A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients.

BACKGROUND: This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19. METHODS: This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18-70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables. RESULTS: The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05). CONCLUSION: The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes. TRIAL REGISTRATION: This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).

Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

Effect of vitamin D supplementation on inflammatory markers and total antioxidant capacity in breast cancer women using a machine learning technique.

Aim: This study aimed to establish a learning system using an artificial neural network (ANN) to predict the effects of vitamin D supplementation on the serum levels of vitamin D, inflammatory factors, and total antioxidant capacity (TAC) in women with breast cancer. Methods: The data set of the current project was created from women with breast cancer who were referred to the Shafa State Hospital of Patients with Cancers in Ahvaz city, Iran. Modeling was implemented using the data set at the serum levels of vitamin D, tumor necrosis factor-α (TNF-α), transforming growth factor ß (TGF-ß), and TAC, before and after vitamin D3 supplement therapy. A prediction ANN model was designed to detect the effects of vitamin D3 supplementation on the serum level changes of vitamin D, inflammatory factors and TAC. Results: The results showed that the ANN model could predict the effect of vitamin D3 supplementation on the serum level changes of vitamin D, TNF-α, TGF-ß1, and TAC with an accuracy average of 85%, 40%, 89.5%, and 88.1%, respectively. Conclusions: According to the findings of the study, the ANN method could accurately predict the effect of vitamin D3 supplementation on the serum levels of vitamin D, TNF-α, TGF-ß1, and TAC. The results showed that the proposed ANN method can help specialists to improve the treatment process more confidently in terms of time and accuracy of predicting the influence of vitamin D supplementation on the factors affecting the progression of breast cancer (https://www.irct.ir/ identifier: IRCT2015090623924N1).

The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet. METHODS: This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit. DISCUSSION: New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20190303042905N2 . Registered on 31 January 2021.

The Effect of Memantine Versus Folic Acid on Cognitive Impairment in Patients with Schizophrenia: A Randomized Clinical Trial.

Objective: Schizophrenia, as one of the most severe psychiatric diseases, has a chronic and debilitating process. The majority of patients with schizophrenia do not respond adequately to treatment with common antipsychotic drugs. Therapeutic problems induced by drug side effects as well as undesired results are major challenging issues regarding this disease. This study aimed at evaluating the effect of memantine supplementation on the improvement of cognitive symptoms in patients with schizophrenia. Method : The present clinical trial was performed on 50 patients with acute schizophrenia who were admitted to Kargarnejad Psychiatric Hospital in Kashan in 2022 and who were diagnosed as schizophrenia cases at least three months ago. Patients were randomly divided into either the intervention group (n = 25) or the placebo group (n = 25). The intervention group received 5 mg of memantine per day for three months. The dose of memantine in this group was increased to the maximum of 20 mg per day. The placebo group received 1 mg of folic acid per day for three months. Moreover, an identical routine schizophrenia therapeutic regimen was administered to all patients. The effectiveness of memantine was evaluated using the Wechsler Adult Intelligence Scale (WAIS-III), which assessed cognitive ability in older adults over a 12-week follow-up period. Results: The WAIS-III score in the 12th week of the study was significantly different between the placebo and intervention groups (P = 0.004), such that the score of the memantine group was higher than that of the placebo group. No significant difference was observed between the two groups in terms of drug side effects. Conclusion: Memantine can be supplemented in the treatment of schizophrenia so as to improve the cognitive symptoms of this disorder. However, subsequent studies involving larger sample sizes and different doses seem to be necessary to provide more accurate results in this respect.

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis.

