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1.
J Agric Food Chem ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720533

RESUMO

In this study, a series of acrylamide derivatives containing trifluoromethylpyridine or piperazine fragments were rationally designed and synthesized. Subsequently, the in vitro antifungal activities of all of the synthesized compounds were evaluated. The findings revealed that compounds 6b, 6c, and 7e exhibited >80% antifungal activity against Phomopsis sp. (Ps) at the concentration of 50 µg/mL. Furthermore, the EC50 values for compounds 6b, 6c, and 7e against Ps were determined to be 4.49, 6.47, and 8.68 µg/mL, respectively, which were better than the positive control with azoxystrobin (24.83 µg/mL). At the concentration of 200 µg/mL, the protective activity of compound 6b against Ps reached 65%, which was comparable to that of azoxystrobin (60.9%). Comprehensive mechanistic studies, including morphological studies with fluorescence microscopy (FM), cytoplasmic leakage, and enzyme activity assays, indicated that compound 6b disrupts cell membrane integrity and induces the accumulation of defense enzyme activity, thereby inhibiting mycelial growth. Therefore, compound 6b serves as a valuable candidate for the development of novel fungicides for plant protection.

2.
Front Pharmacol ; 15: 1399625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720781

RESUMO

Objective: To investigate the immune mechanism of osteosarcoma (OS)-specific markers to mitigate bone destruction in the aggressive OS, prone to recurrence and metastasis. Methods: Gene expression patterns from the Gene Expression Omnibus (GEO) database (GSE126209) were analyzed using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) modeling, and survival analysis to identify charged multivesicular body protein 4C (CHMP4C). Subsequently, its role in regulating the immune system and immune cell infiltration was explored. CHMP4C expression and signaling molecules in OS were assessed in osteosarcoma cell lines (MG63, U2OS, HOS) and hFOB1.19 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The impact of CHMP4C upregulation and interference on OS-related signaling molecules in MG63 cells was studied. Functional validation of CHMP4C in MG63 OS cells was confirmed through cell counting Kit-8 (CCK-8), transwell, and colony formation assays. In vivo experiments were conducted using Specific Pathogen Free (SPF)-grade male BALB/C nude mice for OS xenograft studies. Results: Based on the gene expression profiles analysis of six osteosarcoma samples and six normal tissue samples, we identified 1,511 upregulated DEGs and 5,678 downregulated DEGs in normal tissue samples. A significant positive correlation between the "yellow-green" module and OS was found through WGCNA analysis. Expression levels of CHMP4C, phosphorylated Glycogen Synthase Kinase 3ß (p-GSK3ß), and ß-catenin were notably higher in U2OS, HOS, and MG63 OS cells than in hFOB1.19 human osteoblasts. Overexpressing CHMP4C in MG63 OS cells upregulated CHMP4C, p-GSK3ß, and ß-catenin while downregulating GSK3ß, leading to increased proliferation and migration of MG63 cells. Conversely, interrupting CHMP4C had the opposite effect. High expression of CHMP4C significantly accelerated the growth of OS in nude mice, resulting in substantial upregulation of CHMP4C, p-GSK3ß, and ß-catenin expression and suppression of Glycogen Synthase Kinase 3ß (GSK3ß) expression in OS tissues. Conclusion: CHMP4C may serve as a specific immunomodulatory gene for OS. Its activation of the Wnt/ß-catenin signaling pathway, mainly by increasing the phosphorylation echelon of GSK3ß, promotes the invasion and spread of OS.

