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Cancer is a significant global socioeconomic burden, as millions of new cases and deaths occur annually. In 2020, almost 10 million cancer deaths were recorded worldwide. Advancements in cancer gene therapy have revolutionized the landscape of cancer treatment. An approach with promising potential for cancer gene therapy is introducing genes to cancer cells that encode for chemotherapy prodrug metabolizing enzymes, such as Cytochrome P450 (CYP) enzymes, which can contribute to the effective elimination of cancer cells. This can be achieved through gene-directed enzyme prodrug therapy (GDEPT). CYP enzymes can be genetically engineered to improve anticancer prodrug conversion to its active metabolites and to minimize chemotherapy side effects by reducing the prodrug dosage. Rational design, directed evolution, and phylogenetic methods are some approaches to developing tailored CYP enzymes for cancer therapy. Here, we provide a compilation of genetic modifications performed on CYP enzymes aiming to build highly efficient therapeutic genes capable of bio-activating different chemotherapeutic prodrugs. Additionally, this review summarizes promising preclinical and clinical trials highlighting engineered CYP enzymes’ potential in GDEPT. Finally, the challenges, limitations, and future directions of using CYP enzymes for GDEPT in cancer gene therapy are discussed.

Prolonged fasting has shown beneficial effects in healthy individuals and in people with chronic diseases. In type 1 diabetes, the effect or even the feasibility of fasting is unclear. We aimed to assess the impact and safety of prolonged fasting in adults with type 1 diabetes. Glycemia was assessed during overnight fasting (12 hours) vs. prolonged fasting (36 hours) via an intermittently-scanned continuous glucose monitoring system. Anthropometric data, metabolic and hormonal markers were compared between both trial arms. After each fasting period, a 75 g oral glucose tolerance test was performed and plasma glucose levels and hormones were assessed. Data were compared via paired t-tests and mixed-model regressions (p ≤ 0.05). Twenty individuals with type 1 diabetes (7 females) with a mean ± SD age of 35 ± 11 years, body mass index (BMI) 24.8 ± 2.8 kg/m2 and HbA1c 54 ± 7 mmol/mol were included. Hypoglycemia/hour (70 mg/dL;

The objective of this paper is to analyse impacts of COVID-19 on the nexus of food systems, the environment and sustainable development and propose ways for governments and international agencies to mitigate impacts in the short and medium term. It covers the historic period from early 2020 to early 2021 and also makes an assessment on future prospects. Although evidence is collected from all around the world, the focus is primarily on developing countries. The methods used are a review of the announced actions and preliminary findings in the academic and grey literature as well as on reliable websites from global and international institutions. By October 2020, governments around the world had invested about $12 trillion to counteract the economic effects of COVID-19. This investment could contribute to progress on the SDGs and global climate targets insofar as it was invested within a framework that supports both socio-economic recovery and sustainability. Initial analysis indicates that investments for economic recovery did not sufficiently address food security and sustainability, concentrating instead on immediate economic risk management. The global sustainable development agenda must promote the resilience and sustainability of food systems through policies and measures that: i) account for environmental thresholds and trade-offs; ii) promote food security and healthy diets; iii) enhance and protect rural livelihoods; and iv) address the inequalities and injustices that have emerged and will prevail during a post-COVID transition. National stimulus programs and the actions of international agencies must be assessed and monitored to deliver multiple benefits simultaneously and guide building back better.

To investigate the heart rate during cardio-pulmonary exercise (CPX) testing in individuals with type 1 diabetes (T1D) compared to healthy (CON) individuals. Fourteen people (seven individuals with T1D and seven CON individuals) performed a CPX test until volitional exhaustion to determine the first and second lactate turn points (LTP1 and LTP2), ventilatory thresholds (VT1 and VT2), and the heart rate turn point. For these thresholds cardio-respiratory variables and percentages of maximum heart rate, heart rate reserve, maximum oxygen uptake and oxygen uptake reserve, and maximum power output were compared between groups. Additionally, the degree and direction of the deflection of the heart rate to performance curve (kHR) were compared between groups. Individuals with T1D had similar heart rate at LTP1 (mean difference) −11, [(95% confidence interval) −27 to 4 b.min−1], at VT1 (−12, −8 to 33 b.min−1) and at LTP2 (−7, −13 to 26 b.min−1), at VT2 (−7, −13 to 28 b.min−1), and at the heart rate turn point (−5, −14 to 24 b.min−1) (p = 0.22). Heart rate expressed as percentage of maximum heart rate at LTP1, VT1, LTP2, VT2 and the heart rate turn point as well as expressed as percentages of heart rate reserve at LTP2, VT2 and the heart rate turn point was lower in individuals with T1D (p < 0.05). kHR was lower in T1D compared to CON individuals (0.11 ± 0.25 vs. 0.51 ± 0.32, p = 0.02). Our findings demonstrate that there are clear differences in the heart rate response during CPX testing in individuals with T1D compared to CON individuals. We suggest using submaximal markers to prescribe exercise intensity in people with T1D, as the heart rate at thresholds is influenced by kHR.Clinical Trial Identifier: NCT02075567 (https://clinicaltrials.gov/ct2/show/NCT02075567).