A human papillomavirus 16 E2-TopBP1 dependent SIRT1-p300 acetylation switch regulates mitotic viral and human protein levels and activates the DNA damage response.

An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 and BRD4 is required for E2 plasmid segregation function. The E2-TopBP1 interaction promotes increased mitotic E2 protein levels in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes immortalized by HPV16 (HFK + HPV16). SIRT1 deacetylation reduces E2 protein stability and here we demonstrate that increased E2 acetylation occurs during mitosis in a TopBP1 interacting-dependent manner, promoting E2 mitotic stabilization. p300 mediates E2 acetylation and acetylation is increased due to E2 switching off SIRT1 function during mitosis in a TopBP1 interacting-dependent manner, confirmed by increased p53 stability and acetylation on lysine 382, a known target for SIRT1 deacetylation. SIRT1 can complex with E2 in growing cells but is unable to do so during mitosis due to the E2-TopBP1 interaction; SIRT1 is also unable to complex with p53 in mitotic E2 wild-type cells but can complex with p53 outside of mitosis. E2 lysines 111 and 112 are highly conserved residues across all E2 proteins and we demonstrate that K111 hyper-acetylation occurs during mitosis, promoting E2 interaction with Topoisomerase 1 (Top1). We demonstrate that K112 ubiquitination promotes E2 proteasomal degradation during mitosis. E2-TopBP1 interaction promotes mitotic acetylation of CHK2, promoting phosphorylation and activation of the DNA damage response (DDR). The results present a new model in which the E2-TopBP1 complex inactivates SIRT1 during mitosis, and activates the DDR. This is a novel mechanism of HPV16 activation of the DDR, a requirement for the viral life cycle. IMPORTANCE: Human papillomaviruses (HPVs) are causative agents in around 5% of all human cancers. While there are prophylactic vaccines that will significantly alleviate HPV disease burden on future generations, there are currently no anti-viral strategies available for the treatment of HPV cancers. To generate such reagents, we must understand more about the HPV life cycle, and in particular about viral-host interactions. Here, we describe a novel mitotic complex generated by the HPV16 E2 protein interacting with the host protein TopBP1 that controls the function of the deacetylase SIRT1. The E2-TopBP1 interaction disrupts SIRT1 function during mitosis in order to enhance acetylation and stability of viral and host proteins. We also demonstrate that the E2-TopBP1 interaction activates the DDR. This novel complex is essential for the HPV16 life cycle and represents a novel anti-viral therapeutic target.

Effect of vitamin B1 supplementation on blood creatinine and lactate levels and clinical outcomes in patients in intensive care units: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency. OBJECTIVE: This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU). DATA SOURCES: Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022. STUDY SELECTION: Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected. DATA EXTRACTION: After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process. RESULTS: Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P = .03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71) or the need for renal replacement therapy (P = .14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P = .39). CONCLUSION: This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710).

Watermelon consumption decreases risk factors of cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.

This meta-analysis was conducted to examine the effects of watermelon supplementation on cardiovascular diseases (CVDs) risk factors in randomized controlled trials (RCTs). The comprehensive search was done in Cochrane Library databases, ISI Web of Science, PubMed, and Scopus up to March 2022. A random-effect model was used for computing weighted mean differences (WMD). Standard methods were applied to examine publication bias, sensitivity analysis, and heterogeneity. Of the 8962 identified studies, 9 RCTs were included in the final analysis. Watermelon consumption significantly decreased systolic blood pressure (SBP), totalcholesterol (TC) and low-density lipoprotein (LDL). In addition, watermelon consumption led to a significant increase in fasting blood sugar (FBS). However, there was not any significant difference in other outcomes of interest including diastolic blood pressure (DBP), heart rate (HR), BMI, body fat, and serum levels of arginine, insulin, and CRP after watermelon supplementation. The current findings provide promising evidence of the antihypertensive effect of watermelon. However, due to the lack of evidence in human research, the result regarding the remaining outcomes needs to be used with caution. Furter RCTs with longer follow-ups and larger sample sizes should be done to confirm the current findings.

Human papillomavirus 16 E2 blocks cellular senescence in response to activation of the DNA damage response.

