Mechanism of cryptotanshinone to improve endocrine and metabolic functions in the endometrium of PCOS rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cryptotanshinone is the main bioactive component of Salvia miltiorrhiza, with various mechanisms of action, including antioxidant, anti-inflammatory, cardiovascular protection, neuroprotection, and hepatoprotection. Salvia miltiorrhiza is used clinically by gynecologists in China. AIM OF THE STUDY: Polycystic ovary syndrome (PCOS) has a significant impact on women's quality of life, leading to infertility and reproductive disorders. Hence, this study aims to assess the pharmacological activity of cryptotanshinone in the treatment of PCOS and investigate its therapeutic mechanism. MATERIALS AND METHODS: Human chorionic gonadotropin (HCG) combined with insulin is used to simulate a PCOS-like rat model and attempt to discover the abnormal changes that occur and the means by which the pathway acts in this model. RESULTS: The transcriptome sequencing method is used to identify 292 differential genes that undergo significant changes, of which 219 were upregulated and 73 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the signaling pathways reveals that differential expressed genes are significantly enriched in 23 typical pathways. Estrogen signaling pathways are screened in the cryptotanshinone and model groups, and significant differential changes in Fos, ALOX12, and AQP8 are found. This suggests that these signaling pathways and molecules may be the main signaling targets for regulating the differences in endometrial tissue. CONCLUSION: These results indicate that cryptotanshinone has targets for regulating the proliferation of endometrial tissue via estrogen signaling pathways in PCOS-like rats, providing an experimental basis for the clinical application of cryptotanshinone in the treatment of PCOS.

Emerging photodynamic/sonodynamic therapies for urological cancers: progress and challenges.

Photodynamic therapy (PDT), and sonodynamic therapy (SDT) that developed from PDT, have been studied for decades to treat solid tumors. Compared with other deep tumors, the accessibility of urological tumors (e.g., bladder tumor and prostate tumor) makes them more suitable for PDT/SDT that requires exogenous stimulation. Due to the introduction of nanobiotechnology, emerging photo/sonosensitizers modified with different functional components and improved physicochemical properties have many outstanding advantages in cancer treatment compared with traditional photo/sonosensitizers, such as alleviating hypoxia to improve quantum yield, passive/active tumor targeting to increase drug accumulation, and combination with other therapeutic modalities (e.g., chemotherapy, immunotherapy and targeted therapy) to achieve synergistic therapy. As WST11 (TOOKAD® soluble) is currently clinically approved for the treatment of prostate cancer, emerging photo/sonosensitizers have great potential for clinical translation, which requires multidisciplinary participation and extensive clinical trials. Herein, the latest research advances of newly developed photo/sonosensitizers for the treatment of urological cancers, and the efficacy, as well as potential biological effects, are highlighted. In addition, the clinical status of PDT/SDT for urological cancers is presented, and the optimization of the photo/sonosensitizer development procedure for clinical translation is discussed.

microRNA-1271-5p/TIAM1 suppresses the progression of ovarian cancer through inactivating Notch signaling pathway.

OBJECTIVE: Ovarian cancer (OC) has been regarded as the most malignant gynecological neoplasm and often confers grave outcomes owing to the frequent metastasis and high recurrence. A previous study has demonstrated that miR-1271-5p is implicated in OC progression, however, the possible mechanism of it remains unknown. The purpose of this investigation was to explore how miR-1271-5p regulates the progression of OC. METHODS: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were employed to analyze the differentially expressed miRNAs or genes as well as their corresponding prognostic values. miR-1271-5p expression in OC cells was examined by qRT-PCR. Cell counting kit 8 (CCK-8), colony formation, and transwell tests were conducted to evaluate the proliferation, migration and invasion potentials. Bioinformatics prediction and luciferase activity analysis were utilized to predict and verify the target gene of miR-1271-5p. Western blot assay was carried out to measure protein expression. RESULTS: miR-1271-5p was significantly decreased in OC and its down-regulation was associated with the grave outcome of OC patients. Upregulation of miR-1271-5p inhibited cell viability, but miR-1271-5p knockdown promoted the proliferation of OC cells. TIAM1 was a direct target gene of miR-1271-5p and expressed in OC tissues at higher level. High expression of TIAM1 induced the poorer prognosis of patients with OC. Further functional analyses showed that the suppressive role of miR-1271-5p on OC cell malignant behaviors was overturned by the upregulation of TIAM1. The protein levels of Cyclin D1, HES1, NOTCH and NUMB were remarkably changed due to the abnormal expression of miR-1271-5p and TIAM1. CONCLUSION: To sum up, miR-1271-5p inhibits proliferation, invasion and migration of OC cells by directly repressing TIAM1 to inactivate the Notch signaling pathway, which provides an alternative therapeutic candidate for the advancement of OC treatment.

