RESUMO
Retinoblastomas result from the inactivation of the RB1 gene and the loss of Rb protein, yet the cell type in which Rb suppresses retinoblastoma and the circuitry that underlies the need for Rb are undefined. Here, we show that retinoblastoma cells express markers of postmitotic cone precursors but not markers of other retinal cell types. We also demonstrate that human cone precursors prominently express MDM2 and N-Myc, that retinoblastoma cells require both of these proteins for proliferation and survival, and that MDM2 is needed to suppress ARF-induced apoptosis in cultured retinoblastoma cells. Interestingly, retinoblastoma cell MDM2 expression was regulated by the cone-specific RXRgamma transcription factor and a human-specific RXRgamma consensus binding site, and proliferation required RXRgamma, as well as the cone-specific thyroid hormone receptor-beta2. These findings provide support for a cone precursor origin of retinoblastoma and suggest that human cone-specific signaling circuitry sensitizes to the oncogenic effects of RB1 mutations.
Assuntos
Proliferação de Células , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Retinoblastoma/metabolismo , Transdução de Sinais , Animais , Sobrevivência Celular , Humanos , Camundongos , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-myc/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Receptor X Retinoide gama/metabolismo , Receptores beta dos Hormônios Tireóideos/metabolismo , Transplante HeterólogoRESUMO
A phytochemical investigation of an East China Sea collection of the brown alga Dictyota coriacea has led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A-D (1-4), two rare nitrogenous xenicane diterpenoids, dictyolactams C (5) and D (6), and one known crenulide diterpenoid, hydroxycrenulide (7). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations. Coriaceumins A-D (1-4) represent the first examples of nitrogen-containing crenulide diterpenoids. In a bioassay, compounds 2, 3, 5, and 7 were found to exhibit different levels of inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) with IC50 values ranging from 7.3 to 19 µM. In addition, the primary structure-activity relationships of all the isolates were summarized.
Assuntos
Diterpenos , Phaeophyceae , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Diterpenos/farmacologia , Diterpenos/química , ChinaRESUMO
AIM: To investigate the knowledge level and clinical practice of neonatal intensive care unit nurses on the whole process of hypothermia prevention in preterm infants. DESIGN: A polycentric descriptive cross-sectional study was conducted in 23 hospitals in Shandong province involving 254 neonatal intensive care unit nurses. METHODS: An evidence-based knowledge and clinical practice questionnaire on hypothermia prevention in preterm infants and a general information questionnaire were used to collect data. SPSS and EXCEL 24.0 database were used for data statistics and analysis. RESULTS: Nearly one-third of nurses were unclear about the definition of mild hypothermia and heat preservation measures during labour management and resuscitation. Knowledge about the correct rate of amniotic fluid evaporation was low. The higher the hospital level and nurses' education level, professional title, work experience, and position, the higher the knowledge level. The clinical practice of nurses differed in terms of body temperature assessment tools, measurement sites, and measurement frequency for premature infants. CONCLUSIONS: Nurses in neonatal intensive care units need to apply evidence-based knowledge and carry out practice interventions to ensure preterm infants' safe transition from the delivery room to the neonatal intensive care unit. IMPACT: There have been few studies evaluating neonatal nurses' knowledge and practices with regards to the preventing hypothermia of premature infants from delivery room to neonatal intensive care unit. The study identifies the deficiencies and problems in temperature management that can be attributed to the knowledge level of nurses. The findings will help improve the current curriculum, teaching strategies, and the nurses' knowledge levels, preventing premature hypothermia in infants. REPORTING METHOD: This study adhered to the STROBE statement for observational studies and obtained approval (KYLL-2023LW045) from the ethics committee of The Second Hospital of Shandong University. The other 22 third- and second-level hospitals, as our alliance members, recognized our chairperson status within the alliance and were willing to join our academic activities. Mutual responsibility for ethical filing between alliance units. PUBLIC CONTRIBUTION: 254 nurses were recruited from 23 tertiary and secondary public hospitals in Shandong province. No public or patient involvement. Members of the research group used the Questionnaire Star platform to prepare the electronic questionnaire, including obtaining informed consent, taking precautions for questionnaire completion, and using the aforementioned measurement tools. The project research team contacted the head nurses of 23 neonatal intensive care units in Shandong Province. After obtaining consent from the head nurses, they were asked to send the requirements and link of the electronic questionnaire to their WeChat management group. The nurses go through each question and make a choice which has two options of 'agree' or 'disagree.' Based on their answers, nurses were evaluated as having 'mastered' or 'not mastered' each item. Each 'mastered' item (correct answer) was given a score of 4; an item 'not mastered' (incorrect answer) was given a score of 0. The total score ranged from 0 to 100.
