RESUMEN
INTRODUCTION: Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota. METHODS: In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon. RESULTS: In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota. CONCLUSION: Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.
Asunto(s)
Endometriosis , Infertilidad Femenina , Enfermedades Uterinas , Humanos , Femenino , Endometriosis/metabolismo , Infertilidad Femenina/etiología , Líquido Ascítico/metabolismo , Endometrio/metabolismoRESUMEN
Cervical cancer (CC) is one of the most prevalent malignancies among females. Cytoprotective autophagy could confer cancer cell tolerance to hypoxic stress, promoting cell survival and adaptation. Aspartyl-tRNA synthetase 1 antisense 1 (DARS-AS1) is an oncogenic long non-coding RNA (lncRNA) in various cancers, but how DARS-AS1 regulates cytoprotective autophagy in hypoxic environment in CC remains unclear. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted to explore the interaction between hypoxia-inducible factor 1 subunit alpha (HIF1α) and DARS-AS1 promoter. Methylated RNA immunoprecipitation (MeRIP) followed by quantitative real-time polymerase-chain reaction (RT-qPCR) detected methylated RNA level. The process of autophagic maturation was monitored by immunofluorescence staining. Higher DARS-AS1 expression was found in CC tissues and cytoprotective. We also uncovered that hypoxic exposure induced cytoprotective autophagy via HIF1α/DARS-AS1/DARS axis. Moreover, DARS-AS1 was validated to facilitate DARS translation via recruiting N6-adenosine-methyltransferase methyltransferase like 3 (METTL3) and methyltransferase like 14 (METTL14), which bound with DARS mRNA DARS mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1α/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of CC and might be a promising target of therapeutic strategies for patients afflicted with CC.
Asunto(s)
Autofagia , Metiltransferasas , Neoplasias del Cuello Uterino , Autofagia/genética , Línea Celular Tumoral , Femenino , Humanos , Metiltransferasas/genética , ARN sin Sentido , ARN Mensajero/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
PURPOSE: To investigate the changes in tumor markers (TMs), coagulation function and vascular endothelial growth factor (VEGF) in patients with ovarian cancer (OC) and benign ovarian disease (BOD). METHODS: A total of 68 OC patients admitted to and treated in our hospital were selected (OC group), and another 68 BOD patients in the same time period were enrolled (BOD group). The variations in TMs, coagulation function and VEGF in OC and BOD patients were explored by analyzing the TMs, coagulation function and expression levels of serum VEGF and D-dimer in OC group and BOD group as well as the differences in TMs and coagulation function in patients in different stages. RESULTS: The values of TMs such as cancer antigen 125 (CA125), carbohydrate antigen 19.9 (CA19.9) and human epididymis protein 4 (HE4) in OC group were remarkably higher than those in BOD group, with significant differences (p<0.05). The values of those TMs were relatively low in the patients in stage I-II but relatively high in the patients in stage III-IV, and the patients in stage I-II had evidently lower values of those TMs than those in stage III-IV (p<0.05). The coagulation function was similar in both groups (p>0.05), while OC group exhibited a notably higher serum fibrinogen (FIB) level than BOD group (p<0.05). The levels of coagulation function indexes [prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT)] in the patients in stage I-II were comparable to those in stage III-IV, showing no differences (p>0.05), but the serum FIB level was markedly higher in the patients in stage III-IV than that in in stage I-II (p<0.05). The expression level of serum VEGF was increased distinctly in OC group compared with that in BOD group [(378.15±94.45) pg/mL vs. (164.02±67.38) pg/mL, p<0.05]. Moreover, OC group manifested obviously elevated expression level of serum D-dimer in comparison with BOD group [(4.58±1.48) µg/mL vs. (0.67±0.12) µg/mL, p<0.05]. CONCLUSIONS: TMs, coagulation function indexes and serum VEGF and D-dimer are highly expressed in OC patients, and the combined detection of TMs, coagulation function and serum VEGF can serve as an important method of diagnosing OC.
