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1.
Artigo em Inglês | MEDLINE | ID: mdl-35507777

RESUMO

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have been evaluated in many studies as promising therapeutic agents for pulmonary hypertension (PH). However, low yields and heterogeneity are a major barrier in the translational utility of EVs for clinical studies. To address these limitations, we fabricated MSCs derived nanovesicles (MSC-NVs) by serial extrusion through filters resulting in MSC-NVs with characteristics similar to conventional EVs but with much higher production yields. Herein, we examined the therapeutic efficacy of MSC-NVs in preclinical models of PH in vitro and in vivo. Intervention with MSC-NVs improved the core pathologies of monocrotaline (MCT) induced PH in rat. Intravenous administration of MSC-NVs resulted in significant uptake within hypertensive lungs, pulmonary artery lesions and especially in pulmonary artery smooth muscle cells (PASMCs). In vitro, MSC-NVs inhibited PDGF-induced proliferation, migration, and phenotype switch of PASMCs. miRNA sequencing analysis of the genetic cargo of MSC-NVs revealed that miR-125b-5p and miR-100-5p are highly abundant, suggesting they might account for the therapeutic effects of MSC-NVs in PH. Depletion of miR-125b-5p and miR-100-5p in MSCs almost completely abolished the beneficial effects of MSC-NVs in protecting PASMCs from PDGF stimulated changes in vitro, and also diminished the protective effects of MSC-NVs in MCT induced PH in vivo. These data highlight the efficacy and advantages of MSC-NVs over MSC-EVs as a promising therapeutic strategy against PH.

2.
Anal Bioanal Chem ; 414(13): 3875-3884, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35389096

RESUMO

C-Reactive protein (CRP) is an important marker for in vitro diagnosis (IVD) of inflammation. However, CRP immunoturbidimetric kits from different manufacturers exhibit inconsistency in evaluation, making clinical diagnosis challenging. The use of immunological methods in diagnosis means that the differences in epitopes across kits may directly lead to inconsistent results. Therefore, to provide consistent results, it is essential to perform epitope mapping of different kits. The composition of antibodies in a single kit is typically complex, with a combination of polyclonal antibodies or monoclonal antibodies. Here, we show an epitope screening strategy for complex antibodies in a kit based on hydrogen-deuterium exchange mass spectrometry (HDX-MS). We applied this workflow to successfully map the epitopes for three kits from three different manufacturers and compared their quantitative results. We obtained different quantitative results using kits from different manufacturers upon epitope mapping, confirming the correlation between the quantitative results and the epitopes. Thus, we have established a workflow based on HDX-MS to screen epitopes in IVD kits. This work helps determine the quantitative accuracy of a kit based on structural information, can guide the design and production of IVD reagents, and further improves the accuracy of IVD.


Assuntos
Medição da Troca de Deutério , Espectrometria de Massa com Troca Hidrogênio-Deutério , Proteína C-Reativa , Deutério , Medição da Troca de Deutério/métodos , Mapeamento de Epitopos/métodos , Epitopos
3.
Materials (Basel) ; 15(3)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35161073

RESUMO

The mechanical response characteristics of mudstone from the ingate roadway of the west ventilation shaft in Yuandian No. 2 coal mine, Huaibei City, Anhui Province, China to dynamic loads were quantified in single- and cyclic-impact compression tests, using the split-Hopkinson pressure bar test device. The dynamic stress-strain relationships and the failure characteristics of mudstone samples under different impact loads were analyzed systematically. Considering the "rate effect" of the mudstone dynamic strength, the dynamic strength criterion of mudstone was proposed, and the dynamic damage constitutive model of mudstone was established, based on the statistical damage theory. In response to single-impact loads, with increasing impact pressure, the mudstone peak stress and strain gradually increased, and the peak stress and average strain rate increased nonlinearly. In response to cyclic-impact loads, with an increasing number of impacts, the mudstone peak stress first increased and then decreased, and the peak strain increased gradually. With increasing impact pressure, the number of impacts to the samples' failure decreased gradually. By parameter identification and comparative analysis of the test results, the proposed dynamic damage constitutive model of mudstone was validated. The model can be used for stability analysis of roadway-surrounding rock under dynamic loads.

