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1.
Inorg Chem ; 63(10): 4697-4706, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38407040

RESUMO

Benefiting from the unique photoluminescence behavior of the lanthanide(III) ions and organic ligands, a lanthanide(III) metal-organic framework (Ln-MOF) material can simultaneously demonstrate photoluminescence of lanthanide(III) cations and organic molecules and endow its superior applications of fluorescence sensing behaviors. Herein, we present a europium(III) MOF material {[Eu2(BPTA)·(CH3COO)2·3DMA]·0.5DMA·3H2O}n (1) (where H4BPTA is 3,3',5,5'-biphenyltetracarboxylic acid) for photoluminescence performance of quantitatively sensing the inflammatory marker neopterin (Neo). The obtained 1 comprises Eu2(COO)4 paddlewheel secondary building units, which could be bridged by BPTA4- ligands to extend a 2D framework. The fluorescence titration indicates 1 can achieve simultaneous fluorescence behavior of Eu3+ ions and Neo via on-off ratiometric effects and thus could be exploited as the ratiometric fluorescence sensor matrix. Such a fluorescence phenomenon of 1 as a ratiometric sensor for quantitative detection of Neo via an on-off ratiometric effect is never observed in MOF chemistry. Moreover, naked-eye visible color variations of the fluorescence for 1 could be observed from red to blue with increasing concentrations of Neo, confirmed by fluorescent test strips as well as portable fluorescent hydrogels. And 1 also shows a low detection limit of 15.11 nM. A synergetic contribution of the competitive absorption, fluorescence resonance energy-transfer, and photoinduced electron-transfer mechanisms between Neo and the framework of 1 realizes the on-off ratiometric fluorescence behavior for Neo detection, supported by the UV-vis spectral overlap experiment and DFT calculations.

2.
Differentiation ; 133: 98-108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37643534

RESUMO

Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP. Recently, non-coding RNAs (ncRNAs) have received more attention due to their significant role in cellular functions and bone formation. It is worth noting that ncRNAs have also been demonstrated to participate in the progression of DOP. Meanwhile, nano-delivery systems are considered a promising strategy to treat DOP because of their cellular targeting, sustained release, and controlled release characteristics. Additionally, the utilization of novel technologies such as the CRISPR system has expanded the scope of available options for treating DOP. Hence, this paper explores the functions and regulatory mechanisms of ncRNAs in DOP and highlights the advantages of employing nanoparticle-based drug delivery techniques to treat DOP. Finally, this paper also explores the potential of ncRNAs as diagnostic DOP biomarkers.


Assuntos
Diabetes Mellitus , MicroRNAs , Osteoporose , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Osteoporose/etiologia , Osteoporose/genética
3.
BMC Biol ; 21(1): 168, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553642

RESUMO

BACKGROUND: Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. RESULTS: Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. CONCLUSIONS: Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.


Assuntos
Duplicação Gênica , Tetraploidia , Humanos , Alelos , Poliploidia , Genômica
4.
Mol Biol Evol ; 39(1)2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34687315

RESUMO

Although hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica, and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation.


Assuntos
Juglans , Fluxo Gênico , Genômica , Humanos , Hibridização Genética , Juglans/genética , Árvores
5.
Eur J Clin Pharmacol ; 79(12): 1631-1639, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37755492

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Varfarina/uso terapêutico , Rivaroxabana/uso terapêutico , Dabigatrana/uso terapêutico , Piridonas/uso terapêutico , Administração Oral
6.
Clin Exp Immunol ; 208(3): 340-350, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35511600

RESUMO

Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease (IBD) and is an idiopathic, chronic inflammatory disease of the colonic mucosa with an unclear etiology. Interleukin (IL)-10 has been reported to play a crucial role in the maintenance of immune homeostasis in the intestinal environment. Type 1 regulatory T (Tr1) cells are a subset of CD4+Foxp3- T cells able to secrete high amounts of IL-10 with potent immunosuppressive properties. In this study, we found that the combination of anti-GITR antibody (G3c) and CD28 superagonist (D665) treatment stimulated the generation of a large amount of Tr1 cells. Furthermore, G3c/D665 treatment not only significantly relieved severe mucosal damage but also reduced the incidence of colonic shortening, weight loss, and hematochezia. Dextran sodium sulfate (DSS) upregulated the mRNA levels of IL-6, IL-1ß, IL-17, IL-12, tumor necrosis factor-alpha, C-C chemokine receptor type 5, and Bax in splenic lymphocytes (SPLs) and colon tissues, while G3c/D665 treatment conversely inhibited the increase in mRNA levels of these genes. In addition, G3c/D665 treatment altered the proportion of CD4+ and CD8+ T cells and increased CD4+CD25+Foxp3+ regulatory T cells in SPLs, mesenteric lymph nodes (MLNs), and lamina propria lymphocytes (LPLs). Thus, the combination of G3c and D665 treatment showed efficacy against DSS-induced UC in mice by inducing a large amount of Tr1 cell generation via the musculoaponeurotic fibrosarcoma pathways in vivo and relieving inflammatory responses both systematically and locally.


