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Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. STATEMENT OF SIGNIFICANCE.
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In recent years, studies have shown that low-dose supplemental infrared (IR) irradiation exhibits systemic anti-inflammatory effects. The gut microbiota is increasingly recognized as a potential mediator of these effects due to its role in regulating host metabolism and inflammatory responses. To investigate the role of gut microbiota diversity and metabolite changes in the mechanism of light-emitting diodes (LED) infrared's anti-inflammatory action, we conducted IR irradiation on mice. Serum inflammatory cytokines were measured using ELISA, and fecal samples were subjected to metagenomic, untargeted, and targeted metabolomic analyses. Our results demonstrated a significant increase in the anti-inflammatory cytokine IL-10 in the IR group, accompanied by a declining trend in pro-inflammatory cytokines. Gut microbiome analysis revealed distinct alterations in composition and functional genes between the groups, including the enrichment of beneficial bacteria like various species of Parabacteroides and Akkermansia muciniphila in the IR group. Notably, the IR group exhibited enrichment in carbohydrate metabolism pathways and a reduction in DNA damage and repair pathways. Furthermore, targeted metabolomic analysis highlighted a notable increase in short-chain fatty acids (SCFAs), including butyric acid and isobutyric acid, which positively correlated with the abundance of several beneficial bacteria. These findings suggest a potential interplay between gut microbiota-derived SCFAs and the anti-inflammatory response. In conclusion, our study provides comprehensive insights into the changes in gut microbiota species and functions associated with IR irradiation. Moreover, we emphasize the significance of altered SCFAs levels in the IR group, which may contribute to the observed anti-inflammatory effects. Our findings contribute valuable evidence supporting the role of low-dose infrared light irradiation as an anti-inflammatory therapy.
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Introduction: Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field. Methods: The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer. Results: This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that "cisplatin resistance" is a continuing focus of attention, while "Metastasis" and "Ferroptosis" may be emerging research hotspots. Literature clustering analysis pointed out that "Ferroptosis", "Immunotherapy" and "ERK signaling" were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer. Conclusion: This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.
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MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.
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Activins are members of the transforming growth factor-ß (TGF-ß) superfamily and act as key regulators in various physiological processes, such as follicle and embryonic development, as well as in multiple human diseases, including cancer. They have been established to signal through three type I and two type II serine/threonine kinase receptors, which, upon ligand binding, form a final signal-transducing receptor complex that activates downstream signaling and governs gene expression. Recent research highlighted the dysregulation of the expression or activity of activin receptors in multiple human cancers and their critical involvement in cancer progression. Furthermore, expression levels of activin receptors have been associated with clinicopathological features and patient outcomes across different cancers. However, there is currently a paucity of comprehensive systematic reviews of activin receptors in cancer. Thus, this review aimed to consolidate existing knowledge concerning activin receptors, with a primary emphasis on their signaling cascade and emerging biological functions, regulatory mechanisms, and potential clinical applications in human cancers in order to provide novel perspectives on cancer prognosis and targeted therapy.
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Ativinas , Neoplasias , Gravidez , Feminino , Humanos , Receptores de Ativinas , Ativinas/metabolismo , Proteínas Serina-Treonina Quinases , Fator de Crescimento Transformador beta/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
Laryngeal squamous cell carcinoma (LSCC) is one of the common malignant tumors in the head and neck region, and its high migration and invasion seriously threaten the survival and health of patients. In cancer development, m6A RNA modification plays a crucial role in regulating gene expression and signaling. This study delved into the function and mechanism of the m6A reading protein YTHDF1 in LSCC. It was found that YTHDF1 was highly expressed in the GEO database and LSCC tissues. Cell function experiments confirmed that the downregulation of YTHDF1 significantly inhibited the proliferation, migration, and invasion ability of LSCC cells. Further studies revealed that EIF4A3 was a downstream target gene of YTHDF1, and knockdown of EIF4A3 similarly significantly inhibited the malignant progression of LSCC in both in vivo and in vitro experiments. The molecular mechanism studies suggested that YTHDF1-EIF4A3 may promote the malignant development of LSCC by activating the EMT signaling pathway. This study provides important clues for an in-depth understanding of the pathogenesis of LSCC and is a solid foundation for the discovery of new therapeutic targets and approaches.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , RNA Helicases DEAD-box/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.