4.
Gene ; 820: 146209, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35093450

RESUMO

OBJECTIVE: This study aimed to explore the specific molecular mechanism of the therapeutic effect of quercetin in knee osteoarthritis (KOA). METHODS: The KOA rat model was constructed by excising the medial meniscus and transecting the anterior meniscus. Joint injuries in rats were determined by Hematoxylin-Eosin (H&E) and Safranin O staining. The severity of KOA was then assessed according to the Osteoarthritis Research Society International (OARSI). The expressions of TSC2 and LC2B in joint tissue were measured by immunohistochemistry. Besides, chondrocytes treated with 10 ng/ml IL-1ß were used to construct a chondrocyte arthritis model, while those treated with 4 or 8 µM quercetin were served as treatment groups. MTT, flow cytometry and toluidine blue staining were used to detect cell viability, apoptosis and mucopolysaccharide synthesis, respectively. qRT-PCR or Western blot was performed to determine the expressions of MMP-13, collagen II, Aggrecan, TSC2, RHEB, mTOR, p-mTOR, ULK1, p-ULK1, LC3B-I, LC3B-II and P62 in chondrocytes. RESULTS: Quercetin alleviated the joint injury and suppressed the increase in MMP-13 expression and the decreases in collagen II and Aggrecan expressions in KOA rats. In addition, quercetin suppressed RHEB, p-mTOR, p-ULK1 and P62 expressions but promoted TSC2 and LC3BII expressions in KOA rats. Furthermore, quercetin could relieve the decrease of cell viability and the increase of apoptosis that induced by IL-1ß, and promote the synthesis of IL-1ß-inhibited mucopolysaccharide in chondrocytes. Nevertheless, siTSC2 partially offset the therapeutic effects of quercetin in chondrocytes. CONCLUSION: Quercetin alleviated KOA by mediating the TSC2-RHBE-mTOR signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite do Joelho/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glicosaminoglicanos/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Osteoartrite do Joelho/tratamento farmacológico , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo
5.
Neurocrit Care ; 36(1): 106-115, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34286462

RESUMO

BACKGROUND: Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are linked to intracranial aneurysm (IA) formation and progression. Long antisense noncoding RNA in the INK4 locus (ANRIL) has been reported to regulate VSMC functions in several cardiovascular diseases. However, little is known about how ANRIL influences VSMC proliferation and apoptosis during IA pathogenesis. METHODS: The expression level of ANRIL in the plasma and arterial wall tissues of patients with IA was detected by real-time quantitative polymerase chain reaction. The functional role of ANRIL in the regulation of VSMC proliferation and apoptosis and its downstream regulatory mechanism were determined using Cell Counting Kit 8, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated UTP nick end labeling, western blotting, luciferase reporter assay, and RNA immunoprecipitation assay. RESULTS: ANRIL was downregulated in the plasma and arterial wall tissues of patients with IA, when compared with control groups. Overexpression of ANRIL significantly promoted VSMC proliferation and blocked cell apoptosis. Mechanistic studies demonstrated that ANRIL directly bound to microRNA-7 (miR-7) and that overexpression of miR-7 overturned the increased cell proliferation and decreased cell apoptosis, which was induced by ANRIL restoration. Besides, further study showed that ANRIL positively regulated fibroblast growth factor 2 (FGF2) expression via targeting miR-7. CONCLUSIONS: These results suggested that ANRIL affects VSMC proliferation and apoptosis via regulation of the miR-7/FGF2 pathway in IA, which provided a potential novel strategy for the treatment of IA.


Assuntos
Aneurisma Intracraniano , MicroRNAs , RNA Longo não Codificante , Apoptose , Proliferação de Células/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
6.
J Biomech Eng ; 144(2)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34423809

RESUMO

A combined experimental-numerical work was conducted to comprehensively validate a subject-specific continuum model of voice production in larynx using excised canine laryngeal experiments. The computational model is a coupling of the Navier-Stokes equations for glottal flow dynamics and a finite element model of vocal fold dynamics. The numerical simulations employed a cover-body vocal fold structure with the geometry reconstructed from magnetic resonance imaging scans and the material properties determined through an optimization-based inverse process of experimental indentation measurement. The results showed that the simulations predicted key features of the dynamics observed in the experiments, including the skewing of the glottal flow waveform, mucosal wave propagation, continuous increase of the divergent angle and intraglottal swirl strength during glottal closing, and flow recirculation between glottal jet and vocal fold. The simulations also predicted the increase of the divergent angle, glottal jet speed, and intraglottal flow swirl strength with the subglottal pressure, same as in the experiments. Quantitatively, the simulations over-predicted the frequency and jet speed and under-predicted the flow rate and divergent angle for the larynx under study. The limitations of the model and their implications were discussed.