Following infection by HPV16, the viral proteins E1 and E2 induce viral genome replication in association with host factors. Here we demonstrate that E2 also plays a role in promoting short-term cellular proliferation in the presence of an active DDR. Cisplatin treatment of E2 expressing cells results in short-term proliferation likely due to a block of cellular senescence and apoptosis. However, long-term growth of E2 expressing cells following cisplatin treatment is attenuated due to an accumulation of DNA damage. We discuss a possible role for this E2 function during the viral life cycle. It is also notable that E2 expressing HPV16 positive cancers have a better clinical outcome than non-E2 expressing tumors. While there are a variety of reasons for the better outcome of patients with E2 expressing tumors, this report suggests that E2 regulation of the DNA damage response may be a contributory factor.

A Critical Role for p53 during the HPV16 Life Cycle.

Human papillomaviruses (HPV) are causative agents in ano-genital and oral cancers; HPV16 is the most prevalent type detected in human cancers. The HPV16 E6 protein targets p53 for proteasomal degradation to facilitate proliferation of the HPV16 infected cell. However, in HPV16 immortalized cells E6 is predominantly spliced (E6*) and unable to degrade p53. Here, we demonstrate that human foreskin keratinocytes immortalized by HPV16 (HFK+HPV16), and HPV16 positive oropharyngeal cancers, retain significant expression of p53. In addition, p53 levels increase in HPV16+ head and neck cancer cell lines following treatment with cisplatin. Introduction of full-length E6 into HFK+HPV16 resulted in attenuation of cellular growth (in hTERT immortalized HFK, E6 expression promoted enhanced proliferation). An understudied interaction is that between E2 and p53 and we investigated whether this was important for the viral life cycle. We generated mutant genomes with E2 unable to interact with p53 resulting in profound phenotypes in primary HFK. The mutant induced hyper-proliferation, but an ultimate arrest of cell growth; ß-galactosidase staining demonstrated increased senescence, and COMET assays showed increased DNA damage compared with HFK+HPV16 wild-type cells. There was failure of the viral life cycle in organotypic rafts with the mutant HFK resulting in premature differentiation and reduced proliferation. The results demonstrate that p53 expression is critical during the HPV16 life cycle, and that this may be due to a functional interaction between E2 and p53. Disruption of this interaction has antiviral potential. IMPORTANCE Human papillomaviruses are causative agents in around 5% of all cancers. There are currently no antivirals available to combat these infections and cancers, therefore it remains a priority to enhance our understanding of the HPV life cycle. Here, we demonstrate that an interaction between the viral replication/transcription/segregation factor E2 and the tumor suppressor p53 is critical for the HPV16 life cycle. HPV16 immortalized cells retain significant expression of p53, and the critical role for the E2-p53 interaction demonstrates why this is the case. If the E2-p53 interaction is disrupted then HPV16 immortalized cells fail to proliferate, have enhanced DNA damage and senescence, and there is premature differentiation during the viral life cycle. Results suggest that targeting the E2-p53 interaction would have therapeutic benefits, potentially attenuating the spread of HPV16.

Psychiatric training program during the COVID-19 pandemic: An experience in Iran.

OBJECTIVE: This study aims to report a redesigned psychiatric training program in the internship and the externship courses at Tehran University of medical sciences, in Iran during the COVID-19 pandemic. METHODS: It is a retrospective cohort study which 531 externs and 381 interns enrolled. The students' satisfaction and their exam scores were assessed before and during the COVID-19 pandemic. RESULTS: Blended learning was used for clinical education which theoretical, case-based discussions; and assessments were provided online. Externs' clinical scores and satisfaction were significantly higher while interns' scores got worse. CONCLUSION: E-learning can be effective, applicable and acceptable in clinical education.

Diet and disease-related outcomes in multiple sclerosis: A systematic review of clinical trials.

