Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Graphic abstract

Background Lead exposure (LE) and its attributable deaths and disability-adjusted life years (DALYs) have declined in the recent decade; however, it remains one of the leading public health concerns, particularly in regions with low socio-demographic index (SDI) such as the North Africa and Middle East (NAME) region. Hence, we aimed to describe the attributable burden of the LE in this region. Methods Data on deaths, DALYs, years of life lost (YLLs), and years lived with disability (YLDs) attributable to LE in the NAME region and its 21 countries from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) 2019 study. Results In 2019, the age-standardized death and DALY rates attributable to LE were 23.4 (95% uncertainty interval: 15.1 to 33.3) and 489.3 (320.5 to 669.6) per 100,000 in the region, respectively, both of which were higher among men than women. The overall age-standardized death and DALY rates showed 27.7% and 36.8% decreases, respectively, between 1990 and 2019. In this period, Bahrain, the United Arab Emirates, and Turkey had the highest decreases in the age-standardized death and DALY rates, while Afghanistan, Egypt, and Yemen had the lowest ones. Countries within high SDI quintile had lower attributable burden to LE compared with the low SDI quintile. Cardiovascular diseases and chronic kidney diseases accounted for the 414.2 (258.6 to 580.6) and 28.7 (17.7 to 41.7) LE attributable DALYs per 100,000 in 2019, respectively. The attributable YLDs was 46.4 (20.7 to 82.1) per 100,000 in 2019, which shows a 25.7% reduction (-30.8 to -22.5%) over 1990–2019. Conclusions The overall LE and its attributed burden by cause have decreased in the region from 1990–2019. Nevertheless, the application of cost-effective and long-term programs for decreasing LE and its consequences in NAME is needed.

Mesenchymal stem cells (MSCs), as adult multipotent cells, possess considerable regenerative and anti-neoplastic effects, from inducing apoptosis in the cancer cells to reducing multidrug resistance that bring them up as an appropriate alternative for cancer treatment. These cells can alter the behavior of cancer cells, the condition of the tumor microenvironment, and the activity of immune cells that result in tumor regression. It has been observed that during inflammatory conditions, a well-known feature of the tumor microenvironment, the MSCs produce and release some molecules called “antimicrobial peptides (AMPs)” with demonstrated anti-neoplastic effects. These peptides have remarkable targeted anticancer effects by attaching to the negatively charged membrane of neoplastic cells, disrupting the membrane, and interfering with intracellular pathways. Therefore, AMPs could be considered as a part of the wide-ranging anti-neoplastic effects of MSCs. This review focuses on the possible anti-neoplastic effects of MSCs-derived AMPs and their mechanisms. It also discusses preconditioning approaches and using exosomes to enhance AMP production and delivery from MSCs to cancer cells. Besides, the clinical administration of MSCs-derived AMPs, along with their challenges in clinical practice, were debated.