Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 69
Filter
1.
Hernia ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573484

ABSTRACT

PURPOSE: The safety of laparoscopic inguinal-hernia repair must be carefully evaluated in elderly patients. Very little is known regarding the safety of the laparoscopic approach in elderly patients under surgical and medical co-management (SMC). Therefore, this study evaluated the safety of the laparoscopic approach in elderly patients, especially patients with multiple comorbidities under SMC. METHODS: From January 2012 to December 2021, patients aged ≥ 65 years who underwent open or laparoscopic inguinal-hernia repair during hospitalization were consecutively enrolled. Postoperative outcomes included major and minor operation-related complications, and other adverse events. To reduce potential selection bias, propensity score matching was performed between open and laparoscopic groups based on patients' demographics and comorbidities. RESULTS: A total of 447 elderly patients who underwent inguinal-hernia repair were enrolled, with 408 (91.3%) underwent open and 39 (8.7%) laparoscopic surgery. All postoperative outcomes were comparable between open and laparoscopic groups after 1:1 propensity score matching (all p > 0.05). Moreover, compared to the traditional care group (n = 360), a higher proportion of the SMC group (n = 87) was treated via the laparoscopic approach (18.4% vs. 6.4%, p = 0.00). In the laparoscopic approach subgroup (n = 39), patients in the SMC group (n = 16) were older with multiple comorbidities but were at higher risks of only minor operation-related complications, compared to those in the traditional care group. CONCLUSIONS: Laparoscopic inguinal-hernia repair surgery is safe for elderly patients, especially those with multiple comorbidities under SMC.

3.
Neural Dev ; 17(1): 8, 2022 08 24.
Article in English | MEDLINE | ID: mdl-36002881

ABSTRACT

Molecular profiles of neurons influence neural development and function but bridging the gap between genes, circuits, and behavior has been very difficult. Here we used single cell RNAseq to generate a complete gene expression atlas of the Drosophila larval central nervous system composed of 131,077 single cells across three developmental stages (1 h, 24 h and 48 h after hatching). We identify 67 distinct cell clusters based on the patterns of gene expression. These include 31 functional mature larval neuron clusters, 1 ring gland cluster, 8 glial clusters, 6 neural precursor clusters, and 13 developing immature adult neuron clusters. Some clusters are present across all stages of larval development, while others are stage specific (such as developing adult neurons). We identify genes that are differentially expressed in each cluster, as well as genes that are differentially expressed at distinct stages of larval life. These differentially expressed genes provide promising candidates for regulating the function of specific neuronal and glial types in the larval nervous system, or the specification and differentiation of adult neurons. The cell transcriptome Atlas of the Drosophila larval nervous system is a valuable resource for developmental biology and systems neuroscience and provides a basis for elucidating how genes regulate neural development and function.


Subject(s)
Drosophila , Transcriptome , Animals , Gene Expression Regulation, Developmental , Larva , Neuroglia , Neurons
4.
Anim Genet ; 53(1): 101-107, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34904261

ABSTRACT

Bird feathers are the product of interactions between natural and artificial selection. Feather-related traits are important for chicken selection and breeding. Frizzle feather is characterized by the abnormally development of feathers in chickens. In the current study, frizzle feather characteristics were observed in a local breed called Xiushui Yellow Chicken in Jiangxi, China. To determine the molecular mechanisms that underlie frizzle feather in Xiushui Yellow Chicken, four populations of three breeds (Xiushui Yellow Chicken with frizzle feathers, Xiushui Yellow Chicken with normal feathers, Guangfeng White-Ear Yellow Chicken, and Ningdu Yellow Chicken) were selected for whole-genome resequencing. Using a comparative genome strategy and genome-wide association study, a missense mutation (g.5281494A>G) and a 15-bp deletion (g.5285437-5285451delGATGCCGGCAGGACG) in KRT75L4 were identified as candidate mutations associated with frizzle feather in Xiushui Yellow Chicken. Based on genotyping performed in a large Xiushui Yellow Chicken population, the g.5285437-5285451delGATGCCGGCAGGACG mutation in KRT75L4 was confirmed as the putative causative mutation of frizzle feather. These results deepen the understanding of the molecular mechanisms responsible for frizzle feather, as well as facilitating the molecular detection and selection of the feather phenotype in Xiushui Yellow Chickens.