RESUMO
Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4â-â9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.
Assuntos
Lipopolissacarídeos , Triterpenos , Óxido Nítrico , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Anti-Inflamatórios/farmacologia , Folhas de Planta , Triterpenos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
AIMS AND OBJECTIVES: The aim of this study was to describe the prevalence of reproductive concerns among young female patients with colorectal cancer and explore the associated factors. BACKGROUND: With the trend of longer survival and younger age at diagnosis of colorectal cancer patients, reproductive concerns have become increasingly prevalent among young female colorectal cancer patients. DESIGN: Cross-sectional design. METHODS: The study included 150 young female patients with colorectal cancer who completed cancer treatment at 2 hospitals in Guangzhou, China, between November 2020 and December 2021 completed an investigation comprising A general questionnaire, The Reproductive Concerns After Cancer scale, The Family Adaptation and Cohesion Evaluation Scale II and unmet fertility information needs questionnaire. Multivariable linear regression analysis was performed in order to identify factors that influence reproductive concerns. This study was prepared and is reported according to the STROBE checklist. RESULTS: The mean (SD) score on the Reproductive Concerns After Cancer scale was 54.78 ± 8.97. The highest score was for the children's health subscale (3.84 ± .92) and the lowest was for acceptance (2.24 ± .70). Multiple regression analysis showed that patients with fewer children, female children, lower education level (less than undergraduate degree), earlier disease stage, lower family function and higher unmet need for fertility information had more reproductive concerns, which explained 26.9% of the total variation of the model. CONCLUSIONS: The patients with fewer children, female children, low cultural degree (less than bachelor), early clinical patients, poorer family function and higher unmet fertility information needs had higher reproductive concerns. RELEVANCE TO CLINICAL PRACTICE: These findings can guide the development of interventions to mitigate reproductive concerns, including understand and meet their fertility information needs, improve the level of family function. PATIENT OR PUBLIC CONTRIBUTION: Survey questionnaires were completed by participants among young female with colorectal cancer in this study.
Assuntos
Neoplasias Colorretais , Reprodução , Criança , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , PrevalênciaRESUMO
OBJECTIVE: To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China. METHODS: A total of 6270 healthy children aged 4-17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight. RESULTS: The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P < 0.05). The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of the regression coefficient was the largest). With increasing age and height, the values of Z5, R5, R20, R5-R20, and Fres decreased, while the value of X5 increased. Through height, age, and weight, we obtained the normal predicted values equation of children's IOS parameters. Compared with the other reference equations, our reference equation is more suitable for Chinese children. CONCLUSIONS: The study revealed the reference values of IOS parameters in healthy Chinese children. In the evaluation of results for lung function measurements, this predicted value equation is more consistent with the characteristics of Chinese children than other reference equations. CLINICAL TRIAL: ChiCTR: 1800019029.
Assuntos
Pulmão , Adolescente , Criança , Pré-Escolar , China , Humanos , Oscilometria/métodos , Valores de Referência , Testes de Função Respiratória/métodos , EspirometriaRESUMO
Theileria orientalis is known to be a group of benign cattle parasites with a cosmopolitan distribution, and has been classified into 11 genotypes through MPSP gene phylogenetic analysis. In China, T. orientalis is the most prevalent Theileria species, with several genotypes, but few fatal cases have been reported. In June 2020, dairy cattle in Zhangjiakou, Hebei Province, showed clinical symptoms of piroplasmosis, causing many animals to die. Blood smears and PCR detection results confirmed T. orientalis infection with a 66.7% positive rate of collected blood samples. The MPSP sequences analysis revealed parasite genotypes 1 (Chitose) and 2 (Ikeda). Aiming to isolate the pathogens, experimental animal was infected with T. orientalis via inoculation of the positive blood samples. The results has shown that only T. orientalis genotype 2 (Ikeda) was obtained that has confirmed by MPSP and 18S rRNA sequences analysis, indicating that the Ikeda type was predominant and responsible for the disease. Although many T. orientalis genotypes are present in China, the possibility of T. orientalis genotypes 1 and 2 infections in confined dairy cattle should be considered to avoid additional economic losses.
