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1.
Medicine (Baltimore) ; 102(48): e36319, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050288

RESUMO

BACKGROUND: Cyclin-dependent Kinase Subunit 2 is a protein closely related to the regulation of the cell cycle. In recent years, there has been an increasing number of research articles on this topic. However, there is a lack of comprehensive synthesis and evaluation in the field of CKS2 research. This study aims to summarize and visualize the literature distribution, research hotspots, and development trends of CKS2 based on bibliometric methods. METHODS: Publications from 1999 to 2022 were extracted from the Web of Science. Citespace was used to analyze the relevant information of each article. RESULTS: A total of 138 publications focused on CKS2 showed a positive growth trend from 1999 to 2022 and were published by 27 countries. The most prolific countries are China and the USA. The most prolific institution is Scripps Research Institute. The most prolific author is Steven I. Reed from Scripps Research Institute. The most cited article is published by Todd R Golub. The most cited author is Hanna-Stina Martinsson-Ahlzen. The journal with the most published articles is International Journal of Oncology. The high frequency keywords suggest that expression and function of CKS2 in cancer are dominated topics. The clusters and burst words suggest that expression and function of CKS2 still active in the future. CONCLUSION SUBSECTIONS: The results of this bibliometric analysis provide information on the state and trends in CKS2 from 1999 to 2022. It is helpful for scholars to pinpoint hot issues and discover new areas of study.


Assuntos
Academias e Institutos , Quinases relacionadas a CDC2 e CDC28 , Humanos , Bibliometria , Ciclo Celular , China , Instalações de Saúde , Proteínas de Ciclo Celular
2.
Medicine (Baltimore) ; 102(46): e36105, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986287

RESUMO

Knee osteoarthritis (KOA) is the most common joint disease worldwide and, with the progression of an aging population, is one of the most important causes of disability worldwide. Its main symptoms include articular cartilage damage, periarticular pain, swelling, and stiffness. Intra-articular (IA) injections offer many advantages over systemic administration and surgical treatment, including direct action on the target joint to improve local bioavailability, reduce systemic toxicity, and lower costs. This study analyzed KOA intra-articular injection treatment and its hot literature and research horizons using bibliometric methodologies and graphical tools to aid future research. We performed a bibliometric analysis of 2360 publications in the Web of Science core collection using CiteSpace software. The United States (28.26% of publications) and China (18%) had the biggest publications. Rush University was the most active institution, but Boston University had the greatest citation/publication rate (65.77), suggesting a high literature standard. The majority of publications were in Osteoarthritis and cartilage. Bannuru RR was the most referenced author, while Filardo, Giuseppe was the most productive author. Studies in platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and microsphere formulation are likely to be future research hotspots. The current scientometric study provides an overview of KOA intra-articular injection therapy studies from 2012 to 2022. This study outlines the current research hotspots and potential future research hotspots in the field of intra-articular injection treatment for KOA and may serve as a resource for researchers interested in this topic.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Idoso , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia , Injeções Intra-Articulares , Bibliometria , Resultado do Tratamento
3.
iScience ; 26(5): 106692, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37216089

RESUMO

The complexity of the human intervertebral disc (IVD) has hindered the elucidation of the microenvironment and mechanisms underlying IVD degeneration (IVDD). Here we determined the landscapes of nucleus pulposus (NP), annulus fibrosus (AF), and immunocytes in human IVD by scRNA-seq. Six NP subclusters and seven AF subclusters were identified, whose functional differences and distribution during different stages of degeneration (Pfirrmann I-V) were investigated. We found MCAM+ progenitor in AF, as well as CD24+ progenitor and MKI67+ progenitor in NP, forming a lineage trajectory from CD24+/MKI67+ progenitors to EffectorNP_⅓ during IVDD. There is a significant increase in monocyte/macrophage (Mφ) in degenerated IVDs (p = 0.044), with Mφ-SPP1 exclusively found in IVDD but not healthy IVDs. Further analyses of the intercellular crosstalk network revealed interactions between major subpopulations and changes in the microenvironment during IVDD. Our results elucidated the unique characteristics of IVDD, thereby shedding light on therapeutic strategies.

