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1.
BMC Surg ; 22(1): 2, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996415

RESUMO

BACKGROUND: We have improved and named a new reverse rolling-mat type lymph node dissection, which effectively solves the dilemma faced by the traditional lymph node dissection in hand-assisted laparoscopic D2 radical gastrectomy through the optimization of the surgical procedure. However, the relevant clinical data are still scarce. The study aims to compare the clinical effects of two surgical procedure and explore the safety and feasibility of "reverse procedure". STUDY DESIGN: The clinicopathological data of 195 patients who underwent hand-assisted D2 radical total gastrectomy (HALTG) in our hospital from January 2011 to September 2017 were collected. A retrospective case-control study was used to compare the clinical outcomes of the two patterns of lymph node dissection. Among them, 89 patients underwent "cabbage type" lymph node dissection and 106 patients underwent the "reverse procedure" lymph node dissection. RESULTS: There were no significant differences between the two groups of patients in terms of gender, age, tumor location, incision length, postoperative hospitalization duration, pathological classification, recent complications, long-term recurrence and metastasis. The operation time of "cabbage type" group was shorter than that of "reverse procedure" group (178.35 ± 31.52 min vs 191.25 ± 32.77 min; P = 0.006). While, in the "reverse procedure" group, intraoperative blood loss was less (249.4 ± 143.12 vs 213.58 ± 101.43; P = 0.049), and there were more numbers of lymph nodes dissected (18.04 ± 7.00 vs 32.25 ± 14.23; P < 0.001). CONCLUSION: The pattern of reverse rolling-mat type lymph node dissection in HALTG perform well in terms of safety and feasibility.


Assuntos
Laparoscopia Assistida com a Mão , Laparoscopia , Neoplasias Gástricas , Estudos de Casos e Controles , Gastrectomia , Humanos , Excisão de Linfonodo , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
2.
New Phytol ; 233(1): 373-389, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34255862

RESUMO

Soluble sugars, organic acids and volatiles are important components that determine unique fruit flavor and consumer preferences. However, the metabolic dynamics and underlying regulatory networks that modulate overall flavor formation during fruit development and ripening remain largely unknown for most fruit species. In this study, by integrating flavor-associated metabolism and transcriptome data from 12 fruit developmental and ripening stages of Actinidia chinensis cv Hongyang, we generated a global map of changes in the flavor-related metabolites throughout development and ripening of kiwifruit. Using this dataset, we constructed complex regulatory networks allowing to identify key structural genes and transcription factors that regulate the metabolism of soluble sugars, organic acids and important volatiles in kiwifruit. Moreover, our study revealed the regulatory mechanism involving key transcription factors regulating flavor metabolism. The modulation of flavor metabolism by the identified key transcription factors was confirmed in different kiwifruit species providing the proof of concept that our dataset provides a suitable tool for clarification of the regulatory factors controlling flavor biosynthetic pathways that have not been previously illuminated. Overall, in addition to providing new insight into the metabolic regulation of flavor during fruit development and ripening, the outcome of our study establishes a foundation for flavor improvement in kiwifruit.


Assuntos
Actinidia , Actinidia/genética , Actinidia/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Metaboloma , Proteínas de Plantas/metabolismo , Transcriptoma/genética
3.
Integr Cancer Ther ; 20: 15347354211063504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34866448

RESUMO

Integrative oncology has developed for about 20 years in some countries; however, integrative oncology is still a relative new term for most China's oncologists. Thus, it is essential to summarize the experience and expertise, share details of differing existing models and discuss future perspectives to help define and guide practice in integrative oncology in China. This study presents a summary of the basic characteristics, status, and challenges of integrative oncology in China, and also reports on China's integrative physicians' service delivery, clinical practice and research patterns of integrative oncology by an online national survey, including 405 oncologists. It is easy for cancer patients to access to integrative therapies in China. Public funding is sufficient for integrative oncology in China, and services are often provided through general hospitals and academic hospitals. Most (95.3%) of oncologists showed a positive attitude toward the development of integrative oncology. More than half (55.6%) of the oncologists worried about the influence on integrative oncology of COVID-19, especially for routine treatment, follow-up and holding seminars. We found that integrative oncology in China has swiftly developed in recent years. However, we suggest that standard diagnosis and treatment patterns and national professional guidelines should be set up as soon as possible.

5.
Front Med (Lausanne) ; 8: 755657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34859010

RESUMO

Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.

