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1.
Mycobiology ; 52(1): 58-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415174

RESUMO

The present study sought to propose Ganoderma guixiense sp. nov. as a new species based on phenotypic and genotypic evidence. Phylogenetic analyses were carried out based on the internal transcribed spacer (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), and the second subunit of RNA polymerase II (RPB2) sequence data. G. guixiense has been characterized by pileate basidiomata, long stipe, in addition to reddish-black zonate pileal surface. Basidiospores are broadly ellipsoid with one end tapering at maturity, and measuring 9-12.8 × 6.5-9.3 µm. Basidia are oval to subglobose. This study marks the first exploration of the biological characteristics of G. guixiense. The result indicated that the optimal medium of mycelial growth was observed on malt extract agar (MEA) and yeast extract peptone dextrose agar (YPD) while the optimal temperature was found to be 25-30 °C with pH range of 6-7.

2.
Curr Res Transl Med ; 72(1): 103438, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38244303

RESUMO

Congenital sideroblastic anemia (CSA) is a group of disorders caused by different genetic mutations that result in low iron utilization and ineffective erythropoiesis. Current treatments are limited, and some patients do not respond to vitamin B6 therapy. Luspatercept is a novel erythropoietic maturation agent approved for adult ß-thalassemia and Myelodysplastic syndromes with ring sideroblasts (MDS-RS) associated with ineffective erythropoiesis. Here we report 2 patients with CSA due to mutations in ALAS2 and SLC25A38 genes who became unresponsive after a period of treatment with vitamin B6 and iron chelators but achieved transfusion independence and a markedly reduced spleen after combination with luspatercept.


Assuntos
Receptores de Activinas Tipo II , Anemia Sideroblástica , Doenças Genéticas Ligadas ao Cromossomo X , Proteínas Recombinantes de Fusão , Adulto , Humanos , 5-Aminolevulinato Sintetase , Receptores de Activinas Tipo II/efeitos adversos , Anemia Sideroblástica/tratamento farmacológico , Anemia Sideroblástica/genética , Anemia Sideroblástica/congênito , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Vitamina B 6
3.
Environ Pollut ; 347: 123433, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38278405

RESUMO

The COVID-19 pandemic has resulted in a substantial surge in the usage of disposable plastic masks, generating a significant volume of waste and contributing to environmental pollution. Wetland ecosystems function as crucial repositories for terrestrial pollutants and are highly effective in retaining disposable masks composed mainly of PP material. These masks can endure extended periods in wetlands, experiencing natural degradation that may have potential implications on wetland ecosystems. Our findings demonstrate the natural aging process of disposable masks, resulting in the generation of microplastics (MPs) ranging in diameter from 10 to 30 µm over a 180-day timeframe. Examination of 16S rDNA data unveiled temporal fluctuations in microbial diversity in the wetland ecosystem. Initially, microbial diversity displayed a modest incline, which was succeeded by a subsequent decrease. With the progressive accumulation of plastic within the wetland, an ongoing decline in microbial diversity linked to nitrogen transformation was observed. This study provides valuable insights into the retention of disposable masks by wetlands amidst the COVID-19 pandemic, along with their consequential effects on wetland ecosystems, specifically pertaining to nitrogen cycling. It underscores the urgency of augmenting the safeguarding measures for wetland ecosystems.


Assuntos
COVID-19 , Microbiota , Humanos , Áreas Alagadas , Ecossistema , Polipropilenos , Pandemias , Plásticos , Envelhecimento , Nitrogênio
4.
Clin Exp Med ; 23(2): 437-445, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35451668

