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1.
Neurochem Res ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909329

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic strategy that shows promise in ameliorating the clinical sequelae following traumatic brain injury (TBI). These improvements are associated with neuroplastic changes in neurons and their synaptic connections. However, it has been hypothesized that rTMS may also modulate microglia and astrocytes, potentially potentiating their neuroprotective capabilities. This study aims to investigate the effects of high-frequency rTMS on microglia and astrocytes that may contribute to its neuroprotective effects. Feeney's weight-dropping method was used to establish rat models of moderate TBI. To evaluate the neuroprotective effect of high frequency rTMS on rats by observing the synaptic ultrastructure and the level of neuron apoptosis. The levels of several important inflammation-related proteins within microglia and astrocytes were assessed through immunofluorescence staining and western blot. Our findings demonstrate that injured neurons can be rescued through the modulation of microglia and astrocytes by rTMS. This modulation plays a key role in preserving the synaptic ultrastructure and inhibiting neuronal apoptosis. Among microglia, we observed that rTMS inhibited the levels of proinflammatory factors (CD16, IL-6 and TNF-α) and promoted the levels of anti-inflammatory factors (CD206, IL-10 and TNF-ß). rTMS also reduced the levels of pyroptosis within microglia and pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18). Moreover, rTMS downregulated P75NTR expression and up-regulated IL33 expression in astrocytes. These findings suggest that regulation of microglia and astrocytes is the mechanism through which rTMS attenuates neuronal inflammatory damage after moderate TBI.

2.
Heliyon ; 10(10): e31121, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803920

RESUMO

Background: The intricate regulatory relationship between mitochondrial dysfunction, apoptosis, and immune cells remains largely elusive following traumatic brain injury (TBI). Methods: The GSE45997 dataset from the Gene Expression Omnibus database and utilized GEO2R to screen for differentially expressed genes (DEGs). Functional enrichment analyses were performed. Mitochondrial gene data from the MitoCarta3.0 database were combined with the DEGs to identify mitochondria-related DEGs (MitoDEGs). The hub MitoDEGs related to apoptosis were further screened. Animal models of TBI were established to investigate the mechanisms underlying mitochondrial dysfunction regulation of apoptosis. Furthermore, we explored the relationship between MitoDEGs/hub MitoDEGs and immune cells using the Spearman correlation method. Results: Fifty-seven MitoDEGs were significantly enriched in pathways related to fatty acid degradation and metabolism. We identified three upregulated hub MitoDEGs, namely Dnm1l, Mcl1 and Casp3, were associated with apoptosis. In the animal experiments, we observed significant expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) surrounding the injury site. Most LC3B-expressing cells exhibited positive staining for Beclin 1 and colocalization analysis revealed the simultaneous presence of Beclin 1 and caspase-3. The Western blot analysis further unveiled a significant upregulation of cleaved caspase-3 levels and LC3B II/LC3B I ratio after TBI. Moreover, the quantity of myeloid cell leukaemia-1 immunoreactive cells was notably higher than that in the control group. Spearman correlation analysis demonstrated strong associations between plasma cells, marginal zone B cells, native CD4 T cells, monocytes, and MitoDEGs/hub MitoDEGs. Conclusions: This study sheds light on enhanced fatty acid metabolism following mitochondrial dysfunction and its potential association with apoptosis and immune cell activation, thereby providing new mechanistic insights into the acute phase of TBI.

3.
J Neurosci Res ; 102(1): e25284, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284864

RESUMO

In this study, we explored the application of diffusion kurtosis imaging (DKI) technology in the brains of children with attention-deficit/hyperactivity disorder (ADHD). Seventy-two children with ADHD and 79 age- and sex-matched healthy controls were included in the study. All children were examined by means of 3D T1-weighted image, DKI, and conventional sequence scanning. The volume and DKI parameters of each brain region were obtained by software postprocessing (GE ADW 4.6 workstation) and compared between the two groups of children to determine the imaging characteristics of children with ADHD. The result showed the total brain volume was lower in children with ADHD than in healthy children (p < .05). The gray and white matter volumes in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus, and other brain regions were lower in children with ADHD than in healthy children (p < .05). The axial kurtosis (Ka), mean kurtosis (MK), fractional anisotropy (FA), and radial kurtosis(Kr) values in the frontal lobe, temporal lobe, and caudate nucleus of children with ADHD were lower than those of healthy children, while the mean diffusivity(MD) and fractional anisotropy of kurtosis (FAK) values were higher than those of healthy children (p < .05). Additionally, the Ka, MK, FA, and Kr values in the frontal lobe, caudate nucleus, and temporal lobe could be used to distinguish children with ADHD (AUC > .05, p < .05). In conclusion, DKI showed abnormal gray matter and white matter development in some brain regions of children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Substância Branca , Criança , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Córtex Cerebral
4.
Biol Proced Online ; 25(1): 29, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37953280