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Doenças da Córnea , Ceratocone , Ceratomileuse Assistida por Excimer Laser In Situ , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Topografia da Córnea/métodos , Dilatação Patológica/etiologia , Dilatação Patológica/prevenção & controle , Dilatação Patológica/diagnóstico , Inteligência Artificial , Córnea/cirurgia , Doenças da Córnea/diagnóstico , Doenças da Córnea/etiologia , Doenças da Córnea/prevenção & controle , Ceratocone/diagnóstico , Ceratocone/etiologia , Ceratocone/prevenção & controle , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Objective: The prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research. Methods: Publications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis. Results: A total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the Journal of Glaucoma has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment. Conclusion: Studies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.
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Self-stable precipitation polymerization was used to prepare an enzyme-immobilized microsphere composite. Phosphomannose isomerase (PMI) with His-tag was successfully immobilized on Ni2+ charged pyridine-derived particles. The maximum amount of PMI immobilized on such particles was â¼184â mg/g. Compared with free enzyme, the activity of the immobilized enzymes was significantly improved. In addition, the immobilized enzymes showed a much better thermostability than free enzymes. At the same time, the immobilized enzymes can be reused for multiple reaction cycles. We observed that the enzyme activity did not decrease significantly after six cycles. We conclude that the pyridine-derived particles can be used to selectively immobilize His-tagged enzymes, which can couple the enzyme purification and catalysis steps and improve the efficiency of enzyme-catalyzed industrial processes.
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Quelantes/metabolismo , Histidina/metabolismo , Manose-6-Fosfato Isomerase/metabolismo , Nanopartículas/metabolismo , Níquel/metabolismo , Linhagem Celular Tumoral , Quelantes/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Histidina/química , Humanos , Manose-6-Fosfato Isomerase/química , Nanopartículas/química , Níquel/químicaRESUMO
Background: Nonintubated anesthesia avoids invasive tracheal intubation operations and reduces trauma. in addition, it has advantages in lung surgery in some patients with poor lung function, in line with the concept of rapid recovery. However, few studies have discussed the clinical significance of Enhanced recovery after surgery (ERAS) combined with nonintubated anesthesia in single-port video-assisted thoracoscopic surgery (VATS). We conducted a retrospective study to examine the safety and availability of nonintubated anesthesia single-port video-assisted lung surgery (NI-SP-VALS) combined with ERAS programs in patients. Methods: This was a single-center retrospective study. All patients were preoperatively diagnosed with lung nodules and underwent NI-SP-VALS or intubated anesthesia SP-VALS (I-SP-VALS) combined with ERAS programs between July 2021 and March 2022. Short-term postoperative outcomes were compared in 2 cohorts. Results: In total, 272 patients were included. Among them, 91 patients received NI-SP-VALS combined with ERAS programs (observation group), and 181 underwent intubation anesthesia (control group). Baseline data were statistically different between the two groups, and 1:1 propensity score matching (PSM) matching was used. A total of 73 patients remained in each group after PSM, and baseline characteristics were not significantly different between the 2 cohorts. The time of hospital stay [4.00 (4.00-5.00) vs. 44.50 (0.00-5.75) d; P=0.029] and catheter stay [0.50 (0.20-2.00) vs. 2.00 (2.00-2.00) d; P<0.001] were significantly shorter, the white blood cell count (WBC) [9.45 (8.08-11.30) vs. 11 (8.50-12.80)/L; P=0.009] and the lowest SpO2 in operation [96.00 (94.00-97.50) vs. 97.00 (95.00-98.50); P=0.035] were also lower in the nonintubated group than those of the intubated group. No differences were observed in variables of intraoperation, other routine blood indexes, postoperative drainage, postoperative medicine use, postoperative symptoms, complications, hospitalization expenses, postoperative follow-up index, or self-assessment of anxiety. Conclusions: The data after PSM shows that compared with intubated anesthesia, NI-SP-VALS combined with ERAS programs is safe and effective. Nonintubated anesthesia promotes rapid recovery of patients and reduces postoperative inflammatory reactions. Hence, nonintubated anesthesia may conform to the idea of ERAS and has application value in thoracic surgery.
