Conclusions: There is a significant enrichment in SP cells among different EC cell lines, and these SP cells be more resistant to Taxol, MPA and radiation therapy. The overexpression of BCRP among SP cells may be the cause of resistance to Taxol, progestin and radiotherapy, which may be related to apoptosis and autophagic activity.
Cervical cancer is the second most common gynecological malignancy. Accumulating evidence has suggested that microRNAs (miRNAs) are involved in the occurrence and development of cervical cancer. The present study aimed to investigate the function and underlying molecular mechanism of microRNA (miRNA/miR)-29a in cervical cancer. Reverse transcription-quantitative PCR and methylation-specific PCR were used to examine the expression of miR-29a and methylated status of p16 promoter, respectively. Cell Counting Kit-8 analysis and flow cytometry were performed to evaluate cell viability and cycle, respectively. Dual-luciferase reporter assay was performed to verify the interaction between miR-29a and its targets. Western blot analysis was performed to detect the protein levels of DNA methyltransferases (DNMT)3A and DNMT3B. The results demonstrated that miR-29a expression was downregulated in cervical cancer tissues and cells, and negatively correlated with p16 promoter hypermethylation. Furthermore, cell experiments confirmed that miR-29a suppressed cell proliferation and induced cell cycle arrest in HeLa and C-33A cells. Mechanically, miR-29a restored normal methylation pattern of the p16 gene by sponging DNMT3A and DNMT3B. Taken together, the results of the present study demonstrated the epigenetic regulation of tumor suppressor p16 by miR-29a as a unique mechanism, thus providing a rationale for the development of miRNA-based strategies in the treatment of cervical cancer.
Objectives: Few studies have examined the impacts of structural differences in the urban–rural dichotomy under the new household registration policy on migration and settlement behavior. Nevertheless, the rationale for the settlement policy of local governments should be further elucidated and improved. This study aims to analyze the household registration, land property rights, and differences in migrants’ settlement intentions. Methods: This study used migration survey data from the Pearl River Delta and probit regression to fill this gap in the literature. Findings: Because of the long-term effects of the household registration system and their socioeconomic differences, urban-urban migrants and rural–urban migrants differed in their settlement intentions. Furthermore, the new points-based household registration system affected migrants’ settlement intentions. Relative to the rural–urban migrants, urban–urban migrants more easily met the settlement requirements under the points-based system, and they tended to settle in their current cities. By contrast, migrants with farmland in their hometowns tended to settle there. The findings underscore the relevance of adopting perspectives that consider the urban–rural dichotomy and related structural differences to understand migrants’ settlement intentions in China.
Objective: To study the clinical significance of the change of residual cancer burden (RCB) of epithelial ovarian carcinoma (EOC) between primary (PDS) and interval debulking surgery (IDS) in order to evaluate the effectiveness of adjuvant chemotherapy. Methods: Thirty-eight EOC patients with suboptimal PDS with adjuvant chemotherapy were selected for this retrospective study and divided into pathologically negative (group A) and pathologically positive (group B) groups based on the histopathological examination and the change of size of residual disease after IDS. Patients in group B were further divided into groups B1 (partial remission criteria, n = 9), B2 (consistent with stable disease, n = 12) and B3 (consistent with disease progression, n = 4) based on the changes in RCB between PDS and IDS and the guidelines to evaluate the response to treatment in solid tumors (Response Evaluation Criteria in Solid Tumors, RECIST). The responses to chemotherapy evaluated by pathological examination of RCB versus by CA-125, recurrence patterns, and prognoses were analyzed. Results: The clinical benefit rates evaluated by pathological assessment for groups A, B1, B2 and B3 were 100, 100, 100 and 0%, respectively (p < 0.01), whereas the rates were not statistically different when evaluated by CA-125 (100, 100, 91.7 and 100%, respectively; p > 0.05). The median progression-free survival (PFS) for patients in groups A and B was 36 and 6 months, respectively (p < 0.05); the median overall survival (OS) was 93 and 42 months, respectively (p < 0.05). There were no significant differences in median PFS or OS among patients in groups B1, B2 and B3 (PFS: 16, 6 and 1.5 months; OS: 52, 31 and 30.5 months, respectively; all p > 0.05), but there were significant differences in median PFS or OS between B1 and B3. There was no significant difference in recurrence rates between groups A and B (53.8 vs. 72.0%, p > 0.05), but there were significant differences in the rate of drug-resistant recurrence [28.6% (2/7) vs. 72.2% (13/18), p < 0.05] and in median PFS of relapsed patients (19 vs. 4 months, p < 0.05). Conclusion: The histopathological assessment of RCB between PDS and IDS may be used to evaluate and predict the response to adjuvant chemotherapy in EOC.
Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.
Various studies have described the roles of myeloid-derived suppressor cells (MDSCs) in pathological conditions, but relatively few have described them under normal physiological conditions. Accumulation of MDSCs is important creating an anti-inflammation environment, which is essential for fertilized egg implantation. This study was designed to record the dynamic changes in MDSC-like cells composition during the menstrual period (MP) and ovulation period (OP) in healthy volunteers over the course of a single menstrual cycle to explore the association between MDSCs and the menstrual cycle under normal physiological conditions. The ratio of MDSC-like cells was higher in MP samples, whereas the activity of Arg-1 was higher during the OP window. There was a negative correlation between the ratio of MDSC-like cells and the percentage of lymphocytes and a positive correlation between MDSC-like cells and prostaglandin E2 (PGE2). Furthermore, regular changes in the ratio and function of MDSC-like cells in the peripheral blood were observed during menstruation, all of which corresponded to the cycle stage. During menstruation, MDSCs may promote endometrial repair, whereas they promote pregnancy during the OP. These findings may help to better understand the pathophysiology of pregnancy-related complications and lay a foundation for improving perinatal outcomes.
The Tibetan population has lived and successfully reproduced at high altitude for many generations. Studies have shown that Tibetans have various mechanisms for protection against high-altitude hypoxia, which are probably due, at least in part, to placental adaptation. However, comprehensive in silico analyses of placentas in Tibetans are lacking. We performed a microarray-based comparative transcriptome analysis of 10 Tibetan women from Yushu, Qinghai, CHN (∼3,780 m) and 10 European women living in Leadville, CO, United States (∼3,100 m) for less than three generations. Expression of HIF-1α, STAT3, EGFR, HSP5A, XBP1, and ATF6A mRNA was less in the Tibetan placentas as compared with European placentas. A total of 38 miRNAs were involved in regulating these genes. Differentially expressed genes were enriched for HIF1α signaling pathways, protein processing in the endoplasmic reticulum, PI3K-AKT signaling pathways, and MAPK signaling pathways. Based on the transcriptome profiles, the Tibetan population was distinct from the European population; placental tissues from the Tibetan population are lacking hypoxic responses, and “passivation” occurs in response to hypoxic stress. These results provide insights into the molecular signature of adaptation to high altitudes in these two populations.
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