Background: A growing number of clinical trials have investigated the role of diet in multiple sclerosis (MS) patients. We systematically reviewed the literature for clinical trials to assess the impact of different kinds of diets on MS-related outcomes. Methods: We searched MEDLINE, EMBASE, and Web of Science for relevant studies published before July 2019. The clinical trials included a defined dietary intervention and MS outcomes, including fatigue, relapse rate (RR), quality of life (QOL), and disability. Results: In the present review, 15 trials on 669 MS patients were included. The 2 plant-based diet trials, 1 was low-fat and the other was low-calorie, included in the review showed a large effect (ES: 0.6 to 0.7) on fatigue compared to the regular diet. The other plant-based diet was a low-protein diet and showed moderate to large effects on disability and RR compared to the Western diet. Moreover, 2 studies showed the clinically meaningful effects of the ketogenic diet (KD) on QOL and disability compared to the regular diet. In addition, 2 studies compared fish oil (FO) to placebo and found a small effect on disability (ES: 0.1 to 0.3). There were 2 studies that evaluated evening primrose oil and hemp seed oil and showed medium to large effect (ES: 0.7 to 1.5) on RR compared to olive oil. Finally, we found 2 studies that showed high flavonoid cocoa had a moderate effect (ES: 0.4) on fatigue and a small effect (ES: 0.04) on QOL compared to low flavonoid cocoa. Conclusion: Plant-based diet is a backbone for dietary recommendations in MS patients although low-fat, low-calorie, and KD diets with the addition of fish oil, vegetable oil, and flavonoids could be helpful.

The effects of Anethum graveolens (dill) supplementation on lipid profile and glycemic control: a systematic review and meta-analysis of randomized controlled trials.

There is an increased interest in the potential health benefits of nutraceutical therapies, such as Anethum graveolens (dill). Therefore, this systematic review and meta-analysis aimed to evaluate the effects of Anethum graveolens supplementation on lipid profiles and glycemic indices in adults. A systematic search was performed for literature published through November 2020 via PubMed/Medline, Scopus, ISI Web of Science, and Embase to find randomized controlled trials (RCTs) evaluating the effects of oral supplementation with A. graveolens on lipid profile and measures of glycemic control in adults. The random-effects model was applied to establish the weighted mean difference (WMD) and associated 95% confidence intervals (CI). Seven RCTs with a total number of 330 subjects were included in the final analysis. Pooled results indicated that A. graveolens supplementation significantly decreased low-density lipoprotein cholesterol (LDL) concentration (WMD: -15.64 mg/dL; 95% CI: -24.55 to -6.73; P = 0.001), serum insulin (WMD: -2.28 µU/ml; 95% CI: -3.62 to -0.93; P = 0.001), and HOMA-IR (WMD: -1.06; 95% CI: -1.91 to -0.20; P = 0.01). However, there was no significant effect on serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and fasting blood glucose (FBS). Subgroup analysis suggested that using A. graveolens in higher doses and long-term duration had beneficial effects on lipid profiles. Dose-response analysis also showed a significant reduction in FBS at doses of 1500 mg/d. The present meta-analysis indicated that Anethum graveolens could exert favorable effects on insulin resistance and serum LDL. Further research is necessary to confirm our findings.

Dietary quality indices modify the effects of apolipoprotein B polymorphisms on biochemical and anthropometric factors in type 2 diabetes mellitus.

We tried to identify the interaction between dietary quality indices and apolipoprotein B Ins/Del and EcoR1 polymorphisms on biochemical and anthropometric factors in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study recruited 700 adults with T2DM in Tehran. The genotypes of Ins/Del and EcoR1 single nucleotide polymorphisms (SNP) were explored via polymerase chain reaction (PCR). Dietary quality index-international (DQI-I), healthy eating index-2015 (HEI-2015) and dietary phytochemical index (DPI) were calculated by semi-quantitative food frequency questionnaire (FFQ). In both crude and adjusted model for confounding factors, we observed significant interactions between DQI-I and Ins/Del SNP on leptin in and 8-iso-prostaglandin F2 α (8-iso-PGF2α), DPI and EcoR1 SNP on total cholesterol (TC) and between Ins/Del SNP and HEI-2015 on interleukin-18 (IL-18). Furthermore, in crude model there were close to meaningful interactions between EcoR1 SNP and DQI-I on total antioxidant capacity (TAC) and between EcoR1 SNP and HEI-2015 on serum leptin and superoxide dismutase (SOD) levels. Our finding indicated that the association between DQI-I, HEI-2015 and DPI with IL-18, TC, leptin and 8-iso-PGF2α in patients with T2DM might be dependent on Ins/Del and EcoR1 variants in ApoB gene.

Omega-3 polyunsaturated fatty acids supplementation improve clinical symptoms in patients with Covid-19: A randomised clinical trial.