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. METHODS: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. RESULTS: Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. CONCLUSIONS: These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

6.
Front Psychiatry ; 14: 1064647, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741108

RESUMO

Purpose: To investigate the feasibility of three-dimensional pseudocontinuous arterial spin labeling (3D-pcASL) perfusion imaging in the brain of children with Attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 78 ADHD children aged 5-13 years were prospectively selected as the study group, and 89 healthy children matched in age and sex were selected as the control group. All children underwent MRI conventional sequence, 3D-pcASL, and 3D-T1 sequence scans. The brain gray and white matter volume and cerebral blood flow (CBF) perfusion values were obtained by software post-processing, and were compared and analyzed in the two groups to find out their characteristics in the brain of ADHD children. Results: The total brain volume and total CBF values were lower in ADHD children than in healthy children (P < 0.05); the gray and white matter volumes in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus and other brain regions were lower in ADHD children than in healthy children (P < 0.05); the gray matter CBF values in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, putamen, globus pallidus and other brain regions were lower in ADHD children than in healthy children (P < 0.05); the differences between the white matter CBF values of white matter in the said brain regions of ADHD children and healthy children were not statistically significant (P > 0.05); and the CBF values in frontal lobe and caudate nuclei could distinguish ADHD children (AUC > 0.05, P < 0.05). Conclusion: The 3D-pcASL technique showed reduced cerebral perfusion in some brain regions of ADHD children.

7.
Neural Regen Res ; 18(2): 368-374, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900432

RESUMO

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity-related proteins and their mRNA. On the injured side of the brain, we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, N-methyl-D-aspartic acid receptor 1, and phosphorylated cAMP response element binding protein, which are closely associated with the occurrence of long-term potentiation. rTMS also partially reversed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure. These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

8.
China Tropical Medicine ; (12): 333-2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979679

RESUMO

@#Abstract: Objective To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.38<MHR≤0.48), group Q3 (0.48<MHR≤0.64) and group Q4 (MHR>0.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.

9.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 1027-1036, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34109980

RESUMO

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.


Assuntos
Carcinoma Pulmonar de Lewis , Ácido Fólico , Glutationa/metabolismo , Neoplasias Pulmonares , Nanomedicina , Paclitaxel , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia
10.
BMC Surg ; 21(1): 121, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685424

RESUMO

BACKGROUND: To investigate the readiness for hospital discharge of patients discharged with tubes from the department of hepatobiliary surgery and to explore the influencing factors. METHODS: A cross-sectional survey was conducted for the 161 patients with tubes who were discharged from the department of hepatobiliary surgery of Shaoxing Second Hospital by using the modified Chinese version of Readiness for Hospital Discharge Scale (RHDS) and Quality of Discharge Teaching Scale (QDTS). General data of the patients, such as gender, age, BMI (body mass index), and educational level, were collected. RESULTS: According to the statistical results, the total score of the RHDS was 142.40 ± 23.98, and that of the QDTS was 148.14 ± 17.74. Multiple linear step-wise regression analysis revealed that the total score of the QDTS, residence and educational level were the independent influencing factors of the readiness for hospital discharge (p < 0.05). CONCLUSION: The level of the readiness for hospital discharge of the 161 discharged patients with tubes from the department of hepatobiliary surgery was in the middle and lower level. For the patients who are far away from the hospital and have a low education level, we should pay more attention to health education and discharge teaching, so as to improve the readiness for hospital discharge of relatively vulnerable patients, reduce the incidence of adverse events after discharge with tubes, and ensure the health and safety of patients.


Assuntos
Doenças do Sistema Digestório , Alta do Paciente , Centro Cirúrgico Hospitalar , China , Estudos Transversais , Doenças do Sistema Digestório/cirurgia , Feminino , Humanos , Masculino , Alta do Paciente/estatística & dados numéricos , Fatores Socioeconômicos
11.
J Ethnopharmacol ; 256: 112802, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32240782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfukang has long been used for the clinical treatment of lung cancer. Previous studies have shown that Jinfukang can induce the apoptosis of circulating tumor cells by intervening ROS-mediated DNA damage pathway. However, whether Jinfukang can inhibit the metastasis of circulating tumor cells and its mechanism are still unclear. AIM OF THE STUDY: To further investigate the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of tumor exosomes. MATERIALS AND METHODS: The invadopodia formation was determined with immunofluorescence. Invasion and migration were detected using the Transwell assay. Ultracentrifugation was used to isolate exosomes. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and immunoblotting, and the protein profile was evaluated by proteomic analysis. The molecular functions, biological processes and signaling pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Key differentially expressed proteins were verified by Western blot. RESULTS: Jinfukang can inhibit the expression of MMP14, cortactin, Tks5 and the formation of invadopodia of CTC-TJH-01 cells. Furthermore, Jinfukang can significantly inhibit the invasion and migration of CTC-TJH-01 cells. The diameter of exosomes extracted from the CTC-TJH-01 cells treated by Jinfukang was 30-100 nm, and the exosomal markers CD63, CD81 and TSG101 were expressed. We identified 680 deferentially expressed proteins. Gene oncology analysis indicated that exosomes were mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The ingenuity pathway analysis showed that the EGF pathway was significantly inhibited, whereas the GP6 signaling pathway was significantly activated. We also confirmed that Jinfukang inhibited the expression of EGF pathway-related proteins in CTC-TJH-01 cells. Besides, when EGF was used to activate EGF signaling pathway, the inhibition of Jinfukang on CTC cell metastasis was reversed. CONCLUSION: Jinfukang inhibits the metastasis of CTC-TJH-01 cells through the EGF pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacos
12.
Exp Ther Med ; 18(6): 4249-4258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31772627

