Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
J Vis Exp ; (207)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38767351

RESUMEN

Skeletal diseases are often complex in their etiology and affect millions of people worldwide. Due to the aging population, there is a need for new therapeutics that could ease the burden on healthcare systems. As these diseases are complex, it is difficult and expensive to accurately model bone pathophysiology in a lab setting. The challenge for the field is to establish a cost-effective, biologically relevant platform for modeling bone disease that can be used to test potential therapeutic compounds. Such a platform should ideally allow dynamic visualization of cell behaviors of bone-building osteoblasts and bone-degrading osteoclasts acting in their mineralized matrix environment. Zebrafish are increasingly used as models due to the availability of genetic tools, including transgenic reporter lines, and the fact that some skeletal tissues (including the scales) remain translucent to adulthood, allowing dynamic imaging options. Since zebrafish scales have both osteoblasts and osteoclasts and are highly abundant, they provide an easily accessible and abundantly available resource of independent bone units. Moreover, once removed, adult zebrafish scales fully regenerate, therefore offering a way to study the spatiotemporal growth of mineralized tissue in vivo. Here, we detail protocols for harvesting and tracking the regeneration of the scales. Lastly, a protocol for stable culture of scales ex vivo for a week and following the healing response after controlled damage to the mineralized matrix of the scale over time is also presented.


Asunto(s)
Escamas de Animales , Regeneración , Pez Cebra , Animales , Regeneración/fisiología , Escamas de Animales/fisiología
2.
Phytomedicine ; 129: 155703, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38723527

RESUMEN

BACKGROUND: Non-alcoholic steatohepatitis (NASH), the inflammatory subtype in the progression of non-alcoholic fatty liver disease, is becoming a serious burden threatening human health, but no approved medication is available to date. Mononoside is a natural active substance derived from Cornus officinalis and has been confirmed to have great potential in regulating lipid metabolism in our previous studies. However, its effect and mechanism to inhibit the progression of NASH remains unclear. PURPOSE: Our work aimed to explore the action of mononoside in delaying the progression of NASH and its regulatory mechanisms from the perspective of regulating lipophagy. METHODS AND RESULTS: Male C57BL/6 mice were fed with a high-fat and high-fructose diet for 16 weeks to establish a NASH mouse model. After 8 weeks of high-fat and high-fructose feeding, these mice were administrated with different doses of morroniside. H&E staining, ORO staining, Masson staining, RNA-seq, immunoblotting, and immunofluorescence were performed to determine the effects and molecular mechanisms of morroniside in delaying the progression of NASH. In this study, we found that morroniside is effective in attenuating hepatic lipid metabolism disorders and inflammatory response activation, thereby limiting the progression from simple fatty liver to NASH in high-fat and high-fructose diet-fed mice. Mechanistically, we identified AMPK signaling as the key molecular pathway for the positive efficacy of morroniside by transcriptome sequencing. Our results revealed that morroniside maintained hepatic lipid metabolism homeostasis and inhibited NLRP3 inflammasome activation by promoting AMPKα phosphorylation-mediated lipophagy and fatty acid oxidation. Consistent results were observed in palmitic acid-treated cell models. Of particular note, silencing AMPKα both in vivo and in vitro reversed morroniside-induced lipophagy flux enhancement and NLRP3 inflammasome inhibition, emphasizing the critical role of AMPKα activation in the effect of morroniside in inhibiting NASH progression. CONCLUSION: In summary, the present study provides strong evidence for the first time that morroniside inhibits NASH progression by promoting AMPK-dependent lipophagy and inhibiting NLRP3 inflammasome activation, suggesting that morroniside is expected to be a potential molecular entity for the development of therapeutic drugs for NASH.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38204249

RESUMEN

AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.

4.
World J Pediatr ; 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38141111

RESUMEN

BACKGROUND: Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early. METHODS: We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA. RESULTS: Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score. CONCLUSION: The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB).

