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1.
Artigo em Inglês | MEDLINE | ID: mdl-35510692

RESUMO

Cu-based metal-organic frameworks have attracted much attention for electrocatalytic CO 2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO 2  reduction to C 2 H 4 /CH 4 . By changing the size of ligand side groups, the C 2 H 4 /CH 4 selectivity ratio can be gradually tuned and inversed from 11.8:1 to 1:2.6, giving C 2 H 4 , CH 4 , and hydrocarbon selectivities up to 51%, 56%, and 77%, respectively. After long-term electrocatalysis, they can retain the structures/morphologies without formation of Cu-based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C-C coupling to form C 2 H 4 . Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C 2 H 4 pathway is more sensitive than the CH 4 one.

2.
Fitoterapia ; 160: 105217, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35561838

RESUMO

Two pairs of new enantiomeric flavonolignans, ±stachyols A and B (±1 and ± 2), along with two novel isoflavanelignans, stachyols C and D (3 and 4) were isolated from the roots of Indigofera stachyodes. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism (ECD) spectra, as well as quantum chemical calculations. Of those compounds, 1 and 2 represented the first examples of flavonolignans with 5-deoxyflavonoids adduct phenylpropanoids. Moreover, 3 and 4 possess an unprecedented skeleton with isoflavanes adduct phenylpropanoids. The antioxidant activity was evaluated for all compounds in terms of ABTS+ and DPPH bioassays. Compounds 3 and 4 exhibited significant radical-scavenging activity in the ABTS+ assay, with IC50 values of 15.15 and 5.83 µM, respectively.

3.
Phytochemistry ; 200: 113186, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35500784

RESUMO

Eleven undescribed limonoids, cipacinerasins A-K, involving of four diverse carbon skeletal types, along with fifteen known analogues, were isolated from the branches and leaves of Cipadessa baccifera. Within them, cipacinerasins A and B feature a rearranged tetrahydropyranyl ring B formed between C-8 and C-30, are unusual miscellaneous-type limonoids. Cipacinerasins E and F are rare trijugin-type limonoids, of which the D-ring δ-lactone is cleaved. Their structures were elucidated on the basis of extensive spectroscopic data (HRESIMS, NMR, UV and IR), electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. All compounds were evaluated in vitro cytotoxicity against five human tumor cell lines (K562, HeLa, PC3, LN-Cap and Hell), and cipacinerasin E showed moderate antitumor activity with IC50 values ranging from 8.0 to 24.8 µM.

4.
RSC Adv ; 12(21): 13393-13400, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35520117

RESUMO

In the current work, a series of molybdenum disulfide composite MCNTs@Cu@MoS2 materials with high hydrogen evolution performance are prepared. In the hydrogen evolution reaction, their overpotential is as low as 225 mV at a current density of 10 mA cm-2 in 1 M H2SO4 as electrolyte solution. This excellent catalytic activity has been ascribed to its lower electrical impedance and high double layer capacitance. The encapsulation of copper nanoparticles into MoS2 crystals significantly reduces their resistance, enhancing the electron transfer rate during water electrolysis. Thereby, the introduction of conductive nanoparticles into semi-conductive catalyst crystals would be an efficient measure to improve their electrochemical catalytic activity in the hydrogen evolution reaction.

5.
Front Neurol ; 13: 860083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547390

RESUMO

Background: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD. Methods: The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion: Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients. Trial registration: The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

6.
Virol J ; 19(1): 81, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570279

RESUMO

BACKGROUND: Human rhinovirus C (HRV-C) accounts for a large proportion of HRV-related illnesses, but the immune response to HRV-C infection has not been elucidated. Our objective was to assess the effect of HRV-C on cytokine secretion in human bronchial epithelial (HBE) cells grown at air-liquid interface (ALI) and compare it with that of respiratory syncytial virus (RSV). METHODS: HBE cells were differentiated at ALI culture and the full-length cDNA clones of HRV-C651 and HRV-C15, clinical isolates of HRV-C79 and HRV-C101, and two RSV isolates were inoculated in the HBE cells. The effect of HRV-C on cytokine secretion was assessed and compared with that of RSV. RESULTS: HRV-Cs infect and propagate in fully differentiated HBE cells and significantly increase the secretion of IFN-λ1, CCL5, IP10, IL-6, IL-8, and MCP-1. The virus loads positively correlated with the levels of the cytokines. HRV-C induced lower secretion of CCL5 (P = 0.048), IL-6 (P = 0.016), MCP-1 (P = 0.008), and IL-8 (P = 0.032), and similar secretion of IP10 (P = 0.214) and IFN-λ1 (P = 0.214) when compared with RSV. CONCLUSION: HBE ALI culture system supported HRV-C infection and propagation and HRV-C induced relatively weaker cytokine expression than RSV.

7.
Front Cardiovasc Med ; 9: 871654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571170

RESUMO

Background: The long-term outcomes of ablation with vein of Marshall ethanol infusion (VOM-ABL) compared with ablation alone in patients with atrial fibrillation (AF) remains elusive. We aimed to explore whether VOM-ABL showed better long-term benefits and screen the potential determinants of outcome impact of VOM-ABL procedure. Methods: PubMed, Cochrane Library, Web of Science, and Embase were searched up to 1st September 2021. Studies comparing the long-term (one-year or longer) outcomes between VOM-ABL and ablation alone were included. Subgroup analysis identified potential determinants for VOM-ABL procedure. Results: Compared with ablation alone, VOM-ABL was associated with a significantly higher rate of long-term freedom from AF/AT (risk ratio [RR], 1.28; 95% confidence interval [CI], 1.12-1.47; p = 0.00) and successful mitral isthmus (MI) block (RR, 1.52; 95% CI, 1.16-1.99; p = 0.00), whereas, there was no significant difference in pericardial effusion, stroke/transient ischemic attack (TIA), and all-cause death. Subgroup analysis identified two significant treatment-covariate interactions: one was ablation strategy subgroup (pulmonary vein isolation plus linear and/or substrate ablation [PVI+]; RR, 1.41; 95% CI, 1.27-1.56 vs. PVI; RR, 1.05; 95% CI, 0.92-1.19, p = 0.00 for interaction) for freedom from AF/AT, while the other was VOM-ABL group sample size subgroup (≥ 100; RR, 1.98; 95% CI, 1.24-3.17 vs. <100; RR, 1.20; 95% CI, 1.10-1.30, p = 0.04 for interaction) for MI block. Conclusions: This meta-analysis demonstrates that VOM-ABL has superior efficacy and comparable safety over ablation alone in AF patients with long-term follow-up. Moreover, PVI+ and VOM-ABL group sample size ≥ 100 may be associated with a great impact on freedom from AF/AT and MI block, respectively.

9.
Antimicrob Resist Infect Control ; 11(1): 62, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468830

RESUMO

BACKGROUND: Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. OBJECTIVE: This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. METHODS: We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05). CONCLUSIONS: Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.


Assuntos
Cólera , Vibrio cholerae O139 , Vibrio cholerae O1 , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Cólera/tratamento farmacológico , Cólera/epidemiologia , Ciprofloxacina , Doxiciclina , Farmacorresistência Bacteriana , Eritromicina , Humanos , Testes de Sensibilidade Microbiana , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vibrio cholerae O1/genética
10.
Dig Liver Dis ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35490150

RESUMO

BACKGROUND: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare disorder caused by variants in the ABCB11 gene encoding the bile salt export pump (BSEP). We investigated the molecular defect in a PFIC2 infant and rescued the splicing defect with antisense oligonucleotides (ASOs). METHODS: Whole-exome sequencing (WES) revealed compound heterozygous variants in the ABCB11 gene in a PFIC2 patient. Liver biopsy was immunostained for BSEP. The splicing effect of the candidate variants was investigated by minigene assay. ASOs were designed to rescue aberrant splicing. RESULTS: A Chinese girl of two nonconsanguineous healthy parents suffered from low glutamyl transpeptidase cholestasis and showed no response to the ursodeoxycholic acid. WES revealed that the patient was compound heterozygous for two novel variants in the ABCB11 gene: c.76+29T>G and c.390-2A>G. Liver immunohistochemistry showed the absence of BSEP. The variant c.76+29T>G was confirmed to retain 42 bp in the mature mRNA. The variant c.390-2A>G was confirmed to cause exon 6 skipping. We designed two ASOs and identified one of them that efficiently induced pseudoexon exclusion. CONCLUSION: We reported two novel variants of the ABCB11 gene, c.76+29T>G and c.390-2A>G, in a PFIC2 infant, thereby expanding the genotype of PFIC2. Our findings provide evidence for ASOs as a therapeutic approach for PFIC2 patients carrying intronic variants.