AIM: N-acetylcysteine (NAC), a thiol-containing antioxidant and glutathione (GSH) precursor, attenuates oxidative stress, and possibly improves psychiatric disorders. This study aimed to evaluate the effects of oral NAC on oxidative stress, depression, and anxiety symptoms in patients with multiple sclerosis (MS). METHODS: This clinical trial was conducted on 42 MS patients randomly assigned to intervention (n = 21) and control (n = 21) groups. The intervention group received 600 mg of NAC twice daily for 8 weeks, and the control group received a placebo with the same prescription form. An analysis of serum malondialdehyde (MDA), serum nitric oxide (NO), and erythrocyte GSH was carried out on both groups, along with a complete blood count. The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of depression (HADS-D) and anxiety (HADS-A). RESULTS: Compared to the control group, NAC consumption significantly decreased serum MDA concentrations (-0.33 [-5.85-2.50] vs. 2.75 [-0.25-5.22] µmol/L; p = 0.03) and HADS-A scores (-1.6 ± 2.67 vs. 0.33 ± 2.83; p = 0.02). No significant changes were observed in serum NO concentrations, erythrocyte GSH levels, and HADS-D scores (p > 0.05). CONCLUSIONS: Based on the findings of the present study, NAC supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in MS patients. The aforementioned results suggest that adjunctive therapy with NAC can be considered an effective strategy for MS management. Further randomized controlled studies are warranted.

Effects of chocolate on cognitive function in healthy adults: A systematic review and meta-analysis on clinical trials.

Cognitive function is defined as performance in objective tasks that need conscious mind effort. It has been shown that consuming foods rich in flavanols causes neurobiological effects and improves learning, memory, and global cognitive function. This study aimed to investigate the impact of chronic chocolate consumption on cognitive function in healthy adults based on published trials. The PICO strategy was applied to examine the research question in this study. Researchers searched the Web of Science, Science Direct, Pubmed, Scopus, Cochrane Library, and Google Scholar databases. Related articles of randomized controlled trials that evaluated the chronic effect of chocolate on cognitive function were selected (all published from their inception to February 2021). The difference in means of the last and first measurements was the main effect measure between the control and intervention groups. For quantitative data synthesis, weighted mean difference (WMD) and 95% confidence interval (CI) were performed in the random effect model. Of the initial 340 articles identified, seven trials met the eligibility criteria. Chronic chocolate intake significantly reduced executive function time (WMD: -11.77, 95% CI: -22.49, -1.05, p = 0.03) of the participants. Further, the language and executive function (WMD: 6.38, 95% CI: 5.97, 6.80, p < 0.001) was raised by 6.38 times after the intervention with chocolate. We could not perform subgroup analysis due to insufficient trials and significant heterogeneity in some studies. It is concluded that daily consumption of cocoa may provide short and middle-term effects on young adults and make them better cognitive performance in learning, memory, and attention.

Pomegranate extract supplementation improves lung function parameters and IL-35 expression in participants with mild and moderate persistent allergic asthma: A randomized, double-blind, placebo-controlled trial.

Existing asthma treatments are associated with side effects and limitations, which has led to an interest in alternative and complementary therapies. Given the anti-inflammatory properties of pomegranate, the present study aimed to determine the impact of pomegranate extract supplementation on lung function parameters evaluated through spirometry, high-sensitivity C-reactive protein (hs-CRP), pro-oxidant antioxidant balance, and interleukin 35) (IL-35) in participants with mild and moderate allergic asthma (based on forced expiratory volume in 1 second (FEV1) and clinical symptoms). Participants with mild and moderate allergic asthma (n = 64) were randomly assigned to two groups: the intervention group, which received two pomegranate extract capsules (500 mg/day), or the control group for eight weeks. Also, the physician prescribed similar drugs to the participants in the study. Independent samples T-test and Mann-Whitney U were used to compare the quantitative outcomes between the intervention group and the comparison group. The Wilcoxon test and the paired T-test were applied for within-group comparisons. A p-value <0.05 was considered significant. At the end of the study, the change levels of IL-35 in the intervention group increased significantly compared to the control group. In terms of the lung function parameters, FEV1/ forced vital capacity (FVC) (FEV1/FVC) ratio enhanced significantly in the intervention group compared to the control group. Also, the pomegranate extract significantly improved forced expiratory flow 25-75% (FEF25-75%), FEV1/FVC ratio, and FEV1 in the intervention group. No significant changes in FEV1 values were observed between the two groups at the end of the study. Also, no significant changes were seen in other indicators. It seems that pomegranate extract can improve lung function parameters and IL-35 expression in mild and moderate allergic asthma. Clinical trial registration: https://www.irct.ir/trial/45612; identifier: IRCT20200205046384N1.

