TT-10 may attenuate ibuprofen-induced ovarian injury in mice by activating COX2-PGE2 and inhibiting Hippo pathway.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug that has been found in recent years to cause ovarian damage. The aim of this study is to explore the molecular mechanisms of IBU damage to the ovary and drugs to combat it. We established in vivo (IBU doses of 50, 100 and 200 mg/kg-day) and in vitro (IBU concentrations of 50, 100 and 200 µM in culture medium) models of ovarian damage in mice simulating clinical doses and found that IBU not only caused ovarian damage in mice in a dose-response relationship, but also decreased estradiol (E2) and prostaglandin E2 (PGE2) levels in serum/media with increasing IBU doses. In damaged ovaries, the cyclooxygenase 2 (COX2)-PGE2 pathway is inhibited, the Hippo pathway is activated, circPVT1 is decreased, and miR-149 is elevated. TT-10 is an activator of YES-associated protein (YAP)-transcriptional enhancer factor domain activity. Then, 100 µM IBU-induced ovarian damage model was selected for YAP activation (Hippo pathway inhibition) experiment, and TT-10 was found to interfere with IBU-induced ovarian damage and increase E2 level in the medium, and 10 µM of TT-10 had the best protective effect. TT-10 also inhibited the Hippo pathway, activated the COX2-PGE2 pathway, elevated circPVT1 expression, and decreased miR-149 expression in the ovary. It has been hypothesized that clinical doses of IBU damage mouse ovaries by inhibiting COX2-PGE2 and activating the Hippo pathway, whereas TT-10 protects the ovaries through the inverse regulation of these two pathways.

Organic amendments improved soil quality and reduced ecological risks of heavy metals in a long-term tea plantation field trial on an Alfisol.

Tea plantation can cause strong soil degradation, e.g. acidification, basic nutrient decrease and microbial diversity loss, naturally by its root activity and secondary by practically tremendous synthetic N input. Organic amendments application is considered a practical way to mitigate the above adverse consequence. However, the trade-off between agronomic and environmental effects on the application of the organic amendments is still under debate. Herein, we conducted a long-term field experiment with four treatments, including control (without and fertiliser) (CK), chemical fertiliser treatment (CF), chicken manure treatment (CM) and chicken manure combined with biochar treatment (CMB) to investigate the effects of organic amendments application on soil quality, heavy metal contamination and tea production in a tea plantation. Totally 16 plots were arranged randomly with a completely randomised design. The results showed that CM and CMB treatments improved soil nutrient, mitigated soil acidification and ameliorated soil porosity compared to CF treatment. CMB treatment displayed a relatively high tea yield and quality in three consecutive years of monitoring. However, CM and CMB treatments elevated the heavy metal (HM) potential ecological risk (RI) and Nemerow's composite index (Ps). CM treatment significantly increased available As, Pb, Cu and Zn concentrations compared to CF treatment, while CMB treatment significantly decreased available Cr and Cu concentrations and slightly decreased available Cd, Pb and Ni concentrations compared to CM treatment. But the increase of available As and Zn in CMB treatment compared to CM treatment also indicated adverse effects of biochar addition. The PLS-PM model showed HM risk had direct negative effects on tea quality. Moreover, soil fungal community revealed positive effects on tea yield and negative effects on tea quality. Overall, our study proved that CMB treatment could improve soil quality, reduce available Cr and Ni concentrations, maintain tea yield and increase tea quality.

Purified Vitexin Compound 1 Serves as a Promising Antineoplastic Agent in Ovarian Cancer.

Ovarian cancer is a common gynecologic aggressive neoplasm. The mortality of ovarian cancer is top among gynecologic malignancies due to the insidious onset, atypical early symptoms, and chemoresistance. Therefore, it is urgent to seek another promising treatment for ovarian cancer. Purified vitexin compound 1 (VB1) is a kind of neolignan from the seed of traditional Chinese herb vitex negundo that possessed diverse pharmacological effects. VB1 can exhibit anti-neoplastic activities against various cancers. However, the role of VB1 in ovarian cancer treatment has not been elaborated, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of VB1 in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. In vitro, VB-1 can effectively suppress the proliferation, induce apoptosis, and block cell cycle at G2/M phase with a concentration dependent manner in ovarian cancer cells. Western blot assay showed that VB1 induce apoptosis via upregulating expression of cleaved-caspase3 and block cell cycle at G2/M phase through upregulating expression of P21. Meanwhile, VB1 can effectively inhibit tumor growth in xenograft mouse model. Our research indicated that VB1 can significantly exert its anti-neoplastic effects and may represent a new class of agents in ovarian cancer therapy.

