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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120321, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34481257

RESUMO

Zn1-xMnxAl2O4:0.1 mol% Cr3+ (0.04≤x≤0.16) phosphors with single spinel phase were synthesized by using sol-gel method and the structure, optical and temperature sensing performances were reported herein. The results of X-ray photoelectron spectra indicate that the inversion defects related to octahedral Zn are reduced and the crystal field surrounding Al changes with Mn2+ doping in ZnAl2O4 lattices. Mn2+/Cr3+ co-doped ZnAl2O4 nanophosphors reveal a green emission band assigned to Mn2+ and a series of red emission peaks assigned to Cr3+, respectively. With the concentration of Mn2+ increasing, the intensity of zero phonon line (R line) assigned to Cr3+ increases, reaching the maximum at the optimal Mn2+ concentration of x=0.14. The energy transfer from Mn2+ to Cr3+ is confirmed with the energy transfer efficiency of 83%. The separation between 2E(eg) and 2E(tg) of Cr3+ is enlarged due to Mn2+ dopants giving rise to a change of crystal field. The luminous intensity ratio between two separated emission peaks at 685 nm (R3) and 689 nm (R2) reveals an obvious temperature dependence. The relative sensitivity changes from 3.7 %K-1 to 0.25 %K-1 with the temperature increasing from 80 K to 310 K, which is much larger than that of ZnAl2O4:Cr3+ nanophosphors without Mn2+, indicating its good application prospect in optical thermometry.


Assuntos
Termometria , Transferência de Energia , Íons , Temperatura , Difração de Raios X
2.
J Mater Chem B ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724699

RESUMO

The past decade has witnessed the growing interest and advances in aggregation-induced emission (AIE) molecules as driven by their unique fluorescence/optical properties in particular sensing applications including biomolecule sensing/detection, environmental/health monitoring, cell imaging/tracking, and disease analysis/diagnosis. In sharp contrast to conventional aggregation-caused quenching (ACQ) fluorophores, AIE molecules possess intrinsic advantages for the study of disease-related protein aggregates, but such studies are still at an infant stage with much less scientific exploration. This outlook mainly aims to provide the first systematic summary of AIE-based molecules for amyloid protein aggregates associated with neurodegenerative diseases. Despite a limited number of studies on AIE-amyloid systems, we will survey recent and important developments of AIE molecules for different amyloid protein aggregates of Aß (associated with Alzheimer's disease), insulin (associated with type 2 diabetes), (α-syn, associated with Parkinson's disease), and HEWL (associated with familial lysozyme systemic amyloidosis) with a particular focus on the working principle and structural design of four types of AIE-based molecules. Finally, we will provide our views on current challenges and future directions in this emerging area. Our goal is to inspire more researchers and investment in this emerging but less explored subject, so as to advance our fundamental understanding and practical design/usages of AIE molecules for disease-related protein aggregates.

3.
J Asthma Allergy ; 14: 1307-1321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744440

RESUMO

Background: During asthma progression, the intricate molecular networks, including microRNA (miRNA) transcriptional regulation in airway epithelium, remain largely undefined. The abnormal expression of miRNAs in asthmatic airway epithelium is a recent and fast-growing area in developing diagnostic and therapeutic targets for asthma. Material and Methods: Analyses were conducted to compare airway epithelial miRNAs and gene expression between patients with asthma and healthy subjects from three datasets (two for miRNAs expression profiles and one for gene expression profile). The interactions network between differentially expressed (DE)-miRNAs and mRNAs was further identified for functional analysis. To verify the involvement and functions of all the identified miRNAs in asthma, we constructed two cellular models of asthma. The most promising causal miRNA candidate, miR-1246, was examined in an in vitro system to explore its targets and roles in asthma pathophysiology. Results: Through integrative analysis, we obtained six miRNAs with 31 validated target genes in airway epithelium associated with asthma. Next, we confirmed that these miRNAs were all associated with asthma progression by in vitro functional experiments. They may participate in eosinophilic inflammation (miR-92b-3p, miR-1246, miR-197-3p, and miR-124-5p) or remodeling (miR-197-3p, miR-193a-5p, miR-1246, and miR-92b-3p). Additionally, some other non-screened valuable miRNAs were also examined and identified (miR-21-5p and miR-19b-3p), and some detected in blood correlated with the disease status. Furthermore, we found that miR-1246 could directly target POSTN and influence epithelial-to-mesenchymal transition and fibrosis in airway epithelial cells. Conclusion: We constructed a preliminary epithelial regulatory network in asthma based on six identified miRNAs and their valuable target genes. Candidate factors in the biological miRNA-mRNA network in airway epithelium may provide further information on the pathogenesis of asthma. Strikingly, among all screened miRNAs, miR-1246, which could interact with POSTN may have multifunctional effects in the course of asthma and be a promising agent for asthma treatment and molecular subtyping.