Assuntos
Colite Ulcerativa , Colite , Animais , Antígenos CD28/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Sulfatos , Linfócitos T Reguladores
7.
Liver Transpl ; 28(5): 782-793, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34529892

RESUMO

Small-for-size syndrome (SFSS) is a common complication following partial liver transplantation and extended hepatectomy. SFSS is characterized by postoperative liver dysfunction caused by insufficient regenerative capacity and portal hyperperfusion and is more frequent in patients with preexisting liver disease. We explored the effect of the Mesenchymal-epithelial transition factor (MET)-agonistic antibody 71D6 on liver regeneration and functional recovery in a mouse model of SFSS. Male C57/BL6 mice were exposed to repeated carbon tetrachloride injections for 10 weeks and then randomized into 2 arms receiving 3 mg/kg 71D6 or a control immunoglobulin G (IgG). At 2 days after the randomization, the mice were subjected to 70% hepatectomy. Mouse survival was recorded up to 28 days after hepatectomy. Satellite animals were euthanized at different time points to analyze liver regeneration, fibrosis, and inflammation. Serum 71D6 administration significantly decreased mouse mortality consequent to insufficient regeneration of the cirrhotic liver. Analysis of liver specimens in satellite animals revealed that 71D6 promoted powerful activation of the extracellular signal-regulated kinase pathway and accelerated liver regeneration, characterized by increased liver-to-body weight, augmented mitotic index, and higher serum albumin levels. Moreover, 71D6 accelerated the resolution of hepatic fibrosis as measured by picrosirius red, desmin, and α-smooth muscle actin staining, and suppressed liver infiltration by macrophages as measured by CD68 and F4/80 staining. Analysis of gene expression by reverse-transcription polymerase chain reaction confirmed that 71D6 administration suppressed the expression of key profibrotic genes, including platelet-derived growth factor, tissue inhibitor of metalloproteinase 3, and transforming growth factor-ß1, and of key proinflammatory genes, including tumor necrosis factor-α, interleukin-1ß, chemokine (C-C motif) ligand 3, and chemokine (C-C motif) ligand 5. These results suggest that activating the MET pathway via an hepatocyte growth factor-mimetic antibody may be beneficial in patients with SFSS and possibly other types of acute and chronic liver disorders.


Assuntos
Regeneração Hepática , Transplante de Fígado , Animais , Hepatectomia/efeitos adversos , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos
8.
Proc Natl Acad Sci U S A ; 116(6): 2152-2157, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30659151

RESUMO

What kind of genetic variation contributes the most to adaptation is a fundamental question in evolutionary biology. By resequencing genomes of 80 individuals, we inferred the origin of genomic variants associated with a complex adaptive syndrome involving multiple quantitative traits, namely, adaptation between high and low altitudes, in the vinous-throated parrotbill (Sinosuthora webbiana) in Taiwan. By comparing these variants with those in the Asian mainland population, we revealed standing variation in 24 noncoding genomic regions to be the predominant genetic source of adaptation. Parrotbills at both high and low altitudes exhibited signatures of recent selection, suggesting that not only the front but also the trailing edges of postglacial expanding populations could be subjected to environmental stresses. This study verifies and quantifies the importance of standing variation in adaptation in a cohort of genes, illustrating that the evolutionary potential of a population depends significantly on its preexisting genetic diversity. These findings provide important context for understanding adaptation and conservation of species in the Anthropocene.


Assuntos
Adaptação Biológica , Evolução Biológica , Variação Genética , Aves Canoras/genética , Animais , Meio Ambiente , Genética Populacional , Genoma , Genômica/métodos , Polimorfismo de Nucleotídeo Único , RNA não Traduzido , Seleção Genética , Taiwan
9.
J Perianesth Nurs ; 36(3): 253-261, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33640290

RESUMO

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.


