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1.
FEBS Open Bio ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155431

RESUMO

Migraine is a debilitating neurological condition, with a global prevalence of 10.68% in men and 18.79% in women. Elucidation of the molecular mechanisms underlying migraines is of great importance for improving the quality of life of patients. The release of the neuropeptide calcitonin gene-related peptide (CGRP) from trigeminal nerve terminals is involved in the pathogenesis of migraine. Recent studies have shown that up-regulation of miR-34a-5p expression is associated with acute migraine attacks. Here, we investigated whether alteration of the expression of miR-34a-5p induces the release of the vasoactive peptide CGRP. We isolated primary rat trigeminal ganglion neurons and performed gain and loss-of function assays to alter the expression level of miR-34a-5p. Downregulation of miR-34a-5p inhibited the expression of IL-1ß/COX2/PGE2, decreased IL-1ß, PGE2 and CGRP release and upregulated the expression of SIRT1 in trigeminal ganglion, while overexpression of miR-34a-5p enhanced the expression of IL-1ß/COX2/PGE2, increased the release of IL-1ß, PGE2 and CGRP, and decreased the expression of SIRT1 in trigeminal ganglion. In addition, overexpression of miR-34a induced apoptosis in primary rat trigeminal neurons. In summary, these findings suggest that miR-34a-5p up-regulates the IL-1ß/COX2/PGE2 inflammation pathway, induces apoptosis, and enhances release of CGRP via inhibition of SIRT1 expression in trigeminal ganglion neurons, and thus miR-34a-5p may have potential as a therapeutic target for treatment of migraine.

2.
Medicine (Baltimore) ; 99(47): e23263, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217850

RESUMO

RATIONALE: Double primary clear cell carcinomas of the liver (PCCCL) and kidney are extremely rare; moreover, there have been no reported cases of adrenal metastasis from primary clear cell tumors of the liver. PATIENT CONCERNS: A 47-year-old male patient was admitted to our clinic with space-occupying lesions in the left kidney and liver during a regular medical examination. DIAGNOSES: The tumors in the kidney and liver were diagnosed as primary clear cell carcinoma by histopathological examination. INTERVENTIONS: The patient subsequently underwent nephron-sparing surgery of the left kidney and radical partial excision of the right liver lobe by laparoscopic surgery. Transcatheter arterial chemoembolization (TACE) was performed for the patient 2 weeks after tumor resection. One month after the operation, the patient started adjuvant therapy with sorafenib (400 mg twice per day orally). However, follow-up CT imaging revealed a solid mass measuring 1.9 × 2.0 × 2.0 cm in the right adrenal gland at 2 months postoperatively, and then the patient underwent radiofrequency ablation (RFA) for the right adrenal tumor. OUTCOMES: The patient remained cancer free for 2 years following the diagnosis despite early right adrenal metastasis. LESSONS: Hepatocyte immunostaining is sufficient for the diagnosis of PCCCL.

3.
Cell Death Dis ; 11(11): 999, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33221813

RESUMO

With the development of molecular biotechnology and sequencing techniques, long non-coding RNAs (lncRNAs) have been shown to play a vital role in a variety of cancers including lung cancer. In our previous study, we used RNA sequencing and high-content screening proliferation screening data to identify lncRNAs that were significantly associated with tumour biological functions such as LINC01426. Herein, based on previous work, we report a novel lncRNA UPLA1 (upregulation promoting LUAD-associated transcript-1), which has not been explored or reported in any previous studies. Our results showed that UPLA1 is highly expressed and regulates important biological functions in lung adenocarcinoma. In vitro experiments revealed that UPLA1 promoted the migration, invasion, and proliferation abilities, and is related to cell cycle arrest, in lung adenocarcinoma cells. Moreover, the upregulation of UPLA1 significantly improved the growth of tumours in vivo. We identified that UPLA1 was mainly located in the nucleus using fluorescence in situ hybridisation, and that it promoted Wnt/ß-catenin signalling by binding to desmoplakin using RNA pulldown assay and mass spectrometry. Additionally, luciferase reporter assay revealed that YY1 is the transcription factor of UPLA1 and suppressed the expression of UPLA1 as a transcriptional inhibitor. This finding provides important evidence regarding the two roles of YY1 in cancer. Furthermore, in situ hybridisation assay results showed that UPLA1 was closely related to the prognosis and tumour, node, metastasis (TNM) stage of lung adenocarcinoma. In summary, our results suggest that the novel lncRNA UPLA1 promotes the progression of lung adenocarcinoma and may be used as a prognostic marker, and thus, has considerable clinical significance.