11.
J Am Chem Soc ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35467878

RESUMO

It is vital to differentiate catalytic properties between cationic and metallic single atoms at the atomic level. To achieve this, we fabricated well-defined cationic Ni atoms snugged in and metallic Ni atoms supported on monolayered CuO. The Ni cations are chemically inert for CO adsorption even at 70 K but highly active toward O2 dissociation at room temperature. The adsorbed O atoms are active to oxidize incoming CO molecules from the gas phase into CO2, which follows the Eley-Rideal mechanism, in contrast to the Mars-van Krevelen mechanism on CuO-monolayer-supported metallic Ni atoms as well as our previously reported Au and Pt model catalysts. This study helps understand the chemistry of a supported single-metal cation, which is of great importance in heterogeneous catalysis.

12.
J Cardiovasc Med (Hagerstown) ; 23(5): 308-317, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486682

RESUMO

AIM: Lipid abnormalities often occur in patients with diabetes mellitus and the coexistence of diabetes mellitus and dyslipidaemia will increase the risk of cardiovascular diseases. However, the specific effects of sitagliptin on lipid control remain elusive in diabetic patients. The aim of this meta-analysis is to investigate the effects of sitagliptin alone or with other antidiabetic agents on serum lipid control. METHODS: PubMed, Cochrane Library, Embase and the ClinicalTrials.gov website were systematically searched from 2006 (the first year that sitagliptin entered market) to 16 January 2021. Eligible studies were randomized clinical trials (RCTs) of sitagliptin including outcomes of serum total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). RESULTS: A total of 14 RCTs with 2654 patients were identified. Treatment with sitagliptin alone or in combination with other antidiabetic agents significantly reduced serum TC [mean difference (MD) = -5.52 95% confidence interval (95% CI), -7.88 to -3.15; P < 0.00001] and LDL-C (MD = -0.07; 95% CI, -0.14 to 0.00; P < 0.00001) in patients with type 2 diabetes. No statistical significances were found in serum triglycerides (MD = 1.53; 95% CI, -8.22 to 11.28; P = 0.76) or HDL-C (MD = 0.65; 95% CI, -1.59 to 0.29; P = 0.18). Subgroup analyses suggest that sitagliptin can significantly decrease serum LDL-C, TC and triglyceride levels compared with placebo alone, and no statistical significance was found in comparison with the serum HDLC levels. CONCLUSION: Sitagliptin alone or in combination with other antidiabetic agents significantly reduces serum TC and LDL-C in patients with type 2 diabetes mellitus, while no significant difference was observed in serum triglycerides or HDL-C.


Assuntos
Diabetes Mellitus Tipo 2 , Fosfato de Sitagliptina , HDL-Colesterol , LDL-Colesterol , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Triglicerídeos
13.
Front Oncol ; 12: 829230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480120

RESUMO

Background: Early detection of colorectal cancer (CRC) is crucial to the treatment and prognosis of patients. Traditional screening methods have disadvantages. Methods: 231 blood samples were collected from 86 CRC, 56 colorectal adenoma (CRA), and 89 healthy individuals, from which extracellular vesicle long RNAs (exLRs) were isolated and sequenced. An CRC diagnostic signature (d-signature) was established, and prognosis-associated cell components were evaluated. Results: The exLR d-signature for CRC was established based on 17 of the differentially expressed exLRs. The d-signature showed high diagnostic efficiency of CRC and control (CRA and healthy) samples with an area under the curve (AUC) of 0.938 in the training cohort, 0.943 in the validation cohort, and 0.947 in an independent cohort. The d-signature could effectively differentiate early-stage (stage I-II) CRC from healthy individuals (AUC 0.990), as well as differentiating CEA-negative CRC from healthy individuals (AUC 0.988). A CRA d-signature was also generated and could differentiate CRA from healthy individuals both in the training (AUC 0.993) and validation (AUC 0.978) cohorts. The enrichment of class-switched memory B-cells, B-cells, naive B-cells, and mast cells showed increasing trends between CRC, CRA, and healthy cohorts. Class-switched memory B-cells, mast cells, and basophils were positively associated with CRC prognosis while natural killer T-cells, naive B-cells, immature dendritic cells, and lymphatic endothelial cells were negatively associated with prognosis. Conclusions: Our study identified that the exLR d-signature could differentiate CRC from CRA and healthy individuals with high efficiency and exLR profiling also has potential in CRA screening and CRC prognosis prediction.