5.
Ear Nose Throat J ; : 1455613231210388, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37994533

RESUMEN

Objective: The treatment of oral squamous cell carcinoma (OSCC) is dominated by surgery and radiochemotherapy, but its prognosis is still unsatisfactory, with around five tenths of 5-year survival. This study aimed to assess the prognosis of OSCC patients treated with surgery with and without postoperative radiotherapy. Study Design: Retrospective study. Methods: The clinicopathological information and follow-up datasets on patients with OSCC (T1-4 and/or N+) registered from 2010 to 2015 were downloaded from the Surveillance, Epidemiology, and End Results database. Totally 7231 enrolled subjects were divided into a case group (surgery alone, n = 4167) and a control group (surgery combined with postoperative radiotherapy, n = 3064). One-to-one matching was performed by propensity score matching to make the baseline data comparable between the 2 subgroups. Multivariate Cox regression analysis was used to calculate hazard ratios (HR) of various clinicopathological features. The Kaplan-Meier method and log-rank test were used to plot the survival curves. Results: The majority of patients in case group were tumor stage I (n = 2569, 61.7%), whereas most patients in control group were stages III to IV (n = 2360, 77.1%). In the case group, the 1-, 3-, and 5-year overall survival (OS; 76%, 59.5%, 53.7%) were significantly lower than those of the control group (85.1%, 64.1%, 55.8%; P < .0001). Similarly, the 1-, 3-, and 5-year cancer-specific survival (CSS) of the case group (80.2%, 66.6%, 63.3%) were significantly lower than those of the control group (87.2%, 69.3%, 63.9%, respectively; P < .0001). Cox multivariate analysis indicated that age, differentiation, clinical stage, and tumor-node-metastasis stage affected the prognosis of OSCC patients, while postoperative radiotherapy was a protective factor (OS: HR = 0.649, P < .001; CSS: HR = 0.702, P < .001). Conclusions: Postoperative radiation was an independent protective factor, hence, the combination of surgery plus radiotherapy is more beneficial for the survival of patients with OSCC, particularly for advanced cases.

6.
Bone Res ; 11(1): 49, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37730805

RESUMEN

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.


Asunto(s)
Osteoartritis , Pez Cebra , Masculino , Animales , Ratones , Regulación hacia Abajo , Esclerosis , Proteoglicanos , Osteoartritis/genética
7.
Drug Des Devel Ther ; 17: 2063-2076, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457888

RESUMEN

Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.


Asunto(s)
Antineoplásicos , Silimarina , Ratones , Animales , Silibina/farmacología , Silimarina/farmacología , Glicosilación , Ratones Endogámicos ICR , Antineoplásicos/farmacología , Apoptosis , Agua , Línea Celular Tumoral
9.
Zhongguo Zhong Yao Za Zhi ; 48(4): 1032-1042, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36872274

RESUMEN

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.


Asunto(s)
Estado Prediabético , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Fosfatidilinositol 3-Quinasas , Factor A de Crecimiento Endotelial Vascular , Interleucina-6 , Transcriptoma , Proteína p53 Supresora de Tumor , Insulina , Colesterol
10.
Gastroenterology ; 165(1): e9-e12, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36889549
12.
Gastroenterology ; 164(7): 1056-1058, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36592726
13.
Chinese Journal of Surgery ; (12): 349-352, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970213

RESUMEN

In recent years, the therapeutic concepts and surgical methods of the meandering mesenteric artery involved in atherosclerosis have been reported in the literature, and the importance of this lateral branch circulation in the field of vascular surgery has received more attention. With the improvement of imaging techniques, the discovery rate of this collateral circulation increased. In the presence of major iliac artery occlusion, the meandering mesenteric artery may serve as an important collateral circulation to relieve ischemia in the visceral or lower extremities. The meandering mesenteric artery may also lead to type Ⅱ internal leakage after endovascular repair, while the embolization of inferior mesenteric artery may be performed through the meandering mesenteric artery. The role of meandering mesenteric arteries in vascular surgery needs further study.

14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-994606

RESUMEN

Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.