3.
J Agric Food Chem ; 72(13): 6979-6987, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38520352

RESUMO

Potato virus Y (PVY) is an important plant virus that has spread worldwide, causing significant economic losses. To search for novel structures as potent antiviral agents, a series of chiral indole derivatives containing oxazoline moieties were designed and synthesized and their anti-PVY activities were evaluated. Biological activity tests demonstrated that many chiral compounds exhibited promising anti-PVY activities and that their absolute configurations exhibited obvious distinctions in antiviral bioactivities. Notably, compound (S)-4v displayed excellent curative and protective efficacy against PVY, with EC50 values of 328.6 and 256.1 µg/mL, respectively, which were superior to those of commercial virucide ningnanmycin (NNM, 437.4 and 397.4 µg/mL, respectively). The preliminary antiviral mechanism was investigated to determine the difference in antiviral activity between the two enantiomers of 4v chiral compounds. Molecular docking indicated a stronger binding affinity between the coating proteins of PVY (PVY-CP) and (S)-4v (-6.5 kcal/mol) compared to (R)-4v (-6.2 kcal/mol). Additionally, compound (S)-4v can increase the chlorophyll content and defense-related enzyme activities more effectively than its enantiomer. Therefore, this study provides an important basis for the development of chiral indole derivatives containing oxazoline moieties as novel agricultural chemicals.


Assuntos
Potyvirus , Vírus do Mosaico do Tabaco , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Antivirais/farmacologia , Antivirais/química , Indóis/farmacologia , Desenho de Fármacos
4.
Orthop Surg ; 16(3): 628-636, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38326241

RESUMO

OBJECTIVE: Patients who undergo a biplanar ascending medial open-wedge high tibial osteotomy with an excessive correction angle might experience patella infera and even knee pain after surgery. The purpose of this study was to identify the cut-off points for the degree of knee varus correction of open-wedge high tibial osteotomy, which is related to the symptomatic patellar position change. METHODS: This retrospective study included 124 patients (mean age 61.69 ± 6.28 years; 78 women, 46 men) with varying degrees of varus knee osteoarthritis. All patients had undergone standard biplanar medial open-wedge high tibial osteotomy. They were divided into nine groups according to the change in hip-knee-ankle angle. Plain radiographs and three-dimensional CT images were obtained preoperatively and 18 months postoperatively. Patellar height was assessed using the Caton-Deschamps index, the Insall-Salvati index, and the Blackburne-Peel index. The patellofemoral index and patellar tilt were used to evaluate the degree of horizontal displacement of the patella. The varus correction, medial-proximal tibial angles, joint line convergence angles, and hip-knee-ankle angles were also measured. The subjective score was evaluated using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). RESULTS: There were significant changes in patella indexes in each group after surgery, among which there was no significant difference in patellar height changes for Groups A to F (p > 0.05), which were significantly lower than those in Group G, H, and I (p < 0.001). The patellar tilt and patellofemoral index also followed the same trend. The improvement in WOMAC scores for Groups G, H, and I was also significantly less for Groups A to F (p < 0.001). CONCLUSION: The patellar height, patellar tilt, and patellofemoral index all changed significantly in parallel with increasing degrees of osteotomy correction. The cut-off points for correction angle are 12.5° to 13.4°. When the correction angle is larger than this range, the patellar position can be significantly affected. Postoperative patellofemoral joint pain may be related to the changes in patella position.


Assuntos
Osteoartrite do Joelho , Patela , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Patela/diagnóstico por imagem , Patela/cirurgia , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Osteotomia/métodos , Dor Pós-Operatória
5.
Ecotoxicol Environ Saf ; 269: 115781, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056122

RESUMO

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.


Assuntos
Transtornos de Ansiedade , Arsênio , MicroRNAs , Piroptose , Animais , Humanos , Masculino , Ratos , Transtornos de Ansiedade/induzido quimicamente , Arsênio/efeitos adversos , Arsênio/toxicidade , Caspase 1/metabolismo , Interleucina-18/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/genética , Ratos Wistar
6.
Chem Asian J ; 18(22): e202300731, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37755436

RESUMO

Aldehyde catalysts have proven to be highly effective in facilitating and accelerating a wide range of challenging transformations in organic chemistry. This article is structured into three main sections, focusing on the utilization of aldehydes as organocatalysts, the aldehydes/transition metals catalytic systems, and photochemical initiators. Finally, we provide a concise summary of the advancements in this fascinating research field, offering our perspectives and insights.

