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1.
Int J Cancer ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34914096

RESUMO

Osimertinib, as a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), showed more potent efficacy against brain metastasis (BM) in untreated EGFR-mutant nonsmall cell lung cancer (NSCLC) in the FLAURA study. However, the overall survival (OS) benefit of osimertinib and clinical value of cranial local therapy (CLT) in these patients remain undetermined. Here we conducted a retrospective study involving untreated EGFR-mutant NSCLC patients with BMs receiving first-line osimertinib or first-generation EGFR-TKIs. Upfront CLT was defined as CLT performed before disease progression to the first-line EGFR-TKIs. Pattern of treatment failure and survival outcomes were extensively investigated. Among the 367 patients enrolled, first-generation EGFR-TKI was administered in 265, osimertinib in 102 and upfront CLT performed in 140. Patients receiving osimertinib had more (P < .001) and larger BMs (P = .003) than those receiving first-generation EGFR-TKIs. After propensity score matching, osimertinib was found to prolong OS (37.7 vs 22.2 months, P = .027). Pattern of failure analyses found that 51.8% of the patients without upfront CLT developed their initial progressive disease (PD) in the brain and 59.0% of the cranial PD occurred at the original sites alone, suggesting potential clinical value of upfront CLT. Indeed, upfront stereotactic radiosurgery (SRS) and/or surgery was associated with improved OS among those receiving first-generation EGFR-TKIs (P = .019) and those receiving osimertinib (P = .041). In summary, compared to first-generation EGFR-TKIs, osimertinib is associated with improved OS in untreated EGFR-mutant NSCLC with BMs. Meanwhile, upfront SRS and/or surgery may provide extra survival benefit, which needs to be verified in future studies.

2.
Planta ; 255(1): 23, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923605

RESUMO

MAIN CONCLUSION: GL2-interacting-repressor (GIR) family members may contribute to fiber/fuzz formation via a newly discovered unique pathway in Gossypium arboreum. There are similarities between cotton fiber development and the formation of trichomes and root hairs. The GL2-interacting-repressors (GIRs) are crucial regulators of root hair and trichome formation. The GaFzl gene, annotated as GaGIR1, is negatively associated with trichome development and fuzz initiation. However, there is relatively little available information regarding the other GIR genes in cotton, especially regarding their effects on cotton fiber development. In this study, 21 GIR family genes were identified in the diploid cotton species Gossypium arboreum; these genes were divided into three groups. The GIR genes were characterized in terms of their phylogenetic relationships, structures, chromosomal distribution and evolutionary dynamics. These GIR genes were revealed to be unequally distributed on 12 chromosomes in the diploid cotton genome, with no GIR gene detected on Ga06. The cis-acting elements in the promoter regions were predicted to be responsive to light, phytohormones, defense activities and stress. The transcriptomic data and qRT-PCR results revealed that most GIR genes were not differentially expressed between the wild-type control and the fuzzless mutant line. Moreover, 14 of 21 family genes were expressed at high levels, indicating these genes may play important roles during fiber development and fuzz formation. Furthermore, Ga01G0231 was predominantly expressed in root samples, suggestive of a role in root hair formation rather than in fuzz initiation and development. The results of this study have enhanced our understanding of the GIR genes and their potential utility for improving cotton fiber through breeding.


Assuntos
Fibra de Algodão , Filogenia
3.
Front Oncol ; 11: 757497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778074

RESUMO

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Helicobacter pylori infection can induce GC through a serial cascade of events, with emerging evidence suggesting the important role of epigenetic alterations in the development and progression of the disease. Here, we report on mechanisms responsible for Jumonji AT-rich interactive domain1B (JARID1B) upregulation in GC and its role in the malignant transformation induced by H. pylori infection. We found that upregulation of JARID1B was associated with poorer prognosis, greater tumor purity, and less immune cell infiltration into the tumor. Mechanistically, we showed that the upregulation of JARID1B in human GC was attributed to JARID1B amplification and its induction by H. pylori infection. Furthermore, we identified miR-29c as a negative regulator of JARID1B in GC. H. pylori caused downregulation of miR-29c in human GC and thereby contributed to JARID1B upregulation through relieving posttranscriptional regulation. Functionally, we showed that knockdown of JARID1B reduced GC cell proliferation induced by H. pylori infection. Subsequently, cyclinD1 (CCND1), a key molecule in GC, was shown to be a target gene of JARID1B. In conclusion, these results suggest that JARID1B may be an oncogene upregulated in human GC and could represent a novel therapeutic target to prevent malignant transformation induced by H. pylori infection.