Assuntos
Doenças dos Bovinos , Theileria , Theileriose , Animais , Bovinos , Genótipo , Filogenia , RNA Ribossômico 18S , Theileria/genéticaRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) has quickly spread across the world. However, the nutritional status of COVID-19 patients has not yet been extensively examined. OBJECTIVES: The aim of this study was to evaluate the nutritional status of COVID-19 patients and to identify factors independently associated with malnutrition risk. METHODS: In this single-center, cross-sectional study, we analyzed data from 760 hospitalized COVID-19 patients between 29 January 2020 and 15 March 2020. Based on the Nutrition Risk Screening (NRS) 2002 score, we divided patients into the normal nutrition group (NRS score <3) and the malnutrition risk group (NRS score ≥3). The associations of age, gender, symptoms, comorbidities, BMI, serum albumin and prealbumin concentrations, disease severity, activities of daily living (ADL) score, and clinical outcomes with malnutrition risk were analyzed. Multivariable logistic regression analysis was used to identify independent factors associated with malnutrition risk. RESULTS: Of patients with COVID-19, 82.6% were at risk of malnutrition. There were statistical differences in the age, incidence of fever, BMI, serum albumin and prealbumin concentrations, ADL score, and disease severity between the 2 groups. Multivariable logistic regression analysis revealed that age ≥65 y (vs. <65 y; OR: 5.40; P < 0.001), serum albumin <35 g/L (vs. ≥35 g/L; OR: 3.61; P < 0.001), serum prealbumin <150 mg/L (vs. ≥150 mg/L; OR: 2.88; P = 0.042), critical cases (vs. moderate cases; OR: 4.46; P < 0.001), ADL score 41-60 (vs. ADL score 100; OR: 4.50; P = 0.012), and ADL score ≤40 (vs. ADL score 100; OR: 9.49; P < 0.001) were significantly associated with the risk of malnutrition in COVID-19 patients. CONCLUSIONS: This study showed that prevalence of malnutrition risk was high in COVID-19 patients. Older age, low serum albumin and prealbumin concentrations, ADL score <60, and disease severity were independent factors associated with malnutrition risk.
Assuntos
COVID-19/complicações , Desnutrição/epidemiologia , Idoso , COVID-19/epidemiologia , COVID-19/virologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Fatores de Risco , SARS-CoV-2/isolamento & purificaçãoRESUMO
In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.
Assuntos
Escherichia coli O157 , Probióticos , Animais , Aderência Bacteriana , Células CACO-2 , Enterococcus , Humanos , Lactobacillus , Salmonella typhimurium , SuínosRESUMO
Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).
Assuntos
Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Morus/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , China , Inibidores Enzimáticos/isolamento & purificação , Flavonoides/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , PrenilaçãoRESUMO
Babesia species, the agentic pathogens of human and animal babesiosis, are spread worldwide. Over the last decade, genetic manipulation approaches have been applied with many protozoan parasites, including Plasmodium falciparum, Trypanosoma cruzi, Cryptosporidium parvum, Theileria annulata, Theileria parva, Babesia bovis, Babesia bigemina, Babesia ovata, Babesia gibsoni, and Babesia ovis. For Babesia sp. Xinjiang (BspXJ), which is the causative pathogen of ovine babesiosis mainly in China, the efficiency of these techniques remains unclear. Firstly, a plasmid bearing the elongation factor-1 alpha promoter and the firefly luciferase reporter gene and rap stop region were transfected into BspXJ by electroporation and nucleoporation to determine the most suitable transfection solution. Then, six program settings were evaluated to confirm the best for BspXJ transient transfection, and a series of different amounts of plasmid DNA were transfected to generate relatively high luminescence values. Finally, the activities of four promoters derived from BspXJ were evaluated using the developed transient transfection system. After evaluating of various transfection parameters, the human T cell nucleofector solution, program V-024 and 20 µg of plasmid DNA were selected as the most favorable conditions for BspXJ transient transfection. These findings provide critical information for BspXJ genetic manipulation, an essential tool to identify virulence factors and to further elucidate the basic biology of this parasite.
