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1.
World J Urol ; 40(11): 2649-2656, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36125504

RESUMO

PURPOSE: To assess whether the 5-item Frailty Index (5i-FI) predicts surgical complications of endoscopic surgery for benign prostatic obstruction (BPO) and examine the rates of these complications across BPO surgical modalities adjusting for patient frailty. METHODS: The ACS-NSQIP registry was queried for patients who underwent transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and laser enucleation of the prostate (LEP) between 2009 and 2019. Patients' frailties were estimated using the 5i-FI. We assessed the association between 5i-FI and the following endpoints: all complications, major complications (Clavien-Dindo ≥ 3), length of stay (LOS) ≥ 2 days, and 30-day postoperative readmission. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. IPTW-adjusted rates for 30-day complications were compared between surgical modalities. RESULTS: The cohort included 38,399 (62.6%) TURP, 19,121 (31.2%) PVP, and 3797 (6.2%) LEP. Men with 5i-FI score ≥ 2 were more likely to receive TURP (22.7%) and PVP (22.5%) than LEP (18.8%). 5i-FI ≥ 2 was associated with higher odds of all complications (OR 1.50), major complications (OR 1.63), LOS ≥ 2 (OR 1.31), and readmission (OR 1.65). After IPTW, LEP had the lowest rates for all complications (6.29%; 95%CI 5.48-7.20), major complications (2.30%; 95%CI 1.83-2.89), and readmission (3.80%; 95%CI 3.18-4.53). CONCLUSION: The 5i-FI score is an independent predictor of 30-day postoperative surgical complications after endoscopic BPO surgery. After IPTW, LEP and PVP were associated with lower rates of complications than TURP. However, frail patients were less likely to undergo PVP and LEP. Preoperative frailty assessment could improve risk stratification before BPO surgery.


Assuntos
Fragilidade , Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução Uretral , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Fragilidade/complicações , Resultado do Tratamento , Terapia a Laser/efeitos adversos , Obstrução Uretral/etiologia , Complicações Pós-Operatórias/etiologia
2.
Int J Mol Sci ; 21(9)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403414

RESUMO

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1 transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1 protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 M) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1 pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.


Assuntos
Anilidas/farmacologia , Fator 1 Induzível por Hipóxia/genética , Rim/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nitrilas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Tosil/farmacologia , Antagonistas de Androgênios/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Rim/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células Mesangiais/citologia , Células Mesangiais/metabolismo , Mitocôndrias/metabolismo , Ratos , Regulação para Cima/efeitos dos fármacos
3.
Int J Mol Sci ; 21(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365658

RESUMO

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30 µM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.


Assuntos
Fator 6 Ativador da Transcrição/agonistas , Caspases/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Nifedipino/farmacologia , Animais , Biomarcadores , Caspase 12/metabolismo , Caspase 3/metabolismo , Caspase 7/metabolismo , Rim/patologia , Rim/ultraestrutura , Metabolismo dos Lipídeos , Oxirredução/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais/efeitos dos fármacos
4.
Int J Mol Sci ; 21(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575412

RESUMO

Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague-Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p < 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.


Assuntos
Antígenos CD36/metabolismo , Doxorrubicina/efeitos adversos , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Lipogênese/efeitos dos fármacos , Nifedipino/efeitos adversos , Insuficiência Renal Crônica/terapia , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Transplante de Rim , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/metabolismo , Regulação para Cima
5.
Int J Mol Sci ; 20(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934807

RESUMO

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Rim/metabolismo , Lipogênese/efeitos dos fármacos , Nifedipino/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Transcrição Gênica/efeitos dos fármacos , Animais , Vias Biossintéticas/efeitos dos fármacos , Antígenos CD36/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Regulação para Baixo/efeitos dos fármacos , Espaço Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/lesões , Modelos Biológicos , PPAR alfa/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
6.
Toxicol Appl Pharmacol ; 306: 86-97, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27286660

