RESUMO
The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.
RESUMO
Objective: To analyze, explore and evaluate the clinical characteristics, abnormal thyroid function and follow-up of anti-hyperthyroidism treatment mode in patients with hyperthyroidism (commonly abbreviated as HT) combined with liver injury. Methods: The clinical data of patients with hyperthyroidism combined with liver injury were retrospectively analyzed, and then patients were divided into treated and untreated group according to whether they received anti-hyperthyroidism treatment before the consultation. Patients' thyroid and liver function test indicators at the time of treatment were analyzed to determine the main cause of liver injury. The characteristics of liver injury were analyzed in the treatment group. Patients with severe thyroid toxicity and hyperthyroidism combined with liver injury were followed-up with anti-hyperthyroid therapy, mainly low-dose methimazole (MMI) and radioactive iodine therapy to evaluate its efficacy and safety. The comparison between data groups was performed by t-test, rank sum test and χ( 2) test. Results: Among the 43 cases with hyperthyroidism combined with liver injury, 19 were males and 24 were females, aged 49.0 ± 14.6 years-old; 16 cases (16/43, 37.21%) aged 40 to≤60 years- old, and 15 cases (15/43, 34.88%) aged > 60 years-old. There were 22 untreated cases (untreated group, accounting for 51.16%), and 21 treated cases with anti-hyperthyroidism (treatment group, accounting for 48.84%) at the time of consultation. Thyroid function indicators (FT3, FT4, TSH) and liver function indicators (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin) of the two groups were compared, and the difference was not statistically significant (P > 0.05). The order of liver injury from mild to severe in patients with different treatment options were: methimazole (MMI) < propylthiouracil < radioactive iodine Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia
, Hipertireoidismo
, Neoplasias da Glândula Tireoide
, Adulto
, Idoso
, Antitireóideos/uso terapêutico
, Feminino
, Humanos
, Hipertireoidismo/complicações
, Hipertireoidismo/tratamento farmacológico
, Radioisótopos do Iodo
, Fígado
, Masculino
, Pessoa de Meia-Idade
, Estudos Retrospectivos
RESUMO
Due to the difference in infection time and immune clearance ability, patients with chronic hepatitis B virus (HBV) infection may appear as virus carrier or chronic active hepatitis. Alanine aminotransferase (ALT) is the most sensitive biomarkers for evaluating liver inflammation. Current anti-HBV drugs, nucleoside analogues (NAs) and peginterferon α, can only achieve satisfactory results when liver inflammation is active. Therefore, international authoritative guidelines recommend HBV DNA positive and ALT > 2-fold the upper limit of normal (2×ULN) as indications for treatment. However, many studies have shown that some chronic HBV infected patients with normal ALT have insidious progression to liver cirrhosis or liver failure, because of not initiating antiviral therapy in time. Hence, the disease assessment and initiation indication for treatment have received more and more attention and become a hot topic in clinical research for chronic HBV infected patients with normal ALT.
Assuntos
Hepatite B Crônica , Alanina Transaminase , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática , NucleosídeosRESUMO
Objective: To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients. Methods: HBeAg-positive CHB-naïve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks. Results: As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group (P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log(10) S/CO (OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log(10) IU / ml (OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion: In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log(10) at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.
Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to identify the status of the blood supply in China during 2012-2014. BACKGROUND: China is a middle-income country, which contains more than 20% of the world population. Increasing the blood supply in China, along with increased healthcare coverage, involves many challenges. METHODS: A survey questionnaire regarding blood centre activities was sent to all of the blood centres in 32 provinces via the Internet. The data were collected from the responses and analysed using Microsoft Excel 2013. RESULTS: The total supply of whole blood and red blood cells (RBCs) in 2012 was 18 644 700 units; in 2013, 18 985 800 units; and in 2014, 19 658 800 units. A similar trend of the total platelet supply was also observed during the same period of 2012-2014, as follows: 1 019 100 units in 2012, 1 168 400 units in 2013 and 1 276 200 units in 2014. Similarly, the plasma supply was 27 529 300 units in 2012 and 27 657 600 units in 2013, which rose to 28 307 500 units in 2014. The total cryoprecipitate supply was 1 653 900, 1 891 300 and 2 366 500 units in 2012, 2013 and 2014, respectively. When the blood supply was analysed according to the geographic regional population, large differences in the rates of blood supply between regions were evident. CONCLUSIONS: The blood product supply in China is steadily increasing. Blood centres in China continue to face challenges regarding their ability to provide a sufficient blood supply in the future.
