RESUMO
Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium and ranks the third largest diagnosed malignancy in the world. Many studies have shown that the high risk of CRC is believed to be related to the formation of biofilms. To prove causation, it will be significant to decipher which specific bacteria in biofilms initiate and maintain CRC and fully describe their underlying mechanisms. Here we introduce a bacterial driver-passenger model. This model added a novel and compelling angle to the role of microorganisms, putting more emphasis on the transformation of bacterial composition in biofilms which play different roles in the development of CRC. In this model, bacterial drivers can initiate the formation of CRC through genotoxicity, while bacterial passengers maintain the CRC process through metabolites. On the basis of these pathogens, we further turned our attention to strategies that can inhibit and eradicate these pathogenic biofilms, with the aim of finding new ways to hinder colorectal carcinogenesis.
Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Bactérias , Biofilmes , Carcinogênese/patologia , Neoplasias Colorretais/patologia , HumanosRESUMO
INTRODUCTION: tibial plateau fractures affect functionality of a large load bearing joint such as the knee, due to its multiple compromises, not only articular but also the ones including soft tissues. This study aims to evaluate the stability, function, alignment, associated injuries and complications of the knee after surgery and tibial plateau fractures rehabilitation. MATERIAL AND METHODS: a descriptive prospective observational study was carried out where patients with a tibial plateau fracture who had undergone surgery, that accomplish the inclusion criteria were included, in the period from April 2018 to June 2019. Analysis of variables was performed with t tests for independent samples. RESULTS: from a total of 92 patients with tibial plateau fracture, 66 (71%) were able to achieve the minimum six months follow-up. The most common fracture according to Schatzker classification was type II with 33.3%, and the most common according to Luo classification was the medial, lateral and posterior three column with 39.4%. More than 70% of patients who underwent surgery due to tibial plateau fractures developed soft tissue injury, therefore knee instability, specially with a higher rate of anterior cruciate ligament injuries or anterior instability. CONCLUSION: an important proportion of patients who underwent surgery for tibial plateau fractures have knee ligament injuries.
INTRODUCCIÓN: las fracturas de los platillos tibiales afectan la funcionalidad de una gran articulación de carga como la rodilla debido a sus múltiples compromisos no sólo articulares, sino también de tejidos blandos. Este estudio tiene como objetivo evaluar la estabilidad, función, alineación, lesiones asociadas y complicaciones de la rodilla después de intervención quirúrgica y rehabilitación de fractura de platillos tibiales. MATERIAL Y MÉTODOS: se realizó estudio observacional prospectivo descriptivo, donde se incluyeron los pacientes con fractura de platillos tibiales intervenidos quirúrgicamente que cumplieran los criterios de inclusión en el período comprendido entre Abril de 2018 y Junio de 2019. Se hizo análisis de variables con pruebas t para muestras independientes. RESULTADOS: de un total de 92 pacientes con fractura de platillos tibiales, 66 (71%) lograron completar los seis meses mínimos de seguimiento. La fractura más común según la clasificación de Schatzker fue tipo II con 33.3% y la más común según la clasificación de Luo fue la de tres columnas medial, lateral y posterior con 39.4%. Más de 70% de los pacientes intervenidos por fracturas de platillos tibiales presentaron lesión de tejidos blandos, por ende, una inestabilidad de rodilla, especialmente con mayor índice de lesiones del ligamento cruzado anterior e inestabilidad anterior. CONCLUSIÓN: una proporción importante de los pacientes intervenidos por fractura de platillos tibiales tienen lesión ligamentaria de rodilla.
Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Fraturas da Tíbia , Humanos , Tíbia , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/complicações , Traumatismos do Joelho/cirurgia , Fixação Interna de Fraturas , Estudos RetrospectivosRESUMO
Hip fractures are considered a public health problem in the world. Among hip fractures we find subtrochanteric fractures that are defined as proximal femur fractures located in the trochanteric region within 5 cm below the lesser trochanter; and they have an approximate incidence of 15 to 20 per 100,000 people. The objective of this case is to report the success of the reconstruction of an infected subtrochanteric fracture, with a non-vascularized fibular segment and a distal femur condylar support plate. Clinical case: 41-year-old male patient suffering from a right subtrochanteric fracture as a result of a traffic accident that required the use of osteosynthesis material. With subsequent rupture of the cephalomedullary nail in its proximal third, non-union of the fracture and infections at the fracture site. He was treated with multiple surgical lavages, antibiotic therapy, and an unconventional orthopedic and surgical procedure, such as the use of a distal femur condylar support plate and an endomedullary bone graft with a 10-cm segment of non-vascularized fibula. Patient with satisfactory and favorable evolution.