4.
Front Neurol ; 14: 1120446, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36949855

RESUMO

Objective: Neutrophil gelatinase-associated lipoprotein (NGAL), a protein encoded by the lipocalcin-2 (LCN2) gene, has been reported to be involved in multiple processes of innate immunity, but its relationship with spinal cord injury (SCI) remains unclear. This study set out to determine whether NGAL played a role in the development of cognitive impairment following SCI. Methods: At the Neck-Shoulder and Lumbocrural Pain Hospital, a total of 100 SCI patients and 72 controls were enrolled in the study through recruitment. Through questionnaires, baseline data on the participants' age, gender, education level, lifestyle choices (drinking and smoking) and underlying illnesses (hypertension, diabetes, coronary heart disease, and hyperlipidemia) were gathered. The individuals' cognitive performance was evaluated using the Montreal Cognitive Scale (MoCA), and their serum NGAL levels were discovered using ELISA. Results: The investigation included 72 controls and 100 SCI patients. The baseline data did not differ substantially between the two groups, however the SCI group's serum NGAL level was higher than the control group's (p < 0.05), and this elevated level was adversely connected with the MoCA score (p < 0.05). According to the results of the ROC analysis, NGAL had a sensitivity of 58.24% and a specificity of 86.72% for predicting cognitive impairment following SCI. Conclusions: The changes in serum NGAL level could serve as a biomarker for cognitive impairment in SCI patients, and this holds true even after taking in account several confounding variables.

5.
Dis Markers ; 2022: 2141882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157206

RESUMO

Background: Astragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach. Methods: AM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above. Result: The overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets. Conclusions: Altogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.


Assuntos
Angelica sinensis , Aterosclerose , Medicamentos de Ervas Chinesas , Proteína Quinase 14 Ativada por Mitógeno , Traumatismos da Medula Espinal , Astragalus propinquus , Medicamentos de Ervas Chinesas/farmacologia , Receptores ErbB , Humanos , Quempferóis , Lipídeos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quercetina , Traumatismos da Medula Espinal/tratamento farmacológico
6.
Dis Markers ; 2022: 3860898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157212

RESUMO

Objective: To explore the possible mechanism of fluid shear stress on human nucleus pulposus cells based on label-free proteomics technology. Methods: The human nucleus pulposus cell line was purchased and subcultured in vitro. The Flexcell STR-4000 multiflow field cell fluid shear stress loading culture system was used to apply continuous laminar fluid shear stress (12 dyne/cm2, 45 mins) to the monolayer adherent cells. Those without mechanical loading were used as the control group, and those subjected to fluid shear loading were used as the experimental group. Differential protein expression was identified using mass spectrometry identification technology, and bioinformatics analysis was performed using Gene Ontology GO (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: The proteomics results of the experimental group and the control group showed that the total number of mass spectra was 638653, the number of matched mass spectra was 170110, the total number of identified peptides was 32050, the specific peptide was 30564, and the total number of identified proteins was 4745. Comparing the two groups, 47 proteins were significantly differentially expressed, namely, 25 upregulated proteins and 22 downregulated proteins. Bioinformatics analysis showed that significantly different proteins were mainly manifested in cellular process, biological regulation, metabolic process, binding, catalytic activity, cellular components (cell part), organelle part (organelle part), and other molecular biological functions. Conclusion: Using proteomics technology to screen human nucleus pulposus cells after fluid shear stress loading, the differential protein expression provides a basis for further exploration of the mechanism of mechanical factors on nucleus pulposus.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Núcleo Pulposo/metabolismo , Proteômica , Estresse Mecânico
7.
Eur J Med Chem ; 240: 114567, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35779290