Assuntos
Bancos de Sangue , Segurança do Sangue , Eritrócitos , Plasma , Inquéritos e Questionários , China , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Nutritional intake and reproductive allocation are strongly associated and dietary energy restriction (ER) or surpluses can affect reproductive capacity. The objective of this study was to investigate the effect of energy levels on sheep testicular development. Three-month old Hu sheep were assigned to four groups, and fed diets containing different levels of energy (Control, maintenance energy; ER1, 85% maintenance energy; ER2, 70% maintenance energy; ER3, 55% maintenance energy). Two months later, half the sheep in each group were euthanized, whereas the remaining sheep were euthanized after a further 3 months feeding on a compensatory energy diet. The testicular weight and reproductive hormone levels of the Hu sheep were investigated. Differences in the testes of ER3 and control group sheep were investigated at the transcriptional level using high-throughput sequencing. The results showed that the testicular weights had decreased in the energy-restricted rams compared with the controls, and that the testosterone concentration in ER3 group rams was significantly lower than that in other compared groups (Pâ¯<â¯0.05). After the period of compensatory feeding, however, ER3 sheep testicular weight and testosterone concentrations were similar to those of the control group sheep. In addition, the RNA sequencing results revealed that 81 genes were upregulated and 180 genes were downregulated in the ER3 group compared with the control group. Moreover, based on the enriched steroidogenesis, meiosis and kinases pathways, a number of candidate genes potentially involved in the regulation of testicular development or reproduction of Hu sheep, including CYP11A1, ALDH3B1, FDFT1, WNT2, PGR and INSR, were screened. Quantitative real-time polymerase chain reaction analysis results correlated well with the sequencing data. Taken together, this study provides a first insight into the development of the testis with dietary energy restriction in sheep and shows that these changes are associated with alterations in transcriptomic. The sheep testis mRNA database were extended in this study will provides novel candidate regulators for future genetic and molecular studies on sheep testicular development associated with energy restriction, which will contribute to improving the reproductive performance of sheep.
Assuntos
Dieta/veterinária , Ingestão de Energia/fisiologia , Ovinos/crescimento & desenvolvimento , Testículo/metabolismo , Transcriptoma , Processamento Alternativo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , DNA Complementar , Regulação da Expressão Gênica , Biblioteca Gênica , Masculino , Polimorfismo de Nucleotídeo Único , RNA/genética , RNA/metabolismo , Distribuição Aleatória , Ovinos/metabolismo , Testículo/efeitos dos fármacosRESUMO
BACKGROUND: Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs). METHODS: Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP-9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry. RESULTS: The expression of MMP-9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP-9/2 and relieved plantar incision-induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin-1ß, which is a critical substrate of MMPs. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the expression of neuronal c-Fos. CONCLUSION: These results indicated that MMP-9/2 activation in spinal microglia plays a key role in incision-induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP-9/2 activity might represent a valuable alternative for treating postoperative pain. SIGNIFICANCE: Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1ß signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glucosídeos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Monoterpenos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Glucosídeos/administração & dosagem , Hiperalgesia/metabolismo , Interleucina-1beta/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Camundongos , Microglia/metabolismo , Monoterpenos/administração & dosagem , Dor Pós-Operatória/metabolismo , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
The effects of perilla (Perilla frutescens L.) seed on carcass traits, meat quality, antioxidant status and antioxidant gene expression in the liver and muscle of Hu lambs were investigated in this study. Sixty Hu lambs (23.02 ± 1.36 kg) were randomly divided into four experimental groups receiving diets containing 0%, 5%, 10% or 15% perilla seed (CD, 5%PFSD, 10%PFSD and 15%PFSD, respectively). The addition of perilla seed had no significant impacts on carcass traits (p > .05). There were no differences in pH, meat colour, drip loss, cooking loss or shear force among the four treatments (p > .05). Addition of perilla seed increased (p < .05) deposition of intramuscular lipids but had no effect on other chemical components in the longissimus dorsi (LD) (p > .05). The 15%PFSD diet decreased the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content in the liver (p < .05 for both) but increased the activity of these antioxidant enzymes in LD (p < .05 for both). Compared to CD, addition of perilla seed increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) expression in the liver and LD (p < .05 for all). These results indicate that perilla seed supplementation in lambs' diets can increase deposition of intramuscular lipids and improve muscular oxidative status and meat quality.