Las fracturas de cadera se consideran un problema de salud pública en el mundo, entre las fracturas de cadera encontramos las subtrocantéricas, que se definen como fracturas proximales de fémur situadas en la región trocantérea dentro de los 5 cm debajo del trocánter menor; tienen una incidencia aproximada de 15 a 20 por cada 100,000 personas. El objetivo de este de caso es reportar el éxito de la reconstrucción de una fractura subtrocantérica infectada, con un segmento del peroné no vascularizado y una placa de soporte condíleo de fémur distal. Caso clínico: masculino de 41 años de edad que sufre fractura subtrocantérica derecha producto de un accidente de tránsito que requirió manejo de osteosíntesis. Con posterior ruptura del clavo cefalomedular en su tercio proximal, no unión de la fractura e infecciones en sitio de la fractura. Fue tratado con múltiples lavados quirúrgicos, antibioticoterapia y un procedimiento ortopédico y quirúrgico poco convencional como el uso de una placa de soporte condíleo de fémur distal y un injerto óseo endomedular con un segmento de 10 cm de peroné no vascularizado. Paciente con evolución satisfactoria y favorable.
Assuntos
Fraturas do Quadril , Extremidade Inferior , Masculino , Humanos , Adulto , Autoenxertos , Fêmur , Fraturas do Quadril/cirurgia , FíbulaRESUMO
PURPOSE: Disturbed process of B-cell differentiation into plasmablasts (PBs)/plasma cells (PCs) is involved in multiple myeloma (MM). New strategies will be required to eliminate the MM cell clone for a long-term disease control. Because of its PB-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to search novel targets for PBs/PCs. METHODS/PATIENTS: Affymetrix microarrays and RNA-sequencing assays were used to search a novel different molecule (Gm6377) between PBs/PCs and mature B cells. Cell counting kit-8 (CCK8), flow cytometry (FACS), xenograft mouse model, and the luciferase reporter system were used to assess the effect of Gm6377 on SP 2/0 cell proliferation, cell cycle, tumor growth, and Myc promoter activation, respectively. RESULTS: We found that B cells expressed a high level of Gm6377 mRNA, whereas Gm6377 mRNA was decreased in PCs. In addition, SP 2/0 cells also expressed low levels of Gm6377 mRNA. Critically, Gm6377 overexpression suppressed SP 2/0 cell proliferation but not cell cycle. Furthermore, Gm6377 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. Finally, we found that Gm6377 suppressed SP 2/0 cell proliferation by reducing the activation of the Myc promoter. CONCLUSIONS: These results suggest that Gm6377 suppresses myeloma SP 2/0 cell growth by suppressing Myc. Thus, modulation of Gm6377 may be a potential therapeutic way to treat MM.
Assuntos
Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Apoptose/fisiologia , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Regulação para Baixo , Xenoenxertos , Camundongos , Camundongos Endogâmicos C57BL , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Resumen: La lesión del nervio axilar (o circunflejo) aislada es poco frecuente, ésta suele presentarse asociada a una lesión del plexo braquial. En nuestra institución, en un período comprendido entre los años 2015-2017, se ha observado una frecuencia de sólo 0.4% de esta lesión. Con el presente reporte de caso se resalta la relación de la luxación de hombro con lesión del nervio axilar aislada. Caso clínico: Masculino de 31 años de edad, con trauma en hombro derecho, secundario a caída de su propia altura en accidente laboral. Radiografía de ingreso de hombro derecho muestra luxación anteroinferior de articulación glenohumeral, asociada a fractura de troquiter. Es intervenido quirúrgicamente, con reducción cerrada de articulación glenohumeral y osteosíntesis de troquiter. Posterior a ello, el paciente presenta atrofia marcada del deltoides, se ordena electromiografía que evidencia lesión completa del nervio axilar sin reinervación.
