Mass Spectrometry Applications to Study Human Microbiome.

Microbiotas are an adaptable component of ecosystems, including human ecology. Microorganisms influence the chemistry of their specialized niche, such as the human gut, as well as the chemistry of distant surroundings, such as other areas of the body. Metabolomics based on mass spectrometry (MS) is one of the primary methods for detecting and identifying small compounds generated by the human microbiota, as well as understanding the functional significance of these microbial metabolites. This book chapter gives basic knowledge on the kinds of untargeted mass spectrometry as well as the data types that may be generated in the context of microbiome study. While data analysis remains a barrier, the emphasis is on data analysis methodologies and integrative analysis, particularly the integration of microbiome sequencing data. Mass spectrometry (MS)-based techniques have resurrected culture methods for studying the human gut microbiota, filling in the gaps left by high-throughput sequencing methods in terms of culturing minor populations.

Applications of Proteomics in Probiotics Having Anticancer and Chemopreventive Properties.

Proteomics has grown in importance in molecular sciences because it gives vital information on protein identification, expression levels, and alteration. Cancer is one of the world's major causes of death and is the major focus of much research. Cancer risk is determined by hereditary variables as well as the body's immunological condition. Probiotics have increasing medical importance due to their therapeutic influence on the human body in the prevention and treatment of numerous chronic illnesses, including cancer, with no adverse effects. Several anticancer, anti-inflammatory, and chemopreventive probiotics are studied using different proteomic approaches like two-dimensional gel electrophoresis, liquid chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. To gain relevant information about probiotic characteristics, data from the proteomic analysis are evaluated and processed using bioinformatics pipelines. Proteomic studies showed the significance of different proteomic approaches in characterization, comparing strains, and determination of oxidative stress of different probiotics. Moreover, proteomic approaches identified different proteins that are involved in glucose metabolism and the formation of cell walls or cell membranes, and the differences in the expression of critical enzymes in the HIF-1 signaling pathway, starch, and sucrose metabolism, and other critical metabolic pathways.

Physicians' adherence to evidence-based guidelines as a major predictor of anticoagulant-related medication error incidence and severity.

AIMS: Anticoagulants represent a main source of medication errors (MEs) and complications that have catastrophic implications, posing an obligation on health care providers to assess anticoagulant-related MEs and factors affecting their occurrence. This study investigates the occurrence and severity of prescribing MEs in patients on anticoagulants and explores their potential predictors. METHODS: This study was a prospective cohort study in a tertiary hospital on 116 patients with a total of 2166 anticoagulant doses. RESULTS: Forty-four percent of prescribed anticoagulant doses resulted in MEs with low molecular weight heparin (LMWH) and unfractionated heparin (UFH) causing 61% and 34%, respectively, of the total MEs. More than 50% of all MEs were incorrect doses (high and low) shared between heparin and tinzaparin. The highest severity of error was Category D followed by Category F and Category C. A Poisson regression analysis model revealed that female (incidence rate ratio [IRR] 1.32, 95% confidence interval [CI] 1.13-1.54, P < .001), bridging (IRR 1.52; 95% CI 1.10-2.09; P = .011), venous thromboembolism (VTE) prophylaxis (IRR 7.65; 95% CI 4.88-12.02; P < .001), physician non-adherence (IRR 2.71; 95% CI 2.22-3.29; P < .001), and polypharmacy (IRR 1.68; 95% CI 1.26-2.23; P = .036) were predictors of the higher incidence of MEs. Ordinal logistic regression analysis demonstrated that physician non-adherence (OR 24.67; 95% CI 5.54-207; P < .001) was the main predictor of increased error severity. CONCLUSION: The major predictor in increasing both the incidence and severity of MEs is physician adherence to evidence-based guidelines (EBG). Strict regulations for anticoagulant prescribing through an anticoagulant stewardship program are a necessity.

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers.

