estimate overall survival probability. The performance of the nomogram was assessed using calibration curve, decision curves analysis (DCA) and time-dependent receiver operating characteristic (ROC) curve. RESULTS: Among the 430 patients in this cohort (median [IQR] age, 7 [6.10] months; 189 [43.9%] female; 391 [90.9%] biliary atresia), the overall survival was 91.4% (95%CI; 89.2, 94.4), and most of the death events (36/37) happened within 6 months after the surgery. Multivariate analysis indicated that the Pediatric End-stage Liver Disease (PELD) score, neutrophil lymphocyte ratio (NLR), graft-to-recipient weight ratio (GRWR) and intraoperative norepinephrine (NE) infusion were independent prognostic factors. A novel nomogram was developed based on these prognostic factors. The C-index for the final model was 0.764 (95%CI; 0. 701, 0.819). DCA and time-dependent ROC suggested that this novel nomogram performed well at predicting mortality of pediatric LDLT. CONCLUSIONS: We identified several perioperative risk factors for mortality of pediatric LDLT. And the newly developed nomogram can be a convenient individualized tool in estimating the prognosis of pediatric LDLT.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31827555

RESUMO

Objective: To explore a new treatment that can proceed from the whole, control blood pressure smoothly and coordinate the treatment of multiple factors causing blood pressure fluctuations. Method: We conducted a single-center, double-blinded, and randomized controlled clinical trial. 48 patients with acute Type B aortic dissection were randomly assigned into two groups: the experimental group, who received pinggan formula treatment, and the control group, who received placebo treatment. The drug was taken orally after meals three times a day. Only when the patients' blood pressure fluctuated, conventional antihypertensive drugs were given to maintain the blood pressure within the target range and the dosage was recorded to convert the DDD value. Meanwhile, the international standardized score was used to evaluate the defecation, sleep, pain, anxiety, and depression of patients in the two groups during the hospitalization. Result: Univariate analysis was conducted on variables that might affect the assessment results, and it was found that grouping factors had a significant impact on the outcome variables, that is, after the intervention, the mean value of DDDs used in the perioperative period in the control group was 2.19 (0.38, 4.00). (P=0.0219), defecation score (2.13 (1.59, 2.67); P < 0.0001), sleep score (0.95 (0.40, 1.50); P=0.0014), pain score (1.77 (0.61, 2.93); P=0.0045), depression score (4.04 (2.95, 5.12); and P < 0.0001) were significantly higher than that of the experimental group, and the difference was statistically significant. Conclusion: Pinggan formula has a clear therapeutic regulation effect on the overall hemodynamics of acute Stanford type B aortic dissection during the perioperative period and can be recommended as an auxiliary drug for conventional antihypertensive drugs at the current stage.

14.
World J Gastroenterol ; 25(46): 6728-6742, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31857775

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) is abnormally expressed in various malignant tumors. In recent years, it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer. However, the clinical value of serum HULC in pancreatic cancer remains unclear, and there are few studies on how HULC regulates the biological function of pancreatic cancer cells. AIM: To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer, and its possible biological potential. METHODS: Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital, Central South University were assigned to the pancreatic cancer group and the benign disease group, respectively, and another 60 healthy subjects were enrolled as the normal group during the same period. HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells. Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues, serum, and cells. Western Blot was carried out to determine the expression of ß-catenin, c-myc, and cyclin D1 in cells, and the cell counting kit-8, flow cytometry, and Transwell assay were conducted to determine the proliferation, apoptosis and invasion of cells. RESULTS: Highly expressed in the tissues and serum of pancreatic cancer patients, HULC showed good clinical value in distinguishing between patients with pancreatic cancer, patients with benign pancreatic diseases and healthy subjects. HULC was related to pathological parameters including tumor size, T staging, M staging and vascular invasion, and the area-under-the-curve for evaluating these four parameters was 0.844, 0.834, 0.928 and 0.818, respectively. Patients with low expression of HULC had a significantly higher 3-year overall survival (OS) and 5-year OS than those with high expression. T staging, M staging, vascular invasion, and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer. Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells, promoted apoptosis, and inhibited the expression of Wnt/ß-catenin signaling pathway-related proteins, ß-catenin, c-myc, and cyclin D1. The Wnt/ß-catenin signaling pathway agonist (LiCl) restored proliferation, apoptosis, and invasion of pancreatic cancer cells with inhibited expression of HULC. CONCLUSION: HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer, which may affect the biological function of pancreatic cancer cells through the Wnt/ß-catenin signaling pathway.