RESUMO

To explore the clinicopathological characteristics, survival outcomes, and prognosis of very young gastric cancer (GC). From January 1, 2011 to January 1, 2021, GC patients under 30 years old treated in three tertiary hospitals were enrolled. Clinicopathological characteristics were summarized, prognostic factors and survival outcomes including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were retrospectively analyzed. One hundred patients were finally included, with a median age of 23 years.73 (73.0%) were female. Most patients had initial symptoms of abdominal pain (66.0%). The most common tumor locations were gastric antrum (38.0%) and gastric body (37.0%). The main histological types were diffuse (81.0%) and poorly differentiated (91.0%). Most patients presented with stage III-IV disease (82.0%) at diagnosis and the common sites of metastasis were ovary (39.5%) and peritoneum (27.6%). The mOS of the whole group was 23.3 months (95% CI 17.2-29.4). Moreover, the mOS of patients at stage I-II was not reached. The mOS of patients at stage III and stage IV was 40.6 months (95% CI 10.2-70.9) and 10.3 months (95% CI 8.9-11.6), respectively. The mDFS of stage I-III patients was 28.5 months (95% CI 14.7-42.3), and the mPFS of the metastatic patients was 4.5 months (95% CI 4.0-5.0). TNM stage (P = 0.005) and radical surgery (P = 0.001) were independent prognostic factors of overall survival. The very young GC were predominantly female, diffuse type, and advanced diagnosis. TNM stage and radical surgery were independent prognosis factors for overall survival.


Assuntos
Neoplasias Gástricas , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Prognóstico , Neoplasias Gástricas/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Gastrectomia
5.
Blood Cells Mol Dis ; 98: 102708, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334505

RESUMO

Severe aplastic anemia (SAA) is a bone marrow failure disorder caused by autoimmune dysfunction. The presentation by dendritic cells (DCs) is the key step in initiating the immune response against unknown antigens in SAA patients. In the previous phase, we found that compared to healthy controls, patients with SAA had an increased proportion of circulating myeloid/conventional dendritic cells (mDCs/cDCs) with enhanced phagocytosis, more secretion of Th1-type cytokines (IL-2, TNF-α, IFN-γ) in the bone marrow, and a reduced proportion of Treg cells. In this study, we found that cDCs sorted from SAA patients had higher expression level of HLA-DQ, co-stimulatory molecules CD86, PTK and ERK1/2 than the remission SAA patients and healthy controls. Moreover, downregulation of HLA-DQ protein levels on cDCs derived from SAA patients resulted in reduced phagocytosis rate and CD86 expression of cDCs. When the cDCs above were co-cultured with CD4+ cells from the same patients, reduced secretion of Th1 type of lymphocyte cytokines was observed. Analysis of clinically relevant data suggests that HLA-DQ expression levels were closely related to disease severity and immune status of patients. These findings show that the role of HLA-DQ in the immunopathogenesis of SAA is potentially important and worth further study.


Assuntos
Anemia Aplástica , Humanos , Medula Óssea/patologia , Fator de Necrose Tumoral alfa , Antígenos HLA-DQ/metabolismo
6.
Iran J Public Health ; 51(1): 96-104, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35223630

RESUMO

BACKGROUND: U To analyze the effect of metformin hydrochloride combined with insulin pump for gestational diabetes mellitus (GDM). METHODS: Overall, 216 patients with GDM in Zhangqiu Maternity and Child Care Hospital, Jinan, China from Aug 2018 to Dec 2020 were enrolled and randomized into research and control groups. Patients in the control group were treated with insulin pump, while those in the research group were treated with metformin hydrochloride combined with insulin pump. The clinical efficacy, blood glucose levels, serum Betatrophin, C reactive protein (CRP), Cystatin C (Cys-C), homocysteine (Hcy), adiponectin, tumor necrosis factor (TNF-α), interleukin-6 (IL-6) content, incidence of adverse pregnancy outcomes and incidence of adverse newborns of patients in the two groups were compared. RESULTS: After treatment, the total clinical efficiency of the research group was 84.26%, significantly higher than that of the control group (68.52%). The levels of FPG, 2hPG, HbAlc, serum Betatrophin, CRP, CysC, Hcy, adiponectin factors, TNF-α, and IL-6 in the research group were lower than those in the control group, with statistically significant differences (P<0.05). The overall incidence of adverse pregnancy outcomes was 10.19% in the research group, and 25.93% in the control group. The comparative differences between the two groups were statistically significant (P<0.05). The overall incidence of adverse newborns was 9.26% in the research group, and 21.30% in the control group. The comparative differences between the two groups were statistically significant as well (P<0.05). CONCLUSION: Metformin hydrochloride combined with insulin pump for GDM can significantly reduce blood glucose level, regulate serum protein factor levels, and improve adverse outcomes for mother and child, which deserves clinical promotion.