RESUMO

In this study, a novel carboxymethyl dextran (CMD)-based dual drug delivery system that delivering two water insoluble drugs to tumor sites was developed and evaluated for anticancer activities. Paclitaxel (PTX) and docosahexaenoic acid (DHA) were covalently coupled with CMD to generate CMD-DHA-PTX conjugate S and conjugate L with different linkers containing amino acids Gly-Gly or Lys-Gly-Gly, respectively. Both conjugates possessed high PTX loading contents and enhanced water solubility, as well as the ability of being self-assembled into nanoparticles with the nanoparticle size ranged from 88.7 nm to 94.7 nm. These two conjugates released free PTX continuously in plasma and cancer cells. The conjugate S exhibited improved pharmacokinetic parameters and higher distribution extent in tumor sites than the parent PTX, Abraxane and the conjugate L. The antitumor efficacy of these two conjugates outperformed parent PTX formulation and Abraxane in nude mice bearing breast cancer cells MCF-7. More importantly, the conjugate S treatment eliminated all the xenograft tumors without causing any mice body weight loss in mice model. This study revealed that the dextran-based dual drug conjugates may represent an effective and innovative way to deliver anticancer agents to a variety of tumors.


Assuntos
Neoplasias da Mama , Nanopartículas , Paclitaxel Ligado a Albumina/uso terapêutico , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dextranos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Preparações Farmacêuticas , Água
8.
Biomater Sci ; 10(13): 3454-3465, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35647736

RESUMO

Docetaxel (DTX) has been widely used for the treatment of many types of cancer. However, DTX is poorly water-soluble and commercial DTX is formulated in non-ionic surfactant polysorbate 80 and ethanol, thereby leading to hypersensitivity and serious side effects. Herein, a polymer dual drug conjugate was synthesized by coupling DTX and docosahexaenoic acid (DHA) with bifunctionalized dextran. The polysaccharide conjugate dextran-DHA-DTX possessed high water solubility and was self-assembled into nanoparticles with a diameter of 98.0 ± 6.4 nm. Pharmacokinetic and biodistribution studies showed that the dextran-DHA-DTX dual drug conjugate not only had significantly prolonged blood circulation but was also selectively accumulated in the tumor with reduced drug distribution in normal tissues. The conjugate exhibited a superior therapeutic effect in both xenograft nude mice models without causing any systemic side effects. Notably, the conjugate nearly eliminated all xenograft tumors in nude mice bearing breast cancer cells MCF-7. This study revealed that the dextran-based dual drug delivery system may provide an effective strategy to selectively deliver DTX to tumor sites.


Assuntos
Antineoplásicos , Nanopartículas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dextranos , Docetaxel , Ácidos Docosa-Hexaenoicos , Portadores de Fármacos/uso terapêutico , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Polímeros , Distribuição Tecidual , Água
9.
Clin Interv Aging ; 17: 915-923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686029

RESUMO

Background: Older patients with chronic renal failure (CRF) which currently is referred to as end-stage renal disease (ESRD) are associated with higher mortality. In-center nocturnal dialysis (INHD) is a new blood purification model, which is characterized by longer sessions and nighttime administration. However, no data for the efficacy of INHD in older patients with ESRD are available. This study is to analyze the effect of INHD in the treatment of older patients with ESRD. Methods: A retrospective, observational study was conducted in a university teaching hospital. Seventy-two patients with ESRD receiving INHD were enrolled. They were divided into the older ESRD patients (age ≥60) group (n = 22) and the non-older ESRD patients (age <60) group (n = 50). The causes of older ESRD patients and non-older ESRD patients receiving INHD were analyzed. Differences of laboratory test indicators of older patients with ESRD before INHD and after INHD were compared. Quality of life for older ESRD patients receiving INHD was assessed by using the Kidney Disease Quality of Life-36 Instrument (KDQOL-36). Results: Serum concentration of hemoglobin and serum concentration of albumin of older patients with ESRD increased significantly after INHD (p < 0.05). There were similar results in the non-older cohort (p ≤ 0.05). Scores of five KDQOL-36 subscales increased significantly after INHD (p ≤ 0.001) indicated that the quality of life for old patients with ESRD was significantly improved after INHD. Conclusion: INHD is an effective blood purification therapy that can improve the condition of renal anemia, and it may provide a potential positive impact in the malnutrition of older and non-older patients with ESRD. INHD can improve the quality of life of older patients with ESRD. The results will provide a basis for formulating new policies of blood purification therapy for older patients.


