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1.
Cancer Res Treat ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588704

RESUMO

Purpose: Microtubule-associated protein 1 light chain 3 B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the Third Affiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolled patients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariate Cox regression analysis, independent risk factors for 5-year OS were cancer antigen 125, microvascular invasion, LC3B expression and lymph node metastasis. Except for the above 4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factors for 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and 0.747, respectively. Conclusion: The nomograms based on LC3B can be considered as effective models to predict postoperative survival for ICC patients.

2.
Sensors (Basel) ; 19(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652653

RESUMO

The demand for high-accuracy pressure sensors has increased with the advancement of technology in a wide variety of applications. However, it is generally difficult and expensive to improve the accuracy of the pressure sensor because it usually depends on the sensing principle and the internal physical structure of the pressure sensor, varying with its material and production process. Thus, a simple, low-cost, and generally applied post-processing method is proposed to improve the accuracy of pressure sensors. In this method, a micro-coating is cladded on the surface of the sensor, which effectively isolates the adverse effect of the external environment, similar to applying a "micro-protective clothing" on the pressure sensor. Experiments on seven pressure sensors are conducted, in which the micron-thin parylene polymer is utilized as the surface-deposited coating layer to demonstrate the improvement of accuracy. Results show that the accuracy was improved, with an average increase of approximately 62.54% than before cladding, while the sensitivity was almost unchanged. The principle of improving the accuracy of this method was also analyzed. The proposed simple, efficient, and low-cost method of cladding micro-coating for enhancing the accuracy of sensors can be widely applied in various fields of industrial automatic control.

3.
Neurotherapeutics ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664643

RESUMO

Previously, we reported that the neurosteroid allopregnanolone (Allo) promoted neural stem cell regeneration, restored cognitive function, and reduced Alzheimer's Disease (AD) pathology in the triple transgenic Alzheimer's mouse model (3xTgAD). To investigate the underlying systems biology of Allo action in AD models in vivo, we assessed the regulation of Allo on the bioenergetic system of the brain. Outcomes of these analysis indicated that Allo significantly reversed deficits in mitochondrial respiration and biogenesis and key mitochondrial enzyme activity and reduced lipid peroxidation in the 3xTgAD mice in vivo. To explore the mechanisms by which Allo regulates the brain metabolism, we conducted targeted transcriptome analysis. These data further confirmed that Allo upregulated genes involved in glucose metabolism, mitochondrial bioenergetics, and signaling pathways while simultaneously downregulating genes involved in Alzheimer's pathology, fatty acid metabolism, and mitochondrial uncoupling and dynamics. Upstream regulatory pathway analysis predicted that Allo induced peroxisome proliferator-activated receptor gamma (PPARG) and coactivator 1-alpha (PPARGC1A) pathways while simultaneously inhibiting the presenilin 1 (PSEN 1), phosphatase and tensin homolog (PTEN), and tumor necrosis factor (TNF) pathways to reduce AD pathology. Collectively, these data indicate that Allo functions as a systems biology regulator of bioenergetics, cholesterol homeostasis, and ß-amyloid reduction in the brain. These systems are critical to neurological health, thus providing a plausible mechanistic rationale for Allo as a therapeutic to promote neural cell function and reduce the burden of AD pathology.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31650832

RESUMO

Up to now, ferroptotic therapeutic strategies remain simplex, though ferroptosis has aroused extensive interest owing to its escape from the biocarriers of conventional therapeutic modalities. Herein, we construct a photothermal (PT)- and autophagy-enhanced ferroptotic therapeutic modality based on MnO2@HMCu2-xS nanocomposites (HMCM) for efficient tumor ablation. The HMCM possess PT-enhanced glutathione (GSH) depletion capability, thereby inducing PT-enhanced ferroptosis via the reinforced inactivation of glutathione peroxidase 4 (GPX4). Thereafter, the GSH-responsed Mn2+ release could generate reactive oxygen species (ROS) by Fenton-like reaction to reinforce the intracellular oxidative stress for the lipid hydroperoxides (LPO) accumulation in ferroptosis. Additionally, an autophagy promotor rapamycin (Rapa) was loaded into HMCM for sensitizing cells to ferroptosis, due to the indispensable role of autophagy in the ferroptosis process. The in vitro and in vivo data demonstrated the HMCM exhibited superior anticancer effect in human breast cancer models, and the combination therapeutic system afford the next generation of ferroptotic therapy for combatting malignant tumor.