Assuntos
Laringe , Fonação , Animais , Simulação por Computador , Cães , Glote , Prega Vocal
7.
Front Pharmacol ; 13: 743210, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370713

RESUMO

Background: The current medical treatments for connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) do not show favorable efficiency for all patients, and identification of novel drugs is desired. Methods: Text mining was performed to obtain CTD- and PAH-related gene sets, and the intersection of the two gene sets was analyzed for functional enrichment through DAVID. The protein-protein interaction network of the overlapping genes and the significant gene modules were determined using STRING. The enriched candidate genes were further analyzed by Drug Gene Interaction database to identify drugs with potential therapeutic effects on CTD-PAH. Results: Based on text mining analysis, 179 genes related to CTD and PAH were identified. Through enrichment analysis of the genes, 20 genes representing six pathways were obtained. To further narrow the scope of potential existing drugs, we selected targeted drugs with a Query Score ≥5 and Interaction Score ≥1. Finally, 13 drugs targeting the six genes were selected as candidate drugs, which were divided into four drug-gene interaction types, and 12 of them had initial drug indications approved by the FDA. The potential gene targets of the drugs on this list are IL-6 (one drug) and IL-1ß (two drugs), MMP9 (one drug), VEGFA (three drugs), TGFB1 (one drug), and EGFR (five drugs). These drugs might be used to treat CTD-PAH. Conclusion: We identified 13 drugs targeting six genes that may have potential therapeutic effects on CTD-PAH.

8.
Bone ; 154: 116259, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798298

RESUMO

OBJECTIVE: To observe the effect of AZD0530 on the progression of knee OA after blocking ß-catenin phosphorylation and then dormancy of the Wnt/ß pathway by tyrosine kinase Fyn. METHODS: The levels of Fyn, ß-catenin, p-ß-catenin (Tyr142), the chondrocyte positive marker Aggrecan, and the chondrocyte negative marker MMP13 were observed in human knee tibial plateau chondrocytes in vivo and in vitro. Different doses of AZD0530 were used to treat chondrocytes of the human OA tibial plateau chondrocytes in vitro, and the degree of chondrocyte degeneration was observed. Different doses of AZD0530 were intraarticularly injected into OA rats to observe the degree of tibial plateau cartilage degeneration. RESULTS: When OA occurred in human knee, the levels of tyrosine kinase Fyn,ß-catenin and p-ß-catenin (Tyr142) in chondrocytes increased significantly.The level of Aggrecan decreased and MMP13 increased in chondrocytes. The levels of ß-catenin, p-ß-catenin (Tyr142) and MMP13 in chondrocytes decreased, while the level of Aggrecan increased after AZD0530 was used to intervene chondrocytes in vitro, which was positively correlated with the dose of AZD0530. Intra-articular injection of AZD0530 obviously attenuated the degeneration of articular cartilage, which was positively correlated with the dose of AZD0530. CONCLUSION: The level of Fyn in chondrocytes of human knee tibial plateau increased significantly when OA occurred. AZD0530 can inhibit tyrosine kinase Fyn from ß-catenin phosphorylation, a key Wnt/ß pathway protein, and then inhibit Wnt/ß pathway levels in chondrocytes. This finding also suggests that disruption of the Wnt/ß pathway with AZD0530 provides chondral protection in rat posttraumatic OA.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Benzodioxóis , Cartilagem Articular/patologia , Células Cultivadas , Condrócitos/metabolismo , Osteoartrite/patologia , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteínas Proto-Oncogênicas c-fyn/farmacologia , Quinazolinas , Ratos , Via de Sinalização Wnt , beta Catenina/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-34950216

