RESUMO
Inflammation plays an important role in cerebral ischemia reperfusion, which can cause severe damage to the brain and may lead to cerebral hemorrhage transformation. p38-mitogen-activated protein kinase (p38mapk) has been implicated in the etiology of a number of diseases because it is a cause of inflammation, but comparatively little research has been carried out into its role in the etiology of ischemia reperfusion. We investigated the expression of p38mapk in cerebral ischemia reperfusion to gain a better understanding of its potential role in hemorrhagic transformation (HT). One hundred rats were randomly divided into three groups: an ischemia reperfusion group, an ischemia group, and a sham-operated group. We carried out neurological deficit assessments, infarct volume measurements, histopathological examinations, and immunohistochemistry analyses. p38mapk was overexpressed in the ischemia reperfusion group, which exhibited severe tissue damage and greater edema than the other two groups. These results suggest that p38mapk plays an important role in cerebral ischemia reperfusion, and may be one of the causes of HT.
Assuntos
Isquemia Encefálica/enzimologia , Encéfalo/enzimologia , Traumatismo por Reperfusão/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/cirurgia , Contagem de Células , Ativação Enzimática , Masculino , Necrose , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/cirurgiaRESUMO
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules of about 22 nucleotides in length. miRNAs are highly conserved in both plants and animals, and function as gene regulators by binding to the 3'-untranslated region of target mRNAs for cleavage and/or translational repression. miRNA biogenesis, stability, and regulation of expression are strongly sequence dependent. Sequence variants, such as single nucleotide polymorphisms (SNPs) in pri-miRNA, pre-miRNA, promoter regions, or miRNA-target sites, can influence miRNA function, thereby contributing to the pathological features of human disease. In this review, we focus on miRNA-related SNPs in gastric cancer and comprehensively analyze some commonly studied SNPs.
Assuntos
MicroRNAs/genética , Neoplasias Gástricas/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genéticaRESUMO
Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Galantamina/uso terapêutico , Proteína HMGB1/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/mortalidade , Lesão Pulmonar Aguda/patologia , Análise de Variância , Animais , Ensaio de Imunoadsorção Enzimática , Proteína HMGB1/antagonistas & inibidores , Interleucina-6/sangue , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Mortalidade , Tamanho do Órgão , Peroxidase/metabolismo , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangueRESUMO
We investigated the presence of serum antinuclear antibodies (ANAs) and autoantibodies and their relationship with serum prognostic indicators in lymphoma patients. The study population comprised 127 patients diagnosed with lymphoma and 138 healthy control subjects. The blood samples of the participants were assayed for ANAs by immunofluorescence, and autoantibodies were detected by western blotting. Serum ANAs were detected in 31.5 (40/127) and 6.5% (9/138) of lymphoma patients and control subjects, respectively. There was a statistically significant difference between the lymphoma and the control groups (P < 0.05). The level of lactate dehydrogenase in the ANA-positive subjects was significantly lower than in the ANA-negative subjects (P < 0.05). Low ANA titers (1:100) were commonly found in the ANA-positive subjects and the control subjects, and the fluorescence models were diverse. Autoantibodies were found in 35% (14/40) of the ANA-positive patients by western blotting. Detection of ANAs in lymphoma patients helps in determining the diagnosis and prognosis of lymphoma, but has no independent diagnostic value; there are still various autoantibodies of unknown significance that require further study.
Assuntos
Anticorpos Antinucleares/sangue , Biomarcadores Tumorais/sangue , Linfoma/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the distribution of human leukocyte antigen (HLA)-B27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang. B27-positive patients with ankylosing spondylitis were subtyped by using polymerase chain reaction-sequence-based typing. The HLA-B27 subtype frequencies of Uygur patients were compared with those in Han patients in Xinjiang and the other areas of China. B*2705 was the predominant subtype in Uygur patients with a frequency of 58.95%, which was much higher than that in Han patients in Xinjiang (31.58%, P < 0.05) and the other areas of China (excluding the Shandong region, which was 63.89%). The frequency of B*2704 (27.37%) in Uygur patients was the lowest and significantly lower than that in Han patients (61.18%, P < 0.05) and in 8 other areas of China. B*2710 has not been previously reported in Uygur ankylosing spondylitis patients; B*2704 was the main (61.18%) subtype in Han patients in Xinjiang, followed by B*2705 (31.58%) and was similar to the characteristics of Han patients in the other areas of China. B*2724 in Han ankylosing spondylitis patients has not been previously reported. Additionally, the B*2702/B*2705 homozygote was identified in Uygur patients. B*2702/B*2704, B*2704/B*2705, and B*2705/B*2705 homozygotes were identified in 3 Han patients. The distribution of HLAB27 subtypes in Uygur ankylosing spondylitis patients in Xinjiang significantly differed from that in Han patients. Understanding the distribution of HLAB27 subtypes in ethnic minority populations of Xinjiang is important for anthropological genetic studies and for analyzing the impact of genetic background on ankylosing spondylitis susceptibility.