Abstract: Isolated lesion of the axillary (or circumflex) nerve is infrequent, this is usually associated with a brachial plexus injury. In our institution, in a period comprised between the years 2015-2017, a frequency of only 0.4% of this injury has been observed. Clinical case: Male patient of 31 years of age, with trauma in the right shoulder, caused by fall of his own height in work accident. The admission graph of the right shoulder shows anterior inferior dislocation of the glenohumeral joint, associated with a greater tubercle fracture. He underwent surgery, with closed reduction of the glenohumeral joint and osteosynthesis of the greater tubercle. The patient later presents marked atrophy of the deltoid, electromyography is ordered that shows complete lesion of the axillary nerve without reinnervation.
Assuntos
Humanos , Masculino , Adulto , Luxação do Ombro , Articulação do Ombro , Plexo Braquial , Neuropatias do Plexo Braquial , Ombro , Lesões do OmbroRESUMO
Isolated lesion of the axillary (or circumflex) nerve is infrequent, this is usually associated with a brachial plexus injury. In our institution, in a period comprised between the years 2015-2017, a frequency of only 0.4% of this injury has been observed. Clinical case: Male patient of 31 years of age, with trauma in the right shoulder, caused by fall of his own height in work accident. The admission graph of the right shoulder shows anterior inferior dislocation of the glenohumeral joint, associated with a greater tubercle fracture. He underwent surgery, with closed reduction of the glenohumeral joint and osteosynthesis of the greater tubercle. The patient later presents marked atrophy of the deltoid, electromyography is ordered that shows complete lesion of the axillary nerve without reinnervation.
La lesión del nervio axilar (o circunflejo) aislada es poco frecuente, ésta suele presentarse asociada a una lesión del plexo braquial. En nuestra institución, en un período comprendido entre los años 2015-2017, se ha observado una frecuencia de sólo 0.4% de esta lesión. Con el presente reporte de caso se resalta la relación de la luxación de hombro con lesión del nervio axilar aislada. Caso clínico: Masculino de 31 años de edad, con trauma en hombro derecho, secundario a caída de su propia altura en accidente laboral. Radiografía de ingreso de hombro derecho muestra luxación anteroinferior de articulación glenohumeral, asociada a fractura de troquiter. Es intervenido quirúrgicamente, con reducción cerrada de articulación glenohumeral y osteosíntesis de troquiter. Posterior a ello, el paciente presenta atrofia marcada del deltoides, se ordena electromiografía que evidencia lesión completa del nervio axilar sin reinervación.
Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Luxação do Ombro , Articulação do Ombro , Adulto , Humanos , Masculino , Ombro , Lesões do OmbroRESUMO
Neurokinin-1 receptor (NK1R) is a high affinity Substance P (SP) receptor and plays a key role in visceral hypersensitivity in irritable bowel syndrome (IBS). Early life stress is a significant risk factor in IBS. The aim of the present study was to investigate the influence of neonatal maternal separation on the expression and distribution of SP and its receptor along the brain-gut axis in a neonatal maternally separated rat model with visceral hypersensitivity. Male neonatal Sprague-Dawley rats, 2-21-day old, were randomly distributed into maternal separation groups of 3 h daily maternal separation (MS) or non-handling (NH). These rats underwent colorectal balloon distention (CRD) upon reaching adulthood. Immunofluorescence was used to examine the distal colon, lumbosacral spinal cord, and the brainstem to semi-quantitatively determine SP and NK1R expression before and after CRD. The following features were assessed: percentage SP-positive area in colonic muscle layer, the number of NK1R-positive myenteric plexus, SP-positive area and NK1-positivity score in the dorsal horn and the brainstem. Neither of these was altered in the MS and NH groups before or after CRD. These results suggest that the SP system might play little role in the development of visceral hyperalgesia in the neonatal maternal separation rat model.