5.
Chem Asian J ; 14(20): 3515-3530, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31553124

RESUMO

Metal-organic frameworks (MOFs) offer ample characteristics, such as easy synthesis, high surface area, tunable porosities, open metal sites, post-synthesis modification, making them attractive for diverse applications. Since magnetic particles can be positioned and separated by a magnetic field, magnetic framework composites (MFCs) have attracted tremendous attention. In this review, different methods of preparing MFCs, including direct mixing, in-situ growth of magnetic particles, embedding method, layer-by-layer growth method and encapsulation method, will be discussed in detail. Moreover, their applications in catalysis, adsorption, biomedicine and sensing will also be introduced.

6.
Shanghai Kou Qiang Yi Xue ; 28(3): 325-329, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489425

RESUMO

PURPOSE: To study the effect of quality control circle activity on improving nursing quality of patients with periodontitis. METHODS: One hundred and twenty patients with periodontitis admitted to our hospital from January 2016 to December 2017 were selected and divided into experimental group and control group according to the principle of random control, with 60 patients in each group. Patients in both groups received supragingival scaling, subgingival scaling and related symptomatic treatment, patients in the experimental group conducted nursing under the guidance of quality control circle, while patients in the control group received routine nursing. Satisfaction degree, therapeutic effect and gingival index, probe depth, gingival sulcus bleeding index, plaque index and periodontal attachment levels were recorded and compared between the two groups using SPSS 19.0 software package. RESULTS: After quality control circle to guide nursing, the patients' satisfaction (P=0.003) and the total effective rate of treatment was significantly higher than the control group(P=0.002), the incidence of oral health problems in the experimental group was significantly lower than the control group(P=0.037), PD, GI, SBI, PLI and AL levels in the experimental group were significantly lower than the control group(P=0.000). In addition to the tangible achievements,intangible results, such as quality control circles harmonious degree of nursing, sense of responsibility, communication, and problem solving ability, cohesion and quality control methods are improved distinctly in the experimental group. CONCLUSIONS: Quality control circle activity can improve nursing quality of patients with periodontitis.

7.
Clin Nutr ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472986

RESUMO

BACKGROUND & AIMS: The objective nutritional assessment indicators, body mass index (BMI), upper arm muscle circumference (MAMC), and triceps skinfold thickness (TSF), are often limited due to ascites. This study investigated the prognostic value of the third lumbar vertebrae skeletal muscle mass index (L3 SMI) in addition to the objective nutritional evaluation indicators (BMI, MAMC and TSF) in patients with liver cirrhosis and ascites. METHODS: In this retrospective analysis, a total of 147 patients with liver cirrhosis and ascites were included. The L3 SMI, BMI, MAMC and TSF were detected in all patients. The severity of liver disease was assessed by the Model End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) classification. These variables were compared between non-surviving and surviving patients who were classified according to 5-year mortality. RESULTS: Of the 147 patients, 62 (42.2%) died and 85 (57.8%) survived within 5 years. The L3 SMI of patients was significantly lower than that of the normal control group (39.58 ± 7.18 cm2/m2 vs. 53.73 ± 7.92 cm2/m,2p < 0.001). The L3 SMI (OR 4.02; 95% CI 2.17-9.63; p < 0.001), MELD score (OR 2.11; 95% CI 1.12-4.13; p < 0.001) and CTP class (OR 2.69; 95% CI 1.09-5.06; p < 0.001) were independent predictive indicators of 5-year mortality. Furthermore, the performance of the two variables (L3 SMI and MELD) together (AUROC: 0.812) was significantly better than that of MELD alone (AUROC: 0.787) for prediction of 5-year mortality (p < 0.001). CONCLUSION: Compared with MAMC, TSF and BMI, L3 SMI is an independent risk factor for 5-year mortality in patients with liver cirrhosis and ascites. Further nutritional intervention studies are needed to confirm the impact of the L3 SMI index on clinical outcomes.