Assuntos
Anestesia Geral , Procedimentos Cirúrgicos Eletivos , Adulto , Anestesia Geral/efeitos adversos , China/epidemiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Humanos , Incidência , Dor Pós-Operatória , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco
10.
Angew Chem Int Ed Engl ; 60(40): 21846-21852, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34227191

RESUMO

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial fingerprint output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high sensitivity for high-throughput multi-color biomedical imaging.


Assuntos
Nanopartículas/química , Imagem Óptica , Polímeros/química , Humanos , Células MCF-7 , Estrutura Molecular , Análise Espectral Raman
11.
J Cell Mol Med ; 24(12): 6928-6942, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32364678

RESUMO

Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10-4  mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3ß and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.


Assuntos
Acidose/patologia , Melatonina/farmacologia , Neurônios/patologia , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Espaço Extracelular/metabolismo , Feminino , Concentração de Íons de Hidrogênio , Neurônios/efeitos dos fármacos , Organelas/efeitos dos fármacos , Organelas/metabolismo , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Estresse Fisiológico/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/patologia , Proteínas tau/metabolismo
12.
Med Sci Monit ; 25: 6719-6726, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31493329

RESUMO

BACKGROUND Bariatric procedures such as left gastric artery ligation (LGAL) and sleeve gastrectomy (SG) have emerged as important procedures for treating morbid obesity. In this study, we compared the effects of LGAL vs. SG on obesity-induced adipose tissue macrophage infiltration and inflammation in diet-induced obese rats. MATERIAL AND METHODS Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 16 weeks to induce obesity. SG, GLAL, or corresponding sham surgeries were performed in anesthetized rats. Inflammatory factor expression in serum and epididymal and retroperitoneal adipose tissues were analyzed 4 weeks after surgery. Macrophage infiltration and phenotype transformation were also assessed with Western blot analysis and immunofluorescence. RESULTS Both LGAL and SG strongly attenuated high-fat diet (HFD)-induced fat accumulation in retroperitoneal and epididymal tissues. The expressions of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were downregulated after LGAL and after SG by promoting activation of M2 macrophages, despite continued exposure to HFD. Furthermore, both LGAL and SG resulted in increased macrophage infiltration, but did not contribute to phenotype transformation of macrophages to M1. CONCLUSIONS LGAL and SG both reduced fat accumulation caused by HFD feeding. Therapies designed to ameliorate the inflammatory response by promoting activation of M2 macrophages may be valuable.


Assuntos
Tecido Adiposo/patologia , Dieta Hiperlipídica , Gastrectomia , Artéria Gástrica/ultraestrutura , Inflamação/patologia , Macrófagos/patologia , Obesidade/patologia , Animais , Epididimo/patologia , Mediadores da Inflamação/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Ligadura , Masculino , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais
14.
Pak J Med Sci ; 34(4): 923-928, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30190754

RESUMO

OBJECTIVE: To compare glottis exposure of the same patients with potentially difficult tracheal intubation (PDTI) subjected to Airtraq laryngoscopy and Macintosh laryngoscopy under consciousness and topical anesthesia. METHODS: A total of 147 PDTI patients with American Society of Anesthesiologists (ASA) I-III were subjected to Airtraq and Macintosh laryngoscopy performed by experienced anesthesiologists under consciousness and topical anesthesia. RESULTS: All patients were successfully intubated. Among them, three patients were intubated with fiberoptic bronchoscopy, 13 with Macintosh laryngoscopy and 131 with Airtraq laryngoscopy. Of the patients with Cormack and Lehance (C&L) Grade-I glottic view, 88 were subjected to Airtraq laryngoscopy and five to Macintosh laryngoscopy; Of the patients with C&L Grade-II glottic view, 56 were subjected to Airtraq laryngoscopy and 21 to Macintosh bronchoscopy; Of the patients with C&L Grade-III glottic view, three were subjected to Airtraq laryngoscopy and 112 to Macintosh bronchoscopy; Of the patients with C&L Grade-IV glottic view, none was subjected to Airtraq laryngoscopy and 9 to Macintosh laryngoscopy. CONCLUSIONS: Airtraq laryngoscopy could significantly improve the glottis exposure and reduce the difficulty of intubation for patients with potentially tracheal intubation compared to the traditional Macintosh laryngoscopy.