Assuntos
Predisposição Genética para Doença , Antígeno HLA-B27/genética , Espondilite Anquilosante/genética , Adolescente , Adulto , Idoso , Alelos , Povo Asiático/genética , China , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/patologiaRESUMO
We conducted a cohort study to investigate whether 3 potential single nucleotide polymorphisms (SNPs) in the xeroderma pigmentosum complementation group G (XPG) gene could predict the survival of advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based doublet chemotherapy. We enrolled 262 patients with histologically confirmed NSCLC between November 2007 and December 2008 in this study. The 3 SNPs (rs2296147T>C, rs2094258C>T, and rs873601G>A) were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Older age, Eastern Cooperative Oncology Group performance score ≥2 and higher disease stage were associated with shorter survival. In the Cox proportional hazard model, patients carrying the rs2296147 TT genotype and the T allele had a significantly reduced risk of developing progressive disease or dying from NSCLC. The HRs (95%CI) were 0.31 (0.13-0.73) and 0.44 (0.24-0.83) for progression-free survival and 0.32 (0.14-0.71) and 0.54 (0.32-0.98) for overall survival, respectively. Moreover, advanced NSCLC patients carrying the rs2094258 GG and the G allele had a significantly decreased risk of developing progressive disease. The HRs (95%CI) for the rs2094258 GG genotype and the G allele were 0.35 (0.16-0.80) and 0.45 (0.23-0.86) for overall survival, respectively. We suggest that the rs2296147 and rs2094258 polymorphisms could be used as surrogate markers, leading to individualization of NSCLC treatment strategies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Estudos de Associação Genética , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Fatores de Transcrição/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Demografia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Lumbar intervertebral disc degeneration (IDD) is a common clinical pathology and has become a focus for research in recent years. Matrix metalloproteinases (MMPs) are enzymes responsible for the degradation of almost all extracellular matrix proteins (ECM). The over-expression of MMPs or tissue inhibitors of metalloproteinases (TIMPs) may disrupt the dynamic balance of the ECM. Therefore, in the current study, the expression levels of MMP-1 and TIMP-1 in lumbar IDD patients were evaluated in an attempt to elucidate their role in IDD pathogenesis and progression. In total, 60 IDD patients were recruited as the experimental group, along with 20 cases of lumbar vertebral injury without disc degeneration as the control group. Preoperative venous blood samples were collected, and intervertebral disc tissues were collected from the lesion during surgery. Serum and tissue levels of MMP-1 and TIMP-1 were quantified by enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum and tissue MMP-1 levels in IDD patients were significantly higher than those in the control group (P < 0.05). Additionally, sub-group analysis revealed that severe IDD patients had higher MMP-1 levels compared with mild or moderate IDD patients (P < 0.05). However, there were no significant differences in TIMP- 1 levels in either the serum or tissues of IDD patients compared to patients in the control group (P > 0.05). These results demonstrate that MMP-1 expression is increased in IDD, with higher expression observed in more severe cases, whereas TIMP-1 expression was similarly expressed in both normal and degenerated discs.
Assuntos
Degeneração do Disco Intervertebral/enzimologia , Metaloproteinase 1 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto , Idoso , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Região Lombossacral/patologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Radiografia , Inibidor Tecidual de Metaloproteinase-1/genética , Adulto JovemRESUMO
The aim of this study was to examine the interleukin-1B (IL-1B) gene promoter region -31 (IL-1B-31) polymorphism distribution characteristic of Hakka gastric cancer patients in Guangdong Province and to explore its association with gastric cancer. We used the 1:1 case-control method, matrix-assisted laser desorption ionization flight time mass spectrometry, and MassARRAY-IPLEX technology to genotype IL-1B-31 (-31C> T) in 52 Hakka gastric cancer patients and 52 Hakka control subjects in Meizhou. Three genotypes - CT, TT, and CC - of IL-1B-31 were found in the Meizhou Hakka population. Their distribution frequencies in the gastric cancer group were 40.38, 40.38, and 19.23%, respectively, whereas the frequencies in control subjects were 57.69, 17.31, and 25.00%, respectively. The differences in frequency distributions of the genotypes between the 2 groups were statistically significant (chi-square = 6.78, P < 0.05). Subjects with the TT genotype had a higher risk of gastric cancer compared with that in subjects carrying the CT genotype (odds ratio = 2.857, 95% confidence interval = 1.114-7.328). This risk was more apparent in male subjects. IL-1B-31 locus polymorphism may be associated with gastric cancer susceptibility in this population, but additional studies with larger sample size are needed to confirm the conclusions.
