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1.
Blood ; 142(10): 903-917, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37319434

RESUMEN

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.


Asunto(s)
Proteína 7 Similar a la Angiopoyetina , Proteína 1 Inhibidora de la Diferenciación , Leucemia Mieloide Aguda , Animales , Ratones , Proteína 7 Similar a la Angiopoyetina/genética , Proteína 7 Similar a la Angiopoyetina/metabolismo , Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Microambiente Tumoral , Humanos , Proteína 1 Inhibidora de la Diferenciación/metabolismo
2.
Cell Mol Biol (Noisy-le-grand) ; 68(1): 192-200, 2022 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-35809313

RESUMEN

The current study aimed to explore the correlation between Mir-34A-3p, Mir-31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. For this paper, 120 patients with colorectal cancer were selected as the study group, and their adjacent normal tissues were selected as the control group. The quantitative real-time PCR (QRT-PCR) method was used to detect miR-34a-3p and miR-31 in tissues, and the immunohistochemistry EnVision two-step method was used to detect PLEK2 positive expression. The expressions of miR -34a-3p, miR -31, and PLEK2 in colon cancer tissues and normal cancer tissues were compared, and the correlation between miR -34a-3p, miR -31, and PLEK2 and clinic-pathological characteristics of colorectal cancer patients were analyzed. The results showed that expression of miR -34a-3p, miR -31 and positive expression rate of PLEK2 in colorectal cancer tissues were higher than those in normal adjacent tissues (P<0.05). The expression of miR -34a-3p was related to tumor size, degree of tissue differentiation, lymph node metastasis and TNM stage (P < 0.05). The 3-year survival rate of miR -34a-3p with low expression was lower than miR -34a-3p with high expression, which was a protective factor affecting the poor prognosis of colorectal cancer (P < 0.05). The expression of miR -31 was related to tumor size and TNM stage. The 3-year survival rate of the group with high expression of miR -31 was lower than the group with low expression of miR -31, which was a risk factor affecting the poor prognosis of colorectal cancer (P < 0.05). PLEK2 positive expression was associated with lymph node metastasis, and the 3-year survival rate of the PLEK2 positive group was lower than the PLEK2 low expression group, which was a risk factor for poor prognosis of colorectal cancer (P < 0.05). In general, miR -34a-3p, miR -31, and PLEK2 are closely associated with the occurrence and development of colorectal cancer, and they are all influential factors affecting the prognosis of patients with colorectal cancer, which can provide a basis for the evaluation and treatment of patients, and are worthy of widespread clinical application.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Metástasis Linfática , MicroARNs/genética , MicroARNs/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa
3.
Cancer Cell Int ; 19(1): 109, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31049031

RESUMEN

Background: The aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF). Methods: The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were intralateroventricularly microinjected with miR-103a inhibitors, inhibitors negative control (NC), siRNA-NC and BDNF-siRNA, respectively. The RT-qPCR and western blot analysis were used to detect the expression of miR-103a, BDNF and glial fibrillary acidic protein (GFAP) in hippocampus tissues of rats. TUNEL staining was used to detect the apoptosis of hippocampal neurons. The RT-PCR and ELISA was used to detect the levels of TNF-α and IL-6 in hippocampal tissues and in serum, respectively. Results: Increased expression of miR-103a, GFAP, and number of apoptotic neurons, decreased expression of BDNF and number of surviving neurons were found in hippocampus tissues of epilepsy rats. After miR-103a inhibitors interfered with epilepsy rats, there showed decreased expression of miR-103a and GFAP, increased expression of BDNF and decreased number of apoptotic neuron as well as increased number of surviving neurons. Compared with miR-103a inhibitors alone, epilepsy rats treated with BDNF-siRNA combined with miR-103a inhibitors significantly increased expression of GFAP in hippocampal tissues of epilepsy rats, increased number of apoptotic neurons and significantly decreased the number of surviving neurons. Conclusion: Our study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene.

