The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis.

BACKGROUND: Vitamin D has antineoplastic effects, but the synthesis of vitamin D requires ultraviolet radiation, a known risk factor for melanoma. OBJECTIVE: To investigate the correlations between serum vitamin D levels and risk and prognosis of melanoma. METHODS: A systematic review and meta-analysis were conducted. Online databases were searched on 31 Oct 2018. RESULTS: Twenty-five studies with a total of 11166 patients with melanoma were included. There was no significant difference in serum vitamin D levels between patients with melanoma and controls [standardized mean difference (SMD), -0.185; 95% confidence interval (CI), -0.533 to 0.162]. However, the prevalence of vitamin D deficiency was significantly higher in patients with melanoma than that in controls (odds ratio, 2.115; 95% CI, 1.151-3.885). In terms of prognosis, serum vitamin D levels were significantly higher in melanoma patients with lower Breslow thickness (≦1 vs. >1 mm: SMD, 0.243; 95% CI, 0.160-0.327). Moreover, melanoma patients with lower vitamin D levels had a significantly higher mortality rate (hazard ratio, 1.558; 95% CI, 1.258-1.931). CONCLUSIONS: Vitamin D deficiency is associated with higher Breslow thickness and mortality in melanoma patients.

Melt processing of polypropylene-grafted-maleic anhydride/Chitosan polymer blend functionalized with montmorillonite for the removal of lead ions from aqueous solutions.

Heavy metals such as lead ions Pb (II) are a primary concern in the aquatic environment. These is because Pb (II) is poisonous at a threshold limit above 0.01 mg/L, when consumed over a long period of time. Pb (II) poisoning is very harmful to various organs viz. heart, intestine and kidneys. Besides, it affects bones, tissues, nervous and reproductive systems. Hence, it is important to remove Pb (II) from aquatic environment. Polypropylene (PP) and polypropylene grafted-maleic-anhydride (PP-g-MA) based nanocomposites reinforced with Chitosan (CS) and modified montmorillonite clay nanofiller (CL120DT) were successfully fabricated using twin screw melt extrusion for adsorption of Pb (II). The resulting nanocomposites were characterized by XRD to analyze the dispersion properties of the material, TEM and SEM for surface morphology, FTIR analysis for the functional groups and TGA for thermal stability. Pure PP showed two sharp peaks, but there was decreased in the intensity upon adding of CS and CL120DT. Among series of nanocomposites 2.0 phr and 4.0 phr loaded samples shows better storage module than that of pure PP. The uptake of Pb (II) from lead nitrate aqueous solution by PP + PP-g-MA/CL120DT-CS 2.0 phr nanocomposites followed the Langmuir isotherm model, with a remediation of 90.9% at pH 8 and was verified by pseudo-second order kinetic model. These results indicate that PP + PP-g-MA//CL120DT-CS 2.0 phr nanocomposites performed as a superabsorbent for the Pb (II) ion removal from aqueous solution.

Side-to-side variation in normal femoral morphology: 3D CT analysis of 122 femurs.

BACKGROUND: The contralateral femur is often used as reference for reconstruction in unilateral hip joint pathology. The objective of this study was to quantify the side-to-side variation in proximal femur. We hypothesized that significant side-to-side differences exist between left and right femur with implications for preoperative planning and leg length discrepancy following hip arthroplasty. MATERIALS AND METHODS: CT-based 3D femoral models were reconstructed for 122 paired femurs in 61 young healthy subjects (46.9±6.8 years) with no history of hip pathology. Side-to-side differences of several femoral morphologic parameters, including femoral head diameter, femoral anteversion, horizontal offset and femoral head center location, were compared and correlated with demographic factors using multiple linear regression. RESULTS: Significant side-to-side differences (P<0.01) were found in femoral anteversion (4.3±3.8°; range: 0.2° to 17.3°), horizontal offset (2.5±2.1mm; range: 0.1 to 10.3mm), and femoral head center location (7.1±3.8mm; range: 0.5 to 19.4mm). The difference in femoral anteversion was strongly correlated with the difference in neck diameter (R(2)=0.79), whereas the difference in horizontal femoral offset was highly correlated with the head diameter difference (R(2)=0.72). Femoral head center difference was correlated with the femoral anteversion, horizontal offset and neck-shaft-angle difference (R(2)=0.82). DISCUSSION: Relying on the anatomic landmarks of the contralateral femur during hip arthroplasty may not necessarily result in restoration of native anatomy and leg-length. Knowledge of the baseline side-to-side asymmetry could provide a range of error that would be tolerable following hip reconstruction. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Retrospective observational study.