15.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-994592

RESUMEN

Objective:To evaluate the mid-term results of fenestrated/branched endovascular aortic repair (f/b EVAR) for the treatment of thoracoabdominal aortic aneurysms. M ethods The clinical data of 105 thoracoabdominal aortic aneurysm patients treated with f/b EVAR at the Department of Vascular Surgery of Nanjing Drum Tower Hospital from 2018 to 2019 were retrospectively analyzed. Results:There were 43 cases of thoracoabdominal aortic aneurysm and 62 cases of thoracoabdominal aortic aissection.A total of 336 branch arteries were reconstructed,and technical success rate was 94.3%. 100 cases (95.2%) were followed-up, 6 cases (5.7%) received reoperation interventions, and 11 cases (10.5%) died. During the follow-up period, 69 cases had complete imaging data. Based on the recent CT date of the thoracoabdominal aorta, 58 patients hael positive aortic remodeling and 11 patients hael negative and indeterminate remodeling; there were 31 cases (29.5%) of endoleaks, including 7 cases (6.7%) of type Ⅰb endoleaks, 8 cases (7.6%) of type Ⅱ, 1 case (0.95%) of type Ⅲa, 13 cases (12.4%) of type Ⅲc endoleaks and 2 cases (1.9%) of type Ⅳ. Conclusions:The mid-term follow-up results were satisfactory for TAAA treated with f/b EVAR. Internal leakage remains key point for f/b EVAR.

16.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-990905

RESUMEN

Objective:To investigate an accurate and quantitative method to measure the eyeball morphological parameters of guinea pigs through a method that combines programmed digital techniques and mathematical geometric principles.Methods:Twenty-two three-week-old clean-grade male tricolor guinea pigs were selected and sacrificed by anesthesia overdose.Eyeballs were enucleated.The horizontal and sagittal images of the eyeball were taken with the high-speed photographic model of 13 million pixels macro meter, and the pictures were imported into pycharm programming software.Using the pre-written analysis program of Python 3.9, the conversion coefficient between the photo pixel and the actual length was obtained by a scale, and then the corneal surface was fitted by arc fitting and conic curve fitting.The results of arc fitting were converted to calculate the corneal radius of curvature.The corneal eccentricity was calculated according to the general conic equation (Ax 2+ Bxy+ Cy 2+ Dx+ Ey+ F=0). The corneal asphericity was evaluated by curve fitting between the central 3-mm and the whole cornea.The use and care of the animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Shanghai Public Health Clinical Center (No.2022-A009-01). Results:The digital method of Python programming can show the corneal contour of guinea pigs completely and clearly.In the transverse plane, there was no significant difference in the corneal curvature measurements among the digital fitting in central 3-mm cornea, digital fitting in whole cornea and curvature meter ( F=1.693, P=0.190). In the sagittal plane, there was a significant difference in the corneal curvature measurements among the three methods ( F=3.500, P=0.030), and the corneal curvature measurements of the whole cornea measured by the curvature meter were significantly greater than those measured by the digital fitting ( P<0.05). There was no statistical significance in the measurements of corneal curvature radius among the three methods in the transverse plane and the sagittal plane ( F=1.817, P=0.170; F=2.050, P=0.133). The horizontal and sagittal corneal eccentricity measured by digital fitting in central 3-mm cornea were 0.55±0.15 and 0.53±0.17, which were lower than 0.66±0.10 and 0.64±0.14 measured by digital fitting in whole cornea, and the differences were statistically significant ( t=-4.860, -5.210; both at P<0.01). Conclusions:It is feasible to use Python programming digital method to measure the corneal curvature and eccentricity of guinea pigs.