4.
Ann Palliat Med ; 10(9): 9572-9582, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628883

RESUMO

BACKGROUND: The current focus is largely on whole course medical management of coronavirus disease-19 (COVID-19) with real-time polymerase chain reaction (RT-PCR) and radiological features, while the mild cases are usually missed. Thus, combination of multiple diagnostic methods is urgent to understand COVID-19 fully and to monitor the progression of COVID-19. METHODS: laboratory variables of 40 mild COVID-19 patients, 30 patients with community-acquired pneumonia (CAP) and 32 healthy individuals were analyzed by principal component analysis (PCA), Kruskal test, Procrustes test, the vegan package in R, CCA package and receiver operating characteristic to investigate the characteristics of the laboratory variables and their relationships in COVID-19. RESULTS: The correlations between the laboratory variables presented a variety of intricate linkages in the COVID-19 group compared with the healthy group and CAP patient group. The prediction probability of the combination of lymphocyte count (LY), eosinophil (EO) and platelets (PLT) was 0.847, 0.854 for the combination of lactate (LDH), creatine kinase isoenzyme (CK-MB), and C-reactive protein (CRP), 0.740 for the combination of EO, white blood cell count (WBC) and neutrophil count (NEUT) and 0.872 for the combination of CK-MB and P. CONCLUSIONS: The correlations between the laboratory variables in the COVID-19 group could be a unique characteristic showing promise as a method for COVID-19 prediction and monitoring progression of COVID-19 infection.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Estudos de Coortes , Humanos , Pneumonia/diagnóstico , SARS-CoV-2
5.
Patient Prefer Adherence ; 15: 2327-2334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703215

RESUMO

Background: The prevalence of Crohn's disease (CD) has been increasing rapidly in China, and the role of exclusive enteral nutrition (EEN) in the management of adult patients with active CD is evolving. Adherence is a key factor in the effective treatment of many chronic diseases. Aim: The aim of this study was to assess adherence to EEN of CD patients and to evaluate the relationship between medication belief and EEN adherence. Methods: A cross-sectional study was conducted, and demographic information, adherence to EEN, and beliefs about EEN were investigated. Medication belief was measured using the Beliefs about Medicines Questionnaire (BMQ)-Specific. Results: In all, 131 CD patients completed the questionnaire and were enrolled in this study. The high adherence rate was 73.3% (96 of 131 patients), and we found that medication belief, residency, medical insurance, and history of enteral nutrition therapy were factors affecting EEN adherence. More patients with a high BMQ score had high adherence to EEN (n = 54, 56.2%) compared to those with a low BMQ (n = 42, 43.8%). Moreover, price, taste, storage method, portability, and purchase convenience of EEN were not associated with adherence. Conclusion: The adherence to EEN among patients with CD is relatively high and is related to medication belief, residency and history of enteral nutrition. The type of enteral nutrition, taste, storage, and convenience of purchase were not associated with EEN adherence. Future study is warranted to explore the possible role of improving patients' beliefs in increasing adherence.

