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1.
Mater Today Bio ; 13: 100195, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35024598

RESUMO

Injectable thermo-sensitive hydrogels composed of small intestinal submucosa (SIS) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs) are desired for bone regeneration. However, poor mechanical properties limit the clinical application of SIS hydrogels. Herein, the mechanical properties of SIS hydrogels incorporated with 3-(3,4-dihydroxyphenyl) propionic acid (CA) are assessed. The results show that the mechanical properties of SIS hydrogels are improved. In addition, the retention and stability of exosomes over time at the defect site are also challenges. Fusion peptides are designed by connecting collagen-binding domines (CBDs) of collagen type I/III with exosomal capture peptides CP05 (CRHSQMTVTSRL) directly or via rigid linkers (EAAAK). In vitro experiments demonstrate that fusion peptides are contribute to promoting the positive effect of exosomes on osteogenic differentiation of BMSCs. Meanwhile, the results of hydrogels combining exosomes and fusion peptides in the treatment of rat skull defect models reveal that fusion peptides could enhance the retention and stability of exosomes, thereby strengthen the therapeutic effect for skull defects. Therefore, SIS hydrogels with CA modified by fusion peptides and exosomes appear to be a promising strategy in bone regenerative medicine.

2.
World J Pediatr ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984641

RESUMO

BACKGROUND: This study aimed to describe length of stay (LOS) to discharge and site variations among very preterm infants (VPIs) admitted to 57 Chinese neonatal intensive care units (NICUs) and to investigate factors associated with LOS for VPIs. METHODS: This retrospective multicenter cohort study enrolled all infants < 32 weeks' gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network, within 7 days after birth in 2019. Exclusion criteria included major congenital anomalies, NICU deaths, discharge against medical advice, transfer to non-participating hospitals, and missing discharge date. Two multivariable linear models were used to estimate the association of infant characteristics and LOS. RESULTS: A total of 6580 infants were included in our study. The overall median LOS was 46 days [interquartile range (IQR): 35-60], and the median corrected gestational age at discharge was 36 weeks (IQR: 35-38). LOS and corrected gestational age at discharge increased with decreasing gestational age. The median corrected gestational age at discharge for infants at 24 weeks, 25 weeks, 26 weeks, 27-28 weeks, and 29-31 weeks were 41 weeks, 39 weeks, 38 weeks, 37 weeks and 36 weeks, respectively. Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals. CONCLUSIONS: The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents. Large variation of LOS independent of infant characteristics existed, indicating variation of care practices requiring further investigation and quality improvement.

3.
Curr Med Sci ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34985612

RESUMO

OBJECTIVE: The eukaryotic release factor 3a (eRF3a), a member of the eukaryotic peptide chain release factor family, is overexpressed in several types of cancer. This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer. METHODS: Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. RESULTS: eRF3a was significantly highly expressed in liver cancer cells, and its expression level was negatively correlated with the clinical prognosis of patients. In addition, in vitro experiments showed that eRF3a could promote the proliferation and migration of liver cancer cells through the ERK and JNK signaling pathways. CONCLUSION: This study suggests that eRF3a may be a potential prognostic marker for liver cancer and act as an oncogene by activating JNK and ERK signaling; therefore, eRF3a may be a new target for the treatment of liver cancer.

4.
J Formos Med Assoc ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35022156

RESUMO

BACKGROUND/PURPOSE: The early progression of disease (POD) of Hodgkin lymphoma (HL) leads to a poor prognosis. To identify risk factors for early POD, this retrospective two-center cohort analysis was conducted. METHODS: Medical records of HL patients between 1998 and 2020 from two referral centers were reviewed. RESULTS: Two-hundred and sixty-nine patients were analyzed. The distribution of early vs. advanced stages was 51.1 vs. 48.9%, respectively. The 5-year progression free survival (PFS) was 63%, and the overall survival (OS) was 87% with a median follow-up of 52.0 months. The complete remission (CR) rate was 85.7%. Disease progression or relapsed disease occurred in 33.9% (n = 85) of patients while 17.0% of this cohort had early POD within 12 months of induction therapy. Patients with early POD had a worse median OS than those without (p < 0.001). Failure to achieve post-induction CR and high international prognostic score (IPS, 3-7) were independent risk factors for early POD. Compared with chemotherapy alone, consolidative radiotherapy after induction chemotherapy was associated with a lower risk of early POD (21.3% vs. 6.2%, p = 0.006). CONCLUSION: High IPS was an independent risk factor for early POD, which was less observed in those with consolidative radiotherapy.

