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The chemokine (C-X-C motif) ligand (CXCL) family in tumor tissue is closely related to tumor growth, metastasis, and survival. However, the differential expression profile and prognostic value of the CXCLs in ovarian cancer (OC) have not been elucidated. Therefore, we studied the expression levels and mutations of CXCLs in OC patient in TCGA and various public databases. The expression differences of CXCLs in OC cancer tissues and normal tissues were compared through the Gene Expression Profiling Interactive Analysis (GEPIA) database. The effect of CXCLs on OC prognosis was analyzed using the Kaplan-Meier curves in GEPIA database. The impact of CXCLs on immune infiltration and clinicopathological outcomes in OC was assessed using the TIMER algorithm. Compared with normal tissues, we found that eight CXCLs were significantly differentially expressed in OC. The expression levels of CXCL9 ( P = 0.0201 ), CXCL11 ( P = 0.0385 ), and CXCL13 ( P = 0.0288 ) were significantly associated with tumor stage. CXCL13 was the only gene that significantly affected both disease-free survival (DFS) and overall survival (OS) in OC, and higher CXCL13 transcript levels implied longer DFS and OS. Although there was no significant impact on DFS, CXCL10 ( P = 0.0079 ) and CXCL11 ( P = 0.0011 ) expression levels had a significant effect on OS in OC. At the same time, CXCLs were significantly associated with several immune-infiltrating cells in OC tissues. The CXCLs were significantly associated with one or more immune-infiltrating cells in OC tissue. CXCL13 was differentially expressed in OC and significantly affected the prognosis of patients and was a potential marker of OC prognosis.

Breast cancer is the most common malignant tumor affecting women worldwide and is divided into the following subtypes: Luminal A, Luminal B, HER-2 overexpression and triple-negative breast cancer (TNBC). TNBC accounts for approximately 15-20% of all breast cancer cases. Due to the characteristics of low differentiation, the likelyhood of recurrence and metastasis, strong invasiveness and the lack of hormone receptors and human epidermal growth factor receptor 2 (HER2), patients with TNBC cannot benefit from endocrine therapy or other available targeted agents. Chemotherapy is one of the main treatments for patients with TNBC, and cisplatin is one of the most commonly used and effective drugs. The human far upstream element binding protein 1 (FBP1) is a potent pro-proliferative and anti-apoptotic oncoprotein, which is overexpressed in numerous tumor types. The present study demonstrated that FBP1 and its target, c-Myc, were more highly expressed in breast cancer tissues compared with para-carcinoma tissues, and the FBP1 and c-Myc levels are decreased by cisplatin treatment. The knockdown of FBP1 in TNBC cells decreased cell proliferation by arresting the cell cycle at the G2 phase. The knockdown of FBP1 decreased the expression of G2 phase-associateed protein cyclin A2, whereas it increased that of cyclin B1 and p-CDC2. Furthermore, the knockdown of FBP1 decreased cell migration and metastasis by downregulating matrix metalloproteinase 2 expression, and enhanced the sensitivity of TNBC cells to cisplatin by inducing apoptosis. These results thus suggest that FBP1 is a potential novel biological marker for the diagnosis and treatment of TNBC.

Worldwide, ovarian cancer (OC) is the seventh common cancer and the second most common cause of cancer death in women. Due to high rates of relapse, there is an urgent need for the identification of new targets for OC treatment. The far-upstream element binding protein 1 (FBP1) and enhancer of zeste homolog 2 (EZH2) are emerging proto-oncogenes that regulate cell proliferation and metastasis. In the present study, Oncomine data analysis demonstrated that FBP1 was closely associated with the development of OC, and The Cancer Genome Atlas (TCGA) data analysis indicated that there was a positive correlation between FBP1 and EZH2 in ovarian tissues. Moreover, we found that FBP1 knockdown suppressed tumor formation in nude mice and cisplatin resistance of OC cells, but the role of FBP1 in the cisplatin resistance of OC cells remained unclear. In addition, we verified physical binding between FBP1 and EZH2 in OC cells, and we demonstrated that FBP1 knockdown enhanced cisplatin cytotoxicity in OC cells and down-regulated EZH2 expression and trimethylation of H3K27. These results suggested that FBP1 increases cisplatin resistance of OC cells by up-regulating EZH2/H3K27me3. Thus, FBP1 is a prospective novel target for the development of OC treatment.

