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BACKGROUND: Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification. METHODS AND RESULTS: The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis. CONCLUSIONS: TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.
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Neoplasias Ósseas , Proteínas de Ciclo Celular , Osteossarcoma , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Apoptose/genética , Neoplasias Ósseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Osteossarcoma/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genéticaRESUMO
Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.
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Degeneração do Disco Intervertebral/tratamento farmacológico , Disco Intervertebral/patologia , Dor Lombar/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Disco Intervertebral/citologia , Disco Intervertebral/efeitos dos fármacos , Degeneração do Disco Intervertebral/complicações , Dor Lombar/etiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Terapia de Alvo Molecular/métodos , Receptores de Morte Celular/antagonistas & inibidores , Receptores de Morte Celular/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the new zero-profile (Zero-P) fusion cage with regular cage and plate (CP) in the treatment of anterior cervical single-level cervical degenerative diseases. METHODS: Patients operated from January 2013 to August 2018 were enrolled. They were divided into the Zero-P group (n = 74 cases) and CP groups (n = 116 cases). Follow-up assessment was at 1, 3, 12, and 24 months after surgery, including the incidence of dysphagia, visual analogue scale (VAS) score, Japanese orthopaedic association (JOA)score, C2-C7 Cobb angle, intervertebral disc height (IDH) and adjacent joint degeneration. RESULTS: The operation time and blood loss of patients in Zero-P group were less than those in the CP group, and there was no difference in hospitalization time. All 190 patients were followed up for 24 to 72 months, with an average of 35.29 months. In terms of clinical outcomes, vas and JOA scores of the two groups were significantly improved at one month and the last follow-up. The incidence of dysphagia in the Zero-P group was lower than that in the CP group. On radiological effects, Cobb angle and IDH showed significant correction in both groups, but the degeneration rate of adjacent joints in the Zero-P group was lower than the CP group. CONCLUSIONS: In ACDF, the clinical and radiological results of Zero-P and CP devices are satisfactory, but Zero-P cage may be superior in operation time, blood loss, the incidence of dysphagia and adjacent joint degeneration.
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Transcription factor 19 (TCF19) harbors a forkhead association (FHA) domain, a proline-rich region, a PHD or RING finger region, suggesting that TCF19 possesses a powerful function. However, its expression and function remains unknown in non-small-cell lung cancer (NSCLC). The function cluster analysis was carried out using Metascape website. 3-(4,5-Dimethyl-2-thiazolyl)2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation, and anchorage-independent growth ability assay were carried out to detect the effect of TCF19 on cell proliferation. Bromodeoxyuridine (Brdu) labeling and flow cytometry assay were used to evaluate the effect of TCF19 on cell-cycle progression. Quantitative polymerase chain reaction and chromatin immunoprecipitation assay were performed to investigate the mechanism by which TCF19 is involved in cell-cycle transition. By analyzing the publicly available dataset, The Cancer Genome Atlas (TCGA), we found that TCF19 is significantly increased in the lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC), two primary histological subtype of NSCLC. Besides, further function cluster analysis exhibited that TCF19 may mainly participate in cell cycle. MTT, colony formation, and anchorage-independent growth ability assay confirmed that overexpression of TCF19 enhances the proliferation of both LAC and SCC cells. Besides, further experiments revealed that TCF19 contributes to cell cycle G1/S transition. Not only that, upregulation of TCF19 can inhibit the expression of p21, p27, and p57, while promote the expression of cyclin D1 by inhibiting FOXO1. Our research offers important evidence that TCF19 can promote cell-cycle progression of NSCLC cells, and TCF19 may served as novel therapeutic targets.
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Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1-4) and dihydropyran (5-16) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds 2, 7, 10 and 13 confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound 4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI=3.1-7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI=1.6-1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.