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Sirt1 involved in cellular aging and aging-related diseases, including osteoarthritis (OA). Our previous study showed Sirt1 played a role in the pathogenesis of OA, however, the underlying mechanisms are still poorly elicited. In this study, we investigated the role of Sirt1 in epigenetically regulating P53/P21 pathway in a Sirt1 loss model. Sirt1 deletion male mice (n = 10) with destabilization of the medial meniscus (DMM) were used to observe its role on OA development. Then, the relationships between SIRT1 and P53 were detected by Coimmunoprecipitation (CoIP), and the gain-off function of P53 gene was indicated by P53 activators and inhibitors in vitro. Finally, human cartilage samples from patients with OA were collected. Sirt1 deletion mice displayed a spontaneous OA development, manifesting severe chondrocytes hypertrophy markers MMP13 and ADAMTS5, highly expressed P53 and P21. Strikingly, surgery-induced meniscus injury promoted the OA pathogenesis and apoptosis in Sirt1 deficient mice. Ultimately, our CoIP data demonstrated that Sirt1 directly interacted with P53 in vitro. However inhibition of P53 alleviated OA progression. We also observed that chondrocyte apoptosis and P53 increased in osteoarthritis (OA) progression with a declining expression of Sirt1 in human cartilage. Loss of Sirt1 in cartilage led to accelerated OA pathogenesis via aberrant activation of p53/p21 mediated senescence associated secretory phenotype, hypertrophy and apoptosis.
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Apoptose , Condrócitos/metabolismo , Condrócitos/patologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Epigênese Genética , Osteoartrite/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Idoso , Envelhecimento/patologia , Animais , Apoptose/genética , Cartilagem/patologia , Deleção de Genes , Humanos , Hipertrofia , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Osteoartrite/etiologia , Osteoartrite/patologia , Tíbia/patologiaRESUMO
BACKGROUND: Thymomas are rare malignancies. Thymectomy is the optimal therapy which could prolong the survival of patients. However, prognostic factors of thymomas are not clear. METHODS: Thymomas patients were enrolled from 2001 to 2016. Clinical and pathological prognostic factors of thymomas were evaluated by univariate and multivariate analyses. RESULTS: A total number of 98 patients was eligible for this study. All patients were received complete resection (CR). Diagnostic age [elder than the median 60 vs. younger than 60, hazard ratio (HR) =2.325, P=0.027], Masaoka stage (III vs. I, HR =10.756, P<0.001; IV vs. I, HR =6.558, P=0.014), and diabetes mellitus (DM) (with vs. without, HR =0.142, P=0.004) were independent prognostic factors for overall survival (OS). Immunohistochemistry (IHC) biomarker TP53 expression also influenced OS significantly (positive vs. negative, HR =5.157, P=0.018). Furthermore, age (elder than 60 vs. younger than 60, HR =2.980, P=0.022) was independent prognostic factors for recurrence free survival (RFS). CONCLUSIONS: We found that diagnostic age, clinical stages, DM, TP53 expression in IHC, and quality perioperative nursing are prognostic factors in thymomas.
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Tumor invasion underlies further metastasis, the leading cause for cancer-related deaths. Deregulation of microRNAs has been identified associated with the malignant behavior of various cancers, including lung adenocarcinoma (LUAD), the major subtype of lung cancer. Here, we showed the significantly positive correlation between miR-629-5p level and tumor invasion in LUAD specimens (n = 49). In a human LUAD metastasis mouse model, H1650 cells (high level of miR-629-5p) were more aggressive than A549 cells (low level of miR-629-5p) in vivo, including higher incidence of vascular invasion and pulmonary colonization. Ectopic expression of miR-629-5p in A549 cells also increased their invasive capability. Then we identified that miR-629-5p promotes LUAD invasion in a mode of dual regulation via tumor cells invasion and endothelial cells permeability, respectively. In tumor cells, miR-629-5p enhanced motility and invasiveness of tumor cells by directly targeting PPWD1 (a cyclophilin), which clinically related to tumor invasion in LUAD specimens. Restoring PPWD1 protein significantly attenuated the invasion-promoting effects of miR-629-5p. Besides, exosomal-miR-629-5p secreted from tumor cells could be transferred to endothelial cells and increased endothelial monolayers permeability by suppressing CELSR1 (a nonclassic-type cadherin), which had a low level in the endothelial cells of invasive LUAD specimens. Activating the expression of CELSR1 in endothelial cells markedly blocked the effect of miR-629-5p. Our study suggests the dual roles of miR-629-5p in tumor cells and endothelial cells for LUAD invasion, implying a therapeutic option to targeting miR-629-5p using the "one stone, two birds" strategy in LUAD.
