A comprehensive insight into the molecular and cellular mechanisms of action of resveratrol on complications of sepsis a systematic review.

Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

The effects of selenium supplementation on inflammatory markers in critically ill patients.

Abstract: Low serum selenium (Se) levels have been shown in critical illness, which is associated with poor clinical outcomes and a higher mortality rate. Se plays an important role in inflammation and oxidative stress. Since the overproduction of inflammatory cytokines and increased oxidative stress is a major component of critical illnesses, its supplementation has been demonstrated to have promising effects on critically ill patients. This study aims to review the evidence regarding the effects of Se supplementation on inflammatory and oxidative markers in critically ill patients. The literature review highlights alterations of inflammatory markers, including procalcitonin, leukocyte count, albumin, prealbumin, C-reactive protein (CRP), inflammatory cytokines, and cholesterol following Se supplementation in critically ill patients. Besides, the antioxidant properties of Se due to its presence in the structure of several selenoenzymes have been reported. Article highlights: Low serum Se level have been shown in critical illness, which is associated with poor clinical outcome and higher mortality rate.Se plays an important role in inflammation and oxidative stress.Se supplementation can have promising effects by alterations of inflammatory markers and its antioxidant properties for critically ill patients.

Effects of saffron (Crocus sativus L.) on anthropometric and cardiometabolic indices in overweight and obese patients: A systematic review and meta-analysis of randomized controlled trials.

The worldwide prevalence of obesity is approximately tripled between 1975 and 2016 according to World Health Organization; therefore, obesity is now considered a global pandemic that needs academic and clinical focus. In search of antiobesity agents, Crocus sativus, known widely as saffron, has been praised for its beneficial effects. Several randomized controlled trials (RCTs) have been conducted to investigate the weight lowering effect of saffron. Following PRISMA guidelines, several medical databases were comprehensively searched for RCTs with a population consisting of obese individuals. A random-effects meta-analysis was used to pool estimates across studies, and standardized mean difference (SMD) was used to synthesize quantitative results. Twenty-five RCTs met the inclusion criteria. Meta-analysis showed a nonsignificant decrease for weight (-0.32 kg; CI: -3.15, 2.51; p = 0.82), BMI (-0.06 kg/m2 ;CI:-1.04,0.93; p = .91), waist circumference (-1.23 cm; CI: -4.14, 1.68; p = .41), and hip circumference (-0.38 cm; CI: -5.99, 5.23; p = .89) and a significant decrease of waist-to-hip ratio (SMD = -0.41; CI: -0.73, -0.09; p = .01; I2  = 0%). The mean difference in fasting blood sugar showed a significant reduction in patients with metabolic syndrome (SMD = -0.30; 95% CI: -0.63, 0.03; p = .07; I2  = 0.37%) but a nonsignificant change in the HbA1C level (WMD = 0.05; 95% CI: 0.32, 0.41; p = .79). Despite bearing several limitations, mainly as a result of heterogeneity among included studies, the available evidence indicates saffron supplementation shows promising effects on some cardiometabolic factors among overweight to obese patients; however, further investigations and high-quality evidence are required for more generalizable and comprehensive results.

Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status.

Sepsis is a severe reaction and excessive immune response to infection, which can lead to organ dysfunction, and death. This study aimed to investigate the protective effect of nano-curcumin (NC) on inflammatory biomarkers, endothelial function, oxidative stress indices, biochemical factors, nutritional status, and clinical outcomes in patients with sepsis. In the present double-blind placebo-controlled randomized clinical trial, 40 ICU-admitted patients were randomly allocated into either NC or placebo group for 10 days. Both nano-curcumin (160 mg) and placebo were administered via a nasogastric tube twice a day. The mRNA expression of nuclear-related factor 2 (Nrf-2), BCL2 associated X (BAX), B-cell lymphoma 2 (BCL-2), and toll-like receptor 4 (TLR-4) genes in the peripheral blood mononuclear cells (PBMCs), and the serum levels of primary, secondary, tertiary, and exploratory outcomes were assessed before the baseline and on days 5 and 10. There were significant improvements in the primary outcomes, including inflammatory markers (IL-6, IL-18, IL-1ß, IL-10, TLR-4, BCL-2 and BAX), markers of endothelial function (ICAM-1 and VCAM-1), and oxidative stress indices (malondialdehyde (MDA), nuclear-related factor 2 (Nrf-2), catalase, superoxide dismutase (SOD), and TAC) (p < 0.005) in the NC group compared to the placebo group after 10 days, while no significant increase was observed in the glutathione peroxidase (GPx) level between the two groups. However, no significant decrease was observed in the levels of secondary outcomes, including biochemical factors (creatinine, fasting blood sugar (FBS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, triglycerides (TG) and total cholesterol (TC)) (P > 0.05). Our results showed that in the tertiary outcome (nutritional status), there was no significant increase (P > 0.05) except for TLC (P = 0.003). NC supplementation also resulted in a significant decrease in the exploratory outcomes including the SOFA score and the duration of mechanical ventilation (P < 0.05). Supplementation with NC may be a promising treatment strategy for critically ill patients with sepsis. However, further experiments are suggested to investigate the effects of nano-curcumin on biochemical pathways involved in sepsis.

Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial.

Sepsis is the final common pathway to death for severe infectious diseases worldwide. The present trial aimed to investigate the effects of nano-curcumin supplementation on hematological indices in critically ill patients with sepsis. Fourteen ICU-admitted patients were randomly allocated into either nano-curcumin or placebo group for 10 days. The blood indices, serum levels of inflammatory biomarker and presepsin as well as nutrition status, and clinical outcomes were assessed before the intervention and on days 5 and 10. White blood cells, neutrophils, platelets, erythrocyte sedimentation rate (ESR), and the levels of interleukin-8 significantly decreased in the nano-curcumin group compared to the placebo after 10 days of intervention (p = .024, p = .045, p = .017, p = .041, and p = .004, respectively). There was also a marginal meaningful decrease in serum presepsin levels in the intervention group compared to the placebo at the end of the study (p = .054). However, total lymphocyte count showed a significant increase in the nano-curcumin group compared to the placebo at the end-point (p = .04). No significant differences were found in the level of lymphocyte and the ratios of neutrophil/lymphocyte and platelet/lymphocyte between the study groups. Moreover, no significant between-group differences were observed for other study outcomes, post-intervention. Collectively, nano-curcumin may be a useful adjuvant therapy in critically ill patients with sepsis. However, further trials are suggested to examine the effects of nano-curcumin in the management of sepsis and its complications. PRACTICAL APPLICATIONS: Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5- dione) or diferuloylmethane is widely used in medicine due to its several biological properties. Recent evidence has shown that curcumin possesses multiple pharmacological activities including immune-modulatory, antioxidant, anti-inflammatory, anti-cancer, and anti-microbial effects. In this study, it was observed that nano-curcumin at a dose of 160 mg for 10 days, without side effects, reduced some inflammatory factors and regulated the immune responses in sepsis patients. For the first time, this trial was conducted to determine the effect of nano-curcumin on hematological indices and the serum levels of presepsin and IL-8.

Effects of probiotic supplementation on cognitive function in elderly: A systematic review and Meta-analysis.

OBJECTIVES: Probiotic supplementation has been linked to changes in cognitive function via the gut-brain axis (GBA). However, the current literature lacks a comprehensive review regarding this matter in the elderly population. METHOD: Electronic databases including Medline (PubMed), Scopus, Embase, Web of Science, and Google Scholar were comprehensively searched for identifying studies that assessed the effects of probiotics on the cognitive function of the elderly published until July 2020. Articles were critically reviewed and if met the inclusion criteria, entered the study. RESULTS: Among a total of 1374 studies, 10 were eligible for meta-analysis. No significant alteration was found in the cognition of the elderly (SMD=-0.04; 95% CI [- 1.07,0.98]; P = 0.93). There was a nonsignificant increase in the level of brain-derived neurotrophic factor (SMD = 0.58; 95% CI [-1.40,2.56]; P = 0.56) and a nonsignificant reduction in malondialdehyde levels (SMD=-0.44; 95% CI [-1.07,0.19]; P = 0.17). Levels of total antioxidant capacity (SMD = 39.93; 95% CI [2.92,76.95]; P = 0.03) and total glutathione (SMD = 61.51; 95% CI [12.39,110.62]; P = 0.01) significantly increased. A significant reduction was also noted in total cholesterol levels (SMD=-4.23; 95% CI [-8.32, -0.14]; P = 0.04). CONCLUSION: Our study did not support the hypothesis of the positive effect of probiotics on cognitive function in the elderly population; which might be due to the heterogeneity across the studies.

Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: a preliminary study.

