RESUMO
Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Assuntos
População do Leste Asiático , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
A 56-year-old male patient sought medical attention due to a gradual decline in bilateral visual acuity, which had been ongoing for a year and had rapidly worsened over the past three months. He received an initial diagnosis of bilateral concurrent cataracts and bilateral anterior megalophthalmos. Subsequently, cataract removal surgery was performed. During the surgery, it was observed that the patient had lax and fragile zonules of the crystalline lens. To address this issue, the surgical team employed reverse optic capture technique for the implantation of a three-piece intraocular lens. Following the surgery, the patient experienced a substantial improvement in uncorrected visual acuity. Remarkably, the patient remained free from adverse reactions, such as elevated intraocular pressure, during a follow-up period extending to 11 years.
Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Masculino , Humanos , Pessoa de Meia-Idade , Implante de Lente Intraocular/métodos , Catarata/complicações , Catarata/terapia , Extração de Catarata/métodos , Olho , Complicações Pós-Operatórias , SeguimentosRESUMO
Objective: To explore the CT imaging features of the 2019 novel coronavirus (2019-nCoV) infection in order to summarize the imaging characteristics of the disease and improve the ability of imaging diagnosis and early diagnosis of the disease. Methods: From January 13, 2020 to January 31, 2020, a total of 33 patients with 2019-nCoV infection diagnosed and treated by Suzhou Fifth People's Hospital were analyzed retrospectively, including 20 males and 13 females, with an average age of (50±12) years, ranging from 20 to 70 years old. There were 3 cases of mild type, 27 cases of common type and 3 cases of severe type.There were 2 cases with hypertension, 1 case with postoperative lung,1 case with diabetes, 1 case with chronic bronchitis, and 1 case with bronchiectasis.SPSS25.0 Chi-square test was used to analyze the distribution of lesions in each lung lobe; SPSS25.0 Spearman correlation coefficient was used to analyze the image score and clinical classification. Results: There were 3 cases (9.1%) with normal lung and 30 cases (90.9%) with Novel Coronavirus Pneumonia(COVID-19) of the 2019-nCoV infected patients. In the distribution of COVID-19, 29 cases (87.9%) were involved in bilateral lung and 1 case (3.0%) in unilateral lung. There was no statistically significant difference in the distribution of lesions in each lobe. The correlation coefficient between the degree of lesion distribution and clinical classification was 0.819, and the two were highly correlated.There were 30 cases (90.9%) with subpleural lesions, 17 cases (51.5%) with central lesions. There were many kinds of lesions, 25 cases (75.8%) had ground glass density shadow, 16 cases (48.5%) had consolidation, 12 cases (36.4%) had interstitial change, and 18 cases (54.5%) had interlobular septal thickening. Among the 22 cases, 10 cases had more lesions, 6 cases had no changes and 6 cases had less lesions. Conclusion: Most of the patients with 2019-nCoV infection have pulmonary inflammation.CT manifestations include multiple parts, subpleural area or middle and lateral field of lung, ground glass shadow and consolidation, or coexistence. Some cases have pleural thickening or interlobular septal thickening. CT images can indicate the diagnosis of COVID-19 and provide important basis for early detection and disease monitoring.
Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Betacoronavirus , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Diagnóstico Precoce , Feminino , Humanos , Inflamação , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto JovemRESUMO
Objective: To establish a CT image radiomics-based prediction model for the differential diagnosis of silicosis and tuberculosis nodules. Methods: A total of 53 patients with silicosis and 89 patients with tuberculosis who underwent routine CT scans in Suzhou Fifth People's Hospital from January to August, 2018 were enrolled in this study. AK/ITK software was used to segment the images to obtain 139 silicosis lesions and 119 tuberculosis lesions. For each lesion image, 396 features were extracted, and feature dimension reduction was applied to select the most characteristic feature subset. Support vector machine (SVM) , feedforward back propagation neural network (FNN-BP) , and random forest (RF) were implemented using R software (Rstudio V1.1.463) , and the algorithm that achieved the largest area under of the receiver operating characteristic (ROC) curve (AUC) was selected as the final prediction model. Results: RF was the best prediction model for the differential diagnosis of silicosis and tuberculosis nodules, with an accuracy of 83.1%, a sensitivity of 0.76, a specificity of 0.9, and an AUC of 0.917 (95% confidence interval: 0.8431-0.9758) . RF had a significantly larger AUC than SVM and FNN-BP (P<0.05) . Conclusion: CT image-based RF prediction model can be used to differentially diagnose silicosis and tuberculosis nodules.
