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1.
J Affect Disord ; 320: 667-673, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36209781

RESUMO

OBJECTIVES: To explore the effect of time to remission on residual symptoms, functioning and quality of life (QOL) of the patients with major depressive disorder (MDD). METHOD: A total of 434 patients were enrolled from 16 sites of China. The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) and self-rating scales were assessed at baseline, and months 1, 3 and 6. Baseline remitters were defined as those subjects with a QIDS-SR score ≤ 5 at baseline. Later remitters was defined as those reaching remission one month (Month 1 remitters) or three month (Month 3 remitters) after baseline. Persistent non-remitters were defined as those with QIDS-SR score > 5 at all 3 assessments. A follow-up assessment was done at month 6 to examine outcomes. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL. RESULTS: Totally, 179 patients at baseline achieved remission. An additional 141 participants remitted at month 1 (n = 94) or month 3 (n = 47), and 63 patients were persistent non-remitters. There were significant differences between all groups on depression severity at baseline. QOL was similar for both late remitter groups, which was better than non-remitters, but lower than early-remitters. Late remitters and non-remitters showed significant differences on change of functioning and QOL (P < 0.001) at each visit. By 6 months, all remitting groups showed lower depression severity and better social functioning and QOL than persistent non-remitters. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL. CONCLUSION: We confirmed the association of earlier remission with a better quality of remission at early stage; but the time to remission does not affect future functioning and QOL.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Qualidade de Vida , Escalas de Graduação Psiquiátrica , Autorrelato , China
2.
JACC Asia ; 2(3): 390-394, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36338402

RESUMO

Transcatheter mitral valve intervention treatment is a promising alternative therapy for patients with severe mitral regurgitation (MR). This is a multicenter, prospective, first-in-human study of transcatheter edge-to-edge repair (TEER) using a novel device for severe MR. Safety and efficacy were assessed immediately after the procedure and at 30-day follow-up. Twenty-three patients (age 70.0 ± 5.2 years) who were at high/prohibitive surgical risk underwent successful procedures without major periprocedural complications. All patients achieved residual MR ≤2+ at discharge, with 73.9% with 1+ residual MR. The left ventricular end-systolic diameter improved from 4.1 cm at baseline to 3.4 cm at 30-day follow-up. New York Heart Association functional class I/II after TEER was achieved in 87% of patients. This study demonstrated that TEER with the device was feasible and safe for the treatment of patients with severe MR. (Dragonfly-M Transcatheter Mitral Valve Repair System Early Feasibility Study; NCT04528576).

3.
Psychol Med ; : 1-13, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36349712

RESUMO

BACKGROUND: Depressive symptoms, functional impairment, and decreased quality of life (QOL) are three important domains of major depressive disorder (MDD). However, the possible causal relationship between these factors has yet to be elucidated. Moreover, it is not known whether certain symptoms of MDD are more impairing than others. The network approach is a promising solution to these shortfalls. METHODS: The baseline data of a multicenter prospective project conducted in 11 governances of China were analyzed. In total, 1385 patients with MDD were included. Depressive symptoms, functioning disability, and QOL were evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17), the Sheehan Disability Scale (SDS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). The network was estimated through the graphical Least Absolute Shrinkage and Selection Operator (LASSO) technique in combination with the directed acyclic graph. RESULTS: Three centrality metrics of the graphical LASSO showed that social life dysfunction, QOL, and late insomnia exhibited the highest strength centrality. The network accuracy and stability were estimated to be robust and stable. The Bayesian network indicated that some depressive symptoms were directly associated with QOL, while other depressive symptoms showed an indirect association with QOL mediated by impaired function. Depressed mood was positioned at the highest level in the model and predicted the activation of functional impairment and anxiety. CONCLUSIONS: Functional disability mediated the relationship between depressive symptoms and QOL. Family functionality and suicidal symptoms were directly related to QOL. Depressed mood played the predominant role in activating both anxiety symptom and functional impairment.