Numerous studies have shown that young age is a risk factor in early breast cancer. But for stage IV breast cancer, it is unclear whether age has a similar effect on patient survival. We collected and analyzed data from patients with stage IV breast cancer between January 2010 and December 2015 in SEER database. Multivariate Cox proportional hazard model was used in this study. 13,069 patients with stage IV breast cancer were included in the analysis, of which 1,135 were young breast cancer patients (≤40 years old). In a multivariate analysis that adjusted for sociodemographic factors, clinical-pathological characteristics and therapeutic methods, the risk of death in patients with stage IV ≤40 years was significantly reduced (hazard ratio [HR], 0.72; 95% CI, 0.65-0.79). Subgroup analyses showed that, with the same adjustment of all factors, young age only significantly reduced the risk of death in patients with luminal A (HR, 0.78; 95% CI, 0.68-0.89) and luminal B (HR 0.46; 95% CI, 0.35-0.60) subtypes. Young age at diagnosis is associated with better survival in patients with stage IV breast cancer. The effect of young age at diagnosis on the survival outcome of stage IV breast cancer varies by subtypes.

Background: Osteoarthritis (OA) is common in the elderly. Baicalin (BA) is a flavonoid monomer extracted from Scutellaria baicalensis Georgi, which has been reported to have anti-inflammatory, anti-deformation and anti-bacterial effects. Methods: Cultures of micromass and 3D alginate beads, Alcian blue and Safranin O (SO)/fast green staining were used to investigate chondrocyte viability and extracellular matrix (ECM) synthesis in chondrocytes of all groups. The expression of SOX9, Smad3, Aggrecan (ACAN), type II collagen (Col2α), matrix metallopetidase 9 (MMP9), MMP13 and ADAMTS5 in chondrocytes of all groups were detected by western blot or qRT-PCR. Results: The present study demonstrates that BA neutralized the IL-1β-induced downregulation of chondrocyte viability and ECM secretion, including ACAN and Col2α. The downregulation of SOX9, and the upregulation of MMP9, MMP13 and ADAMTS5 induced by IL-1β were reversed by BA treatment. Moreover, BA increased the nuclear translocation of Smad3 and SOX9 in chondrocytes cultured by micromass and 3D alginate beads. Interestingly, Smad3 inhibitor SIS3 reversed the promoting effect of BA on chondrocyte viability, ECM secretion, SOX9 and Smad3 nuclear translocation, and the inhibiting effect of BA on MMP9 and ADAMTS5 expressions. BA treatment also attenuated the decrease of Smad3 phosphorylation, SOX9 expression and the damage of cartilage integrity in mice which were induced by destabilization of the medial meniscus (DMM). Conclusion: BA promotes chondrocyte viability and the cell matrix synthesis through TGF-β/Smad3 pathway in IL-1β-treated chondrocytes and DMM treated mice. BA is a potential therapeutic target for OA.

