An in silico investigation: Can melatonin serve as an adjuvant in NR1D1-linked chronotherapy for amyotrophic lateral sclerosis?

Chronobiology, which studies biological rhythms and their impacts on health, presents a potential avenue for treating amyotrophic lateral sclerosis. Clock gene-related therapies, focusing on genes responsible for regulating biological rhythms, may hold promise in the treatment. Among these clock genes, nuclear receptor subfamily 1 Group D member 1 (NR1D1) plays a vital role in neurodegenerative diseases. In this particular study, it was aimed to investigate the potential of FDA-approved drugs commonly used in amyotrophic lateral sclerosis treatment and melatonin, a hormone known for its role in regulating sleep-wake cycles, as ligands for clock gene-related therapy. The ligands were subjected to molecular docking and molecular dynamics simulation methods against the NR1D1 clock gene. These results suggested that combining melatonin with FDA-approved medications commonly used in the treatment might yield positive outcomes. This study provides preliminary data and lays the groundwork for future investigations involving in vitro (laboratory-based) and in vivo (animal or human-based) research on chronotherapy. In summary, this research highlights the potential of clock gene-related therapy utilizing melatonin in conjunction with FDA-approved drugs for amyotrophic lateral sclerosis treatment, offering insights into novel treatment strategies. The findings underscore the need for further studies to explore the effectiveness of this hypothetical approach in experimental and clinical settings.

Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.

Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.

Comparing acute effects of extra virgin coconut oil and extra virgin olive oil consumption on appetite and food intake in normal-weight and obese male subjects.

OBJECTIVES: The aim of this study is to compare acute effects of consuming extra virgin coconut oil (EVCO) as a source of medium chain fatty acids and extra virgin olive oil (EVOO) as a source of long chain fatty acids in normal weight and obese subjects. DESIGN: Randomised, crossover design. PARTICIPANTS: Metabolically healthy twenty male subjects (10 normal weight; 10 obese) aged 19-40 years. INTERVENTION: Subjects consumed breakfast meals containing skimmed milk, fat-free white cheese, bread and EVCO (25 g) or EVOO (25 g). OUTCOME MEASURES: Visual analog scale evaluations, resting metabolic rate measurements and selected blood parameters analysis (glucose, triglyceride, insulin and plasma peptide YY) were performed before and after the test breakfast meals. In addition, energy intakes were evaluated by ad libitum lunch meal at 180 min. RESULTS: Visual analogue scale values of hunger and desire to eat decreased significantly after EVCO consumption than EVOO consumption in normal weight subjects at 180 min. There was an increase trend in plasma PYY at 30 and 180 min after EVCO breakfast compared to EVOO breakfast. Ad libitum energy intakes after EVCO and EVOO consumption in normal weight subjects were 924 ± 302; 845 ± 158 kcal (p = 0.272), respectively whereas in obese subjects were 859 ± 238; 994 ± 265 kcal (p = 0.069) respectively. CONCLUSION: The results of this study shows that consumption of EVCO compared to EVOO may have suppressive effect on hunger and desire to eat, may affect postprandial PYY levels differently and have no effect on postprandial energy expenditure. TRIAL REGISTRATION: Clinical Trials NCT04738929.

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.

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.

Inhibitory effect of hawthorn extract on heterocyclic aromatic amine formation in beef and chicken breast meat.

This study focused on the inhibitory effect of different levels of hawthorn extract (0, 0.5, and 1%) on the formation of heterocyclic aromatic amines (HAAs) in beef and chicken breast cooked by either pan-cooking or oven-cooking. All meat samples were cooked at three different temperatures (150, 200, and 250°C) and the levels of twelve HAAs were assessed (IQ, IQx, MeIQ, MeIQx, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, harman, norharman, AαC, MeAαC, and Trp-P-2). Varying levels of IQ (up to 4.47ng/g), IQx (up to 0.69ng/g), MeIQ (up to 0.82ng/g), MeIQx (up to 1.01ng/g), 4,8-DiMeIQx (up to 0.10ng/g), 7,8-DiMeIQx (up to 0.23ng/g), PhIP (up to 0.75ng/g), harman (up to 2.15ng/g), norharman (up to 1.08ng/g), AαC (up to 1.86ng/g), MeAαC (up to 0.48ng/g), and Trp-P-2 (up to 12.88ng/g), were detected. Samples cooked at 150°C had very low amounts of HAAs, and the levels of HAAs increased gradually when the cooking temperature rose from 150 to 250°C. The total HAA content in chicken breast and beef ranged between not detectable to 17.60ng/g, and not detectable to 11.38ng/g, respectively. The inhibitory effects of hawthorn extract at 0.5% and 1% on total HAAs levels were found to be 12-100% and 19-97% in chicken breast, respectively, and 42-100% and 20-35% in beef, respectively. This study demonstrated that hawthorn extracts at 0.5% and 1% could mitigate HAA formation, especially at high cooking temperatures.

Reducing effect of artichoke extract on heterocyclic aromatic amine formation in beef and chicken breast meat.

The aim of this study was to investigate the inhibitory effect of different levels of artichoke extract (0, 0.5, and 1.0%) on the formation of heterocyclic aromatic amines (HAAs) in beef and chicken breast meat cooked by either pan-frying or oven-roasting. All meat samples were cooked at three different temperatures (150, 200, and 250°C) and the levels of 12 HAAs (IQ, IQx, MeIQ, MeIQx, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, harman, norharman, AαC, MeAαC, and Trp-P-2) were assessed. The total HAA content in beef and chicken breast ranged from not detectable to 49.26ng/g, and not detectable to 83.06ng/g, respectively. The inhibitory effects of 0.5 and 1.0% artichoke extracts on total HAAs levels were found to be 6-46% and 25-98% in beef, and 5-97% and 14-95% in chicken breast, respectively. The present study showed that artichoke extracts could mitigate HAA formation especially in oven-roasted beef and chicken breast meat.