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1.
Psychiatry Investig ; 20(1): 43-51, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721885

RESUMO

OBJECTIVE: During the lockdown of cities and home quarantine, media became the only way for people to conveniently get coronavirus disease-2019 (COVID-19)-related information. And media engagement was closely related to psychological outcomes. But fewer researchers took COVID-19-related posting behaviors into consideration. Therefore, the present study aimed at examining the differences in psychological outcomes between people who posted COVID-19-related content on social media and those who did not. METHODS: The present study included 917 participants (304 males, 613 females) who had answered the questionnaires of media engagement, positive affect, negative affect, depression, anxiety, stress, satisfaction with life, death anxiety, and meaning in life. RESULTS: Results of t-tests showed that the Post group had lower levels of negative affect, anxiety, stress, and death anxiety than the Not Post (Npost) group. Network comparison tests indicated that the Npost group's network and the Post group's network differed in global strength, two edge-weights, and node centrality indices. CONCLUSION: The results indicated that more attention should be paid to people who did not post any COVID-19-related content, especially when they have higher levels of stress and depression to prevent comorbidities. And for people who posted content, more attention should be paid when they have a higher level of negative affect.

2.
Nat Metab ; 5(1): 61-79, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36593272

RESUMO

Enhanced glycolysis and accumulation of lactate is a common feature in various types of cancer. Intracellular lactate drives a recently described type of posttranslational modification, lysine lactylation (Kla), on core histones. However, the impact of lactylation on biological processes of tumour cells remains largely unknown. Here we show a global lactylome profiling on a prospectively collected hepatitis B virus-related hepatocellular carcinoma (HCC) cohort. Integrative lactylome and proteome analysis of the tumours and adjacent livers identifies 9,275 Kla sites, with 9,256 sites on non-histone proteins, indicating that Kla is a prevalent modification beyond histone proteins and transcriptional regulation. Notably, Kla preferentially affects enzymes involved in metabolic pathways, including the tricarboxylic acid cycle, and carbohydrate, amino acid, fatty acid and nucleotide metabolism. We further verify that lactylation at K28 inhibits the function of adenylate kinase 2, facilitating the proliferation and metastasis of HCC cells. Our study therefore reveals that Kla plays an important role in regulating cellular metabolism and may contribute to HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Histonas/metabolismo , Lactatos
3.
J Nanobiotechnology ; 21(1): 1, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593461

RESUMO

BACKGROUND: Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed. RESULTS: In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity. CONCLUSIONS: To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity.


Assuntos
Monócitos , Nanoestruturas , Humanos , Nanoestruturas/química , Materiais Biocompatíveis , Citoesqueleto
4.
Biopharm Drug Dispos ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630933

RESUMO

Predicting the brain penetration of drugs has been notoriously difficult however recently, permeability-limited brain models have been constructed. Lead optimization for CNS compounds often focuses on compounds that have low transporter efflux, where passive permeability could be a main driver in determining CSF/brain concentrations. The main objective of this study was to evaluate the translatability of passive permeability data generated from different in vitro systems and its impact on the prediction of human CSF/brain concentrations using PBPK modeling. In vitro data were generated using gMDCK and PAMPA-BBB for comparison and predictions using a QSAR model were also evaluated. PBPK modeling was then performed for seven compounds with moderate-high permeability and a range of efflux in vitro, and the CSF/brain mass concentrations and Kpuu were reasonably predicted. This work provides the first step of a promising approach using bottom-up PBPK modeling for CSF/brain penetration prediction to support lead optimization and clinical candidate selection. This article is protected by copyright. All rights reserved.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36640429