6.
Plant Sci ; 313: 111063, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763857

RESUMO

Kiwifruit is known as 'the king of vitamin C' because of the high content of ascorbic acid (AsA) in the fruit. Deciphering the regulatory network and identification of the key regulators mediating AsA biosynthesis is vital for fruit nutrition and quality improvement. To date, however, the key transcription factors regulating AsA metabolism during kiwifruit developmental and ripening processes remains largely unknown. Here, we generated a putative transcriptional regulatory network mediating ascorbate metabolism by transcriptome co-expression analysis. Further studies identified an ethylene response factor AcERF91 from this regulatory network, which is highly co-expressed with a GDP-galactose phosphorylase encoding gene (AcGGP3) during fruit developmental and ripening processes. Through dual-luciferase reporter and yeast one-hybrid assays, it was shown that AcERF91 is able to bind and directly activate the activity of the AcGGP3 promoter. Furthermore, transient expression of AcERF91 in kiwifruit fruits resulted in a significant increase in AsA content and AcGGP3 transcript level, indicating a positive role of AcERF91 in controlling AsA accumulation via regulation of the expression of AcGGP3. Overall, our results provide a new insight into the regulation of AsA metabolism in kiwifruit.


Assuntos
Actinidia/genética , Actinidia/metabolismo , Ácido Ascórbico/metabolismo , Etilenos/metabolismo , Galactose/metabolismo , Guanosina Difosfato/metabolismo , Fosforilases/metabolismo , Ácido Ascórbico/genética , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Frutas/genética , Frutas/metabolismo , Galactose/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Guanosina Difosfato/genética , Fosforilases/genética
7.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5194-5200, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738419

RESUMO

Arisaematis Rhizoma included in the Chinese Pharmacopoeia is the dried tuber of Arisaema erubescens, A. heterophyllum or A. amurense in the family Araceae. This paper mainly focuses on the classification and summary of the chemical components and structures reported in recent years in the above three varieties of this medicinal material included in the pharmacopoeia, including alkaloids, flavonoids, phenylpropanoids, lignans and benzene ring derivatives, steroids and terpenes, glycosides and esters, etc. Then we reviewed the reported biological activities of these chemical components, including cytotoxicity, antitumor activity, antibacterial activity, nematicidal activity, etc. Although there have been reports on the review of the chemical composition of the medicinal material, the structure and classification of the chemical composition in these reviews are not clear enough. This review provides a basis for the later study of the chemical composition of this medicinal material, especially the identification of the chemical structures. And most of the current reviews on the biological activity of this medicinal material are mainly for the crude extract. This paper mainly summarized the biological activity of related monomer compounds and expected to lay a foundation for the development of novel high-efficiency and low-toxicity active leading compounds from Arisaematis Rhizoma.


Assuntos
Arisaema , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides , Glicosídeos , Rizoma
8.
Plant Physiol ; 187(1): 247-262, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34618133

RESUMO

The reproductive transition is an important event that is crucial for plant survival and reproduction. Relative to the thorough understanding of the vegetative phase transition in angiosperms, a little is known about this process in perennial conifers. To gain insight into the molecular basis of the regulatory mechanism in conifers, we used temporal dynamic transcriptome analysis with samples from seven different ages of Pinus tabuliformis to identify a gene module substantially associated with aging. The results first demonstrated that the phase change in P. tabuliformis occurred as an unexpectedly rapid transition rather than a slow, gradual progression. The age-related gene module contains 33 transcription factors and was enriched in genes that belong to the MADS (MCMl, AGAMOUS, DEFICIENS, SRF)-box family, including six SOC1-like genes and DAL1 and DAL10. Expression analysis in P. tabuliformis and a late-cone-setting P. bungeana mutant showed a tight association between PtMADS11 and reproductive competence. We then confirmed that MADS11 and DAL1 coordinate the aging pathway through physical interaction. Overexpression of PtMADS11 and PtDAL1 partially rescued the flowering of 35S::miR156A and spl1,2,3,4,5,6 mutants in Arabidopsis (Arabidopsis thaliana), but only PtMADS11 could rescue the flowering of the ft-10 mutant, suggesting PtMADS11 and PtDAL1 play different roles in flowering regulatory networks in Arabidopsis. The PtMADS11 could not alter the flowering phenotype of soc1-1-2, indicating it may function differently from AtSOC1 in Arabidopsis. In this study, we identified the MADS11 gene in pine as a regulatory mediator of the juvenile-to-adult transition with functions differentiated from the angiosperm SOC1.

10.
Oxid Med Cell Longev ; 2021: 4158495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426759

RESUMO

Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.