7.
Environ Technol ; 43(23): 3507-3518, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33908820

RESUMO

The performance and energy consumption of a gas-liquid-solid inverse fluidised bed bioreactor (GLS-IFBBR) using polyethylene (PE) particles with different surface coatings (zeolite, lava rock, activated carbon and multi-plastic) as media for synthetic wastewater treatment were investigated at loading rates of 1.64-3.38 kg COD/(m3·d) and 0.17-0.34 kg N/(m3·d) to determine the optimum carrier media. The results showed that PE coated with other inorganic materials could increase the nutrient removal efficiency at the same influent conditions. Compared with other media, PE coated with zeolite (PEZ) was the optimal carrier particles in this study as reflected by the highest COD and nitrogen removal, stable effluent, low biomass yield at different hydraulic retention times (HRT). In addition, the energy consumption of lavarock-coated PE (PEL) with a highest density was the lowest.


Assuntos
Purificação da Água , Zeolitas , Reatores Biológicos , Nitrogênio , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos
8.
Anal Chim Acta ; 1176: 338772, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34399894

RESUMO

The extraction performance of solid-phase microextraction (SPME) fiber is significantly influenced by coating materials and fabricating process. It is urgently needed for fabricating robust SPME fiber with facile preparation methods. Herein, a novel polyimide (PI) @ covalent organic framework (COF) synthesized by 1,3,5-Tris (4-aminophenyl) benzene (TPB) and 2,5-dimethoxyterephthalaldehyde (DMTP) fiber, named PI@TPB-DMTP fiber, was successfully fabricated with facile method at room temperature. Firstly, a COF crystals TPB-DMTP was in situ grown on stainless steel fiber, where the COF crystals was synthesized by the Schiff-base reaction between TPB and DMTP. Subsequently, the COF coating was covered with an ultrathin layer of PI through a simple dip-coating method to improve the fiber stability. By coupled PI@TPB-DMTP SPME fiber with gas chromatography-negative chemical ion-mass spectrometry (GC-NCI-MS), a sensitive analytical method was established for the determination of ultratrace polybrominated diphenyl ethers (PBDEs) in water sample. To achieve the best efficiency and sensitivity for the analysis of PBDEs, six potential influencing factors in extraction step and desorption step were optimized. Under optimized conditions, the established method showed high enhancement factors of 1470-3555, wide linear range of 0.05-100 ng L-1, low detection limits of 0.0083-0.0190 ng L-1, good repeatability for intra-day in the range of 3.71%-7.62% and inter-day in the range of 5.12%-8.81%, good reproducibility in the range of 6.83%-9.21%. The satisfactory recovery was ranged from 79.2% to 117.3% in determining real water samples. The excellent experimental performance was mainly attributed to the large specific surface area of TPB-DMTP, as well as the high permeability of porous PI film. The results demonstrated that the COF-based fiber showed great potential for analysis of PBDEs in complex environmental samples.


Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Éteres Difenil Halogenados/análise , Reprodutibilidade dos Testes , Microextração em Fase Sólida , Temperatura , Poluentes Químicos da Água/análise
9.
Mycobiology ; 49(3): 213-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290546

RESUMO

Two new species of Fulvifomes are described from specimens collected in rainforests of Nonggang Nature Reserve of southern China, based on morphological characteristics and molecular phylogenetic analysis of the internal transcribed spacer (ITS) and nuclear large subunit ribosomal DNA (nLSU) sequences. Fulvifomes nonggangensis sp. nov. is characterized by perennial, sessile and solitary basidiocarps, applanate pileus, small cystidioles of 9.9-15.4 × 2.9-3.5 µm, large pores of 5-6 per mm, a dimitic hyphal system, and broadly ellipsoid basidiospores of 4.3-5.3 × 3.3-4.2 µm. F. tubogeneratus sp. nov. is characterized by perennial, sessile, and imbricate basidiocarps, a duplex context, small pores of 7-8 per mm, a dimitic hyphal system, and ovoid to subglobose basidiospores of 5.72 × 5.00 µm.