RESUMO

BACKGROUND: The long-term efficacy of high-power (50 W) ablation guided by lesion size index (LSI-guided HP) for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) remains undetermined. Our study sought to assess the clinical efficacy of LSI-guided HP ablation for PVI in patients with AF and explore the potential predictors associated with clinical outcomes. METHODS: We consecutively included 186 patients with AF who underwent LSI-guided HP (50 W) ablation at Fuwai Hospital from June 2019 to October 2021. The target LSI values of 4.5-5.5 and 4.0-4.5 at the anterior and posterior walls, respectively, were used in our study. The baseline clinical characteristics, procedural and ablation data, and clinical outcomes were evaluated. The independent potential predictors associated with AF recurrence were further evaluated. RESULTS: The incidence rate of first-pass PVI was 83.9% (156/186). A total of 11883 lesions were analyzed, and compared with posterior walls of pulmonary veins, anterior walls had significantly lower mean contact force (8.2 ± 3.0 vs. 8.3 ± 2.3 g, P =0.015), longer mean radiofrequency duration (16.9 ± 7.2 vs. 12.9 ± 4.5 s, P <0.001) and higher mean LSI (4.8 ± 0.2 vs. 4.4 ± 0.2, P <0.001). The overall incidence of periprocedural complications was 3.7%, and steam pops without pericardial effusion occurred in three patients (1.6%). During a mean follow-up of 24.0 ± 8.4 months, the overall AF recurrence-free survival was 87.1% after a single procedure. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than those with persistent AF (91.2% vs. 80.8%, log-rank P =0.034). Higher LSI (HR 0.50, P <0.001) and paroxysmal AF (HR0.39, P =0.029) were significantly associated with decreased AF recurrence. By receiver operating characteristic analysis, the LSI of 4.7 and 4.3 for the anterior and posterior walls of the PVs had the highest predictive value for AF recurrence, respectively. CONCLUSION: LSI-guided HP (50 W) ablation for PVI was an efficient and safe strategy and led to favorable single-procedure 2-year AF recurrence-free survival in patients with AF. Higher LSI and paroxysmal AF were independent predictors of decreased 2-year AF recurrence. The LSI of 4.7 for the anterior wall and 4.3 for the posterior wall of the PVs were the best cutoff values for predicting AF recurrence after LSI-guided HP ablation. This article is protected by copyright. All rights reserved.

6.
Microbiol Spectr ; : e0380722, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700687

RESUMO

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

7.
Exp Gerontol ; 173: 112080, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36634721

RESUMO

BACKGROUND: Short-chain fatty acids (SCFAs) have been suggested to be associated with skeletal muscle mass maintenance. However, the role of dietary SCFAs in preserving muscle strength in the older population remains unclear. OBJECTIVES: To clarify the longitudinal association between the dietary intake of SCFAs and the development of low muscle strength in older community dwellers. METHODS: Data were obtained from the National Institute for Longevity Sciences-Longitudinal Study of Aging cohort. The participants included 441 men and 382 women who participated in the baseline survey (the fifth wave, between 2006 and 2008) and at least one follow-up examination (sixth to ninth waves, between 2008 and 2022) and were ≥60 years old and did not have low muscle strength (defined as a grip strength of <28 kg for men and <18 kg for women) at baseline. Baseline nutrient intakes were assessed with a 3-day dietary record. A generalized estimating equation was employed to estimate the odds ratio (OR) and 95 % confidence intervals (CIs) for low muscle strength per 1 standard deviation (SD) increase in the intake of SCFAs and other nutrients at baseline (adjusted for sex, age, follow-up time, baseline grip strength, physical activity, smoking, family income, education, and disease histories). RESULTS: The mean (SD) follow-up time and number were 7.8 (3.2) years and 3.2 (1.0) times, respectively. Approximately 8.1 % of the participants exhibited muscle strength loss in at least one follow-up assessment. The multivariate-adjusted OR (95 % CIs) was 0.77 (0.63-0.93) for each 1-SD increase in SCFA intake (268 mg/day), and the ORs for the highest through the lowest tertiles of SCFA intake were 1.00 (reference), 1.44 (0.95-2.17), and 1.83 (1.20-2.78), respectively (trend p = 0.005). The results remained significant after multivariate adjusting for energy or fat intake. CONCLUSION: Dietary intake of SCFAs may prevent muscle strength decline in community-dwelling older adults.

8.
Gene ; 858: 147185, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36632910

RESUMO

Human periodontal ligament stem cells (hPDLSCs) are promising seed cells for oral bone tissue engineering. Dermatopontin (DPT) is a small-molecule protein recognized as a non-collagenous component of the extracellular matrix and is associated with a variety of biological processes. In this study, we first determined that DPT was elevated during the osteogenic differentiation of hPDLSCs. HPDLSCs interfering with DPT expression were established by lentiviral infection. It was found that the proliferation and osteogenic differentiation ability of hPDLSCs were inhibited after interfering DPT with lentivirus. Exogenous recombinant DPT treatment could not alter the proliferation of hPDLSCs. Coincidentally, exogenous DPT can only enhance the osteogenic differentiation of hPDLSCs in the control lentivirus group, but had no significant effect on the DPT interference group. This study expands the understanding of DPT function and implicates DPT as an important target for enhancing osteogenic differentiation of hPDLSCs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36673760