4.
Front Physiol ; 12: 729910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777002

RESUMO

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes. Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.

5.
Front Immunol ; 12: 686809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777331

RESUMO

Immune microenvironment of prostate cancer (PCa) is implicated in disease progression. However, previous studies have not fully explored PCa immune microenvironment. This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunotherapy response rate. Furthermore, consensus clustering was performed to separate the population into three IRSclusters with different clinical outcomes. Patients in IRScluster3 showed the worst prognosis and highest immunotherapy response rate. On the other hand, patients in IRScluster2 showed better prognosis and low immunotherapy response rate. In addition, VGLL3, ANPEP, CD38, CCK, DPYS, CST2, COMP, CRISP3, NKAIN1, and F5 genes were differentially expressed in the three IRSclusters. Furthermore, CMap analysis showed that five compounds targeted IRS signature, thioridazine, trifluoperazine, 0175029-0000, trichostatin A, and fluphenazine. In summary, immune characteristics of PCa tumor microenvironment was explored and an IRS signature was constructed based on 10 immune terms. Analysis showed that this signature is a useful tool for prognosis and prediction of immunotherapy response rate of PCa.

6.
Environ Pollut ; : 118492, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34785286

RESUMO

The inherent oxidation potential (OP) of atmospheric particulate matter has been shown to be an important metric in assessing the biological activity of inhaled particulate matter and is associated with the composition of PM2.5. The current study examined the chemical composition of 388 personal PM2.5 samples collected from students and guards living in urban and suburban areas of Beijing, and assessed the ability to predict OP from the calculated metrics of carcinogenic risk, represented by ELCR (excess lifetime cancer risk), non-carcinogenic risk represented by HI (hazard index), and the composition and sources of the particulate matter using multiple linear regression methods. The correlations between calculated ELCR and HI and the measured OP were 0.37 and 0.7, respectively. HI was a better predictor of OP than ELCR. The prediction models based on pollutants (Model_1) and pollution sources (Model_2) were constructed by multiple linear regression method, and Pearson correlation coefficients between the predicted results of Model_1 and Model_2 with the measured volume normalized OP are 0.81 and 0.80, showing good prediction ability. Previous investigations in Europe and North America have developed location-specific relationships between the chemical composition of particulate matter and OP using regression methods. We also examined the ability of relationships between composition and sources, developed in Europe and North America, to predict the OP of particulate matter in Beijing from the composition and sources determined in Beijing. The relationships developed in Europe and North America provided good predictive ability in Beijing and it suggests that these relationships can be used to predict OP from the chemical composition measured in other regions of the world.

7.
Int Braz J Urol ; 472021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34786926

RESUMO

BACKGROUND: The purpose is to compare the efficacy and safety of mini percutaneous nephrolithotomy (mini-PCNL) versus standard percutaneous nephrolithotomy (standard-PCNL) in patients with renal stones >2cm. MATERIALS AND METHODS: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library databases to identify relevant studies before March 8, 2021. Stone-free rate (SFR), operation time, fever rate, hemoglobin drop, blood transfusion rate, and hospitalization time were used as outcomes to compare mini-PCNL and standard-PCNL. The meta-analysis was performed using the Review Manager version 5.4. RESULTS: Seven randomized controlled trials were included in our meta-analysis, involving 1407 mini-PCNL cases and 1436 standard-PCNL cases. Our results reveal that, for renal stones >2cm, mini-PCNL has a similar SFR (risk ratio (RR)=1.01, 95% confidence interval (CI): 0.98 to 1.04, p=0.57) and fever rate (RR=1.22, 95% CI: 0.97-1.51, p=0.08). Standard-PCNL was associated with a significantly shorter operating time (weighted mean difference (WMD)=8.23, 95% CI: 3.44 to 13.01, p <0.01) and a longer hospitalization time (WMD=-20.05, 95% CI: -29.28 to -10.81, p <0.01) than mini-PCNL. Subgroup analysis showed hemoglobin drop and blood transfusion for 30F standard-PCNL were more common than mini-PCNL (WMD=-0.95, 95% CI: -1.40 to -0.50, p <0.01; RR=0.20, 95% CI: 0.07 to 0.58, p <0.01). CONCLUSION: In the treatment of >2cm renal stones, mini-PCNL should be considered an effective and reliable alternative to standard-PCNL (30F). It achieves a comparable SFR to standard-PCNL, but with less blood loss, lower transfusion rate, and shorter hospitalization. However, the mini-PCNL does not show a significant advantage over the 24F standard-PCNL. On the contrary, this procedure takes a longer operation time. TRIAL REGISTRATION: This meta-analysis was reported consistent with the PRISMA statement and was registered on PROSPERO, with registration number 2021CRD42021234893.