Asunto(s)
Coagulación Sanguínea/fisiología , Enfermedades del Ovario/sangre , Neoplasias Ováricas/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/sangre , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Natural killer (NK) cells have pivotal role in immunotherapy of human ovarian cancer (OC). Although microRNAs (miRNAs) participate in dysfunction of NK cells, how and whether miR-140-3p regulates cytotoxicity of NK cells in OC are uncertain. miR-140-3p and mitogen activated protein kinase 1 (MAPK1) abundances were examined via quantitative real-time polymerase chain reaction or western blot. Tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) abundances were examined via enzyme linked immunosorbent assay. NK cytotoxicity to OC was evaluated via lactate dehydrogenase release. The relevance of miR-140-3p and MAPK1 was proved via luciferase activity analysis. Murine xenograft experiment was applied to assess the function of miR-140-3p on NK cytotoxicity. miR-140-3p was elevated and MAPK1 was declined in NK cells from OC patients, while the levels were reversed after treatment of interleukin-2 (IL-2). MiR-140-3p addition mitigated IFN-γ and TNF-α production induced via IL-2 as well as NK-92 cytotoxicity to OC cells. Additionally, MAPK1 was negatively regulated via miR-140-3p and ablated the influence of miR140-3p on cytotoxicity, cytokines levels. Besides, miR-140-3p enrichment facilitated tumor growth via suppressing function of NK cells in a xenograft model. miR-140-3p suppressed NK cytotoxicity to OC cells via mediating MAPK1, indicating a new avenue of ameliorating NK cells function for OC treatment.
Asunto(s)
Citotoxicidad Inmunológica , Regulación Neoplásica de la Expresión Génica , Células Asesinas Naturales/inmunología , MicroARNs/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Neoplasias Ováricas/genética , Animales , Antagomirs/genética , Antagomirs/metabolismo , Emparejamiento Base , Secuencia de Bases , Estudios de Casos y Controles , Línea Celular Tumoral , Técnicas de Cocultivo , Femenino , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-2/farmacología , Células Asesinas Naturales/patología , Ratones , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , MicroARNs/inmunología , Proteína Quinasa 1 Activada por Mitógenos/inmunología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Cultivo Primario de Células , Ribonucleótidos/genética , Ribonucleótidos/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
MicroRNAs (miRNAs) are known to be dysregulated in many tumors and associated with aggressive or poor prognosis phenotypes. miR-590-5p acts as an oncogene in a variety of human malignancies. However, its mechanism of action in endometrioid endometrial cancer (EEC) is poorly understood. In this study, we performed qRT-PCR to detect the miR-590-5p expression in EEC tissues, and found that miR-590-5p expression levels were significantly upregulated in EEC tissue specimens compared with the noncancerous endometrial tissues. Subsequently, we confirmed that knockdown of miR-590-5p inhibits cell proliferation, and induces cell cycle arrest and apoptosis, and activates the intrinsic apoptotic pathway including upregulating cleaved-caspase-3, Bax and cleaved-PARP. Most importantly, we identified that miR-590-5p inhibits phosphatase and tensin homolog (PTEN), a tumor suppressor gene by directly targeting its 3'-UTR. Meanwhile, our data showed that PTEN level in the cancer tissues was inversely correlated with miR-590-5p expression in 20 EEC patients. Furthermore, the tumor suppressive effects of miR-590-5p downregulation were rescued by knockdown of PTEN in EEC cells. These results demonstrated that miR-590-5p acts as an oncogene and positively regulates EEC cells by targeting PTEN, suggesting that suppression of miR-590-5p may be a novel approach for the treatment of EEC.
RESUMEN
OBJECTIVE: To study the chemical constituents of Psoralea corylifolia. METHODS: Column chromatography was used in the isolation procedure. The structures of isolated compounds were elucidated by spectral data. RESULTS: Seven compounds were isolated and their structures were identified as isopsoralen (1), psoralen (2), bavachalcone (3), 4", 5"-dehydroisopsoralidin (4), methyl 4-hydroxybenzoate (5), psoralidin (6), corylin (7). CONCLUSION: Compounds 4 and 5 are obtained from Psoralea for the first time.