7.
Eur J Nutr ; 62(7): 3097-3111, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37505286

RESUMO

PURPOSE: The purpose of this study was to prepare the novel mussel-derived ACE inhibitory peptides (MEPs) by enzymatic hydrolysis of Mytilus edulis and investigate their antihypertensive effects in vivo. METHODS: After assessing the stability of MEPs in vitro, we investigated the effect of MEPs on hypertension using spontaneously hypertensive rats (SHRs). Subsequently, MEPs were purified and identified by ultrafiltration, gel filtration chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Our study demonstrated that MEPs could keep stable ACE inhibitory activity after treatment with heat, acid, alkali, metal ions and simulated gastrointestinal digestive fluid. Additionally, the animal experiments showed that both short-term and long-term treatment with MEPs resulted in a significant reduction in systolic and diastolic blood pressure in SHRs. Mechanistically, the results suggested that MEPs could reduce vascular remodeling, regulate renin-angiotensin system (RAS), and inhibit kidney and myocardial fibrosis. Finally, we isolated and identified five peptides from MEPs, with the peptide Ile-Leu-Thr-Glu-Arg showed the highest ACE inhibition rate. CONCLUSION: Our findings demonstrate the potential use of MEPs as active components in functional foods designed to lower blood pressure.


Assuntos
Bivalves , Hipertensão , Ratos , Animais , Ratos Endogâmicos SHR , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/química , Cromatografia Líquida , Espectrometria de Massas em Tandem , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/química , Peptídeos/farmacologia , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Bivalves/química , Peptidil Dipeptidase A
8.
Molecules ; 28(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37241792

RESUMO

An N-heterocyclic carbene (NHC)-catalyzed atroposelective annulation reaction is disclosed for quick and efficient access to thiazine derivatives. A series of axially chiral thiazine derivatives bearing various substituents and substitution patterns were produced in moderate to high yields with moderate to excellent optical purities. Preliminary studies revealed that some of our products exhibit promising antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) that causes rice bacterial blight.

9.
JMIR Public Health Surveill ; 9: e38881, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36826980

RESUMO

BACKGROUND: Nearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes. OBJECTIVE: This study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China. METHODS: We performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases. RESULTS: A total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n=5507, 54%); 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n=614, 70.7% vs n=1447, 15.5%; P<.001), while nonstudent cases were more likely to be infected through heterosexual contact (n=7887, 84.5% vs n=254, 29.3%; P<.001). Moreover, nonstudent cases had a significantly lower CD4 count than student cases at the time of HIV diagnosis (332 vs 362 cells/µL; P<.001). Nonstudents also had a delayed antiretroviral therapy (ART) initiation compared to students (93 days vs 22 days; P<.001). Furthermore, the mortality rate of 0.4 and 1.0 deaths per 100 person-years were recorded for student and nonstudent youths with HIV, respectively. Overall, the mortality risk in nonstudent cases was 2.3 times that of student cases (adjusted hazard ratio [AHR] 2.3, 95% CI 1.2-4.2; P=.008). The virologic failure rate was 2.3 and 2.6 per 100 person-years among student and nonstudent youths living with HIV, respectively. Nonstudent cases had double the risk of virologic failure compared to student cases (AHR 1.9, 95% CI 1.3-2.6; P<.001). CONCLUSIONS: Nonstudent youths living with HIV might face a low CD4 count at the time of HIV diagnosis, delayed ART initiation, and increased risk of death and virologic failure. Thus, HIV prevention and interventions should target youths who dropped out of school early to encourage safe sex and HIV screening, remove barriers to HIV care, and promote early ART initiation to curb the HIV epidemic among youths.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Masculino , Humanos , Adolescente , Feminino , Infecções por HIV/diagnóstico , Estudos de Coortes , China , Resultado do Tratamento
10.
Neuroscience ; 513: 126-133, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36681141