4.
BMC Infect Dis ; 20(1): 820, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172401

RESUMO

BACKGROUND: Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. METHODS: To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods. RESULTS: The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4 and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/µL. CONCLUSIONS: TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.


Assuntos
Bactérias/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecções Respiratórias/diagnóstico , Vírus/genética , China/epidemiologia , Primers do DNA , Confiabilidade dos Dados , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Sensibilidade e Especificidade
5.
BMC Nephrol ; 21(1): 479, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187492

RESUMO

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in end-stage renal disease (ESRD) patients, and parathyroidectomy (PTX) is an effective treatment intervention of SHPT. However, the curative impact of PTX on left ventricular function still remains incompletely understood. To evaluate the impact of parathyroidectomy on left ventricular function in ESRD patients, we conducted this retrospective study. METHODS: Between Oct 1, 2010 and Oct 1, 2016, ESRD patients presented with SHPT who underwent parathyroidectomy were enrolled. We retrospectively collected the ultrasonic cardiogram parameter pre- and 1-year post-PTX, and analyzed the influence factor for the overturn of left ventricular hypertrophy (LVH) and the improvement of ejection fraction% (EF%). RESULTS: In all the patients (135), the main ultrasonic cardiogram parameter dramatically improved after PTX. Compared with pre-PTX, the left ventricular mass (LVM) (172.82 (135.90, 212.91) g vs. 192.76 (157.56, 237.97) g, p<0.001) and the left ventricular mass index (LVMI) (107.01 (86.79, 128.42) g/m2 vs. 123.54 (105.49, 146.64) g/m2, p<0.001) significantly declined after 1 year of the PTX. Further, 43.75% patients diagnosed with LVH before the PTX have recovered from LVH. In the subgroup analysis of 35 patients with EF% ≤ 60% pre-PTX, EF% and fractional shortening% (FS%) significantly improved after 1 year of the PTX compared with pre-PTX (EF%: 64.90 ± 7.90% vs. 55.71 ± 4.78%, p<0.001; FS% 35.48 ± 6.34% vs. 29.54 ± 2.88%, p<0.001), and 82.86% patients underwent an improvement of left ventricular systolic function post 1year of the PTX. CONCLUSIONS: tPTX+AT is an effective curative intervention of secondary hyperparathyroidism and can significantly overturn the LVH and increase the left ventricular systolic function.

6.
BMC Genomics ; 21(1): 774, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167853

RESUMO

BACKGROUND: Hibernation in an appropriate environment not only is important for the survival of hibernators in winter, but also is crucial for breeding in the following season for many hibernating species. However, the genetic and epigenetic mechanism underlying this process remain unclear. In the current study, we performed an integrative multi-omics analysis of gonads collected from Chinese alligators that overwintered in wild cave and artificial warmroom to explore transcriptomic and epigenomic alternations in these organs. RESULTS: The data revealed that in the breeding season, female alligators were more strongly affected in terms of gene expression than males by non-hibernation because of overwintering in a warm room, especially for genes related to oocyte maturation, and this effect commenced in winter with the downregulation of STAR, which is the rate limiting factor of steroid biosynthesis. Further, miRNAs were found to play essential roles in this negative effect of overwintering in the warm room on hibernation. The upregulated miRNAs likely were responsible for the suppression of oocyte maturation in the breeding season. Finally, DNA methylome changes, especially hypomethylation, were found to play an important role in the alterations in ovarian function-related gene expression induced by non-hibernation. CONCLUSIONS: Our study revealed the crucial role of hibernation quality for oocyte maturation in the Chinese alligator and the underlying genetic and epigenetic mechanisms, and highlights the importance of habitat, and especially, the overwintering site, in the conservation of not only the Chinese alligator, but also other endangered hibernators.