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Antineoplásicos/química , Cumarínicos/química , Piranos/química , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cumarínicos/síntese química , Cumarínicos/toxicidade , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Conformação Molecular , Piranos/síntese química , Piranos/toxicidade , Relação Estrutura-AtividadeRESUMO
Two series of biscoumarin (1-3) and dihydropyran (4-12) derivatives were successfully synthesized as new antitumor and antibacterial agents. The molecular structures of four representative compounds 2, 4, 7 and 10 were confirmed by single crystal X-ray diffraction study. The synthesized compounds (1-12) were evaluated for their antitumor activities against human intestinal epithelial adenocarcinoma cell line (HuTu80), mammary adenocarcinoma cell line (4T1) and pancreatic cancer cell line (PANC1) and antibacterial activities against one drug-sensitive Staphylococcus aureus (S. aureus ATCC 29213) strain and three MRSA strains (MRSA XJ 75302, Mu50, USA 300 LAC). The further mechanism study demonstrated that the most potent compound 1 could obviously inhibit the proliferation of cancer cells via the mechanism to induce apoptosis.
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Apoptose/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/farmacologia , Piranos/síntese química , Piranos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Carboplatina/síntese química , Carboplatina/química , Carboplatina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Modelos Moleculares , Piranos/químicaRESUMO
A novel series of biscoumarin (1-4) and dihydropyran (5-13) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT) showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB) energy in their structures.
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Antibacterianos/síntese química , Antineoplásicos/síntese química , Cumarínicos/síntese química , Piranos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Cristalografia por Raios X , Humanos , Ligação de Hidrogênio , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piranos/química , Piranos/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.
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Capsaicina/análogos & derivados , Plantas Medicinais/química , Canais de Cátion TRPV/fisiologia , Termogênese , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Animais , Capsaicina/farmacologia , Metabolismo Energético , Gânglios Espinais/citologia , Células HEK293 , Humanos , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , TemperaturaRESUMO
OBJECTIVE: To study the chemical constituents of Pattra Medicine Euodia lepta in Xishuangbanna of Yunnan Province. METHODS: The chemical constituents were isolated and purified by chromatographic techniques, and identified by NMR, MS and other spectral methods. RESULTS: In 60% ethanol extract from the stems,and 95% ethanol extract from the leaves, six compounds and two compounds were isolated and identified as pachypodol( 1) ,3-(3-methyl-but-2-enyl )umbelliferone(2),7-demethylsuberosin (3),beta-sitosterol (4),3,7-dimethoxy kaempferol(5), euolitrine(6), sesamin(7) and p-O-geranyl coumaric acid(8), respectively. CONCLUSION: Compound 7 is obtained from Euodia genus for the first time,and compound 8 is obtained from domestic Euodia lepta for the first time.
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Ácidos Cumáricos/química , Dioxóis/química , Evodia/química , Furocumarinas/química , Lignanas/química , China , Ácidos Cumáricos/isolamento & purificação , Dioxóis/isolamento & purificação , Furocumarinas/isolamento & purificação , Lignanas/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química , Sitosteroides/química , Sitosteroides/isolamento & purificaçãoRESUMO
A common surgical disease, intervertebral disc degeneration (IVDD), is increasing at an alarming rate in younger individuals. Repairing damaged intervertebral discs (IVDs) and promoting IVD tissue regeneration at the molecular level are important research goals.Exosomes are extracellular vesicles (EVs) secreted by cells and can be derived from most body fluids. Mesenchymal stem cell-derived exosomes (MSC-exos) have characteristics similar to those of the parental MSCs. These EVs can shuttle various macromolecular substances, such as proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) and regulate the activity of recipient cells through intercellular communication. Reducing inflammation and apoptosis can significantly promote IVD regeneration to facilitate the repair of the IVD. Compared with MSCs, exosomes are more convenient to store and transport, and the use of exosomes can prevent the risk of rejection with cell transplantation. Furthermore, MSC-exo-mediated treatment may be safer and more effective than MSC transplantation. In this review, we summarize the use of bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AMSCs), nucleus pulposus mesenchymal stem cells (NPMSCs), and stem cells from other sources for tissue engineering and use in IVDD. Here, we aim to describe the role of exosomes in inhibiting IVDD, their potential therapeutic effects, the results of the most recent research, and their clinical application prospects to provide an overview for researchers seeking to explore new treatment strategies and improve the efficacy of IVDD treatment.
