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1.
Appl Environ Microbiol ; 90(1): e0154823, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38112425

RESUMO

In bacteria, the second messenger cyclic di-GMP (c-di-GMP) is synthesized and degraded by multiple diguanylate cyclases (DGCs) and phosphodiesterases. A high level of c-di-GMP induces biofilm formation and represses motility. WspR, a hybrid response regulator DGC, produces c-di-GMP when it is phosphorylated. FlhF, a signal recognition particle-type GTPase, is initially localized to the cell poles and is indispensable for polar flagellar localization in Pseudomonas aeruginosa. In this study, we report that deletion of flhF affected biofilm formation and the c-di-GMP level in P. aeruginosa. Phenotypic analysis of a flhF knockout mutant revealed increased biofilm formation, wrinkled colonies on Congo red agar, and an elevated c-di-GMP level compared to the wild-type strain, PAO1. Yeast and bacterial two-hybrid systems showed that FlhF binds to the response regulator HsbR, and HsbR binds to WspR. Deletion of hsbR or wspR in the ΔflhF background abolished the phenotype of ΔflhF. In addition, confocal microscopy demonstrated that WspR-GFP was distributed throughout the cytoplasm and formed a visible cluster at one cell pole in PAO1 and ΔhsbR, but it was mainly distributed as visible clusters at the lateral side of the periplasm and with visible clusters at both cell poles in ΔflhF. These findings suggest that FlhF influences the subcellular cluster and localization of WspR and negatively modulates WspR DGC activity in a manner dependent on HsbR. Together, our findings demonstrate a novel mechanism for FlhF modulating the lifestyle transition between motility and biofilm via HsbR to regulate the DGC activity of WspR.IMPORTANCECyclic di-GMP (c-di-GMP) is a second messenger that controls flagellum biosynthesis, adhesion, virulence, motility, exopolysaccharide production, and biofilm formation in bacteria. Recent research has shown that distinct diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) produce highly specific outputs. Some DGCs and PDEs contribute to the total global c-di-GMP concentration, but others only affect local c-di-GMP in a microenvironment. However, the underlying mechanisms are unclear. Here, we report that FlhF affects the localization and DGC activity of WspR via HsbR and is implicated in local c-di-GMP signaling in Pseudomonas aeruginosa. This study establishes the link between the c-di-GMP signaling system and the flagellar localization and provides insight for understanding the complex regulatory network of c-di-GMP signaling.


Assuntos
Dietilestilbestrol/análogos & derivados , Proteínas de Escherichia coli , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Proteínas de Escherichia coli/genética , GMP Cíclico/metabolismo , Biofilmes , Fósforo-Oxigênio Liases/genética , Diester Fosfórico Hidrolases/metabolismo , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica
2.
Langmuir ; 40(17): 9265-9279, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38636094

RESUMO

Heterogeneous catalytic systems with water as the solvent often have the disadvantage of cross-contamination, while concerns about the purification and workup of the aqueous phase after reactions are rare in the lab or industry. In this context, designing and developing the functional selective solid adsorbent and revealing the adsorption mechanism can provide a new strategy and guidelines for constructing supported heterogeneous catalysts to address these issues. Herein, we report the stable composite adsorbent (Fe/ATP@PPy: magnetic Fe3O4/attapulgite with the polypyrrole shell) that features an integrated multifunctional surface, which can effectively tune the selective adsorption processes for Cu2+, Co2+, and Ni2+ ions and nitrobenzene via the cooperative chemisorption/physisorption in an aqueous system. The adsorption experiments showed that Fe/ATP@PPy displayed significantly higher adsorption selectivity for Ni2+ than Cu2+ and Co2+ ions, especially which exhibited an approximate 100.00% removal for both Ni2+ ions and nitrobenzene in the mixture system with a low concentration. Furthermore, combined tracking adsorption of Ni2+ ions and X-ray photoelectron spectroscopy characterization confirmed that the effective adsorption occurs via ion transfer coordination; the pathway was further validated at the molecular level through theoretical modeling. In addition, the selective adsorption mechanism was proposed based on the adsorption experiment, characterization, and the corresponding density functional theory calculation.

3.
Support Care Cancer ; 32(8): 561, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085696

RESUMO

Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT.