5.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112177, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34749194

RESUMO

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.


Assuntos
Hipertermia Induzida , Nanopartículas , Animais , Biomimética , Linhagem Celular Tumoral , Células HeLa , Humanos , Verde de Indocianina , Camundongos , Fármacos Fotossensibilizantes , Fototerapia , Terapia Fototérmica , Polifenóis , Serina-Treonina Quinases TOR
6.
Coron Artery Dis ; 31(1): e67-e72, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010192

RESUMO

BACKGROUND: The optimal strategy of percutaneous coronary intervention (PCI) for isolated left anterior descending (LAD) ostial lesions remains debatable. This study aimed to compare clinical outcomes of patients with isolated LAD ostial stenosis treated by single-stent crossover versus accurate ostial stenting. METHODS: A total of 216 eligible consecutive patients with isolated de novo LAD ostial stenosis were enrolled, and were stratified according to the stenting techniques. Clinical follow-up was performed by review of medical charts or telephone contact with the patients, and repeat angiography was made at 9-12 months after the procedure. Major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, non-fatal stroke and target vessel revascularization (TVR) were recorded. RESULTS: Single-stent crossover and accurate ostial stenting were applied to 78 (36%) and 138 (64%) patients, respectively. During a mean of 13 ± 4.1 months of follow-up, the rate of composite MACE (19.6 vs. 8.9%; P = 0.040) was higher in LAD ostial stenosis patients treated with accurate ostial stenting than those treated with single-stent crossover technique, mainly driven by more frequent TVR (17.4 vs. 7.7%; P = 0.048). PCI strategy was an independent predictor of MACE (hazard ratio 2.561; 95% CI, 1.041-6.299; P = 0.021) in the multivariable Cox regression analysis. CONCLUSIONS: Our retrospective study suggests that the single-stent crossover technique is associated with a better 1-year clinical outcome compared with accurate ostial stenting in patients with isolated LAD ostial stenosis.

7.
Infect Drug Resist ; 14: 5131-5136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880637

RESUMO

Purpose: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection. Methods: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement. Results: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin. Conclusion: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection.

8.
J Cell Mol Med ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34866322

RESUMO

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(6): 690-697, 2021 Dec 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34859629

RESUMO

OBJECTIVES: This study was performed to investigate the effects of hyperbaric oxygen and other approaches for treating the osteoradionecrosis of the jaws (ORNJ) systematically. METHODS: According to the preset inclusion and exclusion criteria, randomized controlled trials and cohort studies on hyperbaric oxygen in the treatment of ORNJ were screened, and foreign language databases such as PubMed, EMBASE, and Cochrane library were searched via a computer; Chinese databases such as CNKI, VIP, Wanfang data, and CBM were searched from the established database to September 2020. Relevant books were searched manually to collect all literatures on the efficacy of hyperbaric oxygen and its related therapies in ORNJ treatment. Two researchers were independent and mutually blind, the papers were selected, data were collected, and the bias risk was evaluated. If any difference was detected, it would be decided by discussion or arbitrated by a third party. The data related to the efficacy of hyperbaric oxygen and its related therapy in the treatment of the ORNJ were extracted, and the Revman5.4 software was used for Meta-analysis. In case of large heterogeneity, sensitivity analysis was performed. A funnel chart was used to evaluate possible publication bias qualitatively. RESULTS: Four randomized controlled trials and seven cohort studies were included in Meta-analyses. In ORNJ treatment, no significant differences between the group subjected to hyperbaric oxygen and both surgery and antibiotics and the group that underwent both surgery and antibiotics (RR=1.16, 95%CI: 0.86~1.58, P>0.05); between the group with hyperbaric oxygen and the group with antibiotics (RR=0.83, 95%CI: 0.63~1.09, P>0.05); between the group with hyperbaric oxygen and the group with antifibrotic drugs (RR=0.07, 95%CI: 0.00~155.86, P>0.05); between the group with single or combined use of HBO and the group with other intervention methods (RR=0.89, 95%CI: 0.67~1.19, P>0.05). CONCLUSIONS: Hyperbaric oxygen therapy cannot replace surgery and antibiotic therapy. Hyperbaric oxygen therapy is not superior to antibiotics and antifibrotic drugs, but the benefits of antifibrotic drugs should be further explored.