7.
Autophagy ; : 1-17, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33143524

RESUMO

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn- / - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn- / - mice or infecting optn- / - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn- / - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; µCT: micro computed tomography.

8.
Brief Bioinform ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167027

RESUMO

Almost all currently approved systemic therapies for hepatocellular carcinoma (HCC) failed to achieve satisfactory therapeutic effect. Exploring tailored treatment strategies for different individuals provides an approach with the potential to maximize clinical benefit. Previously, multiple studies have reported that hepatoma cell lines belonging to different molecular subtypes respond differently to the same treatment. However, these studies only focused on a small number of typical chemotherapy or targeted drugs across limited cell lines due to time and cost constraints. To compensate for the deficiency of previous experimental researches as well as link molecular classification with therapeutic response, we conducted a comprehensive in silico screening, comprising nearly 2000 compounds, to identify compounds with subclass-specific efficacy. Here, we first identified two transcriptome-based HCC subclasses (AS1 and AS2) and then made comparison of drug response between two subclasses. As a result, we not only found that some agents previously considered to have low efficacy in HCC treatment might have promising therapeutic effects for certain subclass, but also identified novel therapeutic compounds that were not routinely used as anti-tumor drugs in clinic. Discovery of agents with subclass-specific efficacy has potential in changing the status quo of population-based therapies in HCC and providing new insights into precision oncology.

9.
Inflammation ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180227

RESUMO

Accumulating studies show that microRNAs are candidate biomarkers and therapeutic targets for cardiovascular diseases including myocardial infarction (MI). Bioinformatics analysis suggested that compared with Sprague-Dawley (SD) rats without MI, miR-30e-5p expression in the left ventricle tissue of SD rats with MI was significantly downregulated, suggesting miR-30e-5p may participate in the pathogenesis of MI. In this study, H9c2 cardiomyocytes were exposed to hypoxia to establish a hypoxic cell model. SD rats with left anterior descending coronary artery ligation were used for the MI animal model. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the miR-30e-5p and PTEN mRNA expressions in cells and tissues. Western blot was used for detecting the expression of PTEN protein. miR-30e-5p expression in H9c2 cells was then inhibited or overexpressed, and its effects on viability and apoptosis were examined by cell counting kit-8 (CCK-8) assay and TUNEL assay, respectively. ELISA was used to detect inflammatory factors. The regulatory relationship between PTEN and miR-30e-5p was investigated by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. It was found that miR-30e-5p expression was significantly downregulated in animal models and H9c2 cells under hypoxia. Overexpression of miR-30e-5p led to a dramatic increase of cell viability, accompanied by the decrease of IL-1ß, TNF-α, IL-6, LDH, CK-MB, and cTnI. Furthermore, PTEN was identified as a target of miR-30e-5p, and PTEN overexpression reversed the effects of miR-30e -5p on H9c2 cells. To conclude, we confirm that miR-30e-5p alleviates inflammation and myocardial injury induced by MI via suppressing PTEN.

10.
Acta Pharmacol Sin ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239687

RESUMO

A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the "short" inverse agonist 6. With the increase in the size of the 6-position substituents, the "short" inverse agonist 6 first reversed its function to agonists and then to "long" inverse agonists. The cocrystal structures of RORγt complexed with the representative "short" inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the "long" inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of "short" inverse agonist 6 and "long" inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that "short" or "long" inverse agonists led to different behaviors of helixes H11, H11', and H12 of RORγt. The "short" inverse agonist 6 destabilizes H11' and dislocates H12, while the "long" inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms.