15.
Phys Chem Chem Phys ; 19(3): 2353-2358, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28054693

RESUMO

In this study, we demonstrate a novel method for fabricating polymer stabilized cholesteric liquid crystal (PSCLC) films with non-uniform pitch distribution by utilizing two kinds of photo-induced processes. Based on the large HTP temperature dependence of a chiral dopant, polymer networks were formed at two distant temperature points in sequence. The influence of the polymerization conditions on the reflectance properties of PSCLCs before and after polymerization was investigated. The results strongly suggest that the location and bandwidth of the reflection band can be controlled preferably by adjusting the ultraviolet light intensity and irradiation time of UV-light. In addition, the morphology of the polymer network in the composites was studied using scanning electron microscopy (SEM). A general correlation between polymerization conditions, the network morphology, and the reflective region will be outlined.

16.
J Clin Lab Anal ; 31(5)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27704598

RESUMO

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors that arise from the diffuse neuroendocrine system, and the biggest advances in molecular biology have helped in understanding these biological diversity of tumors over the past decades. It is important to determine the carcinogenesis of GEP-NEN from the perspective of genetic backgrounds. METHODS: Mitochondrial DNA (mtDNA) of peripheral blood from 66 GEP-NEN patients and from 75 healthy controls without history of any cancer were examined for single nucleotide polymorphisms (SNPs) and mutations in the displacement loop (D-loop) region. RESULTS: Single nucleotide polymorphisms were detected in 148 sites within the 982 bp mitochondria D-loop region from blood samples of healthy controls and GEP-NEN patients. SNPs with a rare allele frequency >5% in either controls or GEP-NEN patients were used for cancer risk analysis; a total of 23 SNPs were selected. When individual SNPs of GEP-NEN patients compared with healthy controls were analyzed, a statistically significant increase in the SNP frequency was observed for 73G, 150T, 151T, 492C, 16257A, 16261T, and 16399G in GEP-NEN patients (P<.05). It was also observed that the SNP frequency for 489C and 16519C significantly decreased in GEP-NEN patients compared with controls (P<.05). CONCLUSION: In summary, SNPs in the mutations of the mitochondrial D-loop may be valuable markers for GEP-NEN risk evaluation. Analysis of the genetic polymorphisms in the D-loop may be useful for diagnosis of high-risk individuals.


Assuntos
DNA Mitocondrial/genética , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/genética , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Cytokine ; 72(2): 154-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25647270

RESUMO

Epidemiological studies indicate a genetic contribution to colorectal cancer (CRC), but specific genetic variants remain unknown. Genome-wide association studies have identified rs4444235 at BMP4 as a new colorectal cancer (CRC) and colorectal adenoma (CRA) susceptibility locus in populations of European descent. After that, several validation studies have been conducted among various ethnic populations to investigate if the SNP was associated with CRC/CRA, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis involving 54,631 CRC cases, 3995 CRA cases and 88,098 controls from 15 studies was performed. Potential sources of heterogeneity including ethnicity, sample size, study design and endpoint were also assessed. Overall, the summary OR of CRC was 1.06 (95% CI: 1.04-1.08, P<10(-5)). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians (OR=1.07, 95% CI: 1.01-1.12, P=0.01) and Caucasians (OR=1.07, 95% CI: 1.05-1.10, P<10(-5)); while no significant associations were found among African Americans and other ethnic populations in all genetic models. In addition, significant associations were also detected for CRA with per-allele OR of 1.09 (95% CI: 1.03-1.14, P=0.001). Our findings demonstrated that BMP4-rs4444235 is a risk factor associated with increased CRC and CRA susceptibility, but these associations vary in different ethnic populations.