Assuntos
Silicose/diagnóstico por imagem , Tuberculose/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Interpretação de Imagem Assistida por Computador , Modelos Teóricos , Redes Neurais de Computação , Curva ROC , Máquina de Vetores de Suporte , Tomografia Computadorizada por Raios XRESUMO
Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.
Assuntos
Adipócitos/metabolismo , Proteínas Aviárias/metabolismo , Metabolismo dos Lipídeos , Peptídeo Natriurético Encefálico/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Adipócitos/citologia , Animais , Proteínas Aviárias/genética , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Galinhas , Glicolipídeos/metabolismo , Metabolismo dos Lipídeos/genética , Lipólise , Redes e Vias Metabólicas , Peptídeo Natriurético Encefálico/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Fator Natriurético Atrial/genética , Regulação para CimaRESUMO
This study aimed to screen single nucleotide polymorphisms (SNPs) in the chicken gap junction protein alpha 1 (GJA1) gene, and to investigate their association with five growth traits measured in 269 chickens encompassing Chinese indigenous Beijing-You (BJY) and commercial Cobb broiler (CB) populations. Four variants were detected in the chicken GJA1 gene, in which one synonymous mutation was located in an exon (C61223231T or c.-1110 C>T), two in an intron (A61229799C or c.5460 A>C, T61229928A or c.5589 T>A) and one in the promoter (A61230599C or c. 6260 A>C) regions. Genotyping was performed by high-resolution melting analysis (SNP in an exon) and DNA sequencing (SNP in the introns and promoter). Association analysis revealed that each SNP had a significant effect on growth traits in chicken. A higher level of genetic diversity was observed in the indigenous BJY breed than in the commercial CB breed. Strong linkage disequilibrium was observed between the C61223231T and A61229799C polymorphisms, and four previously undiscovered haplotypes (CA, TC, CC, TA) were constructed from those two mutations. Association analysis between haplotype combinations (diplotypes) and growth traits was highly significant where diplotype CC + CC was dominant for all traits. We speculated that GJA1 either is a major gene, or is associated with a major gene, affecting chicken growth traits. Therefore, further studies are needed in large populations to evaluate polymorphisms located in different regions of this gene, as well as its functional study, to better understand its role in muscle development in chicken.
Assuntos
Peso Corporal/genética , Galinhas/genética , Conexina 43/genética , Músculo Esquelético/metabolismo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Animais , Cruzamento , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Éxons , Feminino , Expressão Gênica , Estudos de Associação Genética , Técnicas de Genotipagem , Haplótipos , Íntrons , Desequilíbrio de Ligação , Masculino , Músculo Esquelético/crescimento & desenvolvimento , Fenótipo , Regiões Promotoras Genéticas , Análise de Sequência de DNARESUMO
OBJECTIVE: To evaluate the influence of the implant-supported porcelain bridges made from non-precious metals using spark erosion techniques, and to discuss the feasibility and details of making the implant restoration by spark erosion technique. METHODS: The study included 12 patients (9 males and 3 females) with 92 units implant-supported non-precious porcelain bridge from Sep. 2011 to Feb. 2013. All the patients received implant treatment in Department of Oral Implantology, Peking University School and Hospital of Stomatology. The total of 52 implants, were from Nobel Biocare implant system, Camlog implant system and Ankylos implant system. The implant analogs were connected in sequence with a copper wire to guarantee conductivity. The implant electrodes represented one electrode and the superstructure the other. During spark-erosion machining, the cast holding the implant electrodes and the prosthetic framework were moved toward one another, causing an electrical erosion of the protruding elements. RESULTS: After the spark-erosion machining, the minimum gap between the framework and abutment was 0.21 mm, which was two units bridge. The maximum was 2.59 mm, which was 11 units bridge with 6 implants. The average gap was 0.68 mm. After the spark-erosion machining, the bridge fitted well with the passive position stability. CONCLUSION: The method of making implant-supported non-precious porcelain bridge reduces costs on patients. Spark erosion has the potential to provide implant framework with an excellent fit. The patients are satisfied with the clinical results.