11.
Phys Chem Chem Phys ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140789

RESUMO

Correction for 'Equations of the state of hard sphere fluids based on recent accurate virial coefficients B5-B12' by Jianxiang Tian et al., Phys. Chem. Chem. Phys., 2019, 21, 13070-13077. DOI: 10.1039/C9CP02116G.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33232942

RESUMO

The quantum anomalous Hall effect (QAHE), carrying dissipationless chiral edge states, occurs without any magnetic field. Two main strategies were proposed to host QAHE: the magnetic topological insulator thin films and graphene systems. Only the former one was realized in experiment at low temperature. In this paper, by dealing with the two-dimensional electron gas with an anti-dot lattice, a realistic platform is proposed to host the QAHE with both Chern number $\mathcal{C}=-1$ and $\mathcal{C}=2$. Based on the calculation of Berry curvature and spacial wave function, the topological nature of the QAH edge states is well demonstrated. In the QAH region, the conductance shows quantized plateaus and their values are robust against Anderson disorder. In addition, we have also studied the effects of the size and shape of the anti-dot lattice on QAHE and they provide extra manners to adjust the system parameters. Taking the advantages of the well developed micro-manufacture technique in semiconductors, the proposal is experimentally accessible in micro-scale.

13.
Ann Palliat Med ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33183038

RESUMO

BACKGROUND: Tracheobronchopathia osteochondroplastica (TO) is a benign rare disease characterized by multiple tracheobronchial nodules, which has not been clearly illuminated and there are no standard guidelines for TO management. The aim of this study was to clarify the clinical features and treatment outcomes of TO and provide basis for clinical diagnosis and treatment. METHODS: A total of 32,215 patients taken bronchoscopy were retrospectively reviewed to select patients diagnosed with TO. Clinical characteristics, bronchoscopic manifestations, CT images, histopathological features, treatments and clinical course were investigated. RESULTS: 13 male and 6 female were identified as TO. The average age was 47.42±12.12 years. The incidence rate of TO in our study by bronchoscopy was 0.06%. The most frequent manifestation was chronic cough. Based on bronchoscopic manifestations, patients were categorized as three groups: the largest proportion was group of Stage II (10/19), followed by Stage III (5/19) and Stage I (4/19). The positive rate of CT in stage I, stage II and stage III was 0%, 50%, 100%, respectively. Histopathological analysis presented inflammatory exudation, squamous metaplasia, submucosal cartilaginous and osseous deposition. Bronchoscopic intervention and inhaled corticosteroids were administered to subjects in stage II and III, which improved their life qualities to some degree. CONCLUSIONS: Not only multi-disciplinary cooperation of clinical, endoscopic and histological assessment, but also awareness are crucial to TO diagnosis, especially in early stage of TO, which was difficult to identify. The stage of TO based on bronchoscopic visualization might be applied to guide the choice of clinical treatment strategy.

14.
BMJ Open ; 10(11): e039405, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158827

RESUMO

OBJECTIVES: To investigate the changes in serum myeloperoxidase (MPO), interleukin (IL)-17A and heparin-binding EGF-like growth factor (HB-EGF) levels before and after percutaneous coronary intervention (PCI), and to evaluate the associations of MPO, IL-17A and HB-EGF levels with the 1-year restenosis rate. DESIGN: Case-control study. SETTINGS: Xiangyang Central Hospital between January 2012 and December 2017. PARTICIPANTS: Patients with coronary heart disease who underwent PCI. INTERVENTIONS: Not applicable. PRIMARY AND SECONDARY OUTCOME MEASURES: Not applicable. RESULTS: Finally, 407 and 132 patients were included in the control and in-stent restenosis (ISR) groups, respectively. The general clinical characteristics of the patients were not significantly different between the two groups. The MPO, IL-17A and HB-EGF levels were not significantly different between the two groups at baseline but significantly increased after PCI. The ISR group showed higher levels of MPO, IL-17A and HB-EGF compared with the control group at all postoperative time points. Multivariable analysis showed that MPO, IL-17A and HB-EGF were associated with increased ISR [MPO (OR=1.003; 95% CI: 1.001 to 1.005; p=0.002), IL-17A (OR=1.015; 95% CI: 1.009 to 1.020; p<0.0001) and HB-EGF (OR=2.256; 95% CI: 1.103 to 4.009; p=0.002)]. All three factors had sensitivity and specificity ≥68% for ISR. CONCLUSIONS: HB-EGF could be used for the detection of ISR after PCI and could be of use for the prediction of ISR, but the value of MPO and IL-17A might be more limited. This will have to be validated in future studies.

