Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations.

Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep-wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as inflammation. Additionally, melatonin has demonstrated promising potential as an anti-cancer agent as its function includes inhibition of tumorigenesis, induction of apoptosis, and regulation of anti-tumor immune response. Although a precise pathophysiological mechanism is yet to be established, several pathways related to the regulation of cell cycle progression, DNA repair mechanisms, and antioxidant activity have been implicated in the anti-neoplastic potential of melatonin. In the current manuscript, we focus on the potential anti-cancer properties of melatonin and its use in treating and managing pediatric osteosarcoma. This aggressive bone tumor primarily affects children and adolescents and is treated mainly by surgical and radio-oncological interventions, which has improved survival rates among affected individuals. Significant disadvantages to these interventions include disease recurrence, therapy-related toxicity, and severe/debilitating side effects that the patients have to endure, significantly affecting their quality of life. Melatonin has therapeutic effects when used for treating osteosarcoma, attributed to its ability to halt cancer cell proliferation and trigger apoptotic cell death, thereby enhancing chemotherapeutic efficacy. Furthermore, the antioxidative function of melatonin alleviates harmful side effects of chemotherapy-induced oxidative damage, aiding in decreasing therapeutic toxicities. The review concisely explains the many mechanisms by which melatonin targets osteosarcoma, as evidenced by significant results from several in vitro and animal models. Nevertheless, if further explored, human trials remain a challenge that could shed light and support its utility as an adjunctive therapeutic modality for treating osteosarcoma.

Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties.

Cancer is a disease that can cause abnormal cell growth and can spread throughout the body. It is among the most significant causes of death worldwide, resulting in approx. 10 million deaths annually. Many synthetic anticancer drugs are available, but they often come with side effects and can interact negatively with other medications. Additionally, many chemotherapy drugs used for cancer treatment can develop resistance and harm normal cells, leading to dose-limiting side effects. As a result, finding effective cancer treatments and developing new drugs remains a significant challenge. However, plants are a potent source of natural products with the potential for cancer treatment. These biologically active compounds may be the basis for enhanced or less toxic derivatives. Herbal medicines/phytomedicines, or plant-based drugs, are becoming more popular in treating complicated diseases like cancer due to their effectiveness and are a particularly attractive option due to their affordability, availability, and lack of serious side effects. They have broad applicability and therapeutic efficacy, which has spurred scientific research into their potential as anticancer agents. This review focuses on Paclitaxel (PTX), a plant-based drug derived from Taxus sp., and its ability to treat specific tumors. PTX and its derivatives are effective against various cancer cell lines. Researchers can use this detailed information to develop effective and affordable treatments for cancer.

Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine.

BACKGROUND: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1α), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer. AIM OF REVIEW: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1α (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1α signaling (glucose transporters and key glycolytic enzymes). KEY SCIENTIFIC CONCEPTS OF REVIEW: The working hypothesis of the manuscript proposes HIF-1α - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence-based recommendations for the 3PM relevant implementation.

Resveratrol as sensitizer in colorectal cancer plasticity.

Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments.

B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention.

B7-H3 (B7 homology 3 protein) is an important transmembrane immunoregulatory protein expressed in immune cells, antigen-presenting cells, and tumor cells. Studies reveal a multifaceted role of B7-H3 in tumor progression by modulating various cancer hallmarks involving angiogenesis, immune evasion, and tumor microenvironment, and it is also a promising candidate for cancer immunotherapy. In colorectal cancer (CRC), B7-H3 has been associated with various aspects of disease progression, such as evasion of tumor immune surveillance, tumor-node metastasis, and poor prognosis. Strategies to block or interfere with B7-H3 in its immunological and non-immunological functions are under investigation. In this study, we explore the role of B7-H3 in tumor plasticity, emphasizing tumor glucose metabolism, angiogenesis, epithelial-mesenchymal transition, cancer stem cells, apoptosis, and changing immune signatures in the tumor immune landscape. We discuss how B7-H3-induced tumor plasticity contributes to immune evasion, metastasis, and therapy resistance. Furthermore, we delve into the most recent advancements in targeting B7-H3-based tumor immunotherapy as a potential approach to CRC treatment.

The Influence of Gut Microbial Species on Diabetes Mellitus.

Diabetes mellitus (DM) is a metabolic disorder with an alarming incidence rate and a considerable burden on the patient's life and health care providers. An increase in blood glucose level and insulin resistance characterizes it. Internal and external factors such as urbanization, obesity, and genetic mutations could increase the risk of DM. Microbes in the gut influence overall health through immunity and nutrition. Recently, more studies have been conducted to evaluate and estimate the role of the gut microbiome in diabetes development, progression, and management. This review summarizes the current knowledge addressing three main bacterial species: Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus rhamnosus and their influence on diabetes and its underlying molecular mechanisms. Most studies illustrate that using those bacterial species positively reduces blood glucose levels and activates inflammatory markers. Additionally, we reported the relationship between those bacterial species and metformin, one of the commonly used antidiabetic drugs. Overall, more research is needed to understand the influence of the gut microbiome on the development of diabetes. Furthermore, more efforts are required to standardize the model used, concentration ranges, and interpretation tools to advance the field further.