Subject(s)
Chickens/physiology , Feathers/anatomy & histology , Gene Deletion , Genome-Wide Association Study/veterinary , Mutation, Missense/physiology , Animals , Chickens/genetics , Feathers/growth & development
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(8): 1243-1249, 2021 Aug 20.
Article in Chinese | MEDLINE | ID: mdl-34549717

ABSTRACT

OBJECTIVE: To explore the risk factors of atrial thrombosis in patients with nonvalvular atrial fibrillation(NVAF)with low CHA2DS2-VASc scores at admission (≤1 for male and ≤2 for female patients). METHODS: We retrospectively analyzed the clinical data of 10 382 patients with NVAF undergoing transesophageal echocardiography in our hospital from 2009 to 2019, and enrolled 48 NVAF patients with thrombosis as the observation group and another 240 NVAF patients without thrombosis as the control group.The baseline characteristics, biochemical indicators, and echocardiographic findings of the patients were analyzed using univariate analysis, multivariate logistic regression analysis and Pearson correlation analysis. RESULTS: The baseline data did not differ significantly between the two groups (P > 0.05).Compared with those in the control group, the patients with atrial thrombosis had an increased left atrial diameter (LAD; P < 0.001), a greater likelihood of hypertrophic cardiomyopathy (HCM; P < 0.001), significantly higher levels of C-reactive protein (CRP; P < 0.05) and uric acid (P < 0.001), and greater standard deviation of red blood cell distribution width(RDW-SD; P < 0.001).LAD(P < 0.001), HCM(P < 0.05)and CRP(P < 0.05) were identified as the independent factors affecting the occurrence of atrial thrombosis in patients with low CHA2DS2-VASc scores. CONCLUSIONS: LAD enlargement, HCM, and an elevated CRP level are independent risk factors for atrial thrombosis in NVAF patients with low CHA2DS2-VASc scores.Active anticoagulation therapy should be administered for these patients once these risk factors are detected to prevent the occurrence of stroke.


Subject(s)
Atrial Fibrillation , Stroke , Thromboembolism , Thrombosis , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Female , Humans , Male , Retrospective Studies , Risk Assessment , Risk Factors , Thrombosis/epidemiology , Thrombosis/etiology
7.
Physiol Res ; 70(5): 671-685, 2021 11 29.
Article in English | MEDLINE | ID: mdl-34505522

ABSTRACT

Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Genes, Tumor Suppressor , Neoplasms/metabolism , Phosphoproteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Humans , Neoplasms/genetics , Phosphoproteins/genetics
8.
Zhonghua Yi Xue Za Zhi ; 101(28): 2228-2232, 2021 Jul 27.
Article in Chinese | MEDLINE | ID: mdl-34333936

ABSTRACT

Objective: To evaluate the clinical effect of oral contraceptive (OC) pretreatment on the outcome of gonadotropin releasing hormone antagonist (GnRH-a) protocol in patients with non-polycystic ovary syndrome. Methods: From January 2017 to May 2019, a total of 436 patients undergoing in vitro fertilization and embryo transfer/Intracytoplasmic sperm injection (IVF-ET/ICSI) treatment in Peking University First Hospital reproductive center clinic were included in this retrospective cohort study. A total of 144 patients (147 cycles) used OC pretreatment prior to GnRH-a protocol and 292 patients (306 cycles) used GnRH-a protocol without OC pretreatment. The drug usage as well as pregnant outcomes between groups were examined. The primary outcome was the cumulative clinical pregnancy rate of oocyte retrieval cycle and the secondary outcome included the number of oocytes, MⅡ oocytes, embryos and clinical pregnancy rate of fresh embryo transfer cycle. Results: The median ages (and Q1, Q3) of OC pretreatment group and non-OC group were 33 (30,36) and 34 (30,38) years old, respectively. The number of MⅡ oocytes was higher in OC pretreatment group (7/9) than in non-OC group (6/8) (P=0.002). The significant difference were not found in the cumulative clinical pregnancy rate of each oocyte retrieval cycle (61.7% vs 54.6%), the clinical pregnancy rate of fresh embryo transfer cycle (34.4% vs 35.6%), and the number of oocytes (9 vs 8) and embryos (6 vs 6) between groups. Conclusion: Our findings suggest that compared to non-OC pretreatment group, pretreatment with OC is associated with more MⅡ oocytes, and with an increasing trend of the cumulative clinical pregnancy rate in non-polycystic ovary syndrome patients undergoing fresh IVF-ET/ICSI.


