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1.
Carbohydr Polym ; 276: 118735, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823771

RESUMO

Chitosan was prepared by hydrothermal deacetylation from multi-step protein purification chitin based on Trypoxylus dichotomus, for treating heavy metals and antibiotics. Chitosan with higher deacetylation degree and lower molecular weight were synthesized. The adult chitosan was composed of nanofibers arranged more evenly, showing higher yield, thermal stabilities and antimicrobial properties. The adsorption capacities of Cu2+ and Fe3+ were 462 and 270 mg/g, lower than 934 mg/g of Pb2+. Levofloxacin and tetracycline hydrochloride adsorption capacity were 26 and 22 mg/g, lower than 67 mg/g of sulfamethoxazole. In addition, compared with single pollutants, the adsorption of sulfamethoxazole and Pb2+ can increase by 6% and 5% when they act as composite contaminants. The adsorption procedure can be well described by pseudo-second-order kinetics and Langmuir isothermal model, indicating it a homogeneous monolayer chemisorption. Therefore, the Trypoxylus dichotomus source chitosan prepared by hydrothermal deacetylation has potential applications in the adsorption of complex pollutants.

2.
J Inorg Biochem ; 226: 111655, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34740040

RESUMO

A novel Cu(II)-based coordination polymer [chemical composition, {[CuL(CH3CO2)](H2O)(DMF)}n (1, DMF = N,N-dimethylformamide) was successfully prepared via Cu(NO3)2·3H2O reaction with HL ligand in DMF and H2O mixture by using a hetero-donor ligand 4-(bis(4-(4H-1,2,4-triazol-4-yl)phenyl)amino)benzoic acid (HL) featuring carboxylic acid and triazole groups. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to determine miR-9-5p expression in cervical cancer cells after compound treatment. Bioinformatic analysis and luciferase reporter assay were utilized to confirm miR-9-5p and BRCA1 interaction to discover the potential goal of miR-9-5p in cervical cancer cells. Cell Counting Kit-8 (CCK-8) and reactive oxygen species (ROS) detection kits were adopted to examine cancer cell proliferation and ROS accumulation after compound treatment.

3.
Phytomedicine ; 94: 153816, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34752969

RESUMO

BACKGROUND: The identification of novel therapeutic candidates from natural products for the development of chemoresistant glioblastoma multiforme (GBM) treatment has been a highly significant and effective strategy. PURPOSE: Sesquiterpenes are a class of naturally occurring 15-carbon isoprenoid compounds, and several types of sesquiterpenes have the ability to induce growth inhibition and apoptosis in a variety of cancer cell lines. In the present study, 56 sesquiterpenes of five types, namely, eudesmane-type (I) (1-24), eremophilane-type (II) (25-32), cadinane-type (III) (33-41), guaiane-type (IV) (42-49), and oplopanone-type (V) (50-56), were screened for their antiglioma activity, structure-activity relationship analysis (SAR), and underlying mechanism based on patient-derived recurrent GBM strains, patient-derived GBM cell sphere, GBM organoid (GBO) models, and temozolomide (TMZ)-resistant GBM cell lines. RESULTS: We found that compound 12 (oxyphyllanene B, OLB) showed the most potent antiglioma activity, and we confirmed that OLB could induce apoptosis in a time- and dose-dependent manner in TMZ-resistant GBM cells and GBOs. SAR announced that the presence of an α, ß-unsaturated carbonyl moiety was likely to enhance cytotoxic activities. Mechanistic studies demonstrated that OLB induced abnormal changes in ER and mitochondria-associated membrane (MAM) networks, which triggered ER stress, mitochondrial dysfunction, and apoptosis. Furthermore, our findings suggested that OLB-triggered PACS2 activation might form a committed step to disrupt ER-mitochondria communication and showed for the first time that the expression levels of PACS2 might positively correlate with the progression and chemotherapy resistance of glioma. CONCLUSION: Our results indicated that OLB might be a promising candidate for treating TMZ-resistant GBM cells by activating PACS2, which triggered a crucial event to promote the disruption of ER-mitochondria communication and overcome chemotherapy resistance of GBM.