Cytotoxicity and antibacterial activity of gold-supported cerium oxide nanoparticles.

BACKGROUND: Cerium oxide nanoparticles (CeO2) have been shown to be a novel therapeutic in many biomedical applications. Gold (Au) nanoparticles have also attracted widespread interest due to their chemical stability and unique optical properties. Thus, decorating Au on CeO2 nanoparticles would have potential for exploitation in the biomedical field. METHODS: In the present work, CeO2 nanoparticles synthesized by a chemical combustion method were supported with 3.5% Au (Au/CeO2) by a deposition-precipitation method. The as-synthesized Au, CeO2, and Au/CeO2 nanoparticles were evaluated for antibacterial activity and cytotoxicity in RAW 264.7 normal cells and A549 lung cancer cells. RESULTS: The as-synthesized nanoparticles were characterized by X-ray diffraction, scanning and transmission electron microscopy, and ultraviolet-visible measurements. The X-ray diffraction study confirmed the formation of cubic fluorite-structured CeO2 nanoparticles with a size of 10 nm. All synthesized nanoparticles were nontoxic towards RAW 264.7 cells at doses of 0-1,000 µM except for Au at >100 µM. For A549 cancer cells, Au/CeO2 had the highest inhibitory effect, followed by both Au and CeO2 which showed a similar effect at 500 and 1,000 µM. Initial binding of nanoparticles occurred through localized positively charged sites in A549 cells as shown by a shift in zeta potential from positive to negative after 24 hours of incubation. A dose-dependent elevation in reactive oxygen species indicated that the pro-oxidant activity of the nanoparticles was responsible for their cytotoxicity towards A549 cells. In addition, cellular uptake seen on transmission electron microscopic images indicated predominant localization of nanoparticles in the cytoplasmic matrix and mitochondrial damage due to oxidative stress. With regard to antibacterial activity, both types of nanoparticles had the strongest inhibitory effect on Bacillus subtilis in monoculture systems, followed by Salmonella enteritidis, Escherichia coli, and Staphylococcus aureus, while, in coculture tests with Lactobacillus plantarum, S. aureus was inhibited to a greater extent than the other bacteria. CONCLUSION: Gold-supported CeO2 nanoparticles may be a potential nanomaterial for in vivo application owing to their biocompatible and antibacterial properties.

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein.

DDX3 is a human RNA helicase with plethoric functions. Our previous studies have indicated that DDX3 is a transcriptional regulator and functions as a tumor suppressor. In this study, we use a bicistronic reporter to demonstrate that DDX3 specifically represses cap-dependent translation but enhances hepatitis C virus internal ribosome entry site-mediated translation in vivo in a helicase activity-independent manner. To elucidate how DDX3 modulates translation, we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G. Point mutations within the consensus eIF4E-binding motif in DDX3 impair its ability to bind eIF4E and result in a loss of DDX3's regulatory effects on translation. All these features together indicate that DDX3 is a new member of the eIF4E inhibitory proteins involved in translation initiation regulation. Most importantly, this DDX3-mediated translation regulation also confers the tumor suppressor function on DDX3. Altogether, this study demonstrates regulatory roles and action mechanisms for DDX3 in translation, cell growth and likely viral replication.

Essential role of mitogen-activated protein kinase pathway and c-Jun induction in epidermal growth factor-induced gene expression of human 12-lipoxygenase.