Subject(s)
Contraceptives, Oral , Ovulation Induction , Female , Fertilization in Vitro , Gonadotropin-Releasing Hormone , Hormone Antagonists , Humans , Pregnancy , Pregnancy Rate , Retrospective Studies
10.
Cancer Cell ; 39(3): 361-379.e16, 2021 03 08.
Article in English | MEDLINE | ID: mdl-33417831

ABSTRACT

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Papillomavirus Infections/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/genetics , Adult , Aged , Aged, 80 and over , ErbB Receptors/genetics , Female , Humans , Immunotherapy/methods , Male , Middle Aged , Papillomavirus Infections/drug therapy , Papillomavirus Infections/virology , Proteogenomics/methods , Proteomics/methods , Young Adult
11.
Clin Gastroenterol Hepatol ; 19(6): 1189-1199.e30, 2021 06.
Article in English | MEDLINE | ID: mdl-32445952

ABSTRACT

BACKGROUND & AIMS: A high-fat diet has been associated with an increased risk of ulcerative colitis (UC). We studied the effects of a low-fat, high-fiber diet (LFD) vs an improved standard American diet (iSAD, included higher quantities of fruits, vegetables, and fiber than a typical SAD). We collected data on quality of life, markers of inflammation, and fecal markers of intestinal dysbiosis in patients with UC. METHODS: We analyzed data from a parallel-group, cross-over study of 17 patients with UC in remission or with mild disease (with a flare within the past 18 mo), from February 25, 2015, through September 11, 2018. Participants were assigned randomly to 2 groups and received a LFD (10% of calories from fat) or an iSAD (35%-40% of calories from fat) for the first 4-week period, followed by a 2-week washout period, and then switched to the other diet for 4 weeks. All diets were catered and delivered to patients' homes, and each participant served as her or his own control. Serum and stool samples were collected at baseline and week 4 of each diet and analyzed for markers of inflammation. We performed 16s ribosomal RNA sequencing and untargeted and targeted metabolomic analyses on stool samples. The primary outcome was quality of life, which was measured by the short inflammatory bowel disease (IBD) questionnaire at baseline and week 4 of the diets. Secondary outcomes included changes in the Short-Form 36 health survey, partial Mayo score, markers of inflammation, microbiome and metabolome analysis, and adherence to the diet. RESULTS: Participants' baseline diets were unhealthier than either study diet. All patients remained in remission throughout the study period. Compared with baseline, the iSAD and LFD each increased quality of life, based on the short IBD questionnaire and Short-Form 36 health survey scores (baseline short IBD questionnaire score, 4.98; iSAD, 5.55; LFD, 5.77; baseline vs iSAD, P = .02; baseline vs LFD, P = .001). Serum amyloid A decreased significantly from 7.99 mg/L at baseline to 4.50 mg/L after LFD (P = .02), but did not decrease significantly compared with iSAD (7.20 mg/L; iSAD vs LFD, P = .07). The serum level of C-reactive protein decreased numerically from 3.23 mg/L at baseline to 2.51 mg/L after LFD (P = .07). The relative abundance of Actinobacteria in fecal samples decreased from 13.69% at baseline to 7.82% after LFD (P = .017), whereas the relative abundance of Bacteroidetes increased from 14.6% at baseline to 24.02% on LFD (P = .015). The relative abundance of Faecalibacterium prausnitzii was higher after 4 weeks on the LFD (7.20%) compared with iSAD (5.37%; P = .04). Fecal levels of acetate (an anti-inflammatory metabolite) increased from a relative abundance of 40.37 at baseline to 42.52 on the iSAD and 53.98 on the LFD (baseline vs LFD, P = .05; iSAD vs LFD, P = .09). The fecal level of tryptophan decreased from a relative abundance of 1.33 at baseline to 1.08 on the iSAD (P = .43), but increased to a relative abundance of 2.27 on the LFD (baseline vs LFD, P = .04; iSAD vs LFD, P = .08); fecal levels of lauric acid decreased after LFD (baseline, 203.4; iSAD, 381.4; LFD, 29.91; baseline vs LFD, P = .04; iSAD vs LFD, P = .02). CONCLUSIONS: In a cross-over study of patients with UC in remission, we found that a catered LFD or iSAD were each well tolerated and increased quality of life. However, the LFD decreased markers of inflammation and reduced intestinal dysbiosis in fecal samples. Dietary interventions therefore might benefit patients with UC in remission. ClinicalTrials.gov no: NCT04147598.


