Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
J Ethnopharmacol ; 282: 114587, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34474140

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. has been used for medical purposes in China for centuries. Standardized Ginkgo biloba L. leaves extract (GBE) is a widely used botanical drug which displays a variety of pharmacological effects against sudden sensorineural hearing loss (SSNHL). AIM OF THE STUDY: To evaluate the efficacy and safety of GBE as an adjuvant therapy, administered with corticosteroids, for the initial management of patients with SSNHL. MATERIALS AND METHODS: We searched seven databases for randomized clinical trials (RCTs) comparing GBE plus corticosteroids with corticosteroids alone for SSNHL treatment. Data analysis was carried out by Review Manager 5.4 and Stata 16.0 software. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. We subsequently evaluated the certainty of evidence using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: A total of 11 RCTs involving 1069 patients were included. Meta-analysis indicated that the clinical cure rate (RR = 1.33, 95% CI = 1.12 to 1.58, P = 0.001) and total effective rate (RR = 1.24, 95%CI = 1.17 to 1.31, P < 0.001) in SSNHL patients receiving GBE plus corticosteroids was superior to patients receiving corticosteroids alone. After treatment, pure tone average (PTA) improvement of observation group was better than that in the control group (WMD = 10.33, 95%CI = 6.46 to 14.21, P < 0.001). The levels of whole blood high shear viscosity (WMD = 0.93, 95%CI = 0.28 to 1.59, P = 0.005), whole blood medium shear viscosity (WMD = 0.53, 95%CI = 0.11 to 0.95, P = 0.01), whole blood low shear viscosity (WMD = 1.26, 95%CI = 0.80 to 1.72, P < 0.001), plasma viscosity (WMD = 0.19, 95%CI = 0.09 to 0.30, P < 0.001) and fibrinogen (WMD = 0.80, 95%CI = 0.25 to 1.35, P = 0.004) were lower than those in the control group. There was no significant difference in the change of hematokrit between two groups (WMD = 4.23, 95%CI = -0.54 to 8.99, P = 0.08). GBE was generally well tolerated, and there was no significant difference in the incidence of adverse reactions between two groups (RR = 1.01, 95%CI = 0.57 to 1.79, P = 0.97). CONCLUSION: The results of the current study suggested that GBE might be effective and promising as an adjuvant to corticosteroids in the initial treatment of moderate to profound SSNHL. However, the GRADE assessment indicated that the overall strength of evidence was not high. Further studies with high methodological quality and low risk of bias are needed to confirm the positive results. PROSPERO registration No. CRD 42020190113.

2.
Mitochondrial DNA B Resour ; 6(11): 3171-3173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746395

RESUMO

The complete chloroplast (cp) genome of Corydalis fangshanensis W.T. Wang ex S.Y. He, a Chinese endemic plant with limestone-specific distribution was first reported. The cp genome was circular in structure and 192,554 bp in length, consisting of a large single copy region (LSC, 98,393 bp), two inverted repeat regions (IRs, 42,263 bp), and a small single copy region (SSC, 9,635 bp). The overall GC content of the genome was 40.26%. It encoded 112 unique genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis resolved C. fangshanensis was closely related to C. saxicola G.S. Bunting within Corydalis sect. Thalictrifoliae (Fedde) Lidén, in line with morphological character-based taxonomy. Our result provides informative data for studying the taxonomy, phylogeny and ecology of Corydalis, especially species with specific-limestone distribution and also for studying the adaptive evolution in plants.

