Zinc Supplementation Enhances the Pro-Death Function of UPR in Lymphoma Cells Exposed to Radiation

We have previously shown that Zinc supplementation triggered ER stress/UPR in cancer cells undergoing treatment by genotoxic agents, reactivated wtp53 in cancer cells harboring mutant p53 (mutp53) and potentiated the activity of wtp53 in those carrying wtp53. In this study, we used Zinc chloride alone or in combination with 2 Gy radiation to treat Primary Effusion Lymphoma (PEL) cells, an aggressive B-cell lymphoma associated with KSHV that harbors wt or partially functioning p53. We found that Zinc triggered a mild ER stress/UPR in these lymphoma cells and activated ERK1/2, molecule known to sustain cell survival in the course of UPR activation. In combination with radiations, Zinc triggered a stronger p53 activation that counteracted its mediated ERK1/2 phosphorylation, further upregulating the UPR molecule CHOP and promoting cell death. These data suggest that Zinc supplementation could be a promising strategy to reduce the doses of radiation and possibly of other DNA-damaging agents to obtain an efficient capacity to induce lymphoma cell death.

Zinc Homeostasis in Diabetes Mellitus and Vascular Complications

Oxidative stress represents an impaired metabolic system that promotes damage to cells and tissues. This is the predominant factor that leads to the development and progression of diabetes and diabetic complications. Research has indicated that zinc plays a consequential mechanistic role in the protection against oxidative stress as zinc is required for the proper functioning of the antioxidant system, the suppression of inflammatory mediators, and the modulation of zinc transporters. Recently, the mechanisms surrounding ZnT8, ZIP7, and metallothionein have shown to be of particular pathogenic importance and are considered as potential therapeutic targets in disease management. The literature has shown that zinc dysregulation is associated with diabetes and may be considered as a leading contributor to the deleterious vascular alterations exhibited by the disease. Although further investigation is required, studies have indicated the favorable use of zinc supplementation in the protection against and prevention of oxidative stress and its consequences over the course of the condition. This review aims to provide a comprehensive account of zinc homeostasis, the oxidative mechanisms governed by zinc status, current therapeutic targets, and the impact of zinc supplementation in the prevention of disease onset and in mitigating vascular complications.

A Randomized Clinical Trial of the Effect of Zinc Supplement on Depression and Anxiety in the Elderly

Background: Anxiety and depression in the elderly are considered important mental disorders. Objective: This study was designed to determine the effect of zinc Supplementation on depression and anxiety in the elderly. Methods: This study was a parallel randomized clinical trial. A total of 150 elderly aged 60 years and older were allocated into intervention and control groups by using the quadruple blocking method. The elderly in the intervention group received a daily dose of 30 mg zinc supplementation pill for 70 days and the elderly in the control group did not receive this supplement. Depression and anxiety in the elderly were measured using the Geriatric Depression Scale and the Beck Anxiety Inventory, respectively. A significance level of 0.05 was considered for all statistical tests. Results: After the intervention, the mean scores of depression and anxiety in the elderly were significantly decreased in the intervention group, as compared with the control group. Moreover, after the intervention, the serum zinc level in the elderly was significantly increased in the intervention group, as compared with the control group (P<0.05). Conclusion: The use of zinc supplements improved depression and anxiety in the elderly. Therefore, it is recommended to use zinc supplements as a new therapeutic strategy for the prevention and treatment of depression and anxiety in the elderly. Registration No: This research was registered in the Iranian clinical trial system with code IRCT2017071635110N1.