11.
Org Lett ; 23(15): 5885-5890, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34279973

RESUMO

A new tandem annulation of p-quinone methides (p-QMs) with ynamides is described. This cascade reaction features a unique combination of (2 + 2) annulation, retro-4π electrocyclization, and imino-Nazarov cyclization, wherein vinyl p-quinone methides (p-VQMs) as one of the key intermediates have been identified chemically. Significantly, an unusual structural reconstruction of p-QMs involving the cleavage of the C5-C6 bond and the late-stage formation of the C4-C6 bond is involved, leading to a methodology development for the construction of functionalized aminoindenes.

12.
Am J Transl Res ; 13(5): 4591-4602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150039

RESUMO

OBJECTIVE: Traditional Chinese medicine has been increasingly used in the prevention and treatment of gastric cancer, especially in application of compound Chinese medicine. The aim of this study was to investigate the effect of Qi Ling decoction (QLD) on the invasion and metastasis of gastric cancer and its related signaling pathways at the cellular and molecular level in vitro, and explore the mechanism of QLD. METHODS: Scratch assay, transwell assay, and adhesion experiments were used to study the effects of QLD and its compounds on gastric cancer. Western blot was employed to detect expression of the PI3K/Akt pathway after administration of QLD. RESULTS: QLD can significantly inhibit the invasion, migration, and adhesion of gastric cancer cells in vitro. The main chemical components of QLD (diosgenin, catechins, and calycosin) can also inhibit the invasion, migration and adhesion of gastric cancer cells. Furthermore, QLD inhibits MMP-9 and affects gastric cancer cell metastasis through the PI3K/Akt pathway. CONCLUSION: QLD and its three main chemical components can inhibit the invasion, migration, and adhesion of gastric cancer cells, and the mechanism may be related to the PI3K/Akt pathway.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33953786

RESUMO

Objective: To explore the mechanism of action of Citri Reticulatae Pericarpium-Pinelliae Rhizoma (CRP-PR) in treating gastric cancer (GC) by using pharmacology network. Methods: Based on oral bioavailability and drug-likeness, the main active components of CRP-PR were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). DisGeNET Database was used to establish target databases for GC. Cytoscape software was used to construct a visual interactive network diagram of "Active Component-Target" and screen out the key targets. The STRING database was used to construct a protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the key targets. Additionally, TCGA and HPA databases were used for key target verification. Results: Thirty-seven active components of CRP-PR were screened. The results of network analysis showed that the main components include 8-octadecenoic acid, stigmasterol, ferulic acid, and naringenin of the CRP-PR herb pair. The key targets of the PPI network mainly involved GAPDH, MAPK3, JUN, STAT3, GSK3B, SIRT1, ERBB2, and SMAD2. GO enrichment analysis involves 540 biological processes, 118 cellular components, and 171 molecular functions. CRP-PR components were predicted to exert their therapeutic effect on the tumor signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and estrogen signaling pathway. The validation of the key genes in the TCGA and HPA database showed that most of the key target verification results were consistent with this article. Conclusion: CRP-PR can treat GC by mediating PI3K-Akt signal pathway, MAPK signal pathway, and other biological processes such as tumor cell proliferation, apoptosis, and vascular regeneration, which embodies the synergistic effect of multi-components, multi-targets, and multi-channels, and provides the theoretical basis and research ideas for further study of CRP-PR in treating GC. 8-octadecenoic acid, stigmasterol, ferulic acid, and naringenin may be the material basis for the treatment of GC.