4.
Front Psychol ; 13: 976213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420386

RESUMO

This paper aims to generate insights about whether, how, and when workplace event criticality spurs employee proactivity. We conducted multilevel analyses with a three-wave time-lagged survey of 179 employees and their 55 direct leaders in China to test our proposed model. The findings indicate that workplace event criticality is conducive to stimulating proactive work behavior through improving employee engagement. Further, employee mindfulness amplifies the positive relationship between workplace event criticality and work engagement. Despite the increasingly unavoidable influence of events in the workplace on employee proactivity, empirical research around the relationship and its underlying mechanism has been rather sparse. Our event-oriented research advances this knowledge by unpacking the salient motivating role of workplace events' criticality in employee work engagement and proactivity. It also increases our understanding by illustrating that employee mindfulness will amplify and intensify the motivational potential of workplace event criticality for work engagement.

5.
CNS Neurosci Ther ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377461

RESUMO

AIMS: This study aimed to explore the neural substrate of hearing loss-related central nervous system in rats and its correlation with cognition. METHODS: We identified the neural mechanism for these debilitating abnormalities by inducing a bilateral hearing loss animal model using intense broadband noise (122 dB of broadband noise for 2 h) and used the Morris water maze test to characterize the behavioral changes at 6 months post-noise exposure. Functional magnetic resonance imaging (fMRI) was conducted to clarify disrupted functional network using bilateral auditory cortex (ACx) as a seed. Structural diffusion tensor imaging (DTI) was applied to illustrate characteristics of fibers in ACx and hippocampus. Pearson correlation was computed behavioral tests and other features. RESULTS: A deficit in spatial learning/memory, body weight, and negative correlation between them was observed. Functional connectivity revealed weakened coupling within the ACx and inferior colliculus, lateral lemniscus, the primary motor cortex, the olfactory tubercle, hippocampus, and the paraflocculus lobe of the cerebellum. The fiber number and mean length of ACx and different hippocampal subregions were also damaged in hearing loss rats. CONCLUSION: A new model of auditory-limbic-cerebellum interactions accounting for noise-induced hearing loss and cognitive impairments is proposed.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36378269

RESUMO

Mandibular distraction osteogenesis (MDO) is an endogenous tissue engineering technology in which bone marrow mesenchymal stem cells (BMSC) play a key role in MDO-related osteogenesis. Activating transcription factor 4 (ATF4) is involved in osteogenesis through activation of PERK (Protein kinase R-like endoplasmic reticulum kinase) in endoplasmic reticulum stress (ERS) condition under hypoxia. However, the specific role of ATF4 in MDO with BMSC remains unknown. The aim of this study was to explore the effects of ATF4 in MDO with BMSC under hypoxia. Briefly, canine BMSCs were cultured in a hypoxic chamber, and effects of hypoxia were evaluated using cell migration assay and Alizarin Red S staining. Expression levels of protein kinase R-like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2α, ATF4, osteocalcin, and bone sialoprotein were evaluated using quantitative polymerase chain reaction and western blotting. BMSCs were transduced with the ATF4-small interfering RNA lentivirus. The effects were evaluated using all the aforementioned experiments. The results showed that hypoxia promoted migration, osteoblast differentiation, and ATF4 expression in BMSC. ATF4 knockdown in BMSC significantly inhibited migration and osteoblast differentiation abilities, while hypoxia reversed these effects to some extent. In addition, the molecular mechanism partly depended on the ERS signaling pathway, with ATF4 as the key factor. In summary, we presented a novel mechanism of ATF4-mediated regulation of BMSC under hypoxia.