RESUMO

BACKGROUND: Shu-Di-Huang (Radix Rehmanniae Praeparata, RR) and Gan-Cao (liquorice, L) are frequently used traditional Chinese herb pair in treating osteoporosis (OP). However, the exact mechanism of the RR and L herb pair (RR-L) remains unclear. To explore the efficacy and possible mechanisms of RR-L in treating OP, in silico, in vitro, and in vivo experiments were conducted in the current study. METHODS: In silico, potential therapeutic target genes and active chemical compounds of RR-L herb pair were predicted and constructed into a network. In vivo, 30 Sprague Dawley rats were divided into 3 groups, including the sham group, the OP model group, and the RR-L-treated OP group. Micro-CT and pathological sections were conducted to validate the therapeutic effects of RR-L in treating OP. MSCs of rats were isolated and cultured in vitro to validate the mesenchymal stem cells (MSCs) related phenotype changes, including Alizarin red staining, Oil red staining, and immunofluorescence. In vitro, cell proliferation analysis, Alizarin red staining, Oil red staining, immunofluorescence of NF-κB, and protein expression of PPARγ, RUNX2, OCN, and p65 were conducted on MSCs to explore the RR-L containing serum in vitro. Also, activator and inhibitor of NF-κB signaling pathway were introduced to determine the possible mechanism of RR-L in the treatment of OP via enhancing MSCs proliferation and differentiation. RESULTS: In silico, 168 chemical compounds with a property of oral bioavailability ≥30% and drug-likeness ≥0.18 were recognized as potentially active compounds in RR-L and 249 genes were found to be the targets of which. Among them, 120 genes were found to be therapeutic genes of RR-L in treating OP and KEGG and GO analysis of which demonstrated that RR-L involves in lipid metabolism and multiple inflammation-related signaling pathways. In vivo, ovariectomy- (OVX-) induced OP phenotypes in Sprague Dawley rats include bone mineral density and microarchitecture damaging, abnormal bone metabolism, upregulation of inflammation markers, and damaged differentiation potential of MSCs. Treatment of RR-L reversed the trend and restored the differentiation potential of MSCs. In vitro, RR-L containing serum promoted the osteogenic differentiation and suppressed adipogenic differentiation of MSCs via downregulation of the NF-κB signaling pathway. Also, RR-L containing serum inhibited the tumor necrosis factor-α (TNF-α) induced activation of the NF-κB signaling pathway. On the opposite, the addition of the NF-κB specific inhibitor significantly reduced the effect of RR-L on MSCs. CONCLUSIONS: In the current study, network pharmacology prediction and experimental validation elucidated that the RR-L herb pair restored damaged MSC differentiation potential via the NF-κB signaling pathway; this could be the possible mechanism of RR-L in treating OP. This finding provides an alternative option in OP therapy.

10.
Front Immunol ; 12: 775758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956205

RESUMO

[This corrects the article DOI: 10.3389/fimmu.2020.583084.].

11.
Zhongguo Gu Shang ; 34(12): 1186-90, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34965640

RESUMO

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.


Assuntos
Doenças da Medula Óssea , Osteoartrite do Joelho , Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Humanos , Articulação do Joelho , Imageamento por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem
12.
Anal Chem ; 93(50): 16947-16955, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34841854

RESUMO

Library matching using carbon-13 nuclear magnetic resonance (13C NMR) spectra has been a popular method adopted in compound identification systems. However, the usability of existing approaches has been restricted as enlarging a library containing both a chemical structure and spectrum is a costly and time-consuming process. Therefore, we propose a fundamentally different, novel approach to match 13C NMR spectra directly against a molecular structure library. We develop a cross-modal retrieval between spectrum and structure (CReSS) system using deep contrastive learning, which allows us to search a molecular structure library using the 13C NMR spectrum of a compound. In the test of searching 41,494 13C NMR spectra against a reference structure library containing 10.4 million compounds, CReSS reached a recall@10 accuracy of 91.64% and a processing speed of 0.114 s per query spectrum. When further incorporating a filter with a molecular weight tolerance of 5 Da, CReSS achieved a new remarkable recall@10 of 98.39%. Furthermore, CReSS has potential in detecting scaffolds of novel structures and demonstrates great performance for the task of structural revision. CReSS is built and developed to bridge the gap between 13C NMR spectra and structures and could be generally applicable in compound identification.