3.
Front Pharmacol ; 12: 747911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712138

RESUMO

Background: Hepatic inflow occlusion proceeded to reduce blood loss during hepatectomy induces ischemia-reperfusion (IR) injury in the remnant liver. Dexmedetomidine, a selective α2-adrenoceptor agonist used as an anesthetic adjuvant, has been shown to attenuate IR injury in preclinical and clinical studies. However, a meta-analysis is needed to systematically evaluate the protective effect of perioperative dexmedetomidine use on IR injury induced by hepatectomy. Methods: A prospectively registered meta-analysis following Cochrane and PRISMA guidelines concerning perioperative dexmedetomidine use on IR injury after hepatectomy was performed via searching Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, Web of Science, CNKI, WanFang, and Sinomed for eligible randomized controlled trials up to 2021.3.31. The main outcome is postoperative liver function. Risk of bias was assessed by the Cochrane Risk of Bias tool. Review Manager 5.3 and Stata12.0 were applied to perform data analyses. Results: Eight RCTs enrolling 468 participants were included. Compared with 0.9% sodium chloride, dexmedetomidine decreased serum concentration of ALT (WMD = -66.54, 95% CI: -92.10--40.98), AST (WMD= -82.96, 95% CI: -106.74--59.17), TBIL (WMD = -4.51, 95% CI: -7.32--1.71), MDA (WMD = -3.09, 95% CI: -5.17--1.01), TNF-α (WMD = -36.54, 95% CI: -61.33--11.95) and IL-6 (WMD = -165.05, 95% CI: -225.76--104.34), increased SOD activity (WMD = 24.70, 95% CI: 18.09-31.30) within postoperative one day. There was no significant difference in intraoperative or postoperative recovery parameters between groups. Conclusions: Perioperative administration of dexmedetomidine can exert a protective effect on liver IR injury after hepatectomy. Additional studies are needed to further evaluate postoperative recovery outcomes of dexmedetomidine with different dosing regimens.

4.
BMJ Open ; 11(10): e044347, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663648

RESUMO

INTRODUCTION: Leiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy. METHODS AND ANALYSIS: We are conducting a phase IV randomised controlled trial in women aged 18-45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17012992.


Assuntos
Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Leiomioma/tratamento farmacológico , Leiomioma/cirurgia , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgia , Conduta Expectante
5.
Int J Endocrinol ; 2021: 5572063, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122542

RESUMO

The pathogenesis of ovarian and endometrial cancers is closely associated with estrogen-related pathways. These estrogen-dependent tumors seriously threaten the health and quality of life in women. Noncoding RNAs (ncRNAs) are defined as RNAs that do not encode proteins, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which have been reported in estrogen-dependent female reproductive system tumors. This review systematically summarizes the role of ncRNAs in estrogen-dependent tumors and common patterns of regulatory mechanisms to explore their future research directions in tumor diagnosis, treatment, and prognosis. This may provide new ideas for the potential application of ncRNAs in estrogen-dependent female reproductive system tumors.

6.
Front Endocrinol (Lausanne) ; 12: 668073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122342

RESUMO

The uterine endometrium, which lines the mammalian uterus, is essential for embryo implantation. This lining undergoes significant changes during sexual and menstrual cycles. The endometrium is also associated with hormone-related diseases such as endometriosis and endometrial cancer. Circular RNAs (circRNAs) play a role in various biological processes. Recent studies have determined that circRNAs function in both normal and pathological endometrial environments. Here, we review high-throughput studies pertaining to circRNAs as well as individual circRNAs active in the endometrium, in order to explore the myriad functions of circRNAs in the endometrium and mechanisms underlying these functions, from panoramic and individual perspectives. Owing to their abundant expression, stability, and small size, circRNAs have displayed potential usefulness as diagnostic markers and treatment targets for endometrial-related diseases. Therefore, the specific role of circRNAs in the endometrium warrants systematic investigation in the future.

7.
Int J Biol Sci ; 17(7): 1744-1756, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994859

RESUMO

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC (P=0.040) and HNSCC (P=0.044), especially in HPV 16 integrated CC (P=0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC (P=0.013) and HNSCC (P=0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC (P=1.76e-67) and HNSCC (P<10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status (P<10e-10), higher mutation count (P<10e-10), higher fraction genome altered value (P=2.078e-4), higher aneuploidy score (P=3.362e-4), and earlier started the smoking year (P=2.572e-4), which were associated with shorter overall survival (P=0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC.