Assuntos
Antagonistas de Androgênios , Cognição , Neoplasias da Próstata , Humanos , Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Masculino , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/etiologia , Fatores de Risco
4.
Genomics ; 115(5): 110667, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315873

RESUMO

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Masculino , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Genes Supressores de Tumor , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , MicroRNAs/genética , Movimento Celular/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Receptores Depuradores Classe A/genética , Receptores Depuradores Classe A/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-38685575

RESUMO

Rumen fungi play an essential role in the breakdown of dietary fibrous components, facilitating the provision of nutrients and energy to the host animals. This study investigated the fermentation characteristics and effects on rumen microbiota of yak rumen anaerobic fungus Orpinomyces sp. YF3 in goat rumen fluid, both with and without fungal flora, utilizing anaerobic fermentation bottles. Crushed and air-dried wheat straw served as the fermentation substrate, and cycloheximide was used to eradicate microorganisms from the rumen fluid of dairy goats. The experiment compromised four treatment groups (2×2 factorial design): control (C); yak fungus group (CF, Orpinomyces sp. YF3); goat fungi eliminated group (CA, antibiotic: 0.25 mg/mL cycloheximide); goat fungi eliminated+yak fungus group (CAF). Each treatment had six replicates. Fermentation characteristics and microbial composition of the fermentation media were analyzed using one-way analysis of variance and high-throughput sequencing technology. The findings revealed that in the Orpinomyces sp. YF3 addition group (CF and CAF groups), there were significant increases in ammonia nitrogen concentration by 70%, total volatile fatty acids (VFA) by 53%, as well as acetate, isobutyrate, and valerate concentrations, and the ratio of acetate to propionate (p < 0.05), while the propionate proportion declined by 13%, alongside a reduction of butyrate concentration (p < 0.05). Similarly, in the CF and CAF groups, there were a notable increase in the relative abundance of Bacteroidota, Synergistota, Desulfobacterota, Actinobacteria, and Fusobacteriota, alongside a decrease in the relative abundance of Fibrobacterota and Proteobacteria (p < 0.05). Bacteria exhibiting increased relative abundance were positively correlated with the activity of carboxymethyl cellulase and avicelase, total VFA concentration, and acetate proportion, while showing a negatively correlation with propionate proportion. In conclusion, supplementing rumen fermentation media with yak rumen anaerobic fungus Orpinomyces sp. YF3 led to an increase in bacteria associated with fibre degradation and acetic acid production, a decrease in propionate-producing bacteria, enhanced the activity of plant cell wall degrading enzymes, and promoted cellulose degradation, ultimately elevating total VAF concentration and acetate proportion. This presents a novel approach to enhance roughage utilization in ruminants.

6.
Biochem Biophys Res Commun ; 676: 149-157, 2023 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-37517217

RESUMO

Glioblastoma (GBM) has a high degree of invasiveness, which is largely attributed to the invalidation of current therapy and the unclear tumor growth mechanism. Ras related GTP binding B (RRAGB) is a family member of the Ras-homologous GTPases. The effect of RRAGB on tumor growth has been recognized, but its influences on GBM progression are ill-defined. Here, in our research, a significantly decreased expression of RRAGB in GBM tissues by using TCGA databases and glioma samples is observed. According to Kaplan-Meier (KM) analysis, RRAGB low expression leads to a significant decrease of overall survival rate of patients, and is associated with the classification of WHO grade, histological type and age increase. Functional enrichment analysis reveals that the pathway of enrichment includes cell cycle arrest, extracellular matrix (ECM) processes and PI3K/AKT signal. Thereafter, our cell experiments confirm an obvious decrease of RRAGB in several GBM cell lines. It should be noted that RRAGB promotion strongly reduces the proliferation, migration and invasion of GBM cells and induces cell cycle arrest in G0/G1 phase. RRAGB up-regulation significantly decreases the expression of PI3K, phosphorylated AKT, mTOR and S6K in GBM cell lines. Surprisingly, we further find that RRAGB-restrained proliferative, migratory and invasive properties of GBM cells are markedly offset after promoting AKT activation, accompanied with restored phosphorylation of mTOR and S6K, elucidating that AKT signaling blockage is partially indispensable for RRAGB to play its anti-cancer role in GBM. Animal studies confirmed that RRAGB over-expression obviously inhibits the tumor growth both in the xenograft and orthotopic mouse glioma models, along with improved overall survival rates. In short, we provide evidence that RRAGB is a potential therapeutic target and prognostic marker for GBM treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Proteínas Monoméricas de Ligação ao GTP , Camundongos , Animais , Humanos , Glioblastoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Monoméricas de Ligação ao GTP/metabolismo
7.
Small ; : e2308002, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084459