8.
Toxicol Lett ; 316: 85-93, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513885

RESUMO

BACKGROUND: Apoptosis-stimulating protein 2 of p53 (ASPP2) has a variety of biological functions, and is involved in cellular apoptosis, autophagy and inflammatory reaction. However, the role of ASPP2 in acute hepatic injury remains unclear. METHODS: We established an animal model of acute hepatic injury by intraperitoneal injection of CCl4. The expression profile of ASPP2 was measured in wild type (ASPP2+/+) mice with acute hepatic injury induced by CCl4. Hepatic pathological changes and liver function, apoptosis, inflammation and autophagic levels were measured in ASPP2+/+and ASPP2 haploid deletion (ASPP2+/-) mice with acute hepatic injury, respectively. After 3-methyladenine (3-MA) treatment, indicators of hepatic injury were observed in ASPP2+/+and ASPP2+/- mice with CCl4 injection. RESULTS: During the development of acute hepatic injury, ASPP2 expression significantly upregulated at 24 h and 48 h after CCl4 injection. ASPP2 haplotype deletion protected against acute hepatic injury, and this was mainly reflected in decreased ALT and AST levels, less hepatic tissue hemorrhage and necrosis, and reduced cellular inflammation and apoptosis in ASPP2+/- mice compared with ASPP2+/+ mice with acute hepatic injury. ASPP2 haploid deletion activates autophagy in mice with acute hepatic injury, and protects mice from acute hepatic injury via the autophagic signal pathway. CONCLUSION: ASPP2 haplotype deletion protected mice against acute hepatic injury through autophagy activation, which inhibited inflammation and apoptosis in acute hepatic injury.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/metabolismo , Proteínas Supressoras de Tumor/deficiência , Alanina Transaminase/sangue , Animais , Apoptose , Aspartato Aminotransferases/sangue , Autofagia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Predisposição Genética para Doença , Haplótipos , Fígado/patologia , Masculino , Camundongos Knockout , Necrose , Fenótipo , Transdução de Sinais , Fatores de Tempo , Proteínas Supressoras de Tumor/genética
9.
Eur J Med Chem ; 182: 111636, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466017

RESUMO

Developing novel antimicrobial agents is a top priority in fighting against bacterial resistance. Thus, a series of new monomer and dimer peptides were designed and synthesized by conjugating fatty acids at the N-terminus of partial d-amino acid substitution analogues of anoplin and dimerization. The new peptides exhibited more efficient killing of gram-negative and gram-positive bacteria, including methicillin-resistant Staphylococcus aureus compared with the parent peptide anoplin, and the dimer peptides were superior to the monomer peptides. It was important that the new peptides displayed low impact on bacterial resistance development. In addition, the antimicrobial activities were not significantly influenced by a physiological salt environment. They also presented high stability in the presence of protease or serum. Almost all of the new peptides had better selectivity towards anionic bacterial membranes over zwitterionic mammalian cell membranes. Moreover, the new peptides displayed synergistic or additive effects when used together with the antibiotics rifampicin and polymyxin B. These results showed that the new peptides could also prevent the formation of bacterial biofilms. Furthermore, outer/inner membrane permeabilization and cytoplasmic membrane depolarization experiments revealed that the new peptides had strong membrane permeabilization and depolarization. Confocal laser scanning microscopy, flow cytometry analysis and scanning electron microscopy further demonstrated that the new peptides could damage the integrity of the bacterial membrane. Finally, a DNA-binding affinity assay showed that the new peptides could bind to bacterial DNA. In summary, the conjugation of fatty acids at the N-terminus of peptides and dimerization are promising strategies for obtaining potent antimicrobial agents.