RESUMO

Alzheimer's disease (AD) is a chronic neurological disorder with high morbidity. Exercise is one of the effective ways to ameliorate AD. In this study, we assessed the effects of exercise on cognition and inflammation and studied the role of miR-148a-3p in AD. In 88 patients with AD, the expression of miR-148a-3p was studied using qRT-PCR. ROC curve and Pearson analysis were utilized to evaluate the roles of miR-148a-3p in AD. MWM test was conducted to investigate the effects of miR-148a-3p and exercise on cognition and memory. Moreover, inflammatory indicators were identified using an enzyme-linked immunosorbent assay. Relative luciferase levels reflected whether miR-148a-3p targeted SYNJ1. miR-148a-3p levels declined in patients with AD, indicating its potential as a biomarker. Interestingly, miR-148a-3p levels were elevated in patients with AD after exercise. MiR-148a-3p levels correlated with cognitive scores and proinflammatory levels. The cognitive situation and pro-inflammatory state were partly recovered in the mice after exercise. MiR-148a-3p silencing reversed these abovementioned tendencies. Patients with AD exhibited a low level of miR-148a-3p, which was increased after exercise. Therefore, exercise might improve the cognitive function and memory of mice with AD by upregulating miR-148a-3p.


Assuntos
Doença de Alzheimer , MicroRNAs , Animais , Camundongos , Biomarcadores , Cognição , Inflamação , MicroRNAs/metabolismo
11.
Comb Chem High Throughput Screen ; 26(2): 410-423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35473522

RESUMO

BACKGROUND: Osteoarthritis (OA) is a worldwide chronic disease of the articulating joints. An increasing body of data demonstrates the immune system's involvement in osteoarthritis. The molecular mechanisms of OA are still unclear. This study aimed to search for OA immunerelated hub genes and determine appropriate diagnostic markers to help the detection and treatment of the disease. METHODS: Gene expression data were downloaded from the GEO database. Firstly, we analyzed and identified the differentially expressed genes (DEGs) using R packages. Meanwhile, ssGSEA was used to determine the activation degree of immune-related genes (IRGs), and WGCNA analysis was applied to search for co-expressed gene modules associated with immune cells. Then, critical networks and hub genes were found in the PPI network. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway enrichment analyzed the biological functions of genes. The ability of the hub genes to differentiate OA from controls was assessed by the area under the ROC curve. A miRNA and transcription factor (TF) regulatory network was constructed according to their relationship with hub genes. Finally, the validation of hub genes was carried out by qPCR. RESULTS: In total, 353 DEGs were identified in OA patients compared with controls, including 222 upregulated and 131 downregulated genes. WGCNA successfully identified 34 main functional modules involved in the pathogenesis of OA. The most crucial functional module involved in OA included 89 genes. 19 immune-related genes were obtained by overlapping DEGs with the darkgrey module. The String database was constructed using the protein-protein interaction (PPI) network of 19 target genes, and 7 hub genes were identified by MCODE. ROC curve showed that 7 hub genes were potential biomarkers of OA. The expression levels of hub genes were validated by qPCR, and the results were consistent with those from bioinformatic analyses. CONCLUSION: Immune-related hub genes, including TYROBP, ITGAM, ITGB2, C1QC, MARCO, C1QB, and TLR8, may play critical roles in OA development. ITGAM had the highest correction on immune cells.


Assuntos
MicroRNAs , Humanos , Biologia Computacional , Bases de Dados Factuais , Ontologia Genética , Redes Reguladoras de Genes
12.
Arch Esp Urol ; 76(10): 796-801, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38186073

RESUMO

OBJECTIVE: This study aimed to explore the clinical and differential diagnostic value of real-time ultrasound elastography combined with transabdominal prostate calcification in prostate cancer (PCa). METHODS: This study retrospectively analysed the clinical pathological data of 97 patients with PCa and 105 patients with benign prostatic hyperplasia (BPH) diagnosed by postoperative pathology in our hospital from May 2020 to May 2021; Comparatively analysed the clinical data of the two groups, including the elastic strain ratio, elastic image compression index, types of prostate calcification and calcification diameter; And used logistic regression analysis to screen out the independent risk factors for identifying PCa and BPH. RESULTS: No significant difference in age, body weight, body mass index, location of calcification and calcification diameter was observed between the two groups (p > 0.05), and overt differences in elastic strain ratio, elastic image compression index, types of calcification, and testosterone were found between the PCa group and BPH group (p < 0.05). Logistic regression analysis showed that the elastic strain ratio, elastic image compression index and types of calcification were independent risk factors for identifying PCa (p < 0.05). The area under curve value of combined diagnosis under receiver operating characteristic curve was as high as 0.756 (95% CI: 0.691-0.813), with a sensitivity of 67.60% and a specificity of 76.30%. CONCLUSIONS: A certain correlation is observed amongst elastic strain ratio, elastic image compression index, types of prostate calcification and the occurrence and development of PCa. The application of real-time ultrasound elastography combined with the detection of transabdominal prostate calcification in clinical diagnosis can improve the detection rate of PCa, which has an important clinical application value.