RESUMO

In order to reveal the dynamic response characteristic of thin film thermocouples (TFTCs), the nichrome/nisil (NiCr/NiSi) TFTCs are prepared onto the glass substrate. With short pulse infrared laser system, NiCr/NiSi TFTCs are dynamically calibrated. The thermoelectric electromotive force (TEF) curves of NiCr/NiSi TFTCs are recorded by the memory hicorder system, which could reflect TEF signals with resolution ratio in nanosecond and microvolt, simultaneously. With increasing laser energy from 15.49 to 29.59 mJ, TEF curves display more and more violent oscillation, even negative value. The results show that the bounce of thermal energy happens between two interfaces of TFTCs because the thermal conductivity of glass and air is significantly lower than that of NiSi/NiCr TFTCs. The bounce of thermal energy results in the obvious decrease of nNiCr and nNiSi , as well as oscillation of TEF. For laser energy in 29.59 mJ, the bounce of thermal energy in NiCr film could result in nNiCr < nNiSi . Then, TEF value appears abnormal negative value. Based on the results, the complex thermal energy transport process in TFTCs dynamic calibration is revealed, which results in the oscillation of thermal energy and TEF signal.

8.
Neuroradiology ; 65(4): 793-804, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36550266

RESUMO

PURPOSE: The aim of this study is to evaluate the safety and effectiveness of endovascular treatment (EVT) for acute ischemic stroke caused by large-vessel obstruction or stenosis (AIS-LVO/S) over 24 h after first AIS symptom recognition (FAISSR). METHODS: A total of 33 AIS-LVO/S cases with EVT over 24 h after FAISSR during the period from January 2019 to February 2022 in our hospital were divided into the 90d mRS ≤ 2 group [favorable outcome (FO) group] and 90d mRS > 2 group [unfavorable outcome (UFO) group] and retrospectively analyzed. RESULTS: The reperfusion was successfully established with EVT in 97% (32/33) of cases, and most (63.6%, 21/33) had 90d mRS ≤ 2 and only 36.4% (12/33) had 90d mRS > 2. Preoperative DWI-ASPECT and ASITN/SIR scores were significantly higher and NIHSS scores were significantly lower in the FO group than those in the UFO group (P < 0.05). In addition, the FAISSR to exacerbation time, FAISSR to groin puncture time, and FAISSR to reperfusion time were significantly longer, and the groin puncture to reperfusion time was significantly shorter in the FO group than those in the UFO group (P < 0.05), but there was no significant difference in the stroke exacerbation to groin puncture time (P > 0.05). The patients with cerebral infarction due to artery dissection had more favorable EVT outcomes, but the patients with posterior cerebral circulation infarction had very poor EVT outcomes. CONCLUSIONS: The FAISSR to groin puncture time over 24 h may not be a taboo for EVT and it may be safe and effective for AIS-LVO/S in anterior cerebral circulation, especially with lower preoperative NIHSS scores.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/etiologia , Estudos Retrospectivos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Resultado do Tratamento , Trombectomia/métodos , Constrição Patológica
9.
Int J Mol Sci ; 24(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36675264

RESUMO

Embryos contain a large number of lipid droplets, and lipid metabolism is gradually activated during embryonic development to provide energy. However, the regulatory mechanisms remain to be investigated. Stearoyl-CoA desaturase 1 (Scd1) is a fatty acid desaturase gene that is mainly involved in intracellular monounsaturated fatty acid production, which takes part in many physiological processes. Analysis of transcripts at key stages of embryo development revealed that Scd1 was important and expressed at an increased level during the cleavage and blastocyst stages. Knockout Scd1 gene by CRISPR/Cas9 from zygotes revealed a decrease in lipid droplets (LDs) and damage in the inner cell mass (ICM) formation of blastocyst. Comparative analysis of normal and knockout embryo transcripts showed a suppression of ribosome protein (RPs) genes, leading to the arrest of ribosome biogenesis at the 2-cell stage. Notably, the P53-related pathway was further activated at the blastocyst stage, which eventually caused embryonic development arrest and apoptosis. In summary, Scd1 helps in providing energy for embryonic development by regulating intra-embryonic lipid droplet formation. Moreover, deficiency activates the RPs-Mdm2-P53 pathway due to ribosomal stress and ultimately leads to embryonic development arrest. The present results suggested that Scd1 gene is essential to maintain healthy development of embryos by regulating energy support.