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos / Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues. / Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos.

BACKGROUND: L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. OBJECTIVES: The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. METHODS: Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. RESULTS: Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). CONCLUSION: The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

FUNDAMENTOS: A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. OBJETIVOS: O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. MÉTODOS: Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. RESULTADOS: A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). CONCLUSÃO: Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

The effects of Taurine supplementation on inflammatory markers and clinical outcomes in patients with traumatic brain injury: a double-blind randomized controlled trial.

BACKGROUND: Traumatic brain injury is a public health concern and is the main cause of death among various types of trauma. The inflammatory conditions due to TBI are associated with unfavorable clinical outcomes. Taurine has been reported to have immune-modulatory effects. Thus, the aim of this study was to survey the effect of taurine supplementation in TBI patients. METHODS: In this study, 32 patients with TBI were randomized into two groups. The treatment group received 30 mg/kg/day of taurine in addition to the Standard Entera Meal and the control group received Standard Entera Meal for 14 days. Prior to and following the intervention, the patients were investigated in terms of serum levels of IL-6, IL-10, hs-CRP and TNF-α as well as APACHEII, SOFA and NUTRIC scores, Glasgow coma scale and weight. In addition, the length of Intensive Care Unit stay, days of dependence on ventilator and 30-day mortality were studied. SPSS software (version 13.0) was used for data analysis. RESULTS: Taurine significantly decreased the serum levels of IL-6 (p = 0.04) and marginally APACHEII score (p = 0.05). In addition, weight loss was significantly lower in taurine group (p = 0.03). Furthermore, taurine significantly increased the GCS (p = 0.03). The groups were not different significantly in terms of levels of IL-10, hs-CRP, and TNF-α, SOFA and NUTRIC scores, 30-day mortality, length of ICU stay and days of dependence on ventilator. CONCLUSION: According to the results of the present study, taurine supplementation can reduce the IL-6 levels as one of the important inflammatory markers in these patients; and enhances the clinical outcomes too. TRIAL REGISTRATION: IRCT, IRCT20180514039657N1 . Registered 22 June 2018.

Ginseng and Cancer-Related Fatigue: A Systematic Review of Clinical Trials.

PURPOSE: The data on the effect of ginseng on general fatigue were previously reviewed. However, there is limited data on the effect of various types of ginseng on cancer-related fatigue (CRF). CRF is one of the most pervasive symptoms of cancer and cancer treatment. The primary objective of the current study was to systematically review trials investigating the safety and efficacy of three different types of ginseng separately used in the treatment protocol for patients with CRF. METHODS: We searched the available online databases for relevant publications up to October 2019. Data were independently extracted by two reviewers. We assessed the risk of bias using the Cochrane Collaboration Review Manager (RevMan, version 5.3) and reported the results in a narrative summary. RESULTS: A total of 210 studies were identified by the initial search, from which seven clinical trials and one retrospective study were included in this systematic review. A total of two clinical trials and one retrospective review examined the impact of American ginseng on CRF symptoms, three studies tested Asian ginseng, and two trials were conducted using Korean ginseng. The quality of the selected studies varied greatly. All three types of ginseng were tolerated well with few low-grade adverse events. American ginseng, containing more than 5% ginsenosides, consumed at the dosage of 2000 mg/day for up to eight weeks significantly reduced fatigue. Asian ginseng, containing ≥ 7% ginsenosides, relieved symptoms of fatigue at the dosage of 400 mg/day in the majority of patients with CRF. Korean ginseng, consumed at the dosage of 3000 mg/day for 12 weeks, decreased symptoms of CRF. CONCLUSIONS: Although our findings support the safety and effectiveness of ginseng in the treatment of CRF, the number of high-quality studies is not adequate to adopt ginseng as a standard treatment option for CRF.