8.
Environ Pollut ; 293: 118521, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34793910

RESUMO

Biochar modification by metals and metal oxides is considered a practical approach for enhancing the adsorption capacity of anionic compounds such as phosphate (P). This study obtained paper mill sludge (PMS) biochar (PMSB) via a one-step process by pyrolyzing PMS waste containing ferric salt to remove anionic P from water. The ferric salt in the sludge was transformed into ferric oxide and zero-valent-iron (Fe0) in N2 atmosphere at pyrolysis temperatures ranging from 300 to 800 °C. The maximum adsorption (Qm) of the PMSBs for P ranged from 9.75 to 25.19 mg P/g. Adsorption is a spontaneous and endothermic process, which implies chemisorption. PMSB obtained at 800 °C (PMSB800) exhibited the best performance for P removal. Fe0 in PMSB800 plays a vital role in P removal via adsorption and coprecipitation, such as forming the ≡Fe-O-P ternary complex. Furthermore, the possible chemical precipitation of P by CaO decomposed from calcite (CaCO3; an additive of paper production that remains in PMS) may also contribute to the removal of P by PMSB800. Moreover, PMSBs can be easily separated magnetically from water after application and adsorption. This study achieved a waste-to-wealth strategy by turning waste PMS into a metal/metal oxide-embedded biochar with excellent P removal capability and simple magnetic separation properties via a one-step pyrolysis process.

9.
Theranostics ; 11(20): 9904-9917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815794

RESUMO

Rationale: Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although N-acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. Methods: We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for in vivo investigation of AKI restoration. Results: The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering in vitro renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Conclusion: Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34732397

RESUMO

INTRODUCTION: Exposure to antibiotics (ABX) during pregnancy can have a systematic effect on both fetal and maternal health. Although previous biomonitoring studies have indicated the effects on children of extensive exposure to ABX, studies on pregnant women remain scarce. To explore the effect on pregnant women of environmental exposure to ABX through accidental ingestion and identify potential health risks, the present study investigated 122 pregnant women in East China between 2019 and 2020. RESEARCH DESIGN AND METHODS: The presence of six categories of ABX (quinolones, sulfonamides, lincosamides, tetracyclines, amide alcohol ABX, and ß-lactams) in plasma samples taken from the pregnant women was investigated using an ABX kit and a time-resolved fluorescence immunoassay. RESULTS: All six ABX were detected in the plasma, with a detection rate of 17.2%. It was discovered that the composition of intestinal flora in pregnant women exposed to ABX was different from that of pregnant women who had not been exposed to ABX. The intestinal flora of pregnant women exposed to ABX also changed at both the phylum and genus levels, and several genera almost disappeared. Furthermore, the metabolic levels of glucose and insulin and the alpha diversity of pregnant women exposed to ABX were higher than those of pregnant women not exposed to ABX. CONCLUSION: Pregnant women are potentially at higher risk of adverse microbial effects. Glucose metabolism and insulin levels were generally higher in pregnant women exposed to ABX than in unexposed women. Also, the composition and color of the gut microbiome changed.

11.
Int J Mol Sci ; 22(21)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34769318

RESUMO

Bulblet formation and development determine the quantitative and qualitative traits, respectively, of bulb yield for most flowering bulbs. For Lycoris species, however, the underlying molecular mechanism remains elusive. Here, clonal bulblets of Lycoris sprengeri (Ls) derived from the same probulb were used as explants to establish efficient and inefficient in vitro regeneration systems by adjusting the 6-benzyladenine (BA) concentrations in media. BA application did not change the biological processes among groups but led to earlier decreases in sucrose and total soluble sugar (TSS) contents. Correlation analyses showed that the BA treatments changed the interaction between carbohydrate and endogenous hormone contents during bulblet regeneration. We found that two sucrose degradation enzyme-related genes, cell wall invertase (CWIN) and sucrose synthase, exhibited exactly opposite expression patterns during the competence stage. In addition, the regeneration system that obtained more bulblets showed significantly higher expression of LsCWIN2 than those that obtained fewer bulblets. Our data demonstrate the essential role of BA in accelerating sucrose degradation and the selection of a dominant sucrose cleavage pattern at the competence stage of in vitro bulblet regeneration. We propose that a relatively active CWIN-catalyzed pathway at the competence stage might promote bulblet regeneration, thus influencing bulb yield.