7.
Eur J Prev Cardiol ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36378543

RESUMO

AIMS: Inspiratory muscle training (IMT) can increase the strength or endurance of the diaphragm and accessory muscles of inspiration, yet there is no evidence that endorses the role of IMT in patients of transcatheter aortic valve replacement (TAVR). This study tested for the first time the effects of IMT plus usual cardiac rehabilitation (CR) on function in patients after TAVR. METHODS: A double-blinded, randomized controlled, single-center clinical trial was undertaken. Participants who had a confirmed diagnosis of valve heart disease and were clinically stable after TAVR were recruited and received a CR program during the hospital stay. RESULTS: A total of 96 patients were recruited and randomly assigned to the IMT + CR group (n = 48) or the CR group (n = 48) in a 1:1 ratio. The group difference in the primary outcome, the six-minute walk distance at the discharge of hospital, significantly favored the IMT + CR group (Mean difference -33.52, 95%CI -64.42 to -2.62, p = 0.034). The significant difference was maintained at the 1-month and 3-month follow-ups (Mean difference 41.51, 95%CI 1.82 to 81.21, p = 0.041). In addition, the mean hospital stays of subjects in the IMT + CR group was 11 days, which was significantly shorter than the 12.5 days in the CR group (p = 0.016). Sensitivity analysis using per-protocol analysis supported these findings. No adverse treatment-related events were reported. CONCLUSIONS: Compared with usual CR, IMT plus CR can effectively improve exercise endurance, pulmonary ventilation function and inspiratory muscle strength in patients after TAVR and shorten the length of hospital stay.

8.
ACS Nano ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383161

RESUMO

The kagome lattice has attracted intense interest with the promise of realizing topological phases built from strongly interacting electrons. However, fabricating two-dimensional (2D) kagome materials with nontrivial topology is still a key challenge. Here, we report the growth of single-layer iron germanide kagome nanoflakes by molecular beam epitaxy. Using scanning tunneling microscopy/spectroscopy, we unravel the real-space electronic localization of the kagome flat bands. First-principles calculations demonstrate the topological band inversion, suggesting the topological nature of the experimentally observed edge mode. Apart from the intrinsic topological states that potentially host chiral edge modes, the realization of kagome materials in the 2D limit also holds promise for future studies of geometric frustration.

9.
Front Pharmacol ; 13: 992421, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339588

RESUMO

Renal fibrosis is a manifestation of kidney injury. Nephropathy 1st is a traditional Chinese herbal medicine that has been used as a therapy for kidney disease, but the underlying mechanisms remain elusive. The aim of this study was to investigate the role and underlying mechanisms of Nephropathy 1st on the progression of kidney disease. In the present study, unilateral ureteral obstruction was performed to establish the renal fibrosis rat model. By hematoxylin-eosin staining and immunohistochemical staining analysis, the severity of renal fibrosis was evaluated in vivo. Serum creatinine (CREA) and urea nitrogen (BUN) were measured by ELISA. The expression levels of Col-I, FN, PPARγ, and Klotho were measured by Western blot in rat NRK-49F cells and in fibrotic rats. GW9662 was used to inhibit PPARγ signaling. Metabonomic analysis showed metabolic differences among groups. Nephropathy 1st administration alleviated the progression of rat renal fibrosis and reduced serum creatinine (Scr) and BUN levels. Mechanistically, Nephropathy 1st promoted the expression of PPARγ and thus activated PPARγ signaling, thereby reducing the pro-fibrotic phenotypes of fibroblasts. The therapeutic effect of Nephropathy 1st was abrogated by the PPARγ inhibitor GW9662. Moreover, Nephropathy 1st normalized the dysregulated lipid metabolism in renal fibrosis rats. In conclusion, Nephropathy 1st alleviates renal fibrosis development in a PPARγ-dependent manner.

10.
Clin Cardiol ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36448412

RESUMO

BACKGROUND: Renal and liver dysfunctions are risk factors for mortality in patients with severe aortic stenosis (AS). Transcatheter aortic valve implantation (TAVI) has the potential to break the vicious cycle between AS and hepatorenal dysfunction by relieving aortic valve obstruction. HYPOTHESIS: A part of patients can derive hepatorenal function improvement from TAVI, and this noncardiac benefit improves the intermediate-term outcomes. METHODS: We developed this retrospective cohort study in 439 consecutive patients undergoing TAVI and described the dynamic hepatorenal function assessed by model for end-stage liver disease model for end-stage liver disease (MELD)-XI score in subgroups. The endpoint was 2-year all-cause mortality. RESULTS: Receiver-operating characteristic analysis showed that the baseline MELD-XI score of 10.71 was the cutoff point. A high MELD-XI score (>10.71) at baseline was an independent predictor of the 2-year mortality hazard ratio (HR: 2.65 [1.29-5.47], p = .008). After TAVI, patients with irreversible high MELD-XI scores had a higher risk of 2-year mortality than patients who improved from high to low MELD-XI scores (HR: 2.50 [1.06-5.91], p = .03). Factors associated with reversible MELD-XI scores improvement were low baseline MELD-XI scores (≤12.00, odds ratio [OR]: 2.02 [1.04-3.94], p = .04), high aortic valve peak velocity (≥5 m/s, OR: 2.17 [1.11-4.24], p = .02), and low body mass index (≤25 kg/m2 , OR: 2.73 [1.25-5.98], p = .01). CONCLUSION: High MELD-XI score at baseline is an independent predictor for 2-year mortality. Patients with hepatorenal function improvement after TAVI have better outcomes. For patients with irreversible hepatorenal dysfunction after TAVI, further optimization of the subsequent treatment after TAVI is needed to improve the outcomes.