Assuntos
Hiperalgesia/metabolismo , Síndrome do Intestino Irritável/metabolismo , Receptores da Neurocinina-1/metabolismo , Substância P/metabolismo , Animais , Colo/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Privação Materna , Músculo Liso/metabolismo , Plexo Mientérico/metabolismo , Especificidade de Órgãos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismoRESUMO
Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.
Assuntos
Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
Castanopsis eyrei (Fagaceae) is one of the dominant tree species in mid-subtropical, evergreen, broad-leaved forests. We obtained 14 pairs of simple sequence repeat (SSR) primers from previous studies, which were used to analyze 90 C. eyrei individuals from three populations at different altitudes. Low heterozygosity was detected (Fis = 0.6124), and the observed heterozygosity was lower than the expected heterozygosity, possibly because of inbreeding and/or the population substructure. The genetic differentiation between populations was relatively low (Fst = 0.0645); only 7% of the total genetic variation occurred between populations. The medium-altitude population had higher genetic diversity than the low-altitude or high-altitude populations.
Assuntos
Fagaceae/genética , Repetições de Microssatélites , Árvores/genética , Altitude , Florestas , Heterogeneidade Genética , Variação Genética , Microclima , Folhas de Planta/genéticaRESUMO
Hemocyanin is an important respiratory protein in many arthropod and mollusk species. Here, four cDNAs (SpHc1, SpHc2, SpHc3, and SpHc4), encoding distinct hemocyanin subunits from Scylla paramamosain were cloned using EST analyses and the rapid amplification of cDNA ends. The four full-length cDNA fragments (SpHc1-4) were 2281, 2002, 2184, and 2069 bp, respectively, and they encoded four putative proteins (570-676 amino acids) with a molecular mass of ~65.0-76.8 kDa. Quantitative real-time PCR analyses revealed that the four genes were mainly expressed in the hepatopancreas, testis, and hemocytes. SpHc mRNA expression during continuous developmental stages in zoeal phases (Z1, Z2, Z3, Z4, and Z5), megalopa, and juvenile crab I stages were also detected. The expression levels of SpHc3 and SpHc4 were higher than that of SpHc1 and SpHc2 during the first six stages, and they sharply declined during the juvenile stage. After infection with Vibrio parahaemolyticus, the temporal expression of both the four SpHc mRNAs in the megalopa stage rapidly declined during the first 3 h, followed by upregulation and peak expression at 12 h after the challenge. The expression levels of the four SpHc subunits were upregulated at 48 h after the challenge, and were then gradually downregulated. These findings suggest that hemocyanin may potentially be involved in the crab immune response, and that the role of the four subunits may differ in different tissues and during various developmental stages.
Assuntos
Braquiúros/metabolismo , Hemocianinas/metabolismo , Vibrio/patogenicidade , Sequência de Aminoácidos , Animais , Braquiúros/genética , Braquiúros/crescimento & desenvolvimento , Braquiúros/microbiologia , Regulação da Expressão Gênica no Desenvolvimento , Hemocianinas/genética , Hemócitos/metabolismo , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Especificidade de Órgãos , Pâncreas/metabolismo , Testículo/metabolismoRESUMO
Mitochondrial DNA mutations play crucial roles in the pathogenesis and progression of human malignancies. Therefore, to determine whether maternal background or mitochondrial DNA somatic mutations were essential cofactors in the lung cancer of Chinese patients as well, the complete mitochondrial DNA displacement loop of the primary cancerous, matched para-cancerous normal and distant normal tissues for 79 Chinese patients with lung cancer were analyzed in this study. Our results indicated that the higher detected frequency of haplogroups prevalent in southern East Asia (53.16%; 42/79) versus those of northern East Asia in the studied population supported the southern East Asian characteristics of the Chinese lung cancer group. Further statistical analysis revealed that the haplogroups F* and G* contributed to the susceptibility to lung cancer in Chinese patients. In addition, by comparing sequences from different tissues of the same patients, a total of eight somatic mutations from six patients were detected. Combined with the fourteen somatic mutations identified in our previous study, the somatic mutation spectrum of the 79 Chinese patients with lung cancer was 25.32% (20/79). Our results suggest that mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Yunnan, Southwest China, and that somatic mitochondrial DNA mutations in the displacement loop can serve as potential biomarkers for clinical utility.