RESUMO

Heavy metal pollution related to non-ferrous metal smelting may pose a significant threat to human health. This study analyzed 58 surface soils collected from a representative non-ferrous metal smelting area to screen potentially hazardous heavy metals and evaluate their health risk in the studied area. The findings demonstrated that human activity had contributed to the pollution degrees of Cu, Cd, As, Zn, and Pb in the surrounding area of a non-ferrous metal smelting plant (NMSP). Cu, Cd, As, Zn, Pb, Ni, and Co pollution within the NMSP was serious. Combining the spatial distribution and Spearman correlations with principal component analysis (PCA), the primary sources of Cd, As, Pb, and Zn in surrounding areas were related to non-ferrous metal smelting and transportation activities. High non-cancer (THI = 4.76) and cancer risks (TCR = 2.99 × 10-4) were found for adults in the NMSP. Moreover, heavy metals in the surrounding areas posed a potential cancer risk to children (TCR = 3.62 × 10-6) and adults (TCR = 1.27 × 10-5). The significant contributions of As, Pb, and Cd to health risks requires special attention. The construction of a heavy metal pollution management system will benefit from the current study for the non-ferrous metal smelting industry.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Solo , Cádmio , Chumbo , Monitoramento Ambiental , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Medição de Risco , Receptores de Antígenos de Linfócitos T , China
10.
Artigo em Inglês | MEDLINE | ID: mdl-36674109

RESUMO

The rapid consumption of fossil energy and the urgent demand for sustainable development have significantly promoted worldwide efforts to explore new technology for energy conversion and storage. Carbon-based supercapacitors have received increasing attention. The use of biomass and waste as a carbon precursor is environmentally friendly and economical. In this study, hydrothermal pretreatment was used to synthetize coke from bio-oil, which can create a honeycomb-like structure that is advantageous for electrolyte transport. Furthermore, hydrothermal pretreatment, which is low in temperature, can create a low graphitization degree which can make heteroatom introduction and activation easier. Then, urea and KOH were used for doping and activation, which can improve conductivity and capacitance. Compared with no heteroatom and activation hydrothermal char (HC) (58.3 F/g at 1 A/g), the prepared carbon material nitrogen doping activated hydrothermal carbon (NAHC1) had a good electrochemical performance of 225.4 F/g at 1 A/g. The specific capacitance of the prepared NAHC1 was improved by 3.8 times compared with that of HC.


Assuntos
Carbono , Cocaína , Biomassa , Eletrodos
11.
Sci Total Environ ; : 161846, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36709898

RESUMO

Phaeocystis is a globally distributed Prymnesiophyte genus and usually forms massive harmful colony blooms, which impact marine ecosystem, mariculture, human health, and even threaten coastal nuclear power plant safety. However, the mechanisms behind the colony formation from the solitary cells remain poorly understood. Here, we investigated metabolic processes of both solitary and non-flagellated colonial cells of Phaeocystis globosa at different colony bloom stages in the subtropical Beibu Gulf using a metaproteomic approach. Temperature was significantly correlated with Phaeocystis colony bloom formation, and the flagellated motile solitary cells with abundant flagellum-associated proteins, such as tubulin and dynein, were the exclusive cellular morphotype at the solitary cell stage featured with temperatures ≥21 °C. When the temperature decreased to <21 °C, tiny colonies appeared and the flagellum-associated proteins were down-regulated in both solitary and non-flagellated colonial cells, while proteins involved in biosynthesis, chain polymerization and aggregation of glycosaminoglycan (GAG), a key constituent of gelatinous matrix, were up-regulated, indicating the central role of active GAG biosynthesis during the colony formation. Furthermore, light utilization, carbon fixation, nitrogen assimilation, and amino acid and protein synthesis were also enhanced to provide sufficient energy and substrates for GAG biosynthesis. This study highlighted that temperature induced re-allocation of energy and substances toward GAG biosynthesis is essential for colony bloom formation of P. globosa.

12.
J Photochem Photobiol B ; 239: 112645, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608400

RESUMO

Photodynamic therapy (PDT) elicits cell death, vascular damage, or/and anti-tumor host immune response upon activating the administered photosensitive drug by an appropriate light source. Because PDT is heavily dependent on tissue oxygen (O2) in essence, the concentration-dependent impact of O2 on tailoring cellular response to PDT remains an in-depth investigation. As a multifaceted modality, optimal combinations of photosensitizer (PS) concentration, light dose, and O2 delivery are critical to achieve ideal therapeutic outcomes. We herein present a fully integrated all-in-one device for the in vitro assessment of PDT efficacy synchronizing the quantitative control of three PDT disciplines simultaneously, aiming at 1) identifying the influence of varying gaseous microenvironments on PDT; and 2) determining the contribution of each PDT factor and estimating the strength of their synergic effect. The gas-gradient-generating unit for contactless headspace O2 delivery and spatial light control filtering layer in our device could either work as a stand-alone module or combine to screen a range of experimental PDT parameters. By sweeping a total of 128 conditions over four 5-aminolevulinic acid (5-ALA) concentrations, four light dosages, and eight O2 levels in one single experiment, we determined the main effects of the three key PDT agents and highlighted the interactive effect between 5-ALA and light after full-factorial statistical analysis. Our device is not only a versatile tool for predicting PDT efficacy during the translational study but also provides valuable multidimensional information for the interrelation between key PDT factors, which may expedite clinical PDT dosimetry and furnish new insights for the fundamental understanding of photobiological processes.