Background: Osteoarthritis (OA) is epidemic in the elderly people as a common chronic joint disease. By now, drug and surgical treatments are two main therapies for OA worldwidely. Baicalin (BA) is a flavonoid monomer extracted from Scutellaria baicalensis Georgi and is reported that BA has anti-inflammatory, anti-deformation and anti-bacterial effects. Methods: Micromass culture, alcian blue and Safran O (SO)/fast green staining were used to investigate chondrocyte viability and ECM synthesis in chondrocytes of all groups. The expression of SOX9 and Smad3 in chondrocytes of all groups were detected by western blot and RT-qPCR, the expression of aggrecan (AGG), type II collagen (Col2α), MMP9/13 and ADAMTS5 were detected by RT-qPCR. In current study, we demonstrated that BA neutralized the down-regulation of chondrocyte viability and extracellular matrix (ECM) secretion, including AGG and Col2α, induced by IL-1β. As the key regulators of ECM, the down-regulation of SOX9, and the up-regulation of MMP9/13 and ADAMTS5 induced by IL-1β were abolished by BA. Moreover, BA increased the nuclear translocation and phosphorylation of Smad3, one key mediator of TGF-β/Smads pathway. Interestingly, the addition of Smad3 inhibitor SIS3 reversed the promotions of BA on chondrocyte viability, ECM secretion, SOX9 expression, Smad3 nuclear translocation and Smad3 phosphorylation, and the down-regulation of BA on the expressions of MMP9/13 and ADAMTS5. Conclusions: These results imply that BA can protect chondrocytes against IL-1β-induced inflammatory injury through the acceleration of Smad3 phosphorylation and nuclear translocation in chondrocytes. This study demonstrates that BA may be a potential drug for OA clinical treatment.

Breast cancer is the most common malignant tumor affecting women worldwide and is divided into the following subtypes: Luminal A, Luminal B, HER‑2 overexpression and triple‑negative breast cancer (TNBC). TNBC accounts for approximately 15‑20% of all breast cancer cases. Due to the characteristics of low differentiation, the likelyhood of recurrence and metastasis, strong invasiveness and the lack of hormone receptors and human epidermal growth factor receptor 2 (HER2), patients with TNBC cannot benefit from endocrine therapy or other available targeted agents. Chemotherapy is one of the main treatments for patients with TNBC, and cisplatin is one of the most commonly used and effective drugs. The human far upstream element binding protein 1 (FBP1) is a potent pro‑proliferative and anti‑apoptotic oncoprotein, which is overexpressed in numerous tumor types. The present study demonstrated that FBP1 and its target, c‑Myc, were more highly expressed in breast cancer tissues compared with para‑carcinoma tissues, and the FBP1 and c‑Myc levels are decreased by cisplatin treatment. The knockdown of FBP1 in TNBC cells decreased cell proliferation by arresting the cell cycle at the G2 phase. The knockdown of FBP1 decreased the expression of G2 phase‑associateed protein cyclin A2, whereas it increased that of cyclin B1 and p‑CDC2. Furthermore, the knockdown of FBP1 decreased cell migration and metastasis by downregulating matrix metalloproteinase 2 expression, and enhanced the sensitivity of TNBC cells to cisplatin by inducing apoptosis. These results thus suggest that FBP1 is a potential novel biological marker for the diagnosis and treatment of TNBC.

The metabolic enzyme phosphoglycerate mutase enzyme 1 (PGAM1) is a key enzyme in the glycolysis pathway, and glycolysis is closely related to cancer progression, suggesting that PGAM1 may have important functions in breast cancer. We used sequencing data from the Oncomine database and UALCAN database to analyze the expression of PGAM1 and its influence on the clinicopathological characteristics of breast cancer. LinkedOmics was used to identify genes related to PGAM1 expression, kinases, miRNAs, and transcription factors that were significantly related to PGAM1 through GSEA. cBioPortal was used to identify the alternation frequency and form of PGAM1 in breast cancer. The expression level of PGAM1 in breast cancer was significantly higher than that in normal tissues. Moreover, the expression level of PGAM1 is closely related to the molecular subtype and TP53 mutation status. The expression level of PGAM1 in HER2-positive and triple-negative tumors was significantly higher than that of luminal type. The expression level of PGAM1 in TP53-mutant tumors was higher than that in non-TP53-mutant tumors. In addition, the overall survival of patients with high PGAM1 expression was significantly worse than that of patients with low expression ( P = 0.0077 ). Through GSEA analysis, we found multiple kinases, miRNAs, and transcription factors significantly related to PFKFB4. cBioPortal analysis showed that the mutation rate of PGAM1 in breast cancer was relatively low (4%), and the main form of mutation was high mRNA expression. This study suggests that PGAM1 is a potential diagnostic and prognostic marker in breast cancer. Through data mining, we revealed the potential regulatory network information of PGAM1, laying a foundation for further research on the role of PGAM1 in breast cancer.

Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In the present study, we confirmed the findings in our previous study that ICA promoted not only chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, the present study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

Chromodomain helicase DNA-binding protein 1-like gene (CHD1L) was initially isolated as a candidate oncogene in hepatocellular carcinoma, and it has been associated with many malignancies. Knockdown of Chd1l in zygote-stage mouse embryos resulted in developmental arrest, suggesting that Chd1l is required for mouse early development. However, the exact role of CHD1L in development, especially in humans, has not been reported. In this study, we found that overexpression of CHD1L in human embryonic cells (hESCs) upregulated the expression of ectoderm genes, especially PAX6. Furthermore, ectopic expression of CHD1L promoted hESCs to differentiate into neuroepithelium both in embryoid bodies and in directed neuronal differentiation. Knockdown of CHD1L significantly impaired neuroepithelial differentiation of hESCs. Interestingly, Chd1l colocalized with a PAX6-positive cell population and was highly expressed in the ventricular (germinal) zone of fetal mice. Taken together, these data suggest that CHD1L promotes neuronal differentiation of hESCs and may play an important role in nervous system development.

Enhancer of zeste homolog 2 (EZH2) is an important member of the epigenetic regulatory factor polycomb group proteins (PcG) and is abnormally expressed in a wide variety of tumors, including osteosarcoma. Scientists consider EZH2 as an attractive target for the treatment of osteosarcoma and have found many potential EZH inhibitors, such as GlaxoSmithKline 343 (GSK343). It has been reported that GSK343 can be used as an inhibitor in different types of cancer. This study demonstrated that GSK343 not only induced apoptosis by increasing cleaved Casp-3 and poly ADP-ribose polymerase (PARP) expression, but also induced autophagic cell death by inhibiting p62 expression. Apoptosis and autophagic cell death induced by GSK343 were confirmed by the high expression of cleaved caspase-3, LC3-II and transmission electron microscopy. GSK343 inhibited the expression of EZH2 and c-Myc. Additionally, GSK343 inhibited the expression of FUSE binding protein 1 (FBP1), which was identified by its regulatory effects on c-Myc expression. Since c-Myc is a common target of EZH2 and FBP1, and GSK343 inhibited the expression of these proliferation-promoting proteins, a mutual regulatory mechanism between EZH2 and FBP1 was proposed. The knockdown of EZH2 suppressed the expression of FBP1; similarly, the knockdown of FBP1 suppressed the expression of EZH2. These results suggest the mutual regulatory association between EZH2 and FBP1. The knockdown of either EZH2 or FBP1 accelerated the sensitivity of osteosarcoma cells to GSK343. Based on these results, this study clarified that GSK343, an EZH2 inhibitor, may have potential for use in the treatment of osteosarcoma. The underlying mechanisms of the effects of GSK343 are partly mediated by its inhibitory activity against c-Myc and its regulators (EZH2 and FBP1).