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Exossomos , Degeneração do Disco Intervertebral , Disco Intervertebral , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Núcleo Pulposo , Humanos , Degeneração do Disco Intervertebral/terapia , Exossomos/metabolismo , Disco Intervertebral/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismoRESUMO
As our research on the physiopathology of intervertebral disc degeneration (IVD degeneration, IVDD) has advanced and tissue engineering has rapidly evolved, cell-, biomolecule- and nucleic acid-based hydrogel grafting strategies have been widely investigated for their ability to overcome the harsh microenvironment of IVDD. However, such single delivery systems suffer from excessive external dimensions, difficult performance control, the need for surgical implantation, and difficulty in eliminating degradation products. Stimulus-responsive composite hydrogels have good biocompatibility and controllable mechanical properties and can undergo solution-gel phase transition under certain conditions. Their combination with ready-to-use particles to form a multiscale delivery system may be a breakthrough for regenerative IVD strategies. In this paper, we focus on summarizing the progress of research on the stimulus response mechanisms of regenerative IVD-related biomaterials and their design as macro-, micro- and nanoparticles. Finally, we discuss multi-scale delivery systems as bioinks for bio-3D printing technology for customizing personalized artificial IVDs, which promises to take IVD regenerative strategies to new heights.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Hidrogéis , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Regeneração , Engenharia Tecidual/métodosRESUMO
Bone Marrow Mesenchymal Stem Cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing Extracellular Matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the Intervertebral Disc Degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they are secreted and can inhibit Nucleus Pulposus Cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.
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Exossomos , Degeneração do Disco Intervertebral , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Exossomos/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/terapia , Células-Tronco Mesenquimais/metabolismoRESUMO
BACKGROUND: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. OBJECTIVE: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. METHODS: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein-protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1ß was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT-PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. RESULTS: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. CONCLUSION: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.
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Degeneração do Disco Intervertebral , MicroRNAs , Núcleo Pulposo , Apoptose/genética , Células Cultivadas , Humanos , Degeneração do Disco Intervertebral/metabolismo , Lactoferrina/genética , Lactoferrina/metabolismo , MicroRNAs/metabolismo , Núcleo Pulposo/metabolismo , RNA Mensageiro/metabolismoRESUMO
Background: The current study attempted to describe the specific patterns of pathological tumor response and locoregional node metastases from surgically resected esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy (NAIC), as well as to explore the association between clinicopathological characteristics and such oncological patterns. Methods: Fifty-one patients with cT3 or deeper esophageal squamous cell cancer underwent subtotal esophagectomy after NAIC. The NAIC regimen included intravenous administration of platinum-based and docetaxel- and taxane-based chemotherapeutics along with a 200 mg fixed dose of one programmed death 1 (PD-1) inhibitor, given every 3 weeks. We divided patients into tumor/nodal good-responders and poor-responders based on the pathological observation of the tumor or nodal responses. We also examined the association between clinicopathological factors and tumor/nodal responses. Further, significant baseline predictors for tumor and nodal good-responders were identified using multivariate binary logistic regression. Results: Of the 51 patients, 68.6% achieved marked primary tumor response. Notably, 21.6% of patients achieved complete pathological response. Significant differences in treatment cycles between tumor good-responders and tumor poor-responders (P = 0.019) were observed. For locoregional nodal responses, only 33.3% of patients achieved down-staged nodal disease. Of the investigated variables, neoadjuvant cycles (odds ratio (OR): 5.271, 95% confidence interval (CI): 1.278 - 21.740, P = 0.022) and pretreatment platelets (OR: 0.979, 95% CI: 0.962 - 0.996, P = 0.017) were identified as independent predictors for good tumor and nodal responses. Conclusions: We conclusively noted that most patients receiving NAIC were tumor good-responders, whereas only one-third of patients were nodal good-responders. Furthermore, we identified that treatment cycle number and baseline platelet counts were independent predictors of combined tumor and nodal responses.