AIMS: We hypothesised that omega-3 fatty acids would be an appropriate adjunct therapy for alleviating the inflammatory response and clinical manifestation in hospitalised patients with Covid-19 disease. METHODS: This was a single-blind randomised controlled trial in Amir-Alam hospital in Tehran. Thirty adult men and women diagnosed with Covid-19 were allocated to either control group (receiving Hydroxychloroquine) or intervention group (receiving Hydroxychloroquine plus 2 grams of Docosahexaenoic acid [DHA] + Eicosapentaenoic acid [EPA]) for 2 weeks. Primary outcome of the intervention including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as clinical symptoms including body pain, fatigue, appetite and olfactory and secondary outcomes including liver enzymes were determined at the baseline and after omega-3 supplementation. Clinical signs were measured using self-reported questionnaires. There were commercial kits for determination of CRP and liver enzymes concentrations in the serum of patients. For determination of ESR automated haematology analyser was applied. The study of "Comparison of the effectiveness of omega-3 and Hydroxychloroquine on Inflammatory factors, liver enzymes and clinical symptoms in diabetic Covid-19 patients" was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20200511047399N1. RESULTS: In comparison to control group, patients receiving omega-3 indicated favourable changes in all clinical symptoms except for olfactory (P < .001 for body pain and fatigue, P = .03 for appetite and P = .21 for olfactory). Reducing effects of omega-3 supplementation compared with control group were also observed in the levels of ESR and CRP after treatment (P < .001 for CRP and P = .02 for ESR). However, no between group differences in the liver enzymes serum concentrations were observed after supplementation (P > .05). CONCLUSION: Current observations are very promising and indicate that supplementation with moderate dosages of omega-3 fatty acids may be beneficial in the management of inflammation-mediated clinical symptoms in Covid-19 patients.

Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

BACKGROUND: Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting. PURPOSE: To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population. DATA SOURCES: Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals. STUDY SELECTION: We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults. DATA SYNTHESIS: The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; I 2 = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; I2 = 66.2%). The certainty of the evidence was assessed as moderate. LIMITATIONS: A limitation of our work was the observational design of studies included in the analyses. CONCLUSIONS: We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.

High carbohydrate intakes may predict more inflammatory status than high fat intakes in pre-menopause women with overweight or obesity: a cross-sectional study.

OBJECTIVE: The associations between dietary carbohydrate, fat intake, and inflammation are controversial. Most existing data are from industrialized societies which low-carbohydrate and high-fat diet is common and so their attribution to other populations remains unclear. We evaluated the association of fat and carbohydrate intakes with inflammatory markers in pre-menopause women with overweight or obesity in Iran. RESULTS: Three hundred and sixty women with body mass index (BMI) ≥ 25 were included to this study. The levels of monocyte chemoattractant protein-1 (MCP-1) indicated a trend towards significance across tertiles of total dietary carbohydrate. We found that the levels of galectin-3 were negatively associated with dietary carbohydrate in adjusted model. In addition, the levels of MCP-1 and transforming growth factor beta (TGF-ß) were positively correlated to dietary carbohydrate. No significant relationship was demonstrated between inflammatory parameters and total fat intake). However, there was a borderline significant negative association between total fat intake and TGF-ß level in adjusted model. Therefore, a total dietary carbohydrate were related to elevated inflammation risk, while a total fat intake were not associated to higher inflammation. This study suggests reconsideration of applying global dietary guidelines in societies with high carbohydrate diet.

The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial.

OBJECTIVE: The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. RESULTS: In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. TRIAL REGISTRATION: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

The effect of vitamin D supplementation on fibroblast growth factor-23 in patients with chronic kidney disease: A systematic review and meta-analysis.

This is a meta-analysis of randomized controlled trials (RCTs) investigating the effects of oral vitamin D supplementation on serum fibroblast growth factor-23 (FGF23) concentrations in patients with chronic kidney disease (CKD). Manuscripts were extracted from PubMed/MEDLINE, Scopus, and ISI Web of Science through February 2020. Subgroup analyses, sensitivity analysis, and meta-regression assessments were performed. A total of eight clinical trials with nine treatment arms were included in the final analysis. The pooled results showed no significant changes in circulating FGF23 following vitamin D supplementation compared to the control group (Standardized mean difference (SMD): 0.24; 95% confidence intervals (CIs): -0.03 to 0.50, p > 0.05). Subgroup analyses found that studies which had participants with a body mass index (BMI) higher than 25 kg/m2 , with an intervention duration shorter than 15 weeks, using phosphate binder medications, and trials that were on both patients with CKD undergoing hemodialysis and patients without hemodialysis treatment produced significant increases in FGF23 when concentration compared with the control group. This meta-analysis provides evidence that vitamin D supplementation does not have a significant effect on plasma FGF23 levels. However, further high-quality trials are required to identify the influence of oral vitamin D supplementation on FGF23 levels in patients with CKD.