4.
J Tradit Chin Med ; 35(4): 417-21, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26427111

RESUMEN

OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis (KOA). METHODS: One hundred patients were randomly divided, into a treatment (50 patients) and control group (50 patients). In the treatment group, patients orally took the Chinese medicine Huqian Wan. Control group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey (SF 36) were used to evaluate the curative effect before treatment and after 8 and 16 weeks of treatment. RESULTS: VAS and WOMAC scores significantly decreased and SF 36 scores significantly increased after treatment in both groups compared with before treatment (P < 0.05). There were significant differences in VAS, WOMAC, and SF 36 score changes between the two groups at week 16 (P < 0.05). There was a significant increase in VAS and WOMAC scores in the control groups (P < 0.05) between weeks 8 and 16, but no significant difference was found in the treatment group (P > 0.05). CONCLUSION: Huqian Wan could effectively improve the clinical symptoms and quality of life in patients with KOA. It could also have a better and longer lasting curative effect without obvious adverse events compared with Votalin.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Osteoartritis de la Rodilla/tratamiento farmacológico , Deficiencia Yin/tratamiento farmacológico , Anciano , Femenino , Humanos , Riñón/fisiopatología , Hígado/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Resultado del Tratamiento , Deficiencia Yin/fisiopatología
5.
Transl Stroke Res ; 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37580538

RESUMEN

p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynamic regulation of the acetylation of p53 at lysine 320 is controlled by acetyltransferase PCAF and histone deacetylases HDAC1 and HDAC6. The in silico simulation have made it possible to suggest the acetylation of p53 at lysine 320 acetylation may facilitate the shuttling of p53 between the nucleus and cytoplasm in penumbra neurons. Acetylation of p53 at lysine 320 is more preferable than acetylation at lysine 373 and probably promotes survival and repair of penumbra neurons after stroke. Strategies to increase p53 acetylation at lysine 320 via increasing PCAF activity, inhibiting HDAC1 or HDAC6, inhibiting p53, or a combination of these interventions may have therapeutic benefits for stroke recovery and would be promising for neuroprotective therapy of stroke.

6.
Leukemia ; 37(1): 164-177, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36352191

RESUMEN

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Animales , Ratones , Humanos , Rituximab/uso terapéutico , Pimozida/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/tratamiento farmacológico , Proteasas Ubiquitina-Específicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
7.
Sci Adv ; 9(48): eadi7375, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38019913

RESUMEN

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.


Asunto(s)
Eritropoyesis , Síndromes Mielodisplásicos , Animales , Humanos , Ratones , Eritropoyesis/genética , Síndromes Mielodisplásicos/genética , Proteínas del Tejido Nervioso/genética , Pronóstico , Receptores Inmunológicos/genética , Proteínas Roundabout
8.
Exp Oncol ; 44(2): 126-131, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35964643

RESUMEN

Histone deacetylases, especially zinc-dependent deacetylases HDACs, are among attractive drug targets for treating cancer in recent years. AIM: To explore the expression level of HDACs in several human cancer cell lines and examine the possible association between their expression and the sensitivity/resistance to the selective- or pan-HDAC inhibitors. MATERIALS AND METHODS: The RNA expression of 11 HDACs isoforms was assayed in HeLa, HepG2, AV3, HEK293, A549, and K562 cells by semiquantitative reverse transcription-polymerase chain reaction. The sensitivity/resistance of these cell lines to the pan- or selective- HDAC inhibitors was estimated by MTS assay. RESULTS: The relative transcription of HDACs genes demonstrated that members of Class I HDAC (HDAC1, 2 and 3) and members of Class II HDAC (HDAC4, 5, 6 and 7) had slight to significant levels of expression in cell lines under study with no dominant HDAC-subtype gene transcription. pan-HDAC inhibitor demonstrated superior antitumor activity compared to HDAC isoform-selective inhibitor. CONCLUSION: The absence of the dominant HDAC-subtype gene transcription in different human cancer cell lines explains the inferior efficacy of HDAC isoform-selective inhibitors as compared to pan-HDAC inhibitors.