A Case-Control Study for the Effectiveness of Oral Zinc in the Prevention and Mitigation of COVID-19

Background: The ongoing coronavirus disease-19 (COVID-19) pandemic (caused by an infection with severe acute respiratory syndrome (SARS)-coronavirus (CoV-2) has put a burden on the medical community and society at large. Efforts to reduce the disease burden and mortality over the course of the pandemic have focused on research to rapidly determine age-stratified seroepidemiologic surveys, a centralized research program to fast-track the most promising rapid diagnostics and serologic assays, and the testing of potential anti-viral agents, immunologic therapies, and vaccine candidates. Despite the lack of official recognition for the role of nutrition in the fight against COVID-19 infection, multiple groups proposed zinc supplementation as an adjuvant for the management of participants.Method: In an ambulatory, interventional, prospective, single-blind study, we evaluated the effectiveness of zinc supplementation in the prevention and mitigation of COVID-19 in two similar participant groups. In Clinic A (n = 104) participants were randomized to receive 10 mg, 25 mg, or 50 mg zinc picolinate daily, and Clinic B control participants paired according to their demographics and clinical parameters (n = 96). All participants were compared based on demographics, clinical comorbidities, blood counts, renal functions, vitamin D levels, and their development of symptomatic COVID-19 infection.Results: Symptomatic COVID-19 infection was significantly higher among the control group participants (N = 9, 10.4%) than the treatment participants (N = 2, 1.9%), p = 0.015. The unadjusted odds ratio indicates that symptomatic COVID-19 infection was 5.93 [95% CI: 1.51, 39.26] higher in the control group, p &lt; 0.01. Controlling for co-morbidities, individuals in the control group were 7.38 (95% CI: 1.80, 50.28) times more likely to develop symptomatic COVID-19 infection as compared with individuals in the treatment group (p &lt; 0.01). For every-one unit increase in the number of co-morbidities, the likelihood of developing symptomatic COVID-19 infection increased 1.57 (95% CI: 1.16, 2.19) (p = 0.01).Discussion: The findings from our study suggest that zinc supplementation in all three doses (10, 25, and 50 mg) may be an effective prophylaxis of symptomatic COVID-19 and may mitigate the severity of COVID-19 infection.Conclusion: Zinc is a relatively inexpensive mineral nutrient that is an effective prophylactic agent to prevent and mitigate the potentially deadly symptomatic SARS-CoV-2 infection. As the COVID-19 pandemic continues with a lag in vaccinations in some regions and the continued emergence of dangerously infectious variants of SARS-CoV-2, it is important to replicate our data in other populations and locations and to engage public health and nutrition services on the emergent need to use zinc supplantation or fortification of staple foods in the prevention and mitigation of COVID-19 infection severity.

Role of Oral Zinc Supplementation in treatment of Acute Dehydrating Diarrhea in age 6 months to 5 years

Background: Oral Rehydration Salt (ORS) is the standard recommended treatment for acute dehydrating diarrhea but it has very little role in decreasing stool frequency and volume. Current studies recommend oral supplementation of zinc as an adjunct to ORS in treating acute dehydrating diarrhea of children especially those who are at risk of zinc deficiency and malnutrition. Aim: To determine the effect of oral zinc supplementation on duration of acute diarrhea and intake of ORS in children between 6 months and 5 years of age. Settings: Tehsil Head Quarters Hospital, Besham District Shangla, Khyber Pakhtunkhwa from October 2019 to September 2020. Methodology: The study was double blinded Randomized Control Clinical Trial in children aged between 6 months to 5 years of age. A total of 90 children were included in the study. In addition to rehydration, 45 children were given oral zinc (20mg daily) while 45 children were given placebo. Results: All 45(100%) patients in zinc group and 39(86.6%) patients in placebo group recovered after 5 days of treatment. Zinc group had significantly reduced duration of diarrhea (68.3±9.4 vs. 99.8±15.2 hours) and consumed less ORS solution (2.3±0.8 vs. 3.4±1.1 liters) as compared to placebo group. Conclusion: It is concluded from this study that oral zinc supplementation in addition to ORS in treating acute dehydrating diarrhea of children has better effect on the clinical course of disease. Key words: Diarrhea, ORS, Zinc, Dehydration.