IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.

Hyperosmotic cold shock mouse melanoma cells encapsulated with doxorubicin for targeted treatment of melanoma.

Background: The primary treatment strategies for melanoma include surgical excision, chemotherapy, and radiotherapy. However, the efficacy of these treatments is often limited by drug resistance, recurrence, and severe side effects. Therefore, we aimed to develop a targeted drug delivery system capable of selectively locating tumor sites to minimize systemic toxicity and enhance therapeutic efficacy.

Sodium oligomannate's amelioration of reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model depends on the gut microbiome†.

It has been well established that there is a connection between polycystic ovary syndrome pathology and gut microbiome dysbiosis. A marine-derived oligosaccharide, GV-971, has been reported to alter gut microbiota and alleviate Aβ amyloidosis. In this study, the effects of GV-971 on polycystic ovary syndrome-like mice were explored.

Leader humility and employees' creative performance: the role of intrinsic motivation and work engagement.

Drawing on the job demand-resource (JD-R) model and self-determination theory (SDT), this study examines the relationship between humble leadership and employees' creative performance, taking into account the sequential mediating role of intrinsic motivation and work engagement. The sequential mediation model was tested using two-wave questionnaire data collected from employees and their supervisors ( = 350) in the telecommunication sector of Pakistan. Data were processed and examined using SPSS and AMOS.

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation.

C5aR1 blockade reshapes immunosuppressive tumor microenvironment and synergizes with immune checkpoint blockade therapy in high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSC), with a modest response to immune checkpoint blockade (ICB) targeting PD-1/PD-L1 monotherapy, is densely infiltrated by M2-polarized tumor-associated macrophages (TAMs) and regulatory T (Treg) cells. The complement C5a/C5aR1 axis contributes to the programming of the immunosuppressive phenotype of TAMs in solid tumors and represents a promising immunomodulatory target for treating HGSCs. Here, we aimed to identify the relevance of C5aR1 in prognosis, immune microenvironment, and immunotherapy response in HGSCs.

Siglec-9 tumor-associated macrophages delineate an immunosuppressive subset with therapeutic vulnerability in patients with high-grade serous ovarian cancer.

Background: The potent immunosuppressive properties of sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on myeloid cells and lymphocytes provide a strong rationale for serving as a therapeutic target. However, the expression profile and critical role of Siglec-9 in high-grade serous ovarian cancer (HGSC) remain obscure. This study aimed to elucidate the prognostic significance of Siglec-9 expression and its predictive value for immunotherapy in HGSC.

Creative Performance and Conflict through the Lens of Humble Leadership: Testing a Moderated Mediation Model.

This study developed and tested a moderated mediation model by examining the relationships between humble leadership (HL), emotional intelligence, employee conflict (EC), and creative performance (CP), using resource-based theory as the theoretical foundation. We conducted a cross-sectional survey of 322 employees and their immediate supervisors ( = 53) from the telecom sector in Pakistan. The data was analyzed using AMOS 21 and SPSS 26.

Attenuation of Sialylation Augments Antitumor Immunity and Improves Response to Immunotherapy in Ovarian Cancer.

Unlabelled: Aberrant sialylation functions as an important modulator of all steps of malignant transformation. Therefore, targeting sialylation regulators, such as sialyltransferases and neuraminidases, is a potential strategy for treating cancer. Here, we found that elevated α2,3-sialyltransferase III (St3gal3) was associated with dismal prognosis in high-grade serous ovarian carcinoma (HGSC).

IL-15 Participates in the Pathogenesis of Polycystic Ovary Syndrome by Affecting the Activity of Granulosa Cells.

Background: Low-grade chronic inflammation may contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the development of chronic inflammation leading to obesity-associated metabolic syndrome. However, the concentration of IL-15 in follicular fluid of patients with PCOS has yet been evaluated.

Scribble downregulation in adenomyosis compromises endometrial stromal decidualization by decreasing FOXO1 expression.

Study Question: Does Scribble (SCRIB) contribute to aberrant decidualization of endometrial stromal cells (ESC) in adenomyosis?

Summary Answer: SCRIB knockdown impairs decidualization of ESC by decreasing Fork-head box O1A (FOXO1) expression through the protein kinase B (AKT) and atypical protein kinase C (aPKC) activated pathways.

What Is Known Already: Stromal SCRIB is required for primary decidual zone formation and pregnancy success in mice. In our previous studies, decidualization was dampened in ESC isolated from adenomyosis patients, yet the underlying molecular mechanisms remain elusive.

Stromal infiltrating mast cells identify immunoevasive subtype high-grade serous ovarian cancer with poor prognosis and inferior immunotherapeutic response.