Assuntos
Porcelana Dentária , Planejamento de Prótese Dentária/métodos , Prótese Dentária Fixada por Implante , Feminino , Humanos , MasculinoRESUMO
This study aimed to evaluate the influence of supplemental dietary nicotinic acid (NA) on lipid metabolism and hepatic expression of related genes in female chickens of two distinct broiler strains [Arbor Acres (AA) and Beijing-You (BJY)]. The treatments were arranged in a 2 × 4 factorial in a completely randomized design. Day-old females (n = 384) were allocated to four treatments with six cages per treatment and fed diets (basal contained approximately 25 mg NA/kg) supplemented with 0, 30, 60 and 120 mg NA/kg. A sample of 72 birds from each breed was slaughtered and sampled at their different market times (8 week for AA and 16 week for BJY). Arbor Acres broilers had thickness of subcutaneous fat plus the skin (SFS), and plasma concentration of low-density lipoprotein cholesterol (LDLC) and lower percentage of abdominal fat (PAF), plasma concentrations of TG, NEFA and adiponectin than the BJY line. The hepatic transcription of apolipoprotein A-I (ApoA-I), apolipoproteinB (ApoB), and adiponectin was significantly higher in AA broilers than in BJY broilers. In both breeds, BW, PAF, SFS, NEFA and TG were increased with increasing supplementation from 0 to 60 mg NA/kg, but then decreased slightly with 120 mg added NA/kg. With increasing supplementation, hepatic expression and plasma concentrations of adiponectin decreased from 0 to 60 mg added NA/kg and then increased with 120 mg added NA/kg. The expression of ApoA-I and ApoB mRNA showed linear response to dietary supplementation with NA. These findings indicate that: (i) supplementation of NA influenced the lipid metabolism and related gene expression; (ii) when supplemented with 120 mg NA/kg, some pharmacologic actions on lipid metabolism appeared; and (iii) changes in BW and fat deposition appeared to be associated with hepatic expression of adiponectin.
Assuntos
Galinhas/genética , Galinhas/metabolismo , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Niacina/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Niacina/administração & dosagemRESUMO
OBJECTIVE: To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients BACKGROUND: EPIC (Evaluation of Patients' Iron Chelation with Exjade(®)) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. METHODS: Efficacy and safety of deferasirox were compared in Chinese (n = 117) and non-Chinese (n = 998) TM patients. Deferasirox was initiated at 20 mg kg(-1) day(-1), with titration increments of 5-10 mg kg(-1) day(-1), based on serum ferritin trends and safety parameters. RESULTS: At baseline, Chinese patients were younger than non-Chinese (mean age 6·8 versus 19·5 years), with higher median serum ferritin (4519 vs 3058 ng mL(-1)). Over 1 year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24·6 and 24·0 mg kg(-1) day(-1), respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340 ng mL(-1), P = 0·102) and significantly decreased in non-Chinese patients (-220 ng mL(-1); P < 0·001). In the 1-year extension in Chinese patients, (mean actual deferasirox dose 33·6 mg kg(-1) day(-1)), median serum ferritin decreased (-756 ng mL(-1); P = 0·0397), with a numerically higher reduction in patients aged ≥6 to < 12 than <6 years (-982 vs -457 ng mL(-1), respectively). The safety profile of deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. CONCLUSION: Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to ≥30 mg kg(-1) day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients.
Assuntos
Benzoatos/administração & dosagem , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/tratamento farmacológico , Triazóis/administração & dosagem , Adolescente , Adulto , Fatores Etários , Idoso , Povo Asiático , Benzoatos/efeitos adversos , Criança , Pré-Escolar , China , Deferasirox , Feminino , Humanos , Lactente , Ferro/sangue , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Talassemia/sangue , Triazóis/efeitos adversosRESUMO
By estimating the genetic parameters of various semen quality traits in Beijing-You chickens, this study aims to elucidate the inheritance patterns of these traits and the correlations between them to facilitate setting up appropriate breeding strategies for enhanced semen quality. Semen samples were collected from 518 Beijing-You roosters at 43 wk of age from 3 selection lines related to meat flavor traits. Seven semen quality traits, consisting of semen volume, pH, and color, and sperm viability, motility, percent deformity, and concentration, were determined. Sizeable variations (18-24% CV) were observed for all traits, except for semen pH. The effects of semen collection time and origin of the chickens (line) were analyzed to optimize the proper models for estimating genetic parameters for each trait. The multiple-trait derivative-free restricted maximum likelihood method was used for estimating variance components. The results revealed that sperm viability, motility, and percent deformity exhibited high heritabilities (h(2) = 0.52, 0.85, and 0.60, respectively). Semen volume, semen color, and sperm concentration had moderate heritabilities (h(2) = 0.28, 0.19, and 0.12, respectively). Semen pH showed low heritability (h(2) = 0.03). Genetic and phenotypic correlations between sperm motility and viability were positive and high (rA = 0.88 and rP = 0.59). In addition, these 2 traits were genetically negatively correlated with percent deformity. This implied the possibility of reducing sperm deformity, which is difficult to measure, by indirect selection. It is concluded from this study that semen quality can be improved by selection. The traits with high variations and heritabilities such as semen volume are promising traits for selection to improve semen quality and likely reproductive performance of native chicken breeds.