10.
Front Cardiovasc Med ; 8: 756213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917661

RESUMO

Background: The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear. Methods: A total of 11,798 middle-aged subjects from the prospective, population-based cohort were included in this analysis. The QTc interval corrected for heart rate was measured on two occasions around 3 years apart in the Atherosclerosis Risk in Communities (ARIC) study. The ΔQTc interval was calculated by evaluating a change in QTc interval from visit 1 to visit 2. Results: After a median follow-up of 19.5 years, the association between the dynamic change of QTc interval and endpoints of death was U-shaped. The multivariate-adjusted hazard ratios (HRs) comparing subjects above the 95th percentile of Framingham-corrected ΔQTc (ΔQTcF) (≥32 ms) with subjects in the middle quintile (0-8 ms) were 2.69 (95% CI, 1.68-4.30) for SCD, 2.51 (1.68-3.74) for coronary heart disease death, 2.10 (1.50-2.94) for cardiovascular death, and 1.30 (1.11-1.55) for death from any cause. The corresponding HRs comparing subjects with a ΔQTcF below the fifth percentile (<-23 ms) with those in the middle quintile were 1.82 (1.09-3.05) for SCD, 1.83 (1.19-2.81) for coronary heart disease death, 2.14 (1.51-2.96) for cardiovascular death, and 1.31 (1.11-1.56) for death from any cause. Less extreme deviations of ΔQTcF were also associated with an increased risk of death. Similar, albeit weaker associations also were observed with ΔQTc corrected with Bazett's formula. Conclusions: A dynamic change of QTc interval is associated with increased mortality risk in the general population, indicating that repeated measurements of the QTc interval may be available to provide additional prognostic information.

11.
Rapid Commun Mass Spectrom ; : e9234, 2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34897870

RESUMO

RATIONALE: Mycoplasma pneumoniae has become one of the common pathogens causing pediatric respiratory infections. In clinical diagnosis, throat swabs are very difficult to obtain from children, and there is a possibility of false positive results; hence, there are few clinically available diagnostic methods. METHODS: In this study, Q Exactive liquid chromatography tandem mass spectrometry was used to analyze the metabolites in the urine of healthy children (HC) and Mycoplasma pneumoniae pneumonia in children (MPPC) patients. A multivariate statistical analysis was performed to screen the differential metabolites. Based on the HMDB and KEGG, the possible metabolic pathways subject to biological alteration were identified. RESULTS: Compared with HC, 73 different metabolites in MPPC patients disrupted nine metabolic pathways through different change trends; after integrating various parameters, 20 significantly different metabolites were identified as MPPC potential biomarkers. Through the above two analysis modes, acetyl phosphate and 2,5-dioxopentanoate were both screened out and used as potential biomarkers for the early diagnosis of MPPC for the first time. CONCLUSION: Through the characterization of 20 potential biomarkers, it provides scientific basis for predicting and diagnosing MPPC. This article further indicates that urine metabolic profiling has great potential in diagnosing MPPC and can effectively prevent the disease from causing further deterioration.