Assuntos
Fotoquimioterapia , Fotoquimioterapia/métodos , Gases , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/metabolismo , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Oxigênio , Microambiente Tumoral
13.
J Hazard Mater ; 448: 130874, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36716559

RESUMO

Membrane separation and sulfate radicals-based advanced oxidation processes (SR-AOPs) can be combined as an efficient technique for the elimination of organic pollutants. The immobilization of metal oxide catalysts on ceramic membranes can enrich the membrane separation technology with catalytic oxidation avoiding recovering suspended catalysts. Herein, nanostructured Co3O4 ceramic catalytic membranes with different Co loadings were fabricated via a simple ball-milling and calcination process. Uniform distribution of Co3O4 nanoparticles in the membrane provided sufficient active sites for catalytic oxidation of 4-hydroxybenzoic acid (HBA). Mechanistic studies were conducted to determine the reactive radicals and showed that both SO4•- and •OH were present in the catalytic process while SO4•- plays the dominant role. The anti-fouling performance of the composite Co@Al2O3 membranes was also evaluated, showing that a great flux recovery was achieved with the addition of PMS for the fouling caused by humic acid (HA).

14.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36716991

RESUMO

INTRODUCTION AND OBJECTIVES: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to < 130 mmHg) and standard (SBP target of 130 to < 150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. RESULTS: Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], < 303.0 µmol/L; tertile 2 [T2], 303.0 to < 375.8 µmol/L; and tertile 3 [T3], ≥375.8 µmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36-0.86; P = .008), T2 (HR, 0.80; 95%CI, 0.56-1.14; P = .22) and T3 (HR, 0.86; 95%CI, 0.60-1.21; P = .39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. CONCLUSIONS: There was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. CLINICAL TRIAL REGISTRATION NUMBER: NCT03015311.X.

15.
Biochem Biophys Res Commun ; 645: 55-60, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680937

RESUMO

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

16.
Cell Biol Int ; 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36682038

RESUMO

Pancreatic cancer is characterized by poor prognosis and high mortality, while its treatment remains unsatisfactory. Cinchonine, a natural compound present in cinchona bark, is a potential anticancer drug. Whether cinchonine is of relevance to pancreatic cancer therapeutics is unclear. This research showed that the ribosomal RNA-processing 15 homolog (RRP15) expression is decreased in the pancreatic cancer, and RRP15 knockdown inhibited autophagy, and caused apoptosis in pancreatic cancer cells. Cinchonine treatment inhibits the expression of RRP15 and autophagy, and caused apoptosis by leading to the activation of Nrf2 axis in pancreatic cancer cells. Taken together, the above results indicate that cinchonine treatment inhibited autophagy and induced apoptosis through activating Nrf2 axis by downregulating RRP15 in pancreatic cancer cells.

17.
Life Sci Space Res (Amst) ; 36: 59-69, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36682830

RESUMO

Microgravity can inhibit osteoblast proliferation and promote apoptosis, which is related to a reduction in mechanical stress on the bones and results in disuse osteoporosis, but the detailed mechanism is still unclear. In this study, we first demonstrated that miR-138-5p was upregulated, inhibited osteoblast proliferation and induced osteoblast apoptosis under simulated microgravity. Moreover, miR-138-5p silencing partially mitigated the effects of proliferation and apoptosis of MC3T3-E1 cells. Our study further showed that sirtuin 1 (SIRT1) was downregulated and negatively correlated with the expression of miR-138-5p under simulated microgravity, which indicated that miR-138-5p inhibited osteoblast proliferation and promoted osteoblast apoptosis by targeting SIRT1. Thus, the miR-138-5p/SIRT1 pathway should be considered for preventative treatment of disuse osteoporosis.