RESUMO

Carbendazim inhibits microtubule assembly, thus blocking mitosis and inhibiting cancer cell proliferation. Accordingly, carbendazim is being explored as an anticancer drug. Data show that carbendazim increased mRNA and protein expressions and promoter activity of CYP1A1. In addition, carbendazim activated transcriptional activity of the aryl hydrocarbon response element, and induced nuclear translocation of the aryl hydrocarbon receptor (AhR), a sign the AhR is activated. Carbendazim-induced CYP1A1 expression was blocked by AhR antagonists, and was abolished in AhR signal-deficient cells. Results demonstrated that carbendazim activated the AhR, thereby stimulating CYP1A1 expression. In order to understand whether AhR-induced metabolic enzymes turn carbendazim into less-toxic metabolites, Hoechst 33342 staining to reveal carbendazim-induced nuclear changes and flow cytometry to reveal the subG0/G1 population were applied to monitor carbendazim-induced cell apoptosis. Carbendazim induced less apoptosis in Hepa-1c1c7 cells than in AhR signal-deficient Hepa-1c1c7 mutant cells. Pretreatment with ß-NF, an AhR agonist that highly induces CYP1A1 expression, decreased carbendazim-induced cell death. In addition, the lower the level of AhR was, the lower the vitality present in carbendazim-treated cells, including hepatoma cells and their derivatives with AhR RNA interference, also embryonic kidney cells, bladder carcinoma cells, and AhR signal-deficient Hepa-1c1c7 cells. In summary, carbendazim is an AhR agonist. The toxicity of carbendazim was lower in cells with the AhR signal. This report provides clues indicating that carbendazim is more potent at inducing cell death in tissues without than in those with the AhR signal, an important reference for applying carbendazim in cancer chemotherapy.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Morte Celular/fisiologia , Citocromo P-450 CYP1A1/metabolismo , Fungicidas Industriais/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1/genética , Humanos , Camundongos , Receptores de Hidrocarboneto Arílico/agonistas , Ativação Transcricional/efeitos dos fármacos
7.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428685

RESUMO

Bladder cancer (BLCA) is one of the most prevalent malignancies worldwide with a high mortality rate and poor response to immunotherapy in patients expressing lower programmed death ligand 1 (PD-L1) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme responsible for the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from nicotinamide was reported to be overexpressed in various cancers; however, the role of NAMPT in BLCA is obscure. Immunohistochemistry of tissue microarrays, a real-time polymerase chain reaction, Western blotting, proliferation assay, NAD+ quantification, transwell-migration assay, and colony-formation assay were performed to measure NAMPT and PD-L1 expression levels in patients and the effect of NAMPT inhibition on T24 cells. Our study revealed that NAMPT expression was upregulated in BLCA patients with different grades and associated with poor T-cell infiltration. Notably, FK866-mediated NAMPT inhibition decreased cell viability by depleting NAD+, and reducing the migration ability and colony-formation ability of T24 cells. Interestingly, NAMPT negatively regulated PD-L1 under an interferon (IFN)-γ-mediated microenvironment. However, exogenous NAMPT activator has no effect on PD-L1. NAD+ supplementation also only increased PD-L1 in the absence of IFN-γ. Conclusively, NAMPT is crucial for BLCA tumorigenic properties, and it regulates expression of the PD-L1 immune checkpoint protein. NAMPT could be considered a target for modulating sensitivity to immunotherapy.


Assuntos
Citocinas , NAD , Nicotinamida Fosforribosiltransferase , Neoplasias da Bexiga Urinária , Humanos , Antígeno B7-H1/genética , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Microambiente Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Citocinas/metabolismo
8.
Nanoscale Adv ; 6(5): 1423-1435, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38419880

RESUMO

Drug delivery systems based on nanoparticles still face challenges of low efficacy and an inability to track treatment effects in tumor therapy due to biological barriers. This limitation hinders clinicians' ability to determine treatment effects and proper drug dosages, thus, ultimately impeding the further application and transformation of nanoplatforms. To address this challenge, an all-in-one nanoplatform for therapy and imaging is proposed. The nanoplatform is constructed by using nanoparticles through the co-encapsulation of the photothermal therapeutic agent IR780, the passively targeted drug OA@Fe3O4, and the chemotherapeutic drug paclitaxel. Under the guidance of magnetic navigation, the nanoparticles can enhance local enrichment of the drug, while the luminescence properties of IR780 enable drug tracking at the same time. Remarkably, the nanoparticles exhibit improved photothermal-chemotherapy synergy under magnetic targeting guidance, demonstrating antitumor effects in both in vitro and in vivo experiments. It is demonstrated that the use of these polymeric nanoparticles has significant potential for future biomedical applications and clinical decisions.