SOX10 - A Novel Marker for the Differential Diagnosis of Breast Metaplastic Squamous Cell Carcinoma.

INTRODUCTION: Differential diagnosis of metaplastic squamous cell carcinoma of breast (MSCCB) is difficult. In particular, in terms of metastatic MSCCB, because of the low speciality of traditional markers such as mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15) and GATA binding protein 3 (GATA3), the most common problem is differentiating the spread of MSCCB to the lung from a primary lung squamous cell carcinoma. It is urgently required to explore a novel marker to aid in differential diagnosis. AIM: The aim of this study is to explore a novel marker to aid in the differential diagnosis of MSCCB from other squamous cell carcinomas (SCC) in other organs. METHODS: We tested the expression of SOX10 in 375 human SCC specimens with immunohistochemistry (IHC). RESULTS: In a series of 20 MSCCB, 9 (45%) were positive for SOX10. All of them were triple-negative MSCCB. Conversely, SOX10 was totally negative in another 205 SCC originating from lung, skin, cervix, oral mucosa, and esophagus. In a series of 150 triple-negative breast cancer and their metastatic foci, SOX10 labeling in the primary tumor and metastasis was 78% and 79.3%, respectively, and the agreement rate was 97.3% (P>0.05). CONCLUSION: Our findings demonstrate that SOX10 was recommended for differentiating MSCCB from non-mammary metastasis to the breast, as well as for distinguishing primary SCC from metastatic MSCCB, and SOX10 may be valuable in the pathological diagnosis of breast-derived metaplastic squamous cell carcinoma.

Heterologous Expression of Panax ginseng PgTIP1 Confers Enhanced Salt Tolerance of Soybean Cotyledon Hairy Roots, Composite, and Whole Plants.

The Panax ginseng TIP gene PgTIP1 was previously demonstrated to have high water channel activity by its heterologous expression in Xenopus laevis oocytes and in yeast; it also plays a significant role in growth of PgTIP1-transgenic Arabidopsis plants under favorable conditions and has enhanced tolerance toward salt and drought treatment. In this work, we first investigated the physiological effects of heterologous PgTIP1 expression in soybean cotyledon hairy roots or composite plants mediated by Agrobacterium rhizogenes toward enhanced salt tolerance. The PgTIP1-transgenic soybean plants mediated by the pollen tube pathway, represented by the lines N and J11, were analyzed at the physiological and molecular levels for enhanced salt tolerance. The results showed that in terms of root-specific heterologous expression, the PgTIP1-transformed soybean cotyledon hairy roots or composite plants displayed superior salt tolerance compared to the empty vector-transformed ones according to the mitigatory effects of hairy root growth reduction, drop in leaf RWC, and rise in REL under salt stress. Additionally, declines in K+ content, increases in Na+ content and Na+/K+ ratios in the hairy roots, stems, or leaves were effectively alleviated by PgTIP1-transformation, particularly the stems and leaves of composite soybean plants. At the whole plant level, PgTIP1-trasgenic soybean lines were found to possess stronger root vigor, reduced root and leaf cell membrane damage, increased SOD, POD, CAT, and APX activities, steadily increased leaf Tr, RWC, and Pn values, and smaller declines in chlorophyll and carotenoid content when exposed to salt stress compared to wild type. Moreover, the distribution patterns of Na+, K+, and Cl- in the roots, stems, and leaves of salt-stressed transgenic plants were readjusted, in that the absorbed Na+ and Cl- were mainly restricted to the roots to reduce their transport to the shoots, and the transport of root-absorbed K+ to the shoots was simultaneously promoted. PgTIP1 transformation into soybean plants enhanced the expression of some stress-related genes (GmPOD, GmAPX1, GmSOS1, and GmCLC1) in the roots and leaves under salt treatment. This indicates that the causes of enhanced salt tolerance of heterologous PgTIP1-transformed soybean are associated with the positive regulation on water relations, ion homeostasis, and ROS scavenging under salt stress both at root-specific and whole plant levels.