Assuntos
Ração Animal/análise , Antioxidantes/metabolismo , Carne/normas , Perilla/química , Sementes/química , Animais , Composição Corporal/efeitos dos fármacos , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Ovinos/fisiologiaRESUMO
Objective: To explore the difference of liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection, and to investigate the relationship between hepatic pathology and alanine aminotransferase (ALT). Methods: 57 patients with chronic HCV infection and 346 patients with chronic HBV infection who were hospitalized at Shengjing Hospital of China Medical University from January 2012 to September 2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were more than two times of upper limited of normal (ALT≥2×ULN) and 258 cases whose ALT were less than two times of upper limited of normal (ALT < 2×ULN).All the patients were underwent liver biopsy. Chronic HBV infection (ALT≥2×ULN and ALT < 2×ULN) and chronic HCV infection were compared respectively. Statistical analyses were performed using a Univariate χ²-test and Mann-Whitney U test for comparison. Correlations between variables were analyzed using Spearman's rank correlation. Results: In chronic HBV infection group, 169 cases (48.8%) had inflammation grade≥2 (G≥2), 98 cases (28.3%) had fibrosis stage≥2 (S≥2), 81 cases (23.4%) with G≥2 and S≥2.In the ALT < 2×ULN group, there were 109 cases (42.2%) with G≥2, 62 cases (24%) with S≥2, 49 cases (19%) with G≥2 and S≥2. In the ALT≥2×ULN group, 60 cases (68.2%) with G≥2, 35 cases (39.8%) with S≥2, 31 cases (35.2%) with G≥2 and S≥2. The grade of inflammation and fibrosis have significantly different between ALT≥2×ULN group and ALT < 2×ULN group (χ² = 17.66, χ² = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%) with G≥2, 20 cases (35.1%) with S≥2, 20 cases (35.1%) with G≥2 and S≥2. ALT had no correlation with inflammation and fibrosis (P > 0.05). The grade of inflammation was significantly different between chronic HCV infection and chronic HBV infection whose ALT < 2×ULN (χ² = 30.19, P < 0.01) but the fibrosis have no difference (χ² = 2.96, P > 0.05). Compared with chronic HBV infection whose ALT≥2×ULN, both inflammation and fibrosis had no significantly different (χ² = 3.65, χ² = 0.32, P > 0.05 respectively). Conclusion: In chronic HBV infection whose ALT < 2×ULN, about 30%-40% liver tissue with significant necroinflammation and /or fibrosis. About 80% chronic HCV infection with significant necroinflammation, and the grade of inflammation has no correlation with ALT. The grade of inflammation has significantly different between chronic HCV infection group and chronic HBV infection group whose ALT < 2×ULN.
