Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer.

Interferon (IFN)-γ is a potent proinflammatory molecule. However, few studies have investigated the expression levels of IFN-γ during pelvic organ prolapse (POP). In the present study, the expression levels and tissue localization of IFN-γ and its pathway-associated genes were detected in the vaginal walls of premenopausal females with POP and asymptomatic controls using quantitative polymerase chain reaction and immunohistochemistry. When compared with the matched controls, an 8.6-fold increase in IFN-γ, 3.8-fold increase in IFN-γ receptor (IFNGR)1, 2.6-fold increase in IFNGR2, 3.4-fold increase in signal transducer and activator of transcription-1, 2.2-fold increase in janus kinase-1 and 5.1-fold increase in nuclear factor (NF)-κB mRNA expression levels were observed in the females with premenopausal POP. In all the females with POP, higher mRNA expression levels of IFN-γ and its receptors were observed when compared with the controls. Expression levels of all the proteins were detected by immunohistochemistry, and the results demonstrated higher staining for IFN-γ, IFNGRs and pathway-associated genes in females with POP. Therefore, the results indicated that IFN-γ may be used as an inflammatory marker for POP development, and is associated with NF-κB.

The occurrence of pelvic floor dysfunctional disease (PFD) is closely related with elasticity, toughness, and functional changes of the connective tissue of the pelvic support tissue. Bone marrow mesenchymal stem cells (BMSCs) have been confirmed to have the capacity to differentiate into a variety of cell types such as osteoblasts, chondroblasts, adipocytes and fibroblasts. Therefore, BMSCs have the potential to improve the clinical outcomes for PFD. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand activated transcription factor, has acquired a great deal of attention as it is involved in the fibrosis and cell differentiation. However, how it is regulated during the process of the differentiation of BMSCs into fibroblasts remains to be defined. The present study investigated the underlying mechanisms of PPAR-γ effect of mechanical stretch on the differentiation of BMSCs induced by pelvic ligament fibroblasts. PPAR-γ expression was decreased during the differentiation of BMSCs into fibroblasts by co-cultured stretched fibroblasts. Addition of transforming growth factor-β1 (TGF-β1) reduced PPAR-γ expression and promoted the differentiation of BMSCs. With the employment of endogenous ligand, activation of PPAR-γ suppressed the BMSC differentiation. Similar effects were also observed with overexpression of PPAR-γ gene. In addition, decrease of PPAR-γ by the use of shRNA targeting rat PPAR-γ significantly contributed to BMSC differentiation to fibroblasts. These results indicate that PPAR-γ negatively regulates the differentiation of BMSCs into fibroblasts.

The occurrence of pelvic organ prolapse (POP) is closely associated with alterations in the extracellular matrix proteins of the supporting ligament. Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into a variety of cell types, including osteoblasts, chondroblasts and adipocytes. Therefore, BMSCs have the potential to improve the clinical outcomes of POP. Tenascin-C is a large glycoprotein that is present in the ECM and is involved in morphogenetic movements, and tissue patterning and repair. The aim of the present study was to investigate the effect of mechanical stretching on tenascin-C expression during the differentiation of BMSCs induced by pelvic ligament fibroblasts. BMSCs were isolated from 7-day-old Sprague Dawley rats. Fibroblasts were obtained from rat pelvic ligaments and, at the fourth passage, were subjected to 10% deformation with 1 Hz, periodic one-way mechanical stretch stimulation, followed by co-culture with BMSCs. The co-culture with stretched fibroblasts increased tenascin-C and transforming growth factor (TGF)-β expression levels, compared with groups without mechanical stimulation. Neutralizing anti-TGF-β1 antibodies, and inhibitors of TGF-β receptor, mitogen-activated protein kinase (MAPK) kinase and MAPK, decreased tenascin-C expression levels induced by TGF-β and mechanical stretching. The results of the present study suggested that the regulation of tenascin-C expression levels in BMSCs co-cultured with mechanically stretched pelvic ligament fibroblasts is mediated via the soluble growth factor TGF-β and the MAPK signaling pathway. In addition, these results indicated that in an indirect co-culture system, pelvic ligament fibroblasts with mechanical stretch stimulation may promote the synthesis of tenascin-C and BMSC differentiation into pelvic ligament fibroblasts.

Pelvic floor dysfunction (PFD) has a severe impact on the quality of life of middle-aged and elderly women and is closely related to the damage of pelvic support tissues, especially ligaments. The incidence of PFD is high in elderly populations. Conventional treatments are associated with high complication and relapse rates. Bone marrow mesenchymal stem cells (BMSCs) are bone marrow-derived pluripotent stem cells that can differentiate into many types of cells. We have found that when cultured with mechanical stretch-stimulated pelvic ligament fibroblasts, rat BMSCs were induced to differentiate into pelvic ligament fibroblasts. Human acellular amniotic membranes (HAAMs) demonstrate a good biocompatibility and can promote BMSC proliferation and BMSC differentiation into ligament fibroblasts.In this study, BMSCs cultured with mechanical stretch-stimulated pelvic ligament fibroblasts were inoculated into and cultured onto HAAMs, which were then implanted into rats with PFD to improve PFD symptoms. These results indicated their potential use as a cell-based therapy for PFD.