6.
Chem Biol Drug Des ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34679238

RESUMO

Breast cancer is a malignant tumor that occurs in the glandular epithelium of the breast, and more than 15% of the patients are triple-negative breast cancer (TNBC). Therefore, finding new targets and targeted therapeutic drugs for TNBC is urgent. Overexpression of the AXL is associated with motility and invasiveness of the TNBC cells, which is a potential target for breast cancer therapy. A compound Y041-5921 (IC50  = 6.069 µm for AXL kinase and IC50  = 4.1 µm for MDA-MB-231 cell line) was identified through structure-based virtual screening and bioassay test for the first time. The compound Y041-5921 could significantly inhibit the proliferation and invasion of the TNBC cells and the toxicity of Y041-5921 to normal immortalized breast epithelial cells was far lower than that of commonly used clinical chemotherapy drugs. Besides, it also had well inhibitory effect on the proliferation of many other malignant tumor cell lines (the IC50  value are 10.0 m, 7.1 m, 10.3 m, 11.4 m and 5.8 m for U251 cell, COLO cell, PC-9 cell, CAKI-1 cell and MG63 cell, respectively). The interaction mechanism between Y041-5921 and AXL was studied by molecular dynamics (MD) simulations and binding free energy calculation, and the key residues whose energy contribution mainly comes from non-polar solvation interaction (such as Ala565, Lys567, Met598, Leu620, Pro621, Met623, Lys624, Arg676, Asn677 and Met679) were identified. The small molecule inhibitors Y041-5921 targeting AXL reported in this work will lay a foundation and provide a theoretical basis for the development of the TNBC.

7.
Angew Chem Int Ed Engl ; 60(39): 21449-21456, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34314545

RESUMO

We successfully synthesized {BiW8 }, a 10-nuclear heteroatom cluster modified {BiW8 O30 }. At 24 h post-incubation, the IC50 values of {BiW8 } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 µM, respectively. The IC50 value of {BiW8 } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8 }. {BiW8 } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post-incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.


Assuntos
Antineoplásicos/farmacologia , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Compostos de Tungstênio/farmacologia , Regulação para Cima/efeitos dos fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Compostos de Tungstênio/química
8.
J Gen Appl Microbiol ; 67(4): 162-169, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34120995

RESUMO

Probiotics have been shown to improve microbial compositions in animal intestine and feces, but the effects of probiotic administration on airborne microbial composition in animal houses remain unclear. In this study, we investigated the effects of dietary Enterococcus faecalis on the bacterial community structure in the air of piglet and layer hen houses. Indoor air and feces from piglet and layer hen houses were sampled after supplementing E. faecalis in feed for 60 days, and bacterial community structures were analyzed using Illumina high-throughput sequencing technology. Results showed that Chao1, ACE, Shannon, and Simpson indices of bacterial diversity did not significantly change in feces or indoor air of piglet or layer hen after supplementation with E. faecalis (P > 0.05). However, E. faecalis administration resulted in a decrease in the relative abundance of Proteobacteria (P < 0.05). In addition, E. faecalis significantly reduced the relative abundance of opportunistic pathogens such as Acinetobacter, Escherichia, and Shigella (P < 0.05), and beneficial bacterial genus such as Lactobacillus was significantly enriched in both feces and indoor air (P < 0.05). These changes should be of benefit to livestock, farm workers, and the surrounding environment.

9.
Cell Death Discov ; 7(1): 128, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059632

RESUMO

Protein acetylation plays potential roles in regulating autophagy occurrence. However, it varies greatly between yeast and mammals, and has not been thoroughly investigated in other organisms. Here, we reported that the components of BmAtg8-PE ubiquitin-like system (BmAtg3, BmAtg4, BmAtg7, and BmAtg8) in Bombyx mori were localized in the nucleus under nutrient-rich conditions, whereas they were exported to the cytoplasm upon autophagy induction. RNAi of BmP300 and inhibition of BmP300 activity resulted in nucleo-cytoplasmic translocation of BmAtg3 and BmAtg8, as well as premature induction of autophagy in the absence of stimulus. Conversely, RNAi of BmHDAC1 and inhibition of class I/II HADCs activities led to the nuclear accumulation of BmAtg3 and BmAtg8. In addition, acetylation sites in Atg proteins of BmAtg8-PE ubiquitin-like system were identified by mass spectrometry, and acetylation-site mutations caused nucleo-cytoplasmic translocation of BmAtg3, BmAtg4, and BmAtg8 along with autophagy promotion. Similarly, the subcellular localization of human ATG4b is determined by acetylation modification. In general, BmP300-mediated acetylation sequesters the components of BmAtg8-PE ubiquitin-like system in the nucleus, thus leading to the autophagy inhibition. Oppositely, BmHDAC1-mediated deacetylation leads to the nucleo-cytoplasmic translocation of the components of BmAtg8-PE ubiquitin-like system and promotes autophagy. This process is evolutionarily conserved between insects and mammals.