Assuntos
Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Risco , Fatores Sexuais , Neoplasias Gástricas/epidemiologiaRESUMO
We investigate the potential association of miR-149C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC). A matched case-control study of 152 cases and 304 controls were conducted. The miR-149C>T and miR-499A>G genotypes were analyzed using duplex polymerase chain reaction with restricted fragment length polymorphism. HCC patients were more likely to be smokers and drinkers, have hepatitis B and C virus infections, and a family history of cancer. The miR-149 CC genotype was associated with a reduced risk of HCC, while the miR-499 GG genotype was associated with an increased risk of HCC. However, we did not find that the miR-149 CC and miR-499 GG genotypes were associated with risk of HCC, and no interaction was found between miR-149C>T and miR-499A>G polymorphisms and hepatitis B virus infection. In conclusion, the miRNA-149C>T and miR-499A>G polymorphisms were found to play an important role for HCC risk in China. This finding could be useful in identifying people at high risk for the disease for early intervention.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Hepatite B/complicações , Hepatite B/genética , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/genética , Hepatite C/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , FumarRESUMO
The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the pre-fusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.
Assuntos
Citoesqueleto de Actina/metabolismo , Osteoclastos/metabolismo , Pseudópodes/metabolismo , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Citoesqueleto de Actina/ultraestrutura , Actinas/genética , Actinas/metabolismo , Animais , Catepsina K/genética , Catepsina K/metabolismo , Adesão Celular , Diferenciação Celular , Fusão Celular , Linhagem Celular , Movimento Celular , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Citoplasma/metabolismo , Citoplasma/ultraestrutura , Filaminas/genética , Filaminas/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Osteoclastos/ultraestrutura , Pseudópodes/ultraestrutura , Fosfatase Ácida Resistente a Tartarato , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
The aim of this study was to investigate the characteristics and polymorphisms of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from patients with uveitis to provide an experimental basis for studying the pathogenesis of this disease. RT-PCR amplification of 26 subfamilies of the TCR BV CDR3 gene and immune spectratyping analysis were used to study the pedigree drift of TCR BV CDR3 in PBMCs from the uveitis patients. The following results were obtained: 1) the vast majority of the TCR BV CDR3 spectra in PBMCs in 5 healthy subjects fit the normal (or Gaussian) distribution. The distributions of the TCR BV CDR3 spectra in 4 patients with uveitis were non-normal and showed an abnormal peak including a widowed peak trend, a partial peak, and an irregular abnormal peak. 2) In the 26 TCR BV subfamilies, the abnormal peak frequency was different in the various subfamilies. The BV2 and BV17 (both 3/4) subfamilies had higher frequencies of the non-normally distributed abnormal peak. The BV5.2, BV6, BV15, and BV18 subfamilies showed no abnormal peaks. 3) TCR BV2 and BV17 yielded an abnormal peak in 3 HLA-B27-negative patients; however, no such abnormalities were detected in HLA-B27-positive patients. The abnormal expression of some TCR BV subfamilies in PBMCs from patients with uveitis may be associated with the immune pathogenesis of the disease. Our study provides the basis for further investigations into the pathogenesis of uveitis.
Assuntos
Regiões Determinantes de Complementaridade/genética , Leucócitos Mononucleares/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Uveíte/sangue , Uveíte/imunologia , Adulto , Feminino , Variação Genética , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Uveíte/genética , Adulto JovemRESUMO
We developed EST-PCR markers specific to barley chromosome 2H, for the purpose of effectively tracing alien chromosomes or chromosome parts in the wheat genetic background. The target alien chromosome 2H confers high resistance to pre-harvest sprouting, which is a worldwide natural disaster in wheat. A total of 120 primer pairs were selected by combining the wheat group 2 chromosomes of the EST database and the genome sequences of the new model plant Brachypodium distachyon. Seventy-seven of 120 primer pairs were polymorphic and 31 of 120 primer pairs were monomorphic between a set of wheat-barley chromosome 2H disomic addition/substitution lines and their parents by agarose gel electrophoresis and polyacrylamide gel electrophoresis. Thirty of 77 polymorphic primer pairs including primer pair P120 derived from the basi gene were chromosome 2H-specific. These markers are expected to be valuable in screening of wheat-barley chromosome 2H recombination lines and pre-harvest sprouting resistant varieties.
Assuntos
Etiquetas de Sequências Expressas/metabolismo , Hordeum/genética , Reação em Cadeia da Polimerase/métodos , Triticum/genética , Sequência de Bases , Cromossomos de Plantas , Primers do DNA/metabolismo , Eletroforese em Gel de Ágar , Genes de Plantas/genética , Marcadores Genéticos , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo , Alinhamento de SequênciaRESUMO
Aralia elata is an important medicinal plant in China; it produces large amounts of oleanane type triterpene saponins. A full-length cDNA encoding ß-amyrin synthase (designated as AeAS) was isolated from young leaves of A. elata by reverse transcription-PCR. The full-length cDNA of AeAS was found to have a 2292-bp open reading frame, encoding a protein with 763 amino acid residues. The deduced amino acid sequence of AeAS showed the highest identity (97%) to Panax ginseng ß-amyrin synthase. When AeAS cDNA was expressed in Escherichia coli, an 87.8-kDa recombinant protein was detected by SDS-PAGE and Western blotting. The sequence was also heterologously expressed in the yeast Pichia pastoris, and production of ß-amyrin was detected by HPLC. Tissue expression pattern analysis by real-time reverse transcription-PCR revealed that AeAS is strongly expressed in leaves and stems, and weakly expressed in roots and flowers.