Interaction between the dietary indices and PPAR-γ Pro12Ala gene variants on cardiovascular risk factors in patients with type 2 diabetes mellitus.

AIMS: We investigated the interaction between peroxisome proliferator-activated receptor gamma (PPAR-γ) Pro12Ala polymorphism and healthy eating index (HEI), Dietary Quality Index-International (DQI-I), and dietary phytochemical index (DPI) on cardiovascular disease (CVD) risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study was conducted on 393 diabetic patients. PPAR-γ Pro12Ala was genotyped by the PCR-RFLP method. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α). Interleukin 18 (IL18), leptin, and ghrelin were measured by standard protocol. Food-frequency questionnaires (FFQ) were used for dietary indices (DQI-I, DPI, HEI) calculation. RESULTS: Homozygous carriers of the rs1801282 C allele showed higher leptin compared G allele carriers (P = .015). The rs1801282-DQI-I interactions were significant on waist circumference (WC) (P = .019). Thus, C-allele carriers in the higher tertile of DQI-I had higher WC compared with GG homozygous. Further, an interaction was observed between PPAR rs1801282 polymorphism and DQI-I on serum IL-18 level (P = .032). Besides, a significant rs1801282-DPI interaction was shown on HDL concentration (P = .041), G allele carriers who were in the highest tertile of DPI, had lower HDL. Moreover, there were significant rs1801282-HEI interactions on serum leptin (P = .021). Individuals with (CC, CG) genotypes in the higher tertile of HEI, had lower leptin concentration. CONCLUSION: Higher dietary indices (DQI-I, DPI, HEI) may affect the relationship between PPAR-γ Pro12Ala polymorphism and WC, ghrelin, leptin, HDL, and IL-18 concentration in patients with T2DM.

The Biochemical Parameters and Vitamin D Levels in ICU Patients with Covid-19: A Cross-Sectional Study.

BACKGROUND: In Covid-19 infection, leukopenia, inflammation, and elevated liver enzymes are found in most patients. Also, vitamin D deficiency attenuates the immune system and predisposes a person to being more susceptible to infection. In this context, we aimed to evaluate vitamin D, electrolytes, complete blood count, liver enzymes, urea, creatinine, albumin, CRP and ESR levels in patients with Covid-19. METHODS: We conducted a cross-sectional study on 118 patients with Covid-19 who were hospitalized from 2020/2/19 to 2020/4/3 in ICU. Serum levels of electrolytes, liver enzymes, blood factors, urea, creatinine, CRP and ESR, as well as anthropometric parameters and serum vitamin D concentration, were measured. RESULTS: A total of 118 patients (80 male and 38 female) were enrolled in the study (65.05±15.75 years). Only 5.08% of patients had no risk factors and 55.9% had ≥ 2 risk factors. Diabetes (44.1%) and obesity (23.7%) were more common among patients. Laboratory findings showed that 80.50% of patients had hyponatremia, but other electrolytes including K, Mg, Ca and P were normal in the majority of participants as well as CBC, Cr, Urea, Alb, ALT and ALKP. The AST concentration increased in most patients (66.94%). All patients had high levels of inflammatory factors such as CRP and ESR. The mean of 25-hydroxy-vitamin D levels in participants (25.95 ± 14.56 ng/mL) was lower than its levels in the general population. However, it was not statistically significant (P= 0.88). A significant negative correlation was found between vitamin D and ALT (P= 0.02, -0.21) as well as vitamin D and CRP (P= 0.05, -0.17). CONCLUSION: Due to the regulatory role of vitamin D in the immune system and low levels of vitamin D in Covid-19 infected patients, the evaluation of vitamin D levels and prescribed supplements, if necessary, is suggested.