14.
Zhongguo Gu Shang ; 34(5): 429-37, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34032044

RESUMO

OBJECTIVE: To compare clinical efficacy and safety of plate internal fixation (ORIF) and external fixator (EF) in treating distal radius fractures by Meta-analysis. METHODS: From establishment of database to August, 2019, randomized controlled trial (RCT) about open reduction and internal fixation (ORIF) and external fixation (EF) in treating distal radius fractures was conducted by using computer-based databases, including CNKI, VIP, Wanfang Data, Medline, Cochrane library databases. Data extraction and quality evaluation of included study according to inclusion and exclusion criteria, RevMan 5.3 software was used to perform Meta-analysis. Palm angle, ulnar deflection angle, radius height, grip strength, ulnar variation, disabilities of arm, shoulder and hand (DASH) score, total complication rate, infection rate and tendon rupture between two groups were compared. RESULTS: Totally 19 RCT were included with 1 730 patients, 873 patients in ORIF group and 857 patients in EF group. Meta analysis result showed that after operation at 12 months, there were no significant difference in radial height [MD=0.04, 95%CI (-0.90, 0.99), P=0.93], tendon rupture [RR=1.82, 95%CI (0.71, 4.67), P=0.21], carpal tunnel syndrome [RR=2.15, 95%CI(0.98, 4.70), P=0.06], complex regional pain syndrom [RR=0.63, 95%CI(0.31, 1.27)P=0.78] between two groups. While there were significant difference in palm inclination angle [MD=1.38, 95%CI (0.83, 1.93), P< 0.000 01], ulnar deflection angle[MD=0.99, 95%CI(0.54, 1.45), P<0.000 1], ulna variability[MD=0.66, 95%CI(0.21, 1.12), P=0.005], DASH score[MD=2.42, 95%CI(0.37, 4.46), P=0.02], incidence of complications[RR=0.83, 95%CI(0.71, 0.96), P=0.01], infection rate[RR=0.20, 95%CI(0.11, 0.36), P<0.000 1]between two groups. There was statistical difference in tendinitis incidence between two groups [MD=3.88, 95%CI (1.56, 9.64), P<0.003]. CONCLUSION: Compared with EF in treating distal radius fracture, ORIF has better clinical effects in postoperative complications, palm angle, ulnar deviation angle, ulnar variation rate and infection rate. While there were no significant difference between in DASH score, radial height, tendon rupture and carpal tunnel syndrome better EF and ORIF. For the patient pursue rapid recovery of function, ORIF is better choice.


Assuntos
Fraturas do Rádio , Placas Ósseas , Fixadores Externos , Fixação de Fratura , Fixação Interna de Fraturas , Humanos , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
15.
World J Clin Cases ; 9(10): 2394-2399, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33869619

RESUMO

BACKGROUND: Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment. CASE SUMMARY: A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient's T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo. CONCLUSION: This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.

16.
ACS Omega ; 6(14): 9667-9671, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33869946

RESUMO

SARS-CoV-2 is the etiologic agent of COVID-19, which has led to a dramatic loss of human life and presents an unprecedented challenge to public health worldwide. The gold standard assay for SARS-CoV-2 identification is real-time polymerase chain reaction; however, this assay depends on highly trained personnel and sophisticated equipment and may suffer from false results. Thus, a serological antibody test is a supplement to the diagnosis or screening of SARS-CoV-2. Here, we develop and evaluate the diagnostic performance of an IgM/IgG indirect ELISA method for antibodies against SARS-CoV-2 in COVID-19. The ELISA was constructed by coating with a recombinant nucleocapsid protein of SARS-CoV-2 on an enzyme immunoassay plate, and its sensitivity and specificity for clinical diagnosis of SARS-CoV-2 infection was assessed by detecting the SARS-CoV-2-specific IgM and IgG antibodies in COVID-19 patient's sera or healthy person's sera. The SARS-CoV-2 positive serum samples (n = 168) were collected from confirmed COVID-19 patients. A commercial nucleocapsid protein-based chemiluminescent immunoassay (CLIA) kit and a colloidal gold immunochromatography kit were compared with those of the ELISA assay. The specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of IgM were 100, 95.24, 100, and 91.84%, whereas those of IgG were 100, 97.02, 100, and 94.74%, respectively. We developed a highly sensitive and specific SARS-CoV-2 nucleocapsid protein-based ELISA method for the diagnosis and epidemiologic investigation of COVID-19 by SARS-CoV-2 IgM and IgG antibody detection.

17.
Medicine (Baltimore) ; 100(13): e25148, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787596

RESUMO

BACKGROUND: The heterogeneity of colorectal cancer (CRC) poses a significant challenge to the precise treatment of patients. CRC has been divided into 4 consensus molecular subtypes (CMSs) with distinct biological and clinical characteristics, of which CMS4 has the mesenchymal identity and the highest relapse rate. Autophagy plays a vital role in CRC development and therapeutic response. METHODS: The gene expression profiles collected from 6 datasets were applied to this study. Network analysis was applied to integrate the subtype-specific molecular modalities and autophagy signature to establish an autophagy-based prognostic signature for CRC (APSCRC). RESULTS: Network analysis revealed that 6 prognostic autophagy genes (VAMP7, DLC1, FKBP1B, PEA15, PEX14, and DNAJB1) predominantly regulated the mesenchymal modalities of CRC. The APSCRC was constructed by these 6 core genes and applied for risk calculation. Patients were divided into high- and low-risk groups based on APSCRC score in all cohorts. Patients within the high-risk group showed an unfavorable prognosis. In multivariate analysis, the APSCRC remained an independent predictor of prognosis. Moreover, the APSCRC achieved higher prognostic power than commercialized multigene signatures. CONCLUSIONS: We proposed and validated an autophagy-based signature, which is a promising prognostic biomarker of CRC patients. Further prospective studies are warranted to test and validate its efficiency for clinical application.