PURPOSE: The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin. METHODS: Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC0-∞), (AUC0-t); Cmax; tmax; t½, ke; ka were measured using validated LC-MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin. RESULTS: Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7-142.3) for AUC0-t, and 167.6% (154.6-181.8) for Cmax. On the other hand, sildenafil pharmacokinetics were not affected. Gmax changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUCg0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs. CONCLUSION: Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered. REGISTRATION: This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019.

The efficacy and safety of itopride in feeding intolerance of critically ill patients receiving enteral nutrition: a randomized, double-blind study.

BACKGROUND: Enteral feeding intolerance (EFI) is a frequent problem in the Intensive care unit (ICU) and is associated with poor clinical outcomes leading to worse prognosis in terms of mortality and ICU stay. Nowadays, prokinetic drugs are the mainstay of therapy in EFI. However, available prokinetics have uncertain efficacy and safety profiles. Itopride, is a prokinetic agent which is different and unique from the available prokinetics because of its dual mode of action as well as its tolerability and safety. The current study compared the efficacy and safety of Itopride against metoclopramide for EFI in critically ill patients. Moreover, it tested the utility and applicability of ultrasonography to measure gastric residual volume (GRV) in this population. METHODS: This randomized, double-blind study included 76 EFI patients who were randomly assigned to either Itopride or metoclopramide group. The primary outcome was to measure GRV by ultrasonography. Secondary outcomes included the percentage ratio of enteral feed volume, energy and protein received by patients over 7 days of treatment, ICU length of stay, safety parameters and occurrence of infectious complications or vomiting. RESULTS: Thirty-five patients of each group completed the study. At day 7, itopride significantly decreased GRV compared with metoclopramide group (p = 0.001). Moreover, there was a significant increase in the ratios of received enteral nutrition feed volume, calories, and protein after the one-week therapy in the itopride group more than the metoclopramide group (p = 0.001), (p = 0.002), (p = 0.01), respectively and there were no differences in any secondary outcomes or adverse events between the two groups. CONCLUSION: In critically ill patients with EFI, itopride was well tolerated with superior efficacy to metoclopramide. In addition, we demonstrated that ultrasonography is a simple, non-invasive, inexpensive, and undemanding method for GRV measurements and can offer reliable assessments in the gastric emptying modality. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03698292). Date: October 5, 2018.

Impact of Docosahexaenoic acid supplementation on proinflammatory cytokines release and the development of Necrotizing enterocolitis in preterm Neonates: A randomized controlled study.

INTRODUCTION: Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current study was conducted to assess the potential immunomodulatory effect of Docosahexaenoic Acid (DHA) supplementation in preterm neonates at neonatal intensive care unit (NICU) and subsequently its effect on preventing or reducing NEC incidence. METHODS: This was a prospective randomized controlled study. A total of 67 neonates, with gestational age equal or less than 32 weeks at birth and weight less than or equal 1500 g, were randomly assigned to either DHA group or the control group. Modified Bell's staging criteria for NEC was used as an objective tool for diagnosis and staging of NEC. Levels of Interleukin 1 beta (IL-1ß) were measured at baseline and after 10 days. Mortality and NICU length of stay (LOS) were also monitored. RESULTS: Thirty neonates of each group completed the study. A statistically significant difference was observed between the two groups regarding diagnosis and staging of NEC (p = 0.0001). There was also a statistically significant difference between DHA group 22(73.3), 95% CI [55.9, 86.5] and the control group 8 (26.7), 95% CI [13.5, 44.1] in the percentage change in IL-1ß levels (p = 0.0001).A statistically significant association was found between IL and 1 ß change and NEC diagnosis (p = 0.001). NICU LOS was significantly lower among DHA group 21.63 ± 6.67 compared to the control group 25.07 ± 4.67 (p = 0.025). Mortality n (%) among the control group 4 (11.8) was higher than DHA group 3 (9.1), however, no significant difference was detected (p = 1.0). CONCLUSION: Findings of this study suggest that enteral DHA supplementation can reduce NEC incidence in preterm neonates through its immunoregulatory effect that modulates production of regulatory cytokines.Trial registration: Registered at clinical trials.gov (NCT03700957), 6 October 2018.