10.
Cell Immunol ; 364: 104343, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33774556

RESUMO

This study investigated the expression status of signaling lymphocytic activation molecule family 6 (SLAMF6) in CD8+ T lymphocytes of patients with severe aplastic anemia (SAA) and its association with the clinical indicators and immune status of the disease. The effects of SLAMF6 on the function and apoptosis of CD8+ T lymphocytes were also investigated. Levels of SLAMF6 and SLAM-associated protein in the CD8+ T lymphocytes of SAA patients were significantly lower than the normal controls, and they were positively correlated with hematopoietic-related indicators but negatively correlated with the levels of functional molecules of CD8+ T lymphocytes. After blocking SLAMF6, CD8+ T lymphocyte functional molecule secretion was upregulated and RICD was downregulated in SAA patients, suggesting that SLAMF6, is involved in the pathogenetic mechanism of SAA by regulating CD8+ T lymphocyte functional molecule secretion and RICD levels. SLAMF6 may be a novel target for the regulation of CD8+ T lymphocyte homeostasis.


Assuntos
Anemia Aplástica/metabolismo , Linfócitos T CD8-Positivos/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Adulto , Idoso , Anemia Aplástica/imunologia , Apoptose , Citotoxicidade Imunológica , Regulação para Baixo , Feminino , Hematopoese , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Adulto Jovem
11.
Immun Inflamm Dis ; 9(2): 340-350, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33657268

RESUMO

Human leukocyte antigen (HLA), also known as human major histocompatibility complex (MHC), is encoded by the HLA gene complex, and is currently known to have the highest gene density and the most polymorphisms among human chromosomal areas. HLA is divided into class I antigens, class II antigens, and class III antigens according to distribution and function. Classical HLA class I antigens include HLA-A, HLA-B, and HLA-C; HLA class II antigens include HLA-DP, HLA-DQ, and HLA-DR; nonclassical HLA class I and II molecules include HLA-F, E, H, X, DN, DO, and DM; and others, such as complement, are class III antigens. HLA is closely related to the body's immune response, regulation, and surveillance and is of great significance in the study of autoimmune diseases, tumor immunity, organ transplantation, and reproductive immunity. HLA is an important research topic that bridges immunology and clinical diseases. With the development of research methods and technologies, there will be more discoveries and broader prospects.


Assuntos
Antígenos HLA-DP , Antígenos de Histocompatibilidade Classe II , Antígenos HLA/genética , Antígenos HLA-DR , Antígenos de Histocompatibilidade Classe I , Humanos
12.
Cancer Manag Res ; 12: 8935-8941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061589

RESUMO

OBJECTIVE: To assess the short-term efficacy and safety of ixazomib in Chinese multiple myeloma (MM) patients in the real world. METHODS: Fifty-nine MM patients who received at least one cycle of ixazomib-based therapy between 1 June 2018 and 30 September 2019 were retrospectively analyzed in Tianjin Medical University General Hospital. Thirteen newly diagnosed MM (NDMM), 13 refractory/relapsed MM (RRMM) and 33 continuous therapy (27 bortezomib peripheral neuritis (PN) intolerant and six maintenance therapy) MM patients were included. The indicated overall response rate (ORR), time to overall response (TOR), and adverse events (AEs) were investigated. RESULTS: The ORR in NDMM was 76.9%, with one complete response (CR), five very good partial response (VGPR), four partial response (PR), median PFS, and TOR were 122 (66-272) days and 49 (22-108) days. The ORR in RRMM was 46.2%, with one CR, two VGPR, three PR, median PFS, and TOR were 79 (28-169) days and 59 (23-88) days. The ORR in continuous therapy MM patients was 100%, with nine stringent CR, 15 CR, six VGPR and three PR, median TOR was 75 (25-141) days. There were no significant differences regarding ORR between patients with cytogenetic high risk and standard risk in three subgroups (all P>0.05). The most frequent hematological AEs were anemia (13.6%) and thrombocytopenia (10.2%). The most common nonhematological AEs were PN (25.0%) and diarrhea (13.6%). CONCLUSION: The real-world data demonstrated that ixazomib-based therapy was generally effective and safe in the short term for MM patients.