Assessment of a New Ginsenoside Rh2 Nanoniosomal Formulation for Enhanced Antitumor Efficacy on Prostate Cancer: An in vitro Study.

INTRODUCTION: Ginsenoside Rh2, purified from the Panax ginseng root, has been demonstrated to possess anticancer properties against various cancerous cells including colorectal, breast, skin, ovarian, prostate, and liver cancerous cells. However, the poor bioavailability, low stability on gastrointestinal systems, and fast plasma elimination limit further clinical applications of Ginsenoside Rh2 for cancer treatments. In this study, a novel formulation of niosomal Ginsenoside Rh2 was prepared using the thin film hydration technique. METHODS: The niosomal formulation contained Span 60 and cholesterol, and cationic lipid DOTAP was evaluated by determining particle size distribution, encapsulation efficiency, the polydispersity index (PDI), and surface morphology. The cytotoxic effects of free Ginsenoside Rh2 and Ginsenoside Rh2-loaded niosomes were determined using the MTT method in the PC3 prostate cancer cell line. For the investigation of the in vitro cellular uptake of Ginsenoside Rh2-loaded niosome, two formulations were prepared: the Ginsenoside Rh2-loaded niosomal formula containing 5% DOTAP and the Ginsenoside Rh2-loaded niosomal formula without DOTAP. RESULTS: The mean size, DPI, zeta potential, and encapsulation efficiency of the Ginsenoside Rh2-loaded nanoniosomal formulation containing DOTAP were 93.5±2.1 nm, 0.203±0.01, +4.65±0.65, and 98.32% ±2.4, respectively. The niosomal vesicles were found to be round and have a smooth surface. The release profile of Ginsenoside Rh2 from niosome was biphasic. Furthermore, a two-fold reduction in the Ginsenoside Rh2 concentration was measured when Ginsenoside Rh2 was administered in a nanoniosomal form compared to free Ginsenoside Rh2 solutions in the PC3 prostate cancer cell line. After storage for 90 days, the encapsulation efficiency, vesicle size, PDI, and zeta potential of the optimized formulation did not significantly change compared to the freshly prepared samples. The cellular uptake experiments of the niosomal formulation demonstrated that by adding DOTAP to the niosomal formulation, the cellular uptake was enhanced. DISCUSSION: The enhanced cellular uptake and cytotoxic activity of the Ginsenoside Rh2 nanoniosomal formulation on the PC3 cell make it an attractive candidate for application as a nano-sized delivery vehicle to transfer Ginsenoside Rh2 to cancer cells.

Red vine leaf extract (AS 195) can improve some signs and symptoms of chronic venous insufficiency, a systematic review.

AIM: Chronic venous insufficiency (CVI) is common in adults. Some complications include skin changes, edema, heavy legs, muscle cramps, pain, and varicose veins. In traditional medicine, red vine leaf extract (AS 195) has been used to cure the symptoms of CVI. This systematic review was aimed to assess the effects of AS 195 in patients with CVI. MATERIAL AND METHODS: A systematic literature search was performed to identify trials that reported the impact of red vine leaf extract on CVI. The primary outcomes investigated were Leg (limb) volume, calf circumference, ankle circumference, tired and heavy legs, a sensation of tension, tingling sensation, and pain. RESULTS: From the 56 studies, 5 trials were selected according to our inclusion criteria. Red vine leaf extract significantly improved numbers of outcomes (lower leg volume, calf and ankle circumference, tired, heavy legs, tingling sensation, pain, the sensation of tension in the legs, cutaneous microcirculation, and transcutaneous oxygen pressure) in only some trials. The tolerability for red vine leaf extract was reported good or satisfactory. CONCLUSIONS: Red vine leaf extract had a beneficial therapeutic role in patients with CVI. Further high-quality trials are required to be carried out to provide strong evidence.

Antioxidant and Anti-Inflammatory Properties of Melatonin in Patients with Type 2 Diabetes Mellitus with Periodontal Disease Under Non-Surgical Periodontal Therapy: A Double-Blind, Placebo-Controlled Trial.