4.
BMJ Open ; 11(11): e049957, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848511

RESUMO

OBJECTIVES: Serum calcium levels (sCa) were reported to be associated with risk of cardiovascular diseases. The aim of this study was to analyse the association between sCa and long-term mortality in patients with acute coronary syndrome (ACS). DESIGN: A retrospective observational cohort study. SETTING: Single-centre study with participants recruited from the local area. PARTICIPANTS: A total of consecutive 13 772 patients with ACS were included in this analysis. Patients were divided based on their sCa profile (≤2.1 mmol/L, 2.1-2.2 mmol/L, 2.2-2.3 mmol/L, 2.3-2.4 mmol/L, 2.4-2.5 mmol/L,>2.5 mmol/L) and followed up for a median of 2.96 years (IQR 1.01-4.07). PRIMARY OUTCOME: Long-term all-cause mortality. RESULTS: During a median follow-up period of 2.96 years, patients with sCa ≤2.1 mmol/L had the highest cumulative incidences of all-cause mortality (16.7%), whereas those with sCa 2.4-2.5 mmol/L had the lowest cumulative incidences of all-cause mortality (3.5%). After adjusting for potentially confounding variables, the Cox analysis revealed that compared with the reference group (sCa 2.4-2.5 mmol/L), all the other groups had higher mortality except for the sCa 2.3-2.4 mmol/L group (HR, 1.32, 95% CI 0.93 to 1.87). Restricted cubic splines showed that the relationship between sCa and all-cause mortality seemed to be U shaped. The optimal sCa cut-off point, 2.35 mmol/L, was determined based on the shape of restricted cubic splines. CONCLUSIONS: Altered serum calcium homeostasis at admission independently predicts all-cause mortality in patients with ACS. In addition, a U-shaped relationship between sCa and all-cause mortality exists, and maintaining sCa at approximately 2.35 mmol/L may minimise the risk of mortality.

5.
Int J Nanomedicine ; 16: 7727-7739, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824531

RESUMO

Introduction: Dental caries is a biofilm-dependent disease that largely relies on the ability of Streptococcus mutans to synthesize exopolysaccharide matrix. Graphene oxide-based metal nanomaterials, as the derivatives of graphene, are potent agents against pathogens by their impressive antibacterial and anti-biofilm biofunctions. Previously, we fabricated the novel graphene oxide-copper nanocomposites (GO-Cu), maintaining a long-term release of copper nanoparticles. Here, the biofunctionalization of GO-Cu nanocomposites against cariogenic S. mutans is investigated. Methods: Growth curve observation and colony forming units counting were applied to detect the antibacterial effect of GO-Cu nanocomposites on S. mutans. Scanning electron microscopy and the crystal violet assay were used to detect nanocomposite effects on biofilm forming ability. The production and distribution of exopolysaccharides within biofilm was analyzed and the expression of genes required for biofilm formation was explored. Moreover, the regulatory landscape of GO-Cu nanocomposites on S. mutans pathogenicity was probed. Results: It has been found that GO-Gu nanocomposites were antibacterial to S. mutans and 10 µg/mL GO-Cu nanocomposites could inhibit the bacteria bioactivity instead of killing them. The biomass of S. mutans biofilm was significantly reduced when treated with 10 µg/mL GO-Cu nanocomposites. Also, 10 µg/mL GO-Cu nanocomposites could alter the biofilm architecture and impair exopolysaccharides production and distribution, and dysregulated the expression of exopolysaccharide-associated genes. Conclusion: In all, we found low-dose GO-Cu nanocomposites could disrupt exopolysaccharide matrix assembly and further impair optimal biofilm development with minimal cytotoxicity. Therefore, GO-Cu nanocomposites can open up a new avenue for the development of alternative anti-caries biomaterials.


