Urinary incontinence in women

Abstract In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes. Recent studies demonstrating EStim's positive osteogenic effects at the cellular and molecular level provide intriguing clues to the underlying mechanisms by which it promotes bone healing. In this review, we discuss results of recent in vitro and in vivo research focused on using EStim to promote bone healing and regeneration and consider possible strategies for its application to improve outcomes in BTE treatments. Technical aspects of exposing cells and tissues to EStim in in vitro and in vivo model systems are also discussed.

/pdf/electrical-stimulation-in-bone-tissue-engineering-treatments-3yske1iues.pdf

Electrical stimulation in bone tissue engineering treatments

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.

/pdf/pharmacological-effects-of-cisplatin-combination-with-3skw4vh5.pdf

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

小児急性嘔吐下痢症に対する五苓散の効果:バングラデシュにおけるRandomized,Double‐blind,Controlled Trial

Electrical stimulation (ES) therapy has good effects in patients with nervous system injury-related diseases. ES promotes nerve cell regeneration and stimulates Schwann cells to express neurotrophic factors. The incidence of stress urinary incontinence (SUI) among elderly people is increasing. Some studies suggest that damage to the pudendal nerve is closely related to the pathogenesis of SUI. It has also been found that pelvic ES can reduce SUI symptoms in a rat model of SUI caused by pudendal nerve injury. Clinically, pelvic floor electrical stimulation is effective in patients with mild to moderate SUI. These studies indicate that ES may ameliorate damage to the pudendal nerve and thus achieve the goal of SUI treatment, although the mechanism of action of this treatment remains unclear. Therefore, the purpose of the present study was to clarify the relationships among ES, neural cells and Schwann cells at the cellular level. We applied ES to nerve cells at 100 mV/mm or 200 mV/mm for 0, 0.5, 1, or 2 h to investigate changes in nerve cell activity. We then co-cultured the nerve cells with Schwann cells to explore the influence of single-culture and co-culture conditions on the nerve cells. Compared to non-ES, ES of the nerve cells increased their activity. Compared to those in single culture, co-cultured nerve cells exhibited an additional increase in activity. We also found that Schwann cell derived exosomes could promote the activity of nerve cells, with glutamate and calcium ions playing a potential role in this process. These results suggest that the mutual regulation of neural cells and Schwann cells plays an important role in the process by which ES ameliorates neurological function, which may provide a basis for subsequent studies.

/pdf/electrical-stimulation-enhances-neuronal-cell-activity-2f5sjd5oc9.pdf

Electrical stimulation enhances neuronal cell activity mediated by Schwann cell derived exosomes

Multidrug resistance in malignant tumours hinders the treatment of tumours. Studies showed that astragalus polysaccharides (APS), one major active ingredient of astragalus, enhanced the sensitivity of non-small cell lung cancer and liver cancer cells to chemotherapeutic drug. However, the effect of APS on ovarian cancer is still unclear. In this study, we will examine the sensitizing effect of APS on SKOV3 cells to cisplatin and explore the possible mechanism. MTT assay was employed to examine the viability of SKOV3 after treatment with APS and cisplatin. The cell apoptosis rate was determined by flow cytometry. The expression of Bax, Bcl-2, Caspase-3, and c-Jun N-terminal kinases 1/2 (JNK1/2) was measured using Western blotting and RT-PCR. APS synergistically promoted the inhibitory effect of cisplatin on SKOV3 cell viability. Flow cytometry showed that APS promoted cisplatin-induced apoptosis of SKOV3 cell lines. Further studies showed that APS down-regulated the expression of Bcl2, increased the expression of Bax and caspase 3 and activated JNK1/2 signalling pathway. The JNK inhibitors significantly rescued the proliferation inhibition induced by the drugs. Astragalus polysaccharides increased the sensitivity of SKOV3 cells to cisplatin potentially by activating the JNK pathway. The apoptosis-related genes may contribute to the process. Thus, APS may be useful for the treatment of ovarian cancer as an enhancer of chemosensitivity.

Astragalus polysaccharides increase the sensitivity of SKOV3 cells to cisplatin.