Assuntos
Anemia , Falência Renal Crônica , Desnutrição , Insuficiência Renal Crônica , Idoso , Anemia/terapia , Doença Crônica , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Desnutrição/complicações , Desnutrição/terapia , Qualidade de Vida , Diálise Renal , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos
10.
Dis Markers ; 2022: 2141854, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571610

RESUMO

Objective: Spinal cord injury (SCI) has become prevalent worldwide in recent years, and its prognosis is poor and the pathological mechanism has not been fully elucidated. Nogo-A is one of the isoforms of the neurite outgrowth inhibitory protein reticulon 4. The purpose of this study was to determine whether Nogo-A could be used as a marker for predicting the prognosis of SCI. Methods: We screened eligible SCI patients and controls based on inclusion and exclusion criteria. We also collected baseline clinical information and peripheral venous blood of the enrolled population. Participants' baseline serum Nogo-A levels were measured by enzyme-linked immunosorbent assay (ELISA). The American Spinal Injury Association (ASIA) scale was used to evaluate the prognosis of SCI patients after 3 months. Results: Baseline clinical information (age; gender; smoking; drinking; SBP, systolic blood pressure; DBP, diastolic blood pressure; fasting blood glucose; WBC, white blood cells; CRP, C-reactive protein) of SCI patients and controls were not statistically significant academic differences (p > 0.05). The baseline serum Nogo-A levels of SCI patients and controls were 192.7 ± 13.9 ng/ml and 263.1 ± 22.4 ng/ml, respectively, and there was a statistically significant difference between the two groups (p < 0.05). We divided SCI patients into 4 groups according to their baseline serum Nogo-A quartile levels and analyzed their relationship with ASIA scores. The trend test results showed that with the increase of Nogo-A level, the ASIA sensation score and ASIA motor score were significantly decreased (p < 0.001). Multivariate regression analysis showed that serum Nogo-A levels remained a potential cause affecting the prognosis of SCI after adjusting for confounding factors in multiple models. Conclusions: Serum Nogo-A levels were significantly elevated in SCI patients. Moreover, elevated Nogo-A levels often indicate poor prognosis and can be used as a marker to predict the prognosis of SCI.


Assuntos
Traumatismos da Medula Espinal , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Humanos , Proteínas Nogo , Prognóstico , Traumatismos da Medula Espinal/epidemiologia
11.
Biosci Trends ; 16(1): 73-90, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35153276

RESUMO

Acupuncture has been used to treat various disease for more than 3,000 years in China and other Asian countries. As a complementary and alternative therapy, it has gained increasing popularity and acceptance among public and healthcare professionals in the West. Over the past few decades, basic and clinical research on acupuncture has made considerable progress. Internationally recognized evidence from clinical studies has been published, a preliminary system to clinically evaluate acupuncture has been created, and some clinical guidelines have been formulated. Moreover, scientists have strived to explore the physiological and biological mechanisms of acupuncture. Some basic studies have indicated that acupuncture has various actions, such as analgesic, muscle relaxing, anti-inflammatory, mild anxiolytic, and antidepressant actions, with possible biological mechanisms such as central sensitization, neurotransmitters, the intestinal flora, immune regulation, oxidative stress, and neuroinflammation. The current review describes the common indications for acupuncture recommended by the WHO and the use of acupuncture in China, the United States, Australia, and several other countries. This review then summarized the mechanisms by which acupuncture treats common conditions including lower back pain (LBP), ischemic stroke, depression, and irritable bowel syndrome (IBS) and it also cited specific acupuncture points for treating these conditions. The hope is that this review will provide useful information for both acupuncturists and researchers to better understand the mechanisms of acupuncture and reasons for its usage.