12.
Oral Dis ; 2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-34954846

RESUMO

OBJECTIVES: To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia. METHODS: We searched PubMed, Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases. Literature search, screening, study selection, data collection, data extraction and assessment of bias risk were independently conducted by two reviewers. The study appraisal was performed by Cochrane Collaboration's tool for assessing bias risk. The systematic review registration number was PROSPERO-CRD42021241322. All statistical analyses were performed using Review Manager version 5.4. RESULTS: Five original articles involving 244 patients with xerostomia who received topical sialogogue spray (malic acid 1%) or placebo for two weeks were included in this review. Based on the questionnaire survey, the topical sialogogue spray (malic acid 1%) improved the symptoms of dry mouth significantly better than the placebo, which was reflected in the Dry Mouth Questionnaire (DMQ), Xerostomia Inventory (XI) and Visual Analogue Scale (VAS) scores. Regarding the increase in unstimulated and stimulated saliva flow rates, the intervention group was also better than the placebo group after a two-week course of treatment. CONCLUSIONS: Although the included studies are limited, our results show that topical sialogogue spray (malic acid 1%) is an effective method for the treatment of xerostomia. Additional randomised controlled trials in the future are needed to provide high-quality evidence of this therapy and to improve clinical practice guidelines.

13.
Bioorg Chem ; 119: 105547, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34906858

RESUMO

CDK4/6 were attractive chemotherapeutic targets for the treatment of malignant tumors, CDK4/6 selective inhibitors have made outstanding contributions in the treatment of breast cancer. However, these inhibitors share a single skeleton of N-(pyridin-2-yl) pyrimidin-2-amine which cannot overcome the side effects in clinical application. In our previous study, an N'- acetylpyrrolidine-1-carbohydrazide was hit as the initial fragment by analyzing the active site characteristics of CDK6. Two series of N-(pyridin-3-yl) proline were obtained by fragment growth method. The QSAR study was carried out according to the in vitro activities data against CDK4/6, and two compounds 7c and 7p with potent inhibitory activities were found to interact with CDK4 in different binding conformation. They showed potential inhibition of cell proliferation against the breast cancer cell, and 7c exhibited promised anti-breast cancer effect in vivo.

14.
Cell Rep ; 37(13): 110177, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34965426

RESUMO

The hippocampus is a temporal lobe structure critical for cognition, such as learning, memory, and attention, as well as emotional responses. Hippocampal dysfunction can lead to persistent anxiety and/or depression. However, how millions of neurons in the hippocampus are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing the coagulation factor c homolog (COCH) gene. COCH-expressing neurons or COCH neurons are topographically segregated in the distal region of the ventral CA3 hippocampus and express Mtf1 and Cacna1h. MTF1 activation of Cacna1h transcription in COCH neurons encodes the ability of COCH neurons to burst action potentials and cause social-stress-induced anxiety-like behaviors by synapsing directly with a subset of GABAergic inhibitory neurons in the lateral septum. Together, this study provides a molecular and circuitry-based framework for understanding how COCH neurons in the hippocampus are assembled to engage social behavior.

15.
Chemosphere ; : 132771, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34740698

RESUMO

In this study, a two-step functionalizing strategy by combining co-condensation with grafting procedures was employed to synthesize well-ordered Amino- and Thiol-Bifunctionalized SBA-15 (ATBS) mesoporous silica. Its physicochemical properties, performance, and mechanisms in immobilization of toxic metals Pb and Cd in water and soil were investigated. After bi-functionalization, X-ray diffractometer, transmission electron microscope, and N2 adsorption-desorption measurements confirmed that the ATBS maintained a highly-ordered mesoporous structure, large surface area and pore volume. The elemental analysis, Fourier transform infrared spectroscopy and X-ray Photoelectron Spectroscopy (XPS) evidenced the successful incorporation of amine and thiol groups into ATBS. These structure and functional characteristics of ATBS benefited Pb and Cd sorption. Sorption isotherms of Pb and Cd were better fit with Sips and Redlich-Peterson models. Sorption kinetics suggested that Pb sorption was mainly regulated by chemical reactions, whereas both diffusion process and chemical reactions were rate-regulating steps in Cd sorption. ATBS showed the maximum sorption capacities for Pb and Cd at 120 and 38 mg g-1, respectively. The sorption mechanisms revealed by XPS measurements suggested that Cd sorption was mainly attributed to thiol groups while Pb was efficiently bond to both thiol and amino groups. High and stable sorption efficiencies were attained in the pH range of 4-6, with a higher affinity towards Pb than Cd. Furthermore, its ability to immobilize Pb and Cd in soils was examined with an incubation experiment, which showed that ATBS reduced 30-56% of MgCl2-extractable Pb and Cd in a contaminated soil. The synthesized sorbent via the two-step functionalizing strategy shows high sorption efficiency towards Pb and Cd, and thus it has potential application in remediating Pb and Cd contaminated water and soils.