Role of flavonoids in controlling obesity: molecular targets and mechanisms.

Obesity presents a major health challenge that increases the risk of several non-communicable illnesses, such as but not limited to diabetes, hypertension, cardiovascular diseases, musculoskeletal and neurological disorders, sleep disorders, and cancers. Accounting for nearly 8% of global deaths (4.7 million) in 2017, obesity leads to diminishing quality of life and a higher premature mortality rate among affected individuals. Although essentially dubbed as a modifiable and preventable health concern, prevention, and treatment strategies against obesity, such as calorie intake restriction and increasing calorie burning, have gained little long-term success. In this manuscript, we detail the pathophysiology of obesity as a multifactorial, oxidative stress-dependent inflammatory disease. Current anti-obesity treatment strategies, and the effect of flavonoid-based therapeutic interventions on digestion and absorption, macronutrient metabolism, inflammation and oxidative stress and gut microbiota has been evaluated. The use of several naturally occurring flavonoids to prevent and treat obesity with a long-term efficacy, is also described.

Metabolic heterogeneity in TNBCs: A potential determinant of therapeutic efficacy of 2-deoxyglucose and metformin combinatory therapy.

Breast cancers (BCs) remain the leading cause of cancer-related deaths among women worldwide. Among the different types of BCs, treating the highly aggressive, invasive, and metastatic triple-negative BCs (TNBCs) that do not respond to hormonal/human epidermal growth factor receptor 2 (HER2) targeted interventions since they lack ER/PR/HER2 receptors remains challenging. While almost all BCs depend on glucose metabolism for their proliferation and survival, studies indicate that TNBCs are highly dependent on glucose metabolism compared to non-TNBC malignancies. Hence, limiting/inhibiting glucose metabolism in TNBCs should curb cell proliferation and tumor growth. Previous reports, including ours, have shown the efficacy of metformin, the most widely prescribed antidiabetic drug, in reducing cell proliferation and growth in MDA-MB-231 and MDA-MB-468 TNBC cells. In the current study, we investigated and compared the anticancer effects of either metformin (2 mM) in glucose-starved or 2-deoxyglucose (10 mM; glycolytic inhibitor; 2DG) exposed MDA-MB-231 and MDA-MB-468 TNBC cells. Assays for cell proliferation, rate of glycolysis, cell viability, and cell-cycle analysis were performed. The status of proteins of the mTOR pathway was assessed by Western blot analysis. Metformin treatment in glucose-starved and 2DG (10 mM) exposed TNBC cells inhibited the mTOR pathway compared to non-treated glucose-starved cells or 2DG/metformin alone treated controls. Cell proliferation is also significantly reduced under these combination treatment conditions. The results indicate that combining a glycolytic inhibitor and metformin could prove an efficient therapeutic approach for treating TNBCs, albeit the efficacy of the combination treatment may depend on metabolic heterogeneity across various subtypes of TNBCs.

Curcumin, calebin A and chemosensitization: How are they linked to colorectal cancer?

Colorectal cancer (CRC) is one of the leading malignant diseases worldwide with a high rate of metastasis and poor prognosis. Treatment options include surgery, which is usually followed by chemotherapy in advanced CRC. With treatment, cancer cells could become resistant to classical cytostatic drugs such as 5-fluorouracil (5-FU), oxaliplatin, cisplatin, and irinotecan, resulting in chemotherapeutic failure. For this reason, there is a high demand for health-preserving re-sensitization mechanisms including the complementary use of natural plant compounds. Calebin A and curcumin, two polyphenolic turmeric ingredients derived from the Asian Curcuma longa plant, demonstrate versatile anti-inflammatory and cancer-reducing abilities, including CRC-combating capacity. After an insight into their epigenetics-modifying holistic health-promoting effects, this review compares functional anti-CRC mechanisms of multi-targeting turmeric-derived compounds with mono-target classical chemotherapeutic agents. Furthermore, the reversal of resistance to chemotherapeutic drugs was presented by focusing on calebin A's and curcumin's capabilities to chemosensitize or re-sensitize CRC cells to 5-FU, oxaliplatin, cisplatin, and irinotecan. Both polyphenols enhance the receptiveness of CRC cells to standard cytostatic drugs converting them from chemoresistant into non-chemoresistant CRC cells by modulating inflammation, proliferation, cell cycle, cancer stem cells, and apoptotic signaling. Therefore, calebin A and curcumin can be tested for their ability to overcome cancer chemoresistance in preclinical and clinical trials. The future perspective of involving turmeric-ingredients curcumin or calebin A as an additive treatment to chemotherapy for patients with advanced metastasized CRC is explained.

The Juggernaut of Adaptive Metabolism in Cancers: Implications and Therapeutic Targets.

The disease of cancer instills a sense of fear and dread among patients and the next of kin who are indirectly affected by the deteriorating quality of life of their loved ones [...].

Tirzepatide-Friend or Foe in Diabetic Cancer Patients?