RESUMO

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-associated mortality. Recent studies revealed that long non-coding (lnc)RNAs have crucial roles in human cancers. The present study was the first, to the best of our knowledge, to indicate that the lncRNA transducer of ERBB2, 1-antisense 1 (TOB1-AS1) acts as a tumor suppressor in NSCLC. Knockdown of TOB1-AS1 significantly induced NSCLC cell migration, invasion and proliferation. It was also demonstrated that the higher expression of TOB1-AS1 in NSCLC samples was associated with longer overall survival time. Furthermore, a TOB1-AS1-mediated competing endogenous RNA network in NSCLC was constructed, including Homo sapiens (hsa)-microRNA (miR)-27a-3p, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-27b-3p, hsa-miR-23c, dynein cytoplasmic 2 light intermediate chain 1, E4F transcription factor 1, TSPY-like 4, component of oligomeric Golgi complex 7, inositol hexakisphosphate kinase 2 and deltex E3 ubiquitin ligase 3. Of note, dysregulation of targets of TOB1-AS1 was associated with the prognosis of NSCLC patients. The present study suggested that TOB1-AS1 may serve as a novel biomarker for NSCLC.

13.
J Colloid Interface Sci ; 533: 47-58, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144692

RESUMO

Herein, novel mesoporous carbon-doped g-C3N4 ultrathin nanosheets (C/CNNS) have been synthesized for the first time through a facile one-step thermal condensation method using agar-melamine gel (AMG) as precursor. A series of characterizations were carried out to explore the structure, morphology and optoelectronic properties of the C/CNNS photocatalyst. The resultant C/CNNS-0.5 exhibited the optimum photocatalytic performance with respect to bulk g-C3N4 by using Rhodamine B, Phenol, Bisphenol A and Phenanthrene as target pollutants under visible light irradiation. Such remarkable enhancement of photocatalytic activity was mainly attributed to the synergistic effect of onion-like carbon (OLC) and ultrathin 2D nanosheets structure. The introduction of OLC could effectively expand visible-light absorption regions. Besides, OLC can act as an electron receiver to facilitate charge separation and inhibit the recombination of photogenerated carriers. 2D nanosheets structure provides more active sites for photocatalytic reactions, which further improve photocatalytic activity of C/CNNS-0.5 photocatalyst. The photocatalytic mechanism of C/CNNS for removing organic pollutants was explored by electron spin resonance (ESR) technique. Much different from the bulk g-C3N4, superoxide radical (O2-) and hydroxyl radical (OH) were the two main radicals, while for the bulk g-C3N4, there is only the O2- radical worked in the photocatalytic reaction.

15.
Oncol Lett ; 7(6): 1885-1888, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24932253

RESUMO

The current study presents the case of a patient with multiple pulmonary nodules as observed by computed tomography. Furthermore, a marginal increase in fluorodeoxyglucose uptake was identified by positron emission tomography. Due to the appearance of multiple small nodules and a history of radical nephrectomy, a hypothetical diagnosis of pulmonary metastasis of a previously excised renal carcinoma was determined, which was confirmed by biopsy. Video-assisted thoracoscopic surgical resection of the nodules was proposed and pathological examination exhibited an unforeseen and rare observation.