Subject(s)
Colitis, Ulcerative , Quality of Life , Cross-Over Studies , Diet , Dysbiosis , Feces , Female , Humans , Inflammation , Male
12.
Zhonghua Yi Xue Za Zhi ; 100(32): 2503-2506, 2020 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-32829596

ABSTRACT

Objective: To compare the effects of vestibular rehabilitation training and drug therapy on the symptoms of vertigo and disability in patients with vestibular peripheral vertigo. Methods: This prospective study was enrolled 43 patients with vestibular peripheral vertigo who admitted to the outpatient department of Eye & ENT Hospital of Fudan University from January 2018 to December 2018. They were randomly divided into two groups: control group (drug treatment group) and experimental group (drug treatment combined rehabilitation training group). All patients filled in the first vertigo disability rating scale (DHI), specific activity balance confidence scale (ABC) and anxiety self-rating scale (SAS) on the day of treatment and at two, four and eight weeks after treatment intervention, and the data were statistically analyzed. Results: There was no significant difference in gender, age and body weight between the two groups (P>0.05). After treatment (Control group (4w) : DHI (45.5±30.6) , ABC (86.9±12.4) , SAS (37.9±8.2) Experimental group (8w) : DHI (34.8±28.5) , SAS (35.7±7.9) ) , the three scales of the two groups were better than before treatment (Control group: DHI (59.2±25.9) , ABC (79.7±16.7) ,SAS (41.1±6.8) ; Experimental group: DHI (55.2±20.5) , ABC (80.3±18.3) , SAS (41.9±9.1) ) . The comparison of data before and after treatment in each group according to treatment time indicated that DHI and ABC scores in the experimental group showed that the DHI and ABC scores of the experimental group changed significantly at 2 weeks after treatment, and the SAS scores changed at 4 weeks after treatment. The difference was statistically significant (P<0.05). However, there was a statistically significant difference between the control group DHI score 4 weeks after treatment and SAS score 8 weeks after treatment (P<0.05). ABC score did not show statistical difference (P>0.05). Conclusion: The subjective symptoms and anxiety of vertigo and disability in the two groups improved obviously after treatment. Compared with drug therapy alone, drug therapy combined with vestibular rehabilitation training can significantly improve patients' subjective symptoms of vertigo and disability, as well as their anxiety and depression, so as to improve their overall quality of life.


Subject(s)
Dizziness , Quality of Life , Vertigo , Anxiety , Humans , Prospective Studies , Vertigo/therapy
13.
Ann Oncol ; 31(6): 760-768, 2020 06.
Article in English | MEDLINE | ID: mdl-32240794