14.
Front Hum Neurosci ; 16: 829688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463928

RESUMO

Purpose: To explore the changes of cerebral blood flow (CBF) and fractional anisotropy (FA) in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation (rTMS) treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level. Materials and Methods: In total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls (HCs) were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales. Results: After rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex (CPC) loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment (FMA) scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract (CST). The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus. Conclusion: Our results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST.

15.
Mikrochim Acta ; 189(5): 189, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412090

RESUMO

A novel ratiometric electrochemical sensor was developed based on a carbon cloth electrodeposited with silver nanoparticles and drop-coated by covalent organic framework (COF-LZU1) for simultaneous determination of bisphenol A (BPA) and bisphenol S (BPS). Carbon cloth exhibited a significantly larger electrochemical active area than common glassy carbon electrodes (27.5 times). Silver nanoparticles not only provided a stable reference signal but also enhanced electroactivity for the oxidation of BPA and BPS. COF-LZU1 with good adsorption performance and large periodic π-arrays promoted the enrichment of BPA and BPS to further increase the current response. Compared with the traditional single-signal electrochemical sensor, the developed ratiometric sensor exhibited better reproducibility and a wider linear range for BPA and BPS from 0.5 to 100 µM with a limit of detection of 0.15 µM. Furthermore, the developed sensor showed excellent stability and superior anti-interference ability. The real sample analysis for BPA and BPS has been successfully carried out in mineral water, electrolyte drink, tea, juice, and beer with recoveries of 88.3-111.7%. The developed ratiometric sensor is expected to be a candidate for the preparation of other electrochemical sensors and the analysis of additional practical samples.


Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Compostos Benzidrílicos , Carbono , Fenóis , Reprodutibilidade dos Testes , Prata
16.
Dermatology ; : 1-10, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35378530

RESUMO

BACKGROUND: Vitiligo is a skin depigmentation disorder that results from the autoimmune destruction of cutaneous melanocytes. Several ocular abnormalities, including uveitis, dry eye, glaucoma, and retinal diseases, have been reported in patients with vitiligo. The aim of our study was to investigate the association of ocular abnormalities with vitiligo. METHODS: This meta-analysis was registered in PROSPERO (CRD42021224167) and adhered to MOOSE checklist and PRISMA guidance for all processes. PubMed, Embase, Web of Science, and Cochrane databases were searched for studies examining the association between ocular abnormalities and vitiligo from inception to December 10, 2020. Studies recruiting patients with Sjogren's syndrome or Vogt-Koyanagi-Harada syndrome were excluded. The primary outcomes were the Schirmer test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) of vitiligo patients compared to the controls. The risk of bias of the selected studies was assessed using the Newcastle-Ottawa Scale (NOS) of case-control studies. RESULTS: This meta-analysis of 16 case-control studies showed that patients with vitiligo had significantly lower Schirmer test values (mean difference [MD], -1.65; 95% CI, -2.81 to -0.49), shorter TBUTs (MD, -4.66; 95% CI, -7.05 to -2.26), higher ocular surface disease indices (MD, 18.02; 95% CI, 5.7-30.35), and thinner subfoveal choroidal thicknesses (MD, -53.10; 95% CI, -69.84 to -36.36). No significant differences were found in the prevalence of glaucoma and the level of intraocular pressure. CONCLUSIONS: Our study supports an association between dry eye and thinner subfoveal choroidal thickness in patients with vitiligo. Dermatologists should be aware of these possible comorbidities and refer vitiligo patients with ocular symptoms to ophthalmologists for further management.