11.
Brain Imaging Behav ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36327020

RESUMO

Presbycusis is a major public issue that affecting elderly adults. However, the neural substrates between normal cognition and cognitive deficits in these patients need to be illustrated. 47 patients with presbycusis and 33 well-matched healthy controls were recruited in present study. Each subject underwent pure-tone audiometry (PTA), MRI scanning and cognition evaluations, then we found 22 patients with cognitive deficits and 25 patients with common cognition. We analyzed the Degree centrality (DC) characteristics among three groups, and try to recognize key nodes which contribute significantly. Subsequent functional connectivity analysis was applied using the key nodes as seeds. Compared with controls, presbycusis without cognitive impairments showed deceased DC in superior temporal gyrus (STG), inferior frontal gyrus (IFG) and supramarginal gyrus (SMG). Additionally, presbycusis with cognitive impairments showed enhanced DC in fusiform gurus (FFG), cerebellum and para-hippocampal gyrus (PHG), while weakened DC in SMG, middle frontal gyrus (IFG) and inferior Parietal lobule (IPL). Compared with normal cognition, increased DC value of cerebellum and STG, as well as decreased DC value of IPL in presbycusis with cognitive impairments were observed. We noticed that SMG may play an important role. Then the left and right SMG were used as seeds in functional connections analysis. With the seed set at left SMG, presbycusis without cognitive impairments showed decreases connections with cerebellum, temporal pole (TP), superior temporal gyrus (STG) and median cingulate cortex (MCC). Presbycusis with cognitive impairments showed weakened connectivity with cerebellum, IFG, IPL and superior frontal gyrus (SFG). The right SMG showed decrease connections with cerebellum, middle temporal gyrus (MTG), STG and increase connection with middle frontal gyrus (MFG) in presbycusis without cognitive impairments. While the right SMG showed enhanced connections with left TP, caudate, anterior cingulate cortex (ACC), angular, SFG and weakened connectivity with right SFG presbycusis with cognitive impairments. In comparison with normal cognition and impaired cognition, MFG, IFG, PHG, rolandic operculum and cerebellum were involved. These findings enriched our understanding of the neural mechanisms underlying cognitive impairments associated with presbycusis and may serve as a potential imaging biomarker for investigating and predicting cognitive difficulties.

12.
Front Psychol ; 13: 942931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211902

RESUMO

Studies show that research and development (R&D) may not always benefit entrepreneurial firms. This paper focuses on the double-edged effect of R&D activities on attracting institutional investment in entrepreneurial firms. Based on a panel dataset of 700 listed entrepreneurial firms in ChiNext, we document: (1) an inverted-U relationship between R&D intensity and future institutional investment, which we argue is evidence that institutional investors are concerned about R&D overinvestment; (2) an inverted-U relationship between R&D capitalization and future institutional investment, which we argue shows suspicion of the institutional investors towards high R&D capitalization. Furthermore, by splitting institutional investors into venture capitals (VCs) and non-venture capitals (non-VCs), we confirm that VCs have higher acceptance of both R&D intensity and capitalization as VCs have more expertise to alleviate a certain level of risks.