Asunto(s)
Histona Desacetilasas , Neoplasias , Células HEK293 , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Neoplasias/genética , Isoformas de Proteínas/genética , Zinc/farmacología
9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 27(3): 481-4, 2010 Jun.
Artículo en Zh | MEDLINE | ID: mdl-20649002

RESUMEN

The study of water molecule self-diffusion process is of importance not only for getting anatomical information of brain inner tissue, but also for shedding light on the diffusion process of some medicine in brain tissue. In this paper, we summarized the self-diffusion model of water molecule in brain inner tissue, and calculated the self-diffusion coefficient based on Monte Carlo simulation under different conditions. The comparison between this result and that of Latour model showed that the two self-diffusion coefficients were getting closer when the diffusion time became longer, and that the Latour model was a long time-depended self-diffusion model.


Asunto(s)
Agua Corporal/metabolismo , Encéfalo/metabolismo , Modelos Biológicos , Método de Montecarlo , Permeabilidad de la Membrana Celular , Difusión , Imagen de Difusión por Resonancia Magnética/métodos , Espacio Extracelular/metabolismo , Humanos
10.
Front Vet Sci ; 7: 571730, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33335918

RESUMEN

Murine Norovirus (MNV) is one of the most known viruses among viruses in mice. Because of the high prevalence of MNV in frequently used laboratory animals in biomedical researches, there is a significant impact of MNV. There may be different prevalence degrees and molecular characteristics of MNV in different regions around the world. Here, we reported an MNV strain "designated HBTS-1806" isolation from commercial mice's feces that caused a detectable cytopathic effect (CPE) in RAW264.7 cells. According to electron microscopy, the virus was 50-70 nm in diameter. The complete genome of HBTS-1806 is 7383 nucleotides with a structure similar to that of MNV reference strains. According to phylogenetic analysis on the basis of the whole genome, HBTS-1806 shared nucleotide sequence identities of 90.2-95.4% with other Chinese isolates reported. Analysis of amino acid sequence on the basis of ORF1 and ORF2 suggested that the isolated strain may be derived from recombination. Although no gross lesions or histopathological changes were found from mice infected with 5 × 105 TCLD50 of MNV by oral gavage inoculation, the intestinal virus loads lasted 12 weeks, suggesting a persistent infection strain of MNV isolate in China.

11.
Artículo en Zh | WPRIM | ID: wpr-1028754

RESUMEN

AIM To investigate the protective effects and the mechanism of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes.METHODS To screen and determine the effective concentration of corosolic acid,the injury models of H9c2 cardiomyocytes established by 1 μmol/L doxorubicin were exposed to 24 h different concentrations of corosolic acid,followed by detections of their cell activity by MTT method;their cell apoptosis morphology by Hoechst 33342 staining method;their cell apoptosis rate by Annexin V-FITC/PI double staining method;their intracellular ROS level by DCFH-DA probe;their intracellular iron level by iron ion colorimetry;and their protein expressions of Bax,Bcl-2,cleaved-caspase3,Nrf2,GPX4 and Ptgs2 by Western blot.RESULTS Upon the doxorubicin-induced injury models of H9c2 cardiomyocytes,corosolic acid improved their viability and survival rate(P<0.05),decreased their levels of ROS and Fe2+ and the apoptosis rate(P<0.05),up-regulated the protein expressions of Bcl-2,Nrf2 and GPX4(P<0.05),and down-regulated the protein expressions of Bax,cleved-caspase 3 and Ptgs2(P<0.05).CONCLUSION Corosolic acid can inhibit the ROS level and apoptosis of doxorubicin-induced injury models of H9c2 cardiomyocytes,and the iron death as well via activating Nrf2/GPX4 pathway.