Assuntos
Hepatite B Crônica/patologia , Inflamação/patologia , Cirrose Hepática/patologia , Fígado/patologia , Alanina Transaminase/sangue , China , Hepatite B Crônica/sangue , Humanos , Inflamação/sangue , Cirrose Hepática/virologiaRESUMO
Since there are no studies on the reversal of multidrug resistance by curcumin in the human colorectal cancer cell line HCT-8/5-FU, our aim was to search for highly efficient reversal agents and investigate the underlying mechanisms of this reversal. The cytotoxic effects of curcumin and 5-FU on HCT-8 and HCT-8/5-FU cells and the reversal effects of 5-FU in combination with curcumin on HCT-8/5-FU cells were measured using cell counting kit-8. Apoptosis and the cell cycle were analyzed by flow cytometry. Protein and mRNA expression levels of BCL-2, survivin, P-gp, and HSP-27 were detected by western blotting and quantitative real-time reverse transcription polymerase chain reaction, respectively. Curcumin inhibited the growth of HCT-8 and HCT-8/5-FU cells. It significantly reduced the IC50 of 5-FU for HCT-8/5-FU cells (P < 0.01) and the expression of BCL-2, survivin, P-gp, and HSP-27 in the cells. Curcumin can effectively reverse multidrug resistance in human colorectal cancer drug-resistant HCT-8/5-FU cells. The mechanism through which this occurs may be associated with decreased expression of BCL-2, survivin, P-gp, and HSP-27. Curcumin may therefore have clinical implications as a new agent for colorectal cancer.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Curcumina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Curcumina/toxicidade , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Chaperonas Moleculares , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , SurvivinaRESUMO
The mammalian hair follicle (HF) is a unique, highly regenerative organ with a distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided into two categories based on structure and development time: primary and secondary follicles. To identify differentially expressed genes (DEGs) in the primary and secondary HFs of cashmere goats, the RNA sequencing of six individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were identified; 297 were upregulated while 320 were downregulated. Gene ontology analysis revealed that the main functions of the upregulated genes were electron transport, respiratory electron transport, mitochondrial electron transport, and gene expression. The downregulated genes were mainly involved in cell autophagy, protein complexes, neutrophil aggregation, and bacterial fungal defense reactions. According to the Kyoto Encyclopedia of Genes and Genomes database, these genes are mainly involved in the metabolism of cysteine and methionine, RNA polymerization, and the MAPK signaling pathway, and were enriched in primary follicles. A microRNA-target network revealed that secondary follicles are involved in several important biological processes, such as the synthesis of keratin-associated proteins and enzymes involved in amino acid biosynthesis. In summary, these findings will increase our understanding of the complex molecular mechanisms of HF development and cycling, and provide a basis for the further study of the genes and functions of HF development.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Cabras/genética , Folículo Piloso/metabolismo , Transcriptoma , Animais , Autofagia , Transporte de Elétrons , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Cabras/crescimento & desenvolvimento , Cabras/imunologia , Folículo Piloso/crescimento & desenvolvimento , Imunidade Inata/genética , Queratinas/genética , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , MicroRNAs/genética , Proteínas Mitocondriais/genética , Anotação de Sequência Molecular , Análise de Sequência de RNARESUMO
OBJECTIVE: To observe the success rate of telbivudine (LdT) for the prevention of perinatal transmission of hepatitis B virus (HBV) and the incidence of alanine aminotransferase (ALT) elevation during LdT treatment and after LdT withdrawal in HBV-infected pregnant woman with high viremia in immune-tolerant phase and receiving LdT treatment at the end of pregnancy, and to evaluate the efficacy of LdT in the prevention of perinatal transmission and the safety for pregnant women. METHODS: Pregnant women infected with HBV in immune-tolerant phase who had normal ALT levels (≤40 U/L) and high viremia (HBV DNA ≥6 log10 IU/ml) with positive HBeAg were enrolled as subjects. All pregnant women received antiviral treatment with LdT at the end of pregnancy to prevent perinatal transmission of HBV. All infants received standard combined immunoprophylaxis. Failure for prevention of perinatal transmission of HBV was defined as positive HBsAg or HBV DNA in infants 7 months of age (or at one month after the third injection of hepatitis B vaccine). Liver function, HBV DNA, and HBV serological markers were evaluated at baseline, after 1 month of treatment, before childbirth, and 1, 3, and 6 months after drug withdrawal. SPSS 16.0 software was used to analyze the data. Between-group comparison of continuous data was made by t test, and comparison of categorical data was made by chi-square test. RESULTS: One hundred and four pregnant women (treatment group) received oral administration of 600 mg LdT once a day, and 25 pregnant women (observation group) did not receive any antiviral therapy. The success rate for the prevention of perinatal transmission was significantly higher in the treatment group than in the observation group (100% vs 89.47%, χ (2) = 9.862, P = 0.028). There was no significant difference in the incidence of ALT elevation during treatment and within 6 months after drug withdrawal between the treatment group and the observation group (4.81% (5/104) vs 4.00% (1/25), χ (2) = 0.030, P = 1.000). In the treatment group, the mean HBV DNA at baseline was significantly higher than that before childbirth (8.20±0.78 vs 3.98±0.90 log10IU/ml, t = 6.979, P < 0.001). One hundred patients with drug withdrawal had HBV DNA increased to 8.11±0.80 log10 IU/ml at one month after childbirth. CONCLUSION: LdT treatment at the end of pregnancy can effectively reduce the incidence of perinatal transmission of HBV in pregnant women with high viremia in immune-tolerant phase. The immediate drug withdrawal after childbirth is safe for the mother. The incidence of hepatitis is low after drug withdrawal.