BACKGROUND: Critically ill patients frequently suffer from vitamin C deficiency. Previous studies showed that high doses of vitamin C administration had conflicting results on clinical outcomes in patients with severe sepsis, burns, and trauma. Because of the high incidence and morbidity/mortality with severe pneumonia, we aimed to investigate the effect of administration of high dose vitamin C in critically ill patients with severe pneumonia. METHODS: Eighty critically ill patients with pneumonia were enrolled in this randomized double-blinded clinical trial. Patients with a CURB-65 score > 3, one major criterion, or ≥ 3 minor criteria were considered as severe pneumonia. Patients were randomly assigned to intervention or placebo groups receiving standard treatment plus 60 mg/kg/day vitamin C as a continuous infusion or normal saline in the same volume correspondingly for 96 h. Serum levels of vitamin C were noted at baseline and 48 h after vitamin C administration. Duration of mechanical ventilation, ICU length of stay, PaO2/FiO2, and mortality rate were noted for all patients till the 28th day. Any complications related to the vitamin C administration were recorded. RESULTS: Duration of mechanical ventilation and vasopressor use were significantly lower in the intervention group (p: < 0.001 and 0.003, respectively). Baseline levels of vitamin C in both groups did not have a significant difference but its levels increased in the intervention group and decreased in the control group during the study period. Mortality rate insignificantly decreased in the intervention group (p = 0.17). Three patients showed hypotension and tachycardia during the administration of vitamin C which was self-limited with decreasing the dose of vitamin C. Our results showed that the intravenous administration of a relatively high dose of vitamin C to critically ill patients with severe pneumonia was safe and could decrease the inflammation, duration of mechanical ventilation, and vasopressor use without any significant effect on mortality. TRIAL REGISTRATION: IRCT registration number: IRCT20190312043030N1, Registration date: 2019-08-26, Seied Hadi Saghaleini.

Daily parenteral selenium therapy in critically ill patients: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Patients hospitalized at the intensive care unit (ICU) are more prone to oxidative stress. Antioxidants such as selenium (Se) may have beneficial effects on outcomes in these patients. Studies and systematic reviews in this field have inconclusive results. METHODS: An updated systematic search was done to find clinical trials published in PubMed, Cochrane's library, ISI web of Science, Scopus, and Ovid databases from January 1980 up to April 2020, to assess the effects of daily Se supplementation on patient's survival, hospital and ICU stay, duration of mechanical ventilation, infection, acute renal failure (ARF) occurrence and serum creatinine levels. RESULTS: From 1394 papers found in the first step of the search, after deleting duplicate findings, 24 studies were included in this meta-analysis. Results of the pooled random-effect size analysis of 24 trials showed no remarkable effect of daily parenteral Se administration on patient's hospital and ICU stay, duration of mechanical ventilation, infectious complications, ARF, survival and serum creatinine levels (p > 0.05). The subgroup analysis showed that daily parenteral Se administration (in doses higher than 1000 µg/d) increased the length of ICU stay by 4.48-folds (95%CI: -0.5, 9.46, p = 0.07). Parenteral Se supplementation at the first and following dose of ≤1000 µg reduced the number of ARF at the hospitalized patients by 76% and 45%, respectively (p = 0.02, and p = 0.05). CONCLUSIONS: High doses of Se increases days of ICU stay, but low doses decreases the number of ARF occurrence in ICU patients. More trials are needed to assess its effect on ARF occurrence.

Copper as a potential adjunct therapy for critically ill COVID-19 patients.

COVID-19 is a major health problem affecting all people worldwide and has a high mortality rate especially in critically ill patients. Although much is known about its different clinical symptoms, there are significant knowledge gaps about its pathology and cellular responses to the virus. Copper plays an essential role in respiration, immune function and free-radical defense. Despite its important action in physiochemical properties, only small amount of copper is presented in biological fluid, none of which presents as free ion form that readily affirms its depletion in critically ill patients. Recent studies confirmed its anti-viral capacity. Closer understanding of copper signaling, its vulnerability, method of assessment and interpretation, administration rout and dosage opens up new perspectives regarding therapeutic copper administration against critically ill COVID-19 patients. So, it seems that physicians should consider copper insufficiency in their critically ill COVID-19 patients. However, an attention should be paid to copper toxicity and estimating the adverse responses depending on copper dose or severity of copper limitation, as well as the duration of copper misbalance.

Stabilization of telomere by the antioxidant property of polyphenols: Anti-aging potential.

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.

The Effect of Intravenous Selenium on Oxidative Stress in Critically Ill Patients with Acute Respiratory Distress Syndrome.