12.
Artículo en Zh | WPRIM | ID: wpr-1021400

RESUMEN

BACKGROUND:The preoperative planning of traditional X-ray films is often inaccurate,which can lead to some intraoperative and postoperative complications,increase the operation time and intraoperative blood loss,and to some extent affect the surgical outcome of total hip arthroplasty. OBJECTIVE:To investigate the accuracy and effectiveness of artificial intelligence preoperative planning in total hip arthroplasty. METHODS:Sixty patients who underwent primary total hip arthroplasty on the affected side were selected.30 of them used artificial intelligence 3D preoperative planning(trial group)and 30 used conventional X-ray film 2D preoperative planning(control group),and there were no statistically significant differences between the two groups in terms of gender,age,condition and other general data(P>0.05).The actual intraoperative prosthesis placement and preoperative planning prosthesis matching,intraoperative operation time,intraoperative blood loss,bilateral femoral eccentric distance difference,bilateral joint eccentric distance difference and bilateral lower limb length difference,and Harris score at 3 months after operation were compared between the two groups,and the accuracy and application effect of the two preoperative plans were analyzed. RESULTS AND CONCLUSION:(1)Patients in both groups were followed up for 4-6 months postoperatively.One patient in the control group had a posterior dislocation of the prosthesis at 5 days postoperatively,which recovered after performing manual repositioning without re-dislodgement.The rest of the patients did not have postoperative complications or postoperative death.(2)Complete matching rate of the prosthesis on the acetabular side and femoral side was significantly better in the trial group than that in the control group(P<0.05).(3)Operation time and intraoperative blood loss were significantly less in the trial group than those in the control group(P<0.05).(4)The difference in bilateral lower limb length between the two groups was statistically significant(P<0.05),and the difference in bilateral femoral eccentric distance and bilateral joint eccentric distance was not statistically significant(P>0.05).(5)Harris score of patients in the trial group was significantly higher than that in the control group 3 months after operation(P<0.05).(6)These results confirm that compared with traditional film planning,artificial intelligence preoperative planning can predict the prosthesis type more accurately,shorten the operation time,reduce intraoperative blood loss,diminish the occurrence of postoperative bilateral lower limb inequality,and accelerate postoperative recovery.

13.
Artículo en Zh | WPRIM | ID: wpr-1025412

RESUMEN

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

14.
Ying Yong Sheng Tai Xue Bao ; 30(6): 1807-1814, 2019 Jun.
Artículo en Zh | MEDLINE | ID: mdl-31257750

RESUMEN

Zooplankton plays a mediating role in the food web of aquatic ecosystems, the stable carbon and nitrogen isotopes (δ13C and δ15N) of which have been widely used to study the utilization of food resources, material cycling pathways, and trophic relationships. The δ13C and δ15N values of zooplankton have been used to predict primary productivity, sources and sinks of pollutants and environmental changes. To better use δ13C and δ15N of zooplankton as ecological and environmental indicators, it is particularly important to understand their temporal and spatial variations and the influencing factors. Based on related literature, we synthesized spatial and temporal variations in δ13C and δ15N of zooplankton in different aquatic ecosystems and taxa groups, and the use of δ13C and δ15N indicators for ecological processes and environmental changes. The δ13C and δ15N of zooplankton are largely affected by its food sources, and its stable isotope compositions are in turn affected by primary productivity and nitrogen sources. We proposed that the combination of δ13C and δ15N in zooplankton with transportation and transformation of emerging pollutants would form a multi-means, multi-disciplinary and multi-scale research direction in the fields of earth science and biology.


Asunto(s)
Ecosistema , Zooplancton/química , Animales , Isótopos de Carbono , Cadena Alimentaria , Nitrógeno , Isótopos de Nitrógeno
15.
Artículo en Zh | WPRIM | ID: wpr-1017995