Assuntos
Adenoma/genética , Proteína Morfogenética Óssea 4/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Variação Genética , Polimorfismo de Nucleotídeo Único/genética , Adenoma/etnologia , Adenoma/etiologia , Alelos , Povo Asiático/genética , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/etiologia , Etnicidade , Estudo de Associação Genômica Ampla , Humanos , Descoberta do Conhecimento , Fatores de Risco , População Branca/genética
18.
Eur J Oral Sci ; 123(4): 249-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26058789

RESUMO

Since focal adhesion kinase (FAK) was proposed as a mediator of the inflammatory response, we have investigated the role of this molecule in the release of inflammatory cytokines by cultured human periodontal ligament fibroblasts (HPDLFs), cells that are thought to be important in the patient's response to periodontal infection. Human periodontal ligament fibroblasts were stimulated by tumor necrosis factor alpha (TNF-α) and its effects on interleukin (IL)-6 and IL-8 release were measured by ELISA. Expression of matrix metalloproteinase 2 (MMP-2) protein was analysed by western blotting. The levels of IL6, IL8, and MMP2 mRNA were evaluated by real-time PCR. Tumor necrosis factor alpha dose-dependently induced the phosphorylation of FAK, whereas small interfering FAK (siFAK) inhibited TNF-α-induced FAK phosphorylation. Tumor necrosis factor alpha also stimulated the production of IL-6, IL-8, and MMP-2 in a dose-dependent manner. Knockdown of FAK significantly suppressed TNF-α-induced expression of IL6 and IL8 mRNA and release of IL-6 and IL-8 protein in HPDLFs. Similarly, MMP-2 down-regulation was significantly prevented by siFAK. Our results strongly suggest that knockdown of FAK can decrease the production of TNF-α-induced IL-6, IL-8, and MMP-2 in HPDLFs. These effects may help in understanding the mechanisms that control expression of inflammatory cytokines in the pathogenesis of periodontitis.


Assuntos
Fibroblastos/efeitos dos fármacos , Quinase 1 de Adesão Focal/efeitos dos fármacos , Interleucina-6/análise , Interleucina-8/efeitos dos fármacos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/enzimologia , Quinase 1 de Adesão Focal/genética , Técnicas de Silenciamento de Genes , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/enzimologia , Fosforilação , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/administração & dosagem
19.
World J Surg Oncol ; 12: 262, 2014 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25142438

RESUMO

BACKGROUND: A nonrecurrent laryngeal nerve (NRLN) is a rare but potentially serious anatomical variant. Although the incidence is reported to be 0.3% to 1.3%, it carries a much higher risk of palsy during thyroid surgery. The objective of this study is to investigate the usefulness of computed tomography (CT) for preoperative identification and intraoperative neuromonitoring identification (IONM) of NRLN in thyroid cancer patients. METHODS: The preoperative neck CT scans from 1,574 patients who needed thyroid surgery were examined. Absence of the brachiocephalic artery (BCA) and the presence of arteria lusoria were defined as positive with NRLN. Systematic intraoperative neuromonitoring (IONM) was also carried out for these 1,574 patients to localize and identify NRLN. A negative electromyography (EMG) response from lower vagal stimulation but a positive EMG response from the upper position indicated the occurrence of an NRLN. RESULTS: Nine NRLN (0.57%) were intraoperatively identified out of the 1,574 patients, and no patient with a NRLN showed preoperative clinical symptoms related to NRLN. Prior to the operation, surgeons identified only seven suspected NRLN cases based on identification of arteria lusoria. But a review of CT scans revealed that all cases could be identified by vascular anomalies. All patients were successfully detected at an early stage of operation using intraoperative neuromonitoring (IONM). Postoperative vocal cord function was normal in all patients. CONCLUSIONS: CT of the neck is a reliable method for predicting NRLN before thyroid cancer surgery. However, some image features can be easily missed. Neurophysiology helps the surgeon to identify the NRLNs more precisely. Combining the two evaluation methods may decrease the incidence of nerve palsy, especially in cases of NRLN. Considering that CT is expensive, requires an X-ray, and achieves less information than ultrasound (US) concerning thyroid nodules, we suggest that applying US and IONM is more reasonable.


Assuntos
Complicações Intraoperatórias/prevenção & controle , Monitorização Neurofisiológica Intraoperatória/métodos , Traumatismos do Nervo Laríngeo/prevenção & controle , Nervos Laríngeos/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tireoidectomia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
20.
J Asian Nat Prod Res ; 16(12): 1119-25, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25367455

RESUMO

Three new phenolic glycosides, named as glycopentosides A-C (1-3), along with nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis pentaphylla. Their structures were determined by using spectroscopic and chemical methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide production in lipopolysaccharides-stimulated RAW 264.7 cells with IC50 value of 12.14 µM.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Fenóis/isolamento & purificação , Rutaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Fenóis/química , Fenóis/farmacologia , Caules de Planta/química
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