Assuntos
Babesia bovis , Babesia , Babesiose , Doenças dos Bovinos , Criptosporidiose , Cryptosporidium , Animais , Babesia/genética , Babesia bovis/genética , Bovinos , Humanos , Ovinos , TransfecçãoRESUMO
Traumatic myiasis causes substantial economic losses to farmers worldwide. In the present study, six flocks of sheep (2261 sheep) were investigated in Gansu, China, and 207 of 552 larvae were genetically characterized based on three genes, including cyt b, EF-1α, and white gene, by polymerase chain reaction and sequence analysis. A survey of sheep in China revealed that the prevalence of vulvar myiasis of six sheep flocks was 5.00% (11/220, Flock1), 4.85% (10/206, Flock2), 4.50% (9/200, Flock3), 5.00% (15/300, Flock4), 4.68% (15/320, Flock5), 0% (0/1015, Flock6), respectively. The sequence and phylogenetic analysis showed that only Wohlfahrtia magnifica was detected in the field samples. This is the first report of ovine vulvar myiasis caused by W. magnifica in Gansu, China. Some prophylactic measures are strongly recommended to reduce the risk of sheep acquiring traumatic myiasis in Gansu, China.
Assuntos
Miíase/veterinária , Sarcofagídeos/fisiologia , Doenças dos Ovinos/epidemiologia , Doenças da Vulva/veterinária , Animais , China/epidemiologia , Feminino , Proteínas de Insetos/análise , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , Miíase/epidemiologia , Miíase/parasitologia , Filogenia , Prevalência , Sarcofagídeos/genética , Sarcofagídeos/crescimento & desenvolvimento , Análise de Sequência de DNA/veterinária , Ovinos , Doenças dos Ovinos/parasitologia , Doenças da Vulva/epidemiologia , Doenças da Vulva/parasitologiaRESUMO
Theileria annulata is the pathogen of bovine tropical theileriosis. It is extremely harmful to the cattle industry, with huge economic losses. The toll-like receptor (TLR) and NOD-like receptor (NLR) signaling pathways are crucial for resistance to infection of the protozoa, such as Plasmodium falciparum, Toxoplasma gondii, and Trypanosoma cruzi. However, the role of these immune-related pathways is unclear during T. annulata infection. In the present study, peripheral blood mononuclear cells and serum were separated from blood samples of calves infected with homogenized tick supernatants carrying T. annulata sporozoites at 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h and 168 h postinoculation. The Custom RT2 Profiler PCR Array was used to explore the mRNA levels of 42 TLR and NLR signaling pathway relevant genes. The TLR1, TLR6, TLR10, NLRP1, and MyD88 genes and their downstream signaling molecules significantly differed after the T. annulata infection in comparison with that of preinfection from 72 h to 168 h postinoculation. The serum concentrations of IL-6, IL-1ß, and TNFα were significantly increased at 96 h and 168 h postinfection. These findings provided novel information to help determine the mechanisms of TLR and NLR signaling pathway involvement in protection against T. annulata infection.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doenças dos Bovinos/metabolismo , Doenças dos Bovinos/parasitologia , Theileria annulata/fisiologia , Theileriose/metabolismo , Theileriose/parasitologia , Receptores Toll-Like/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Bovinos , Doenças dos Bovinos/genética , Feminino , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/parasitologia , Masculino , Transdução de Sinais , Theileria annulata/genética , Theileriose/genética , Carrapatos/parasitologia , Receptores Toll-Like/genéticaRESUMO
The apicomplexan parasite Theileria orientalis is a tick-borne intracellular protozoan parasite that is widely distributed throughout China. It causes bovine theileriosis in infected cattle, which results in huge economic losses to the cattle industry. In this study, the infection status of T. orientalis was determined in 260 blood samples from cattle from seven provinces across China. Results of a major piroplasm surface protein (MPSP)-PCR assay revealed that an average of 36.5% (95/260) of cattle was positive for T. orientalis infection. Based on the MPSP gene sequences, phylogenetic analysis revealed that these isolates of T. orientalis comprised of eight MPSP types, 1, 2, 3, 4, 5, 7, N1, and N2. This is the first report of new T. orientalis MPSP genotypes N1 and N2 in cattle in China.