9.
Int J Biol Macromol ; 262(Pt 1): 129974, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331068

RESUMO

Mitochondria in breast cancer play a critical role in survival and adaptation to dynamic environments. Thus, targeting mitochondria emerges as a promising therapeutic strategy for breast cancer. However, the adaptive unfolded protein response in mitochondria (UPRmt) due to mitochondrial unspecific distribution might contribute to diminished therapeutic outcomes. Herein, mitochondrial targeting liposome agents (CTPP-Lipid) are constructed and adopted for delivering the copper ion (CuET-DSF), which is especially sensitive for mitochondria-abundant breast tumors. In brief, the CTPP-Lipid@CuET achieves the goal of Cu2+ overloading by mitochondria targeting delivery. This rapidly increases ROS production, disrupts mitochondrial structure, and avoids the adaptive UPRmt formation, finally leading to apoptosis of breast cancer cells. In general, the Cu2+ overloading at mitochondria by CTPP-Lipid@CuET is a potential strategy for antitumor therapy, providing new insights into breast tumor therapy.


Assuntos
Neoplasias da Mama , Lipossomos , Humanos , Feminino , Cobre/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resposta a Proteínas não Dobradas , Lipídeos
10.
ACS Nano ; 18(26): 16658-16673, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38907726

RESUMO

Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.


Assuntos
Colite Ulcerativa , Células Epiteliais , Mucosa Intestinal , Piroptose , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Piroptose/efeitos dos fármacos , Animais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Camundongos , Humanos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Lipossomos/química , Camundongos Endogâmicos C57BL , Sistemas de Liberação de Medicamentos
11.
Front Microbiol ; 14: 1227147, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37655345

RESUMO

The detection rate of Klebsiella pneumoniae in food is increasing, and it has emerged as a food pathogen. Global health is threatened due to the emergence of multidrug-resistant (MDR) and hypervirulent (hv) K. pneumoniae. Phages have a promising application as antibacterial agents and have the ability to lyse MDR strains. Hence, phage vB_KpP_HS106 against MDR-hv K. pneumoniae strains was isolated from sewage collected from a hospital. It can maintain stable activity at a pH range of 4-12 and a temperature range of 4°C to 50°C. The maximum adsorption rate of phage HS106 was found to be approximately 84.2% at 6 min. One-step growth curve analysis showed that the latent period of HS106 was 10 min and the burst size was approximately 183 PFU/cell. Furthermore, whole genome analysis indicated that the genome of phage HS106 was a double-stranded linear 76,430-bp long DNA molecule with 44% GC content. A total of 95 open reading frames were annotated in the HS106 genome, which did not contain any virulence genes or antibiotic resistance genes. Phage HS106 reduced MDR K. pneumoniae in milk by approximately 1.6 log10 CFU/mL at 25°C and in chicken by approximately 2 log10 CFU/cm3 at 25°C. Therefore, vB_KpP_HS106 is a promising alternative to antibiotics for biocontrol against multidrug-resistant K. pneumoniae in foods.

12.
Heliyon ; 9(3): e14222, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938437

RESUMO

This paper aims to explore the influence mechanism of powder particle sizes on the microstructure and properties of coatings and identify the effect of powder particle size difference on the coating graphite phase. NbC-reinforced Ni-based coatings were in-situ synthesized by laser cladding to investigate the impact of powder particle sizes on the morphology, structure, and properties of coatings. The results indicate that increasing powder particle size enlarges the coating area and decreases the coating width and dilution ratio. Meanwhile, the defect ratio first increases and then decreases. The XRD test suggests that the coating mainly consists of NbC, solid solution (Fe, Ni), B4C, Cr2C, and CrB2. Different powder particle sizes do not change the phase composition of coatings but affect the graphite phase morphology. The morphology transforms from spherical to flocculent as the powder size varies from micrometer to nanometer. The hardness of coatings gradually increases, and the friction and wear properties decrease with the growth of powder particle size. The dispersed graphite phase in the nano coating plays a self-lubricating role in the friction and wear process. This research provides a reference and theoretical basis for selecting powder particle size in laser cladding.