Assuntos
DNA Mitocondrial/genética , Predisposição Genética para Doença , Genoma Mitocondrial , Haplótipos , Neoplasias Pulmonares/genética , Mutação , Povo Asiático , Sequência de Bases , Feminino , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , FilogeniaRESUMO
We explored the mechanism of the development from sensitivity to resistance to carbapenem in Pseudomonas aeruginosa. Two P. aeruginosa strains were collected during treatment with carbapenem. Strain homology was investigated using pulsed-field gel electrophoresis. Porin oprD2 expression was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The minimum inhibitory concentrations (MICs) of imipenem and meropenem with or without MC207110 were determined using the agar dilution method. The expression level of efflux pump mRNA was tested using real-time polymerase chain reaction. Metallo-lactamases (MBLs) were screened using the EDTA-disk synergy test. Genes encoding MBLs were amplified and then analyzed by DNA sequencing. The two treated strains belonged to the same pulsed-field gel electrophoresis type. The SDS-PAGE profile of the P. aeruginosa strains revealed that the 46-kDa membrane protein OprD2 of IMP(R)MEM(R) type strains was lost, whereas OprD2 of 1 IMP(S)MEM(S) strain was normal. With or without MC207110 treatment, the MIC of carbapenem-resistant P. aeruginosa decreased by 4-fold, while the MIC of carbapenem-sensitive P. aeruginosa did not. Compared with the carbapenem-sensitive strain, MexX mRNA expression in the carbapenem-resistant strain increased by 102.5-fold, while the mRNA expression of other efflux pumps did not markedly increase. Neither carbapenem-resistant nor carbapenem-sensitive P. aeruginosa produced MBL. The mechanism of development from sensitivity to resistance of P. aeruginosa to carbapenem during carbapenem treatment is due to porin oprD2 loss and an increased expression level of MexXY-OprM.
Assuntos
Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana Transportadoras/genética , Porinas/genética , Pseudomonas aeruginosa/genética , Resistência beta-Lactâmica/genética , Proteínas da Membrana Bacteriana Externa/agonistas , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/agonistas , Proteínas de Bactérias/metabolismo , Dipeptídeos/farmacologia , Combinação de Medicamentos , Eletroforese em Gel de Campo Pulsado , Eletroforese em Gel de Poliacrilamida , Imipenem/farmacologia , Proteínas de Membrana Transportadoras/agonistas , Proteínas de Membrana Transportadoras/metabolismo , Meropeném , Testes de Sensibilidade Microbiana , Porinas/deficiência , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Tienamicinas/farmacologia , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Liver metastasis is associated with poor prognosis in gastric cancer. Surgical resection and systemic chemotherapy have been reported to be effective in gastric cancer with liver metastasis (GCLM). However, the best strategy for GCLM has not been established. METHODS: From May 2009 to July 2014, a consecutive series of GCLM patients in Zhongshan Hospital of Fudan University were studied. Treatment strategies were evaluated with regard to different extents of metastases. RESULTS: A total of 163 patients were included. The overall survival was 10.1 months. Active treatment significantly prolongs the survival of GCLM patients. The overall survival time for patients with liver-limited metastases and extra-hepatic liver metastases was 11.6 mo and 8.7 mo, respectively (P = 0.012). The median survival time for liver-limited disease of H1, H2 and H3 was 14.2, 15.8, and 8.5 months, respectively (H3 vs H2, P = 0.001; H3 vs H1, P = 0.000; H1 vs H2, P = 0.900). Systemic chemotherapy was chosen as the main strategy for the 'extensive' patients with extra-hepatic metastases and H3 type liver-limited metastases. Patients' survival was benefited by multi-line chemotherapy. No differences were shown between systemic chemotherapy and curative resection or palliative resection in H1 and H2 liver-limited metastases (16.0 mo vs 12.0 mo, P = 0.711; 16.0 vs 18.8 months, P = 0.654). CONCLUSION: Systemic chemotherapy was the main treatment for gastric cancer patients with liver metastases. Curative resection could be considered for highly selected patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidadeRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by non-excessive alcohol consumption and is the most common cause of elevated levels of serum liver enzymes. We examined changes in adiponectin (APN) and tumor necrosis factor-α (TNF-α) in