Ovarian cancer is the seventh most common cancer and the second most common cause of cancer-associated mortality among gynecological malignancies worldwide. The combination of antimitotic agents, such as taxanes, and the DNA-damaging agents, such as platinum compounds, is the standard treatment for ovarian cancer. However, due to chemoresistance, development of novel therapeutic strategies for the treatment of ovarian cancer remains critical. Amentoflavone (AMF) is a biflavonoid derived from the extracts of Selaginella tamariscina, which has been used as a Chinese herb for thousands of years. A previous study demonstrated that AMF inhibits angiogenesis of endothelial cells and induces apoptosis in hypertrophic scar fibroblasts. In order to check the influence of AMF on cell proliferation, the effects of AMF on cell cycle and DNA damage were measured by cell viability, flow cytometry, immunofluorescence and western blotting assays in SKOV3 cells, an ovarian cell line. In the present study, treatment with AMF inhibited ovarian cell proliferation, increased P21 expression, decreased CDK1/2 expression, interrupted the balance of microtubule dynamics and arrested cells at the G2 phase. Furthermore, treatment with AMF increased the expression levels of phospho-Histone H2AX (γ-H2AX; a variant of histone 2A, that belongs to the histone 2A family member X) and the DNA repair protein RAD51 homolog 1 (Rad51), indicating the occurrence of DNA damage since γ-H2AX and Rad51 are both key markers of DNA damage. Consistent with previous findings, the results of the present study suggest that AMF is a potential therapeutic agent for the treatment of ovarian cancer. In addition, the effects of AMF on cell cycle arrest and DNA damage induction may be the molecular mechanisms by which AMF might exert its potential therapeutic benefits in ovarian cancer.

Background Articular cartilage is a unique avascular tissue in which chondrocytes are embedded in extracellular matrix (ECM). The decreased ECM resulting from the loss of articular chondrocyte viability leads to degenerative diseases such as osteoarthritis (OA). This study aims to investigate the effect of icariin (ICA) on ECM synthesis and chondrocyte viability. Methods Micromass culture, alcian blue, and Safran O (SO)/fast green staining were used to investigate chondrocyte viability and ECM synthesis in chondrocytes treated with ICA. The expression of hypoxia-inducible factor-1α (HIF-1α), SOX9, and anaerobic glycolysis enzymes were detected by western blot and reverse transcription-quantitative polymerase chain reaction. Results ICA, an active flavonoid component of Herba epimedii, was demonstrated to increase chondrocyte viability and ECM synthesis. HIF-1α is a key mediator of chondrocyte response to fluctuations in oxygen availability during cartilage development or damage, and its expression was unregulated by ICA treatment. Meanwhile, ICA treatment increased SOX9 expression, which is a key regulator of ECM synthesis. Furthermore, ICA treatment increased the expression of glucose transporter 1 (GLUT1), glucose-6-phosphate dehydrogenase (G6PD), phosphoglycerate kinase 1 (PGK1), and pyruvate dehydrogenase kinase 1 (PDK1), which contribute to glucose transfer and anaerobic glycolysis. Conclusions The present study revealed that ICA treatment facilitates chondrocyte vitality by promoting HIF-1α expression and anaerobic glycolysis. Therefore, ICA could be a novel clinical treatment for OA.

The pathological mechanism of vascular cognitive impairment (VCI) involves ischemic lesions in the hippocampus. Prostaglandin E1 (PGE1) serves roles in the promotion of vascular endothelial growth factor (VEGF) expression, angiogenesis and enhances blood flow to ischemic regions. However, the effect of PGE1 on cognitive function in VCI rats and the underlying mechanism are unknown. In the current study, learning and memory function in VCI rats treated by lipo‑PGE1 injection was assessed through Morris Water Maze test. Furthermore, the histological alterations, blood vessel numbers in the hippocampal CA1 region and relative VEGF protein and mRNA expression were researched. The results confirmed that VCI rats treated with lipo‑PGE1 presented improved cognitive function, less neuronal cell loss, a greater number of blood vessels in the hippocampal region and higher VEGF protein and mRNA expression. However, the role of lipo‑PGE1 in VCI rats can be inhibited by SU5416 (a specific VEGFR2 antagonist). The results indicated that lipo‑PGE1 may alleviate cognitive deficits in VCI rats. The underlying mechanism may be associated with angiogenesis promoted by lipo‑PGE1, which may involve the VEGF/VEGFR pathway. These findings may have therapeutic implications for cognitive impairment induced by hypoperfusion or chronic ischemic lesions.