OBJECTIVE: To modulate the inflammatory response in respiratory distress syndrome (ARDS) with selenium. BACKGROUND: Selenium replenishes the glutathione peroxidase proteins that are the first line of defense for an oxidative injury to the lungs. METHODS: Forty patients with ARDS were randomized into two groups: the SEL+ group being administered sodium selenite and the SEL- group receiving normal saline for 10 days. Blood samples were taken on Day-0, DAY-7, and Day-14 for assessment of IL-1 beta, IL-6, C-reactive protein, GPx-3, and selenium. Ferric reducing antioxidant power (FRAP) was measured in the bronchial wash fluids. Pearson correlation and repeated measure analysis were performed to examine the effects of selenium on the inflammatory markers. RESULTS: Sodium selenite replenished selenium levels in the SEL+ group. Selenium concentrations were linearly correlated to serum concentrations of GPx3 (R value: 0.631; P < 0.001), and FRAP (R value: -0.785; P < 0.001). Serum concentrations of both IL 1-beta (R value: -0.624; P < 0.001) and IL-6 (R value: -0.642; P < 0.001) were inversely correlated to the serum concentrations of selenium. There was a meaningful difference between two groups in airway resistance and pulmonary compliance changes (P values 0.008 and 0.028, respectively). CONCLUSION: Selenium restored the antioxidant capacity of the lungs, moderated the inflammatory responses, and meaningfully improved the respiratory mechanics. Despite these changes, it had no effect on the overall survival, the duration of mechanical ventilation, and ICU stay. Selenium can be used safely; however, more trials are essential to examine its clinical effectiveness.

Antioxidant reserve of the lungs and ventilator-associated pneumonia: A clinical trial of high dose selenium in critically ill patients.

PURPOSE: To evaluate the effect of supplemental selenium administration on the incidence of ventilator-associated pneumonia (VAP) in critically ill patients. METHODS: Ninety-nine mechanically ventilated patients were randomized to receive either selenium or isotonic saline infusion for 10days. The primary endpoint was serum glutathione peroxidase-3 (GPX-3) activity and secondary endpoints were development of VAP or death, ICU stay and vasopressor requirement. Serum concentrations of selenium and GPX-3 were measured on Day-1, Day-4 and Day-10. Chi Square and log-rank analyses were used for statistical analyses and odds ratios were calculated. RESULTS: Serum selenium and GPX-3 activity levels increased steadily in the treatment group within 10days (P<0.025), while they remained unchanged in the placebo group. The incidence of VAP was 19.4/1000days of mechanical ventilation in the placebo group while it was 15.8/1000 ventilated days in the treatment group (P=0.250). The risk of VAP or death was similar between the treatments and placebo groups. CONCLUSION: Despite increasing the antioxidant activity, selenium supplementation did not affect the incidence of VAP in critically ill patients. The risk of developing VAP or death within 30days of ICU admission remained the same in the treatment and the controls.

Vitamins, Are They Safe?

The consumption of a daily multivitamin among people all over the world is dramatically increasing in recent years. Most of the people believe that if vitamins are not effective, at least they are safe. However, the long term health consequences of vitamins consumption are unknown. This study aimed to assess the side effects and possible harmful and detrimental properties of vitamins and to discuss whether vitamins can be used as safe health products or dietary supplements. We performed a MEDLINE/PubMed, EMBASE, Scopus and Google Scholar search and assessed reference lists of the included studies which were published from 1993 through 2015. The studies, with an emphasis on RCTs (randomized controlled clinical trials), were reviewed. As some vitamins such as fat-soluble vitamins (vitamin A, vitamin D, vitamin E), and also some of the water-soluble vitamins like folic acid may cause adverse events and some like vitamin C is widely taken assuming that it has so many benefits and no harm, we included relevant studies with negative or undesired results regarding the effect of these vitamins on health. Our recommendation is that taking high-dose supplements of vitamins A, E, D, C, and folic acid is not always effective for prevention of disease, and it can even be harmful to the health.

Contributions of Medieval Islamic physicians to the history of tracheostomy.

Tracheostomy was first described by Greco-Roman physicians, including Paulus of Aegina. Medieval Islamic clinicians extended the Greco-Roman ideas with substantial contributions to the field of surgery, including tracheostomy. Although Al-Zahrawi (936-1013 CE) stated that he had not heard or read of any Islamic physicians having performed tracheostomy, there is evidence that many prominent Islamic surgeons did practice this lifesaving procedure during medieval times. Throughout the Islamic Golden Age, Muslim physicians advanced the practice of tracheostomy with many modifications of the procedure, instrumentation, and adjuvant medicinal prescriptions.