17.
Front Cell Neurosci ; 15: 768059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744634

RESUMO

Microglia dynamically monitor the microenvironment of the central nervous system (CNS) by constantly extending and retracting their processes in physiological conditions, and microglia/macrophages rapidly migrate into lesion sites in response to injuries or diseases in the CNS. Consequently, their migration ability is fundamentally important for their proper functioning. However, the mechanisms underlying their migration have not been fully understood. We wonder whether the voltage-gated proton channel HVCN1 in microglia/macrophages in the brain plays a role in their migration. We show in this study that in physiological conditions, microglia and bone marrow derived macrophage (BMDM) express HVCN1 with the highest level among glial cells, and upregulation of HVCN1 in microglia/macrophages is presented in multiple injuries and diseases of the CNS, reflecting the overactivation of HVCN1. In parallel, myelin debris accumulation occurs in both the focal lesion and the site where neurodegeneration takes place. Importantly, both genetic deletion of the HVCN1 gene in cells in vitro and neutralization of HVCN1 with antibody in the brain in vivo promotes migration of microglia/macrophages. Furthermore, neutralization of HVCN1 with antibody in the brain in vivo promotes myelin debris clearance by microglia/macrophages. This study uncovers a new role of HVCN1 in microglia/macrophages, coupling the proton channel HVCN1 to the migration of microglia/macrophages for the first time.

18.
Cell Regen ; 10(1): 34, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725734

RESUMO

Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensive investigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regeneration took place in the beautiful ocean city of Zhoushan, Zhejiang, China. This biennial conference attracted ~ 300 academic attendees: students, postdoctoral fellows, and principal investigators, in addition to few industrial investigators. The mixed live and virtual talks covered the broad field of organ regeneration from different animal organisms to human organoids, and concluded with some impressive advances on inflammatory signaling, regenerative signaling mechanisms, new technologies, and applications for organ regeneration.

19.
Nucleic Acids Res ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751395

RESUMO

LncRNAWiki, a knowledgebase of human long non-coding RNAs (lncRNAs), has been rapidly expanded by incorporating more experimentally validated lncRNAs. Since it was built based on MediaWiki as its database system, it fails to manage data in a structured way and is ineffective to support systematic exploration of lncRNAs. Here we present LncRNAWiki 2.0 (https://ngdc.cncb.ac.cn/lncrnawiki), which is significantly improved with enhanced database system and curation model. In LncRNAWiki 2.0, all contents are organized in a structured manner powered by MySQL/Java and curators are able to submit/edit annotations based on the curation model that includes a wider range of annotation items. Moreover, it is equipped with popular online tools to help users identify lncRNAs with potentially important functions, and provides more user-friendly web interfaces to facilitate data curation, retrieval and visualization. Consequently, LncRNAWiki 2.0 incorporates a total of 2512 lncRNAs and 106 242 associations for disease, function, drug, interacting partner, molecular signature, experimental sample, CRISPR design, etc., thus providing a comprehensive and up-to-date resource of functionally annotated lncRNAs in human.

20.
Int J Pharm ; 611: 121297, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822966

RESUMO

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H2O2-responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1ß, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE-/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy.

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