Assuntos
Técnicas de Imagem por Elasticidade , Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Diagnóstico Diferencial , Próstata/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem
13.
ACS Appl Mater Interfaces ; 14(41): 46481-46490, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36194841

RESUMO

Developing bifunctional catalysts with good performance at a high current density for the urea oxidation reaction (UOR) and the hydrogen evolution reaction (HER) can effectively relieve the severe environmental and energy pressures. Herein, amorphous NiMoO4 decorated Ni3S2 grown on nickel foam (Ni3S2-NiMoO4/NF) is prepared to accelerate UOR and HER. The crystalline-amorphous heterostructure could regulate the interfacial electron structure to reduce the electron density near Ni3S2 for optimizing UOR and HER. The decoration of NiMoO4 enhances its anti-poisoning ability for CO-intermediate species to show good stability at high current densities. Meanwhile, the nano-/microstructure with high hydrophilicity improves mass transfer and the accessibility of electrolyte. Driving high current densities of ±1000 mA cm-2, it merely needs 1.38 V (UOR) and -263 mV (HER). For urea electrolysis, it can deliver 1000 mA cm-2 at 1.73 V and stably operate at 500 mA cm-2 for 120 h. Therefore, this study provides new ideas for durable urea electrolysis-assisted H2 production.

14.
Sensors (Basel) ; 22(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36080870

RESUMO

With the development of modern industry, small UAVs have been widely used in agriculture, mapping, meteorology, and other fields. There is an increasing demand for the core attitude-solving algorithm of UAV flight control. In this paper, at first, a novel attitude solving algorithm is proposed by using quaternions to represent the attitude matrix and using Allan variance to analyze the gyroscope error and to quantify the trend of the error over time, so as to improve the traditional Mahony complementary filtering. Simulation results show that the six-axis data from the initial sensors (gyroscope and accelerometer) agree well with the measured nine-axis data with an extra magnetometer, which reduces the complexity of the system hardware. Second, based on the hardware platform, the six-axis data collected from MPU6050 are sent to FPGA for floating-point operation, transcendental function operation, and attitude solution module for processing through IIC communication, which effectively validates the attitude solution by using the proposed method. Finally, the proposed algorithm is applied to a practical scenario of a quadrotor UAV, and the test results show that the RMSE does not exceed 2° compared with the extended Kalman filter method. The proposed system simplifies the hardware but keeps the accuracy and speed of the solution, which may result in application in UAV flight control.

15.
Oxid Med Cell Longev ; 2022: 7887782, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148412

RESUMO

Tendon injury repair has been a clinical challenge, and little is known about tendon healing scar generation, repair, and regeneration mechanisms. To explore the cellular composition of tendon tissue and analyze cell populations and signaling pathways associated with tendon repair, in this paper, single-cell sequencing data was used for data mining and seven cell subsets were annotated in the tendon tissue, including fibroblasts, tenocytes, smooth muscle cells, endothelial cells, macrophages, T cells, and plasma cells. According to cell group interaction network analysis, pattern 4 composed of macrophages was an important communication pattern in tendon injury. Furthermore, the heterogeneity of M1 macrophages in tendons, the correlation of KEGG enriched pathway with inflammatory response, and the core regulatory role of the transcription factor NFKB and REL were observed; in addition, the heterogeneity of T cell isoforms in tendons was found and indicated that different isotypes of T cells involve in different roles of tendon injury and repair. This study demonstrated the heterogeneity of M1 macrophages and T cells in the tendon tissue, being involved in different physiological processes such as tendon injury and healing, providing new thinking insights and basis for subsequent clinical treatment of tendon injury.