RESUMEN

Objective:To explore the molecular mechanism of Matrine Injection in treating colorectal cancer based on network pharmacological analysis and molecular docking.Methods:Taking matrine as the object, the corresponding potential drug targets in matrine were obtained from Swiss Target Prediction database, and SuperPred database, and the database of traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Differential genes were obtained from gene expression omnibus (GEO), and GeneCards, OMIM, DrugBank, and CTD databases were used to collect colorectal cancer-related genes. Furthermore, core targets were screened by establishing protein-protein interaction (PPI) networks. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed by bioconductor of R language. Finally, the molecular docking calculation was performed to evaluate the interaction between matrine and core targets.Results:Matrine contained 63 targets. A total of 14 198 targets for colorectal cancer were obtained. The topology analysis results of the PPI network showed that 5 main targets such as myelocytomatosis proteins (MYC), interleukin-6 (IL-6), Caspase-3 (CASP3), mammalian target of rapamycin (mTOR), and amphiregulin (AR). GO enrichment analysis found that biological process (BP) mainly includes hydrogen peroxide reaction, cell reaction to hydrogen peroxide and cell response to chemical stress, etc; Cell components (CC) mainly include lipid rafts, membrane microregions and synaptic membranes, etc; Molecular functions (MF) mainly include transcriptional coregulatory factor binding, postsynaptic neurotransmitter receptor activity and core promoter sequence-specific DNA binding. KEGG pathway analysis showed that it involved chemical carcinogenesis-receptor activation, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway, etc. Molecular docking showed that matrine had good binding with the core target.Conclusions:Matrine acts on targets such as MYC, IL-6, CASP3, mTOR, and AR, and exerts therapeutic effects on colorectal cancer by regulating chemical carcinogenesis-receptor activation, TNF signaling pathway, Toll-like receptor signaling, etc.

16.
Artículo en Zh | WPRIM | ID: wpr-989623

RESUMEN

Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.

17.
Artículo en Zh | WPRIM | ID: wpr-1023218

RESUMEN

Objective:To explore the feasibility and superiority of integrating the image teaching of "hand and foot together" into the theoretical teaching of femoral neck fracture.Methods:Sixty five-year clinical medical students of Batch 2017 in Inner Mongolia Medical University were selected as the research objects and were randomly divided into the experimental group and the control group (30 students each group). The teaching content is femoral neck fracture theory course. The experimental group used PPT + "hand and foot together" image teaching, while the control group used PPT + model teaching aids of traditional teaching. The teaching effect of the two groups of students was evaluated after class. SPSS 22.0 statistical software was used for t-test and Chi-square test. Results:Classroom satisfaction survey evaluation of students in the experimental group is as follow: interest in learning (8.60±0.72); motivation and participation (8.40±0.93); classroom activity (8.37±1.07); teacher-student interaction (8.57±1.01); theoretical knowledge mastery (8.57±0.97). Classroom satisfaction survey evaluation of students in the control group is as follow: interest in learning (7.10±1.03); motivation and participation (7.30±0.92)classroom activity (6.83±1.18); teacher-student interaction (6.73±0.78); theoretical knowledge mastery (7.17±0.75). The difference between the groups was statistically significant ( P<0.05). The theoretical test scores in the experimental group (81.90±7.93) were significantly higher than those in the control group (75.33±7.79), and the difference between the groups was statistically significant ( P<0.05). Conclusion:The "hand and foot together" image teaching method is an advanced and novel teaching method that can be widely used in clinical teaching. This method not only improves the teaching effect, but also enlivens the classroom atmosphere and enhances the interaction between teachers and students, which make the students' learning process changed from abstract to intuitive and from simple rote to understanding memory. It has achieved satisfactory results.