Assuntos
Metabolismo dos Lipídeos , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Metabolismo dos Lipídeos/genética , Ácidos Graxos Monoinsaturados/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Blastocisto/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo
10.
Funct Integr Genomics ; 22(5): 865-877, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35576023

RESUMO

Gastrointestinal helminths are a global health issue, for humans as well as domestic animals. Most studies focus on the tissues that are infected with the parasite, but here we studied the ileum, a tissue that is rarely infected by helminths. We tested whether inflammation in the ileum contributes to the development and severity of diarrhoea, by comparing sheep that are susceptible (n = 4) or resistant (n = 4) to the disease. We analyzed the ileum transcriptome using RNASeq sequencing approach and various bioinformatics tools including FastQC, STAR, featureCounts, DESeq2, DAVID, clusterProfiler, Cytoscape (ClusterONE) and EnrichR. We identified 243 differentially expressed genes (DEGs), of which 118 were up-regulated and 125 were down-regulated DEGs in the diarrhoea-susceptible animals compared to the diarrhoea-resistant animals. The resulting DEGs were functionally enriched for biological processes, pathways and gene set enrichment analysis. The up-regulated DEGs suggested that an inflammatory immune response was coupled with genes involved in 'Th2 immune response' and 'anti-inflammatory response'. The down-regulated DEGs were related to ion transport, muscle contraction and pathways preventing inflammation. We conclude that i) susceptibility to helminth-induced diarrhoea involves an inflammatory response at a non-infectious site; ii) down-regulation of pathways preventing inflammation can contribute to the severity of diarrhoea; and iii) genes involved in anti-inflammatory responses can reduce the inflammation and diarrhoea.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Animais , Anti-Inflamatórios , Diarreia/genética , Humanos , Íleo , Imunidade , Inflamação , Ovinos
11.
BMC Neurosci ; 23(1): 56, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171542

RESUMO

BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. RESULTS: A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM-receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA-miRNA-mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. CONCLUSIONS: We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.


Assuntos
MicroRNAs , RNA Longo não Codificante , Envelhecimento , Animais , Redes Reguladoras de Genes , Hipocampo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Ratos , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/genética , Tirosina
12.
Langmuir ; 38(48): 14941-14958, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36398792

RESUMO

Coal-water interactions induced by water retention in coals control the performance of coalbed methane reservoirs and coal utilizations. Experimental measurements on Illinois coal samples using X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, low-temperature N2 adsorption, low-pressure CO2 adsorption, and dynamic water vapor sorption were carried out. A mechanism-based isothermal model of water vapor sorption was proposed to estimate the water adsorption capacity at varied relative humidity, which implicitly considered both monolayer and multilayer adsorptions and capillary condensation. The analytical models for quantifying the stage-based diffusion coefficients as well as the apparent diffusion coefficients at different relative humidities were proposed and well validated. The contributions of different diffusion regimes to the total mass flow were discussed. At the first stage, both free water vapor diffusion and surface diffusion of adsorbed water molecules contribute to the total mass flow whereas the apparent diffusion at this stage is dominated by latter flow regime; during the second stage, the contribution of free water vapor flow to the apparent flow can be neglected and the mass transfer at this stage is still dominated by the surface diffusion flow; upon reaching the critical relative humidity, the flow in capillary condensation will dominate the total mass flow.