The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kinase (JNK) in a time-dependent manner. Treatment of the cells with an mitogen-activated protein kinase kinase inhibitor, PD098059 (30 microM), inhibited the EGF- and pSV2ras-induced expression of 12-lipoxygenase mRNA. Transfection of the cells with Ras, ERK2, Rac, JNK dominant negative mutants pMMrasDN, K52R ERK2, RacN17, and mJNK all inhibited the EGF-induced promoter activation of the 12-lipoxygenase gene. EGF induced the expression of c-Jun and the activity of transcription factor activator protein 1 in cells, and these effects were blocked by the treatment with K52R ERK2 and mJNK. Overexpression of c-Jun increased the expression of 12-lipoxygenase mRNA and enzyme activity. Furthermore, the Sp1-binding sites in the promoter region of the 12-lipoxygenase gene were requisite for c-Jun response, which was similar to that previously observed in EGF response. The results indicate that the EGF-induced expression of 12-lipoxygenase in A431 cells was mediated through the Ras-ERK and Ras-Rac-JNK signal pathways. Subsequent induction of c-Jun led by ERK and JNK activation was essential for this EGF response.

Effects of chronic treatment with (+)-nicotine on the stress-induced hypertension and downregulation of central nicotinic receptors in rats: comparative study with (-)-nicotine.

The effects of chronic treatment with (+)-nicotine on the immobilization stress-induced changes in blood pressure, body weight, and [3H]cytisine binding to brain nicotinic receptors were examined in rats and were compared with those of (-)-nicotine. Immobilization stress (2 hr/day(-1), for 2 weeks) induced a moderate elevation of blood pressure, loss of body weight gain, and downregulation of [3H]cytisine binding sites in cerebral cortex and midbrain. Chronic treatment with (+)- or (-)-nicotine inhibited the stress-induced hypertension but did not suppress the inhibition of body weight gain by stress. Body weight before stress load was also reduced by (-)-nicotine but not (+)-nicotine treatment. Treatment with each isomer increased the maximum number of [3H]cytisine binding sites (Bmax) of brain stem, cerebral cortex, and hippocampus. The Bmax in midbrain was also increased by (+)-nicotine but not by (-)-nicotine. Stress-induced downregulation in cerebral cortex was inhibited by both isomers. These results suggest that (+)- and (-)-nicotine cause various effects, including anti-stress effect, on the central nervous system in rats, which are slightly different between the isomers.

Hepatitis C virus core protein interacts with cellular putative RNA helicase.

The nucleocapsid core protein of hepatitis C virus (HCV) has been shown to trans-act on several viral or cellular promoters. To get insight into the trans-action mechanism of HCV core protein, a yeast two-hybrid cloning system was used for identification of core protein-interacting cellular protein. One such cDNA clone encoding the DEAD box family of putative RNA helicase was obtained. This cellular putative RNA helicase, designated CAP-Rf, exhibits more than 95% amino acid sequence identity to other known RNA helicases including human DBX and DBY, mouse mDEAD3, and PL10, a family of proteins generally involved in translation, splicing, development, or cell growth. In vitro binding or in vivo coimmunoprecipitation studies demonstrated the direct interaction of the full-length/matured form and C-terminally truncated variants of HCV core protein with this targeted protein. Additionally, the protein's interaction domains were delineated at the N-terminal 40-amino-acid segment of the HCV core protein and the C-terminal tail of CAP-Rf, which encompassed its RNA-binding and ATP hydrolysis domains. Immunoblotting or indirect immunofluorescence analysis revealed that the endogenous CAP-Rf was mainly localized in the nucleus and to a lesser extent in the cytoplasm, and when fused with FLAG tag, it colocalized with the HCV core protein either in the cytoplasm or in the nucleus. Similar to other RNA helicases, this cellular RNA helicase has nucleoside triphosphatase-deoxynucleoside triphosphatase activity, but this activity is inhibited by various forms of homopolynucleotides and enhanced by the HCV core protein. Moreover, transient expression of HCV core protein in human hepatoma HuH-7 cells significantly potentiated the trans-activation effect of FLAG-tagged CAP-Rf or untagged CAP-Rf on the luciferase reporter plasmid activity. All together, our results indicate that CAP-Rf is involved in regulation of gene expression and that HCV core protein promotes the trans-activation ability of CAP-Rf, likely via the complex formation and the modulation of the ATPase-dATPase activity of CAP-Rf. These findings provide evidence that HCV may have evolved a distinct mechanism in alteration of host cellular gene expression regulation via the interaction of its nucleocapsid core protein and cellular putative RNA helicase known to participate in all aspects of cellular processes involving RNA metabolism. This feature of core protein may impart pleiotropic effects on host cells, which may partially account for its role in HCV pathogenesis.