17.
Onco Targets Ther ; 15: 299-311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35388272

RESUMO

Background: Aerobic glycolysis plays an important role in bladder cancer (BLCA) progression and chemoresistance. Cyclin-dependent kinase inhibitor-3 (CDKN3), a dual-specificity protein tyrosine phosphatase, has aberrant upregulation in multiple cancer types and is associated with tumorigenesis. However, the role of CDKN3 in BLCA progression and glycolysis has not been elucidated. Purpose: In this study, we investigated the effect and underlying mechanisms of CDKN3 on bladder cancer chemoresistance. Results: This study confirmed that CDKN3 was overexpressed in BLCA tissues and promoted proliferation and migration. Additionally, our results showed a CDKN3-dependent mechanism on chemoresistance; chemoresistance cells were transformed into chemosensitivity cells by CDKN3 knockdown. Additionally, we showed that CDKN3 knockdown decreased glycolysis by inhibiting LDHA expression in BLCA chemoresistance cells. The results also proved that LDHA was an important mediator of CDKN3-regulated BLCA resistance. LDHA overexpression reversed glycolysis inhibition and chemosensitivity induced by CDKN3 downregulation. Conclusion: These data collectively identified a vital role of CDKN3 in glycolysis and chemoresistance by regulating LDHA expression in BLCA cells, providing a possible therapeutic strategy for treating BLCA.

18.
Oxid Med Cell Longev ; 2022: 5585384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450406

RESUMO

Heat shock protein 90 (HSP90) is widely found in brain tissue. HSP90 inhibition has been proven to have neuroprotective effects on ischemic strokes. In order to study the role of HSP90 in traumatic brain injury (TBI), we carried out the present study. A novel inhibitor of the HSP90 protein, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DA), has been investigated for its function on the blood-brain barrier (BBB) damage after traumatic brain injury (TBI) in mouse models. These C57BL/6 mice were used as a TBI model and received 17-DA (0.1 mg/kg/d, intraperitoneally) until the experiment ended. To find out whether 17-DA may protect against TBI in vitro, bEnd.3 cells belonging to mouse brain microvascular endothelium were used. The HSP90 protein expressions were raised after TBI at the pericontusional area, especially at 3 d. Our study suggested that 17-DA-treated mice improved the recovery ability of neurological deficits and decreased brain edema, Evans blue extravasation, and the loss of tight junction proteins (TJPs) post-TBI. 17-DA significantly promoted cell proliferation and alleviated apoptosis by inhibiting the generation of intracellular reactive oxygen species (ROS) to downregulate cleaved caspase-3, matrix metallopeptidase- (MMP-) 2, MMP-9, and P-P65 in bEnd.3 cells after the injury. As a result, we assumed that the HSP90 protein was activated post-TBI, and inhibition of HSP90 protein reduced the disruption of BBB and improved the neurobehavioral scores in a mouse model of TBI through the action of 17-DA, which inhibited ROS generation and regulated MMP-2, MMP-9, NF-κB, and caspase-associated pathways. Thus, blocking HSP90 protein may be a potential therapeutic strategy for TBI.


Assuntos
Barreira Hematoencefálica , Lesões Encefálicas Traumáticas , Animais , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP90 , Proteínas de Choque Térmico/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
19.
Commun Biol ; 5(1): 324, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388143

RESUMO

Alcohol-induced osteonecrosis of the femoral head (ONFH) is a disabling disease with a high incidence and elusive pathogenesis. Here, we used single-cell RNA sequencing to explore the transcriptomic landscape of mid- and advanced-stage alcohol-induced ONFH. Cells derived from age-matched hip osteoarthritis and femoral neck fracture samples were used as control. Our bioinformatics analysis revealed the disorder of osteogenic-adipogenic differentiation of stromal cells in ONFH and altered regulons such as MEF2C and JUND. In addition, we reported that one of the endothelial cell clusters with ACKR1 expression exhibited strong chemotaxis and a weak angiogenic ability and expanded with disease progression. Furthermore, ligand-receptor-based cell-cell interaction analysis indicated that ACKR1+ endothelial cells might specifically communicate with stromal cells through the VISFATIN and SELE pathways, thus influencing stromal cell differentiation in ONFH. Overall, our data revealed single cell transcriptome characteristics in alcohol-induced ONFH, which may contribute to the further investigation of ONFH pathogenesis.


Assuntos
Osteonecrose , Transcriptoma , Células Endoteliais/patologia , Etanol , Cabeça do Fêmur/patologia , Perfilação da Expressão Gênica , Humanos , Osteonecrose/patologia , Células Estromais
20.
Front Endocrinol (Lausanne) ; 13: 862545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399943

RESUMO

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal , Fator B de Crescimento do Endotélio Vascular , Nefropatias Diabéticas/etiologia , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Fator B de Crescimento do Endotélio Vascular/sangue
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