8.
Biomed Pharmacother ; 139: 111605, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901872

RESUMO

Chimeric antigen receptor (CAR)-T cell therapy has been shown to be an effective treatment for hematological tumors, but the treatment of solid tumors still lacks effectiveness. In the tumor microenvironment, macrophages are the innate immune cells with the highest infiltration rate. Tumor-associated macrophages (TAMs) stimulate angiogenesis, increase tumor invasion, and mediate immunosuppression. Because macrophages can infiltrate solid tumor tissue and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T-cells, NK cells, DCs, and other resident non-immune cells), researchers are trying to use macrophages modified with CAR (CAR-M) against solid tumors. This review describes recent reports of CAR-M-based tumor treatments and summarizes their shortcomings and future applications.


Assuntos
Imunoterapia , Macrófagos/imunologia , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Animais , Humanos , Neoplasias/imunologia
9.
Medicine (Baltimore) ; 100(16): e25604, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879727

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common chronic gastrointestinal diseases, and the current diagnosis of IBS is still based on symptoms and examination. Pinaverium bromide is commonly used as an antispasmodic in the treatment of IBS. But adverse effects of pinaverium bromide are common. Meta-analyses show that acupuncture has a positive therapeutic effect on IBS. METHODS: Randomized controlled trials of comparing the efficacy of acupuncture and pinaverium bromide in the treatment of IBS will be searched in the relevant database: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies selected will be exported to EndNote V.9.1 software. Data will be carried out independently from the selected articles by 2 reviewers. Any disagreement will be solved in consultation with a third reviewer. RESULTS: Our study aims to compare the efficacy of acupuncture and pinaverium bromide in the treatment of IBS and to fill the lack of relevant evidence. CONCLUSION: Through the inclusion of relevant literature, the overall efficacy of acupuncture and pinaverium bromide in the treatment of IBS will be evaluated, and the gap between various acupuncture treatment measures will be further analyzed. INPLASY REGISTRATION NUMBER: INPLASY 202130068.


Assuntos
Terapia por Acupuntura/métodos , Síndrome do Intestino Irritável/terapia , Morfolinas/uso terapêutico , Parassimpatolíticos/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
10.
Biosens Bioelectron ; 184: 113235, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33887614

RESUMO

Epithelial-mesenchymal transition (EMT) is closely related to tumor metastasis and invasion. Thereinto, mesenchymal tumor mitochondria are the critical target for tumor inhibition. Therefore, real-time in vivo monitoring of EMT as well as inhibiting mesenchymal tumor mitochondria is of great diagnosis and therapy significance. Herein, we construct a multi-stage recognition and morphological transformable self-assembly-peptide nano biosensor NDRP which can response the EMT marker and specifically damage the mesenchymal tumor cell in vivo. This nano-molar-affinity sensor is designed and screened with sensitive peptides containing a molecular switching which could be specifically triggered by the receptor to achieve the vesicle-to-fibril transformation in living system with enhanced fluorescent signal. NDRP nanosensor could target the tumor lesion in circulatory system, recognize mesenchymal tumor marker DDR2 (Discoidin domain receptor 2) in cellular level and specifically achieve mitochondria in subcellular level as well as damaged mitochondria which could be applied as a in vivo theranostic platform.


Assuntos
Técnicas Biossensoriais , Transição Epitelial-Mesenquimal , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Camundongos , Camundongos Nus , Mitocôndrias , Peptídeos
11.
Medicine (Baltimore) ; 100(11): e25198, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33726014