17.
PLoS One ; 8(5): e62377, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23667473

RESUMO

Keloid is benign fibroproliferative dermal tumors with unknown etiology. Recently, a genome-wide association study (GWAS) in Japanese population has identified 3 susceptibility loci (rs873549 at 1q41, rs940187 and rs1511412 at 3q22.3, rs8032158 at 15p21.3) for keloid. In order to examine whether these susceptibility loci are associated with keloid in the Chinese Han population, twelve previously reported SNPs were selected for replication in 714 cases and 2,944 controls by using Sequenom MassArray system. We found three SNPs in two regions showed significant association with keloid in the Chinese Han population: 1q41 (rs873549, P = 3.03×10(-33), OR = 2.05, 95% CI: 1.82-2.31 and rs1442440, P = 9.85×10(-18), OR = 0.56, 95% CI: 0.49-0.64, respectively) and 15q21.3 (rs2271289 located in NEDD4, P = 1.02×10(-11), OR = 0.66, 95% CI: 0.58-0.74). We also detected one risk haplotype AG (P = 1.36×10(-31), OR = 2.02) and two protective haplotypes of GA and AA (GA, P = 1.94×10(-19), OR = 0.53, AA, P = 0.00043, OR = 0.78, respectively) from the two SNPs (rs873549 and rs1442440). Our study confirmed two previously reported loci 1q41 and 15q21.3 for keloid in the Chinese Han population, which suggested the common genetic factor predisposing to the development of keloid shared by the Chinese Han and Japanese populations.


Assuntos
Povo Asiático/etnologia , Povo Asiático/genética , Etnicidade/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Queloide/genética , Adulto , Feminino , Haplótipos/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
18.
Nat Genet ; 44(10): 1156-60, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22983302

RESUMO

Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.


Assuntos
Exoma , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Mutação Puntual , Poroceratose/genética , Apoptose , Estudos de Casos e Controles , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Humanos , Queratinócitos/fisiologia , Masculino , Linhagem , Poroceratose/patologia , Sítios de Splice de RNA
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(8): 488-91, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17708848

RESUMO

OBJECTIVE: To investigate the effects of the integrated traditional Chinese medicine Xuebijing injection on protein C (PC) and tumor necrosis factor-alpha (TNF-alpha) mRNA in rats with sepsis. METHODS: Sepsis was induced in Wistar rats by cecal ligation and puncture (CLP). Ninety-six healthy animals were randomly divided into four groups: normal group, sham-operation group, CLP model group, and Xuebijing-treated group. The two latter groups were divided into 2, 8, 24, 48, and 72-hour subgroups with 8 rats in each subgroup. Platelet count of blood obtained from abdominal aorta was determined and tissue samples from liver and lungs were collected to measure tissue PC and TNF-alpha mRNA expression. RESULTS: PC gene expression levels in lung tissues were significantly lowered (all P<0.01), but they were dramatically raised by Xuebijing injection during 8-72 hours post-CLP (all P<0.01). Compared with normal group, TNF-alpha mRNA levels in liver and lungs were significantly elevated at 2 hours post-CLP (P<0.05 or P<0.01). However, treatment with Xuebijing injection markedly reduced TNF-alpha mRNA both in liver and lungs at 2-24 hours (P<0.05 or P<0.01). In CLP group, blood platelet count was significantly decreased to certain extent at different intervals within 8-72 hours, and it was markedly elevated in the Xuebijing-treated group (P<0.05 or P<0.01). CONCLUSION: The current study suggests that Xuebijing injection could exert preventing effect on the development of severe sepsis by suppressing PC and TNF-alpha mRNA.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Proteína C/metabolismo , Sepse/tratamento farmacológico , Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Proteína C/genética , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(6): 365-8, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17577447

RESUMO

OBJECTIVE: To investigate effects of the integrated traditional Chinese medicine Xuebijing injection on thrombomodulin (TM) and endothelial cell protein C receptor (EPCR) in septic rats. METHODS: Ninety-six healthy Wistar rats were randomly divided into four groups: control group, sham operation group, cecal ligation and puncture (CLP) model group, and Xuebijing-treated group. Sepsis was reproduced by CLP. The two latter groups were divided into five subgroups of 2, 8, 24, 48 and 72-hour with 8 rats in each subgroup. Tissue samples from liver and lung were collected to determine tissue TM and EPCR mRNA expression. RESULTS: TM and EPCR mRNA expressions were observed in liver and lung in control group and sham operation group, while with no significant differences at 2 hours post-CLP (both P>0.05). TM and EPCR gene expression levels in tissues were significantly increased to certain extent at 8-48 hours (all P<0.01), and were dramatically decreased following Xuebijing injection at 72 hours post-CLP (both P>0.05). Also, treatment with Xuebijing injection markedly decreased TM and EPCR mRNA levels to certain extents at 8 and 24 hours, and markedly increased at 48 and 72 hours compared with those of model group. CONCLUSION: These data suggest that Xuebijing injection could raise TM and EPCR mRNA expression, thereby it might be effective in prevention of development of severe sepsis.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Receptores de Superfície Celular/metabolismo , Sepse/metabolismo , Trombomodulina/metabolismo , Animais , Modelos Animais de Doenças , Fígado/metabolismo , Pulmão/metabolismo , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Sepse/tratamento farmacológico
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