It is a well-accepted fact that obesity and diabetes increase the risk of incidence of different cancers and their progression, leading to a decrease in the quality of life among affected cancer patients. In addition to decreasing the risk of cancers, maintaining a healthy body mass index (BMI)/body weight and/or blood glucose levels within the normal range critically impacts the response to anti-cancer therapy among affected individuals. A cancer patient managing their body weight and maintaining blood glucose control responds better to anti-cancer therapy than obese individuals and those whose blood glucose levels remain higher than normal during therapeutic intervention. In some cases, anti-diabetic/glucose-lowering drugs, some of which are also used to promote weight loss, were found to possess anti-cancer potential themselves and/or support anti-cancer therapy when used to treat such patients. On the other hand, certain glucose-lowering drugs promoted the cancer phenotype and risked cancer progression when used for treatment. Tirzepatide (TRZD), the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) agonist, has recently gained interest as a promising injectable drug for the treatment of type 2 diabetes and was approved by the FDA after successful clinical trials (SURPASS 1/2/3/4 and 5, NCT03954834, NCT03987919, NCT03882970, NCT03730662, and NCT04039503). In addition, the reports from the SURMOUNT-1 clinical trial (NCT04184622) support the use of TRZD as an anti-obesity drug. In the current review article, we examine the possibility and molecular mechanisms of how TRZD intervention could benefit cancer therapeutics or increase the risk of cancer progression when used as an anti-diabetic drug in diabetic patients.

Antithrombotic and antiplatelet effects of plant-derived compounds: a great utility potential for primary, secondary, and tertiary care in the framework of 3P medicine.

Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both - the central and peripheral veins. Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet effects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.

COVID-19 Vaccines and Hyperglycemia-Is There a Need for Postvaccination Surveillance?

The COVID-19 vaccines currently in use have undoubtedly played the most significant role in combating the SARS-CoV-2 virus and reducing disease severity and the risk of death among those affected, especially among those with pre-existing conditions, such as diabetes. The management of blood glucose levels has become critical in the context of the COVID-19 pandemic, where data show two- to threefold higher intensive care hospital admissions and more than twice the mortality rate among diabetic COVID-19 patients when compared with their nondiabetic counterparts. Furthermore, new-onset diabetes and severe hyperglycemia-related complications, such as hyperosmolar hyperglycemic syndrome (HHS) and diabetic ketoacidosis (DKA), were reported in COVID-19 patients. However, irrespective of the kind of vaccine and dosage number, possible vaccination-induced hyperglycemia and associated complications were reported among vaccinated individuals. The current article summarizes the available case reports on COVID-19 vaccination-induced hyperglycemia, the possible molecular mechanism responsible for this phenomenon, and the outstanding questions that need to be addressed and discusses the need to identify at-risk individuals and promote postvaccination monitoring/surveillance among at-risk individuals.

Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person.

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

Treating Cancers Using Nature's Medicine: Significance and Challenges.

There was a time when plant-derived natural formulations were the cornerstone of ancient therapeutic approaches for treating many illnesses [...].

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects.

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing.

Coronavirus Disease 2019 (COVID-19), caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on March 11, 2020. Soon after its emergence in late December 2019, it was noticed that diabetic individuals were at an increased risk of COVID-19-associated complications, ICU admissions, and mortality. Maintaining proper blood glucose levels using insulin and/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19. Interestingly, in diabetic COVID-19 patients, while insulin administration was associated with adverse outcomes, Metformin treatment was correlated with a significant reduction in disease severity and mortality rates among affected individuals. Metformin was extensively studied for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral capabilities that would explain its ability to confer cardiopulmonary and vascular protection in COVID-19. Here, we describe the various possible molecular mechanisms that contribute to Metformin therapy's beneficial effects and lay out the scientific basis of repurposing Metformin for use in COVID-19 patients.

Flavonoids against the SARS-CoV-2 induced inflammatory storm.

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.

Therapeutic Potential of Metformin in COVID-19: Reasoning for Its Protective Role.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections present with increased disease severity and poor clinical outcomes in diabetic patients compared with their nondiabetic counterparts. Diabetes/hyperglycemia-triggered endothelial dysfunction and hyperactive inflammatory and immune responses are correlated to twofold to threefold higher intensive care hospitalizations and more than twice the mortality among diabetic coronavirus disease 2019 (COVID-19) patients. While comorbidities such as obesity, cardiovascular disease, and hypertension worsen the prognosis of diabetic COVID-19 patients, COVID-19 infections are also associated with new-onset diabetes, severe metabolic complications, and increased thrombotic events in the backdrop of aberrant endothelial function. While several antidiabetic medications are used to manage blood glucose levels, we discuss the multifaceted ability of metformin to control blood glucose levels and possibly attenuate endothelial dysfunction, inhibit viral entry and infection, and modify inflammatory and immune responses during SARS-CoV-2 infections. These actions make metformin a viable candidate drug to be considered for repurposing and gaining ground against the SARS-CoV-2-induced tsunami in diabetic COVID-19 patients.