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) has a high morbidity rate worldwide, but there are no effective treatment measures, which seriously affect people's lives. Previous clinical studies on Tong-Xie-Yao-Fang (TXYF) combined with Si-Ni-San (SNS) in the treatment of IBS have been increasing, but there is no systematic evaluation. This study aims to systematically study the effectiveness of TXYF combined with SNS in the treatment of IBS. METHODS: The PubMed, EMBASE, Science Network, Cochrane Library, Chinese Biomedical Literature, Wanfang Chinese Digital Journal and Conference Database, China National Knowledge Infrastructure Database and VIP China Science and Technology Journal Database (VIP) will be used Search related literature, and the search time is from the date of establishment to February 2021. The National Institutes of Health clinical registry Clinical Trials, International Clinical Trials Registry Platform and the Chinese clinical trial registration platform will be searched to find ongoing or unpublished trials. After screening the literature according to the criteria, two researchers independently extracted data according to a predetermined table. The primary outcome is total effective rate. The RevMan 5.3.5 software will be used for statistical analysis. Finally, the recommendation, evaluation, development and evaluation system will be used to evaluate the quality evidence for each result. RESULTS: This study will provide the latest evidence of efficacy for the TXYF combined with SNS for IBS. CONCLUSION: The effectiveness of TXYF combined with SNS for IBS will be evaluated. UNIQUE INPLASY NUMBER: INPLASY202120075.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Síndrome do Intestino Irritável/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
12.
Medicine (Baltimore) ; 100(8): e24958, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663136

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is the most commonly gastrointestinal diseases. The Rome Foundation's global study on 33 countries shows the total prevalence of IBS under the Rome IV Diagnostic Criteria was 3.8%. It is well established that people with IBS have higher levels of anxiety and depression. The impact of the acupuncture associated with anxiety and depression has been widely studied in Western countries. Acupuncture may be a promising choice for the treatment of anxiety and depression in IBS. METHODS: RCTs of acupuncture for depression and anxiety in IBS will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreement will be solved in consultation with a third reviewer. RESULTS: Our study aims to explore the efficacy of acupuncture for depression and anxiety in IBS and to provide up-to-date evidence for clinical of IBS. CONCLUSION: This study will perform a comprehensive systematic review and meta-analysis on the efficacy of acupuncture for depression and anxiety in IBS, making up for the lack of relevant evidence of the clinical use of acupuncture. INPLASY REGISTRATION NUMBER: INPLASY 202120014.


Assuntos
Terapia por Acupuntura/métodos , Ansiedade/terapia , Depressão/terapia , Síndrome do Intestino Irritável/psicologia , Ansiedade/complicações , Depressão/complicações , Humanos , Síndrome do Intestino Irritável/complicações , Revisões Sistemáticas como Assunto
13.
Eur J Clin Nutr ; 75(2): 335-344, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32366994

RESUMO

BACKGROUND: A health program aiming at college students is pressingly needed to improve their lifestyle and prevent diseases. However, a health intervention often requires health facilities and the many efforts of health workers. This project attempts to evolve traditional health intervention by using integrated methods based on social media and multiple mobile tools. METHODS: A total of 110 undergraduates from Zhejiang University were recruited. In all, 87 participants volunteered to enroll in the intervention group, whereas 23 stayed in a control group. Fifteen staff (dietitians, health assistants and a sports coach) used the WeChat app and its plugin Zhishi mini-program for health education, diet and physical activity (PA) supervision during 21 days. Pre-to-post changes of eating habits, physical fitness tests and anthropometry data were measured. The RE-AIM framework was employed to evaluate the intervention, dimensions of which were Reach, Effectiveness, Adoption, Implementation, and Maintenance. RESULTS: The recruitment rate of students was 79.1%. The intervention group showed significant progress in terms of healthy food intake (all P < 0.05), and an improvement in PA level (P = 0.004) over 21 days. About 60.9% subjects were satisfied with the whole program and 64.4% would like to join the program again. CONCLUSIONS: This intervention showed a great improvement in healthy behavior with great feasibility for further dissemination.