13.
Materials (Basel) ; 16(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38068006

RESUMO

Rare earth oxides have been proven for their ability to refine grains and have high melting points. In this paper, different contents of rare earth oxide La2O3 were added into the Ni60/WC-Ni composite coating, in order to study its effect on the coating properties. SEM observation confirmed that the grain was refined significantly after the addition of La2O3. Energy Dispersive Spectroscopy (EDS) was applied to investigate the composition and X-Ray Diffraction (XRD) was used to measure the residual stress in the coating samples. In addition, the microhardness and wear resistance of the samples were tested. The results showed that the dilution ratio of coatings with different additions of La2O3 was in the range of 2.4 to 9.8%, and the sample with 1.0% addition of La2O3 exhibited the highest hardness of 66.1 HRC and best wear resistance with a wear volume of 9.87 × 106 µm3, and the residual stress increased from 159.4 MPa to 291.0 MPa. This implies that the performance of the coating has been obviously improved after the addition of La2O3.

14.
Materials (Basel) ; 16(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37834501

RESUMO

The optimal process parameters of ultrasonic-assisted processing were studied to further improve the molding quality and mechanical properties of Ni60/WC-TiO2+La2O3 composite coating. A single-factor experiment was used to explore the influences of ultrasonic vibration frequencies on Ni60/WC-TiO2+La2O3 composite coating. The microstructure, elemental composition, phase composition, hardness, and wear resistance of the coating were studied using scanning electron microscopy (SEM), an X-ray diffractometer (XRD), an energy spectrometer, a microhardness meter, a friction and wear tester, and other equipment. Ultrasonic vibrations significantly improved the problems of pores in the coating, and the porosity was reduced from 0.13 to 0.014%. When the vibration frequency was 32 kHz in the experiment, the aspect ratio of the coating was optimized from 2.06 to 2.48, the dilution rate increased from 5.60 to 5.79%, the hardness increased from 960.25 to 988.45 HZ1.0, and the friction coefficient was reduced from 0.34 to 0.27. The coating performance was significantly improved, and the research results provide a reference for preparing excellent Ni60/WC-TiC+La2O3 composite coating.

15.
Front Microbiol ; 14: 1124454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213506

RESUMO

Introduction: Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota. Methods: A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed. Results: After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of "affective disorder microbiota" from psychologically stressed mice increased stress sensitivity relative to FMT of "normal microbiota" from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites. Discussion: Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.

16.
JAMA Netw Open ; 6(7): e2325291, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37498602

RESUMO

Importance: Geographic access, including mode of transportation, to health care facilities remains understudied. Objective: To identify sociodemographic factors associated with public vs private transportation use to access health care and identify the respondent, trip, and community factors associated with longer distance and time traveled for health care visits. Design, Setting, and Participants: This cross-sectional study used data from the 2017 National Household Travel Survey, including 16 760 trips or a nationally weighted estimate of 5 550 527 364 trips to seek care in the United States. Households that completed the recruitment and retrieval survey for all members aged 5 years and older were included. Data were analyzed between June and August 2022. Exposures: Mode of transportation (private vs public transportation) used to seek care. Main Outcomes and Measures: Survey-weighted multivariable logistic regression models were used to identify factors associated with public vs private transportation and self-reported distance and travel time. Then, for each income category, an interaction term of race and ethnicity with type of transportation was used to estimate the specific increase in travel burden associated with using public transportation compared a private vehicle for each race category. Results: The sample included 12 092 households and 15 063 respondents (8500 respondents [56.4%] aged 51-75 years; 8930 [59.3%] females) who had trips for medical care, of whom 1028 respondents (6.9%) were Hispanic, 1164 respondents (7.8%) were non-Hispanic Black, and 11 957 respondents (79.7%) were non-Hispanic White. Factors associated with public transportation use included non-Hispanic Black race (compared with non-Hispanic White: adjusted odds ratio [aOR], 3.54 [95% CI, 1.90-6.61]; P < .001) and household income less than $25 000 (compared with ≥$100 000: aOR, 7.16 [95% CI, 3.50-14.68]; P < .001). The additional travel time associated with use of public transportation compared with private vehicle use varied by race and household income, with non-Hispanic Black respondents with income of $25 000 to $49 999 experiencing higher burden associated with public transportation (mean difference, 81.9 [95% CI, 48.5-115.3] minutes) than non-Hispanic White respondents with similar income (mean difference, 25.5 [95% CI, 17.5-33.5] minutes; P < .001). Conclusions and Relevance: These findings suggest that certain racial, ethnic, and socioeconomically disadvantaged populations rely on public transportation to seek health care and that reducing delays associated with public transportation could improve care for these patients.