ABSTRACT

BACKGROUND: The tumor immune microenvironment can provide prognostic and predictive information. A previously validated ImmunoScore of Gastric Cancer (ISGC) evaluates both lymphoid and myeloid cells in the tumor core and invasive margin with immunohistochemical staining of surgical specimens. We aimed to develop a noninvasive radiomics-based predictor of ISGC. PATIENTS AND METHODS: In this retrospective study including four independent cohorts of 1778 patients, we extracted 584 quantitative features from the intratumoral and peritumoral regions on contrast-enhanced computed tomography images. A radiomic signature [radiomics ImmunoScore (RIS)] was constructed to predict ISGC using regularized logistic regression. We further evaluated its association with prognosis and chemotherapy response. RESULTS: A 13-feature radiomic signature for ISGC was developed and validated in three independent cohorts (area under the curve = 0.786, 0.745, and 0.766). The RIS signature was significantly associated with both disease-free and overall survival in the training and all validation cohorts [hazard ratio (HR) range: 0.296-0.487, all P < 0.001]. In multivariable analysis, the RIS remained an independent prognostic factor adjusting for clinicopathologic variables (adjusted HR range: 0.339-0.605, all P < 0.003). For stage II and stage III disease, patients with a high RIS derived survival benefit from adjuvant chemotherapy {HR = 0.436 [95% confidence interval (CI) 0.253-0.753], P = 0.002; HR = 0.591 (95% CI 0.428-0.818), P < 0.001, respectively}, whereas those with a low RIS did not. CONCLUSION: The RIS is a reliable tool for evaluation of immunoscore and retains the prognostic significance in gastric cancer. Future prospective studies are required to confirm its potential to predict treatment response and select patients who will benefit from chemotherapy.


Subject(s)
Stomach Neoplasms , Chemotherapy, Adjuvant , Humans , Prognosis , Prospective Studies , Retrospective Studies , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/drug therapy , Tumor Microenvironment
14.
Eur Rev Med Pharmacol Sci ; 23(18): 8109-8114, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31599438

ABSTRACT

OBJECTIVE: To explore the correlations of interleukin-6 (IL-6) and C-reactive protein (CRP) gene polymorphisms with pulmonary heart disease (PHD). PATIENTS AND METHODS: A total of 98 patients with PHD and 102 healthy persons receiving physical examinations were enrolled. Their general clinical information was collected, and the levels of IL-6 and CRP in the plasma were determined. The pulmonary functions and blood gas were detected, and the TaqMan-minor groove binder (MGB) probe was used to detect the polymorphisms of IL-6 rs1800796 and CRP rs1800796. RESULTS: Observation group had higher levels of IL-6 and CRP than control group (p<0.05). The forced expiratory volume in 1 second (FEV1) (%), FEV1/forced vital capacity (FVC) ratio (%), and arterial partial pressure of oxygen (PaO2) in observation group were lower than those in control group (p<0.05), but the arterial partial pressure of carbon dioxide (PaCO2) was higher than that in control group (p<0.05). There were differences in the distribution frequencies of the genotypes and alleles of IL-6 rs1800796 and CRP rs1800796 between the two groups (p<0.05). CONCLUSIONS: IL-6 and CRP are correlated with the onset of PHD, and there are also correlations between the polymorphisms of IL-6 rs1800796 and CRP rs2794521 and the disease.


Subject(s)
C-Reactive Protein/genetics , Interleukin-6/genetics , Pulmonary Heart Disease/genetics , Blood Gas Analysis , Carbon Dioxide/metabolism , Case-Control Studies , Female , Forced Expiratory Volume , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Oxygen/metabolism , Partial Pressure , Polymorphism, Single Nucleotide , Pulmonary Heart Disease/metabolism , Pulmonary Heart Disease/physiopathology , Vital Capacity
15.
J Agric Food Chem ; 67(38): 10774-10781, 2019 Sep 25.
Article in English | MEDLINE | ID: mdl-31479258

ABSTRACT

The released milk N-glycome has been found to possess antipathogenic activity. Natively, they are covalently linked onto proteins. Whether the conjugated N-glycans still have antipathogenic properties and how the glycosylation influences the antipathogenic activity of proteins remain unclear. Herein, we compared the quantitative differences of milk protein N-glycosylation and the antilisterial differences of native milk proteins, released N-glycan pools, and deglycosylated proteins between human and bovine milk. N-glycosylation exhibited to be quantitatively species-specific. The entire growth inhibitory activity and the majority of the antiadhesive activity against Listeria monocytogenes of milk whey proteins, although not as high as the released N-glycans, are attributed to N-glycosylation. Moreover, all N-glycan-bearing samples from human milk showed better growth inhibitory activities than those from bovine milk. Generally, N-glycosylation significantly contributes to the antilisterial function of milk proteins and to the functional differences between species. This gives novel insights into the role of these glycoconjugates in nature.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Listeria monocytogenes/drug effects , Milk Proteins/chemistry , Milk Proteins/pharmacology , Milk, Human/chemistry , Animals , Bacterial Adhesion/drug effects , Caco-2 Cells , Cattle , Glycosylation , Humans , Listeria monocytogenes/growth & development , Listeria monocytogenes/physiology , Polysaccharides/chemistry , Species Specificity
16.
Oncogene ; 38(39): 6599-6614, 2019 09.
Article in English | MEDLINE | ID: mdl-31375747