Assuntos
Mídias Sociais , China , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Estilo de Vida Saudável , Humanos , Estudantes
14.
Brief Bioinform ; 22(4)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33059369

RESUMO

Human papillomavirus (HPV) integrating into human genome is the main cause of cervical carcinogenesis. HPV integration selection preference shows strong dependence on local genomic environment. Due to this theory, it is possible to predict HPV integration sites. However, a published bioinformatic tool is not available to date. Thus, we developed an attention-based deep learning model DeepHPV to predict HPV integration sites by learning environment features automatically. In total, 3608 known HPV integration sites were applied to train the model, and 584 reviewed HPV integration sites were used as the testing dataset. DeepHPV showed an area under the receiver-operating characteristic (AUROC) of 0.6336 and an area under the precision recall (AUPR) of 0.5670. Adding RepeatMasker and TCGA Pan Cancer peaks improved the model performance to 0.8464 and 0.8501 in AUROC and 0.7985 and 0.8106 in AUPR, respectively. Next, we tested these trained models on independent database VISDB and found the model adding TCGA Pan Cancer performed better (AUROC: 0.7175, AUPR: 0.6284) than the model adding RepeatMasker peaks (AUROC: 0.6102, AUPR: 0.5577). Moreover, we introduced attention mechanism in DeepHPV and enriched the transcription factor binding sites including BHLHA15, CHR, COUP-TFII, DMRTA2, E2A, HIC1, INR, NPAS, Nr5a2, RARa, SCL, Snail1, Sox10, Sox3, Sox4, Sox6, STAT6, Tbet, Tbx5, TEAD, Tgif2, ZNF189, ZNF416 near attention intensive sites. Together, DeepHPV is a robust and explainable deep learning model, providing new insights into HPV integration preference and mechanism. Availability: DeepHPV is available as an open-source software and can be downloaded from https://github.com/JiuxingLiang/DeepHPV.git, Contact: huzheng1998@163.com, liangjiuxing@m.scnu.edu.cn, lizheyzy@163.com.

15.
Mol Ther Nucleic Acids ; 22: 1107-1120, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33294296

RESUMO

Synovitis refers to the inflammation of the synovial membrane and is commonly detected in patients with osteoarthritis (OA). Recent reports have suggested that microRNAs (miRNAs) could be a promising target for diagnosis and prognosis in OA. This study examines the effect of microRNA-10a (miR-10a) in fibroblast-like synoviocyte (FLS)-mediated synovitis obtained from patients with OA. Expression of miR-10a is negatively associated with the severity of synovitis. miR-10a inhibited proliferation, migration, and secretion of pro-inflammatory cytokines of OA-FLS that were obtained from OA patients in vitro. By using a patient-derived xenograft (PDX) model, miR-10a repressed proliferation of OA-FLSs and production of OA synovium-derived pro-inflammatory cytokines in vivo. Twist Family BHLH Transcription Factor 1 (TWIST1) and mitogen-activated protein kinase kinase kinase 7 (MAP3K7) were identified as an upstream regulator and direct target of miR-10a in OA-FLSs, respectively. Nuclear factor κB (NF-κB) signaling pathway, a downstream pathway of MAP3K7, was also repressed by miR-10a in OA-FLSs. To summarize, the TWIST1-miR-10a-MAP3K7-NF-κB pathway mediates the development of synovitis in OA. miR-10a functions as an anti-inflammatory mediator in OA-FLS.