A personalised diet study: The interaction between ApoA2 -265T > C polymorphism and dietary inflammatory index on oxidative and inflammatory markers and lipid profile in patients with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: This study aimed to investigate the interaction between dietary inflammatory index (DII) and apolipoproteinA2 265T > C (ApoA2 -265T > C) polymorphism on inflammatory and oxidative markers and lipid profile in type 2 diabetes mellitus (T2DM) patients. METHODS: In this cross-sectional study, 157 patients with T2DM were recruited. A food-frequency questionnaire was used for DII calculation. Inflammatory, oxidative and lipid biomarkers were measured. Real-time polymerase chain reaction (PCR) method was used for ApoA2 genotyping determination. RESULTS: In the current study, serum 8-iso-PGF2α and CRP were significantly higher, and serum SOD activity was significantly lower in subjects with CC genotype than TT homozygous in both crude and adjusted (for DII and AAs intake) models. Also, C-allele carriers compared with people with TT genotype had lower PTX3 in both models. In addition, serum TG level was significantly higher in TC genotype than TT homozygous in adjusted model. Moreover, subjects with CC homozygous and high DII level had significantly higher 8-iso-PGF2α level compared to those with TT genotype and low DII (reference group) in adjusted (for BMI, age, sexuality and AAs intake) model. Our results also showed that in TC genotypes with low DII and CC homozygous with both low and high DII, PTX3 concentrations were significantly lower than the reference group. In addition, CC carriers with low DII had significantly higher CRP level compared to the reference group. Moreover, our results reported significant higher TG in TC genotype with low DII and also higher total cholesterol level in CC genotype with low DII than the reference group. CONCLUSION: These findings indicate that CC genotype might predict higher inflammatory and oxidative status level compared to T allele carriers. An inflammatory diet may accelerate oxidative stress in subjects with CC genotype. However, the association between APOA2 -265T > C polymorphism and inflammation and lipid profile is presented less modifiable by DII.

Impact of supplementation with "multivitamin-mineral" specially formulated to improve fatigue and inflammatory state in patients with multiple sclerosis: A triple-blind, randomized, placebo-controlled trial.

Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with the most common complaint of fatigue. A high number of patients with MS are interested in taking dietary supplements as a complementary therapy. We propose a specially formulated supplement for patients with MS and aim to evaluate its effects on fatigue. Methods: This study was a triple-blind, randomized, placebo-controlled trial using a stratified randomization method according to sex. 46 eligible patients participated in the study, 23 in the placebo group and 23 in the intervention group. The intervention group received two capsules of multivitamin-mineral (MVM) daily for 3 months. Measurements of fatigue and cytokines were performed in all patients at the baseline and after the 3-month intervention Results: Finally, information of 41 participants was used for data analysis. However, fatigue was decreased after supplementation than before, in the intervention group (P = 0.005). There was no significant difference (P = 0.090) between the change of fatigue score in the MVM group (-3.00 ± 4.42) and the control group (-0.40 ± 5.14). Among cytokines, Interleukin 4 (IL-4) significantly increased in the intervention group compared to the placebo (P = 0.030). Conclusion: Our study showed that the present MVM probably could improve the inflammatory state and fatigue in patients with MS.

Anti-hypertensive effects of cinnamon supplementation in adults: A systematic review and dose-response Meta-analysis of randomized controlled trials.

Background & Objectives: Despite controversies, no earlier study has systematically summarized findings from earlier studies on the effect of cinnamon supplementation on blood pressure. Therefore, current systematic review and meta-analysis was done on the effect of cinnamon supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults.Methods: Relevant studies published up to July 2019 were searched through PubMed/Medline, Scopus, ISI Web of Science, Embase and Google Scholar. All randomized clinical trials investigating the impact of oral cinnamon supplementation on any of the blood pressure parameters including SBP or/and DBP were included.Results: Out of 469 citations, 9 trials that enrolled 641 subjects were included. Cinnamon supplementation resulted in significant reduction in SBP (Weighted Mean Differences (WMD): -6.23 mmHg, 95% CI: -10.69 to -1.77, P = 0.006) and DBP (WMD: -3.93 mmHg, 95% CI: -6.33 to -1.52, P = 0.001). Greater effects on SBP were detected in trials using ≤2 g cinnamon, lasted ≥12 weeks and participants aged <50 years' old. DBP was also reduced by using lower doses. However, no significant non-linear associations were found between cinnamon supplementation dosage and study duration with both SBP (For dosage: Pnon-linearity = 0.35, for duration: Pnon-linearity = 0.21) and DBP (For dosage: Pnon-linearity = 0.27, for duration: Pnon-linearity = 0.41).Conclusions: We found a significant reduction in both SBP and DBP following cinnamon supplementation in adults. It could be proposed as a hypotensive supplement in hypertension management.