12.
Medicine (Baltimore) ; 100(46): e27647, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797287

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a chronic degenerative joint disease commonly occurring in middle-aged and elderly people. The main clinical manifestations are joint pain, limited activity, and decreased muscle strength resulting in decreased motor control ability. Exercise therapy is an effective method to enhance muscle strength of lower limbs, while China's traditional skill Tai Chi (TC) is a combination of activity and inertia, internal and external exercise therapy. In recent years, scholars at home and abroad have found that regular TC can effectively improve patients' lower limb function and balance ability. The purpose of this study is to explore the effects of TC on lower limb function and balance ability in patients with KOA. METHODS: This is a prospective randomized controlled clinical trial. One hundred forty-six cases of KOA patients will be randomly divided into experimental group and control group according to 1:1 ratio, 73 cases in each group, the control group: sodium hyaluronate; experimental group: TC added on the basis of the control group. Both groups will receive standard treatment for 5 weeks and will be followed up for 3 months. Observation indicators include: the western Ontario and McMaster universities osteoarthritis index; hospital for special surgery knee score; balance stability index, liver and kidney function, adverse reaction rate, etc. SPSS 23.0 software will be used for data analysis. DISCUSSION: This study will evaluate the effects of TC on lower limb function and balance ability of patients with KOA. The results of this trial will provide a clinical basis for the selection of exercise therapy for patients with KOA.

13.
Phytomedicine ; 93: 153795, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735905

RESUMO

BACKGROUND: Bao Yuan Capsule (BYC) is a patented Chinese medicinal formula for health promotion but its application for ischemic stroke remains unknown. In this study, we proposed the hypothesis that BYC could promote neurogenesis and neurological functional recovery through promoting mitochondrial function and activating PI3K/Akt signaling pathway. METHODS: We firstly performed chemical identification studies by using QIT-TOF-MS technology. Then, we investigated the effects of BYC (1 g/kg, 2 g/kg, 4 g/kg per day) on improving the recovery of the neurological functions in transient middle cerebral artery occlusion (MCAO) ischemic mice. RESULTS: We tentatively characterized 36 compounds from the BYC extractions. At dosage of 4 g/kg, BYC effectively improved locomotor ability, attenuated anxiety-like behaviors, and enhanced the exploring behaviors, learning and memory capability in the transient MCAO ischemic mice. BYC treatment promoted neural stem cell differentiations in the subventricular zone (SVZ) and subgranular zone (SGZ) of the MCAO mice. BYC also up-regulated the expression of Aconitase 2 (ACO2), Succinate dehydrogenase complex, subunit A (SDHA), phosphorylation of AMP-activated protein kinase (p-AMPK), protein kinase B (p-Akt) and glycogen synthase kinase 3ß (p-GSK3ß) in the hippocampus of the MCAO mice. BYC (200 µg/ml) significantly improved the mitochondrial functions in cultured mouse multipotent neural stem like C17.2 cells. BYC treatment also promoted neuronal differentiations in the C17.2 cells under oxygen-glucose deprivation (OGD) condition. The neurogenetic effects were abolished by co-treatments of ATP synthesis inhibitor oligomycin and PI3K/Akt inhibitor wortmannin. Moreover, Akt phosphorylation was dramatically reduced by oligomycin. CONCLUSION: BYC could promote neurogenesis and neurological functional recovery in post ischemic brains by regulating the mitochondrial functions and Akt signaling pathway.


Assuntos
Isquemia Encefálica , Proteínas Proto-Oncogênicas c-akt , Animais , Isquemia Encefálica/tratamento farmacológico , Camundongos , Mitocôndrias/metabolismo , Neurogênese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
14.
Front Pharmacol ; 12: 770329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795593

RESUMO

Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism. Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated. Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain. Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.