16.
EBioMedicine ; 58: 102897, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32711250

RESUMO

BACKGROUND: Gene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery. METHODS: Using a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs' vagina, which were made up of poly (ß-amino ester) (PBAE)-plasmid polyplex nanoparticles (NPs) based two gel materials, modified montmorillonite (mMMT) and hectorite (HTT). FINDINGS: By conducting flow cytometry of the cervical cells, we found that PBAE-GFP-NPs-mMMT gel was more efficient than PBAE-GFP-NPs-HTT gel in delivering exogenous DNA intravaginally. Next, we designed specific CRISPR/SpCas9 sgRNAs targeting porcine endogenous retroviruses (PERVs) and evaluated the genome editing efficacy in vivo. We discovered that PERV copy number in vaginal epithelium could be significantly reduced by the local delivery of the PBAE-SpCas9/sgRNA NPs-mMMT gel. Comparable genome editing results were also obtained by high-fidelity version of SpCas9, SpCas9-HF1 and eSpCas9, in the mMMT gel. Further, we confirmed that the expression of topically delivered SpCas9 was limited to the vagina/cervix and did not diffuse to nearby organs, which was relatively safe with low toxicity. INTERPRETATION: Our data suggested that the PBAE-NPs mMMT vaginal gel is an effective preparation for local gene therapy, yielding insights into novel therapeutic approaches to sexually transmitted disease in the genital tract. FUNDING: This work was supported by the National Science and Technology Major Project of the Ministry of science and technology of China (No. 2018ZX10301402); the National Natural Science Foundation of China (81761148025, 81871473 and 81402158); Guangzhou Science and Technology Programme (No. 201704020093); National Ten Thousand Plan-Young Top Talents of China, Fundamental Research Funds for the Central Universities (17ykzd15 and 19ykyjs07); Three Big Constructions-Supercomputing Application Cultivation Projects sponsored by National Supercomputer Center In Guangzhou; the National Research FFoundation (NRF) South Africa under BRICS Multilateral Joint Call for Proposals; grant 17-54-80078 from the Russian Foundation for Basic Research.


Assuntos
Colo do Útero/citologia , Retrovirus Endógenos/genética , Dosagem de Genes/efeitos dos fármacos , Polímeros/química , RNA Guia/administração & dosagem , Administração Intravaginal , Animais , Bentonita/química , Sistemas CRISPR-Cas , Células Cultivadas , Colo do Útero/química , Retrovirus Endógenos/efeitos dos fármacos , Feminino , Edição de Genes , Terapia Genética , Camundongos , Modelos Animais , Nanopartículas , Plasmídeos/administração & dosagem , Plasmídeos/genética , Silicatos/química , Suínos , Cremes, Espumas e Géis Vaginais
17.
J Cell Physiol ; 235(11): 8768-8778, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32633026

RESUMO

Mutation in the tumor suppressor gene p53 is the most frequent molecular defect in endometrial carcinoma (EC). Recently, CP-31398, a p53-stabilizing compound, has been indicated to possess the ability to alter the expression of non-p53 target genes in addition to p53 downstream genes in tumor cells. Herein, we explore the alternative mechanisms underlying the restoration of EC tumor suppressor function in mutant p53 by CP-31398. A p53-mutated EC cell was constructed in AN3CA cells with restored or partial loss of Slug using lentiviral vectors, followed by treatment with 25 µM CP-31398. A p53-independent mechanism of CP-31398 was confirmed by the interaction between mouse double minute 2 homolog (MDM2) and Slug AN3CA cells treated with IWR-1 (inhibitor of Wnt response 1). Furthermore, the AN3CA cells were treated with short hairpin RNA against Slug, Wnt-specific activators (LiCl) or inhibitors (XAV-939) followed by CP-31398 treatment. Moreover, AN3CA cell proliferation and apoptosis were examined. A tumorigenicity assay was conducted in nude mice. CP-31398 could promote the apoptosis of p53-mutated EC cells, while Slug reversed this effect. Slug ubiquitination was found to occur via binding of Slug to MDM2 in AN3CA cells. We found that CP-31398 increased the GSK-3ß, p-Slug, Puma, Wtp53, and Bax expressions whereas Wnt, Mtp-53, Slug, Bcl-2, and Ki-67 expressions were decreased. However, these findings were reversed following the activation of the Wnt pathway and overexpression of Slug. Finally, the in vivo experimental evidence confirmed that CP-31398 with depleted Slug suppressed tumor growth by downregulating the Slug. Collectively, CP-31398-regulated Slug downregulation represses the p53-mutated EC via the p53/Wnt/Puma pathway.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Pirimidinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Camundongos Nus , Proteínas Proto-Oncogênicas c-mdm2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/genética
18.
J Ovarian Res ; 13(1): 63, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503679