Assuntos
Acessibilidade aos Serviços de Saúde , Viagem , Feminino , Humanos , Masculino , Estudos Transversais , Inquéritos e Questionários , Estados Unidos , Pessoa de Meia-Idade , Idoso
17.
J Hepatol ; 57(4): 720-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22634131

RESUMO

BACKGROUND & AIMS: This study aimed at investigating mutations in the hepatitis B surface protein (HBsAg) in occult hepatitis B virus (HBV) infection (OBI) and their influence on viral antigenicity and phenotype. METHODS: The characteristics of 61 carriers with OBI (OBI group), 153 HBsAg(+) carriers with serum HBsAg ≤ 100 IU/ml (HBsAg-L group) and 54 carriers with serum HBsAg >100 IU/ml (HBsAg-H group) from 38,499 blood donors were investigated. Mutations in the major hydrophilic region (MHR) of the viral sequences were determined. Thirteen representative MHR mutations observed in OBI sequences were antigenically characterized with a panel of monoclonal antibodies (MAbs) and commercial HBsAg immunoassays and functionally characterized in HuH7 cells and hydrodynamically injected mice. RESULTS: Of 61 OBI sequences, 34 (55.7%) harbored MHR mutations, which was significantly higher than the frequency in either the HBsAg-L (34.0%, p=0.003) or the HBsAg-H group (17.1%, p<0.001). Alterations in antigenicity induced by the 13 representative MHR mutations identified in the OBI group were assessed by reacting recombinant HBV mutants with 30 different MAbs targeting various epitopes. Four out of the 13 mutations (C124R, C124Y, K141E, and D144A) strongly decreased the analytical sensitivity of seven commercial HBsAg immunoassays, and 10 (G119R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E, D144A, and G145R) significantly impaired virion and/or S protein secretion in both HuH7 cells and mice. CONCLUSIONS: MHR mutations alter antigenicity and impair virion secretion, both of which may contribute to HBsAg detection failure in individuals with OBI.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Mutação , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Adolescente , Adulto , Animais , Anticorpos Monoclonais Murinos , Portador Sadio/virologia , Linhagem Celular Tumoral , Análise Mutacional de DNA , DNA Viral/sangue , Feminino , Genótipo , Vírus da Hepatite B/genética , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Fenótipo , RNA Viral/biossíntese , Proteínas do Envelope Viral/metabolismo , Vírion/genética , Vírion/metabolismo , Adulto Jovem
18.
Chem Biol Interact ; 356: 109858, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35151640

RESUMO

Bicalutamide (Bic), frequently used in androgen-deprivation therapy for treating prostate cancer, was demonstrated to induce multiple apoptosis and fibrosis pathways and mitochondrial dysfunction in renal mesangial cells. Whether Bic also damages the glycolytic pathway has never been cited. To investigate this, we performed an in vitro model study with mesangial cells, and at the same time, collected data from an in vivo experiment. Bic induced hypoxia-inducible factor (HIF)-1 which upregulates phosphorylated-5'-AMP-activated protein kinase (p-AMPK) and severely suppresses the rate of adenosine triphosphate (ATP) production in both the oxidative phosphorylation and glycolysis pathways. Bic suppressed the oxygen consumption rate, extracellular acidification rate, and mitochondrial proton efflux rate, downregulated in vivo but upregulated in vitro glucose transporter (GLUT)-1, reduced glucose uptake, inhibited key glycolytic enzymes, including phosphofructokinase (PFK), pyruvate kinase (PK), and pyruvate dehydrogenase (PDH), and upregulated hexokinase II (HKII) and lactic dehydrogenase A (LDHA). In vivo, Bic downregulated renal cubilin levels, thereby disrupting the glomerular reabsorption function. Conclusively, Bic can damage bioenergenesis from both mitochondria and glycolysis. It was suggested that long-term administration of Bic can initiate renal damage depending on the duration and dose of treatment, which requires cautious follow-up.


