Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma.

Melanoma is a very aggressive form of skin cancer. Although BRAF inhibitors have been utilized for melanoma therapy, advanced melanoma patients still face a low five-year survival rate. Recent studies have shown that CRAF can compensate for BRAF depletion via regulating DNA synthesis to remain melanoma proliferation. Hence, targeting CRAF either alone or in combination with other protein pathways is a potential avenue for melanoma therapy. Based on our previously reported CRAF-selective inhibitor for renal cancer therapy, we have herein discovered an analogue (complex 1) from the reported CRAF library suppresses melanoma cell proliferation and melanoma tumour growth in murine models of melanoma via blocking the S100B and RAF pathways. Intriguingly, we discovered that inhibiting BRAF together with S100B exerts a novel synergistic effect to significantly restore p53 transcription activity and inhibit melanoma cell proliferation, whereas blocking BRAF together with CRAF only had an additive effect. We envision that blocking the pan-RAF and S100B/p53 pathways might be a novel synergistic strategy for melanoma therapy and that complex 1 is a potential inhibitor against melanoma via blocking the pan-RAF and S100B pathways.

A Review: Hair Health, Concerns of Shampoo Ingredients and Scalp Nourishing Treatments.

Human hair serves a biological purpose of protecting the scalp, as well as physical attractiveness to the perception of beauty. Hair loss, graying of hair, dandruff and other conditions affecting hair conditions can be distressing to patients, as hair condition is often considered important in people's own assessment of physical beauty. Different hair types can benefit from different treatment methods to promote hair health and growth. External factors like exposure to the sun and smoking, dietary factors including malnutrition of essential fatty acids and vitamins, and chemicals applied to the hair and scalp in shampoos and other treatments can all cause damage to existing hair and impair hair growth. Specific chemicals found in many shampoos, including antimicrobial agents, surfactants and preservatives, can all impair different aspects of hair health. In this review, we aim to discuss the main hair issues, such as hair loss, followed by the safety assessments of selected ingredients in shampoo, and possible nourishment for scalp improvement. This review highlights areas of disagreement in the existing literature, and points to new directions for future studies. Key conclusions include the carcinogenic chemicals to avoid, alternatives of such ingredients, and scalp nourishing treatments with micronutrients.

Natural Products Mediated Regulation of Oxidative Stress and DNA Damage in Ultraviolet Exposed Skin Cells.

Data obtained through high-throughput technologies have gradually revealed that a unique stratified epithelial architecture of human skin along with the antioxidant-response pathways provided vital defensive mechanisms against UV radiation. However, it is noteworthy that skin is a major target for toxic insult by UV radiations that can alter its structure and function. Substantial fraction of information has been added into the existing pool of knowledge related to natural products mediated biological effects in UV exposed skin cells. Accumulating evidence has started to shed light on the potential of these bioactive ingredients as protective natural products in cosmetics against UV photodamage by exerting biological effects mainly through wide ranging intracellular signalling cascades of oxidative stress and modulation of miRNAs. In this review, we have summarized recently emerging scientific evidences addressing underlying mechanisms of UV induced oxidative stress and deregulation of signalling cascades and how natural products can be used tactfully to protect against UV induced harmful effects.

Synergistic Effects of Linderanolide B Combined with Arbutin, PTU or Kojic Acid on Tyrosinase Inhibition.

Melanin uncontrollable accumulation is a serious social problem to not only women, but also men, and causes pigment over-expression disorders such as freckles, melasma or pigmented acne scars. The synergism is used widely in medication, and the effectiveness makes the drug applications more valuable. Within this experiment, three well-known compounds were chosen: kojic acid, 1-phenyl-2-thiourea (PTU) and arbutin, and they were combined individually with our substance linderanolide B, which is purified from Cinnamomum subavenium. Hence, deciphering the synergistic action of possible whitening agents was the goal of this study. The tyrosinase activity, melanin content, and the combination index (CI) values were observed in B16F10 cells, in addition, the consequences were detected by isobologram analysis. We discovered that certain melanin inhibitors showed synergistic properties when they were combined together to suppress tyrosinase activities. As a result, linderanolide B has a potential synergy on tyrosinase inhibition, and it can be used widely in cosmetic and medication industries.