10.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066899

RESUMO

Plant NAC (NAM, ATAF1/2, and CUC2) family is involved in various development processes including Programmed Cell Death (PCD) associated development. However, the relationship between NAC family and PCD-associated cotton pigment gland development is largely unknown. In this study, we identified 150, 153 and 299 NAC genes in newly updated genome sequences of G. arboreum, G. raimondii and G. hirsutum, respectively. All NAC genes were divided into 8 groups by the phylogenetic analysis and most of them were conserved during cotton evolution. Using the vital regulator of gland formation GhMYC2-like as bait, expression correlation analysis screened out 6 NAC genes which were low-expressed in glandless cotton and high-expressed in glanded cotton. These 6 NAC genes acted downstream of GhMYC2-like and were induced by MeJA. Silencing CGF1(Cotton Gland Formation1), another MYC-coding gene, caused almost glandless phenotype and down-regulated expression of GhMYC2-like and the 6 NAC genes, indicating a MYC-NAC regulatory network in gland development. In addition, predicted regulatory mechanism showed that the 6 NAC genes were possibly regulated by light, various phytohormones and transcription factors as well as miRNAs. The interaction network and DNA binding sites of the 6 NAC transcription factors were also predicted. These results laid the foundation for further study of gland-related genes and gland development regulatory network.


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Gossypium/anatomia & histologia , Gossypium/genética , Pigmentação/genética , Proteínas de Plantas/genética , Cromossomos de Plantas/genética , Diploide , Duplicação Gênica , Perfilação da Expressão Gênica , Inativação Gênica , Genes de Plantas , Modelos Biológicos , Família Multigênica , Filogenia , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Sintenia/genética
11.
Front Genet ; 12: 666371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968141

RESUMO

Tobacco smoking is an established risk factor for squamous cell carcinoma (SCC). We obtained smoking-related SCC, including cervical SCC (CSCC), esophageal SCC (ESCC), head and neck SCC (HNSC), and lung SCC (LUSC), from The Cancer Genome Atlas (TCGA) database to investigate the association between smoking status (reformed and current smoking) and prognosis. We found that reformed smokers had a better prognosis than current smokers in CSCC (p = 0.003), HNSC (p = 0.019), and LUSC (p < 0.01) cohorts. Then, we selected LUSC cohorts as the training cohort and other SCC cohorts as the test cohorts. Function analysis revealed that homologous recombination (HR) was the most significant pathway involved in smoking-induced LUSC. Moreover, the effect of cross-talk between the smoking status and HR deficiency (HRD) on the prognosis was further evaluated, revealing that quitting smoking with high HRD scores could significantly improve patients' prognosis (p < 0.01). To improve prognosis prediction and more effectively screen suitable populations for platinum drugs and poly-ADP-ribose polymerase (PARP) inhibitors, we constructed a risk score model using smoking- and HRD-related genes in LUSC. The risk score model had high power for predicting 2-, 3-, and 5-year survival (p < 0.01, AUC = 0.67, 0.66, and 0.66). In addition, the risk scores were an independent risk factor for LUSC (HR = 2.34, 95%CI = 1.70-3.23). The practical nomogram was also built using the risk score, smoking status, and other clinical information with a good c-index (0.72, 95%CI = 0.70-0.74). Finally, we used other TCGA SCC cohorts to confirm the reliability and validity of the risk score model (p < 0.01 and AUC > 0.6 at 2, 3, and 5 years in CSCC and HNSC cohorts). In conclusion, the present study suggested that smoking cessation should be a part of smoking-related SCC treatment, and also provided a risk score model to predict prognosis and improve the effectiveness of screening the platinum/PARP population.