15.
Cancer Gene Ther ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799723

RESUMO

Prostate cancer (PCa) is a commonly diagnosed malignancy in men. The transcription factor p53, a well-known cancer suppressor, has been extensively analyzed in the progression of many tumor types, but its involvement in PCa remains not fully understood. Hence, this study aims to explore the possible molecular mechanism underlying p53 in the growth and metastasis of PCa. Based on bioinformatics analysis findings of GEPIA and starBase databases, p53 was demonstrated to be involved in the development of PCa by transcriptionally activating microRNA-519d-3p (miR-519d-3p) expression to suppress the expression of E2F transcription factor 1 (E2F1) and CD147. In order to verify this finding, clinically-obtained PCa tumor tissues were enrolled and commercially-purchased PCa cell lines were used to detect the cell viability, cycle, and apoptosis, as well as invasion and migration by CCK-8, flow cytometry, and Transwell assays respectively. The results of clinical tissue experiments and in vitro cell experiments showed that miR-519d-3p and p53 were poorly-expressed in PCa tissues and cell lines, while E2F1 was highly-expressed. Overexpression of miR-519d-3p led to inhibited PCa cell proliferation, invasion and migration, and p53 overexpression was found to promote miR-519d-3p expression to suppress the malignant characteristics of PCa cells, while the additional E2F1 overexpression restored the malignant traits. Moreover, ChIP analysis and dual-luciferase reporter assay confirmed the interactions among p53, miR-519d-3p, and E2F1. Mechanistically, it was found that p53 transcriptionally activated miR-519d-3p to suppress E2F1 expression. Finally, the in vitro results were further validated by in vivo experiments, which showed that miR-519d-3p prevents tumorigenesis and lymph node metastasis of PCa in nude mice via negatively regulation of E2F1 and CD147. Taken together, the findings uncover that the transcription factor p53 could upregulate miR-519d-3p expression to directly suppress the expression of E2F1, thus inhibiting PCa growth and metastasis. It highlights a novel therapeutic strategy against PCa based on the p53/miR-519d-3p/E2F1 regulatory pathway.

16.
Chemosphere ; : 132778, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34742759

RESUMO

To develop novel catalysts of high-performance and cost-effectiveness, and to investigate the reaction kinetics of CO oxidation, ternary CuCeFeOx catalysts supported on zeolite/PSF (porous stainless-steel fibers) were synthesized for the first time. Effects of different Ce/Fe ratios, loading amounts, calcination temperatures, and reaction kinetics were investigated. Remarkably improved catalytic performance was achieved in the PSF-supported catalysts compared to the granular ones, owing to the increased mass/heat transfer efficiency and the high dispersion of active metal oxide species anchored on the zeolite layer. The Cu3Ce12Fe4-400 sample exhibited the best catalytic activity with a temperature difference in T90 of almost 40 °C lower than the worst one. Characterization results from XRD, FTIR, TEM, XPS, H2-TPR, etc. revealed that the promoted reducibility of metal oxides and formation of more oxygen vacancies significantly contributed to the enhanced catalytic activity. Furthermore, a generalized rate expression was derived from intrinsic and macro kinetic studies by assuming the conversion of CO to CO2 as the rate-determining step, in which CO oxidation over the PSF-supported catalysts followed the pseudo-first-order kinetic established by the Langmuir-Hinshelwood type mechanism.

17.
Food Sci Nutr ; 9(11): 6020-6030, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34760234

RESUMO

In this clinical trial, the safety and effectiveness of Lactobacillus paracasei N1115 (LP N1115) were investigated as a potential probiotic to enhance gut development in young children born by caesarean section. Infants and young children between the ages of 6 months and 3 years were administered with a probiotic consisting of LP N1115 strain (n = 30) or placebo supplement (n = 30) over an 8 weeks intervention. And the stool consistency, bowel habits, salivary cortisol, fecal microbiota, and short-chain fatty acid metabolism were investigated. Efficacy data were obtained from 58 participants who completed the study. Overall, the placebo functioned similarly to LP N1115 group in relation to stool consistency, gastrointestinal symptoms, salivary cortisol, and short-chain fatty acids. However, the scoring data relating to the 6-18 months subgroup receiving LP N1115 remained stable over 8 weeks in comparison to placebo. Analysis of the fecal microbiota using 16S rRNA amplicon sequencing revealed that the phyla Firmicutes represented 62% of the microbial relative abundance in the feces of the subjects during the intervening period. No significant changes in alpha- or beta-diversity were noted between the placebo and LP N1115 groups overtime and at each time point. Differential abundance analysis indicated an increase in Lactobacillus in LP N1115 group at weeks 4 (p < .05) and 8 (p < .05) in comparison to the placebo group. These results suggest that probiotic supplementation with LP N1115 was well tolerated by the young children and subtle changes in the microbiome were noted throughout the intervention period.