15.
J Cell Mol Med ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135394

RESUMO

Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differentiation, are essential to explore therapeutic strategies. Our previous research showed that the up-regulation of miR-503 alleviated silica-induced pulmonary fibrosis in mice. In this study, we investigated whether miR-503 can regulate the TGF-ß1-induced effects in lung fibroblasts. Mimic-based strategies aiming at up-regulating miR-503 were used to discuss the function of miR-503 in vivo and in vitro. We found that the expression level of miR-503 was decreased in fibroblasts stimulated by TGF-ß1, and the up-regulation of miR-503 reduced the release of fibrotic factors and inhibited the migration and invasion abilities of fibroblasts. Combined with the up-regulation of miR-503 in a mouse model of silica-induced pulmonary fibrosis, we revealed that miR-503 mitigated the TGF-ß1-induced effects in fibroblasts by regulating VEGFA and FGFR1 and then affecting the MAPK/ERK signalling pathway. In conclusion, miR-503 exerted protective roles in silica-induced pulmonary fibrosis and may represent a novel and potent candidate for therapeutic strategies in silicosis.

16.
Ann Rheum Dis ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109602

RESUMO

OBJECTIVES: Despite preclinical studies involving miRNA therapeutics conducted in osteoarthritis (OA) over the years, none of these miRNAs have yet translated to clinical applications, owing largely to the lack of efficient intra-articular (IA) delivery systems. Here, we investigated therapeutic efficacy of the chondrocyte-specific aptamer-decorated PEGylated polyamidoamine nanoparticles (NPs)-based miRNAs delivery for OA. METHODS: The role of miR-141/200c cluster during skeletal and OA development was examined by miR-141/200cflox/flox mice and Col2a1-CreERT2; miR-141/200cflox/flox mice. Histological analysis was performed in mouse joints and human cartilage specimens. Chondrocyte-specific aptamer-decorated NPs was designed, and its penetration, stability and safety were evaluated. OA progression was assessed by micro-CT analysis, X-ray and Osteoarthritis Research Society International scores after destabilising the medial meniscus surgery with miR-141/200c manipulation by NPs IA injection. Mass spectrometry analysis, molecular docking and molecular dynamics simulations were performed to investigate the interaction between aptamer and receptor. RESULTS: Increased retention of NPs inside joint space is observed. The NPs are freely and deeply penetrant to mice and human cartilage, and unexpectedly persist in chondrocytes for at least 5 weeks. OA chondrocytes microenviroment improves endo/lysosomal escape of microRNAs (miRNAs). Therapeutically, IA injection of miR-141/200c inhibitors provides strong chondroprotection, whereas ectopic expression of miR-141/200c exacerbates OA. Mechanistically, miR-141/200c promotes OA by targeting SIRT1, which acetylates histone in the promoters of interleukin 6 (IL-6), thereby activating IL-6/STAT3 pathway. CONCLUSIONS: Our findings indicate that this nanocarrier can optimise the transport kinetics of miR-141/200c into chondrocytes, fostering miRNA-specific disease-modifying OA drugs development.

17.
Nanoscale ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112348

RESUMO

The structure and phase transformation of a cobalt (Co) catalyst, during single walled carbon nanotube (SWCNT) growth, is elucidated for inactive, active and deactivated nanoparticles by in situ imaging using an environmental transmission electron microscope. During nanotube growth, the structure was analyzed using Miller indices to determine the types of planes that favor anchoring or liftoff of nanotubes from the Co catalyst. Density functional theory was further applied to model the catalyst interactions to compare the work of adhesion of the catalyst's faceted planes to understand the interactions of different Miller planes with the graphene structure. Through in-depth studies of multiple distinct Co nanoparticles, we established a dominant nanoparticle phase for SWCNT growth. In addition, we identified the preferred lattice planes and a threshold for work of adhesion to allow the anchoring and liftoff of SWCNTs.