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Osteosarcoma (OS) is a rare soft-tissue malignant tumor with high lung metastasis and mortality rates. Preoperative chemotherapy, surgical resection of the lesion and postoperative chemotherapy are still the main treatments for osteosarcoma. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Recent studies have shown that targeted therapy for OS based on the characteristics of exosomes is very attractive. Exosomes are nanosized extracellular vesicles (EVs) that participate in cell-to-cell communication by transporting biologically active cargo molecules, causing changes in OS cell function and playing important roles in OS disease progression. With the characteristics of secretory cells, exosomes transport cargo (e.g., microRNAs) that can be used to detect the progress of a disease and can serve as markers and/or therapeutic targets for clinical diagnosis of OS. In this review, the roles of exosomes in OS pathogenesis, invasion, metastasis, drug resistance, diagnosis and treatment are summarized. In addition, this article elaborates a series of challenges to overcome before exosomes are applied in clinical practice and provides suggestions based on current evidence for the direction of future research.
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The spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Cinetocoros/metabolismo , Neoplasias Hepáticas/genética , Proteínas Associadas aos Microtúbulos/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Prognóstico , Fuso Acromático , Taxa de SobrevidaRESUMO
OBJECTIVES: Postmenopausal osteoporosis (PMO) and osteoporotic fracture seriously impair human health in developed countries. The present study aims to explore whether sensory nerves, calcitonin gene-related peptide (CGRP), and brain-derived serotonin are related to bone loss in ovariectomized (OVX) rats. METHODS: Female rats were grouped into the ovariectomized (OVX) and sham surgery (SHAM) groups. Immunocytochemistry, western blotting, and qPCR were performed to detect CGRP expression in the femurs. The expression levels of serotonin and CGRP in the spinal cord and brainstem were estimated using western blotting, immunofluorescence, and qPCR. ELISA was used to evaluate the serum biomarkers of bone formation and resorption. Bone mineral density was measured using dual-energy X-ray (DXA) analysis. Femur microstructure was imaged by Micro CT. P values less than 0.05 were considered statistically significant. RESULTS: ELISA showed that serum bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), ß-crosslaps, and ß-ctx were increased in the OVX group. In the OVX group, in vivo bone mineral density, trabecular bone mineral density, bone volume fraction (BV/TV), and trabecular number (Tb. N) were significantly decreased, while trabecular spacing (Tb. Sp) and trabecular bone pattern factor (Tb. Pf) were markedly increased. In the OVX group, the expression levels of CGRP of the femur were significantly downregulated. In contrast, CGRP and serotonin expression was increased in the spinal cord of the OVX group. Serotonin expression was increased in the brainstem, brainstem nucleus raphe magnus (RMG), and nucleus raphe dorsalis (DRN). CONCLUSION: Our results indicated that the activation of osteoclast triggered the release of CGRP from nociceptive sensory nerve fibers and transmitted this painful stimulus to the dorsal horn of the spinal cord to release increased CGRP. The descending serotonergic inhibitory system was activated by increased CGRP levels of the spinal cord and promoted serotonin release in the brainstem RMG, DRN, and the spinal cord, contributing to the decreased CGRP level in bone tissue, which revealed a novel mechanism of bone loss in PMO.