18.
Artículo en Zh | WPRIM | ID: wpr-1018207

RESUMEN

Objective:To investigate the potential key targets of Liujun Anwei Prescription and its effects on NF-κB/iNOS-NO in small intestine of mice with chemotherapy- associated diarrhea; To reveal the anti-inflammatory components and molecular mechanism.Methods:UPLC-Q/TOF MS combined with UNIFI software was used to analyze the chemical components of Liujun Anwei Prescription. PubChem database was searched to obtain the active components of Liujun Anwei Prescription, and the Swiss Target Prediction was used to predict the targets. The database of DisGeNET, OMIM and GeneCards were searched to obtain the targets of chemotherapy-related diarrhea. The potential targets of Liujun Anwei Prescription in the treatment of chemotherapy-related diarrhea diseases were obtained by crossing the targets of active components of Liujun Anwei Prescription and those related to diarrhea diseases. The PPI network and component-target-pathway network were constructed by Cytoscape 3.7.1 software, and the intersecting targets were analyzed by GO and KEGG based on David Database. The potential active components and potential targets predicted in the network were verified by using Autodock software. 60 C57BL/6J male mice were divided into normal control group, model group, positive control group and Liujun Anwei Prescription high-, medium- and low-dosage groups according to random number table method, with 10 mice in each group. In addition to the normal control group, the other groups of mice were intraperitoneally injected with 5-fluorouracil injection 50 mg/kg preparation to construct CID mouse model. After 14 days, the expressions of NF-κB and iNOS in jejunum were detected by Western blot.Results:A total of 197 compounds were identified, and 156 key compounds of Liujun Anwei Prescription were screened, involving 82 potential targets, mainly through NOS2 and other key targets, playing a role through cancer pathway, PI3K-Akt, NF-κB signal pathway. The experimental results showed that Liujun Anwei Prescription could significantly down-regulate the protein expressions of NF-κB and iNOS.Conclusion:This study reveals the pharmacodynamic material basis of Liujun Anwei Prescription, which can be achieved by decreaseing the levels of NF-κB and iNOS to affect the inflammatory response of intestinal tissue, improve intestinal mucosal barrier function, and thus improve chemotherapy related diarrhea.

19.
Artículo en Zh | WPRIM | ID: wpr-993238

RESUMEN

Objective:To analyze the prognostic value of nomogram model for cervical cancer based on the imaging features of diffusion kurtosis imaging (DKI) histogram.Methods:The DKI and clinical data of 272 patients with cervical cancer who were admitted to Affiliated Hospital of Guangdong Medical University from March 2015 to February 2022 were collected and retrospectively analyzed. All patients were randomly divided into the training group ( n=190) and validation group ( n=82) at a ratio of 7 vs. 3. The parameters of DKI histogram were obtained by GE AW 4.2 MRI software. The best prognostic imaging features were screened by LASSO regression. The DKI radiomics score was calculated by linear combination. The independent risk factors of prognosis were identified by univariate and multivariate regression analyses, and a nomogram model was constructed. The model discrimination was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The internal consistency of the model was evaluated by the calibration map. Results:Adenocarcinoma ( HR=2.496, 95% CI=1.312-4.749, P=0.005), DKI score ( HR=24.087, 95% CI=6.062-95.711, P<0.001), depth of invasion ≥ 1/2 muscular layer ( HR=2.277, 95% CI=1.156-4.487, P=0.017) and neutrophil to lymphocyte ratio (NLR) ( HR=1.800, 95% CI=1.313-2.468, P<0.001) were the independent risk factors for prognosis of cervical cancer. The AUC of the nomogram model in the training and validation groups were 0.860 and 0.757, respectively. The calibration curve was well fitted with the 45° diagonal. The prediction results of long-term prognosis of this model were in good agreement with the actual situation. Conclusions:Adenocarcinoma, NLR, DKI score and depth of invasion ≥ 1/2 muscular layer are the independent risk factors for the prognosis of patients with cervical cancer. The constructed nomogram model could reliably predict the 3-year survival rate of patients with cervical cancer.

20.
Artículo en Zh | WPRIM | ID: wpr-994578

RESUMEN

Objective:To investigate the effect of carotid endarterectomy(CEA) in the treatment of symptomatic carotid artery near-occlusion(CNO).Methods:Clinical symptoms, imaging examination, treatment and prognosis of 122 symptomatic CNO patients admitted to China-Japan Friendship Hospital from Jan 2014 to Jan 2020 undergoing CEA were retrospectively analyzed. Patients were divided into two groups based on the collapse condition,full collapse group(54 cases) and non-full collapse group(68 cases).Results:The difference was insignificant between the two groups at the 30-day and 12-month occurrence rate of primary endpoints(1.85% vs. 4.41%, P=0.629;7.41% vs. 4.41%, P=0.698).Postoperative re-stenosis occurred in one case in the non-full collapse group 8 months after CEA. Conclusions:CEA can achieve good curative effect for patients with CNO with recurrent symptoms, irrelevant to the existence of distal full collapse. The shunt can prevent intraoperative hypoperfusion and postoperative hyperperfusion.

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