18.
J Med Chem ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762429

RESUMO

FTO catalyzes the Fe(II) and 2-oxoglutarate (2OG)-dependent modification of nucleic acids, including the demethylation of N6-methyladenosine (m6A) in mRNA. FTO is a proposed target for anti-cancer therapy. Using information from crystal structures of FTO in complex with 2OG and substrate mimics, we designed and synthesized two series of FTO inhibitors, which were characterized by turnover and binding assays, and by X-ray crystallography with FTO and the related bacterial enzyme AlkB. A potent inhibitor employing binding interactions spanning the FTO 2OG and substrate binding sites was identified. Selectivity over other clinically targeted 2OG oxygenases was demonstrated, including with respect to the hypoxia-inducible factor prolyl and asparaginyl hydroxylases (PHD2 and FIH) and selected JmjC histone demethylases (KDMs). The results illustrate how structure-based design can enable the identification of potent and selective 2OG oxygenase inhibitors and will be useful for the development of FTO inhibitors for use in vivo.

19.
J Sleep Res ; : e13515, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34766410

RESUMO

Sleep behaviour is an important contributing factor in healthy human ageing and cognitive function. Previous studies have linked sleep deficiency with cognitive decline in older adults. However, there is need for more prospective investigations that focus on specific domains of cognitive function. The present study analysed cross-sectional and prospective associations between self-reported sleep and cognitive function in the Midlife in the United States (MIDUS) study. Weekday and weekend sleep duration and habitual sleep quality were obtained via questionnaire data. Brief Test of Adult Cognition by Telephone was conducted to assess overall cognitive function, as well as episodic memory and executive function. We found significant trend for both long weekday and weekend sleep (>8 hr) and lower episodic memory scores in the overall sample. Sex-specific cross-sectional analysis demonstrated men with longer weekend sleep duration have lower overall cognitive function scores, and a negative association between weekend sleep and episodic memory scores. Women demonstrated a positive association between weekend sleep duration and executive function scores. There was no prospective significance for overall or sex-specific analysis. Our present results suggest that sleep duration may contribute to cognitive function, and future studies should include objective sleep measurements and focus on the potential cognitive benefits of improving sleep to further elucidate this association.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34767133

RESUMO

PURPOSE: Endoplasmic reticulum stress (ERS) plays a crucial role in myocardial ischemia-reperfusion injury (MIRI). Cellular FLICE-inhibitory protein (cFLIP) is an essential regulator of apoptosis and plays a major role in regulating ERS. The present study aimed to investigate the effects of long isoform cFLIP (cFLIPL) on endogenous apoptosis and the mechanism of ERS in MIRI. METHODS: The cFLIPL recombinant adenovirus vector was used to infect H9c2 cells and Sprague-Dawley (SD) rats. After infection for 72 h, ischemia was induced for 30 min, and reperfusion was then performed for 2 h to establish the MIRI model in SD rats. H9c2 cells were hypoxic for 4 h and then reoxygenated for 12 h to simulate ischemia/reperfusion (I/R) injury. Model parameters were evaluated by assessing cardiomyocyte viability, cell death (apoptosis), and ERS-related protein expression. In addition, tunicamycin (TM), an ERS agonist, was also added to the medium for pretreatment. Coimmunoprecipitation (Co-IP) of cFLIPL and p38 MAPK protein was performed. RESULTS: cFLIPL expression was decreased in I/R injury and hypoxia/reoxygenation (H/R) injury, and cFLIPL overexpression reduced myocardial infarction in vivo and increased the viability of H9c2 cells in vitro. I/R and H/R upregulated the protein expression of GRP78, IRE-1, and PERK to induce ERS and apoptosis. Interestingly, overexpression of cFLIPL significantly inhibited ERS and subsequent apoptosis, which was reversed by an agonist of ERS. Moreover, Co-IP showed that cFLIPL attenuated ERS and was associated with inhibiting the activation of p38 protein. CONCLUSION: The expression of cFLIPL is significantly downregulated in MIRI, and it is accompanied by excessive ERS and apoptosis. Upregulated cFLIPL suppresses ERS to reduce myocardial apoptosis, which is associated with inhibiting the activity of p38 MAPK. Therefore, cFLIPL may be a potential intervention target for MIRI.

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