10.
J Agric Food Chem ; 67(34): 9468-9476, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31379158

RESUMO

The aroma quality of citrus fruit is determined by volatiles that are present at extremely low levels in the citrus fruit juice sacs; it can be greatly improved by increasing volatiles. In this study, we showed that the contents of cis- and trans-linalool oxides were significantly increased in the juice sacs of three pummelos artificially pollinated with the Citrus mangshanensis (MS) pollen. A novel cytochrome P450 78A7 gene (CitLO1) was significantly upregulated in the juice sacs of Huanong Red pummelo pollinated with MS pollen in comparison to that with open pollination. Compared to wild-type tobacco Bright-Yellow2 cells, transgenic cells overexpressing CitLO1 promoted a 3- to 4-fold more conversion of (-)-linalool to cis- and trans-linalool oxides. Overall, our results suggest that MS pollen has a xenia effect on pummelo fruit aroma quality, and CitLO1 is a linalool oxide synthase gene that played an important role in the xenia effect.


Assuntos
Citrus/metabolismo , Cicloexanóis/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Frutas/metabolismo , Monoterpenos/metabolismo , Proteínas de Plantas/genética , Compostos de Tritil/metabolismo , Citrus/química , Citrus/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Frutas/química , Frutas/genética , Humanos , Odorantes/análise , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/metabolismo , Paladar , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo
11.
Endocr J ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31366822

RESUMO

In the present study, we investigate the effect of reduced cystathionine-γ-lyase (CSE) expression in high glucose induced metalloproteinases14 (MMP14) expression in adipocytes and visceral adipose tissues. Diabetic mice were prepared by injections of STZ and the expression of CSE, MMP14 in visceral adipose tissues were determined. Adipocytes were differentiated from 3T3-L1 cells and treated with high glucose (HG), H2S slow-releasing compound GYY4137 or transfected with CSE siRNA. Then the expression of CSE, MMP14 were determined by western blotting. CSE knockout mice were generated by crossing CSE+/- heterozygous mice and given intraperitoneally (i.p.) injections of GYY4137, and then the expression of CSE and MMP14 in visceral adipose tissues were determined by quantitative real-time PCR and western blotting. The following results were obtained from the study. In adipose tissues of diabetic mice, the mRNA and protein expression of MMP14 increased while the mRNA and protein expression of CSE decreased. In 3T3-L1 adipocytes, both HG DMEM and CSE siRNA transfection increased the mRNA and protein of MMP14. The addition of GYY4137 inhibited HG-induced upregulation of MMP14 expression. In CSE knockout mice, the mRNA and protein expression of MMP14 in adipose tissues increased, which could be inhibited by i.p. injections of GYY4137. In conclusion, high glucose increased the expression of MMP14 in adipocytes and visceral adipose tissues through inhibiting the expression of CSE.

12.
Discov Med ; 28(151): 17-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31465722

RESUMO

Hepatobiliary cancers have poor prognosis due to their high level of invasiveness, distant metastasis, and chemotherapy resistance. Hepatocellular carcinoma is the most common type of hepatobiliary cancers representing the fourth leading cause of cancer death worldwide. There is an urgent need to identify the molecular drivers of hepatobiliary cancers to improve the therapeutic outcomes and patient prognosis. Histone modification is an important biological process that is critical in the regulation of epigenetic maintenance and modifications which in turn exert critical impacts on gene expression and chromatin structure stability. Histones may undergo a series of enzyme-catalyzed post-translational modifications such as acetylation, methylation, phosphorylation, ubiquitination, SUMOylating, crotonylation, and 2-hydroxyisobutyrylation. Dysregulation of histone-modifying enzyme may cause multiple diseases including cancers. As such, histone-modifying enzymes constitute a group of potential therapeutic targets. The aim of this review is to summarize the current understanding of the role of histone modification enzymes in regulating epigenetic alterations, cancer development, and their potential as therapeutic targets for hepatobiliary cancers.

13.
Asian J Androl ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31187778

RESUMO

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg-1) on day 36 or a dose of 40 mg kg-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.