12.
Int J Radiat Oncol Biol Phys ; 111(3): 804-815, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058255

RESUMO

PURPOSE: As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib has a powerful ability to penetrate the blood-brain barrier and a high potency for controlling brain metastases (BMs) from EGFR-mutant non-small cell lung cancer (NSCLC). The clinical value of cranial radiation therapy in osimertinib-treated NSCLC with BMs remains largely unknown. METHODS AND MATERIALS: Patients with NSCLC and BMs and receiving osimertinib treatment as the standard of care were retrospectively enrolled from 2 institutions. Cranial radiation therapy (RT; whole-brain radiation therapy [WBRT] or/and stereotactic radiosurgery [SRS]) performed before disease progression (PD) to osimertinib was categorized as upfront cranial radiation therapy (ucRT group), excluding those treatments performed during prior EGFR-TKI treatment. Overall survival (OS), progression-free survival (PFS), and the time to intracranial progression (iTTP) were compared between the 2 groups, with adjustment by covariates in propensity-score matched (PSM) analyses. The state of having 1 to 3 BM lesions, with a maximal size of ≤3 cm, was defined as having oligo-BM; otherwise; the cases were defined as having multiple BMs. RESULTS: Of the 205 patients enrolled, osimertinib was used as first-line therapy in 74 and second-line therapy in 131. There were 48 patients who received ucRTs, including WBRT in 24 and SRS in 24. All patients with oligo-BM in the ucRT group received SRS alone (n = 17), whereas most (n = 28; 90.3%) patients with multiple BMs received WBRT. Failure pattern analyses indicated that in the non-ucRT group, 40.2% of the initial PD involved the brain and 76.9% of the cranial PD involved the original sites, indicating the potential roles of ucRT. Indeed, the iTTP was significantly prolonged (P = .010) in the ucRT group among the whole population. In the PSM oligo-BM cohort, the ucRT group showed superior PFS (P = .033) and OS (P = .026) compared with the non-ucRT group, and the differences remained after multivariate Cox analyses. No such differences were observed in the subpopulation with multiple BMs. CONCLUSIONS: In osimertinib-treated NSCLC patients with BMs, oligo-BM status could be used as a potential factor to select patients for upfront cranial RT. Further investigation by well-designed clinical trials is warranted.

13.
J Int Med Res ; 49(3): 300060521990249, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33682506

RESUMO

Catheter ablation of accessory pathways can be challenging depending on the location of these pathways, and accessory pathways are rare through the aortic cusps. We report a patient who underwent radiofrequency catheter ablation for manifestation of a left anterior accessory pathway from the left coronary sinus of Valsalva near the aortic-mitral continuity. Anterior accessory pathways can be safely and effectively ablated from the aortic cusps with favorable long-term outcomes.


Assuntos
Ablação por Cateter , Seio Coronário , Seio Aórtico , Fascículo Atrioventricular , Seio Coronário/diagnóstico por imagem , Seio Coronário/cirurgia , Eletrocardiografia , Sistema de Condução Cardíaco/cirurgia , Humanos , Seio Aórtico/diagnóstico por imagem , Seio Aórtico/cirurgia
14.
Aging (Albany NY) ; 13(8): 11010-11025, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535179

RESUMO

Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.


Assuntos
Benzoxepinas/farmacologia , Limoninas/farmacologia , Degeneração Macular/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Benzoxepinas/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , DNA de Cadeia Simples/efeitos dos fármacos , DNA de Cadeia Simples/efeitos da radiação , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Injeções Intravítreas , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Limoninas/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Degeneração Macular/etiologia , Degeneração Macular/patologia , Camundongos , Membranas Mitocondriais/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/efeitos da radiação , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação
15.
Andrologia ; 53(4): e14005, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33565168