type 2 diabetes mellitus (T2DM) complicated by NAFLD and their relationships with insulin resistance (IR). Forty-two T2DM, 39 NAFLD, and 45 T2DM complicated with NAFLD (complicated group) patients were enrolled in this study. Body mass index, fasting blood plasma glucose (FPG), fasting insulin, triglyceride (TG), alanine aminotransferase, gamma-glutamyl transpeptidase, APN, TNF-α, and homeostasis model of assessment (HOMA)-IR were determined. The degree of fatty liver was graded according to liver/spleen computed tomography ratio and intrahepatic vessel manifestations. Compared with the T2DM and NAFLD groups, fasting blood plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, TG, TNF-α, and HOMA-IR in the complicated group were significantly increased, while APN was significantly reduced. Body mass index in the complicated group was significantly higher than in the T2DM group. The complicated group was prone to severe fatty liver compared with the NAFLD group. APN was negatively correlated with body mass index, fasting blood plasma glucose, TG, TNF-α, and HOMA-IR. TNF-α was negatively correlated with APN, but positively correlated with FPG, fasting insulin, TG, and HOMA-IR. The complicated group had clear IR. A more severe degree of fatty liver was associated with higher HOMA-IR and TNF-α and lower APN. APN was an important factor for antagonizing inflammation and mitigating IR.
Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Pesos e Medidas Corporais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.
Assuntos
Análise Mutacional de DNA , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Mitocôndrias/genética , Sequência de Bases/genética , Humanos , Mutação/genéticaRESUMO
Transforming growth factor-beta 1 (TGF-ß1), a member of the transforming growth factor beta family, functions as a multi-functional cytokine and plays a key role in cellular growth, proliferation, and differentiation. The 509 C/T polymorphism in the TGF-ß1 gene has been implicated in the outcome of hepatitis C virus (HCV) infection; however, little is known regarding the relationship between TGF-ß1 gene mutations and the development of hepatocellular carcinoma (HCC) in HCV-infected patients. The aim of the study was to evaluate the effect of the TGF-ß1 polymorphisms 509 C>T on the occurrence of HCC in patients chronically infected with HCV in a Chinese Han population. The results showed that HCC patients had a higher frequency of the TGF-ß1 -509 TT genotype distribution of the TGF-ß1 -509 polymorphism and a lower frequency of the CC genotype. Serum TGF-ß1 levels were significantly higher in patients with the TT genotype than in those with the CC genotype. In this study, we confirmed that the TGF-ß1 polymorphism 509 C>T is associated with the risk of HCC in HCV-infected patients.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Hepatite C/complicações , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/genética , Povo Asiático/genética , Carcinoma Hepatocelular/etiologia , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Clinical and experimental data have demonstrated that genetic factors play an important role in determining the susceptibility to ischemic stroke (IS). The present study was performed to clarify the association between the pre-microRNA-149 (miR-149) single nucleotide polymorphism rs71428439 and the risk of IS in the Jiangsu Han population. Polymerase chain reaction and restriction fragment length polymorphism were performed to identify the genotypes of the miR-149 single-nucleotide polymorphism rs71428439 in 730 unrelated subjects (IS, 348; healthy controls, 382). Plasma levels of homocysteine were determined using a radioassay kit. Compared to healthy controls, IS patients had a lower frequency of GG genotype distribution of the hsa-mir-149 polymorphism (11.5 vs 16.0%) and a higher frequency of TT (46.6 vs 39.0%). The risk of IS was significantly lower among subjects carrying the GG genotype than subjects carrying the AA genotype (odds ratio (95% confidence interval): 0.603 (0.382- 0.952), P = 0.030) or at least carrying the G allele than patients carrying the A allele (odds ratio (95% confidence interval): 0.769 (0.620-0.954), P = 0.019). Levels of folate were statistically higher in patients with the TT genotype (8.59 ± 7.75 ng/mL) than in those with the CC genotype (6.32 ± 5.97 ng/mL) in IS patients. Our results suggest that the miR- 149 single nucleotide polymorphism rs71428439 influences plasma levels of homocysteine and is associated with IS risk in the Jiangsu Han population.