Assuntos
Terapia por Acupuntura , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Austrália , China , Humanos , Síndrome do Intestino Irritável/terapia
12.
Dis Markers ; 2022: 5389162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082930

RESUMO

OBJECTIVE: Spinal cord injury (SCI) has become popular in recent years, and cognitive decline is a common complication. Adiponectin is a common protein hormone involved in the course of many diseases, but its relationship with SCI has not yet been elucidated. The purpose of our prospective study is to explore whether adiponectin can be used as a biomarker of cognitive decline in SCI. METHODS: A total of 64 healthy volunteers and 92 patients with acute SCI were recruited by us. Serum adiponectin levels, demographic data (age and gender), lifestyle (smoking and drinking), medical history (diabetes and hypertension), and clinical baseline data (low-density lipoprotein, high-density lipoprotein, and fasting blood glucose) were recorded. Three months after enrollment, we used the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function. Based on a quarter of the serum adiponectin levels, SCI patients were divided into 4 groups, and the differences in their MoCA scores were compared. In addition, we used multivariate linear regression to predict the risk factors of the MoCA score. RESULTS: The serum adiponectin level (6.1 ± 1.1 µg/ml) of SCI patients was significantly lower than that of the healthy control group (6.7 ± 0.9 µg/ml), and there was a significant difference between the two (p < 0.001). The group with higher serum adiponectin levels after 3 months of spinal cord injury had higher MoCA scores. Multivariate regression analysis showed that serum adiponectin level is a protective factor for cognitive function after SCI (ß = 0.210, p = 0.043). CONCLUSIONS: Serum adiponectin levels can be used as an independent predictor of cognitive function in patients with acute SCI.


Assuntos
Adiponectina/sangue , Disfunção Cognitiva/sangue , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Traumatismos da Medula Espinal/fisiopatologia
13.
Dis Markers ; 2021: 3532716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876931

RESUMO

OBJECTIVE: Angiopoietin-like protein 4 (ANGPTL4), encoding a glycosylated secreted protein, has been reported to be closely related to many kinds of diseases, including diabetes, tumor, and some musculoskeletal pathologies, such as rheumatoid arthritis, osteoarthritis, and osteoporosis. The aim of the current study is to investigate the role of ANGPTL4 in intervertebral disc degeneration and analyze the association of ANGPTL4 expression with Pfirrmann grades. METHODS: A total of 162 nucleus pulposus tissues were collected from lumbar intervertebral disc herniation patients undergoing interforaminal endoscopic surgery. Real-time quantitative PCR and western blot were performed to determine the mRNA and protein expression of ANGPTL4 in nucleus pulposus samples. Statistical analysis was performed to analyze the association of ANGPTL4 expression with Pfirrmann grades. RESULTS: Based on the clinical data of 162 patients, results showed that Pfirrmann grades were significantly associated with patients' age (r = 0.162, P = 0.047) and were not significantly associated with patients' gender (P > 0.05). RT-qPCR and western blot results showed that the mRNA (r = 0.287, P < 0.05) and protein (r = 0.356, P < 0.05) expressions of ANGPTL4 were both closely associated with Pfirrmann grades. The expression of ANGPTL4 was remarkably increased in the groups of high IVDD Pfirrmann grades. CONCLUSION: The results demonstrated that ANGPTL4 expression was positively associated with the Pfirrmann grades and the severity of intervertebral disc degeneration. ANGPTL4 may be served as a candidate biomarker for intervertebral disc degeneration.


Assuntos
Proteína 4 Semelhante a Angiopoietina/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Adolescente , Adulto , Proteína 4 Semelhante a Angiopoietina/genética , Western Blotting , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
14.
Oxid Med Cell Longev ; 2021: 6699326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815660

