Possible cytoprotective mechanisms of oxytocin against 5-fluorouracil-induced gastrointestinal mucositis.

Gastrointestinal mucositis is a common and dose-limiting side effect characterized by ulcerative lesions in the mucosa of the digestive tract in patients receiving anticancer drugs such as 5-fluorouracil (5-FU), a potent antineoplastic drug. Several protocols have reported the efficacy of therapeutic interventions to prevent this side effect, although complete success has not yet been achieved and mucositis remains one of the most serious complications associated with 5-FU therapy. Oxytocin, a well-known antistress agent, has been reported to have comparable effects to ranitidine. Previous studies have shown that oxytocin inhibits gastric acid secretion and the expression of proinflammatory cytokines in rats. If oxytocin can reduce stress-induced ulcers via antioxidant, antiapoptotic, and anti-inflammatory pathways, then it may have a dose-dependent effect on gastrointestinal mucositis caused by 5-FU.

Role of Melatonin in Angiotensin and Aging.

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.

The circadian clock gene Bmal1: Role in COVID-19 and periodontitis.

The physiological processes of most living organisms follow a rhythmic pattern, which is controlled by the interaction between environmental cues and the internal circadian timing system. Different regulatory circadian genes are expressed in most cells and tissues, and disruptions in the sleep-wake cycle affect these genes, which may result in metabolic disorders and cause alterations of the immune system. The manifestations of these disrupted genes are evident in inflammatory conditions such as periodontitis and some viral diseases, including COVID-19. The brain and muscle ARNT-like protein-1 (Bmal1), an important circadian regulatory gene, decreases when the sleep-wake cycle is disrupted. Circadian genes have been linked to different events, including cytokine storm in inflammatory conditions and virus invasion. The evaluation of the effects of these regulatory circadian genes, especially Bmal1, in periodontitis and viral infection suggests that both diseases may have a common pathogenesis via the NF-κB pathway. This brief review highlights the role and importance of the circadian clock gene Bmal1 in the disease process of periodontitis and suggests its role and importance in viral infections, including COVID-19.

COVID-19-related arrhythmias and the possible effects of ranolazine.

The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection. Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias, apart from ranolazine; however, some of these drugs are administered with caution because of their significant side effects. In this study, we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19. Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris. Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body's hemodynamics; hence, blood pressure is not altered. Due to its reduced side effects, ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias, since it produces its antiarrhythmic effect by modulating sodium, potassium and calcium channels, and suppressing cytokine expression.

Acute kidney injury due to COVID-19 and the circadian rhythm.

The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) affects several organs including the kidneys. When examining patients with acute kidney injury (AKI) due to COVID-19, it is important to consider the circadian rhythm because in addition to its biological clock function, disruption of the circadian rhythm has been reported to be associated with the pathogenesis of several disorders, including AKI. Angiotensin-converting enzyme 2 (ACE2), an important component of the renin-angiotensin-aldosterone system (RAAS), displays circadian rhythmicity. Studies have shown that over-expression of human ACE2 increases the replication of SARS-CoV-2, which may lead to disruptions and tissue damage due to the suppression of the brain and muscle ARNT-like protein-1(Bmal1) gene and high pro-inflammatory cytokines expressions in the tissues. Therefore, understanding and regulating the circadian rhythm and expression pattern of the key components of RAAS can prevent or reduce the severity of acute kidney injury that may occur with COVID-19 infection.