Assuntos
Antígenos de Protozoários/genética , Doenças dos Bovinos/epidemiologia , Variação Genética/genética , Proteínas de Protozoários/genética , Theileria/genética , Theileriose/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária , Animais , Bovinos , Doenças dos Bovinos/parasitologia , China , Genoma de Protozoário/genética , Genótipo , Proteínas de Membrana/genética , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase/veterinária , Theileria/isolamento & purificação , Theileriose/parasitologiaRESUMO
CONTEXT: d-Glucaro-1,4-lactone (1,4-GL) exists in many vegetables and fruits. Metabonomics has not been used to investigate the role of 1,4-GL in preventing liver cancer. OBJECTIVE: The pharmacological effects and metabolite alterations of 1,4-GL on the prevention of diethylnitrosamine (DEN)-induced liver cancer were investigated. MATERIALS AND METHODS: Ten healthy Sprague-Dawley rats served as control and 46 were used to establish rat liver cancer model. 1HNMR-based metabonomics was used to compare the effects of oral 1,4-GL (50 mg/kg) in liver cancer rats (n = 26) after 10 consecutive weeks of intervention. The amino acids in rat serum were quantified by HPLC-UV, and the changes in Fischer's ratio were calculated. RESULTS: The 20-week survival rate of DEN-induced liver cancer rats administered with oral 1,4-GL was increased from 45.0 to 70.0% with reduced carcinogenesis of the liver and significantly lowered serum α-fetoprotein level (14.28 ± 2.89 ng/mL vs. 18.56 ± 4.65 ng/mL, p = 0.012). The serum levels of leucine, valine, 3-hydroxybutyrate, lactate, acetate and glutamine in the DEN + 1,4-GL group returned to normal levels compared with those of the DEN group on week 20. Fischer's ratio in the rat serum of DEN group was 1.62 ± 0.21, which was significantly lower than that in healthy rats (2.3 ± 0.12). However, Fischer's ratio increased to 1.89 ± 0.22 in the DEN + 1,4-GL group. DISCUSSION AND CONCLUSIONS: 1,4-GL exerted positive effects on liver carcinogenesis in rats by pathological examination and metabonomic analysis. Its mechanism may be related to the restoration of amino acid and energy metabolism.
Assuntos
Dietilnitrosamina/toxicidade , Ácido Glucárico/análogos & derivados , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Metabolômica/métodos , Alquilantes/toxicidade , Animais , Ácido Glucárico/metabolismo , Ácido Glucárico/uso terapêutico , Neoplasias Hepáticas Experimentais/induzido quimicamente , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To identify independent prognostic factors to be included in a nomogram to predict the prognosis of gastric cancer patients with peritoneal dissemination. METHODS: This is a retrospective study on 684 patients with a histological diagnosis of gastric cancer with peritoneal dissemination from the Sun Yat-sen University Cancer Center as the development set, and 62 gastric cancer patients from the Sixth Affiliated Hospital of Sun Yat-sen University as the validation group. Chi-square test and Cox regression analysis were used to compare the clinicopathological variables and the prognosis of gastric cancer patients with peritoneal dissemination. The Harrell's concordance index (C-index) and calibration curve were determined for comparisons of predictive ability of the nomogram. RESULTS: Univariate and multivariate analyses showed that serum carcinoembryonic antigen (CEA) level (P=0.032), ascites grading (P=0.008), presence of extraperitoneal metastasis (P<0.001), seeding status (P=0.016) and performance status (P=0.009) were independent prognostic factors for gastric cancer patients with peritoneal dissemination in the development set. The nomogram model was constructed using these five factors. Internal validation showed that the C-index of the model was 0.641. For the external validation, the C-index of this model was 0.709. CONCLUSIONS: We developed and validated a nomogram to predict the prognosis for gastric cancer patients with peritoneal dissemination. This nomogram may play an important clinical role in guiding palliative therapy for these types of patients, although it may need more data for optimization.