RESUMO

BACKGROUND: Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain and motor deficiency. Nucleus pulposus (NP) degeneration plays a key role in the process of IVDD. The mechanical and biological interactions involved in NP degeneration have not been elucidated. The present study is aimed at investigating the effect and mechanism of cyclic mechanical stretch in regulating the function and degeneration of NP cells. METHODS: NP cells were subjected to cyclic tensile stress (10% deformation) of 0.1 Hz for 8640 cycles. Cell proliferation was conducted through the MTT assay. The cell cycle and apoptosis were detected by flow cytometry. A gene expression profile chip was used to analyze the differentially expressed genes between the tensile stress group and the control group. Enrichment analysis of Gene Ontology (GO) annotation and signaling pathways were analyzed. Western blot and RNA interference were carried out to investigate the role of the ITGA2/PI3K/AKT pathway in the effect of cyclic mechanical stretch on NP cells. RESULTS: NP cells exhibited a greater (P < 0.05) growth rate in the tensile stress group compared to the control group. Cyclic mechanical stress significantly promoted the cell cycle transition of NP cells from the S phase to the G2/M phase. A fewer proportion of apoptotic cells were found in the tensile stress group (P < 0.05), indicating that cyclic mechanical stretch inhibits NP cell apoptosis. Microarray analysis revealed 689 significant differentially expressed genes between the two groups (P < 0.05), of which 333 genes were upregulated and another 356 genes were downregulated. Cyclic mechanical stretch altered the expression of 31 genes involved in the ITGA2/PI3K/AKT pathway and remarkably promoted this pathway in NP cells. Downregulation of ITGA2 and AKT further demonstrated that the PI3K/AKT pathway was responsible for the proliferation and COL2A1 expression of NP cells upon cyclic mechanical stretch. CONCLUSIONS: Cyclic mechanical stretch promoted the proliferation and cell cycle and reversely inhibited the apoptosis of NP cells. Cyclic mechanical stretch promoted COL2A1 expression and ameliorated the degeneration of NP cells via regulation of the ITGA2/PI3K/AKT signaling pathway. Our results may provide a potential target and a possibility of IVDD disease treatment by ameliorating the degenerative changes.


Assuntos
Integrina alfa2/metabolismo , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estresse Mecânico , Adulto , Ciclo Celular , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Degeneração do Disco Intervertebral/genética , Pessoa de Meia-Idade
15.
Expert Opin Ther Targets ; 23(12): 1015-1030, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31747802

RESUMO

Introduction: Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.Areas covered: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided.Expert opinion: There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Desenvolvimento de Medicamentos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Animais , Doenças Autoimunes/fisiopatologia , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Epigênese Genética , Humanos
16.
Mol Genet Genomic Med ; 6(6): 1249-1254, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30461224

RESUMO

BACKGROUND: A 30-year-old oligoasthenozoospermia man was found to have unbalance mosaic translocation between chromosome 22 and four other chromosomes (5, 6, 13, and 15) during the investigations for a couple with infertility for 3 years, which is a rare event in human pathology. METHODS: Classical cytogenetics analysis, fluorescence in situ hybridization (FISH), and chromosome microarray analyses (CMA) were performed on peripheral blood lymphocytes; copy number variation sequencing (CNV-Seq) analysis was performed on sperm DNA. RESULTS: Classical cytogenetics analysis showed the presence of six cell lines on peripheral blood lymphocytes: 45, XY, der (13) t(13;22),-22[10]/46, XY, t(13;22)[6]/45, XY, der(15)t(15;22),-22[4]/46, XY, t(13;22)[1]/45, XY, der(5)t(5;22),-22[1]/45, XY, der(6)t(6;22)[1]. FISH and CMA performed on peripheral blood cells showed the presence of a 6.9 Mb mosaic 22q11 deletion (approximately 50% of cells); it is unexpected that the phenotypes of this man were merely oligoasthenozoospermia, mild bradycardia, and mild tricuspid regurgitation. CNV-Seq analysis performed on sperm DNA revealed the rate of 22q11 deletion cells was obviously lower compared with peripheral blood cells. And the frequency of gametes exhibiting a normal or balance chromosomal equipment was above 80% in sperm samples. CONCLUSION: To the best of our knowledge, this report is the first case of a de novo gonosomal mosaic of chromosome 22q11 deletion just associated with male infertility.