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Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/metabolismo , Células Endoteliais/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Neoplásico/metabolismo , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Biomarcadores Tumorais/genética , Caderinas/genética , Caderinas/metabolismo , Células Endoteliais/patologia , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Permeabilidade , RNA Neoplásico/genéticaRESUMO
OBJECTIVE: The objective of the study is to evaluate the safety and feasibility of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients by short-term surgical effects. METHODS: We retrospectively collected clinical data of 55 non-elderly patients (< 70 years), 27 elderly patients (≥ 70 years) underwent LPD, and 19 elderly patients underwent open pancreaticoduodenectomy (OPD) in biliopancreatic surgery department of Huadong Hospital, affiliated to Fudan University, from Jan 2015 to Jan 2018. Patients were divided into 3 groups: LPD aged < 70 years, LPD aged ≥ 70 years, and OPD aged ≥ 70 years, according to their age at admission and surgical approach in order to compare baseline characteristics and short-term surgical outcomes. RESULTS: Totally 101 patients were included in this study; 59 cases were male; 42 cases were female; mean age was 66 years old. Elderly LPD patients seemed to have higher overall morbidity (41% vs. 20%, P = 0.05) compared to non-elderly patients. This difference is even more significant in our multivariable analysis model with an odds ratio of 4.48 (95% CI 1.31-17.87, P = 0.018). The 90-days mortality, operative time, estimated blood loss (EBL), and post-operative hospital stay (POHS) were similar in two groups. Elderly LPD patients had less EBL and shorter POHS than elderly OPD patients. However, the mortality and morbidity rate were comparable in these two groups. CONCLUSIONS: Aging patients have higher overall morbidity than younger patients in LPD. However, for aging population who need to undergo pancreaticoduodenectomy, LPD might have some advantages over OPD.
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Laparoscopia/métodos , Pancreaticoduodenectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Several studies have demonstrated the core circadian rhythm gene Bmal1 could regulate the clock control genes (CCGs) expression and maintain the integrity in cartilage tissue. In addition, its abnormal expression is connected with the occurrence and development of several diseases including osteoarthritis (OA). However, the relationship between Bmal1 and cartilage development still needs to be fully elucidated. Here, we bred tamoxifen-induced cartilage-specific knockout mice to learn the effects of Bmal1 on the cartilage development and its underlying mechanisms at specific time points. We observed that Bmal1 ablated mice showed growth retardation during puberty, and the length of whole growth plate and the proliferation zone were both shorter than those in the control group. Deletion of Bmal1 significantly inhibited the chondrocytes proliferation and activated cells apoptosis in the growth plate. Meanwhile, knockout of Bmal1 attenuated the expression of VEGF and HIF1α and enhanced the level of MMP13 and Runx2 in the growth plate chondrocytes. Consistent with these findings in vivo, ablation of Bmal1 could also lead to decrease chondrocytes proliferation, the expression of HIF1α and VEGF and elevate apoptosis in cultured chondrocytes. These findings suggest that Bmal1 plays a pivotal role in cartilage development by regulating the HIF1α-VEGF signaling pathway.
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Fatores de Transcrição ARNTL/metabolismo , Condrócitos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/fisiologia , Cartilagem/metabolismo , Células Cultivadas , Condrogênese/fisiologia , Ritmo Circadiano/fisiologia , Feminino , Camundongos , Camundongos Knockout , Camundongos TransgênicosRESUMO
Tumor necrosis factor receptor-associated factor 6 (TRAF6) acts as a central intracellular signal adapter molecule that mediates the tumor necrosis factor receptor superfamily and the interleukin-1 receptor/Toll-like receptor family in vertebrates and invertebrates. In the present study, HcTRAF6, a molluscan homologue of TRAF6 from Hyriopsis cumingii, has been cloned and identified. The entire open reading frame of HcTRAF6 was found to comprise a 1965-bp region that encodes a predicted protein of 654 amino acids, which contains conserved characteristic domains including a RING domain, two TRAF-type zinc finger domains, a typical coiled coil and the MATH domain. Phylogenetic analysis revealed that HcTRAF6 was aggregated closely with CsTRAF6 from Cyclina sinensis in the invertebrate cluster of mollusks. Further, qRT-PCR analysis showed that HcTRAF6 mRNA was extensively distributed in mussel tissues with a high expression in gills. After immune stimulation with Aeromonas hydrophila and lipopolysaccharides, the transcription of HcTRAF6 was obviously induced in the gills and hemocytes. In addition, significant fluctuation in HcTRAF6 expression was observed in the pearl sac, gills and hemocytes after mantle implantation. These findings confirmed its role in the alloimmune response. Dual-luciferase reporter assay showed that over-expression of HcTRAF6 could enhance the activity of the NF-κB reporter in a dose-dependent manner. Further, the RNA interference showed that the up-regulation of antimicrobial peptides in anti-bacterial infection was strongly suppressed in HcTRAF6-silenced mussels and that depletion of HcTRAF inhibited the elimination of A. hydrophila. All these findings together prove that HcTRAF6 functions as an efficient regulator in innate immune mechanisms against invading pathogens and the alloimmune mechanism after mantle implantation in H. cumingii.