Assuntos
Diabetes Mellitus , Neoplasias da Próstata , Trifosfato de Adenosina , Antagonistas de Androgênios , Anilidas , Glicólise , Humanos , Rim , Masculino , Nitrilas , Compostos de Tosil
19.
J Clin Med ; 11(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35011880

RESUMO

Bicalutamide (Bic) is an androgen deprivation therapy (ADT) for treating prostate cancer, while ADT is potentially associated with acute kidney injury. Previously, we recognized Bic induced renal mitochondria dysfunction in vitro and in vivo via the ROS -HIF1α pathway. Whether OXPHOS complex, as well as mitochondrial dynamics, can be influenced by Bic via modulation of peroxisome proliferator-activated receptor coactivator 1α (PGC1α), NADPH oxidase 4 (Nox4), mitofusins 1/2 (MFN 1/2), optic atrophy 1 (OPA1), and sirtuins (SIRTs) has not been documented. Renal mesangial cell line was treated with Bic (30~60 µM) for the indicated time. SIRTs, complex I, mitochondrial dynamics- and oxidative stress-related proteins were analyzed. Bic dose-dependently reduced mitochondrial potential, but dose- and time-dependently suppressed translocase of the outer mitochondrial membrane member 20 (Tomm 20), complex I activity. Nox4 and glutathione lead to decreased NAD+/NADH ratio, with upregulated superoxide dismutase 2. SIRT1 was initially stimulated and then suppressed, while SIRT3 was time- and dose-dependently downregulated. PGC1α, MFN2, and OPA1 were all upregulated, with MFN1 and pro-fission dynamin-related protein I downregulated. Bic exhibits potential to damage mitochondria via destroying complex I, complex I activity, and mitochondrial dynamics. Long-term treatment with Bic should be carefully followed up.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(1): 16-23, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33441224

RESUMO

Objective To investigate the changes of subsets of thymocytes, thymic epithelial cells (TECs) and T lymphocytes in the spleen of mice at different growth stages, and to explore the effect of Rho-associated coiled-coil protein kinase (ROCK) inhibitor on thymus regeneration in aged mice. Methods The thymus and spleens were harvested from female C57BL/6 mice at juvenile, mature adult, middle-aged and aged phases. The subsets of thymocytes, TECs and T cells in the spleen were analyzed by flow cytometry (FCM). TECs of aging mice were treated with ROCK inhibitor in vitro. Cell proliferation was observed using fluorescence immune-linked spot analyzer. Aged mice of 20-month old were treated with ROCK inhibitor in vivo. The changes of thymocytes, TECs and T cell subgroups in the spleen were detected with FCM. Results The total numbers of thymocytes and TECs as well as the number of each cell subpopulation decreased significantly with aging. The proportions of CD4+ naive T cells, CD8+ naive T cells and CD4+ recent thymus emigrant cells (RTEs) in the spleen showed significant decreasing trends although there were not obvious changes in the proportions of CD4+ T cells and CD8+ T cells in the spleen of mice during aging. ROCK inhibitor facilitated the proliferation of TECs in aging mice in vitro. ROCK inhibitor also increased the numbers of the subsets of thymocytes, TECs and T cells in the spleen of aged mice significantly. Conclusion The mouse thymus undergoes progressing degeneration with aging. ROCK inhibitor has potential of relieving the atrophy of thymus, facilitating thymus regeneration in aged mice.


Assuntos
Linfócitos T CD8-Positivos , Baço , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração , Subpopulações de Linfócitos T , Timo , Quinases Associadas a rho
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