ABSTRACT

Chromatin regulation through histone modifications plays an essential role in coordinated expression of multiple genes. Alterations in chromatin induced by histone modifiers and readers regulate critical transcriptional programs involved in both normal development and tumor differentiation. Recently, we identified that histone deacetylases HDAC1 and HDAC7 are necessary to maintain cancer stem cells (CSCs) in both breast and ovarian tumors. Here, we sought to investigate the CSC-specific function of HDAC1 and HDAC7 mechanistically by using a stem-like breast cancer (BrCa) cell model BPLER and matched nonstem tumor cell (nsTC)-like HMLER, along with conventional BrCa cell lines with different CSC enrichment levels. We found that HDAC1 and HDAC3 inhibition or knockdown results in HDAC7 downregulation, which is associated with a decrease in histone 3 lysine 27 acetylation (H3K27ac) at transcription start sites (TSS) and super-enhancers (SEs) prominently in stem-like BrCa cells. Importantly, these changes in chromatin landscape also correlate with the repression of many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA, and XBP1. In stem-like BrCa cells, HDAC7 binds near TSS and to SEs of these oncogenes where it appears to contribute to both H3K27ac and transcriptional regulation. These results suggest that HDAC7 inactivation, directly or through inhibition of HDAC1 and HDAC3, can result in the inhibition of the CSC phenotype by downregulating multiple SE-associated oncogenes. The CSC selective nature of this mechanism and the prospect of inhibiting multiple oncogenes simultaneously makes development of HDAC7 specific inhibitors a compelling objective.


Subject(s)
Breast Neoplasms/genetics , Enhancer Elements, Genetic , Histone Deacetylases/metabolism , Histones/metabolism , Lysine/metabolism , Neoplastic Stem Cells/metabolism , Transcription, Genetic , Acetylation , Benzamides/pharmacology , Breast Neoplasms/pathology , Down-Regulation , Female , Gene Knockdown Techniques , Histone Deacetylase 1/drug effects , Histone Deacetylase 1/genetics , Histone Deacetylase 1/metabolism , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/drug effects , Histones/chemistry , Humans , Neoplastic Stem Cells/pathology , Pyridines/pharmacology , Transcription Factors/metabolism
17.
Anim Genet ; 50(5): 475-483, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31305959

ABSTRACT

Ten indigenous chicken breeds were originally distributed in Jiangxi Province, China, and they define a critical component of Chinese chicken genetic resources. We have investigated the population genetics of seven Jiangxi chicken breeds using 600K chicken BeadChip SNP data. To provide a genome-wide perspective for the population structure of all 10 Jiangxi chicken breeds, we herein genotyped 78 additional individuals from the seven breeds and 63 chickens from three uninvestigated breeds-Yugan Black (YG), Nancheng Black (NC) and Wanzai Yellow using 55K chicken SNP arrays. We then explored merged data of 17 101 SNPs from 235 individuals to infer the population structure of the 10 breeds. We showed that NC and YG are two regional populations of the same breed, as individuals from the two populations clustered together to form a branch separate from the other breeds in the neighbor-joining tree, they always grouped together in multidimensional principal component analyses and they displayed an identical pattern of ancestral lineage composition. Hence, NC and YG should be considered a single breed in the state-supported conservation scheme. Moreover, we conducted a genome scan for signatures of selection for black plumage. bayescan and hapflk analyses of two contrasting groups (three black-feathered breeds vs. six non-black-feathered breeds) consistently detected 25 putative regions under selection. Nine pigmentation- associated genes (DCT, SLC24A5, SLC30A4, MYO5A, CYP19A1, NADK2, SLC45A2, GNAQ and DCP2) reside within these regions, and these genes are interesting candidates for black plumage and provide a starting point for further identification of causative mutations for black feathers in chicken.