Randomized controlled open-label study of the effect of vitamin E supplementation on fertility in clomiphene citrate-resistant polycystic ovary syndrome.

AIM: To evaluate the effect of vitamin E on ovulation and pregnancy in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: A prospective, randomized, controlled, open label study was conducted on women with CC-resistant PCOS. Patients were randomized, to either control group (n = 30), who received metformin 500 mg thrice daily, in addition to 150 mg/day CC for 5 days starting from day 3 of menstruation for three menstruation cycles, or vitamin E group (n = 30) who received vitamin E 1500 IU/day for the whole study period in addition to metformin and CC with the same previous regimen. The primary outcome was cumulative ovulation rate, while secondary outcomes were pregnancy rate, serum midluteal progesterone, mean follicular diameter, number of dominant follicles and endometrial thickness. RESULTS: Ovulation was reported in 57 (64.8%) of 88 cycles in the control group and 63 (73.3%) of 86 cycles in the vitamin E group (P = 0.227), while pregnancy was reported in 4 (4.5%) of 88 cycles in the control group and 6 (7%) of 86 cycles in the vitamin E group (P = 0.491).There were nonsignificant differences between groups regarding serum midluteal progesterone, number of dominant follicles and mean follicular diameter. Endometrial thickness was significantly higher in the vitamin E group compared to the control group. CONCLUSION: The findings of this trial do not support the hypothesis that vitamin E may increase the ovulation and pregnancy rates in women with clomiphene citrate-resistant PCOS.

Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans.

Indapamide is an effective and safe antihypertensive medication showing a beneficial effect in combination with other antihypertensive agents regarding morbidity and mortality. A comparative study was performed under fasting and fed conditions to investigate the effect of food and selected single nucleotide polymorphisms in the uridine diphosphate glucuronyl transferase (UGT2B7) gene on the pharmacokinetics and pharmacodynamics behavior of indapamide 1.5 mg sustained release. Forty-nine healthy volunteers aged 18-55 years were randomized into two groups; 25 volunteers were administered indapamide under fasting conditions and 24 under fed conditions. Genotyping of the UGT2B7 rs7438135 and rs11740316 was done before commencing the study using predesigned TaqMan assays. Results showed that food independently decreased the value of indapamide' Tmax by 5.5 h and increased the value of Cmax by 8.7 ng/mL. On the other hand, all genetic variants of both UGT2B7 SNPs had no significant impact on the values of Tmax, Cmax, and AUC0-t; however, it was found that rs11740316 variant AG was correlated with a 2.8 h lower MRTinf. Finally, BMI positively correlated with longer MRTinf. It was concluded that none of rs7438135, rs11740316, or food had a significant impact on the pharmacodynamic properties. Food had a modest impact on indapamide Cmax and Tmax values, while there were unremarkable differences in safety and efficacy.

Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study.

BACKGROUND: Hepatitis C virus (HCV) is the primary contributor to chronic hepatic diseases. A rapid change in the situation took place with the advent of oral direct-acting antivirals (DAAs). However, a comprehensive review of the adverse event (AE) profile of the DAAs is lacking. This cross-sectional study aimed to analyze the reported Adverse Drug Reactions (ADRs) with DAA treatment using data from VigiBase, the WHO Individual Case Safety Report (ICSR) database. METHODS: All ICSRs reported to VigiBase with sofosbuvir (SOF), daclatasvir (DCV), sofosbuvir /ledipasvir (SOF/LDV) and ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in Egypt were extracted. Descriptive analysis was performed to summarize patients' and reactions' characteristics. Information components (ICs) and proportional reporting ratios (PRRs) for all reported ADRs were calculated to identify signals of disproportionate reporting. Logistic regression analysis was performed to identify the DAAs association with serious events of concern while adjusting for age, gender, pre-existing cirrhosis, and ribavirin use. RESULTS: Out of 2925 reports, 1131 (38.6%) were serious. The most commonly reported reactions; anaemia (21.3%), HCV relapse (14.5%) and headache (14%). For the disproportionality signals; HCV relapse was reported with SOF/DCV (IC 3.65, 95% CrI 3.47-3.79) and SOF/RBV (IC 3.69, 95% CrI 3.37-3.92), while anaemia (IC 2.85, 95% CrI 2.26-3.27) and renal impairment (IC 2.12, 95% CrI 0.7-3.03) were reported with OBV/PTV/r. CONCLUSION: The highest severity index and seriousness were reported with SOF/RBV regimen. A significant association was found for OBV/PTV/r with renal impairment and anaemia although being the superior regimen in terms of efficacy. The study findings call for further population-based studies for clinical validation.