RESUMO

This study evaluates the protective role of oyster peptide (OP) on the occurrence of Exercise-Hypogonadal Male Condition. Male rats were given heavy-load swimming training and / or OP was supplemented for 6 consecutive weeks. After heavy-load training, sperm count, sperm viability and sperm motility in epididymis, testosterone in serum and testis, glutathione peroxidase (GSH-px) and androgen receptor (AR) in testis and mating times were remarkably decreased, malondialdehyde (MDA), capture latency and mating latency were significantly increased, mRNA expression of steroidogenic acute regulatory (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc) were obviously down-regulated, but serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) were not statistically changed. Conversely, when OP was supplemented at heavy-load training, sperm count, sperm viability and sperm motility in epididymis, serum FSH, LH, testosterone, GSH-px, superoxide dismutase (SOD), testosterone, AR in testis and mating times were dramatically increased, while testicular MDA, capture latency and mating latency were significantly decreased, and mRNA expression of StAR, StARD7, P450scc and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were significantly up-regulated. In conclusion, heavy-load training causes testicular spermatogenic and steroidogenic disorders by enhancing the generation of reactive oxygen species (ROS), which can be protected by the co-administration of OP by enhancing the function of pituitary gonad axis and lowering ROS generation.


Assuntos
Ostreidae , Motilidade Espermática , Animais , Proteínas de Transporte , Hormônio Luteinizante , Masculino , Ratos , Contagem de Espermatozoides , Testículo , Testosterona
16.
BMC Plant Biol ; 21(1): 102, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602142

RESUMO

BACKGROUND: Gossypium hirsutum L. (cotton) is one of the most economically important crops in the world due to its significant source of fiber, feed, foodstuff, oil and biofuel products. However, the utilization of cottonseed was limited due to the presence of small and darkly pigmented glands that contain large amounts of gossypol, which is toxic to human beings and non-ruminant animals. To date, some progress has been made in the pigment gland formation, but the underlying molecular mechanism of its formation was still unclear. RESULTS: In this study, we identified an AP2/ERF transcription factor named GhERF105 (GH_A12G2166), which was involved in the regulation of gland pigmentation by the comparative transcriptome analysis of the leaf of glanded and glandless plants. It encoded an ERF protein containing a converved AP2 domain which was localized in the nucleus with transcriptional activity, and showed the high expression in glanded cotton accessions that contained much gossypol. Virus-induced gene silencing (VIGS) against GhERF105 caused the dramatic reduction in the number of glands and significantly lowered levels of gossypol in cotton leaves. GhERF105 showed the patterns of spatiotemporal and inducible expression in the glanded plants. CONCLUSIONS: These results suggest that GhERF105 contributes to the pigment gland formation and gossypol biosynthesis in partial organs of glanded plant. It also provides a potential molecular basis to generate 'glandless-seed' and 'glanded-plant' cotton cultivar.


Assuntos
Gossypium/crescimento & desenvolvimento , Gossypium/genética , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Gossypium/química , Gossypium/metabolismo , Gossipol/análise , Gossipol/metabolismo , Folhas de Planta/química , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Domínios Proteicos , Fatores de Transcrição/química , Fatores de Transcrição/genética
17.
Environ Sci Pollut Res Int ; 28(14): 17981-17991, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33405112

RESUMO

This study compared different types and addition amounts of phosphorous additives on nitrogen conservation and maturity during pig manure composting. Phosphogypsum and superphosphate were applied with the same amount of phosphorus (5% of the initial total nitrogen, molar basis) or weight (10% of initial dry matter) and compared to a control treatment without additives. Results show that phosphorous additives could effectively conserve nitrogen. Adding phosphogypsum could significantly reduce NH3 emission and total nitrogen loss, but increase N2O emission. Application of 10% superphosphate mitigated NH3 emissions and total nitrogen loss but inhibited the organic matter degradation and compost maturity. More importantly, with the addition of 5% initial total nitrogen (i.e., 2.5% dry matter), superphosphate could synchronously reduce NH3 and N2O emissions and improve compost quality by introducing additional nutrients into the compost. In comprehensive evolution of gaseous emissions, nitrogen loss, and compost maturity, superphosphate addition with 2.5% of initial dry matter was suggested to be used in practice.