BACKGROUND AND AIM: The imbalance between pro-oxidant and antioxidant systems often leads to further oxidative damage in the pathogenesis of both diabetes and periodontal disease. This study aimed to investigate the antioxidant and anti-inflammatory properties of melatonin in type 2 diabetes mellitus (T2DM) patients with periodontal disease (PD) under non-surgical periodontal therapy (NSPT). MATERIALS AND METHODS: In this double-blind clinical trial study, 50 T2DM patients with PD were randomly allocated to intervention and control groups and received 250 mg/day (2 tablets) either melatonin or placebo 1 h before bedtime for 8 weeks. The NSPT was performed for all patients in both groups at the beginning of the study. The serum levels of interleukin-1b (IL-1b), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured pre- and post-intervention. RESULTS: Supplementation with melatonin in adjunct to NSPT significantly increased the serum levels of TAC, SOD, CAT, and GPx in the intervention group (P = 0.02, 0.008, 0.004 and 0.004, respectively). The mean changes of SOD, CAT, and GPx were significantly (P = 0.02, 0.04 and 0.04, respectively) greater in the intervention group compared with the control group. Also, after adjusting for confounding factors, the results did not change in terms of significance (P < 0.05). After the intervention, serum levels of MDA and IL-1b were significantly reduced in the intervention group (P < 0.001 and P = 0.008, respectively). The intervention group exhibited lower mean changes of MDA compared with the control group, and these changes were statistically significant (P = 0.008). In addition, after adjusting for confounding factors, the results did not change in terms of significance. CONCLUSION: The adjunctive effects of melatonin and NSPT may improve inflammatory and antioxidant parameters in T2DM patients with PD.

Effect of Ginger Powder Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders. The main causes of NAFLD are associated with insulin resistance, severe lipid metabolism disorders, oxidative stress and inflammation. Previous studies have reported that ginger has positive metabolic results. AIM: The aim of this study was to determine the effect of ginger powder supplement on lipid profiles, insulin resistance, liver enzymes, inflammatory cytokines and antioxidant status in patients with NAFLD. METHODS: In this randomized clinical trial, 46 people with NAFLD were parted into two groups and subjected to the ginger or placebo capsules (3 capsules daily, each containing 500 mg of ginger or wheat flour) over 12 weeks. All patients received a diet with balanced energy and physical activity during the intervention period. Liver ultrasonography, anthropometric indices and biochemical parameters were measured before and after intervention. RESULTS: No significant difference was found between the two groups in the baseline variables at the beginning of the study. At the end of the study, serum levels of alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL-C), fasting blood glucose, and insulin resistance index (HOMA), C-reactive protein (hs-CRP), and fetuin-A in the group receiving a ginger supplement significantly decreased compared to placebo. However, there was no significant difference between the two groups in body weight, fasting insulin, HDL-C, triglyceride, adiponectin, alpha-tumor necrosis factor (TNF-α), total antioxidant capacity (TAC), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), fatty liver index (FLI), fatty liver grade and blood pressure. CONCLUSION: The ginger supplement may be used as a complementary therapy along with existing therapies to reduce insulin resistance, liver enzymes and inflammation in patients with non-alcoholic fatty liver.

A Rare Case Report of Acute Necrotizing Encephalopathy of Childhood.

OBJECTIVE: Acute necrotizing encephalopathy of childhood (ANEC) is a fast growing disease, accompanied by progressive encephalopathy. The aim of this study was to report a rare case of ANEC in a four-year-old boy with bilateral thalamic necrosis and non-fatal outcomes. CASE REPORT: The patient was a four-year-old Iranian boy, without any history of health problems or hospitalization, except for jaundice and phototherapy in the neonatal period. He had no neurological signs or symptoms during admission, and he was admitted only with chief complaints of acute onset of fever, coryza, and icterus. In the neurological consultation, brain MRI was requested to analyze the possibility of brain damage. The results indicated the involvement of cerebellum, thalamus, and basal ganglia, which led to the diagnosis of ANEC. CONCLUSION: Based on our findings, although ANEC is a rare disease, it should not be underestimated.