13.
Zhonghua Nan Ke Xue ; 28(11): 1044-1048, 2022 Nov.
Artigo em Zh | MEDLINE | ID: mdl-37846123

RESUMO

Ferroptosis is a new type of cell death found in recent years, which is characterized by iron overload, excessive accumulation of lipid peroxide and destruction of mitochondrial structure. Testicular spermatogenic dysfunction (TSD) is an important factor affecting the health and quality of life of middle-aged and elderly men. Studies show that ferroptosis plays an important role in the development and progression of TSD, mainly involved in the mechanisms of abnormal iron metabolism, lipid peroxidation, oxidative stress response and mitochondrial damage. It is believed that ferroptosis can induce a series of symptoms, such as sperm quality and quantity reduction and spermatogenesis disorder. Therefore, inhibiting the development of ferroptosis can provide a new basis for the study of the mechanisms of the disease. This review focuses on the concept and characteristics of ferroptosis and the advances in the studies of the its mechanism in regulating TSD, with the purpose of introducing the clinical application prospect of targeted inhibition of ferroptosis in the prevention and treatment of TSD and expanding the ideas for the treatment of TSD and other male reproductive diseases.


Assuntos
Ferroptose , Doenças Testiculares , Idoso , Pessoa de Meia-Idade , Humanos , Masculino , Qualidade de Vida , Sêmen , Espermatogênese , Espermatozoides , Peroxidação de Lipídeos
14.
Cancer Immunol Immunother ; 70(11): 3261-3275, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33837850

RESUMO

Rb1-inducible coiled-coil 1 (RB1CC1) has been demonstrated to function as an inhibitor of proline-rich/Ca-activated tyrosine kinase 2 (PYK2) by binding to the kinase domain of PYK2, which promotes the proliferation, invasion, and migration of renal cell carcinoma (RCC) cells. Additionally, in breast cancer, PYK2 positively regulates the expression of transcriptional co-activator with PDZ-binding motif (TAZ) which in turn can enhance PDL1 levels in breast and lung cancer cells. The current study was performed to decipher the impact of RB1CC1 in the progression of RCC via regulation of the PYK2/TAZ/PDL1 signaling axis. Expression of RB1CC1 and PYK2 was quantified in clinical tissue samples from RCC patients. The relationship between TAZ and PYK2, TAZ and PDL1 was then validated. The cellular processes of doxorubicin (DOX)-induced human RCC cell lines including the abilities of proliferation, colony formation, sphere formation and apoptosis, as well as the tumorigenicity of transfected cells, were evaluated after the alteration of RB1CC1 expression. RB1CC1 exhibited decreased expression in RCC tissues and was positively correlated with patient survival. RB1CC1 could inhibit the activity of PYK2, which in turn stimulated the stability of TAZ protein by phosphorylating TAZ. Meanwhile, TAZ protein activated PDL1 transcription by binding to the promoter region of PDL1. RB1CC1 overexpression or PYK2 knockdown could help everolimus (EVE) to inhibit tumor proliferation and activate immune response. Taken together, RB1CC1 can potentially augment the response of RCC cells to immunotherapy by suppressing the PYK2/TAZ/PDL1 signaling axis.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma de Células Renais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/patologia , Adulto , Animais , Proteínas Relacionadas à Autofagia/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Feminino , Quinase 2 de Adesão Focal/metabolismo , Genes Supressores de Tumor , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
15.
Adv Exp Med Biol ; 1285: 63-79, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33770403

RESUMO

In sheep and goats, amino acid nutrition is essential for the maintenance of health and productivity. In this review, we analysed literature, mostly from the past two decades, focusing on assessment of amino acid requirements, especially on the balance of amino acid profiles between ruminal microbial protein and animal production protein (foetal growth, body weight gain, milk and wool). Our aim was to identify amino acids that might limit genetic potential for production. We propose that much attention should be paid to amino acid nutrition of individuals with greater abilities to produce meat, milk or wool, or to nourish large litters. Moreover, research is warranted to identify interactions among amino acids, particularly these amino acids that can send positive and negative signals at the same time.