14.
Mol Genet Genomic Med ; 7(6): e689, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31044564

RESUMO

BACKGROUND: Liver transplantation is an effective therapy for end-stage liver diseases and acute liver failure. After the operation, however, recipients may suffer grafts loss induced by alloimmune reaction, which is termed as acute allograft rejection. The interaction between costimulatory molecules, CD276, and its ligand, TREML2, promotes T cell-mediated immune response, as well as acute or chronic allograft rejection. Our research aimed at correlating genetic polymorphisms of CD276/TREML2 with acute rejection, and evaluating its prognostic value of acute rejection after liver transplantation. METHODS: The study enrolled a total of 388 recipients. Among them, acute allograft rejection was observed in 54 cases. We performed single nucleotide polymorphism genotyping of CD276, including rs11072431, rs11574495, rs12593558, rs12594627, rs2127015, rs3816661 and rs7176654, and TREML2, including rs4714431, rs6915083, rs7754593, and rs9394767 from preoperative peripheral blood genome DNA. RESULTS: We found rs2127015 of CD276, rs6915083 and rs7754593 of TREML2, and HBV infection as well were associated with acute rejection. And, rs2127015 influences CD276 expression. Moreover, we established a risk assessment model, composited by statistically proved risk factors. CONCLUSION: By integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.

15.
Hereditas ; 156: 14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057347

RESUMO

Background: Grapevine is an important fruit crop grown worldwide, and its cultivars are mostly derived from the European species Vitis vinifera, which has genes for high fruit quality and adaptation to a wide variety of climatic conditions. Disease resistance varies substantially across grapevine species; however, the molecular mechanisms underlying such variation remain uncharacterized. Results: The anatomical structure and disease symptoms of grapevine leaves were analyzed for two grapevine species, and the critical period of resistance of grapevine to pathogenic bacteria was determined to be 12 h post inoculation (hpi). Differentially expressed genes (DEGs) were identified from transcriptome analysis of leaf samples obtained at 12 and 36 hpi, and the transcripts in four pathways (cell wall genes, LRR receptor-like genes, WRKY genes, and pathogenesis-related (PR) genes) were classified into four co-expression groups by using weighted correlation network analysis (WGCNA). The gene VdWRKY53, showing the highest transcript level, was introduced into Arabidopsis plants by using a vector containing the CaMV35S promoter. These procedures allowed identifying the key genes contributing to differences in disease resistance between a strongly resistant accession of a wild grapevine species Vitis davidii (VID) and a susceptible cultivar of V. vinifera, 'Manicure Finger' (VIV). Vitis davidii, but not VIV, showed a typical hypersensitive response after infection with a fungal pathogen (Coniella diplodiella) causing white rot disease. Further, 20 defense-related genes were identified, and their differential expression between the two grapevine species was confirmed using quantitative real-time PCR analysis. VdWRKY53, showing the highest transcript level, was selected for functional analysis and therefore over-expressed in Arabidopsis under the control of the CaMV35S promoter. The transgenic plants showed enhanced resistance to C. diplodiella and to two other pathogens, Pseudomonas syringae pv. tomato DC3000 and Golovinomyces cichoracearum. Conclusion: The consistency of the results in VID and transgenic Arabidopsis indicated that VdWRKY53 might be involved in the activation of defense-related genes that enhance the resistance of these plants to pathogens. Thus, the over-expression of VdWRKY53 in transgenic grapevines might improve their resistance to pathogens.

16.
Plant Sci ; 283: 116-126, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128681

RESUMO

Ethylene response factors (ERFs) are known to regulate fruit ripening. However, the ERF regulatory networks are not clear. In this study, we have shown that peach (Prunus persica) PpeERF2 regulates fruit ripening through suppressing the expression of two ABA biosynthesis genes (PpeNCED2, PpeNCED3) and a cell wall degradation gene (PpePG1). The transcript levels of PpeERF2 in fruit were opposite to that of PpeNCED2, PpeNCED3 and PpePG1 during ripening and in response to various ripening treatments. PpeERF2 was found to bind to the PpeNCED2, PpeNCED3 and PpePG1 promotors as demonstrated by yeast one-hybrid (Y1H) and EMSA assays; and further found to repress the promoter activities of the three genes in tobacco leaf tissues after Agrobacterium infiltration. Taken together, these results provide new information for a better understanding of the crosstalk network between ethylene signaling, cell wall degradation and ABA biosynthesis during fruit ripening.