Assuntos
Antivirais/uso terapêutico , Hepatite B/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Timidina/análogos & derivados , Feminino , Hepatite B/diagnóstico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Humanos , Lactente , Gravidez , Complicações Infecciosas na Gravidez/virologia , Telbivudina , Timidina/uso terapêutico , Resultado do Tratamento , Viremia/tratamento farmacológicoRESUMO
OBJECTIVE: We investigated the involvement of miR-18a upregulation in autophagy regulation and paclitaxel (PTX) resistance in triple negative breast cancer (TNBC) cells. MATERIALS AND METHODS: PTX resistant MDA-MMB-231/PTX cells were generated using an intermittent, stepwise method. MiR-18a expression was assessed using qRT-PCR. The level of autophagy was assessed by Western blot analysis of LC3B expression and observation of LC3-GFP puncta formation under a fluorescence microscope. The effect of miR-18a mediated autophagy on PTX sensitivity was assessed by measuring IC50 and PTX induced cell apoptosis. RESULTS: MDA-MB-231/PTX cells had both higher miR-18a expression and basal autophagy than MDA-MB-231 cells. Enforced miR-18a overexpression directly led to increased autophagy in MDA-MB-231 cells, the effect of which was similar to that of rapamycin, a mTOR signaling inhibitor. Following Western blot analysis showed that miR-18a overexpression decreased the expression of p-mTOR and p-p70S6. Therefore, we infer that miR-18a increases autophagy level in MDA-MB-231 cells via inhibiting mTOR signaling pathway. Both drug sensitivity assay and flow cytometry analysis confirmed that the effect of miR-18a on increasing IC50 and decreasing PTX induced apoptosis in MDA-MB-231 cells could largely be abrogated by treatment with bafilomycin A1 (Baf. A1). CONCLUSIONS: MiR-18a upregulation results in enhanced autophagy via inhibiting mTOR signaling pathway in TNBC cells, which is a mechanism contributing to paclitaxel resistance.
Assuntos
Autofagia/efeitos dos fármacos , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima , Humanos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Genomic imprinting is an important epigenetic mechanism that has vital effects on fetal growth and development. We observed the differences in four tissues (heart, spleen, liver, and kidney) from dead transgenic cloned goats using hematoxylin and eosin (H&E) staining. Eight imprinted genes in the tissues of dead transgenic cloned and normal goats were analyzed using reverse transcription polymerase chain reaction. H&E staining results from the abortion group indicated the lack of obvious morphological changes in heart and spleen tissues, while inflammatory cell infiltration and glomerular nephritis characteristics were observed in liver and kidney tissues, respectively. Compared to the control group, CDKN1C, H19, IGF2R, and SNRPN were significantly (P < 0.05) overexpressed in the heart tissue of the abortion group, while XIST was significantly reduced. In the liver tissues, CDKN1C and DLK1 expression decreased, while GNAS, H19, IGF2R, PEG3, and XIST expression increased significantly. In the spleen tissues, DLK1 expression increased, while GNAS, H19, IGF2R, PEG3, SNRPN, and XIST expression decreased. In the kidney tissues, CDKN1C, DLK1, GNAS, IGF2R, and PEG3 expression increased, while H19 and XIST expression decreased. The overall expression of imprinted genes was abnormal in different tissues of transgenic cloned goats, and the degree of abnormal genomic imprinting was more severe in the abortion group compared to the death and control groups. These results suggest that abnormal expression of imprinted genes may cause developmental defects in transgenic cloned goats. Moreover, abnormal epigenetic modifications may affect the reprogramming of transgenic donor cells.