The aim of the present study was to explore the underlying mechanisms of the roles of mechanical factors in the pathogenesis of pelvic organ prolapse (POP). The experiments were performed on fibroblasts derived from uterosacral ligaments and cardinal ligaments of patients who received total hysterectomy due to benign disease excluding POP. Fibroblasts were cultured after collagenase digestion and identified by morphological observation and immunocytochemical methods. A four‑point bending device was used to subject fibroblasts at passage 4‑6 to strains of 0, 1,333 µ (1 mm), 2,666 µ (2 mm) or 5,333 µ (4 mm) at a frequency of 0.1 Hz for 4 h. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe 2',7'‑dichlorodihydrofluorescein diacetate. Changes in the mitochondrial membrane potential were verified using the fluorescent dye JC‑1, and apoptosis was detected using Annexin V/propidium iodide staining and flow cytometric analysis. Mechanical strain changed the morphology and adherence ability of parametrial ligament fibroblasts. Furthermore, the production of ROS was significantly increased and the mitochondrial membrane potential obviously declined with the enhancement of mechanical stress loading. In addition, the apoptotic rate of fibroblasts subjected to high mechanical strain was significantly increased compared with that in fibroblast under low‑intensity strain. In conclusion, the present study showed that mechanical strain enhanced intracellular ROS levels, decreased the mitochondrial membrane potential and increased the apoptotic rate in human parametrial ligament fibroblasts, which may contribute to POP.

/pdf/oxidative-damage-to-human-parametrial-ligament-fibroblasts-2nv9lulres.pdf

Oxidative damage to human parametrial ligament fibroblasts induced by mechanical stress.

BACKGROUND Stress urinary incontinence is a common condition in women and can be associated with peripheral nerve injury. Exosomes. derived from Schwann cells, can enhance the regeneration of axons of the peripheral nervous system. This study aimed to investigate the effects of RSC96 Schwann cell-derived exosomes in a novel in vitro model of dorsal root ganglion (DRG) cell injury induced by cyclic mechanical strain (CMS). MATERIAL AND METHODS RSC96 Schwann cells and DRG cells were cultured in vitro. CMS in DRG cells involved mechanical stretch trauma with 5333 μ strain. ExoQuick-TC polymer was used to precipitate exosomes from RSC96 Schwann cell culture medium and identified by nanoparticle tracking analysis, electron microscopy, and Western blot for detection of CD9 and tumor susceptibility gene 101 (Tsg101) protein. Cultured DRG cells were treated with RSC96 Schwann cell-derived exosomes, followed by measurement of cell viability, proliferation, senescence, and apoptosis using the cell counting kit-8 (CCK-8) assay, senescence-associated beta-galactosidase (SA-β-gal) staining, and Hoechst 33258 (blue) fluorescence nucleic acid staining using flow cytometry. RESULTS Mechanical stretch with 5333 μ strain for 8 hours at 1 Hz decreased the activity of cultured DRG cells. RSC96 Schwann cell-derived exosomes promoted cell proliferation and significantly inhibited apoptosis and senescence of DRG cells following injury induced by CMS. CONCLUSIONS An in vitro model of DRG cell injury induced by CMS, showed that RSC96 Schwann cell-derived exosomes had a protective effect. The effects of Schwann cell-derived exosomes on peripheral nerve injury, including in stress urinary incontinence, require future in vivo studies.

Effects of RSC96 Schwann Cell-Derived Exosomes on Proliferation, Senescence, and Apoptosis of Dorsal Root Ganglion Cells In Vitro.

Natural botanical drugs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties in cancer. Punicalagin (PUN) is the major bioactive component of pomegranate peel, and has been shown to have antioxidant, anti-inflammatory, antiviral, antiproliferation and anticancer properties. PUN has been shown to induce apoptosis in several cancer cell lines. The aim of the present study was to investigate the effect of PUN on HeLa human cervical cancer cells in vitro. The viability of the HeLa cells was assessed following treatment with PUN (0, 12.5, 25, 50, 100 and 200 µM) for 24, 36 and 48 h using a Cell Counting Kit‑8 assay. In addition, the cell cycle distribution, protein expression levels of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax), Bcl‑2, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP‑3 and the β‑catenin pathway, and the activities of matrix metalloproteinase (MMP)‑2 and MMP‑9 were analyzed following treatment with PUN (0, 25, 50 and 100 µM) for 36 h using cell cycle analysis, western blot analysis and gelatin zymography, respectively. In addition, a wound‑healing assay was used to detect cell migration. PUN led to a number of effects on the HeLa cells, including the inhibition of cell proliferation and cell migration, downregulation of MMP‑2 and MMP‑9, upregulation of TIMP‑2 and TIMP‑3, cell‑cycle arrest in the G1 phase, induction of apoptosis via alterations of Bcl‑2 and Bax, and downregulation of β‑catenin and its downstream proteins, cyclin D1 and c-myc. These results suggested that PUN may have chemopreventive and chemotherapeutic effects against cervical cancer in humans through inhibition of the β-catenin signaling pathway.

/pdf/punicalagin-suppresses-the-proliferation-and-invasion-of-2boba6jdd0.pdf

Punicalagin suppresses the proliferation and invasion of cervical cancer cells through inhibition of the β-catenin pathway

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