Assuntos
Compostagem , Animais , Esterco , Nitrogênio , Fósforo , Solo , Suínos
18.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33057581

RESUMO

In order to extract useful information from a huge amount of biological data nowadays, simple and convenient tools are urgently needed for data analysis and modeling. In this paper, an automatic data mining tool, termed as ABCModeller (Automatic Binary Classification Modeller), with a user-friendly graphical interface was developed here, which includes automated functions as data preprocessing, significant feature extraction, classification modeling, model evaluation and prediction. In order to enhance the generalization ability of the final model, a consistent voting method was built here in this tool with the utilization of three popular machine-learning algorithms, as artificial neural network, support vector machine and random forest. Besides, Fibonacci search and orthogonal experimental design methods were also employed here to automatically select significant features in the data space and optimal hyperparameters of the three algorithms to achieve the best model. The reliability of this tool has been verified through multiple benchmark data sets. In addition, with the advantage of a user-friendly graphical interface of this tool, users without any programming skills can easily obtain reliable models directly from original data, which can reduce the complexity of modeling and data mining, and contribute to the development of related research including but not limited to biology. The excitable file of this tool can be downloaded from http://lishuyan.lzu.edu.cn/ABCModeller.rar.


Assuntos
Mineração de Dados , Aprendizado de Máquina , Redes Neurais de Computação , Interface Usuário-Computador
19.
Mol Cancer Res ; 19(1): 74-85, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004623

RESUMO

Reactivated telomerase is a crucial event in the development and progression of a variety of tumors. However, how telomerase is activated in gastric carcinogenesis has not been fully uncovered yet. Here, we identified a key role of the NF-κB/LIN28A/let-7a axis to promote human telomerase reverse transcriptase (hTERT) expression for gastric cancer initiation. Mechanistically, LIN28A expression was upregulated by H. pylori-induced NF-κB activation. And LIN28A, in turn, suppressed let-7a expression, forming the NF-κB/LIN28A/let-7a axis to regulate gene expression upon H. pylori infection. Of note, we first discovered hTERT as a direct target of let-7a, which inhibited hTERT expression by binding to its 3'UTR of mRNA. Therefore, H. pylori-triggered let-7a downregulation enhanced hTERT protein translation, resulting in telomerase reactivation. Furthermore, hTERT enhanced LIN28A expression, forming the positive feedback regulation between hTERT and NF-κB/LIN28A/let-7a axis to maintain the sustained overexpression of hTERT in gastric cancer. IMPLICATIONS: The NF-κB/LIN28A/Let-7a axis was crucial for the overexpression of hTERT upon H. pylori infection during gastric cancer development and may serve as a potential target to suppress hTERT expression for gastric cancer prevention and treatment.


Assuntos
Carcinogênese/metabolismo , Helicobacter pylori/patogenicidade , NF-kappa B/metabolismo , Neoplasias Gástricas/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias Gástricas/patologia
20.
Brief Bioinform ; 22(1): 536-544, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-32010933

RESUMO

Gastric cancer (GC) continues to be one of the major causes of cancer deaths worldwide. Meanwhile, liquid biopsies have received extensive attention in the screening and detection of cancer along with better understanding and clinical practice of biomarkers. In this work, 58 routine blood biochemical indices were tentatively used as integrated markers, which further expanded the scope of liquid biopsies and a discrimination system for GC consisting of 17 top-ranked indices, elaborated by random forest method was constructed to assist in preliminary assessment prior to histological and gastroscopic diagnosis based on the test data of a total of 2951 samples. The selected indices are composed of eight routine blood indices (MO%, IG#, IG%, EO%, P-LCR, RDW-SD, HCT and RDW-CV) and nine blood biochemical indices (TP, AMY, GLO, CK, CHO, CK-MB, TG, ALB and γ-GGT). The system presented a robust classification performance, which can quickly distinguish GC from other stomach diseases, different cancers and healthy people with sensitivity, specificity, total accuracy and area under the curve of 0.9067, 0.9216, 0.9138 and 0.9720 for the cross-validation set, respectively. Besides, this system can not only provide an innovative strategy to facilitate rapid and real-time GC identification, but also reveal the remote correlation between GC and these routine blood biochemical parameters, which helped to unravel the hidden association of these parameters with GC and serve as the basis for subsequent studies of the clinical value in prevention program and surveillance management for GC. The identification system, called GC discrimination, is now available online at http://lishuyan.lzu.edu.cn/GC/.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Gástricas/sangue , Humanos , Aprendizado de Máquina , Software , Neoplasias Gástricas/patologia
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