Assuntos
Cárie Dentária , Grafite , Nanocompostos , Antibacterianos/farmacologia , Biofilmes , Cariostáticos , Cobre/farmacologia , Humanos , Streptococcus mutans
6.
Pharmgenomics Pers Med ; 14: 1457-1461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819743

RESUMO

Screening and prevention in the early stage of cervical cancer could improve the 5-year survival rate of cervical cancer by up to 90%. The occurrence rate of human papillomavirus (HPV) integration has gradually increased with the development of cervical lesions. Here, we report the case of a 43-year-old woman diagnosed with chronic cervicitis based on cervical biopsy results. After medical consultation, surgery was recommended to the patient considering her 64 HPV integration sites and other biochemical and clinical test results. The pathology result of the conical biopsy obtained during operation confirmed that both her cervix and the glands had high-grade squamous intraepithelial lesion or cervical intraepithelial neoplasia III (HSIL/CIN III). The patient underwent uterectomy and bilateral salpingectomy and was discharged thereafter. The diagnosis of the patient was revised to stage Ia1 cervical cancer. The number of HPV integration sites is suggested to be an auxiliary indicator in the early screening of cervical cancer for predicting high-grade CIN and invasive cervical cancer.

7.
FEBS Open Bio ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826215

RESUMO

Dental pulp tissue engineering is a promising alternative treatment for pulpitis and periapical periodontitis, and dental pulp stem cells (DPSCs) are considered to be the gold standard for dental seed cell research. It has recently been reported that periapical lesions harbor mesenchymal stem cells with the capacity for self-renewal and multilineage differentiation. However, it remains unknown whether these periapical lesion-derived stem cells (PLDSCs) are suitable for dental pulp tissue engineering. To investigate this possibility, PLDSCs and DPSCs were isolated using the tissue outgrowth method and cultured under identical conditions. We then performed in vitro experiments to study their biological characteristics. Our results indicate that PLDSCs proliferate actively in vitro and exhibit similar morphology, immunophenotype and multilineage differentiation ability as DPSCs. Simultaneously, PLDSCs exhibit stronger migrative ability and express more VEGF and GDNF than DPSCs, and PLDSC-derived conditioned medium was more effective in tube formation assay. The mRNA expression levels of immunomodulatory genes HLA-G, IDO and ICAM-1 were also higher in PLDSCs. However, in respect to osteo/odontogenic differentiation, PLDSCs showed weaker ALP staining and lower calcified nodule formation as compared to DPSCs, as well as lower expression of ALP, RUNX2 and DSPP, as confirmed by qRT-PCR. The osteo/odontogenic protein expression levels of DSPP, RUNX2, DMP1 and SP7 were also higher in DPSCs. The present study demonstrates that PLDSCs might have use as seed cells for dental pulp regeneration, especially in achieving enhanced neurovascularization.

8.
J Ginseng Res ; 45(6): 665-675, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34764721

RESUMO

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aß) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aß generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aß deposition by inhibiting NOX2 activation in APP/PS1 mice.

9.
Clin Rheumatol ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626262

RESUMO

OBJECTIVES: Detection of antinuclear antibodies (ANA) by immunofluorescence assay (IFA) is increasingly substituted by multiplex bead-based immunoassay (MBA) and line-blot immunoassay (LIA). This study is to compare the diagnostic performance of MBA and LIA ANA assays on clinically characterized patient samples. METHODS: A total of 728 serum samples from 385 patients with systemic autoimmune rheumatic diseases (SARD), 204 patients with non-SARD diseases, and 139 apparently healthy subjects were tested with the BioPlex 2200 ANA Screen and EuroLine ANA Profile 3 as the representative MBA and LIA technologies and HEp-2 ANA IFA. Clinical data were collected independent of laboratory analysis and later related to the ANA test results. The clinical diagnostic performances were analyzed using Analyse-it software. RESULTS: The MBA demonstrated higher area under curve (AUC) compared to LIA (0.814 vs 0.761, p = 0.002) and HEp-2 IFA (0.814 vs 0.771, p = 0.008). The MBA and LIA ANA methods showed higher specificity (83.8% and 77.0% vs 67.6%, p < 0.001 and p = 0.005) but lower sensitivity (79.0% and 75.3% vs 86.5%, p < 0.001) compared to HEp-2 IFA. The MBA and LIA ANA revealed substantial to excellent agreements on specific antinuclear antibodies except anti-dsDNA, with the total agreement from 92.3 to 99.9% and Cohen's kappa from 0.71 to 0.98. The MBA demonstrated significantly higher sensitivity (58.1% vs 19.8%, p < 0.001) and comparable specificity (95.9% vs 97.5%, p = 0.221) on anti-dsDNA assay for the diagnosis of SLE compared to LIA. CONCLUSIONS: The MBA and LIA ANA assays have higher specificity but lower sensitivity compared to HEp-2 IFA. There are good agreements between MBA and LIA ANA for the specific antinuclear antibodies except for anti-dsDNA. The MBA ANA demonstrated better assay performance compared to LIA as the MBA possesses higher sensitivity and specificity in the diagnosis of SARD. Key Points • The multiplex bead-based immunoassay (MBA) ANA outperformed line-blot immunoassay (LIA) and traditional HEp-2 IFA. • There are good agreements between the MBA BioPlex 2200 ANA Screen and LIA EuroLine ANA Profile 3 for the most of specific antinuclear antibodies except anti-dsDNA. • Additional anti-dsDNA testing is suggested when EuroLine ANA Profile 3 is used for the aid of SLE diagnosis and management. • The positive predictive value of both multiplex ANA assays can be substantially increased without significantly affecting negative predictive value by using at least two specific antinuclear antibodies for reporting a positive ANA result.

