Decoding the synergistic potential of MAZ-51 and zingerone as therapy for melanoma treatment in alignment with sustainable development goals.

Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment-producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor-beta 1 (TGF-ß1), vascular endothelial growth factor-C (VEGF-C) and C-X-C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3-(4-dimethylaminonaphthelen-1-ylmethylene)-1,3-dihydroindol-2-one) MAZ-51 is an indolinone-based molecule that inhibits VEGF-C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR-3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well-being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun-safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy.

Linking African ancestral substructure to prostate cancer health disparities.

Prostate cancer (PCa) is a significant health burden in Sub-Saharan Africa, with mortality rates loosely linked to African ancestry. Yet studies aimed at identifying contributing risk factors are lacking within the continent and as such exclude for significant ancestral diversity. Here, we investigate a series of epidemiological demographic and lifestyle risk factors for 1387 men recruited as part of the multi-ethnic Southern African Prostate Cancer Study (SAPCS). We found poverty to be a decisive factor for disease grade and age at diagnosis, with other notably significant PCa associated risk factors including sexually transmitted diseases, erectile dysfunction, gynaecomastia, and vertex or complete pattern balding. Aligned with African American data, Black ethnicity showed significant risk for PCa diagnosis (OR = 1.44, 95% CI 1.05-2.00), and aggressive disease presentation (ISUP ≥ 4: OR = 2.25, 95% CI 1.49-3.40). New to this study, we demonstrate African ancestral population substructure associated PCa disparity, observing increased risk for advanced disease for the southern African Tsonga people (ISUP ≥ 4: OR = 3.43, 95% CI 1.62-7.27). Conversely, South African Coloured were less likely to be diagnosed with aggressive disease overall (ISUP ≥ 3: OR = 0.38, 95% 0.17-0.85). Understanding the basis for PCa health disparities calls for African inclusion, however, lack of available data has limited the power to begin discussions. Here, focusing on arguably the largest study of its kind for the African continent, we draw attention to the contribution of within African ancestral diversity as a contributing factor to PCa health disparities within the genetically diverse region of southern Africa.

Clinic-Integrated Mobile Health Intervention ("JomPrEP" App) to Improve Uptake of HIV Testing and Pre-exposure Prophylaxis Among Men Who Have Sex With Men in Malaysia: Protocol for an Intervention Development and Multiphase Trial.

BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by the HIV epidemic in Malaysia and globally. Cross-cutting prevention strategies such as mobile health (mHealth), particularly smartphone apps, hold great promise for HIV prevention efforts among Malaysian MSM, especially when linked to HIV testing and pre-exposure prophylaxis (PrEP). OBJECTIVE: This study aims to adapt an existing app to create and test a clinic-integrated app (JomPrEP), a virtual platform to deliver HIV testing and PrEP services for MSM in Malaysia. METHODS: The JomPrEP project involves developing and testing an app-based platform for HIV prevention among Malaysian MSM and will be conducted in 2 phases. In phase I (development phase), we will adapt an existing mHealth app (HealthMindr) to create a new clinic-integrated app called "JomPrEP" to deliver holistic HIV prevention services (eg, HIV testing, PrEP, support services for mental health and substance use) among MSM in Malaysia. During phase II (testing phase), we will use a type I hybrid implementation science trial design to test the efficacy of JomPrEP while gathering information on implementation factors to guide future scale-up in real-world settings. RESULTS: As of September 2022, we have completed phase I of the proposed study. Based on a series of formative work completed during phase I, we developed a fully functional, clinic-integrated JomPrEP app, which provides a virtual platform for MSM in Malaysia to facilitate their engagement in HIV prevention in a fast and convenient manner. Based on participant feedback provided during phase I, we are currently optimizing JomPrEP and the research protocols for a large-scale efficacy trial (phase II), which will commence in January 2023. CONCLUSIONS: Scant HIV prevention resources coupled with entrenched stigma, discrimination, and criminalization of same-sex sexual behavior and substance use hamper access to HIV prevention services in Malaysia. If found efficacious, JomPrEP can be easily adapted for a range of health outcomes and health care delivery services for MSM, including adaptation to other low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05325476; https://clinicaltrials.gov/ct2/show/NCT05325476. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43318.