Assuntos
Espectroscopia de Ressonância Magnética
13.
Basic Res Cardiol ; 116(1): 53, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546460

RESUMO

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-ß signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-ß-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-ß/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-ß signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-ß signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-ß pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-ß-associated mechanisms.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Proteínas Morfogenéticas Ósseas , Células Endoteliais , Humanos , Hipertensão Pulmonar/genética , Hipóxia , MicroRNAs/genética , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina , Artéria Pulmonar , Fator de Crescimento Transformador beta
14.
J Mol Graph Model ; 109: 108003, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34500246

RESUMO

Based on the interesting Janus-type all-cis1,2,3,4,5,6-hexafluorocyclohexane (1) molecule, a novel type of excess electron compounds MF-1-MH (MF = Li, Na and K, MH = Zn, Cd and Hg) were designed theoretically. The geometric structures, electronic structures and nonlinear optical properties of MF-1-MH compounds were studied by density functional theory. Our results show that in Li-1-MH, the obvious charge transfer between Li and MH can be observed while in Na/K-1-MH, the charge transfer between Na/K and MH is negligible. Particularly, the MF-1-MH exhibit remarkable nonlinear optical (NLO) response and the first hyperpolarizability of the K-1-Zn almost achieve 1.0 × 106 au. We hope this work will further enrich the family of excess electron compounds, so that more experimental interests and efforts can be attracted to propose and synthesize new excellent NLO materials.


Assuntos
Elétrons , Mercúrio , Cádmio , Lítio , Zinco
15.
Cartilage ; 13(2_suppl): 796S-807S, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34493119

RESUMO

OBJECTIVE: The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. DESIGN: Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group, and a 3-methyladenine (3-MA) group. Intracellular glycogen accumulation and chondrocyte apoptosis were assessed by altering the level of autophagy in chondrocytes in vivo. RESULTS: When spontaneous OA occurred in guinea pigs, autophagy levels in tibial plateau chondrocytes decreased, while intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the level of autophagy in tibial plateau chondrocytes in guinea pigs with OA, intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased, while inhibiting autophagy had the opposite effects. CONCLUSION: The results indicate that the function of autophagy in chondrocytes may at least partly involve the catabolism of glycogen. In guinea pigs with OA, the level of autophagy in tibial plateau chondrocytes decreased, and chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for chondrocytes and increased apoptosis.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Animais , Apoptose , Autofagia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Feminino , Cobaias , Osteoartrite do Joelho/metabolismo
17.
Front Cell Dev Biol ; 9: 693342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458257

RESUMO

Increasing evidence suggests that triggering receptor expressed on myeloid cells 2 (TREM2) is implicated in the pathophysiology of neuroinflammation. The aim here was to investigate the neuroprotective role of TREM2 and its regulatory mechanism after subarachnoid hemorrhage (SAH). TREM2 siRNA was administered to measure the detrimental role of TREM2 in mediating microglial polarization in vivo and in vitro after experimental SAH. The relationship between Toll-like receptor 4 (TLR4) signaling and TREM2 was further explored. The soluble TREM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The results showed that TREM2 mainly located in the microglia and presented a markedly delayed elevation after SAH. TREM2 knockdown triggered increased pro-inflammatory productions, aggravated microglial activities, and further exacerbated neurological dysfunction after SAH. Significantly, TLR4 knockout increased the expression of TREM2, accompanied by ameliorated neuroinflammation and improved neurological function. Corresponding to different clinical Hunt-Hess grades, obviously enhanced accumulation of soluble TREM2 was detected in the CSF of patients with SAH. TREM2 played a pivotal role in mediating microglial polarization after SAH, and the neuroprotective effect of TREM2 might be potentially suppressed by the hyperactive TLR4 in the early phase of SAH. Pharmacological targeting of TREM2 may be a promising strategy for SAH therapy.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34462644