Effects of epigallocatechin-3-gallate of Camellia sinensis leaves on blood pressure, lipid profile, atherogenic index of plasma and some inflammatory and antioxidant markers in type 2 diabetes mellitus patients: a clinical trial.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) the inflammatory and metabolic responses to epigallocatechin-3-gallate (EGCG) are unknown. OBJECTIVES: Evaluate the impacts of EGCG on metabolic factors and some biomarkers of stress oxidative in patients with T2DM. METHODS: In this randomized, double-blind, placebo-controlled trial, 50 patients with T2DM consumed either 2 tablets (300 mg) EGCG (n=25) or wheat flour as placebo (n=25) for 2 months. The total antioxidant capacity (TAC), interleukin-6 (IL-6), lipid profile, mean arterial pressure (MAP), atherogenic index of plasma (AIP) were evaluated before and after the intervention. RESULTS: The finding of present study exhibited a significant increase in the serum levels of TAC after the EGCG supplementation (p=0.001). Also, in compare with control group, the mean changes of TAC were significantly higher in supplement group (p=0.01). In intervention group, a significant decrease was observed in the mean levels of triglyceride, total cholesterol, diastolic blood pressure (DBP), AIP, and MAP (p<0.05). Taking EGCG resulted in the mean changes of total cholesterol, MAP and DBP were significantly lower in compare with control group (p<0.05). CONCLUSIONS: This study recommended that EGCG supplementation may be improved blood pressure, lipid profile, AIP, and oxidative status in patients with T2DM.

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial.

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitamin D3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstrate the power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDR polymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation on the serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in the VDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56 breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention. Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and after the intervention to measure the 25(OH) D3, TNF-α, TGF- ß and TAC. Genotyping was performed for FokI, BsmI, ApaI, and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017). Changes in TNF-α, TGF- ß1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes were more responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breast cancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive to vitamin D supplement compared with those with the FF/ff and tt genotypes.

Effect of herbal antioxidant-rich formula on improvement of antioxidant defense system and heat shock protein-70 expression in recreational female athletes: A randomized controlled trial.

BACKGROUND: The aim of the present study was to evaluate the effect of natural antioxidant formula (blend of herbs: ginger root, cinnamon bark and raw almond fruit powder, rosemary leaf powder, and honey) on oxidative status, antioxidant enzyme activity, and relative heat shock protein (HSP-70) expression in recreational female athletes. MATERIALS AND METHODS: Eighteen female participants trained for 4 weeks and randomly received either antioxidant formula (FormEX) (n = 8) or placebo (PlcEX) (n = 10) in a randomized controlled trial. Blood samples were obtained 1-h before, 1 h and 24 h postexercise to measure malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidases (GPx), and HSP70 mRNA expression. Data analysis was performed using 2 (treatment = grouping factor) ×6 (time = within-factor) repeated measurements analysis of variance or generalized estimating equations (GEE) test. We used the independent t-test to evaluate any significant differences for real-time polymerase chain reaction data. RESULTS: Antioxidant formula increased the relative HSP-70 mRNA expression more than Plc-EX group in all time points (P = 0.001). The time main effect was significant with regard to TAC and SOD concentrations (P = 0.001 and 0.002, respectively). However, there were no statistically significant differences between groups for TAC, SOD, and MDA (P = 0.25, 0.06, and 0.38, respectively). Neither the time main effect for MDA nor time and intervention interaction was not statistically significant for MDA, TAC, and SOD (P = 0.19, 0.13, and 0.10, respectively). GEE results for GPx showed that there were no significant differences between the groups (P = 0.11). CONCLUSION: The results presented herein revealed that natural antioxidant rich formula had variable effects on oxidative status. However, in contrast to many antioxidant supplements, this formulation increases the HSP-70 mRNA expression which might improve the antioxidant ability of cells in the long-term period and exercise-induced adaptation.