Subject(s)
Chickens/classification , Chickens/genetics , Feathers/physiology , Animals , Chickens/physiology , China , Genetic Variation , Genome-Wide Association Study , Pigmentation , Polymorphism, Single Nucleotide
18.
Neuropharmacology ; 136(Pt C): 362-373, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29138080

ABSTRACT

Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets for a number of different diseases, disorders, and conditions of the CNS. Although the present review will focus on Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), a number of conditions such as Parkinson's disease (PD), schizophrenia, and others represent significant unmet medical needs for which selective muscarinic agents could offer therapeutic benefits. Numerous advances have been made regarding mAChR localization through the use of subtype-selective antibodies and radioligand binding studies and these efforts have helped propel a number of mAChR therapeutics into clinical trials. However, much of what we know about mAChR localization in the healthy and diseased brain has come from studies employing radioligand binding with relatively modest selectivity. The development of subtype-selective small molecule radioligands suitable for in vitro and in vivo use, as well as robust, commercially-available antibodies remains a critical need for the field. Additionally, novel genetic tools should be developed and leveraged to help move the field increasingly towards a systems-level understanding of mAChR subtype action. Finally, functional, proteomic, and genetic data from ongoing human studies hold great promise for optimizing the design and interpretation of studies examining receptor levels by enabling patient stratification. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.


Subject(s)
Central Nervous System/metabolism , Receptors, Muscarinic/metabolism , Aging/metabolism , Alzheimer Disease/metabolism , Animals , Humans
19.
Climacteric ; 20(2): 151-156, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28145818

ABSTRACT

OBJECTIVE: This study aimed to evaluate the effect of health education combining diet and exercise supervision on menopausal symptoms and diet/exercise habits. METHODS: The randomized controlled study enrolled 60 patients with perimenopausal syndrome (Kupperman Menopause Index (KMI) score ≥15). The participants were randomized into either an intervention group (n = 30) or a control group (n = 30). Women were interviewed with questionnaires about perimenopausal symptoms, diet pattern and exercise habit. Their height and weight were measured. Women in the intervention group received health education, diet supervision and exercise supervision twice a week while those in the control group continued as normal. The total KMI score, scores of individual symptoms, diet pattern and exercise habit were measured after intervention. RESULTS: The total KMI score, the individual KMI scores for paresthesia, irritability, depression/suspicious, fatigue, arthralgia/myalgia, and palpitations of the intervention group were significantly lower compared with the control group after intervention. The intake of cereal, meat, fats and oils of the intervention group were significantly lower at week 12 compared with baseline. The percentage of women with a regular exercise habit was significantly higher in the intervention group than in the control group after intervention. CONCLUSIONS: Twelve weeks intervention of health education combining diet and exercise supervision could improve perimenopausal symptoms and help the patients establish good living habits.


Subject(s)
Counseling , Diet Therapy/methods , Exercise Therapy/methods , Patient Education as Topic/methods , Perimenopause , China , Diet , Diet Surveys , Exercise , Female , Healthy Lifestyle , Humans , Middle Aged , Surveys and Questionnaires , Symptom Assessment/methods , Treatment Outcome
20.
Phys Chem Chem Phys ; 18(28): 18719-26, 2016 Jul 28.
Article in English | MEDLINE | ID: mdl-27198938

ABSTRACT

The thickness-dependent electronic states and physical properties of two-dimensional materials suggest great potential applications in electronic and optoelectronic devices. However, the enhanced surface effect in ultra-thin materials might significantly influence the structural stability, as well as the device reliability. Here, we report a spontaneous phase transformation of gallium telluride (GaTe) that occurred when the bulk was exfoliated to a few layers. Transmission electron microscopy (TEM) results indicate a structural variation from a monoclinic to a hexagonal structure. Raman spectra suggest a critical thickness for the structural transformation. First-principle calculations and thermodynamic analysis show that the surface energy and the interlayer interaction compete to dominate structural stability in the thinning process. A two-stage transformation process from monoclinic (m) to tetragonal (T) and then from tetragonal to hexagonal (h) is proposed to understand the phase transformation. The results demonstrate the crucial role of interlayer interactions in the structural stability, which provides a phase engineering strategy for device applications.

SELECTION OF CITATIONS
SEARCH DETAIL
...