Assuntos
MicroRNAs , Osteoporose , Ausência de Peso , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Sirtuína 1/metabolismo , Proliferação de Células , Apoptose , Osteoblastos/metabolismo , Osteoporose/metabolismo
18.
J Mol Model ; 29(2): 39, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36640252

RESUMO

CONTEXT: The UV(ultraviolet) absorption spectrum of PETN under different electric field loading directions(X, Y, and Z) with the value of strength range from 0.001 a.u. to 0.006 a.u. was calculated with the TDDFT(Time-dependent density functional) in this work. With the increase of electric field strength, the absorbance of PETN in the ultraviolet band decreases. To explain the action mechanism of the electric field on PETN UV(ultraviolet) absorption spectrum, we analyzed and counted the contribution rate, oscillator strength, and vertical excitation energy of the main excitation process whose contribution rate to the UV absorption spectrum is greater than 10%. The contribution of PETN to the UV spectrum in all directions without an electric field was also listed to investigate the anisotropy of PETN in the excitation process under an electric field. The hole-electron analysis showed that the electric field will enhance the charge transfer characteristics in the excitation process of PETN. To investigate the anisotropy of the response under different electric field application directions, the contribution of the UV absorption spectrum in different directions was studied. METHODS: Optimization and TDDFT calculation were performed at the level of M06-2X/def2-TZVP and PBE0/def2-TZVP respectively, with Gaussian09 program. The hole-electron analysis and UV absorption spectrum plotting were performed with Multiwfn3.8.

19.
J Palliat Care ; : 8258597231152126, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36654483

RESUMO

Objective: The development process of self-growth among Chinese hospice volunteers is poorly understood. This study aimed to explore and delineate their dynamic progression toward self-growth. Methods: This qualitative study used grounded theory to analyze semi-structured interview data using individual in-depth face-to-face interviews with 15 volunteers at a hospice care center in Ningbo, China, between January 2021 and January 2022. Data analysis was based on the open, axial, and selective coding stages of grounded theory and used the constant comparative method. Results: From the interview data, we extracted 1 core category (Death awakening life), 4 categories, and 19 subcategories that pertained to the process of self-growth. The 4 categories delineated the process of self-growth; respondents progressed through self-salvation, self-reflection, self-healing, and self-transcendence stages. The 19 subcategories are introduced and illustrated with interview extracts. Conclusions: The study findings can inform the development of training projects aimed at improving hospice care volunteer services.

20.
Int Immunopharmacol ; 114: 109619, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36700781

RESUMO

Traumatic brain injury often causes poor outcomes and has few established treatments. Neuroinflammation and ferroptosis hinder therapeutic progress in this domain. Annexin A5 (A5) has anticoagulant, anti-apoptotic and anti-inflammatory bioactivities. However, its protective effects on traumatic brain injury remain unclear. Thus, we explored whether inhibiting ferroptosis and neuroinflammation using A5 could ameliorate traumatic brain injury. We injected recombinant A5 (50 µg/kg) in the tail vein of mice 30 min after fluid percussion injury. We then assessed modified neurologic severity scores, Morris water maze performance, rotarod test performance, brain water content, and blood-brain barrier permeability to document the neuroprotective effects of A5. Two days after the traumatic brain injury, we collected injured cortex tissues for western blot, Perl's staining, apoptosis staining, Nissl staining, immunofluorescence/immunohistochemistry, and enzyme-linked immunosorbent assay. We also quantified superoxide dismutase and glutathione peroxidase activity and glutathione and malondialdehyde levels. A5 improved neurological deficits, weight loss, cerebral hypoperfusion, brain edema, blood-brain barrier disruption, neuronal apoptosis, and ferroptosis. It also increased the ratio of M2/M1 phenotype microglia, reduced interleukin 1ß and 6 levels, decreased peripheral immune cell infiltration, and increased interleukin 10 levels. A5 reduced neuronal iron accumulation, p53-related cell death, and oxidative stress damage. Finally, A5 downregulated HMGB1 and NF-ĸB pathways and upregulated the nuclear erythroid 2-related factor (Nrf2) and HO-1 pathways. These results suggest that A5 exerts neuroprotection in traumatic brain injury mice and ameliorates neuroinflammation, oxidative stress, and ferroptosis by regulating the NF-kB/HMGB1 pathway and the Nrf2/HO-1 antioxidant system.


Assuntos
Lesões Encefálicas Traumáticas , Ferroptose , Proteína HMGB1 , Camundongos , Animais , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Anexina A5/metabolismo , Doenças Neuroinflamatórias , Proteína HMGB1/metabolismo , Fatores de Transcrição NFI , Transdução de Sinais , Lesões Encefálicas Traumáticas/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia
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