13.
Front Immunol ; 13: 1005426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203584

RESUMO

Mesenchymal stem cell (MSC) is a potential therapeutic material that has self-renewal, multilineage differentiation, and immunomodulation properties. However, the biological function of MSCs may decline due to the influence of donor differences and the in vitro expansion environment, which hinders the advancement of MSC-based clinical therapy. Here, we investigated a method for improving the immunomodulatory function of MSCs with the help of small-molecule compounds, A-83-01, CHIR99021, and Y27632 (ACY). The results showed that small-molecule induced MSCs (SM-MSCs) could enhance their immunosuppressive effects on T cells and macrophages. In vivo studies showed that, in contrast to control MSCs (Ctrl-MSCs), SM-MSCs could inhibit the inflammatory response in mouse models of delayed hypersensitivity and acute peritonitis more effectively. In addition, SM-MSCs showed the stronger ability to inhibit the infiltration of pro-inflammatory T cells and macrophages. Thus, small-molecule compounds ACY could better promote the immunomodulatory effect of MSCs, indicating it could be a potential improving method in MSC culture.


Assuntos
Imunomodulação , Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Imunomodulação/fisiologia , Macrófagos , Camundongos , Linfócitos T
14.
Micromachines (Basel) ; 13(10)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36295989

RESUMO

Development of a G-band broadband continuous wave (CW) traveling wave tube (TWT) for wireless communications is described in this paper. This device provides the saturation output power over 8 W and the saturation gain over 30.5 dB with a bandwidth of 27 GHz. The maximum output power is 16 W and the bandwidth of 10 W output power is 23 GHz. The 3 dB bandwidth is greater than 12.3% of fc (center frequency). The gain ripple is less than 10 dB in band. A pencil beam of 50 mA and 20 kV is used and a transmission ratio over 93% is realized. The intercept power of the beam is less than 70 W and the TWT is conduction cooled through mounting plate and air fan, which makes the device capable of operating in continuous wave mode. A Pierce's electron gun and periodic permanent magnets are employed. Chemical vapor deposition diamond disc is used in the input and output radio frequency (RF) windows to minimize the loss and voltage standing wave ratios of the traveling wave tube. Double stages deeply depressed collector is used for improving the total efficiency of the device, which can be over 5.5% in band. The weight of the device is 2.5 kg, and the packaged size is 330 mm × 70 mm × 70 mm.

15.
J Mater Chem B ; 10(43): 8918-8930, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36259986

RESUMO

Shape memory polymers (SMPs) with multiple functionalities have great potential in implantable biomedical devices, especially vascular stents. However, stents made of SMPs are generally faced with the problem of insufficient radial support due to the sharp decline of the modulus after shape recovery. Therefore, it is necessary to improve the modulus of SMPs after opening the narrow part by other means. In this study, the novel SMPs available for vascular stents were developed with impressive water-induced stiffening when shape recovered in a physiological environment. Herein, a series of shape memory polyurethanes (SMPUs) containing full hard segments on the main chains and bearing hydrophilic tertiary amine soft segments on the side chains were synthesized. When immersed in water, the soft segments were dramatically separated from the hard segments, which were aggregated more to form densely packed hard domains with stronger hydrogen bonding and higher crystallinity. Both Young's modulus and the shape recovery ratio were thus promoted due to the segmental rearrangement in water. At the same time, hydrophilic side chains migrated to the surface driven by the segmental rearrangement in water, which promotes the adhesion and growth of vascular endothelial cells and inhibits the activation of the coagulation system. The ingenious structural design provided SMPUs with adequate mechanical strength and hemocompatibility to qualify for potential applications in self-expanding vascular stents.


Assuntos
Poliuretanos , Materiais Inteligentes , Poliuretanos/química , Água , Células Endoteliais , Stents
18.
Can Respir J ; 2022: 9656278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311545

RESUMO

Background: Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods: Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results: We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001; COPD: P = 0.001); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001; COPD: p = 0.012). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO (p < 0.001). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions: In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Masculino , Feminino , Humanos , Eosinófilos , Asma/epidemiologia , Contagem de Leucócitos , Citocinas
19.
Ren Fail ; 44(1): 1687-1697, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36226438