18.
Inquiry ; 57: 46958020964421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33111605

RESUMO

Nursing skill education plays a very important part for the nursing education. It's necessary to analyze the role of the case-based teaching (CBT) in nursing skill education, to provide insights into the nursing education. The sophomore nursing students who received nursing skill teaching from September 2019 to January 2020 were selected. The students either underwent traditional teaching (control group) or CBT (CBT group) intervention. The objective structure clinical examination (OSCE), autonomous learning ability, questionnaire for effects evaluation of CBT, and student's satisfaction level on CBT were analyzed. A total of 146 participants were included. There were no significant differences in the gender, age and the final exam score as freshman between 2 groups (all P > .05). The OSCE scores and autonomous learning ability in CBT group were significantly higher than that of control group (all P < .05). The most students favored the use of CBT, and most students were satisfied with CBT. CBT is beneficial to improve the nursing skill and comprehensive ability of students, and it's conducive to increase the interest of students, which merits application in nursing education.

19.
Mol Ther ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33010818

RESUMO

A hostile tumor microenvironment is one of the major obstacles for the efficacy of chimeric antigen receptor modified T (CAR-T) cells, and combination treatment might be a potential way to overcome this obstacle. Poly(ADP-ribose) polymerase inhibitor (PARPi) has demonstrated tremendous potential in breast cancer. In this study, we explored the possible combination of the PAPRi olaparib with EGFRvIII-targeted CAR (806-28Z CAR) T cells in immunocompetent mouse models of breast cancer. The results indicated that the administration of olaparib could significantly enhance the efficacy of 806-28Z CAR-T cells in vivo. Interestingly, we observed that olaparib could suppress myeloid-derived suppressor cell (MDSC) migration and promote the survival of CD8+ T cells in tumor tissue. Mechanistically, olaparib was shown to reduce the expression of SDF1α released from cancer-associated fibroblasts (CAFs) and thereby decreased MDSC migration through CXCR4. Taken together, this study demonstrated that olaparib could increase the antitumor activities of CAR-T cell therapy at least partially through inhibiting MDSC migration via the SDF1α/CXCR4 axis. These findings uncover a novel mechanism of PARPi function and provide additional mechanistic rationale for combining PARPi with CAR-T cells for the treatment of breast cancer.

20.
Lipids Health Dis ; 19(1): 217, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028331

RESUMO

BACKGROUND: This study explored the relationships between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and other clinical indicators and ischaemic stroke (IS) in patients with non-valvular atrial fibrillation (NVAF) in Xinjiang. The findings could provide a theoretical and therapeutic basis for NVAF patients. METHODS: NVAF patients who were admitted to 10 medical centres across Xinjiang were divided into stroke (798 patients) and control (2671 patients) groups according to the occurrence of first acute IS. Univariate and multivariate logistic regression analysis were used to examine the independent risk factors for IS in NVAF patients. Factor analysis and principal component regression analysis were used to analyse the main factors influencing IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory ability of LDL-C/HDL-C for predicting the occurrence of IS. RESULTS: The stroke group had an average age of 71.64 ± 9.96 years and included 305 females (38.22%). The control group had a mean age of 67.30 ± 12.01 years and included 825 females (30.89%). Multivariate logistic regression showed that the risk of IS in the highest LDL-C/HDL-C quartile (≥2.73) was 16.23-fold that of the lowest quartile (< 1.22); IS risk was 2.27-fold higher in obese patients than in normal-weight subjects; IS risk was 3.15-fold higher in smoking patients than in non-smoking patients. The area under the ROC curve of LDL-C/HDL-C was 0.76, the optimal critical value was 2.33, the sensitivity was 63.53%, and the specificity was 76.34%. Principal component regression analysis showed that LDL-C/HDL-C, age, smoking, drinking, LDL-C and hypertension were risk factors for IS in NVAF patients. CONCLUSIONS: LDL-C/HDL-C > 1.22, smoking, BMI ≥24 kg/m2 and CHA2DS2-VASc score were independent risk factors for IS in NVAF patients; LDL-C/HDL-C was the main risk factor.

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