Assuntos
Clonagem de Organismos/mortalidade , Epigênese Genética , Genes Letais , Impressão Genômica , Cabras/genética , Lactoferrina/genética , Animais , Animais Geneticamente Modificados , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Feminino , Perfilação da Expressão Gênica , Cabras/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Rim/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Lactoferrina/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Gravidez , Transdução de Sinais , Baço/metabolismo , TransgenesRESUMO
This research aimed to define the energy requirement of Dorper and Hu Hybrid F1 ewes 20 to 50 kg of body weight, furthermore to study energy requirement changes with age and evaluate the effect of age on energy requirement parameters. In comparative slaughter trial, thirty animals were divided into three dry matter intake treatments (ad libitum, n = 18; low restricted, n = 6; high restricted, n = 6), and were all slaughtered as baseline, intermediate, and final slaughter groups, to calculate body chemical components and energy retained. In digestibility trial, twelve ewes were housed in individual metabolic cages and randomly assigned to three feeding treatments in accordance with the design of a comparative slaughter trial, to evaluate dietary energetic values at different feed intake levels. The combined data indicated that, with increasing age, the net energy requirement for maintenance (NEm) decreased from 260.62±13.21 to 250.61±11.79 kJ/kg(0.75) of shrunk body weight (SBW)/d, and metabolizable energy requirement for maintenance (MEm) decreased from 401.99±20.31 to 371.23±17.47 kJ/kg(0.75) of SBW/d. Partial efficiency of ME utilization for maintenance (km, 0.65 vs 0.68) and growth (kg, 0.42 vs 0.41) did not differ (p>0.05) due to age; At the similar condition of average daily gain, net energy requirements for growth (NEg) and metabolizable energy requirements for growth (MEg) for ewes during late fattening period were 23% and 25% greater than corresponding values of ewes during early fattening period. In conclusion, the effect of age upon energy requirement parameters in the present study were similar in tendency with previous recommendations, values of energy requirement for growth (NEg and MEg) for Dorper and Hu crossbred female lambs ranged between the NRC (2007) recommendation for early and later maturating growing sheep.
RESUMO
Previous molecular genetic studies of the goat hair life cycle have focused primarily on a limited number of genes and proteins. To identify additional genes that may play important roles in hair follicle cycle regulation, Illumina sequencing technology was used to catalog differential gene expression profiles in the hair growth cycle (anagen to catagen) of goat, comparing the primary hair follicle with the secondary hair follicle. There were 13,769 and 12,240 unigenes assembled from the reads obtained from primary hair follicle and secondary hair follicle, respectively. Genes encoding keratin proteins and keratin-associated proteins were the most highly expressed. A total of 5899 genes were differentially expressed in anagen vs catagen primary hair follicles, with 532 genes up-regulated and 5367 genes down-regulated. A total of 5208 genes were differentially expressed in anagen vs catagen secondary hair follicle, including 545 genes that were up-regulated and 4663 genes that were down-regulated. Numerous hair growth genes are expressed in the goat hair follicle, of which 73 genes showed co-up-regulation in both hair follicles during the anagen stage. Many of these up-regulated genes, such as STC2, VEGFR, and ROR2, are known to be transfactors in the process of cell differentiation and in the cell cycle. The differential gene expression profiles between primary hair follicles and secondary hair follicles obtained provide a foundation for future studies examining the network of gene expression controlling hair growth cycle in Cashmere goat.