Assuntos
Síndrome da Deleção 22q11/genética , Astenozoospermia/genética , Mosaicismo , Oligospermia/genética , Síndrome da Deleção 22q11/patologia , Adulto , Astenozoospermia/patologia , Humanos , Cariótipo , Masculino , Oligospermia/patologia
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(1): 61-64, 2017 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-28186596

RESUMO

OBJECTIVE: To explore the correlation between cytogenetic findings and clinical manifestations of Turner syndrome. METHODS: 607 cases of cytogenetically diagnosed Turner syndrome, including those with a major manifestation of Turner syndrome, were analyzed with conventional G-banding. Correlation between the karyotypes and clinical features were analyzed. RESULTS: Among the 607 cases, there were 154 cases with monosomy X (25.37%). Mosaicism monosomy X was found in 240 patients (39.54%), which included 194 (80.83%) with a low proportion of 45,X (3 ≤ the number of 45, X ≤5, while the normal cells ≥ 30). Structural X chromosome abnormalities were found in 173 patients (28.50%). A supernumerary marker chromosome was found in 40 cases (6.59%). Most patients with typical manifestations of Turner syndrome were under 11 years of age and whose karyotypes were mainly 45,X. The karyotype of patients between 11 and 18 years old was mainly 45,X, 46,X,i(X)(q10) and mos45,X/46,X,i(X)(q10), which all had primary amenorrhea in addition to the typical clinical manifestations. The karyotype of patients over 18 years of age were mainly mosaicism with a low proportion of 45,X, whom all had primary infertility. 53 patients had a history of pregnancy, which included 48 with non-structural abnormalities of X chromosome and 5 with abnormal structure of X chromosome. CONCLUSION: Generally, the higher proportion of cells with an abnormal karyotype, the more severe were the clinical symptoms and the earlier clinical recognition. Karyotyping analysis can provide guidance for the early diagnosis of Turner syndrome, especially those with a low proportion of 45,X.


Assuntos
Análise Citogenética/métodos , Síndrome de Turner/genética , Síndrome de Turner/patologia , Aborto Espontâneo/genética , Adolescente , Adulto , Amenorreia/genética , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Pessoa de Meia-Idade , Mosaicismo , Gravidez , Aberrações dos Cromossomos Sexuais , Adulto Jovem
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(1): 15-8, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22455123

RESUMO

OBJECTIVE: To establish in vitro culture procedure for human amniotic fluid-derived CD117 positive stem cells, and to identify the characteristics of CD117 positive stem cells. METHODS: 86 amniotic fluid samples (10 mL of each) were obtained by second-trimester amniocentesis. Isolation of amniotic fluid-derived stem cells expressing CD117 antigen was performed via magnetic cell sorting using the CD117 MicroBead Kit. The karyotype of CD117 positive stem cells was analysed through repeated freezing. Adipogenic differentiation of these CD117 positive stem cells was displayed by Oil Red O staining. Osteogeneic differentiation of these CD117 positive stem cells was confirmed by Alizarin Red staining. RESULTS: The CD117 positive stem cells were successfully isolated and cultured from 61 samples, with all showing normal karyotype. Product analysis of specific staining confirmed that under specific culture mediums, these cells could be successfully induced to differentiate into adipocytes and osteocytes. CONCLUSION: Based on this study, we estimate that isolating CD117 positive stem cells from second-trimester amniotic fluid obtained by amniocentesis has a success rate of 70.93%. These cells maintain morphological and genetic stability in vitro. Human amniotic fluid-derived CD117 positive stem cells have the ability to differentiate in vitro into adipocytes and osteocytes under specific culture mediums and may be applied in cell transplantation and regenerative medicine.


Assuntos
Líquido Amniótico/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Células-Tronco/citologia , Adipócitos/citologia , Adolescente , Adulto , Separação Celular , Células Cultivadas , Feminino , Humanos , Osteoblastos/citologia , Gravidez , Segundo Trimestre da Gravidez , Proteínas Proto-Oncogênicas c-kit/metabolismo , Adulto Jovem
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