RESUMO
The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell-based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound-healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re-epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier.
Assuntos
Epitélio Corneano/metabolismo , Homeostase , Proteínas com Homeodomínio LIM/metabolismo , Fatores de Transcrição/metabolismo , Cicatrização , Animais , Células Cultivadas , Epitélio Corneano/citologia , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Proteínas com Homeodomínio LIM/genética , Camundongos , Camundongos Knockout , Fatores de Transcrição/genéticaRESUMO
Bovine theileriosis, a tick-borne protozoan disease caused by Theileria annulata, Theileria orientalis and Theileria sinensis, is widespread in China and is a serious economic problem for the Chinese livestock industry. In this study, recombinant major piroplasma surface proteins (MPSP) of T. annulata, T. orientalis and T. sinensis based on MPSP genes were expressed in Escherichia coli BL21(DE3). The immunogenicity and specificity of the three purified recombinant MPSP proteins were evaluated with the reference positive sera of T. annulata, T. orientalis, T. sinensis, Babesia bovis, B abesia bigemina, Babesia major, Babesia motasi, Theileria luwenshuni, Theileria uilenbergi and Anaplasma ovis using an enzyme-linked immunosorbent assay (ELISA) or western blotting. The results showed that all three of the rMPSP proteins had a strong reaction with the sera from cattle infected with T. annulata, T. orientalis and T. sinensis via western blotting but not with other piroplasma and Anaplasma species. Then, the rMPSP protein of T. sinensis was used to develop an iELISA for detecting the three Theileria species infections. The specificity and sensitivity were 95.7 and 95.5 %, respectively, with a threshold of 28.8 % of the specific mean antibody rate (AbR). Finally, 2473 field-collected bovine sera, from 42 prefectures of 17 provinces in China, were tested using the ELISA to evaluate the prevalence of bovine theileriosis, and the average positive rate was 43.6 %. The developed iELISA could be a suitable tool to detect the three bovine Theileria species, and the data also provided important information regarding the current prevalence of bovine theileriosis in China.
Assuntos
Babesia bovis/genética , Doenças dos Bovinos/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Proteínas de Membrana/análise , Theileria annulata/genética , Theileriose/diagnóstico , Animais , Babesia bovis/isolamento & purificação , Babesiose/diagnóstico , Babesiose/parasitologia , Western Blotting , Bovinos/parasitologia , Doenças dos Bovinos/epidemiologia , China/epidemiologia , Proteínas Recombinantes , Sensibilidade e Especificidade , Theileria annulata/isolamento & purificação , Theileriose/classificação , Theileriose/epidemiologia , Doenças Transmitidas por Carrapatos/parasitologiaRESUMO
Four new prenylated bibenzyls, named aglaiabbrevins A-D (2, 4-6), were isolated from the leaves of Aglaia abbreviata, along with two known related analogues, 3,5-dihydroxy-2-[3,7-dimethyl-2(E),6-octadienyl]bibenzyl (7) and 3,5-dihydroxy-2-(3-methyl-2-butenyl)bibenzyl (8). The structures of the new compounds were elucidated on the basis of extensive spectroscopic experiments, mainly one and two dimensional (1D- and 2D)-NMR, and the absolute configuration of 5 was determined by the measurement of specific rotation. The isolated compounds were evaluated for their protein tyrosine phosphatase-1B (PTP1B) inhibitory activity. The results showed that compounds 5-7 exhibited more potent PTP1B inhibitory effects with IC50 values of 2.58±0.52, 2.44±0.35, and 2.23±0.14 µM, respectively, than the positive control oleanolic acid (IC50=2.74±0.20 µM). On the basis of the data obtained, these bibenzyls with the longer C-2 prenyl groups may be considered as potential lead compounds for the development of new anti-obesity and anti-diabetic agents. Also, the PTP1B inhibitory effects for prenylated bibenzyls are being reported for the first time.