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1.
Kaohsiung J Med Sci ; 40(6): 530-541, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647095

RESUMO

We previously found that the relative abundance of Bifidobacterium was increased after chemotherapy; however, the role of Bifidobacterium longum in chemotherapeutic drug resistance in ovarian cancer (OVC) remains unclear. This study aimed to understand the potential effects and mechanism of B. longum extracellular vesicles (B. longum-EVs) on carboplatin (CBP) resistance in OVC. Eight normal and 11 ovarian tissues were collected and the expression of B. longum genomic DNA and its association with acquired CBP resistance in OVC patients was determined. After isolating EVs by ultracentrifugation from B. longum (ATCC 15707), CBP-resistant A2780 cells were treated with PBS, CBP, B. longum-EVs, or CBP + B. longum-EVs, and subsequently analyzed by CCK-8, Edu staining, Annexin V/PI double staining, wound healing, and Transwell assays to detect cell viability, proliferation, apoptosis, migration, and invasion, respectively. MRP1, ATP7A, ATP7B, and p53 expression as well as p53 phosphorylation were measured by western blot analysis. S15A mutation of p53 was assessed to examine the potential role of p53 Ser15 phosphorylation in CBP-resistant OVC. B. longum levels were elevated and positively associated with CBP resistance in OVC patients. Only high concentrations of B. longum-EVs attenuated A2780 cell proliferation, apoptosis, migration, and invasion. B. longum-EVs exposure significantly enhanced the sensitivity of CBP-resistant A2780 cells to CBP and decreased the expression of drug resistance-related proteins. The effect of B. longum-EVs on reversing CBP resistance was completely inhibited by S15A mutation of p53. B. longum-EVs enhanced the sensitivity of OVC cells to CBP through p53 phosphorylation on Ser15.


Assuntos
Bifidobacterium longum , Carboplatina , Resistencia a Medicamentos Antineoplásicos , Vesículas Extracelulares , Neoplasias Ovarianas , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Feminino , Fosforilação , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Linhagem Celular Tumoral , Bifidobacterium longum/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos
2.
Drug Discov Ther ; 17(3): 157-169, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37357394

RESUMO

The steady-state gut microbiome not only promotes the metabolism and absorption of nutrients that are difficult to digest by the host itself, but also participates in systemic metabolism. Once the dynamic balance is disturbed, the gut microbiome may lead to a variety of diseases. Recurrent pregnancy loss (RPL) affects 1-2% of women of reproductive age, and its prevalence has increased in recent years. According to the literature review, the gut microbiome is a new potential driver of the pathophysiology of recurrent abortion, and the gut microbiome has emerged as a new candidate for clinical prevention and treatment of RPL. However, few studies have concentrated on the direct correlation between RPL and the gut microbiome, and the mechanisms by which the gut microbiome influences recurrent miscarriage need further investigation. In this review, the effects of the gut microbiome on RPL were discussed and found to be associated with inflammatory response, the disruption of insulin signaling pathway and the formation of insulin resistance, maintenance of immunological tolerance at the maternal-fetal interface due to the interference with the immune imbalance of Treg/Th17 cells, and obesity.


Assuntos
Aborto Habitual , Microbioma Gastrointestinal , Aborto Habitual/epidemiologia , Humanos , Feminino , Gravidez
3.
Drug Discov Ther ; 17(2): 73-86, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36990765

RESUMO

With the in-depth study of the human genome and the increasing popularity of gene sequencing, it has been gradually confirmed that genetics can play a crucial role in infertility. To provide references for clinical treatment, we have focused on genes and drug therapy for genetic infertility. This review recommends adjuvant therapy and drug substitution. Examples of these therapies include antioxidants (such as folic acid, vitamin D, vitamin E, inositol, coenzyme Q10 etc.), metformin, anticoagulants, levothyroxine, dehydroepiandrosterone, glucocorticoids, and gonadotropins etc. Based on the pathogenesis, we provide an overview of the current knowledge, including randomized controlled trials and systematic reviews, and predict potential target genes and signaling pathways, proposing possible future strategies for the use of targeted drugs to treat infertility. Non-coding RNAs are anticipated to become a novel target for the treatment of reproductive illnesses since they have a significant role in controlling the occurrence and development of reproductive diseases.


Assuntos
Substituição de Medicamentos , Infertilidade , Humanos , Infertilidade/tratamento farmacológico , Ácido Fólico/uso terapêutico , Antioxidantes/uso terapêutico , Inositol/uso terapêutico
4.
Funct Integr Genomics ; 23(1): 27, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598700

RESUMO

We aimed to investigate the inhibitory effect of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (hucMSC-Exos) transmitting microRNA-342-5p (miR-342-5p) on the development of preeclampsia (PE) by targeting programmed cell death 4 (PDCD4). The primary hucMSCs were cultured and transfected with miR-342-5p, and the exosomes (Exo) were extracted from the hucMSCs. PE rats were performed with an intraperitoneal injection of L-NAME from days 11 to 19 of gestation, and injection of Exo, Exo-negative control (NC), Exo-miR-342-5p agomir, Exo-miR-342-5p antagomir, and overexpressing PDCD4 (oe-PDCD4) vector into the placenta on the 16th day of pregnancy. HE staining was utilized to observe the pathological changes in placental tissues. TUNEL staining was implemented to evaluate cell apoptosis in placental tissues. Blood pressure and 24-h urinary protein in pregnant rats were measured by a non-invasive rat tail artery blood pressure measurement and protein auto-analyzer. Expressions of miR-342-5p, PDCD4, proinflammatory cytokines (TNF-α and IL-1ß), and anti-inflammatory cytokines (IL-10 and TGF-ß) were detected by RT-qPCR, and PDCD4 protein expression was determined by Western blot. The interaction between miR-342-5p and PDCD4 was analyzed by luciferase activity assay. MiR-342-5p was downregulated while PDCD4 was upregulated in the placental tissues of PE rats. HucMSC-Exo relieved pathology and suppressed inflammatory response, and apoptosis in the placental tissues, as well as reducing blood pressure and 24-h urinary protein of PE rats. Elevated miR-342-5p enhanced the promoting influence of hucMSC-Exo on PE rats, while inhibited miR-342-5p reversed the functions of hucMSC-Exo on PE rats. miR-342-5p targeted PDCD4. Overexpression of PDCD4 worsened the development of PE in rats. HucMSC-Exo conveying elevated miR-342-5p inhibits the development of PE in a rat model through downregulating PDCD4.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Pré-Eclâmpsia , Humanos , Ratos , Feminino , Gravidez , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Citocinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo
5.
Reprod Biol ; 22(3): 100670, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35810709