Assuntos
Cabras/genética , Folículo Piloso/metabolismo , Queratinas/biossíntese , Transcriptoma , Animais , Regulação da Expressão Gênica no Desenvolvimento , Cabras/crescimento & desenvolvimento , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Queratinas/genética , Pele/crescimento & desenvolvimentoRESUMO
MSTN, IGF-Ð(insulin-like growth factor-Ð) and IGF-II (insulin-like growth factor-II) regulate skeletal muscle growth. This study investigated the effects of different dietary intake levels on skeletal muscles. Sheep was randomly assigned to 3 feeding groups: 1) the maintenance diet (M), 2) 1.4 x the maintenance diet (1.4M), and 3) 2.15 x the maintenance diet (2.15M). Before slaughtering the animals, blood samples were collected to measure plasma urea, growth hormone, and insulin concentrations. After slaughtering, the longissimus dorsi, semitendinosus, semimembranosus, gastrocnemius, soleus, and chest muscle were removed to record various parameters, including the mRNA expression levels of MSTN and IGFs, in addition to skeletal muscle fiber diameter and cross-sectional area. The result showed that as dietary intake improved, the mRNA expression levels of MSTN and IGF-II decreased, whereas IGF-Ðexpression increased. The mRNA expression levels of MSTN and IGFs were significantly different in the same skeletal muscle under different dietary intake. The skeletal muscle fiber diameter and cross-sectional area increased with greater dietary intake, as observed for the mRNA expression of IGF-Ð; however, it contrasted to that observed for the mRNA expression of MSTN and IGF-II. In conclusion, dietary intake levels have a certain influence on MSTN and IGFs mRNA expression levels, in addition to skeletal muscle fiber diameter and cross-sectional area. This study contributes valuable information for enhancing the molecular-based breeding of sheep.
Assuntos
Dieta/veterinária , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like I/genética , Carne/análise , Músculo Esquelético/metabolismo , Miostatina/genética , RNA Mensageiro/genética , Ração Animal , Animais , Cruzamento , Quimera/genética , Dieta/métodos , Regulação da Expressão Gênica , Hormônio do Crescimento/sangue , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Músculo Esquelético/química , Miostatina/metabolismo , RNA Mensageiro/metabolismo , Carneiro Doméstico , Ureia/sangueRESUMO
Mesenchymal stem cells derived from bone marrow (BMSCs) are a population of self-renewing multipotent cells that are capable of differentiating into various cellular lineages, and are widely employed in tissue engineering and cell therapy. Recently, clinical research involving BMSCs has become increasingly popular. In order to conduct appropriate research, it is first necessary to amplify large amounts of functional BMSCs in vitro. However, after several passages of expanding in vitro, the proliferation and differentiation potential of BMSCs gradually decline. To determine whether overexpression of Oct4 or Sox2 might prevent this decline, we transfected Oct4 or Sox2, which are essential for the pluripotency and self-renewal of embryonic stem cells, into BMSCs of Xiaomeishan porcine by a lentivirus. The results showed that overexpression of Sox2 or Oct4 BMSCs in culture media containing a basic fibroblast growth factor resulted in higher proliferation and differentiation compared to controls, suggesting that genetic modification of stemness-related genes is an efficient way to maintain the proliferation and differentiation potential of BMSCs.
Assuntos
Adipogenia , Proliferação de Células , Células-Tronco Mesenquimais/fisiologia , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Células Cultivadas , Fatores de Crescimento de Fibroblastos/fisiologia , Expressão Gênica , Células HEK293 , Humanos , Fator 3 de Transcrição de Octâmero/genética , Osteogênese , Fatores de Transcrição SOXB1/genética , Sus scrofaAssuntos
Transtornos Cognitivos/patologia , Transtornos Cognitivos/psicologia , Inflamação/patologia , Fatores de Crescimento Neural/metabolismo , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/psicologia , Proteínas S100/metabolismo , Feminino , Humanos , Masculino , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
We experimentally demonstrate cavity phase matching for the first time using a sheet optical parametric oscillator which is made of an x-cut KTiOPO(4) crystal sheet. This microcavity presents 220 kW peak power capability for near-frequency-degenerate parametric outputs with up to 23.8% slope efficiency. It also features unique spectral characteristics such as single-longitudinal-mode and narrow linewidth. These attractive properties predict broad applications of such a mini-device, such as terahertz generation, photonic integration, spectroscopy, and quantum information, etc.