Assuntos
Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Povo Asiático/genética , Isquemia Encefálica/genética , China/etnologia , Feminino , Homocisteína/sangue , Homocisteína/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , RiscoRESUMO
φC31 integrase encoded by Streptomyces phage can mediate site-specific recombination between phage and host genomes. The recombination direction is generally considered to be accurately regulated, but the regulatory mechanisms involved are still unclear. Recently, some hyperactive mutants of φC31 integrase that can bypass the regulatory steps have been isolated and extensively studied. A putative coiled-coil region is found to play a critical role in controlling recombination direction. Further analysis led us to the speculation that at least two regions in the N-terminal domain of φC31 integrase are involved in the tetrameric interfaces and that the putative coiled coil interacts with one of the regions to regulate the recombination direction.
Assuntos
Bacteriófagos/enzimologia , Integrases/metabolismo , Recombinação Genética , Sequência de Aminoácidos , Pareamento Cromossômico , Integrases/química , Modelos Genéticos , Dados de Sequência Molecular , Mutação/genética , Multimerização Proteica , Estrutura Terciária de Proteína , Alinhamento de SequênciaRESUMO
PURPOSE: The role of interleukin-17 (IL-17) in the tumor microenvironment is controversial. We analyzed the in situ tumor expression of IL-17 in colorectal cancer (CRC), adenoma and non-tumor tissue to explore the possible correlation of IL-17 expression to clinicopathological characteristics, tumor-infiltrating neutrophils (TINs) and survival in CRC. METHODS: We reviewed the records of 78 consecutive patients diagnosed with CRC. Archival tissues were used. Thirty-six patients with colorectal adenoma were also included. From the 78 CRC patients, we randomly chose 40 cases and collected non-tumor tissue at 10 cm from the edge of the resected tumor. Immunohistochemistry was performed using anti-IL-17 and anti-CD15 (targeting neutrophils) antibody, respectively. Real-time PCR was used to detect IL-17 mRNA in different tissues. Associations between IL-17 expression, clinicopathological parameters and prognosis were evaluated. RESULTS: The level of IL-17 mRNA was higher in CRC than in adenoma and non-tumor tissue (P < 0.05). Positive IL-17 protein expression was observed more frequently in CRC as compared to colorectal adenoma and non-tumor tissue, respectively (P < 0.01). IL-17 expression correlated to well differentiation and early stage CRC. The number of CD15+ neutrophils significantly increased in CRC and positively correlated to the expression of IL-17 (P < 0.05). Both KaplanMeier analysis and multivariate Cox regression analysis indicated that patients with positive IL-17 expression showed better overall survival. CONCLUSIONS: The association between IL-17 expression and the clinicopathological parameters, as well as the clinical outcome suggests a significant role of IL-17 in CRC. IL-17 is a marker of favorable prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Interleucina-17/metabolismo , Adenoma/metabolismo , Idoso , Neoplasias Colorretais/diagnóstico , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígenos CD15/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento , Microambiente TumoralRESUMO
The cucumber (Cucumis sativus L.) is an important crop grown worldwide. In this study, the genetic diversity of 42 cucumber cultivars in China was analyzed using 51 pairs of simple sequence repeat (SSR) primers. These primers identified 129 polymorphic loci, 95.6% of which were polymorphic. The mean effective number of alleles, mean Nei's gene diversity, and mean Shannon's information index were 0.36, 0.16, and 0.21, respectively. A cluster analysis demonstrated that the 42 cultivars could be divided into three groups, a result that was largely consistent with those of a principal component analysis (PCA). The PCA indicated that the three groups displayed significant variation in fruit traits. The cultivars of group 1 tended to have longer fruits (>30 cm), longer fruit ends (>4 cm), larger fruit diameters (>5 cm), a sharp strigose fruit spine, and the same fruit end shape. The basal color of the fruit in group 2 was dark green. Group 3 cultivars have no wax or mottling on the fruit surface. Our study demonstrates the value of our SSR primers for assessing genetic diversity in cucumber.