RESUMO

OBJECTIVE: To investigate the efficacy and safety of performing primary unilateral total knee arthroplasty (TKA) in the "Si hour-period" meaning 09:00 a.m. to 11:00 a.m. (one of the 12 two-hour periods into which the day was traditionally divided, each being given the name of one of the 12 earthly branches), compared with the "Wei hour-period" (13:00-15:00). METHODS: Patient documentations were studied for those who underwent a primary unilateral TKA performed by the same surgical team with a tourniquet between January 2018 and January 2021 at our medical center. Eighty-four patients were enrolled and assigned into group A (in Si hour-period) and group B (in Wei hour-period). The main outcomes were total blood cell loss (TBL), hidden blood loss (HBL), visible blood loss (VBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were length of hospital stay (LOS), postoperative femorotibial mechanical axis (FTMA), FTMA correction, platelet count, plasma D-dimer (D-D), prothrombin time (PT), international normalized ratio (INR), and the incidence of postoperative complications. RESULTS: Group A showed statistical significance lower at the mean TBL, the mean HBL, and the maximum Hb drop (95% CI: -352.8 to -46.1,P=0.011, 95% CI: -348.0 to -40.1,P=0.014, and 95% CI: -9.5 to -0.7,P=0.023, respectively) after TKA than group B. The postoperative platelet count of group A was more significant than that of group B (95% CI:3.1 to 52.9, P=0.028). The VBL, transfusion rate, the LOS, postoperative FTMA, FTMA correction, plasma D-D, PT, INR, and the incidence of postoperative complications (wound complications, calf muscular vein thrombosis, infection, pulmonary embolism, and deep vein thrombosis) were similar between the two groups (P > 0.05, respectively). CONCLUSION: Our study shows that blood loss can be reduced when TKA is performed in the "Si hour-period," which may be due to increasing platelet count, and postoperative complications did not increase, compared with the Wei hour-period. We recommend that the selective operation, such as TKA, should be performed in the "Si hour-period" in clinical practice between the two hour-period.

19.
Small ; 17(36): e2102461, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34313386

RESUMO

Heterostructures for charge-carrier manipulation have laid the foundation of modern optoelectronic devices, such as photovoltaics and photodetectors. High-performance heterostructure devices usually impose stringent requirements on the material quality to sustain efficient carrier transport and charge transfer, thus leading to sophisticated fabrication processes. Here, a simple yet efficient strategy is proposed to develop ultrasensitive photodetectors based on heterostructures of chemical vapor deposition-grown MoS2 and polycrystalline-layered perovskites. The layered perovskites possess pure crystallographic orientation with conductive edges in contact with MoS2 , which gives rise to efficient light absorption, exciton diffusion, and interfacial charge transfer. In dark state, the mismatch of work functions of two materials facilitates low dark currents by the depletion of electrons in MoS2 . Under light irradiation, efficient exciton diffusion and interfacial charge transfer are realized in the heterostructures with type-II band alignment, which produces drifting electrons in MoS2 and leaves trapped holes in layered perovskites. The photodetectors present suppress noises and boost photocurrents, yielding a champion device with a responsivity of 2.5 × 104  A W-1 , and a specific detectivity of 4.1 × 1014  Jones. The results demonstrate a scalable approach for the integration of high-performance devices with high tolerance to defects.

20.
Front Cell Dev Biol ; 9: 659809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178985

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through interactions with its receptor, Angiotensin-converting enzyme 2 (ACE2), causing severe acute respiratory syndrome and death in a considerable proportion of people. Patients infected with SARS-CoV-2 experience digestive symptoms. However, the precise protein expression atlas of ACE2 in the gastrointestinal tract remains unclear. In this study, we aimed to explore the ACE2 protein expression pattern and the underlying function of ACE2 in the gastrointestinal tract, including the colon, stomach, liver, and pancreas. METHODS: We measured the protein expression of ACE2 in the gastrointestinal tract using immunohistochemical (IHC) staining with an ACE2-specific antibody of paraffin-embedded colon, stomach, liver, and pancreatic tissues. The correlation between the protein expression of ACE2 and the prognosis of patients with gastrointestinal cancers was analyzed by the log-rank (Mantel-Cox) test. The influence of ACE2 on colon, stomach, liver, and pancreatic tumor cell line proliferation was tested using a Cell Counting Kit 8 (CCK-8) assay. RESULTS: ACE2 presented heterogeneous expression patterns in the gastrointestinal tract, and it showed a punctate distribution in hepatic cells. Compared to that in parallel adjacent non-tumor tissues, the protein expression of ACE2 was significantly increased in colon cancer, stomach cancer, and pancreatic cancer tissues but dramatically decreased in liver cancer tissues. However, the expression level of the ACE2 protein was not correlated with the survival of patients with gastrointestinal cancers. Consistently, ACE2 did not affect the proliferation of gastrointestinal cancer cells in vitro. CONCLUSION: The ACE2 protein is widely expressed in the gastrointestinal tract, and its expression is significantly altered in gastrointestinal tumor tissues. ACE2 is not an independent prognostic marker of gastrointestinal cancers.

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