Metformin is a widely used drug in today’s prescriptions by physicians due to its specific effects in treating and curing type II diabetes. Diabetes is a common disease that may occur throughout human life, and can increase the likelihood of the occurrence of various types of cancer, such as colon, rectum, pancreas and liver cancers, compared to non-diabetic patients. Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. Metformin can activate p53 by activating AMPK and thereby ultimately stop the cell cycle. Given the potential of metformin in the treatment of cancer, it can be used in radiotherapy, chemotherapy and to improve the response to treatment in androgen derivatives (ADT), and also, according to available evidence, metformin can also be used to prevent various types of cancers. Generally, metformin can: 1) reduce the incidence of cancers, 2) reduce the mortality from cancers, 3) increase the response to treatment in cancer cells when using radiotherapy and chemotherapy, 4) optimize tumor movement and reduce the malignancy, 5) reduce the likelihood of relapse, and 6) reduce the damaging effects of ADT. Therefore, this drug can be used as a complementary therapeutic agent for cancer treatment and prevention. In this review, we have summarized the data from various experimental and clinical studies and highlight the possible potential effects of metformin on cancer therapeutic responses.
Despite current controversies, some reports show a paradoxical mitigating effect associated with smoking in individuals with symptomatic COVID-19 compared to the general population. To explain the potential mechanisms behind the lower number of hospitalized COVID-19 patients, it has been hypothesized that cigarette smoking may reduce the odds of cytokine storm and related severe inflammatory responses through cholinergic-mediated anti-inflammatory mechanisms. Japanese scientists have recently identified a potential mechanism behind the lower numbers of COVID-19 cases amongst smokers compared to non-smokers. However, we believe that this mitigative effect may be due to the relatively high concentration of deposited energy of alpha particles emitted from naturally occurring radionuclides such as Po-210 in cigarette tobacco. Regarding COVID-19, other researchers and our team have previously addressed the anti-inflammatory and immune-modulating effects of low doses of ionizing radiation. MC-simulation using the Geant4 Monte Carlo toolkit shows that the radiation dose absorbed in a spherical cell with a radius of .9 μm for a single 5.5 MeV alpha particle is about 5.1 Gy. This energy deposition may trigger both anti-inflammatory and anti-thrombotic effects which paradoxically lower the risk of hospitalization due to COVID-19 in smokers.
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