Assuntos
Cruzamento , Galinhas/fisiologia , Variação Genética , Sêmen/fisiologia , Criação de Animais Domésticos , Animais , Galinhas/genética , Masculino , Reprodução , Análise do Sêmen/veterináriaRESUMO
Fatty acid synthase (FAS) is a key enzyme of lipogenesis. In this study, the FAS mRNA expression patterns were examined in three fat related tissues (liver, breast and thigh) at different developmental stages in two chicken breeds (Beijing-You, BJY and Arbor Acres broiler, AA). Results of the Real time-qPCR showed that the expression of FAS mRNA level in liver was significantly higher (P < 0.01) than that in breast and thigh in both two chicken breeds. Significant differences of FAS mRNA expression in liver were found between BJY and AA chickens during different developmental stages. After the contents of intramuscular-fat (IMF) and the liver fat were measured, the correlation analysis was performed. In liver, the FAS mRNA level was highly correlated with hepatic fat content (r = 0.891, P < 0.01 for BJY; r = 0.901, P < 0.01 for AA). On the contrary, the FAS expression level in both breast and thigh tissues were relatively low, stable and there was no correlation between the FAS mRNA level and IMF content in breast and thigh tissues of each breed. The results here can contribute to the knowledge on the developmental expression pattern of FAS mRNA and facilitate the further research on the molecular mechanism underlying IMF deposition in chicken.
Assuntos
Adiposidade/genética , Cruzamento , Galinhas/genética , Ácido Graxo Sintases/genética , Regulação da Expressão Gênica no Desenvolvimento , Fígado/enzimologia , Desenvolvimento Muscular/genética , Animais , Galinhas/classificação , Galinhas/crescimento & desenvolvimento , Dieta , Ácido Graxo Sintases/metabolismo , Regulação Enzimológica da Expressão Gênica , Especificidade de Órgãos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
This paper, the second from a comprehensive study, describes the effects of varying growth rate by feeding at different planes of nutrition with a constant ME:CP ratio on muscle characteristics and meat quality in 2 distinct broiler breeds of male chickens (Arbor Acres, a commercial line; and Beijing-You, a Chinese nonimproved line). Experimental diets, differing on average by 2% CP, were formulated with high-, medium-, or low-nutrient densities for 3 growing phases. Male hatchlings (216 of each breed) were randomly assigned to 6 pens of 12 birds in each treatment. Altered histological characteristics of muscle fibers, early postmortem muscle metabolism, and meat quality were investigated in the pectoralis major and biceps femoris. At their market age, Arbor Acres broilers had significantly higher concentrations of plasma protein and lipid metabolites, ratios of white to red and intermediate fibers, pH, L* and b* values, and lower concentrations of plasma glucose metabolites, muscle-fiber diameter, muscle contents of energy stores, a* value, drip loss, and shear force than the values found for the Beijing-You chickens (P < 0.01). Higher nutrient density increased the size of the muscle fibers, decreased glycogen reserve, and reduced the rate and extent of acidification in the Arbor Acres chickens, while accelerating transformation of red and intermediate-to-white fibers, enhancing energy stores, and hastening the decrease in pH postmortem in the Beijing-You chickens (P < 0.05). In each breed, most meat quality variables (e.g., shear force, drip loss, and color) were consistent with the histological and biochemical changes caused by the feeding strategy. Together, dietary nutrient density can influence meat quality as a result of altered histological and initial energy and metabolic characteristics of the muscle. Many of the responses to diet are breed and tissue dependent in broiler chickens.