13.
J Pharm Biomed Anal ; 187: 113355, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32442869

RESUMO

Duvelisib, a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor, was recently approved in the USA as the therapeutic drug for patients with the diseases of relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In the present study of our research, a quick and simple bioanalytical method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was fully explored and established for the quantification of plasma duvelisib concentrations from beagle dog in which gilteritinib was used as the internal standard (IS). After a simple and quick protein precipitation treated with acetonitrile, the chromatographic separation of the analyte was carried out on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 µm) conducted in a gradient elution procedure where acetonitrile (solvent A) and 0.1 % formic acid in water (solvent B) consisted as the mobile phase. The measurements of the analyte and IS were explored using a XEVO TQS triple quadrupole tandem mass spectrometer, which was comprised with electrospray ionization (ESI) source in positive ion mode. Selected reaction monitoring (SRM) mode was employed to detect the parent-to-daughter ion transitions as follows: m/z 416.88 → 281.88 for duvelisib, and m/z 553.09 → 436.01 for IS, respectively. The assay was successfully established in the calibration range from 0.5 to 3000 ng/mL for duvelisib, where the lower limit of quantification (LLOQ) was set at 0.5 ng/mL. The precisions of intra-day and inter-day for duvelisib were all below 12.6 %, and the accuracies were from -2.5% to 14.1%. Both matrix effect and mean recovery of the analyte and IS were all acceptable, and the analyte was stable during the assay and storage in dog plasma samples. The novel established bioanalytical method based on UPLC-MS/MS technique was effectively employed to the investigation of the pharmacokinetic profile of duvelisib in beagle dogs following a 1.34 mg/kg single dose of oral administration.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Isoquinolinas/análise , Inibidores de Fosfoinositídeo-3 Quinase/análise , Purinas/análise , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Calibragem , Cães , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacocinética , Limite de Detecção , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética , Purinas/administração & dosagem , Purinas/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
14.
Int J Lab Hematol ; 42(3): 308-315, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32202703

RESUMO

INTRODUCTION: Severe aplastic anemia (SAA) is a disease characterized by severe pancytopenia and hematopoietic failure of bone marrow. Natural killer (NK) cells are a class of large granular lymphocytes that perform killing and immunomodulatory functions. Our previous study demonstrated that NK cells played the "protective" role in SAA, which is weakened. However, the mechanism remains unclear. METHODS: Peripheral blood NK cells from SAA patients and normal controls were sorted and total proteins were extracted. Then, mass spectrometry was performed to screen differentially expressed proteins (DEPs). RESULTS: Significant differences in the expression levels of 93 proteins were observed in NK cells of SAA patients compared with normal controls. Among them, 48 were upregulated proteins, including histone H1.2, histone H1.3, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), and interferon regulatory factor 1 (IRF-1), and 45 were downregulated proteins, including actin-related complex (ARP2/3), histone H3, histone H4, phosphoglycerate kinase 1 (PGK1), talin-1. Gene Ontology (GO) function indicated that the DEPs most involved were vesicle-mediated transport, innate immune response, and DNA binding. KEGG analysis showed 3 upregulated and 12 downregulated pathways, in which cell endocytosis and FC-γ receptor-mediated phagocytosis were most closely related to NK cell functions. CONCLUSION: Our study is the first analysis of proteomic profile in NK cells in SAA and found many DEPs involving in dysfunction of NK cells, which provides potential targets for deeper research of inadequate immunomodulation.


Assuntos
Anemia Aplástica/metabolismo , Células Matadoras Naturais/metabolismo , Proteômica , Regulação para Cima , Adulto , Idoso , Anemia Aplástica/patologia , Feminino , Humanos , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
15.
Biomed Res Int ; 2020: 8789275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190686

RESUMO

OBJECTIVE: We studied bone marrow plasma (BMP) cytokines in severe aplastic anemia (SAA) patients and healthy volunteers to investigate differences in the cytokine profiles between them and propose a cytokine signature of SAA. METHODS: A Bio-Plex suspension array system was used to measure 27 analytes in BMP samples from 47 SAA patients and 30 healthy donors. RESULTS: Compared to healthy people, SAA patients had higher levels of tumor necrosis factor α (TNF-α (TNF-γ (IFN-γ (IFN-ß (MIP-1ß (MIP-1α (TNF-α (TNF-ß (MIP-1ß (MIP-1ß (MIP-1γ (IFN-α (TNF. CONCLUSIONS: The current study demonstrated distinct cytokine profiles among untreated SAA patients, recovering SAA (RSAA) patients, and healthy people. The cytokines of RSAA patients showed similar characteristics to those of untreated SAA patients and healthy people, respectively, which may reflect that the immune status of RSAA patients is in different stages of recovery after IST; thus, it may provide an important tool in diagnosing and evaluating or predicting curative effects in clinics.