Osteosarcoma is the primary cancer of leaf tissue and is regarded as a differentiation disease caused by genetic and epigenetic changes which interrupt the osteoblast differentiation from mesenchymal stem cells. Because of its high malignancy degree and rapid development, the morbidity and mortality are high. The enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressive complex 2 (PRC2) and has been demonstrated to be involved in a variety of biological processes, such as cell proliferation and program cell death. EZH2 impairs gene expression by catalyzing the tri-methylation of histone H3 lysine 27 (H3K27me3) which controls gene transcription epigenetically. It is reported that EZH2 expression is higher in osteosarcoma than in osteoblastoma and the highest expression of EZH2 is found in osteosarcoma with metastasis. In the past few years, several potent inhibitors of EZH2 have been discovered, and GSK343 is one of them. In this study, we found that GSK343 inhibited osteosarcoma cell viability, restrained cell cycle transition and promoted programmed cell death. GSK343 not only inhibited the expression of EZH2 and its target, c-Myc and H3K27me3, but it also inhibited fuse binding protein 1 (FBP1) expression, another c-Myc regulator. Furthermore, we found that FBP1 physically interacts with EZH2. Based on these results, we believe that GSK343 is a potential molecule for osteosarcoma clinical treatment. Other than the inhibition on EZH2-c-Myc signal pathway, we postulate that the inhibition on FBP1-c-Myc signal pathway is another potential underlying mechanism with which GSK343 inhibits osteosarcoma cell viability.

Epithelial ovarian cancer (EOC) is the fifth most common malignancy in women, with a 5-year mortality of >70% in North America. As the symptoms are often not observed until the cancer has spread extensively, few women are diagnosed at an early stage of disease. Large-scale gene expression analyses have identified molecular subtypes within high-grade ovarian cancer with variable survival rates and drug resistance. The understanding of gene expression, the mechanisms underlying cancer processes and drug resistances have facilitated the development of targeted therapies. The far-upstream element (Fuse)-binding protein 1 (FBP1) is overexpressed in a number of malignancies such as hepatocellular carcinoma, and has been identified as an oncoprotein. In our early studies, FBP1 was demonstrated to physically interact with p53 and suppresses p53 transcription activity. In the present study, FBP1 expression increased as ovarian cancer developed. Among ovarian normal, adenoma and carcinoma tissues, the highest FBP1 expression was identified in carcinoma tissues. Furthermore FBP1 did not influence the apoptosis of ovarian carcinoma cells, yet enhanced cell cycle transition and metastasis. Therefore, it was hypothesized that FBP1 promotes ovarian cancer development through the acceleration of cell cycle transition and metastasis, and FBP1 is a novel potential biological marker for epithelial ovarian cancer diagnosis.

OBJECTIVE: To explore the DNA repair effect of rat adipose-derived stem cells (ADSCs) on chond-rocytes exposed to ultraviolet (UV) radiation. METHODS: ADSCs were isolated and cultured from the inguinal adipose tissue of Sprague Dawley rat by digestion with collagenase type I. ADSCs cell phenotype was assayed with flow cytometry. Multiple differentiation capability of ADSCs at passage 3 was identified with osteogenic and adipogenic induction. The chondrocytes were obtained from rat articular cartilage by digestion with collagenase type II and were identified with toluidine blue staining. The chondrocytes at passage 3 were irradiated with 40 J/m(2) UV and cultured with normal medium (irradiated group), and medium containing the ADSCs supernatant (ADSCs supernatant group) or ADSCs was used for co-culture (ADSCs group) for 24 hours; no irradiation chondrocytes served as control group. The cell proliferation was estimated by MTS method. The expression of phosphorylated histone family 2A variant (γH2AX) was detected by immunofluorescence and Western blot. RESULTS: ADSCs presented CD29(+), CD44(+), CD106(-), and CD34(-); and results of the alizarin red staining and oil red O staining were positive after osteogenic and adipogenic induction. Cell proliferation assay demonstrated the absorbance (A) values were 2.20±0.10 (control group), 1.34±0.04 (irradiated group), and 1.57±0.06 (ADSCs supernatant group), showing significant difference between groups (P0.05). CONCLUSION: ADSCs can increase the cell proliferation and down-regulate the γH2AX protein expression of irradiated cells, indicating ADSCs contribute to the repair of irradiated chondrocyte.