RESUMO

Recurrent miscarriage (RM) is one of the common complications of pregnancy, which is closely related to gene mutation. The profiling of non-coding RNAs showed that the expression level of long non-coding RNA LINC01347 (LINC01347) in the serum of patients with recurrent abortion was significantly increased, which could serve as a potential marker for early diagnosis. However, the biological functions of LINC01347 in the miscarriage remain to be elucidated. In this study, LINC01347 expression levels in HTR-8/SVneo cells and placenta samples were measured by RT-qPCR. The migration ability of HTR-8/SVneo cells was detected by wound-healing assay. Western blotting (WB) assay was conducted to measure E-cadherin, Vimentin, N-cadherin, PTEN, phospho-AKT(S473), phospho-AKT(T308) and AKT levels. Dual luciferase reporter assay and RNA pull-down analysis were performed to validate the molecular interactions. The results showed an upregulation of LINC01347 in the placenta samples of RM patients and HTR-8/SVneo cells. LINC01347 overexpression impaired the invasion and migration of trophoblast cells, while LINC01347 silencing promoted cell migration and invasion. LINC01347 level was also negatively correlated with the changes of epithelial-mesenchymal transition (EMT) markers in trophoblasts. We further demonstrated that miR-101-3p/PTEN/AKT axis played an important role in mediating the biological roles of LINC01347 in the invasion and migration of trophoblasts. In conclusion, our results revealed that LINC01347 suppresses the migratory ability and regulates the EMT processes in trophoblasts by regulating miR-101-3p/PTEN/AKT axis, suggesting that targeting LINC01347 may serve as a strategy to ameliorate RM.


Assuntos
Aborto Habitual , RNA Longo não Codificante , Trofoblastos , Aborto Habitual/genética , Aborto Habitual/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo
6.
J Biochem Mol Toxicol ; 35(6): 1-9, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33759321

RESUMO

Among the various gynaecological cancers, ovarian cancer (OC) is the third most severe cancer worldwide affecting women. Syringic acid (SRA) exhibits several hypoglycaemia, antioxidant, and anti-inflammatory properties. The study aimed to examine the proapoptotic activities of SRA on OC in PA-1 cells. SRA has been shown to decrease cell viability, increase the rate of cell apoptosis, and cause mitochondrial membrane potential to dissipate and induce over-accumulation of intracellular reactive oxygen species in PA-1 cells after 24 h of exposure. We examined the anticancer efficacy of SRA with its responsible molecular mechanism in the PA-1 cell lines of human OC. In a dose-dependent manner, SRA substantially suppressed cell proliferation and migration. SRA exhibited significant downregulation of cyclins including CDK2, CDK4, and Cyclin D1 responsible for cell-cycle regulation. The apoptosis-mediated anticancer activity was mainly mediated through caspase-3, caspase-8, caspase-9 and Bax upregulation, and Bcl-2 downregulation. We report that SRA significantly inhibits the expression of signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), P65, and protein kinase B (AKT) pathways. These findings depict the effective inhibition of STAT3, p38, and AKT expression by SRA, making it a potential therapeutic candidate for human OC.


Assuntos
Proliferação de Células/efeitos dos fármacos , Ácido Gálico/análogos & derivados , MAP Quinase Quinase 4/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Teratoma/metabolismo , Linhagem Celular Tumoral , Feminino , Ácido Gálico/farmacologia , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia
7.
Int J Gynaecol Obstet ; 135(3): 264-267, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27634053

RESUMO

OBJECTIVE: To evaluate direct puncture embolization of the internal iliac artery with hemostatic gelatin sponge particles to treat pernicious placenta previa coexisting with placenta accreta during cesarean delivery. METHODS: A retrospective study was conducted of data from women with pernicious placenta previa and placenta accreta who underwent direct puncture embolization of the internal iliac artery during cesarean delivery at a center in China between September 1, 2013, and February 28, 2015. Information regarding surgical procedures, operative data, and outcomes during hospitalization were obtained from medical records. RESULTS: The procedure was successful in all 16 cases included. Mean operative time was 78 minutes (range 65-90) and mean estimated blood loss was 1550 mL (range 1000-2500). Complications such as fever, buttock pain, or acute limb ischemia were not observed. The procedure was performed after partial cystectomy for two patients with bladder invasion. Postoperative Doppler imaging indicated uterine recovery and normalized uterine blood flow in all patients. CONCLUSION: Direct puncture embolization of the internal iliac artery during cesarean delivery was a safe, effective, simple, and rapid method to control hemorrhage among women with pernicious placenta previa and placenta accreta.


Assuntos
Embolização Terapêutica , Artéria Ilíaca/cirurgia , Placenta Acreta/cirurgia , Placenta Prévia/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Cesárea/métodos , China , Feminino , Humanos , Duração da Cirurgia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Útero/diagnóstico por imagem
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