Assuntos
Aminoácidos , Cabras , Animais , Ácidos Graxos , Leite , Ovinos ,
16.
Cancer Sci ; 111(7): 2423-2430, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32350965

RESUMO

The transmembrane receptors integrins are the bridges for cell-cell or cell-ECM interaction, which is strictly correlated to cancer development in several tumor types. Here, we revealed that integrin ß8 serves as a driver to mediate sustained growth of bladder cancer and development of drug resistance. The elevated expression of integrin ß8 was observed in highly malignant bladder tumor tissues from patients. The in vitro and in vivo results further indicated that integrin ß8 overexpression in Biu87/T24 bladder cancer could mediate and strengthen cell proliferation and resistance to mitomycin C and hydroxycamptothecin. Mechanistically, integrin ß8 on the cellular surface might recruit phosphorylated Y-box binding protein 1, leading to the activation of c-Myc and nuclear factor-κB signals. Pharmacological targeting of integrin ß8 by Arg-Gly-Asp-Ser efficiently suppressed sustained growth and drug resistance in bladder cancer cells. Our findings identified integrin ß8 as a marker of bladder cancer diagnosis and development, and provides an innovative approach for clinical bladder cancer therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Cadeias beta de Integrinas/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Cadeias beta de Integrinas/genética , Camundongos , NF-kappa B/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proteína 1 de Ligação a Y-Box/genética
17.
J Nutr ; 150(10): 2755-2763, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32856057

RESUMO

BACKGROUND: High rumen-degradable starch (RDS) diets decrease milk fat. The increase of LPS in plasma associated with increased RDS impairs liver function, immune response and lipid metabolism, which depress the precursors for milk fat. OBJECTIVE: This study investigated the mechanism of depression of milk fat precursors in the liver and small intestine of dairy goats fed different RDS diets. METHOD: Eighteen Guanzhong lactating goats (second lactation, 45.8 ± 1.54 kg) and 6 ruminally cannulated dairy goats (aged 2-3 y, 54.0 ± 2.40 kg) were fed 3 different diets with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) for 36 and 21 d, respectively, in experiments 1 and 2. The liver metabolites and jejunal microbiota in experiment 1 and LPS concentrations in rumen fluid and plasma in experiment 2 were measured. One-way ANOVA was used to analyze the biochemical parameters and mRNA or protein expression. The MIXED procedure was used to analyze LPS concentrations. RESULTS: In experiment 1, the HRDS diet showed increased activity of alkaline phosphatase (27.4 to 41.4 U/L) in plasma (P < 0.05) compared with LRDS treatment. The HRDS diet significantly increased the hepatic concentrations of l-carnitine (129%), l-palmitoylcarnitine (306%), taurochenodeoxycholate (856%), and taurodeoxycholic acid (588%) in liver (variable importance in the projection > 1, P < 0.10) compared with the LRDS treatment. Goats fed the HRDS diet had 33.6% greater liver protein expression of carnitine palmitoyltransferase-1 (P < 0.05), and greater relative abundance of Firmicutes and Ruminococcus 2 in the jejunal content (linear discriminant analysis > 2.0, P < 0.05) than did goats fed LRDS diet. In experiment 2, goats fed the HRDS diet had greater LPS concentrations in rumen fluid (7.57 to 13.6 kEU/mL) and plasma (0.037 to 0.179 EU/mL) (P < 0.05) than did goats fed LRDS diet. CONCLUSIONS: Feeding the HRDS diet promoted hepatic lipid ß-oxidation and disrupted phospholipid and bile acids metabolisms in liver, thereby reducing the supply of lipogenic precursors to the mammary gland in dairy goats.


Assuntos
Ácidos e Sais Biliares/metabolismo , Carboidratos da Dieta/farmacologia , Cabras/fisiologia , Fígado/metabolismo , Rúmen/metabolismo , Amido/farmacologia , Animais , Carboidratos da Dieta/administração & dosagem , Feminino , Lactação , Metabolismo dos Lipídeos , Amido/administração & dosagem , Amido/metabolismo
18.
Biomed Microdevices ; 22(2): 24, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166408

RESUMO

The porous TiO2 coatings containing Ca/P/Ag were separately prepared on titanium (Ti) surface by one-step (micro-arc oxidation) and two-step methods (micro-arc oxidation and cathodic deposition), and then their surface morphology, composition, biological and antibacterial properties were compared. The results showed that the porous coatings containing Ca/P/Ag achieved by different methods showed similar surface morphology and elemental composition, however, by one-step method, silver existed in the coating as silver phosphate, while in the coatings prepared by two-step method, silver existed as metallic silver. Although both coatings showed excellent antibacterial property (the antimicrobial rate is over 99.9%), the surface coating prepared by one-step method had a more suitable release curve of Ag. In addition, the surface coating prepared by one-step method also presented better biological property, which was due to its enhanced surface roughness and hydrophilicity. Combining with its easy operation and long-term antibacterial property, its prospect for clinical application is more promising.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cálcio/química , Fósforo/química , Prata/química , Titânio/química , Titânio/farmacologia , Eletrodos , Oxirredução , Porosidade , Propriedades de Superfície
19.
Environ Res ; 190: 109849, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32763275