10.
Front Med (Lausanne) ; 8: 724344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604259

RESUMO

Topical antiaging products are often a first-line intervention to counter visible signs of facial photoaging, aiming for sustained cosmetic improvement. However, prolonged application of a single active topical compound was observed clinically to lead to a plateau effect in improving facial photoaging. In view of this, we set out to reduce this effect systematically using a multi-tiered approach with laboratory evidence and clinical trials. The objective of the study was to evaluate the effects of active topical ingredients applied either alone, in combination, or in a rotational manner on modulation of facial photoaging. The study methodology included in vitro, organotypic, and ex vivo skin explants; in vivo biopsy study; as well as clinical trials. We demonstrate for the first time that a pair of known antiaging ingredients applied rotationally, on human dermal fibroblasts, maximized pro-collagen I production. Indeed, rotational treatment with retinol and phytol/glycolic acid (PGA) resulted in better efficacy than application of each active ingredient alone as shown by explants and in vivo biopsy study, with penetration of active ingredients confirmed by Raman spectroscopy. Furthermore, two split-face, randomized, double-blinded clinical trials were conducted, one for 12 months to compare treated vs. untreated and the other for 6 months followed by a 2-month regression to compare treated vs. commercially marketed products. In both studies, rotational regimen showed superior results to its matching comparison as assessed by clinical grading and image analysis of crow's feet wrinkles. In conclusion, rotational regimen using retinol and PGA is effective in treating facial photoaging signs with long-lasting benefits.

11.
Int J Hypertens ; 2021: 3275081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646579

RESUMO

Objective: Preeclampsia (PE) is a severe complication in pregnancy and a leading cause of maternal and infant mortality. However, the exact underlying etiology of PE remains unknown. Emerging evidence indicates that the cause of PE is associated with genetic factors. Therefore, the aim of this study is to identify susceptibility genes to PE. Materials and Methods: Human Exome BeadChip assays were conducted using 370 cases and 482 controls and 21 loci were discovered. A further independent set of 958 cases and 1007 controls were recruited for genotyping to determine whether the genes of interest ROS1 and PTPRK are associated with PE. Immunohistochemistry was used for localization. Both qPCR and Western blotting were utilized to investigate the levels of PTPRK in placentas of 20 PE and 20 normal pregnancies. Results: The allele frequency of PTPRK rs3190930 differed significantly between PE and controls and was particularly significant in severe PE subgroup and early-onset PE subgroup. PTPRK is primarily localized in placental trophoblast cells. The mRNA and protein levels of PTPRK in PE were significantly higher than those in controls. Conclusion: These results suggest that PTPRK appears to be a previously unrecognized susceptibility gene for PE in Han Chinese women, and its expression is also associated with PE, while ROS1 rs9489124 has no apparent correlation with PE risk.