Assuntos
Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Carne/normas , Animais , Composição Corporal , Galinhas/anatomia & histologia , Galinhas/sangue , Galinhas/genética , Proteínas Alimentares/farmacologia , Concentração de Íons de Hidrogênio , Masculino , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/química , Especificidade da EspécieRESUMO
On the basis of meat quality traits, muscle fiber characteristics, and nutrient components and contents in chickens at market age, 120-d-old Beijing-you (BJY) chickens (the Chinese local breed) had distinct breast muscle features when compared with 42-d-old Arbor Acres (AA) chickens (the genetically improved broiler line). The phospholipid (P < 0.05) and essential fatty acid (P < 0.05) contents in BJY chickens were significantly higher than those in AA chickens. No differences (P > 0.05) were found between the breeds in the contents of polyunsaturated fatty acids, unsaturated fatty acids, protein, or amino acids. Breast muscle fiber diameter was significantly smaller (~55.76%) and fiber density was higher (~174.86%) in BJY chickens than in AA chickens (P < 0.05). In this study, breast muscle from 120-d-old BJY chickens was judged to have better quality of phospholipids and essential fatty acid contents and muscle fiber characteristics than breast muscle from 42-d-old AA chickens.
Assuntos
Galinhas , Carne/análise , Músculo Esquelético/química , Aminoácidos/análise , Animais , Ácidos Graxos Insaturados/análise , Feminino , Fibras Musculares Esqueléticas/citologia , Proteínas Musculares/análise , Controle de Qualidade , Especificidade da EspécieRESUMO
Objective: To investigate the regulatory effect of targeted siRNA on ß-globin in erythroid cells cultured by targeted differentiation in vitro and provide new theoretical support for gene therapy for hemoglobin H (HbH) disease. Methods: Based on the ß-globin gene expression results, the optimal siRNA sequence and its effective action dose were screened in erythroid cells, and the effect of the effective dose of the optimal siRNA on the regulation of ß-globin expression and apoptosis in erythroid cells was examined. The effective dose of the optimal siRNA was applied to erythroid cells with HbH disease. The effects of transfected siRNAs on red line cells with HbH disease were comprehensively evaluated by measuring the expression of ß-globin, reactive oxygen species (ROS) , and apoptosis rates. Results: Within 96 hours after transfection, siRNA2 significantly downregulated ß-globin expression in in vitro cultured erythroid cells, but not α-globin. siRNA silencing effect and duration of effect were dose-dependent. siRNA2 downregulated ß-globin expression, reduced intracellular ROS production, and decreased apoptosis rate in erythroid cells with HbH disease. Conclusion: Targeted siRNAs can downregulate ß-globin expression, reduce intracellular ROS production, and downregulate apoptosis rate in erythroid cells with HbH disease.
Assuntos
Talassemia alfa , Eritrócitos , Terapia Genética , Humanos , RNA Interferente Pequeno/genética , Globinas beta/genéticaRESUMO
The production of new neurons continues throughout adulthood in the dentate gyrus of the hippocampal formation, and is believed to play a role in hippocampus-dependent learning and memory. Seizure-induced changes in adult neurogenesis have been examined primarily in convulsive rodent seizure models, but not in models of nonconvulsive absence seizures. This study examined progenitor cell proliferation in the gamma-hydroxybutyrate (GHB) model of typical absence seizures and the AY-9944 model of atypical absence seizures, and compared these results with changes seen in the rat amygdala kindling model. Kindled subjects were found to have 189% more proliferating cells than sham-kindled control subjects, whereas no significant difference was found between the GHB or AY-9944 model and control subjects. These results suggest that changes in adult neurogenesis in models of absence seizures do not occur, and that seizure-induced enhancement of neurogenesis could depend on the characteristics of the seizure discharge.
Assuntos
Giro Denteado/fisiopatologia , Epilepsia Tipo Ausência/patologia , Excitação Neurológica/fisiologia , Neurogênese/fisiologia , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Animais Recém-Nascidos , Anticolesterolemiantes/uso terapêutico , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Modelos Animais de Doenças , Eletroencefalografia/métodos , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/etiologia , Regulação da Expressão Gênica , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/efeitos dos fármacos , Ratos , Ratos Long-Evans , Dicloridrato de trans-1,4-Bis(2-clorobenzaminometil)ciclo-hexano/uso terapêuticoRESUMO
Intramuscular fat is important in improving meat quality; however, the lack of high-purity intramuscular preadipocyte (IMP) in vitro has severely limited the in-depth research on the mutual regulation of myocytes and adipocytes in chicken. In this study, we establish a new method by combining the mature adipocyte ceiling method and the transwell co-culture system. Mature intramuscular adipocyte (MIA) and muscle satellite cell (MSC) were obtained from digested pectoralis major, and MIAs were transformed into IMPs by dedifferentiation with ceiling culture. MSCs were then purified by differential adhesion for 2 h. The results by inverted-microscope observation, MTT assay, Oil Red O staining, and q-PCR revealed that the de-differentiated cells from MIA were identified as the IMPs, and had the same the cellular morphology, the capacity on differentiation, proliferation and passage with the abdominal fat preadipocytes (P > 0.05). The applicability of the obtained IMPs in co-cultured experiment with the MSC revealed that it could meet the requirements of the experimental study. Finally, a co-culture system of IMPs and MSCs was established using a transwell chamber. The co-cultured results indicated that MSCs in the proliferative stage tend to accelerate the differentiation of IMPs to induce more fat content in co-cultured IMPs than in single-culture IMPs (P < 0.05), in the non-proliferative stage, the results tend to show the opposite (P < 0.05). The mRNA levels of related genes significantly changed in accordance with the fat content in cells. The results strongly supported the view that the established co-culture system was effective and feasible. In summary, we successfully found a new method to explore the interaction between myocytes and adipocytes of chicken. Our findings can deepen research on the regulation of chicken myocytes and adipocytes.