RESUMO

As one of the most important energy resources in the world, coal contributes a great deal to the world economy. Coal mining and processing involve multiple dust generation processes including coal cutting, transport, crushing and milling etc. Coal dust is one of the main sources of health hazard for the coal workers. Exposure of coal dusts can be prevented through administrative controls and engineering controls. Ineffective control of coal dust exposure can harm coal workers' health. Although many efforts have been made to eliminate these threats, recent years have seen an unexpected increase in coal workers' pneumoconiosis (CWP) in Appalachian basin in US. To explore the reasons for this phenomenon, in this review, we first reviewed the historical studies on coal mine dust including the regulation and engineering controls. Then, the effects of coal dust on human health was comprehensively reviewed. Next, the effects of nanoparticles on human health were reviewed, with an emphasis on toxicity of nanoparticles such as carbon nanotubes in other industries. From all this information, we hypothesize that nano-sized coal dust has contributed to the increase of CWP prevalence in recent years. As no research has been reported in this area, four directions which may need further investigation and future studies are recommended in this review. They include: 1) Systematic characterization of physicochemical properties of nano-size coal dust; 2) Toxicity and pathogenesis of nano-sized coal dust; 3) Development of real-time monitoring technology and equipment for nano-sized coal dust; 4) Development of exposure control technology and equipment. The intent of this review paper is to demonstrate the variation of coal dust properties and their impact on the mine worker's health. We suggest that the impact of nano-sized coal mine dust on miner's health has not yet been understood well and further improvements are necessary.


Assuntos
Minas de Carvão , Mineradores , Nanotubos de Carbono , Exposição Ocupacional , Carvão Mineral , Poeira , Humanos
20.
J Anim Physiol Anim Nutr (Berl) ; 104(4): 1043-1051, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32383244

RESUMO

Four Small-tail Han male hogget sheep, fitted with rumen cannula and fed the same basal diet were used to study the impacts of docusate (DOC) and fauna-free on the voluntary feed intake (VFI), and ruminal protozoal, bacterial and fungal counts and the digestive enzyme activities. By a 4 × 4 Latin square design, sheep were given no DOC (the control), 2 doses of DOC: 1.2 and 3.0 g/kg diet or oral dose of 6.0 g/d DOC for three days (fauna-free treatment) in each period of 18 days, the last three days of which were for sampling the rumen fluid. Compared with the control, 1.2 g/kg of DOC supplementation significantly resulted in increases of 18.0% VFI and 44% bacterial count, and no significant change in the fungal number. Supplementing DOC reduced protozoal number in a dose-dependent manner. The fibre degradation enzyme activity in rumen fluid increased by 17.7% with a concomitant 10% increase in volatile fatty acids (VFA); the protease activity was reduced by 23% with a corresponding reduction in rumen ammonia by 42%. In contrast, supplementing 3.0 g/kg of DOC has adverse effects on those measures compared with 1.2 g/kg of DOC. Defaunation was accompanied with substantial increases in the bacterial and fungal counts, but had no significant influences on VFI and the enzyme activity for starch, protein and pectin digestion, and small changes in fibre digestion enzymes and the total VFA compared with the control. A high correlation (r2  = 0.82) was noted between VFI and the total activity of fibre digestion enzymes and VFA. It was proposed that fibre digestion rate in the rumen is a primary factor for determining VFI in sheep, and dietary supplementation of 1.2 g/kg of DOC could partially result in enhanced activity of fibre digestive enzyme in the rumen and increase VFI.


Assuntos
Antiprotozoários/farmacologia , Digestão/efeitos dos fármacos , Ácido Dioctil Sulfossuccínico/farmacologia , Enzimas/metabolismo , Rúmen/parasitologia , Ovinos/fisiologia , Amônia , Ração Animal , Animais , Dieta/veterinária , Ácidos Graxos Voláteis , Conteúdo Gastrointestinal , Concentração de Íons de Hidrogênio , Masculino
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