Chemoresistance has been the biggest obstacle in ovarian cancer treatment, and STAT3 may play an important role in chemoresistance of multiple cancers, but the underlying mechanism of STAT3 in ovarian cancer chemoresistance has long been truly illusive, particularly in association with p53 and RAS signaling. In this study, by using wild type, constitutive active, and dominant negative STAT3 constructs, wild-type p53, and RAS-mutant V12, we performed a series of in vitro and in vivo experiments by gene overexpression, drug treatment, and animal assays. We found that phosphorylation of STAT3 Y705 but not S727 promoted cancer cell EMT and metastasis through the Slug-mediated regulation of E-cadherin and Vimentin. The phosphorylation of STAT3 at Y705 also activated the MAPK and PI3K/AKT signaling to inhibit the ERS-mediated autophagy through down-regulation of pPERK, pelf2α, ATF6α, and IRE1α, which led to increased cisplatin resistance. Induction of wild type p53 in STAT3-DN-transfected cells further diminished the chemoresistance and tumor growth through the upregulation of the MAPK- and PI3K/AKT-mediated ERS and autophagy. Introduction of STAT3-DN deprived the RASV12-induced ERS, autophagy, oncogenicity, and cisplatin resistance, whereas introduction of p53 in STAT3-DN/RASV12 expressing cells induced additional tumor retardation and cisplatin sensitivity. Thus, our data provide strong evidence that the crosstalk between STAT3 and p53/RAS signaling controls ovarian cancer cell metastasis and cisplatin resistance via the Slug/MAPK/PI3K/AKT-mediated regulation of EMT and autophagy.

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Endometrial stem/progenitor cells have been proved to exist in periodically regenerated female endometrium and can be divided into three categories: endometrial epithelial stem/progenitor cells, CD140b+CD146+ or SUSD2+ endometrial mesenchymal stem cells (eMSCs), and side population cells (SPs). Endometrial stem/progenitor cells in the menstruation blood are defined as menstrual stem cells (MenSCs). Due to their abundant sources, excellent proliferation, and autotransplantation capabilities, MenSCs are ideal candidates for cell-based therapy in regenerative medicine, inflammation, and immune-related diseases. Endometrial stem/progenitor cells also participate in the occurrence and development of endometriosis by entering the pelvic cavity from retrograde menstruation and becoming overreactive under certain conditions to form new glands and stroma through clonal expansion. Additionally, the limited bone marrow mesenchymal stem cells (BMDSCs) in blood circulation can be recruited and infiltrated into the lesion sites, leading to the establishment of deep invasive endometriosis. On the other hand, cell derived from endometriosis may also enter the blood circulation to form circulating endometrial cells (CECs) with stem cell-like properties, and to migrate and implant into distant tissues. In this manuscript, by reviewing the available literature, we outlined the characteristics of endometrial stem/progenitor cells and summarized their roles in immunoregulation, regenerative medicine, and endometriosis, through which to provide some novel therapeutic strategies for reproductive and cancerous diseases.

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BackgroundWith growing recognition of the social determinants of health, social capital is an increasingly important construct in international health. However, the application of social capital discourse in response to HIV infection remains preliminary. The aim of this study was to assess the impact of social capital on quality of life (QoL) among adult patients with acquired immune deficiency syndrome (AIDS).MethodsA convenient sample of 283 patients receiving antiretroviral treatment (ART) was investigated in Anhui province, China. QoL data were collected using the Medical Outcomes Study HIV Survey (MOS-HIV) questionnaire. Social capital was measured using a self-developed questionnaire. Logistic regression models were used to explore associations between social capital and QoL.ResultsThe study sample had a mean physical health summary (PHS) score of 50.13±9.90 and a mean mental health summary (MHS) score of 41.64±11.68. Cronbach's α coefficients of the five multi-item scales of social capital ranged from 0.44 to 0.79. When other variables were controlled for, lower individual levels of reciprocity and trust were associated with a greater likelihood of having a poor PHS score (odds ratio [OR] = 2.02) or PHS score (OR = 6.90). Additionally, the factors of social support and social networks and ties were associated positively with MHS score (OR = 2.30, OR = 4.17, respectively).ConclusionsThis is the first report to explore the effects of social capital on QoL of AIDS patients in China. The results indicate that social capital is a promising avenue for developing strategies to improve the QoL of AIDS patients in China, suggesting that the contribution of social capital should be fully exploited, especially with enhancement of QoL through social participation. Social capital development policy may be worthy of consideration.

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.

The objective of this study was to explore the relationship between non-disclosure of sexual orientation to parents and sexual risk behaviors among gay and bisexual men who have sex with men (MSM) in China. A total of 295 eligible participants (gay n = 179, bisexual n = 116) were recruited from MSM venues and MSM organizations in Anhui Province, China. Overall, 16.6 % of participants chose to disclose their sexual orientation to parents. Fewer bisexual participants chose to disclose their sexual orientation than gay participants (9.5 vs. 21.2 %, p < 0.01). A multivariate logistic regression analysis indicated that non-disclosers were more likely than disclosers to report having one or more female sex partners among gay and bisexual MSM (AOR = 2.91), non-disclosure of sexual orientation to parents was positively associated with the number of female sex partners (AOR = 3.40) and with engagement in unprotected anal intercourse with men (AOR = 2.49) among gay MSM, in the past 6 months. Our findings indicated that HIV/AIDS intervention programs should promote the disclosure of sexual orientation and should design interventions specific to gay and bisexual MSM separately.

REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Polζ protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Polζ in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients.