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Homeobox B9 (HOXB9), a homeodomain-containing transcription factor, may play a role in hepatocellular carcinoma (HCC) progression. However, the exact mechanisms underlying its action remain unclear.HOXB9 expression was significantly increased in HCC tissues and cell lines. Patients with higher HOXB9 levels were associated with poor prognosis. Overexpression of HOXB9 in BEL-7405 cells promoted proliferation, migration, and invasion, whereas knockdown of HOXB9 in HepG2 cells significantly reduced cell proliferation, migration, and invasion abilities. Mechanically, a positive correlation was found between HOXB9 expression and transforming growth factor-These findings validated that HOXB9 promoted proliferation, migration, and invasion in HCC cells by stimulating the TGF

Gastric cancer is a common malignant tumor in China; however, its carcinogenesis remains unknown. Focadhesin (FOCAD) is a tumor suppressor gene in gliomas, its expression, role, and mechanism in gastric cancer have not been defined. The aim of the present study was to explore the expression pattern of FOCAD in human normal tissues and cancer tissues and elucidate the role and regulatory mechanism of Early Growth Response 1 (EGR1) in FOCAD and its intron, miR-491-5p, in gastric cancer. Immuno histochemical staining revealed that FOCAD is widely and highly expressed in normal gastric mucosa, but is absent in gastric cancer tissue. Based on an association analysis FOCAD expression was found to be negatively associated with lymph node metastasis (P = 0.004); higher FOCAD levels were associated with longer survival in patients with gastric cancer (P = 0.001). MTT, colony, Transwell chamber, and flow cytometry assays revealed that siFOCAD promoted cell proliferation, growth, and migration, and inhibited apoptosis. Furthermore, bioinformatic analysis, Fluorescence reporter gene and chromatin immunoprecipitation analyses confirmed that EGR1 binds to the promoter and negatively regulates FOCAD and miR-491-5p at the transcriptional level. The overexpression of EGR1 was also found to promote cell proliferation, growth, and migration, and inhibit apoptosis. Overall, FOCAD is specifically overexpressed in the gastric mucosa and is significantly downregulated in gastric cancer. To our knowledge, this is the first study to demonstrate that FOCAD is a tumor suppressor, higher FOCAD levels might be a better prognostic marker of gastric cancer, and FOCAD/miR-491-5p may be negatively regulated by EGR1.

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and has a prevalence of 1 in 15 women worldwide. This study aims to investigate the role of lncRNA SRA in the pathological processes of polycystic ovary syndrome (PCOS). Methods Twenty five-day old female C57BL/6 mice received subcutaneous injection of 60 mg/kg dehydroepiandrosterone for 20 days to induce PCOS. Lentivirus containing lncRNA SRA-specific shRNA was subcapsularly injected into the ovaries of PCOS mice. Granulosa cell was primary cultured to explore the mechanism of DHEA-induced inflammatory responses. H&E staining was used to examine the histological changes of ovaries. ELISA was used to assess serum insulin level and proinflammatory cytokines and angiogenetic factors contents in ovary tissue. The expression levels of LncRNA SRA and proteins involved in the NF-κB signaling pathway were detected through Quantitative real-time PCR and Western blot. The nuclear translocation of NF-κB was observed by immunofluorescence and the activity of NF-κB-DNA binding was detected using EMSA. Results Silencing of lncRNA SRA changed insulin release, attenuated ovary injury and reduced the production of angiogenetic factors in the PCOS mice. In addition, shRNA targeting lncRNA SRA inhibited DHEA-induced pro-inflammatory cytokines production and NF-κB nuclear translocation in the ovary of PCOS mice and primary granulosa cells. Conclusion Silencing of lncRNA Steroid Receptor RNA Activator (SRA) attenuates polycystic ovary syndrome (PCOS) in mice. LncRNA SRA plays important roles in the development of PCOS.

Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular drug release remains a major hindrance to the use of homodimeric prodrugs-based nanomedicine. We sought to develop a reactive oxygen species (ROS) responsive POD dimeric prodrug by incorporating vitamin K3 (VK3) and Pluronic F127 to synthesize a spheroid nanoparticle (PTV-NPs). PTV-NPs with high POD content could release drugs under the ROS enrichment microenvironment in cancer cells. The released VK3 could produce abundant ROS selectively in tumor cells catalyzed by the overexpressed NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme. In turn, the resultant high ROS concentration promoted the conversion of POD dimeric prodrug to POD monomer, thereby achieving the selective killing of cancer cells with weak system toxicity. In vitro and in vivo studies consistently confirmed that PTV-NPs exhibit high drug loading potential and upstanding bioavailability. They are also effectively internalized by tumor cells, induce abundant intracellular ROS generation, and have high tumor-specific cytotoxicity. This ROS-responsive dimeric prodrug nanoplatform characterized by selective self-amplification drug release may hold promise in the field of antitumor drug delivery.

BACKGROUND Increasing evidence indicates that long noncoding RNAs (LncRNAs) play a key role in multiple pathological processes. It has been shown that LncRNA steroid receptor RNA activator (SRA) is elevated in peripheral blood of patients with polycystic ovary syndrome (PCOS). The aim of this study was to assess the effect of elevated LncRNA SRA on ovarian granular cells of mice in vitro. MATERIAL AND METHODS We firstly isolated granular cells from mouse ovaries and over-expressed the LncRNA SRA by means of lentiviral transfection in this cell line. Then, we assessed the effects of LncRNA SRA on granular cells through real-time PCR, CCK-8 assay, flow cytometry, Hoechst staining, and Western blot assay. RESULTS We demonstrated that elevated LncRNA SRA stimulated cell growth, changed distribution of cell cycle phases with increase of Cyclin B, Cyclin E, and Cyclin D1, and inhibited cell apoptosis with up-regulation of bcl2 and down-regulation of bax, cleaved-caspase 3, and cleaved-PARP. Moreover, the contents of estradiol (E2) and progesterone (PG) and expressions of their key enzymes (CYP19A1 and CYP11A1) were up-regulated following over-expression of LncRNA SRA. CONCLUSIONS Taken together, our results indicate that abnormal LncRNA SRA may be a risk factor for evoking PCOS.

The epithelial-mesenchymal transition (EMT) is crucial for cancer progression. Evidence has shown that miR-22 and miR-214 play a key role in colon cancer progression; however, the underlying mechanism remains to be known. The effects of miR-22 and miR-214 on EMT are contradictory in different cancers, and whether miR-22 and miR-214 are involved in the colon cancer EMT process needs to be elucidated. In this study, we evaluated the exact role and the regulation mechanism of miR-22 and miR-214 in colon cancer. After transfection with miR-22 expression vector, the cell proliferation and migration capacity of HCT116 and RKO cells were significantly suppressed. Also, E-cadherin was increased and vimentin was decreased by miR-22 overexpression. Similar effects were also observed after miR-214 expression vector transfection. Dual-luciferase reporter confirmed that BCL9L is the target gene of both miR-22 and miR-214. Silencing of BCL9L inhibits cell proliferation and migration, and the expression of E-cadherin and vimentin was also altered by BCL9L knockdown, which was consistent with miR-22 or miR-214 transfection. Furthermore, miR-22 and miR-214 inhibited tumor growth in nude mice. Moreover, although the association between BCL9L's lower expression and longer survival time was statistically nonsignificant, a trend existed; further studies in a larger cohort are needed. Collectively, these data suggest that miR-22 and miR-214 inhibit cell proliferation, migration, and EMT of colon cancer, most likely by targeting BCL9L.-Sun, R., Liu, Z., Han, L., Yang, Y., Wu, F., Jiang, Q., Zhang, H., Ma, R., Miao, J., He, K., Wang, X., Zhou, D., Huang, C. miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signliang in colon cancer.

PURPOSE To investigate the effect(s) of screw-access hole (SAH) in different diameters on the cement-retained implant prosthodontic systems and surrounding cortical bones. MATERIALS AND METHODS Twenty finite element models were divided into 4 groups: 2 types of full-contour (FC) crowns (Y-TZP, gold alloy) and 2 types of porcelain-fused-to-metal crowns (based on Co-Cr, Au-Pd alloy). For each group, 5 crowns were simulated by varying the diameter of SAH (0, 1, 2, 3, and 4 mm). A vertical load of 200 N and an oblique load of 100 N (45°s) were applied. All models were analyzed with finite element analysis software. RESULTS The stress on the occlusal surface of crowns was almost unchanged when the SAH was within 0 to 3 mm, whereas it showed an obvious increase when it reached 4 mm. The stress concentration was also suddenly changed from the loading area to the hole margin under vertical loading. As for the screw, a lower stress level was observed in vertical loading when an FC crown with an SAH within 0 to 1 mm was applied. The stress concentration was constantly located at the beginning of the first thread. Stresses of other components remained almost unchanged. CONCLUSIONS From the aspect of biomechanics, an FC crown with a 1-mm access hole is recommended when a combined cement- and screw-retained crown was used in the posterior region.

Oral squamous cell carcinoma (OSCC) cells are usually resistant to doxorubicin, resulting in limited application of doxorubicin in OSCC treatment. MicroRNA (miR)‑221 has been reported to be involved in the development of OSCC; however, it remains unclear if and how miR‑221 is implicated in modulating the sensitivity of OSCC cells to doxorubicin. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to assess miR‑221 expression in OSCC cells in response to doxorubicin treatment. In addition, the SCC4 and SCC9 OSCC cell lines were transfected with anti‑miR‑221 oligonucleotides and cell viability and apoptosis following doxorubicin treatment were evaluated using an MTT assay and Annexin V‑fluorescein isothiocyanate/Hoechst double staining, respectively. The mRNA and protein expression levels of tissue inhibitor of metalloproteinase‑3 (TIMP3) in anti‑miR‑221‑transfected cells were assessed using RT‑qPCR and western blot analysis, respectively. Furthermore, a luciferase reporter assay was performed to investigate whether TIMP3 may be a direct target gene of miR‑221. To explore the roles of TIMP3 in miR‑221‑mediated cell responses, TIMP3 expression was silenced following transfection with TIMP3‑targeting small interfering (si)RNA in cells overexpressing miR‑221, and cell viability and apoptosis in response to doxorubicin treatment were measured. The results of the present study demonstrated that miR‑221 expression was upregulated in SCC4 and SCC9 cells following treatment with doxorubicin. However, inhibiting the doxorubicin‑induced upregulation of miR‑221 through transfection with anti‑miR‑221 oligonucleotides led to an increase in the sensitivity of OSCC cells to doxorubicin. In addition, the results indicated that TIMP3 was a direct target of miR‑221 in OSCC cells, as determined by a 3'‑untranslated region luciferase reporter assay. Co‑transfection of cells with anti‑miR‑221 oligonucleotides and TIMP3‑specific small interfering RNA resulted in reduced sensitivity to doxorubicin compared with the cells transfected with the miR‑221 inhibitor alone. In conclusion, these results indicated that OSCC cells are resistant to doxorubicin through upregulation of miR‑221, which in turn downregulates TIMP3. Therefore, silencing miR‑221 or upregulating TIMP3 may be considered promising therapeutic approaches to enhance the sensitivity of OSCC to doxorubicin.

A sensitive and reliable ultra-high performance liquid chromatography coupled with tandem quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for quantitation of plantamajoside in rat plasma. First, this study compared the pharmacokinetic properties of plantamajoside after oral administration of Plantago asiatica extract and pure plantamajoside in rat plasma with approximately the same dosage of 8.98 mg/kg. Second, chromatographic separation was performed on an Acquity HSS C

Formaldehyde (FA), a ubiquitous environmental pollutant, is extensively used in hospitals, laboratories, and industrial settings. Previous studies showed that FA exerts adverse effects on testicular function and as epididymis is known to play an important role in the maturation and storage of sperm, the effects of FA were examined on epididymis. In particular, this study was designed to investigate the influence of FA on structure and function of epididymis in adult male rats using histological and biochemical methods. Sprague-Dawley adult rats were randomly allotted to three groups and exposed to FA at a 0 (control), 0.5, or 10 mg m−3 by inhalation for 28 days. The results indicated that epididymal toxicity of FA was concentration dependent. Epdididymal structure and function in rats of 0.5 mg m−3 FA exposure group showed no apparent difference from control. However, epididymal weight, sperm count and motility, the activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were signifi...

A sensitive and reliable ultra-high performance liquid chromatography coupled with tandem quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for quantitation of plantamajoside in rat plasma. First, this study compared the pharmacokinetic properties of plantamajoside after oral administration of Plantago asiatica extract and pure plantamajoside in rat plasma with approximately the same dosage of 8.98 mg/kg. Second, chromatographic separation was performed on an Acquity HSS C18 column (50*2.1 mm, p.d.1.7 µm) with isocratic elution using methanol-water (80:20, v/v) as mobile phase at a flow rate of 0.25 mL/min. The calibration curves were linear over the range of 0.1–100 ng/mL for plantamajoside. At different time points (0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, and 8 h) after administration, the concentrations of plantamajoside in plasma were measured and the main pharmacokinetic parameters were estimated. The study indicates that the pharmacokinetics of plantamajoside in rat plasma have significant differences between two groups. This article is protected by copyright. All rights reserved.

Formaldehyde (FA), a ubiquitous environmental pollutant, is extensively used in hospitals, laboratories and many industrial settings. Previous studies have showed that short-term, high-dose FA exposure is toxic to male reproduction of mammals. In this paper, we evaluated the male reproductive toxicity of long-term, low-dose formaldehyde exposure in rats, and explored the potential mechanisms. A total of 30 Sprague-Dawley male rats were randomly allotted to three groups, rats were exposed to FA at a dose of 0 (control), 0.5, 2.46 mg/m3 respectively by inhalation for consecutive 60 days. The results indicated that the reproductive toxicity of FA is dose-dependent. Testicular, epididymal structure and function in rats of 0.5 mg/m3 FA exposure group showed no obvious difference compared with those in control group. However, sperm quantity and quality, testicular seminiferous tubular diameter, the activities of superoxide dismutase and glutathione peroxidase was significantly decreased whereas the level of malondialdehyde was significantly increased in rats of 2.46 mg/m3 FA exposure group compared with those in control group. Moreover, histopathological results showed atrophy of seminiferous tubules, decreases of spermatogenic cells and the lumina were oligozoospermic in testes of 2.46 mg/m3 FA exposure rats. In conclusion, the level of 0.5 mg/m 3 can be considered as a safe level for FA exposure, but long-term FA exposure at a dose of 2.46 mg/m3 has a harmful effect on male reproduction by inducing oxidative stress in male rats.

Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products including plastics, cosmetics, and medical devices. Some studies have shown that DBP has potential testicular toxicity. However, the mechanism of action of DBP on male reproduction is not clear. The present study was designed to further investigate the potential male reproductive toxicity of DBP . Oxidative stress was assessed in rat testes as an underlying mechanism. Forty SD adult rats were randomly allotted to four groups, and DBP was administered to each group by oral gavage at doses of 0 (control), 100, 250, and 500 mg/kg/d for 2 consecutive weeks. The results indicated that the reproductive toxicity of DBP is dose-dependent. Body and testicular weight was significantly decreased in rats of DBP exposure at a dose of 500 mg/kg/d. Sperm count and motility were significantly decreased at doses of 250 and 500 mg/kg/d. The same two doses significantly inhibited the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) while the level of malondialdehyde (MDA) was significantly increased in testes of rats. Microscopy with hematoxylin and eosin (HE) staining showed that seminiferous tubules atrophy and seminiferous epithelial cells disintegrated and shed in rats of DBP exposure at doses of 500 mg/kg/d. In conclusion, DBP alters the testicular structure and function, at least partly, by inducing oxidative stress in testes of adult rats.

Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products including plastics, cosmetics and medical devices. Previous studies have shown that DBP has potential testicular toxicity. Epididymis is known to play an important role in the maturation and storage of sperm. However, the effect and mechanism of action of DBP on epididymis is unclear. The present study was designed to investigate the effect of DBP on structure and function of epididymis in adult male rats by histological and biochemical study. Oxidative stress was also assessed in rat epididymis as an underlying mechanism. Forty SD adult rats were randomly allotted to four groups, and DBP was administered to each group by oral gavage at doses of 0 (control), 100, 250 and 500 mg/kg/day for 2 consecutive weeks. The results indicated that the epididymal toxicity of DBP is dose-dependent. Epididymal weight, activities of epididymal alpha-glucosidase and glutathione peroxidase (GSH-Px) was significantly decreased in rats of 500 mg/kg DBP exposure group compared to the control. The activity of superoxide dismutase (SOD) was significantly decreased while the level of malondialdehyde (MDA) was significantly increased in the epididymal tissue of the 250 and 500 mg/kg DBP exposure groups compared with the control group. Moreover, microscopy with hematoxylin and eosin (HE) staining showed that atrophy of epididymal tubules, the interstitial vascular was hyperemia and the lumina were oligozoospermic in rats of 500 mg/kg DBP exposure group. In conclusion, DBP exposure alters the epididymal structure and function by inducing oxidative stress in epididymis of adult rats.

The results of several recent studies indicated that free radicals are involved in the biochemical mechanisms that underlie neuropsychiatric disorders. In the present study, we evaluated changes in oxidative stress and human 8-hydroxyguanine glycosylase1 gene (hOGG1) expression in depressive patients with acute leukemia. Ninety two cases were assessed using the Zung self-rating depression scale (SDS) and multiple-item questionnaires. We measured total antioxidant capacity (T-AOC) and the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) during a pre-treatment period. The steady-state expression of hOGG1 mRNA transcripts was monitored. The incidence of depression was 47.83%. There was a significant decrease in serum T-AOC and SOD concentrations in depressive patients compared to the control subjects, whereas the opposite was the case for serum concentrations of ROS, NO and MDA. Real-time polymerase chain reaction (PCR) revealed that hOGG1 mRNA expression was greater in depressive patients than in the controls. Person correlation analysis revealed that depression was correlated positively with sex, the course of the disease and hOGG1 mRNA expression; depression was correlated negatively with T-AOC. Based on these results, we conclude that the antioxidant system is impaired in leukemic patients with affective disorders. Therefore, oxidative stress may play an important role in the pathophysiology of depression.