Tumor infiltrating mast cells (TIMs), with pro- or anti-tumorigenic role in different types of malignancies, have been implicated in resistance to anti-PD1 therapy. Here, we aimed to identify the relevance of TIMs with the prognosis, immune contexture, and immunotherapy in high-grade serous ovarian cancer (HGSOC). Tissue microarrays containing 197 HGSOC patients were assessed by immunohistochemistry (IHC) for detecting the expression of mast cell tryptase and other immune markers.

Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high-grade serous ovarian cancer.

Although the association between tumor-infiltrating CD3 T and CD8 T cells and superior survival in high-grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor-infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3 T, CD8 T, and CD45RO cells in HGSOC. Different density of spatial localization of CD3 T, CD8 T, and CD45RO cells exhibited heterogeneous association with OS.

The prognostic significance of tumor-infiltrating lymphocytes in cervical cancer.

Objective: To predict the prognosis of cervical cancer, we constructed a novel model with 5 specific cell types and identified a potential biomarker.

Methods: We employed CIBERSORT and xCell method to evaluate the abundances of 23 cells types in tumor microenvironment. Five specific cell types were filtrated to determine different immunotypes by applying least absolute shrinkage and selection operator (LASSO) Cox regression method.

The immune landscape during the tumorigenesis of cervical cancer.

Objective: Deciphering the determinants of the intralesional immune reaction in cervical carcinogenesis may be conducive to improving the understanding of the disease and then improve outcomes.

Methods: Public gene-expression data and full clinical annotation were searched in Gene Expression Omnibus in the joint analysis of the array-based four eligible cohorts. The infiltrating estimation was quantified using microenvironment cell populations-counter algorithm and absolute-mode CIBERSORT and verified by flow cytometry analysis.

Impaired decidualization of human endometrial stromal cells from women with adenomyosis†.

Differentiation of endometrial stromal cells (ESCs) into secretory decidualized cells (dESCs) is essential for embryo implantation. Adenomyosis is a common benign gynecological disease that causes infertility. However, whether adenomyosis affects decidualization of human ESCs is elusive.

CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer.

Background: Most patients with high-grade serous ovarian cancer (HGSC) lack an effective response to immune checkpoint blockade, highlighting the need for more knowledge about what is required for successful treatment. As follicular cytotoxic CXCR5CD8 T cells are maintained by reinvigoration by immune checkpoint blockade in tumors, we attempted to reveal the relationship between CXCR5CD8 T cells and the tumor microenvironment to predict immunotherapy responses in HGSC.

Methods: 264 patients with HGSC from two cohorts and 340 HGSC cases from The Cancer Genome Atlas cohort were enrolled.

Targeting senescent cells and tumor therapy (Review).

Cell senescence is caused by the activation of cell cycle inhibition pathways induced by an accumulation of cellular damage, where cells permanently leave the cell cycle. Senescent cells undergo changes in cell morphology, transcription, protein homeostasis, metabolism and other characteristic alterations. At the same time, senescent cells are able to resist apoptosis and accumulate in multiple organs and tissues in vivo.

Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer.

Background: Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC).

Methods: We characterised TANs using flow cytometric analysis and immunofluorescence analysis.

Celecoxib, a selective COX-2 inhibitor, markedly reduced the severity of tamoxifen-induced adenomyosis in a murine model.

The aim of the present study was to evaluate the effects of the selective cyclooxygenase (COX)-2 inhibitor celecoxib on the development of uterine adenomyosis in mice. ICR neonatal mice were first exposed to tamoxifen to establish a mouse model of adenomyosis. Following 60 days of celecoxib treatment, pathological formation of adenomyosis lesions and the depth of myometrial infiltration were evaluated using hematoxylin and eosin staining.

Rosiglitazone ameliorates senescence and promotes apoptosis in ovarian cancer induced by olaparib.

Objective: Senescence mechanisms are vital to resistance to long-term olaparib maintenance treatment. Recently, peroxisome proliferator-activated receptor-γ agonists (e.g.

Elevated GALNT10 expression identifies immunosuppressive microenvironment and dismal prognosis of patients with high grade serous ovarian cancer.

High grade ovarian serous cancer (HGSC) is a malignant disease with high mortality. Glycosylation plays important roles in tumor invasion and immune evasion, but its effect on the immune microenvironment of HGSC remains unclear. This study examined the association of glycosyltransferase expression with HGSC prognosis and explored the underlying mechanism using clinical specimens and integrated bioinformatic analyses.

Estrogen degrades Scribble in endometrial epithelial cells through E3 ubiquitin ligase HECW1 in the development of diffuse adenomyosis†.

Despite its prevalence and the severity of symptoms, little is known about the pathogenesis and etiology of adenomyosis. In previous studies, the protein expression level of the polarity protein Scribble in the eutopic endometrium of patients with adenomyosis was found to be significantly decreased; however, little is known about its regulatory mechanism. In consideration of the important role of supraphysiologic estrogen production in the endometrium in the development of adenomyosis, we analyzed the effect and mechanism of estrogen on the expression of Scribble in vivo and in vitro.