12.
Ann Phys Rehabil Med ; 65(4): 101570, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536570

RESUMO

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction requires an extended period of postoperative rehabilitation. Psychological factors can affect recovery after surgery. Study of psychological factors is still limited to self-motivation, fear and pain. Study of personality traits associated with early rehabilitation outcome after ACL reconstruction is scarce. OBJECTIVE: We aimed to explore the effect of personality traits on early rehabilitation after ACL reconstruction and provide a reference for clinicians in designing a personalized rehabilitation plan. METHODS: This prospective analysis investigated 155 patients at 3 and 6 months after ACL reconstruction. Follow-up involved administration of a general data questionnaire, the Chinese Big Five Personality Inventory Brief Version, the Tegner activity score, the International Knee Documentation Committee Subjective Knee Score, the Knee injury and Osteoarthritis Outcome Score, the Lysholm Score and a balance test. RESULTS: Among the 155 patients included (124 males), Neuroticism was negatively correlated with subjective knee scores at 3 and 6 months after surgery (p<0.001). The odds of a poor balance test result was increased for each 1-point increase in Neuroticism score (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.28-2.36, p<0.001). We found a positive correlation between Conscientiousness score and subjective knee scores at 3 and 6 months after surgery (p<0.001). For every 1-point increase in Conscientiousness score, the odds of a poor balance test result were decreased (OR 0.29, 95% CI 0.16-0.54, p<0.001). Agreeableness and Openness to experience scores were positively correlated with subjective knee scores at 3 and 6 months after surgery (p<0.001). We found no correlation between Extraversion and subjective knee scores at 3 and 6 months after surgery (p>0.05) but a positive correlation with the Tegner activity score at 3 and 6 months after surgery (p<0.05). CONCLUSION: We found a significant correlation between the Big Five personality dimensions and the early rehabilitation effect after ACL reconstruction, which can provide a reference for clinicians in designing a personalized rehabilitation plan.

13.
ACS Appl Mater Interfaces ; 13(39): 46213-46224, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34546708

RESUMO

Acute ischemic stroke has become the major cause of mortality and disability worldwide. Following ischemic stroke, the reperfusion injury is mainly mediated by the burst of reactive oxygen and nitrogen species (RONS). Therefore, blocking the excessive production or removing RONS holds great promise as a potential therapeutic strategy. Herein, we developed a Co-doped Fe3O4 nanozyme that is capable of scavenging H2O2, O2•-, •NO, and ONOO- in vitro and in vivo and provides neuroprotection against ischemic stroke. In vitro experiments showed that pre-incubation with the Co-Fe3O4 nanozyme could prevent neurotoxicity and neuroinflammation induced by H2O2 or lipopolysaccharide, respectively, in HT22 cells. After intravenous administration, the Co-Fe3O4 nanozyme showed no signs of toxicity in peripheral organs of C57BL/6J mice, even after prolonged delivery for 4 weeks. In permanent photothrombotic stroke model and transient middle cerebral artery occlusion stroke model, the Co-Fe3O4 nanozyme specifically accumulated in the infarct rim at 72 h post-stroke and was endocytosed by neurons, astrocytes, microglia, and endothelial cells. Importantly, the Co-Fe3O4 nanozyme delivery reduced the infarct volume in both stroke models. The observation that the Co-Fe3O4 nanozyme was efficacious in two well-characterized ischemic stroke models provides strong evidence that it represents a powerful tool for targeting oxidative and nitrosative stress in the ischemic brain.

14.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34523690

RESUMO

Aging is often accompanied by liver injury and fibrosis, eventually leading to the decline in liver function. However, the mechanism of aging­induced liver injury and fibrosis is still not fully understood, to the best of our knowledge, and there are currently no effective treatment options available for liver aging. Ginsenoside Rg1 (Rg1) has been reported to exert potent anti­aging effects due to its potential antioxidant and anti­inflammatory activity. The present study aimed to investigate the protective effect and underlying mechanism of action of Rg1 in aging­induced liver injury and fibrosis in senescence­accelerated mouse prone 8 (SAMP8) mice treated for 9 weeks. The histopathological results showed that the arrangement of hepatocytes was disordered, vacuole­like degeneration occurred in the majority of cells, and collagen IV and TGF­ß1 expression levels, that were detected via immunohistochemistry, were also significantly upregulated in the SAMP8 group. Rg1 treatment markedly improved aging­induced liver injury and fibrosis, and significantly downregulated the expression levels of collagen IV and TGF­ß1. In addition, the dihydroethylene staining and western blotting results showed that Rg1 treatment significantly reduced the levels of reactive oxygen species (ROS) and IL­1ß, and downregulated the expression levels of NADPH oxidase 4 (NOX4), p47phox, p22phox, phosphorylated­NF­κB, caspase­1, apoptosis­associated speck­like protein containing a C­terminal caspase recruitment domain and the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which were significantly upregulated in the liver tissues of elderly SAMP8 mice. In conclusion, the findings of the present study suggested that Rg1 may attenuate aging­induced liver injury and fibrosis by reducing NOX4­mediated ROS oxidative stress and inhibiting NLRP3 inflammasome activation.

15.
ACS Omega ; 6(34): 22410-22421, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34497930

RESUMO

Endothelial cell damage is an important pathological basis for the deterioration of acute ischemia stroke. Our previous studies have been exploring the mechanism of blood-brain barrier (BBB) endothelial cell injury in the early stage of cerebral ischemia. Exosomes act as an important intercellular player in neurovascular communication. However, the characteristic of exosomes derived from BBB endothelial cells in early ischemic stroke is poorly understood. We exposed cultured brain microvascular endothelial cells (bEnd.3) to 3 h oxygen glucose deprivation (OGD) to mimic early cerebral ischemia in vitro and compared miRome and surface protein contents of exosomes derived from bEnd.3 cells by miRNA sequencing and the proximity barcoding assay (PBA). A total of 346 differentially miRNA (159 upregulated and 187 downregulated) were identified via miRNA-Seq in bEnd.3 cells after exposure to OGD for 3 h. Moreover, Gene Ontology (GO) and KEGG pathway analyses showed that cell proliferation- and angiogenesis-associated miRNAs were significantly affected. The abnormal changes in top eight miRNAs were further verified by a quantitative polymerase chain reaction (qPCR). PBA experiments showed that the numbers of exosomes carrying the following proteins increased significantly under ischemia, including bFGF, CD146, EPHA2, ABCB5, and ITGB2. These proteins were related to angiogenesis, cell proliferation, and cell inflammation. The network analysis combining PBA data with miRNA-Seq data showed that 79 miRNAs were related to 24 membrane proteins and predicted that there were surface proteins associated with a variety of miRNA molecules, such as ITGA9, XIAP, ADAM1, ITGA2, ITGA3, PDPN, and ITGB1. Meanwhile, there were miRNAs related to various surface proteins including miR-410-3p, miR-378b, and miR-1960. Taken together, our data demonstrated for the first time the changes of exosomal miRNAs and surface protein profiles derived from ischemic microvascular endothelial cells, which may provide new therapeutic targets for BBB protection in ischemic stroke.

16.
Elife ; 102021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590578

RESUMO

Astrocytes are essential cells of the central nervous system, characterized by dynamic relationships with neurons that range from functional metabolic interactions and regulation of neuronal firing activities, to the release of neurotrophic and neuroprotective factors. In Parkinson's disease (PD), dopaminergic neurons are progressively lost during the course of the disease, but the effects of PD on astrocytes and astrocyte-to-neuron communication remain largely unknown. This study focuses on the effects of the PD-related mutation LRRK2 G2019S in astrocytes generated from patient-derived induced pluripotent stem cells. We report the alteration of extracellular vesicle (EV) biogenesis in astrocytes and identify the abnormal accumulation of key PD-related proteins within multivesicular bodies (MVBs). We found that dopaminergic neurons internalize astrocyte-secreted EVs and that LRRK2 G2019S EVs are abnormally enriched in neurites and fail to provide full neurotrophic support to dopaminergic neurons. Thus, dysfunctional astrocyte-to-neuron communication via altered EV biological properties may participate in the progression of PD.