Assuntos
Anemia Aplástica/sangue , Anemia Aplástica/metabolismo , Medula Óssea/metabolismo , Citocinas/sangue , Adolescente , Adulto , Idoso , Quimiocina CCL4/sangue , Quimiocinas/sangue , Criança , Feminino , Humanos , Linfotoxina-alfa/sangue , Masculino , Pessoa de Meia-Idade , Plasma , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
16.
Prostate ; 80(5): 367-375, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31967357

RESUMO

BACKGROUND: Glucagon-like peptide 1 (GLP-1) and its analogs are first-line choices for the treatment of type 2 diabetes mellitus. Recent studies have shown that they exhibit antitumor properties in some tumors. We previously found that a GLP-1 analog, exendin-4 (Ex-4), inhibited the growth of prostate cancer cells through suppressing the PI3K/Akt/mTOR pathway, which is activated in response to enzalutamide treatment and reported to be closely related to resistance to enzalutamide. So we speculated that exendin-4 may enhance the sensitivity of prostate cancer to enzalutamide through inhibiting Akt activation. METHODS: LNCap and CWR22RV1 cell lines, as well as mice bearing xenografts formed from the two cells, were used. RESULTS: Exendin-4 in combination with enzalutamide dramatically suppressed tumor growth of prostate cancer cells compared to enzalutamide alone; exendin-4 is capable of antagonizing enzalutamide-induced invasion and migration of both prostate cancer cells (P < .05). Furthermore, the combination treatment significantly reduced Akt and mTOR levels that were triggered by enzalutamide administration, caused a further decrease in nuclear AR localization compared with the enzalutamide as a monotherapy (P < .5), though exendin-4 treatment alone showed no effect on nuclear AR. CONCLUSION: Our study demonstrated that exendin-4 alleviated resistance to enzalutamide, and suggested that exendin-4 combined with enzalutamide may be a more efficacious treatment for patients with advanced prostate cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Exenatida/farmacologia , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Benzamidas , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Exenatida/administração & dosagem , Receptor do Peptídeo Semelhante ao Glucagon 1/biossíntese , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/farmacologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Distribuição Aleatória , Receptores Androgênicos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
iScience ; 19: 256-266, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31400748

RESUMO

How cells adapt to oncogenic transformation-associated cellular stress and become fully transformed is still unknown. Here we identified a novel GGCT-regulated glutathione (GSH)-reactive oxygen species (ROS) metabolic pathway in oncogenic stress alleviation. We identified GGCT as a target of oncogenic Ras and that it is required for oncogenic Ras-induced primary mouse cell proliferation and transformation and in vivo lung cancer formation in the LSL-Kras G12D mouse model. However, GGCT deficiency is compatible with normal mouse development, suggesting that GGCT can be a cancer-specific therapeutic target. Genetically amplified GGCT locus further supports the oncogenic driving function of GGCT. In summary, our study not only identifies an oncogenic function of GGCT but also identifies a novel regulator of GSH metabolism, with implications for further understanding of oncogenic stress and cancer treatment.

18.
Clin Lab ; 64(6): 1041-1048, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945307

RESUMO

BACKGROUND: Immuno-related hemocytopenia (IRH) is defined as idiopathic cytopenia of undetermined significance (ICUS) patients with autoantibodies. In our previous studies, we found that IgG1 levels were increased in IRH patients and might cause the destruction of hematopoietic cells. METHODS: In this study, we analyzed IgG subclasses in 30 IRH patients (male:female = 13:17, median age 32 years, range 18 - 56), 15 IRH remission patients (IRH-R) (male:female = 6:9, median age 34, range 20 - 52) and 20 normal controls (male:female = 8:12, median age 27, range 24 - 36) by Cytometric Bead Array, Flow Cytometry and Immunohistochemical staining. RESULTS: Levels of IgG1/IgG3 in the bone marrow supernatant of IRH patents, as well as the proportion of CD5+ B lymphocytes and Th2 cells (CD3+CD8-IL-4+) were higher than those of IRH-R patients and normal controls, and IgG1 levels had a positive correlation with the proportion of Th2 cells. In IRH patients, IgG1 and IgG3 were positive on nucleated erythrocytes and granulocytes, which were negative in IRH-R patients and healthy controls and had inverse correlations with hematopoietic function. Using immunohistochemical staining, IgG1 were also detected on bone marrow biopsies of IRH patients. CONCLUSIONS: The results indicated that IgG1 and IgG3 autoantibodies in IRH patients might play a key role in the IRH pathogenesis and in the abnormal immune function of IRH patients.