RESUMO

Granulosa cells (GCs) are somatic cells surrounding oocytes within follicles and are essential for folliculogenesis. Pathological changes in GCs are found in several ovarian disorders. Recent reports have indicated that long non-coding RNAs (lncRNAs), which modulate gene expression via multiple mechanisms, are key regulators of the normal development of GCs, follicles, and ovaries. In addition, accumulating evidence has suggested that lncRNAs can be utilized as biomarkers for the diagnosis and prognosis of GC-related diseases, such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Therefore, lncRNAs not only play a role in GCs that are involved in normal folliculogenesis, but they may also be considered as potential candidate biomarkers and therapeutic targets in GCs under pathological conditions. In the future, a detailed investigation of the in vivo delivery or targeting of lncRNAs and large-cohort-validation of the clinical applicability of lncRNAs is required.


Assuntos
Células da Granulosa/metabolismo , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico/genética , RNA Longo não Codificante/genética , Feminino , Predisposição Genética para Doença , Humanos , Ovário/patologia
19.
Crit Rev Oncol Hematol ; 152: 103010, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32540781

RESUMO

This study aimed to evaluate the benefits and risks of patients with diffuse large B-cell lymphoma (DLBCL) treated with ibrutinib. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for relevant studies. The pooled overall response (OR), complete response (CR), and partial response (PR) were 57.9 %, 35.0 %, and 20.1 %, respectively. The pooled OR and CR of ibrutinib monotherapy were 41.6 % and 15.2 % and of ibrutinib + rituximab-based therapy were 72.0 % and 47.5 %, respectively. The relapsed/refractory DLBCL achieved a pooled OR and CR of 49.7 % and 27.7 %, respectively. The pooled OR and CR were 64.2 % and 56.9 % in non-germinal center B-cell-like (non-GCB) DLBCL and 68.3 % and 36.0 % in relapsed/refractory central nervous system lymphoma (CNSL), respectively. The pooled median progression-free and overall survival were 4.54 months and 11.5 months, respectively. 70.7 % and 52.6 % patients experienced ≥ grade 3 adverse events and serious adverse events. The ibrutinib-contained therapy was well tolerated and showed the potential to improve tumor response of patients with non-GCB DLBCL and relapsed/refractory CNSL.


Assuntos
Linfoma Difuso de Grandes Células B , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab
20.
Antiviral Res ; 178: 104794, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32298665

RESUMO

Sustained infection of high-risk human papillomavirus (HR-HPVs), especially HPV16 and HPV18, is a major cause of cervical cancer. E6 and E7 oncoproteins, encoded by the HPV genome, are critical for transformation and maintenance of malignant phenotypes of cervical cancer. Here, we used an emerging programmable clustered regularly interspaced short palindromic repeat (CRISPR)/Cas13a system to cleave HPV 16/18 E6/E7 messenger RNAs (mRNAs). The results showed that customized CRISPR/Cas13a system effectively and specifically knocked down HPV 16/18 E6/E7 mRNAs, inducing growth inhibition and apoptosis in HPV16-positive SiHa and HPV18-positive HeLa Cell lines, but not in HPV-negative C33A cell line. Simultaneously, we detected downregulation of E6/E7 oncoproteins and upregulation of tumor suppressor P53 and RB proteins. In addition, we used subcutaneous xenograft tumor growth assays to find that the weight and volume of tumors in the SiHa-16E6CR1 group knocked down by the CRISPR/Cas13a system were significantly lower than those in the SiHa-VECTOR group lacking crRNA. Our study demonstrated that targeting HPV E6/E7 mRNAs by the CRISPR/Cas13a system may be a candidate therapeutic strategy for HPV-related cervical cancer.


Assuntos
Sistemas CRISPR-Cas , Proteínas de Ligação a DNA/genética , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Quebras de DNA de Cadeia Dupla , Regulação para Baixo , Feminino , Terapia Genética , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Papillomavirus/virologia , RNA Mensageiro/genética , RNA Viral/genética , RNA Viral/metabolismo , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Regulação para Cima , Neoplasias do Colo do Útero/virologia , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...