17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970441

RESUMEN

Objective To analyze the risk factors and build a clinical prediction model for hemodynamic depression (HD) after carotid artery stenting (CAS). Methods A total of 116 patients who received CAS in the Department of Vascular Surgery,Drum Tower Clinical College of Nanjing Medical University and the Department of Vascular Surgery,the Affiliated Suqian First People's Hospital of Nanjing Medical University from January 1,2016 to January 1,2022 were included in this study.The patients were assigned into a HD group and a non-HD group.The clinical baseline data and vascular disease characteristics of each group were collected,and multivariate Logistic regression was employed to identify the independent predictors of HD after CAS and build a clinical prediction model.The receiver operating characteristic (ROC) curve was drawn,and the area under the ROC curve (AUC) was calculated to evaluate the predictive performance of the model. Results The HD group had lower proportions of diabetes (P=0.014) and smoking (P=0.037) and higher proportions of hypertension (P=0.031),bilateral CAS (P=0.018),calcified plaque (P=0.001),eccentric plaque (P=0.003),and the distance<1 cm from the minimum lumen level to the carotid bifurcation (P=0.009) than the non-HD group.The age,sex,coronary heart disease,symptomatic carotid artery stenosis,degree of stenosis,and length of lesions had no statistically significant differences between the HD group and the non-HD group (all P>0.05).Based on the above predictive factors,a clinical prediction model was established,which showed the AUC of 0.807 and the 95% CI of 0.730-0.885 (P<0.001).The model demonstrated the sensitivity of 62.7% and the specificity of 87.7% when the best cut-off value of the model score reached 12.5 points. Conclusions Diabetes,smoking,calcified plaque,eccentric plaque,and the distance<1 cm from the minimum lumen level to the carotid bifurcation are independent predictors of HD after CAS.The clinical prediction model built based on the above factors has good performance in predicting the occurrence of HD after CAS.


Asunto(s)
Humanos , Estenosis Carotídea , Depresión , Modelos Estadísticos , Pronóstico , Stents , Hemodinámica , Placa Amiloide
18.
Proteome Sci ; 20(1): 17, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36517846

RESUMEN

BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics. METHODS: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD. RESULTS: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data. CONCLUSIONS: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.

19.
BMC Biol ; 20(1): 21, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-35057801

RESUMEN

BACKGROUND: Scales are mineralised exoskeletal structures that are part of the dermal skeleton. Scales have been mostly lost during evolution of terrestrial vertebrates whilst bony fish have retained a mineralised dermal skeleton in the form of fin rays and scales. Each scale is a mineralised collagen plate that is decorated with both matrix-building and resorbing cells. When removed, an ontogenetic scale is quickly replaced following differentiation of the scale pocket-lining cells that regenerate a scale. Processes promoting de novo matrix formation and mineralisation initiated during scale regeneration are poorly understood. Therefore, we performed transcriptomic analysis to determine gene networks and their pathways involved in dermal scale regeneration. RESULTS: We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases (P< 2× 10-3). The DEGs were also enriched for human orthologues associated with polygenetic skeletal traits, including height (P< 6× 10-4), and estimated bone mineral density (eBMD, P< 2× 10-5). Zebrafish mutants of two human orthologues that were robustly associated with height (COL11A2, P=6× 10-24) or eBMD (SPP1, P=6× 10-20) showed both exo- and endo- skeletal abnormalities as predicted by our genetic association analyses; col11a2Y228X/Y228X mutants showed exoskeletal and endoskeletal features consistent with abnormal growth, whereas spp1P160X/P160X mutants predominantly showed mineralisation defects. CONCLUSION: We show that scales have a strong osteogenic expression profile comparable to other elements of the dermal skeleton, enriched in genes that favour collagen matrix growth. Despite the many differences between scale and endoskeletal developmental processes, we also show that zebrafish scales express an evolutionarily conserved sub-population of genes that are relevant to human skeletal disease.


Asunto(s)
Proteínas de Pez Cebra , Pez Cebra , Animales , Perfilación de la Expresión Génica , Humanos , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-958435

RESUMEN

Primary aortic mural thrombus(PAMT) is a relatively rare clinical disease with unclear pathogenesis. In addition to hypercoagulability as a recognized risk factor, other related factors have been mentioned in the literatures. Aortic isthmus is the most common site of thrombosis, which may be related to its anatomical characteristics and hemodynamics. The onset of this disease is insidious, but the complications are dangerous. At present, the best treatment strategy for this disease is not clear, and simple anticoagulant therapy, aortic open surgery and endovascular treatment have been reported successfully. This article reviews the research progress of primary aortic mural thrombosis and reports as follows.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...