Assuntos
Ácido Abscísico/biossíntese , Parede Celular/metabolismo , Frutas/metabolismo , Proteínas de Plantas/fisiologia , Prunus persica/metabolismo , Proteínas Repressoras/fisiologia , Ácido Abscísico/metabolismo , Clonagem Molecular , Ensaio de Desvio de Mobilidade Eletroforética , Frutas/crescimento & desenvolvimento , Frutas/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase , Prunus persica/genética , Prunus persica/crescimento & desenvolvimento , Prunus persica/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Alinhamento de Sequência , Técnicas do Sistema de Duplo-Híbrido
17.
Proc Natl Acad Sci U S A ; 116(18): 9078-9083, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30979801

RESUMO

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

18.
Dermatol Surg ; 45(10): 1245-1252, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30893166

RESUMO

BACKGROUND: Striae gravidarum is a common skin condition resulting after pregnancy, caused by fibroblast dysfunction. Although not considered a disease, it may be considered cosmetically unpleasant to sufferers and remains as a therapeutic challenge to date. OBJECTIVE: To evaluate the efficacy and safety of a sublative bipolar fractional radiofrequency (FRF) system, associated with 0.1% topical tretinoin, in treating striae gravidarum. MATERIALS AND METHODS: Eighteen Chinese women with striae gravidarum on the abdomen were enrolled in the study. The target area of each patient was divided into 4 sites randomly: control, tretinoin, FRF, and tretinoin and FRF. Fractional RF was used 3 times, with 3-month intervals. Changes to striae gravidarum were evaluated through subjective scaling and objective measures, using both high-frequency ultrasound and histological study. RESULTS: Both subjective assessment and skin thickness differences demonstrated significant improvement in the combination site (p < .001). Average optical density and density percentage of neocollagen and elastic fibers were also markedly increased in the combination site (p < .05). The adverse effects of FRF were limited to mild pain and transient erythema, edema, and microcrusts. CONCLUSION: The combined therapy of FRF and topical tretinoin may be a potential method in treating striae gravidarum, with satisfactory efficacy and limited side effects.

19.
Target Oncol ; 14(2): 187-195, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30887420

RESUMO

BACKGROUND: Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE: We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics. METHODS: Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman's correlation coefficient. RESULTS: Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399-3.966, p = 0.001; and HR 1.994; 95% CI 1.360-2.923, p < 0.001, respectively). In our cohort, α1-globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α1-globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001). CONCLUSIONS: High serum α1-globulin correlates with high tumor load. Serum α1-globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.

20.
J Exp Bot ; 70(10): 2759-2771, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-30840066

RESUMO

Neohesperidosides are disaccharides that are present in some flavonoids and impart a bitter taste, which can significantly affect the commercial value of citrus fruits. In this study, we identified three flavonoid-7-O-di-glucosyltransferase (dGlcT) genes closely related to 1,2-rhamnosyltransferase (1,2RhaT) in citrus genomes. However, only 1,2RhaT was directly linked to the accumulation of neohesperidoside, as demonstrated by association analysis of 50 accessions and co-segregation analysis of an F1 population derived from Citrus reticulata × Poncirus trifoliata. In transgenic tobacco BY2 cells, over-expression of CitdGlcTs resulted in flavonoid-7-O-glucosides being catalysed into bitterless flavonoid-7-O-di-glucosides, whereas over-expression of Cit1,2RhaT converted the same substrate into bitter-tasting flavonoid-7-O-neohesperidoside. Unlike 1,2RhaT, during citrus fruit development the dGlcTs showed an opposite expression pattern to CHS and CHI, two genes encoding rate-limiting enzymes of flavonoid biosynthesis. An uncoupled availability of dGlcTs and substrates might result in trace accumulation of flavonoid-7-O-di-glucosides in the fruit of C. maxima (pummelo). Past human selection of the deletion and functional mutation of 1,2RhaT has led step-by-step to the evolution of the flavor-related metabolic network in citrus. Our research provides the basis for potentially improving the taste in citrus fruit through manipulation of the network by knocking-out 1,2RhaT or by enhancing the expression of dGlcT using genetic transformation.

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