Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.

Photodynamic therapy (PDT) is a groundbreaking approach involving the induction of cytotoxic reactive oxygen species (ROS) within tumors through visible light activation of photosensitizers (PS) in the presence of molecular oxygen. This innovative therapy has demonstrated success in treating various cancers. While PDT proves highly effective in most solid tumors, there are indications that certain cancers exhibit resistance, and some initially responsive cancers may develop intrinsic or acquired resistance to PDT.

Red Palm Oil Ameliorates Oxidative Challenge and Inflammatory Responses Associated with Lipopolysaccharide-Induced Hepatic Injury by Modulating NF-κβ and Nrf2/GCL/HO-1 Signaling Pathways in Rats.

Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant and anti-inflammatory effects. In this study, we assess the protective effect and mechanistic action of RPO using a lipopolysaccharide (LPS)-induced hepatic injury model.

A survey evaluating knowledge, perception, and use of skin lightening products among South African students.

Background: In sub-Saharan Africa, the use of skin-lightening products (SLPs) for cosmetic purposes has become common practice among women with dark skin tones. Despite the associated risks, the practice is still significantly increasing in Africa. The objective of this study was to determine the knowledge, perceptions and practice toward skin lightening among young adults.

Desensitization of metastatic melanoma cells to therapeutic treatment through repeated exposure to dacarbazine.

Aberrant anti-cancer drug efflux mediated by membrane protein ABC transporters (ABCB5 and ABCG2) is thought to characterize melanoma heterogeneous chemoresistant populations, presumed to have unlimited proliferative and self-renewal abilities. Therefore, this study primarily aimed to investigate whether continuous exposure of melanoma cells to dacarbazine (DTIC) chemotherapeutic drug enriches cultures with therapy resistant cells. Thereafter, we sought to determine whether combining the genotoxic activity of DTIC with the oxidative insults of hypericin activated photodynamic therapy (HYP-PDT) could synergized to kill heterogenous chemoresistant melanoma populations.

Rooibos (Aspalathus linearis) and honeybush (Cyclopia species) modulate the oxidative stress associated injury of diesel exhaust particles in human umbilical vein endothelial cells.

Background: Previous evidence show foods and beverages rich in polyphenolic compounds to have favourable effects on the cardiovascular system.

Hypothesis: The current study assessed the modulation of oxidative stress and associated inflammation induced by diesel exhaust particles (DEP - SRM 2975) by pre-treatment of human umbilical vein endothelial cells (HUVECs) with aqueous extracts of rooibos [fermented (FR) as well as green form (GR)] and honeybush [fermented form (FH)].

Study Design: HUVEC are either exposed to DEP (10 µg/ml) for 4 h or pre-treated with 40 and 60 µg/ml of FR or GH or FR, or 50 µg/ml orientin (OR) for 6 h prior to DEP exposure.

Antimicrobial and inflammatory properties of South African clinical Lactobacillus isolates and vaginal probiotics.

Bacterial vaginosis (BV) causes genital inflammation and increased HIV acquisition risk. The standard-of-care for BV, antibiotic therapy, is associated with high recurrence rates. Probiotics may improve treatment outcomes, although substantial heterogeneity in efficacy has been observed during clinical trials.

Skin cells for use in an alternate diagnostic method for Duchenne muscular dystrophy.

The importance of molecular diagnosis and identification of disease-associated variants for Duchenne muscular dystrophy (DMD) is evident in the age of gene-based therapies and personalised medicine. Detection of the causative DMD variant and determination of its effects on dystrophin expression is best achieved by analysis of RNA extracted from muscle biopsy material. However, this is not done routinely, as the procedure can be traumatic, especially to young children, and carries risk of complications related to the use of anaesthetic.

Fifty Shades of African Lightness: A Bio-psychosocial Review of the Global Phenomenon of Skin Lightening Practices.

Skin-lightening is an aesthetic practice of global concern. By adopting a biopsycho-social approach, we consider the interplay between the biological, psychological and social factors that underpin the circulation and consumption of skin lighteners in South Africa. This paper reflects on biological aspects of skin lightening, interpersonal relationships, individual beliefs and expectations about the maintenance of health and well being that informs cosmetic practices.

Cancer stem cells: A product of clonal evolution?

The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells.

Intravenous glutathione for skin lightening: Inadequate safety data.

Glutathione (GSH) is the most abundant naturally occurring non-protein thiol that protects mammalian cells from oxidative stress. Intravenous (IV) GSH for skin lightening is advertised by clinics in South Africa and internationally online, yet to date no published review on the subject exists. Methods.

