Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.

BackgroundRecently, many studies explored the role of inflammation parameters such as neutrophil-to-lymphocyte ratio (NLR) in the prognosis of urinary cancers, but the results were not consistent.MethodsWe carried out a meta-analysis of published studies to assess the prognostic value of NLR in patients with urinary cancers. Hazard ratio (OR) with 95% confidence interval (CI) was used to assess the association of NLR and OS and RFS/CSS.ResultsThe pooled results showed that high NLR was a poor predictor for OS with HR of 1.81 (95%CI: 1.48–2.21; Pheterogeneity = 0.005) and RFS/CSS (HR = 2.07, 95% CI: 1.65–2.6; Pheterogeneity = 0.849). Subgroup analyses revealed that high NLR yielded a worse OS in RCC (HR = 1.9, 95%CI: 1.47–2.45; Pheterogeneity = 0.003) and a poor RFS/CSS in RCC (HR = 1.83, 95%CI: 1.35–2.48; Pheterogeneity = 0.709), bladder cancer (HR = 2.2, 95%CI: 1.27–3.8; Pheterogeneity = 0.447) and urothelial carcinoma (HR = 2.58, 95%CI: 1.66–4.01; Pheterogeneity = 0.784).ConclusionOur results showed that NLR could act as a significant biomarker in the prognosis of urinary cancers.

The kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of the renal cell carcinoma, accounting for 80–90% of patients. Currently, the N6-methyladenosine (m6A) epitranscriptional modification draws much attention. The m6A RNA modification, the most plentiful internal modification of mRNAs and noncoding RNAs in the majority of eukaryotes, regulates mRNAs at different levels and is involved in disease occurrence and progression. The GTExPortal and TCGAportal were applied to investigate the METTL14 mRNA expression in different tissues and KIRC stages. The Human Protein Atlas was used to verify the location of METTL14 in KIRC tissues. The main microRNAs (miRNAs) related to KIRC were analyzed using OncoLnc and starBase, while corresponding circular RNAs (circRNAs) interacting with miRNAs were predicted via circBank; then, the METTL14-miRNA-circRNA interaction network was established. The level of methyltransferase-like 14 (METTL14) mRNA was significantly lower in KIRC tissues compared with normal kidney tissues, which was relative to clinical and pathological stages. circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the KIRC progression. METTL14 mRNA is likely to regulate PTEN mRNA expression via changing its m6A RNA modification level. METTL14 mRNA expression negatively correlated with the KIRC stages and positively correlated with KIRC patients’ overall survival, which has great potential to serve as a clinical biomarker in KIRC.

Cancer related inflammation (CRI) is now recognized as the seventh hallmark in the pathogenesis of many types of malignancies. Paeonol, a natural phenolic component isolated from the root bark of Paeonia moutan, has significant antiinflammatory activity. Recently, accumulating body of research has revealed potent anti-tumor effects mediated by paeonol. However, little is known about its anticancer mechanism on the basis of CRI. In this study, we observed that paeonol exerted direct anticancer activity through inhibition of cell proliferation, induction of apoptosis, and evident antiinflammatory effects by reducing proinflammatory cytokines secretion (TNF-a, IL-1b, IL-6, and TGF-b) in the conditioned medium of B16F10 mouse melanoma cells. Interestingly, we found that paeonol significantly reversed motility phenotypes in TNF-a-or IL-6-induced B16F10 singe cell and collective migration and invasion in vitro, which were related to affecting epithelial-to-mesenchymal transition (EMT) makers and MMPs expression. In particular, paeonol disrupted both TNFa-activated NF-jB and IL-6-activated STAT3 signaling pathways in B16F10 cells. EMSA and luciferase assays showed that paeonol abrogated NF-jB binding and NF-jB-driven promoter activity in the presence of TNF-a. Finally, we showed that paeonol attenuated B16F10 spontaneous lung metastases in C57/BL6J mice with down-regulated levels of serum proinflammatory cytokines. Therefore, paeonol possessed antitumor activity in melanoma cells and mice model by 778IUBMB Life interruption of the aggressive feedback through proinflammatory cytokines mediated NF-jB and STAT3 signaling activation. These findings provide a novel treatment strategy that paeonol might be a promising versatile adjuvant therapy for cancer related inflammation. V C 2015 IUBMB Life, 67(10): [778][779][780][781][782][783][784][785][786][787][788] 2015

8-Gingerol is one of the principal components of ginger, which is widely used in China and elsewhere as a food, spice and herb. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, we found that 8-gingerol suppressed lipopolysaccharide (LPS) and concanavalin A (ConA)-stimulated splenocyte proliferation in vitro. In vivo, 8-gingerol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation (P < 0.05) but also decreased the percentage of CD19+ B cells and CD3+ T cell (P < 0.05) at high doses (50, 100 mg/kg). Moreover, OVA-specific IgG, IgG1 and IgG2b levels in OVA-immunized mice were reduced by 8-gingerol at doses of 50, 100 mg/kg. These results suggest that 8-gingerol could suppress humoral and cellular immune responses in mice. The mechanism might be related to direct inhibition of sensitized T and B lymphocytes.

Diabetes can cause various complications and affect the normal functioning of the human body. A theranostic and diagnostic platform for real-time glycemia sensing and simultaneous self-regulated release of insulin is...

Activated platelets have been recognized as an accessory character in the cascade of tumor hematogenous metastasis, and intervention of tumor cell attachment to the activated platelets or microemboli formation might be a leading strategy to prevent tumor cells surviving in the blood vessels and sequential metastasis. Recently, we have demonstrated that holothurian glycosaminoglycan (hGAG), a sulfated polysaccharide with potent anticoagulant activity extracted from the sea cucumber Holothuria leucospilota Brandt, was highly efficacious against tumor metastasis. In this study, we identified the potential effects of hGAG on the disruption of interactions of cancer cells and platelets and the underlying mechanisms, which were supported by the following evidence: hGAG (1) inhibited thrombin-induced platelet activation and aggregation, (2) reduced adhesion between platelet and breast cancer cells, and abrogated platelets/cancer cells adhering to fibrinogen, (3) attenuated platelet-cancer cell complex formation (the number and size of aggregates) and (4) suppressed both mRNA and protein levels of β₁ and β₃ integrins, matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of the MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 in MDA-MB-231 cells. These results suggested that both the antiplatelet properties and mitigation of the levels of cellular adhesion molecules contributed to the anticancer effects of hGAG, and might thus be exploited for clinical adjuvant therapy to attenuate tumor hematogenous metastasis.

Salidroside, a major component of Rhodiola rosea L., has shown various pharmacological functions, including antioxidant effects, but the signal transduction pathway of its antioxidant effects is not very clear. In this study, we found that salidroside could attenuate hydrogen peroxide (H2O2)-induced HL-7702 cell damage, inhibit H2O2-induced cytosolic free Ca2+ ([Ca2+]i) elevation, scavenge reactive oxygen species (ROS) and increase 3’-5’-cyclic adenosine monophosphate (cAMP) level in a dose-dependent manner, but it couldn’t influence 3’-5’-cyclic guanosine monophosphate (cGMP) levels. Therefore, these results indicated that the antioxidant effects of salidroside were associated with down-regulation of [Ca2+]i, ROS occur via a cAMP-dependent pathway.