Assuntos
Astrócitos/enzimologia , Comunicação Celular , Neurônios Dopaminérgicos/enzimologia , Exossomos/enzimologia , Células-Tronco Pluripotentes Induzidas/enzimologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Células-Tronco Neurais/enzimologia , Doença de Parkinson/enzimologia , Animais , Astrócitos/ultraestrutura , Atrofia , Estudos de Casos e Controles , Linhagem Celular , Neurônios Dopaminérgicos/patologia , Endocitose , Exossomos/genética , Exossomos/ultraestrutura , Humanos , Células-Tronco Pluripotentes Induzidas/ultraestrutura , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Células-Tronco Neurais/ultraestrutura , Biogênese de Organelas , Doença de Parkinson/genética , Doença de Parkinson/patologia
17.
Exp Hematol ; 101-102: 58-67, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34450221

RESUMO

Huaier, a traditional Chinese medicine, is currently used to treat certain types of cancer in the clinic and is also regarded as an immune-modulating and immune-enhancing agent that regulates immune cells. Emerging evidence indicates that an imbalance of immune cells, such as CD4+ T helper (Th) lymphocytes, contributes to the progression of immune thrombocytopenia (ITP), but the effects of Huaier on the regulation of CD4+ T cells are not yet fully elucidated. In the present study, Jurkat cells and peripheral blood mononuclear cells (PBMCs) from patients with ITP and healthy volunteers were treated with Huaier aqueous extract (HR). The CCK-8 assay revealed that HR suppressed the proliferation of Jurkat cells in a dose-dependent manner, whereas 3 mg/mL could decrease cell viability by 50%. At the latter concentration, the activation of CD4+ T cells from patients with ITP was partially attenuated. In addition, HR could correct the unbalanced Th1/Th2 polarization and inhibit the secretion of pro-inflammatory factors interleukin (IL)-2, tumor necrosis factor-α, and interferon-γ. It also suppressed Treg and facilitated Th17 differentiation, but did not change the levels of IL-10 and transforming growth factor-ß. Thus, this study provides more information on how Huaier regulates cellular immunity and improves our understanding of the use of Huaier in ITP.

18.
Orthop J Sports Med ; 9(7): 2325967121991930, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34368375

RESUMO

Background: Few studies have compared the clinical outcomes of using 1 versus 2 suture anchors for anterior talofibular ligament (ATFL) repair. Purpose: To compare the function and activity-related outcomes of arthroscopic ATFL repair using 1 versus 2 suture anchors. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study involved 46 patients (22 patients in the 1-anchor group, 24 patients in the 2-anchor group) who underwent ATFL repair between January 2015 and December 2017. American Orthopaedic Foot & Ankle Society score, Karlsson and Peterson score, and Tegner activity level were evaluated preoperatively and ≥2.5 years postoperatively. At follow-up, patients were also asked about time to return to sport as well as level and intensity of physical fitness. Satisfaction was evaluated with the Sefton grading system. Results: After ≥2.5 years of follow-up (30 months in the 1-anchor group, 33 months in the 2-anchor group), patients in the 2-anchor group had a higher Tegner activity level than those in the 1-anchor group (mean ± SD, 4.75 ± 1.07 vs 4.05 ± 1.17; P = .039). As compared with patients in the 2-anchor group, fewer patients in the 1-anchor group returned to their preoperative activity level (54.2% vs 22.9%; P = .029); the rate of activity at the same or higher intensity as preinjury was also lower in the 1-anchor group (50% vs 79.2%; P = .038). However, there were no differences between the groups in terms of American Orthopaedic Foot & Ankle Society and Karlsson and Peterson scores, time to return to work/sport, duration of activity participation, level of physical fitness, or satisfaction according to Sefton grading. Conclusion: Arthroscopic ATFL repair appears to be an effective treatment regardless of whether 1 or 2 suture anchors are used. The techniques had similar functional outcome scores, but 1-anchor repair produced inferior activity-related outcomes.

19.
Transl Neurosci ; 12(1): 309-319, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34434564

RESUMO

Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

20.
J Transl Med ; 19(1): 372, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461927

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People's Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.


Assuntos
Neoplasias Encefálicas , Receptores ErbB/genética , Glioblastoma , Proteínas de Membrana/genética , Proteínas de Ligação a Fosfato/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Variações do Número de Cópias de DNA/genética , Receptores ErbB/metabolismo , Glioblastoma/genética , Humanos , Mutação , Recidiva Local de Neoplasia , Prognóstico , RNA Mensageiro/genética
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