15.
Indian J Cancer ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31736467

RESUMO

Objective: This study aimed to evaluate the changes and clinical significance of thrombomodulin (TM) and plasma protein C (PC) in patients with cancer before and after peripherally inserted central catheter placement (PICC). Materials and Methods: The levels of plasma TM and PC in 35 patients with cancer before and after PICC were measured by enzyme-linked immunosorbent assay, and the significance of the differences was analyzed. Results: TM was 3.57 ± 1.01 µg/L at 1 day after catheterization, which was significantly lower than the value of 4.41 ± 1.26 µg/L before catheterization; these values were 4.30 ± 1.81 and 4.73 ± 0.97 µg/L at 30 and 90 days after catheterization, respectively (F = 4.14, P < 0.05). PC was 3.32 ± 1.35 µg/L at 1 day after catheterization, which was significantly lower than the value of 5.32 ± 2.12 µg/L before catheterization; these values were 4.64 ± 2.44 and 5.83 ± 3.14 µg/L at 30 and 90 days after catheterization, respectively (F = 6.28, P < 0.01). There were no significant differences in platelet (PLT) counts, plasma D-D, and coagulation parameters among the four time points before and after catheterization. There was a positive correlation between TM and PC (r = 0.5420, P < 0.01) on day 1 after PICC line insertion. The levels of TM and PC were not related to PLT, plasma D-dimer, or various coagulation parameters. Conclusions: The levels of TM and PC in the patients 1 day after PICC were significantly decreased and showed a positive correlation, but were not related to PLT, plasma D-dimer, or coagulation function.

16.
Mutagenesis ; 34(5-6): 395-401, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31748817

RESUMO

There is overwhelming evidence that inflammation plays a key role in the pathogenesis of cancer and its progression. Inflammation is regulated through a complex network of genes and polymorphic variants in these genes have been found to be associated to risk of various human cancers, alone or in combination with environmental variables. Despite this, not much is known on the genetic variability of genes that regulate inflammation and risk of pancreatic ductal adenocarcinoma (PDAC). We performed a two-phase association study considering the genetic variability of 76 genes that are key players in inflammatory response. We analysed tagging single nucleotide polymorphisms (SNPs) and regulatory SNPs on 7207 PDAC cases and 7063 controls and observed several associations with PDAC risk. The most significant association was between the carriers of the A allele of the CCL4-rs1719217 polymorphism, which was reported to be also associated with the expression level of the CCL4 gene, and increased risk of developing PDAC (odds ratio = 1.12, 95% confidence interval = 1.06-1.18, P = 3.34 × 10-5). This association was significant also after correction for multiple testing, highlighting the importance of using potentially functional SNPs in order to discover more genetic variants associated with PDAC risk.

17.
Int J Med Sci ; 16(9): 1215-1220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588186

RESUMO

OBJECTIVE: Though living donor liver transplantation (LDLT) is commonly performed for pediatric patients with biliary atresia (BA), pulmonary hypertension (PH) is seldom encountered or reported previously. The aim of this study is mainly to identify the prevalence of PH in pediatric patients undergoing liver transplantation and assess whether PH significantly augment the operative risk and evaluate the outcomes in this series of patients. DESIGN: Retrospectively cohort study. SETTING: Renji hospital, Shanghai, China. PARTICIPANTS: This study comprised 161 pediatric patients undergoing LDLT. INTERVENTIONS: Patient diagnosed of PH in preoperative examination was compared to those without PH in intra- or post- operative complications or outcomes. MEASUREMENTS AND MAIN RESULTS: We collected clinical records of LDLT surgery for pediatric patients during the year of 2016 in our hospital. Results suggested that pediatric patients undergoing LDLT had a substantial number of PH with a prevalence of 16.1% in this study. No significant difference was identified between two groups of patients regarding intraoperative outcomes and postoperative complications and mortality. CONCLUSION: LDLT is a safe procedure in a selected group of BA patients with PH, however, further long-term clinical investigations and mechanical researches are needed.