Assuntos
Autofagia/genética , Neoplasias Colorretais/genética , Heterogeneidade Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas de Choque Térmico HSP40/genética , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Prognóstico , Proteínas R-SNARE/genética , Proteínas Repressoras/genética , Proteínas de Ligação a Tacrolimo/genética , Transcriptoma , Proteínas Supressoras de Tumor/genética
18.
Stem Cell Res Ther ; 12(1): 175, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712030

RESUMO

BACKGROUND: Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. METHODS: In the present study, the bone marrow samples of patients with ONFH (n = 16) and patients with the fracture of the femoral neck (n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups (n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. RESULTS: The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. CONCLUSION: Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.


Assuntos
Necrose da Cabeça do Fêmur , Células-Tronco Pluripotentes Induzidas , Células-Tronco Mesenquimais , Animais , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Humanos , Masculino , Osteogênese , Ratos , Esteroides
19.
Sci Rep ; 11(1): 1905, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479376

RESUMO

Sparganii rhizoma (SL) has potential therapeutic effects on gastric cancer (GC), but its main active ingredients and possible anticancer mechanism are still unclear. In this study, we used HPLC-Q-TOF-MS/MS to comprehensively analyse the chemical components of the aqueous extract of SL. On this basis, a network pharmacology method incorporating target prediction, gene function annotation, and molecular docking was performed to analyse the identified compounds, thereby determining the main active ingredients and hub genes of SL in the treatment of GC. Finally, the mRNA and protein expression levels of the hub genes of GC patients were further analysed by the Oncomine, GEPIA, and HPA databases. A total of 41 compounds were identified from the aqueous extract of SL. Through network analysis, we identified seven main active ingredients and ten hub genes: acacetin, sanleng acid, ferulic acid, methyl 3,6-dihydroxy-2-[(2-hydroxyphenyl) ethynyl]benzoate, caffeic acid, adenine nucleoside, azelaic acid and PIK3R1, PIK3CA, SRC, MAPK1, AKT1, HSP90AA1, HRAS, STAT3, FYN, and RHOA. The results indicated that SL might play a role in GC treatment by controlling the PI3K-Akt and other signalling pathways to regulate biological processes such as proliferation, apoptosis, migration, and angiogenesis in tumour cells. In conclusion, this study used HPLC-Q-TOF-MS/MS combined with a network pharmacology approach to provide an essential reference for identifying the chemical components of SL and its mechanism of action in the treatment of GC.


Assuntos
Curcuma/química , Medicamentos de Ervas Chinesas/química , Rizoma/química , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinases/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Espectrometria de Massas em Tandem
20.
Signal Transduct Target Ther ; 5(1): 295, 2020 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-33361763

RESUMO

In tauopathies, memory impairment positively strongly correlates with the amount of abnormal tau aggregates; however, how tau accumulation induces synapse impairment is unclear. Recently, we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1 (STAT1) to inhibit the transcription of synaptic N-methyl-D-aspartate receptors (NMDARs). Here, overexpressing human P301L mutant tau (P301L-hTau) increased the phosphorylated level of Signal Transduction and Activator of Transcription-3 (STAT3) at Tyr705 by JAK2, which would promote STAT3 translocate into the nucleus and activate STAT3. However, STAT3 was found mainly located in the cytoplasm. Further study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm, and thus inhibited the nuclear translocation and inactivation of STAT3. Knockdown of STAT3 in STAT3flox/flox mice mimicked P301L-hTau-induced suppression of NMDARs expression, synaptic and memory impairments. Overexpressing STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs expression. Further study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs promoters. These findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression, revealed a novel mechanism for tau-associated synapse and cognition deficits, and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.


Assuntos
Disfunção Cognitiva/metabolismo , Demência Frontotemporal/metabolismo , Transtornos da Memória/metabolismo , Receptores de N-Metil-D-Aspartato/biossíntese , Fator de Transcrição STAT3/metabolismo , Animais , Disfunção Cognitiva/genética , Modelos Animais de Doenças , Demência Frontotemporal/genética , Humanos , Masculino , Transtornos da Memória/genética , Camundongos , Camundongos Knockout , Receptores de N-Metil-D-Aspartato/genética , Fator de Transcrição STAT3/genética , Proteínas tau/genética , Proteínas tau/metabolismo
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