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Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/imunologia , Unionidae/genética , Unionidae/imunologia , Aeromonas hydrophila , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Brânquias/imunologia , Células HEK293 , Hemócitos/imunologia , Humanos , Imunidade Inata , Lipopolissacarídeos , Filogenia , RNA Interferente Pequeno/genéticaRESUMO
INTRODUCTION: Propolis is a natural product with many biological activities. The present study was designed to evaluate the effects of Chinese propolis on glucose metabolism, antioxidant function, and inflammatory cytokines in patients with type 2 diabetes mellitus (T2DM). METHODS: In the 18-week study, recruited T2DM patients were randomly divided into a Chinese propolis group (900 mg/day) (n = 31) and a control group (n = 30) according to fasting serum glucose levels at baseline. RESULTS: At the end of the study, no significant difference was found between the groups in serum glucose, glycosylated hemoglobin, insulin, aldose reductase, or adiponectin. However, serum GSH, flavonoids, and polyphenols were significantly increased, and serum lactate dehydrogenase activity was significantly reduced in the Chinese propolis group. Meanwhile, serum IL-6 was significantly increased in the Chinese propolis group. CONCLUSION: Chinese propolis is effective at improving antioxidant function in T2DM patients, partly by increasing serum antioxidant parameters.
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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alteration of bowel movements. The pathogenesis of visceral hypersensitivity in IBS patients remains largely unknown. Hydrogen sulfide (H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2S at spinal dorsal horn level remains elusive in visceral hypersensitivity. The aim of this study is designed to investigate how H2S takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation (NCI). Visceral hypersensitivity was induced by neonatal colonic injection of diluted acetic acid. Expression of an endogenous H2S synthesizing enzyme cystathionine ß-synthetase (CBS) was determined by Western blot. Excitability and synaptic transmission of neurons in the substantia gelatinosa (SG) of spinal cord was recorded by patch clamping. Here, we showed that expression of CBS in the spinal dorsal horn was significantly upregulated in NCI rats. The frequency of glutamatergic synaptic activities in SG was markedly enhanced in NCI rats when compared with control rats. Application of NaHS increased the frequency of both spontaneous and miniature excitatory post-synaptic currents of SG neurons in control rats through a presynaptic mechanism. In contrast, application of AOAA, an inhibitor of CBS, dramatically suppressed the frequency of glutamatergic synaptic activities of SG neurons of NCI rats. Importantly, intrathecal injection of AOAA remarkably attenuated visceral hypersensitivity of NCI rats. These results suggest that H2S modulates pain signaling likely through a presynaptic mechanism in SG of spinal dorsal horn, thus providing a potential therapeutic strategy for treatment for chronic visceral pain in patients with IBS.
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The allograft inflammatory factor-1 (AIF-1) is one of the key factors associated with inflammatory response and immune defense. In the present study, we report the identification and characterization of AIF-1 from triangle sail mussel Hyriopsis cumingii (HcAIF-1). The full-length cDNA of HcAIF-1 consisted of a 5'-terminal untranslated region (UTR) of 80 bp, a 3'-UTR of 420 bp with a poly (A) tail, and an open reading frame of 444 bp encoding a polypeptide of 147 amino acids with two conserved EF-hand Ca2+-binding motifs. HcAIF-1 mRNA and protein were expressed in all examined tissues and showed higher mRNA expression levels were observed in immune tissues, especially hemocytes and mantle, and the highest protein expression level was in mantle. The expression level of HcAIF-1 mRNA was significantly upregulated in hemocytes 12-48 h after lipopolysaccharide challenge. After mantle tissue implantation, the expression level of this gene in pearl sac decreased significantly at 3-48 h (P < 0.01), and then was significantly upregulated at 96 h (P < 0.05) and recovered to the control level at 21-28 d. There was significant increase HcAIF-1 transcript abundance in hemocytes 96 h (P < 0.05) after mantle tissue implantation. The phagocytosis rate was significantly enhanced in hemocytes 3-24 h (P < 0.01) after the injection of recombinant HcAIF-1 protein. These findings suggest that HcAIF-1 is important in the underlying mechanism of the innate immune responses and pearl sac formation of H. cumingii.