Complete Genome Sequence of Human Enterovirus Strain 71 (EV71/Taipei/3118/2011), Isolated from a Patient in Taiwan.

This full-length genome sequence of human enterovirus strain 71 (EV71/Taipei/3118/2011) was isolated from a clinical patient in Taiwan in 2011. According to the phylogenetic analysis, the complete genome sequence in this study is part of the subgenotype C4.

Fabrication and properties of TiO2 nanofilms on different substrates by a novel and universal method of Ti-ion implantation and subsequent annealing.

We report a new, novel and universal method to fabricate high-quality titanium dioxide (TiO2) nanofilms on different substrates by a solid phase growth process of ion implantation and subsequent annealing in oxygen atmosphere. Ti ions were implanted into fused silica, soda lime glass, Z-cut quartz, or (0001) α-sapphire by a metal vapor vacuum arc (MEVVA) ion source implanter to fluences of 0.75, 1.5 and 3 × 10(17) ions cm(-2) with a nominal accelerating voltage of 20 kV. To understand the influence of the annealing temperature, time, and substrate on the formation and phase transformation of the TiO2 nanofilms, the Ti-ion-implanted substrates were annealed in oxygen atmosphere from 500 to 1000 °C for 1-6 h. The formation of TiO2 nanofilms resulted from the slow out-diffusion of implanted Ti ions from the substrates which were then oxidized at the surfaces. The thickness and phase of the nanofilms can be tailored by controlling the implantation and annealing parameters. Since the TiO2 nanofilms are formed under high temperature and low growth rate, they show good crystallinity and antibacterial properties, with good film adhesion and stability, suggesting that the TiO2 nanofilms formed by this method have great potential in applications such as antibacterial and self-cleaning transparent glass.

[Controlling effect of berberine on in vitro synthesis and metabolism of steroid hormones in insulin resistant ovary].

OBJECTIVE: To investigate the functional and metabolic alterations in cultured insulin resistant ovary model in vitro, and to observe the effect of berberine (Ber, a Chinese medical monomer) in improving insulin resistance (IR). METHODS: Ovary of mouse was cultured in vitro and treated by dexamethasone (Dex) to induce IR for establishing IR model ovary. The functional alteration in model ovary was assessed through detecting glucose and hormone levels in medium using RT-PCR, meanwhile, the expression of key molecules in insulin signal and steroid synthetic pathway were detected, and condition of IR improved by berberine was evaluated also. RESULTS: (1) The model ovary was made by Dex in dose- and acting time-dependent manner. After being treated by 300 nmol/L Dex for 48 h, the glucose uptake of ovary reduced from 9.05 +/- 0.75 mg/g to 2.48 +/- 0.29 mg/g (P < 0.05); it further decreased (from 9.59 +/- 1.74 mg/g to 1.94 +/- 0.19 mg/g, P < 0.01) under the stimulation of insulin, which proved that the IR model ovary was made successfully. Berberine significantly increased the glucose uptake of model ovaries (1.89 +/- 0.33 mg/g to 13.95 +/- 3.30 mg/g, P < 0.05). (2) As compared with control group, levels of testosterone (T) and androstenedione (A2) were higher, and levels of progesterone (P) and 17-hydroxyprogesterone (17-OHP) were lower significantly in the model. Berberine reversed the alternations of T, A2 and 17-OHP levels, but did not influence the level of P. (3) RT-PCR showed that the mRNA expressions of cytochrome 17-hydroxylase (CYP17) and mini-chromosome maintenance protein-2 (MCM-2) elevated, but extracellular regulated protein-1 (ERK-1), protein kinase B (AKT-2) and glycogen synthase kinase-3 (GSK-3beta) lowered in the medium after Dex inducing. Berberine treatment restored these molecular index obviously. CONCLUSIONS: (1) Dex could induce IR in mouse ovary, which might enhance the androgenic synthesis. (2) Berberine could alleviate the degree of IR and the androgen synthesis, indicating that the Chinese sensitizing agents has favorable therapeutic effect for the treatment of polycystic ovaries.