P53 is a famous cancer suppressor and plays key roles in metabolism. Intervertebral disc (IVD) is the largest avascular cartilaginous structure in humans and its degeneration is a common cause of spine diseases initiated from damaged nucleus pulposus (NP) cells. The potential cause of disc degeneration has been attributed to aging, genetic factors, mechanical factors and nutrition. In this study, we found that p53 decreased and leaked to the cytoplasm in NP cells as the glucose level decreases, in contrast to cancer cells in which p53 increases and concentrates to the nuclei. Comparing with in p53 knockdown NP cells, relative high p53 expression in normal control NP cells inhibited autophagy and the pentose phosphate pathway. Furthermore, the expression of Sox 9 and type II collagen were higher in p53 normal control than p53 knockdown NP cells. Based on these results, we believe that relative high p53 facilitates NP cell viability and integrity.

Amentoflavone (8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl) chromen-4-one; AF) is a biflavonoid derived from the extracts of Selaginella tamariscina. It has been shown that AF has diverse biological effects such as antitumour, etc. It is well known that high cell proliferation, viability, angiogenesis and low apoptosis are key factors in hypertrophic scar formation. In this study, we report that AF inhibited viability and stimulated apoptosis in hypertrophic scar fibroblasts (HSFBs). Incubation of HSFBs with AF showed its inhibitory effect on cell viability and the exhibition of a series of cellular changes that were consistent with apoptosis. By Western-blot analysis, our data indicated significant increases in the amounts of cleaved caspases 3, 8, 9 and Bax, several apoptotic promoters and a significant decrease in translationally controlled tumour protein (TCTP), an apoptotic inhibitor, in HSFBs treated with AF. Furthermore, AF showed significant inhibitions on the viability, migration and tube formation of endothelial cells, which are associated with angiogenesis. In conclusion, this study suggests that AF stimulates apoptosis in HSFBs and inhibits angiogenesis of endothelial cells. Therefore, AF is a promising molecule that can be used in hypertrophic scar treatment.

Epithelial ovarian cancer (EOC) affects almost 25,000 women annually and is the fifth most common malignancy in women in North America. A combination of surgery and cytotoxic chemotherapy may produce a favorable clinical response. The platinum-paclitaxel combination regimen is the chemotherapy gold-standard for advanced ovarian cancer, and carboplatin is one of the agents in this combination therapy. However, the majority of patients eventually experience a relapse due to the development of platinum resistance. FUSE binding protein 1 (FBP1) has been identified as an anti-apoptotic and pro-proliferative oncoprotein that is overexpressed in hepatocellular carcinoma. Its high expression is also associated with carboplatin resistance. In the present study, it was identified that the expression of FBP1 was significantly higher in EOC tissues than in normal epithelial ovarian or in epithelial ovarian adenoma tissue. FBP1 expression was significantly correlated with the grade of epithelial ovarian cancer. Carboplatin inhibited the expression of FBP1 in epithelial ovarian cancer cells and the knockdown of FBP1 enhanced the inhibition of cell viability and migration by carboplatin. In addition to FBP1, carboplatin also inhibited the expression of β-catenin and matrix metalloproteinase (MMP)-9. Furthermore, the expression of β-catenin and MMP-9 were lower in FBP1 knockdown cells compared with control EOC cells. FBP1 may thus serve a role in the regulation of the expression of β-catenin and MMP-9; the inhibition of β-catenin and MMP-9 by carboplatin may be mediated through the inhibition of FBP1. The inhibition of FBP1 expression by carboplatin may be a mechanism in the treatment of EOC by carboplatin.