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Densidade Óssea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Osteoporose/metabolismo , Serotonina/metabolismo , Absorciometria de Fóton , Fosfatase Alcalina/sangue , Animais , Osso e Ossos/diagnóstico por imagem , Tronco Encefálico/metabolismo , Feminino , Osteoporose/diagnóstico por imagem , Ovariectomia , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Fosfatase Ácida Resistente a Tartarato/sangueRESUMO
Osteoarthritis (OA) is a chronic degenerative disease of the bone and joints. Immune-related genes and immune cell infiltration are important in OA development. We analyzed immune-related genes and immune infiltrates to identify OA diagnostic markers. The datasets GSE51588, GSE55235, GSE55457, GSE82107, and GSE114007 were downloaded from the Gene Expression Omnibus database. First, R software was used to identify differentially expressed genes (DEGs) and differentially expressed immune-related genes (DEIRGs), and functional correlation analysis was conducted. Second, CIBERSORT was used to evaluate infiltration of immune cells in OA tissue. Finally, the least absolute shrinkage and selection operator logistic regression algorithm and support vector machine-recurrent feature elimination algorithm were used to screen and verify diagnostic markers of OA. A total of 711 DEGs and 270 DEIRGs were identified in this study. Functional enrichment analysis showed that the DEGs and DEIRGs are closely related to cellular calcium ion homeostasis, ion channel complexes, chemokine signaling pathways, and JAK-STAT signaling pathways. Differential analysis of immune cell infiltration showed that M1 macrophage infiltration was increased but that mast cell and neutrophil infiltration were decreased in OA samples. The machine learning algorithm cross-identified 15 biomarkers (BTC, PSMD8, TLR3, IL7, APOD, CIITA, IFIH1, CDC42, FGF9, TNFAIP3, CX3CR1, ERAP2, SEMA3D, MPO, and plasma cells). According to pass validation, all 15 biomarkers had high diagnostic efficacy (AUC > 0.7), and the diagnostic efficiency was higher when the 15 biomarkers were fitted into one variable (AUC = 0.758). We developed 15 biomarkers for OA diagnosis. The findings provide a new understanding of the molecular mechanism of OA from the perspective of immunology.
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Osteoartrite/diagnóstico , Biomarcadores/metabolismo , Redes Reguladoras de Genes , Humanos , Osteoartrite/genética , Osteoartrite/imunologiaRESUMO
Airway stenosis is a common problem in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). A tissue-engineered trachea is a new therapeutic method and a research hotspot. Successful vascularization is the key to the application of a tissue-engineered trachea. However, successful vascularization studies lack a complete description. In this study, it was assumed that rabbit bone marrow mesenchymal stem cells were obtained and induced by ascorbic acid to detect the tissue structure, ultrastructure, and gene expression of the extracellular matrix. A vascular endothelial cell culture medium was added in vitro to induce the vascularization of the stem cell sheet (SCS), and the immunohistochemistry and gene expression of vascular endothelial cell markers were detected. At the same time, vascular growth-related factors were added and detected during SCS construction. After the SCS and decellularized tracheal (DT) were constructed, a tetrandrine allograft was performed to observe its vascularization potential. We established the architecture and identified rabbit bone marrow mesenchymal stem cell membranes by 14 days of ascorbic acid, studied the role of a vascularized membrane in inducing bone marrow mesenchymal stem cells by in vitro ascorbic acid, and assessed the role of combining the stem cell membranes and noncellular tracheal scaffolds in vivo. Fourteen experiments confirmed that cell membranes promote angiogenesis at gene level. The results of 21-day in vitro experiments showed that the composite tissue-engineered trachea had strong angiogenesis. In vivo experiments show that a composite tissue-engineered trachea has strong potential for angiogenesis. It promotes the understanding of diseases of airway stenosis and tissue-engineered tracheal regeneration in newborns and small infants.
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OBJECTIVE: To research the changes of chemical constituent in Inula nervosa during the processing. METHOD: Inula nervosa processed with different conditions was determined by HPLC,with acetonitrile--water as a mobile phase using gradient elution, and the detective wavelength was 280 nm. The emerging compounds 1 was extracted by 50% ethanol, isolated and purified using chromatography, and identified according to the physicochemical properties and spectral analysis. RESULTS: The HPLC chromatogram of lnula nervosa changes before and after processing. A monomer compounds was isolated from processed Inula nervosa. It was Identified as 5-hydroxymethylfurfural. CONCLUSION: The chemical constituent of Inula nervosa changes during the processing. It is the first time that compound 1 were isolated from Inula.