Assuntos
Adipócitos/citologia , Técnicas de Cultura de Células/veterinária , Galinhas , Técnicas de Cocultura/veterinária , Músculos Peitorais/fisiologia , Células Satélites de Músculo Esquelético/citologia , Animais , Técnicas de Cultura de Células/métodos , Técnicas de Cocultura/métodos , Células Musculares/citologiaRESUMO
Calpain 9 (CAPN9) is expressed in the stomach and small intestine. CAPN9 has regulatory roles in hypertension, heart disease, gastric mucosal defense, and kidney disease. The involvement of CAPN9 has not been reported in the development of chickens. CAPN9 mRNA was found in adipose and muscle tissue in this study. Two linkage single nucleotide polymorphisms (SNP; G7518A and C7542G) in intron 4 were screened from 160 birds of the D2 chicken line. The 2 mutation sites were associated with carcass weight, evisceration weight, abdominal fat weight (AFW), abdominal fat percentage (AFP), and breast muscle percentage (all P < 0.05). Intramuscular fat (IMF) content was not significantly different in the 3 genotypes. But, the AA(7518)/GG(7542) genotype had the highest IMF content, highest breast muscle weight, and lower AFW and AFP. Moreover, the mRNA level of CAPN9 in abdominal fat tissue was significantly different (P < 0.05 or P < 0.01) between any 2 genotypes, consistent with AFW and AFP. In summary, the expression of CAPN9 in adipose and breast muscle tissue is reported for the first time. CAPN9 affected production performance of chickens. As a marker, the linkage G7518A and C7542G polymorphisms in intron 4 of CAPN9 could affect the production traits by regulating mRNA expression. The findings concerning the marker enrich the theoretical foundation for molecular breeding of high-quality broilers.
Assuntos
Proteínas Aviárias/genética , Calpaína/genética , Galinhas/genética , Regulação da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Gordura Abdominal/metabolismo , Animais , Proteínas Aviárias/metabolismo , Sequência de Bases , Peso Corporal/genética , Calpaína/metabolismo , Galinhas/metabolismo , Músculos Peitorais/crescimento & desenvolvimento , Músculos Peitorais/metabolismoRESUMO
Objective: To explore the diagnosis, treatment and prognosis of autoimmune hemolytic anemia (AIHA) after allo-HSCT in patients with thalassemia major (TM). Methods: A retrospective analysis of AIHA status after allo-HSCT in 291 TM patients from July 2007 to December 2017 was conducted. Results: Five of the 291 TM patients (1.72%) were diagnosed with post-transplant AIHA. The median time of AIHA was 7 (5-12) months after HSCT. All post-transplant AIHA patients were positive in direct and indirect Coombs test, the main clinical manifestations were dizziness, fatigue, pale complexion, skin and sclera yellow, and soy sauce urine. The incidence of AIHA was higher after unrelated donor transplantation (6.36%, 4/63) compared with that of sibling donor transplantation (0.43%, 1/228). One patient who received only prednison was dead. Four patients who received rituximab combined with prednisolone were alive, Coombs test in two of them were negative. Conclusions: AIHA after allo-HSCT developed in 1.72% patients with TM. Monitoring of Coombs test was important for diagnosis of post-transplant AIHA. The incidence of post-transplant AIHA was higher in unrelated donors compared with that of sibling donors transplantation. Treatment of rituximab combined glucocorticoid was effective strategy for post-transplant AIHA.