Assuntos
Autoanticorpos/sangue , Imunoglobulina G/sangue , Pancitopenia/sangue , Adolescente , Adulto , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Criança , Eritrócitos/imunologia , Eritrócitos/metabolismo , Feminino , Citometria de Fluxo , Granulócitos/imunologia , Granulócitos/metabolismo , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Pancitopenia/imunologia , Pancitopenia/metabolismo , Adulto Jovem
19.
Nat Commun ; 9(1): 594, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426870

RESUMO

Activation of innate immunity by membrane-localized receptors is conserved across eukaryotes. Plant genomes contain hundreds of such receptor-like genes and those encoding proteins with an extracellular leucine-rich repeat (LRR) domain represent the largest family. Here, we develop a high-throughput approach to study LRR receptor-like genes on a genome-wide scale. In total, 257 tobacco rattle virus-based constructs are generated to target 386 of the 403 identified LRR receptor-like genes in Nicotiana benthamiana for silencing. Using this toolkit, we identify the LRR receptor-like protein Response to XEG1 (RXEG1) that specifically recognizes the glycoside hydrolase 12 protein XEG1. RXEG1 associates with XEG1 via the LRR domain in the apoplast and forms a complex with the LRR receptor-like kinases BAK1 and SOBIR1 to transduce the XEG1-induced defense signal. Thus, this genome-wide silencing assay is demonstrated to be an efficient toolkit to pinpoint new immune receptors, which will contribute to developing durable disease resistance.


Assuntos
Glicosídeo Hidrolases/genética , Nicotiana/genética , Proteínas de Plantas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas/genética , Sequência de Aminoácidos , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Glicosídeo Hidrolases/metabolismo , Proteínas de Repetições Ricas em Leucina , Filogenia , Phytophthora/fisiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Proteínas de Plantas/classificação , Plantas Geneticamente Modificadas , Proteínas Serina-Treonina Quinases/classificação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/classificação , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Homologia de Sequência de Aminoácidos , Nicotiana/metabolismo , Nicotiana/microbiologia
20.
Int J Syst Evol Microbiol ; 68(2): 602-608, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29388545

RESUMO

A novel thermophilic actinomycete, designated strain 3-12XT, was isolated from mushroom compost in Guangxi University, Nanning, China. The novel isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were glucose and ribose. The predominant menaquinones were MK-9(H4) and MK-9(H6). The polar phospholipids were diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, ninhydrin-positive phosphoglycolipids and glycolipids. Major fatty acids were so-C16 : 0 and C17 : 0. The G+C content of the genomic DNA was 74.6 %. The 16S rRNA gene sequence analysis showed that the closest phylogenetic neighbour of strain 3-12XT was Thermomonospora chromogena ATCC 43196T (97.0 %), other closely related strains all belonged to the family Streptosporangiaceae and showed more than 6 % divergence. The chemotaxonomic characteristics of strain 3-12XT were significantly different from Thermomonospora chromogena ATCC 43196T and DNA-DNA hybridization showed low relatedness (48.6-55.6 %) between them, so they should be different species. Thermomonospora chromogena was removed from the genus Thermomonospora by Zhang et al. 1998 on the basis of phylogenetic, chemotaxonomic and phenotypic evidence, but its taxonomic position remains uncertain. Based on the phenotypic and phylogenetic data, strain 3-12XT represents a novel species in a new genus in the family Streptosporangiaceae. The name Thermostaphylospora griseoalba gen. nov., sp. nov. is proposed. The type strain of Thermostaphylospora grisealba is 3-12XT (=DSM 46781T=CGMCC 4.7160T). We also propose transferring Thermomonospora chromogenaZhang et al. 1998 to Thermostaphylospora chromogena comb. nov. (type strain ATCC 43196T=JCM 6244T).


Assuntos
Actinomycetales/classificação , Agaricales , Filogenia , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Compostagem , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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