Assuntos
Traumatismos dos Tendões , Transcriptoma , Células Endoteliais/metabolismo , Humanos , Isoformas de Proteínas/metabolismo , Traumatismos dos Tendões/genética , Traumatismos dos Tendões/metabolismo , Fatores de Transcrição , Transcriptoma/genética
16.
Front Chem ; 10: 908312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860629

RESUMO

Objective: Tendons are the special connective tissue that connects bones to muscles and governs joint movement in response to loads passed by muscles. The healing of tendon injuries is still a challenge. In recent years, adipose-derived mesenchymal stem cells (ADSCs) have been increasingly used for tissue regeneration, but the underlying mechanism of tendon injury still remains unclear. Methods: High-throughput sequencing was used to identify a novel lncRNA, whose expression was significantly decreased in injured tendon compared with normal tendon. Furthermore, pyrosequencing, nuclear-cytoplasmic separation, FISH assay and qRT-PCR analysis were used to verify the level of lncRNA methylation in the injured tenocytes. lncRNA was confirmed to promote the proliferation of tenocytes by flow cytometry, wound healing assay, qRT-PCR, and western blot, and the target gene of lncRNA was predicted and verified. To confirm that ADSCs could repair injured tendons, ADSCs and injured tenocytes were co-cultured in vitro, and ADSCs were injected into injured tendons in vitro, respectively. Results: The lncRNA Morf4l1 promoter methylation in injured tendons led to down-regulation of its expression and inhibition of tenocyte proliferation. LncRNA Morf4l1 promoted the expression of TGF-ß2 by targeting 3'U of miR-145-5p. After co-cultured ADSCs and injured tenocytes, the expression of lncRNA Morf4l1 was up-regulated, and the proliferation of injured tenocytes in vitro was promoted. The ADSCs were injected into the injured tendon to repair the injured tendon in vivo. Conclusion: This study confirmed that ADSCs promoted tendon wound healing by reducing the methylation level of lncRNA Morf4l1.

17.
BMC Musculoskelet Disord ; 23(1): 370, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443641

RESUMO

BACKGROUND: The surgical treatment of complex acetabular fractures is one of the most challenging procedures for orthopedic surgeons. The Pararectus approach, as a reasonable alternative to the existing surgical procedures, was performed for the treatment of acetabular fractures involving the anterior column. This study aimed to evaluate outcome using the Pararectus approach for acetabular fractures involving anterior columns. METHODS: Thirty-seven with displaced acetabular fractures involving anterior columns were treated between July 2016 and October 2019 using the Pararectus approach. The functional outcomes (using the Merle d Aubigné and Postel scoring system, WOMAC and modified Harris scoring), the quality of surgical reduction (using the Matta criteria), and postoperative complications were assessed during approximately 26 months follow-up period. RESULTS: Thirty-seven patients (mean age 53 years, range: 30-71; 28 male) underwent surgery. Mean intraoperative blood loss was 840 ml (rang: 400-2000 ml) and mean operating time was 210 min (rang: 140-500 min). The modified Merle d Aubigné score was excellent and good in 27 cases (73%), fair in 6 cases (16%), and poor in 3 cases (11%). The mean score was 88.5 (range:77-96) for the modified Harris Hip scores, and 22 (range:7-35) for the WOMAC scores after operation. Postoperative functional outcomes were significantly improved compared with preoperative outcomes (P < 0.0001). The quality of reduction was anatomical in 21 cases (57%), satisfactory in 9 cases (24%), and unsatisfactory in 7 cases (19%). At follow-up, four patients developed a DVT, and heterotopic bone formation was observed in one patient. The hip osteoarthritis was not observed. CONCLUSION: The Pararectus approach achieved good functional outcomes and anatomical reduction in the treatment of acetabular fractures involving anterior column with minimal access morbidity.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Lesões do Pescoço , Fraturas da Coluna Vertebral , Acetábulo/diagnóstico por imagem , Acetábulo/lesões , Acetábulo/cirurgia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Front Neurosci ; 16: 800513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250447