18.
Mutagenesis ; 34(5-6): 391-394, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31606007

RESUMO

Pancreatic ductal adenocarcinoma is an aggressive and relatively rare cancer with a dismal 5-year survival rate and a clear genetic background. Genetic variants in taste receptors and taste-related genes have been associated with a variety of human traits and phenotypes among which several cancer types and pancreatic cancer risk factors. In this study, we analysed 2854 single-nucleotide polymorphisms in 50 taste-related genes, including 37 taste receptors. To cover all the genetic variability of the selected genes and to include also regulatory elements, we added 5000 nucleotides to both ends of each gene. We used a two-phase approach, with the PanScan data set (3314 cases and 3431 controls) as the discovery phase and PanC4 (3893 cases and 3632 controls) as validation phase, for a total of 7207 cases and 7063 controls. The datasets were downloaded from the NCBI database of genotypes and phenotypes (dbGaP). We observed that the taste 1 receptor member 2 (TAS1R2)-rs11261087 variant was associated with pancreatic cancer risk in both phases independently, with a consistent association of the T allele with decreased risk of developing the disease [phase 1 odds ratio (OR) = 0.89, 95% confidence interval (CI) 0.80-0.98; phase 2 OR = 0.91, 95% CI 0.83-0.99; all subjects together OR = 0.90, 95% CI 0.84-0.96, P = 0.002]. However, neither the association observed in the validation phase nor those observed in the joint analysis were statistically significant considering multiple testing. Functional studies are warranted to better understand the impact of the genetic variability of TAS1R2 on PDAC risk.

19.
Oncol Rep ; 42(5): 1689-1698, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545465

RESUMO

The aim of the present study was to screen differentially expressed miRNAs in vulvar squamous cell carcinoma (VSCC), observe the role of microRNA­4712­5p in VSCC and investigate its targets and regulatory mechanism. Differentially expressed miRNAs in human VSCC tissues were screened. microRNA­4712­5p was selected and its expression level was verified in clinical tissue samples and the VSCC cell line A431 by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis. The overexpression vector of microRNA­4712­5p was prepared and transfected into A431 cells; subsequently, cell invasion and metastasis were examined by Cell Counting Kit­8 and Transwell migration assays. Furthermore, the target gene of miRNA­4712­5p was predicted by bioinformatics and verified by The Dual­Luciferase® Reporter (DLR™) Assay System. The expression of phosphatase and tensin homologue (PTEN) and its downstream proteins, such as protein kinase B (PKB; AKT), glycogen synthase kinase (GSK)3ß and cyclin D1, were detected by western blot assays. The expression level of microRNA­4712­5p in VSCC tissues and the A431 cell line was found to be significantly increased, promoting proliferation and invasion of VSCC. The DLR™ assay indicated that PTEN was a target of miR­4712­5p. RT­qPCR revealed that PTEN expression was markedly lower in VSCC tissues compared with that in adjacent tissues. After A431 cells were transfected with the miRNA­4712­5p overexpression vector, phospho­AKT (p­AKT) and cyclin D1 expression were notably increased, but miRNA­4712­5p­targeted PTEN and phospho­GSK3ß (p­GSK3ß) protein markedly decreased. Therefore, microRNA­4712­5p can reduce the expression of PTEN, further affecting its downstream p­AKT, p­GSK3ß and cyclin D1 signaling pathways, promoting the proliferation and invasion of VSCC.

20.
J Clin Neurosci ; 69: 250-256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477463

RESUMO

Electroacupuncture (EA) is an adjuvant therapy for peripheral nerve injury (PNI). Both peripheral and central alterations contribute to the rehabilitation process. We employed diffusion tensor imaging (DTI) to investigate the diffusion plasticity of afferent and efferent pathways caused by EA in model of peripheral nerve injury and reparation. Twenty-four rats were divided into three groups: normal group, model group and intervention group. Rats of the model group and the intervention group underwent sciatic nerve transection and anastomosis. EA intervention was performed on the intervention group at ST-36 and GB-30 for three months. Gait assessment and DTI were conducted at days post-operative (DPO) 30, 60 and 90. We selected corticospinal tract, spinothalamic tract and internal capsule as regions of interest and analyzed diffusion metrics including fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). FA values and RD values displayed significant differences or obvious tendency while AD values maintained a stable level. RD values displayed better indicative performance than FA in internal capsule. The intervention group presented significant correlation between RD values and Regularity Index (RI) during the intervention period. The effect of EA on peripheral nerve injury repairing rats appeared to be accelerated recovery process of sensory and motor neural pathway. We proposed that RD was a potential in vivo indicator for structural plasticity caused by EA and PNI.


Assuntos
Eletroacupuntura , Cápsula Interna/fisiopatologia , Vias Neurais/fisiopatologia , Plasticidade Neuronal/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Animais , Imagem de Tensor de Difusão/métodos , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões
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