St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death.

Hypericin, an extract from St John's Wort (Hypericum perforatum L.), is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms including apoptosis, necrosis and autophagy-related cell death.

Melanocyte migration is influenced by E-cadherin-dependent adhesion of keratinocytes in both two- and three-dimensional in vitro wound models.

During wound healing, melanocytes are required to migrate into the wounded area that is still in the process of re-construction. The role and behaviour of melanocytes during this process is poorly understood, that is, whether melanocyte migration into the wound is keratinocyte-dependent or not. This paper attempts, through the use of both two- and three-dimensional in vitro models, to understand the role and behaviour of melanocytes during the process of wound healing.

Novel, biocatalytically produced hydroxytyrosol dimer protects against ultraviolet-induced cell death in human immortalized keratinocytes.

Compounds derived from botanicals, such as olive trees, have been shown to possess various qualities that make them function as ideal antioxidants and, in doing so, protect them against the damaging effect of ultraviolet (UV)-derived oxidative stress. The aim of this study was to biocatalytically synthesize a dimeric product (compound II) from a known botanical, 3-hydroxytyrosol, and test it for its antioxidant ability using a human immortalized keratinocyte cell line (HaCaT). 2,2-Diphenyl-picryhydrazyl (DPPH) antioxidant assays showed 33 and 86.

Hypericin-PDT-induced rapid necrotic death in human squamous cell carcinoma cultures after multiple treatment.

PDT (photodynamic therapy) has been used for the treatment of NMCC (non-melanoma cutaneous cancer) particularly, human SCC (squamous cell carcinoma). However, the nature of the photosensitizer, the activation light source and the mode of cell death induced post-PDT remains elusive. We tried to optimize PDT using the light-activated (320-400 nm) St John's Wort-derived compound, Hyp (hypericin).

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Depigmentation in melanomas increases the efficacy of hypericin-mediated photodynamic-induced cell death.

Melanoma is the main cause of death in skin cancers. Despite combating with early detection, resection and post-operative therapy, melanoma treatment remains unsuccessful and investigations into other forms of adjuvant therapy such as photodynamic therapy (PDT) are prudent. This study proposes that depigmentation i.

Simultaneous immunofluorescent labeling using anti-BrdU monoclonal antibody and a melanocyte-specific marker in formalin-fixed paraffin-embedded human skin samples.

Immunolabeling of tissue sections requires careful optimization of protocols in order to achieve accurate and consistent data. Multiple immunolabeling is desirable when determining the exact location and phenotype of cell populations in the same cellular compartment. 5-bromodeoxyuridine (BrdU)-immunolabeling is commonly used to assess cellular proliferation in vitro.

Photodynamic therapy-induced killing is enhanced in depigmented metastatic melanoma cells.

The resistance of pigmented human melanomas over their unpigmented counterparts to a number of therapies has suggested that the presence of intracellular melanin plays a role in rendering these cells less susceptible to cell death, probably through the ability of this pigment to act as an intracellular antioxidant, thus neutralizing chemotherapeutic-induced ROS (reactive oxygen species). PDT (photodynamic therapy) was recently suggested as an attractive, adjunctive therapy owing to its cellular specificity and limited side effects. In the present study, we propose that first depigmenting melanomas with a reversible TYR (tyrosinase) inhibitor such as PTU (phenylthiourea) increases their susceptibility to HYP-PDT (hypericin-mediated PDT).

Photoprotection by honeybush extracts, hesperidin and mangiferin against UVB-induced skin damage in SKH-1 mice.

The possible mechanism of photoprotection by polyphenolic extracts of honeybush and the two most abundant polyphenols found in honeybush, hesperidin and mangiferin were determined using a mouse model. Ethanol: acetone soluble extracts and pure honeybush compounds were applied topically to the skin of SKH-1 mice before daily exposures to ultraviolet B (UVB) (180 mJ/cm²) for 10 days. The honeybush extracts reduced signs of sunburn, such as erythema, peeling and hardening of the skin and also significantly (P < 0.

Melanomas display increased cytoprotection to hypericin-mediated cytotoxicity through the induction of autophagy.

Photodynamic therapy (PDT) as a regime for melanoma is of limited success due to factors such as the efficacy of the photosensitizer used, penetration depth and the presence of pigment. We characterised a pigmented and an unpigmented melanoma cell line with respect to their phenotypes. Cell viability was assessed after exposure to hypericin, a UVA-activated photosensitizer.