RESUMO

Spinal cord injury (SCI) can result in sensorimotor impairments or disability. Studies of the cellular response to SCI have increased our understanding of nerve regenerative failure following spinal cord trauma. Biological, engineering and rehabilitation strategies for repairing the injured spinal cord have shown impressive results in SCI models of both rodents and non-human primates. Cell transplantation, in particular, is becoming a highly promising approach due to the cells' capacity to provide multiple benefits at the molecular, cellular, and circuit levels. While various cell types have been investigated, we focus on the use of Schwann cells (SCs) to promote SCI repair in this review. Transplantation of SCs promotes functional recovery in animal models and is safe for use in humans with subacute SCI. The rationales for the therapeutic use of SCs for SCI include enhancement of axon regeneration, remyelination of newborn or sparing axons, regulation of the inflammatory response, and maintenance of the survival of damaged tissue. However, little is known about the molecular mechanisms by which transplanted SCs exert a reparative effect on SCI. Moreover, SC-based therapeutic strategies face considerable challenges in preclinical studies. These issues must be clarified to make SC transplantation a feasible clinical option. In this review, we summarize the recent advances in SC transplantation for SCI, and highlight proposed mechanisms and challenges of SC-mediated therapy. The sparse information available on SC clinical application in patients with SCI is also discussed.

19.
Small ; 18(12): e2106773, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35064640

RESUMO

The development of efficient and stable Pt-based catalysts is significant but challenging for fuel cells. Herein, Sn and Co elements are introduced into Pt to form PtCo-PtSn/C heterostructure for enhancing the oxygen reduction reaction (ORR). Electrochemical results indicate that it has remarkable ORR intrinsic activity with a high mass activity (1,158 mA mg-1 Pt) at 0.9 V in HClO4 solution, which is 2.18-, 6.81-, and 9.98-fold higher than that of PtCo/C, PtSn/C, and Pt/C. More importantly, the catalytic activity attenuation for PtCo-PtSn/C is only 27.4% after 30 000 potential cycles, showing high stability. Furthermore, theoretical calculations reveal that the enhancement is attributed to charge transfer and the unique structure of PtCo-PtSn/C heterostructure, which regulate the d-band center of Pt and prevent non-noble metals from further dissolution. This work thus opens a way to design and prepare highly efficient Pt-based alloy catalysts for proton exchange membrane fuel cells.

20.
J Orthop Surg Res ; 17(1): 50, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090522

RESUMO

BACKGROUND: To identify medial open-wedge high tibial osteotomy (MOWHTO) prognostic factors with wedge-shaped spacer implantation (spacer-type MOWHTO) for varus medial compartment knee osteoarthritis. METHODS: Patients who underwent spacer-type MOWHTO between August 2018 and September 2019 were prospectively enrolled in this study. Patients were divided into effective group and invalid group based on the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) score one year postoperatively. The variables assessed at baseline and one year postoperatively including age, sex, body mass index (BMI), Kellgren-Lawrence (K-L) grade, hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), posterior tibial slope angle (PTSA), Blackburn-Peel index (BPI), duration of symptoms, and WOMAC score were compared. Prognostic factors were analyzed using logistic regression, and the corresponding odds ratios were also calculated. RESULTS: A total of 104 patients were enrolled in the study protocol at one year postoperatively. The WOMAC score decreased from 72.39 ± 12.95 at baseline to 20.06 ± 12.96 at one year postoperatively. Univariate analysis revealed that the significant predictors of the WOMAC score were age > 70 years, BMI > 30 kg/m2, K-L grade IV, and pre-HKAA > 10° (P < 0.1 for all). Multivariable logistic regression analysis revealed that age > 70 (OR = 4.861) and K-L grade IV (OR = 6.590) were significantly associated with the higher WOMAC score at one year postoperatively. CONCLUSIONS: Spacer-type MOWHTO is an effective treatment for osteoarthritis with varus deformity. The prognostic factors for spacer-type MOWHTO are age and K-L grade.


Assuntos
Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Implantes Absorvíveis , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tíbia/diagnóstico por imagem
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