RESUMO

Evidence suggests that intracellular angiotensin II type 1 receptor (AT1) contributes to peritoneal fibrosis (PF) under high glucose (HG)-based dialysates. It is generally believed that AT2 antagonisticly affects AT1 function. The aim of this study was to explore whether AT2 activation is beneficial for attenuating human peritoneal mesothelial cell (HPMC) injury due to HG. We treated a HPMC line with HG to induce extracellular matrix (ECM) formation. AT2 was increased and blocked using CGP42112A and AT2 siRNA. Lipid deposition was detected, signaling molecules associated with lectin-like oxidized lipoprotein receptor-1 (LOX-1) and ECM proteins were evaluated by real-time PCR and western blot. The results showed that HG led to AT2 inhibition in HPMCs, inhibition of AT2 further aggravated the expression of ECM proteins, including α-smooth muscle actin, fibroblast specific protein-1 and collagen I, while AT2 decreased the expression of ECM proteins, even during HG stimulation. Interestingly, there was a parallel change in lipid accumulation and ECM formation when AT2 was increased or depressed. Moreover, AT2-mediated decreased ECM production was associated with reduced lipid accumulation in HPMCs and depended on the downregulation of LOX-1. Further analysis showed that HG increased oxidized low-density lipoprotein (ox-LDL) deposition in HPMCs concomitant with an enhanced expression of ECM components, whereas blocking LOX-1 reversed ox-LDL deposition even in the presence of HG. This effect was also accompanied by the remission of ECM accumulation. Our results suggested that AT2 prevented ECM formation in HG-stimulated HPMCs by ameliorating lipid via LOX-1 suppression.


Assuntos
Receptor Tipo 2 de Angiotensina , Receptores de Lipoproteínas , Actinas , Angiotensina II , Colágeno Tipo I/genética , Soluções para Diálise/farmacologia , Matriz Extracelular , Glucose/farmacologia , Humanos , Lectinas/farmacologia , Lipoproteínas LDL/metabolismo , RNA Interferente Pequeno , Receptor Tipo 1 de Angiotensina , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/metabolismo
20.
Adv Clin Exp Med ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36306116

RESUMO

BACKGROUND: Parkinson's disease (PD) is characterized as a neurodegenerative disease; however, the mechanisms regarding its pathogenesis have not been fully explored. OBJECTIVES: To explore the role of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in the progression of PD. MATERIAL AND METHODS: The circHIPK3 and microRNA-124 (miR-124) expression in human serum and cerebral fluid was detected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 92 PD patients and 95 controls. The circHIPK3 was overexpressed and/or silenced in cells to explore its molecular mechanisms and effects on neuroinflammation. The production of intracellular reactive oxygen species (ROS) was assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Interleukin 6 (IL-6), IL-1ß and tumor necrosis factor alpha (TNF-α) production in BV2 cells after the indicated treatment was measured using enzyme-linked immunosorbent assay (ELISA). The protein expression of microglia markers (cluster of differentiation molecule 11b (CD11b) and ionized calcium-binding adapter molecule 1 (Iba-1)), pyroptosis-related factors, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC), and caspase-1, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) were examined using western blot analysis. Furthermore, the interaction between circHIPK3, miR-124 and STAT3 was predicted with bioinformatics and examined using fluorescence in situ hybridization (FISH), luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP). RESULTS: The expression of circHIPK3 in human serum and cerebral fluids was significantly higher than in controls, whereas miR-124 expression was drastically reduced. In addition, lipopolysaccharide (LPS)-treated BV2 cells exhibited higher expression of circHIPK3 and lower miR-124 expression. The SH-SY5Y cells exhibited a significantly impaired viability and elevated apoptotic rate, along with an upregulation of circHIPK3 and a downregulation of miR-124 expression after being treated with supernatants collected from LPS-treated BV2 cells. The upregulation of circHIPK3 increased IL-6, IL-1ß and TNF-α secretion in BV2 cells. The protein expressions of microglia markers (CD11b and Iba-1), as well as pyroptosis-related factors, NLRP3, caspase-1, and ASC, were also increased following the expression of circHIPK3. All these effects were reversed by the addition of miR-124. CONCLUSIONS: The circHIPK3 enhances neuroinflammation by sponging miR-124 and regulating the miR-124-mediated STAT3/NALP3 pathway in PD.

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