ß1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

Aim: To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS). Patients & methods: Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping. Results: Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5% ± 7.8% vs -0.76% ± 8.7%, p = 0.000218), and (-9.5% ± 9.7% vs -0.80% ± 11.5%, p = 0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49. Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Pharmacogenetics is a field of study that explores how our genes can affect how well certain medicines work. In this study, scientists looked at a specific gene called beta1-adrenergic receptor to see how it can influence a drug called bisoprolol. They wanted to find out if some people's genes made bisoprolol work better for them. They studied 77 patients with a heart problem called acute coronary syndrome (ACS) who were taking bisoprolol for 4 weeks. The researchers discovered that people with a particular gene piece called Arg389Arg responded better to bisoprolol. They had bigger reductions in their blood pressure compared with those who had a different gene called Gly389. This finding suggests that by looking at a person's genes, doctors might be able to predict how well bisoprolol will work for them. This way, doctors can choose the best treatment for each patient, making sure they get the most benefit from the medicine.

Advances in the Applications of Bioinformatics and Chemoinformatics.

Chemoinformatics involves integrating the principles of physical chemistry with computer-based and information science methodologies, commonly referred to as "in silico techniques", in order to address a wide range of descriptive and prescriptive chemistry issues, including applications to biology, drug discovery, and related molecular areas. On the other hand, the incorporation of machine learning has been considered of high importance in the field of drug design, enabling the extraction of chemical data from enormous compound databases to develop drugs endowed with significant biological features. The present review discusses the field of cheminformatics and proposes the use of virtual chemical libraries in virtual screening methods to increase the probability of discovering novel hit chemicals. The virtual libraries address the need to increase the quality of the compounds as well as discover promising ones. On the other hand, various applications of bioinformatics in disease classification, diagnosis, and identification of multidrug-resistant organisms were discussed. The use of ensemble models and brute-force feature selection methodology has resulted in high accuracy rates for heart disease and COVID-19 diagnosis, along with the role of special formulations for targeting meningitis and Alzheimer's disease. Additionally, the correlation between genomic variations and disease states such as obesity and chronic progressive external ophthalmoplegia, the investigation of the antibacterial activity of pyrazole and benzimidazole-based compounds against resistant microorganisms, and its applications in chemoinformatics for the prediction of drug properties and toxicity-all the previously mentioned-were presented in the current review.

Assessment of neonatal intensive care unit nurses' compliance with standard precautions of infection control and identification of enabling factors.

Background: Rigorous implementation of infection prevention and control practices by healthcare workers in different healthcare settings is of utmost importance. Neonates, particularly preterm babies in neonatal intensive care units, are a vulnerable population at high risk for developing nosocomial infections. Nurses have the greatest risk of spreading healthcare-associated infections among patients and healthcare workers. This study was conducted to assess the compliance of neonatal intensive care unit nurses with standard precautions of infection control and to identify the potential influencing factors. Results: This was a cross-sectional study, whereby the compliance of a total of 58 neonatal intensive care unit nurses with standard precautions of infection control was assessed using the Arabic version of the Compliance with Standard Precautions Scale (CSPS-A). Student's t test, ANOVA test, and post hoc test were used for analysis.A suboptimal compliance rate (66.7%) was detected, with the highest for disposal of sharp articles into sharps boxes (86.2%) and the lowest for disposal of sharps box not only when full (27.6%). Significant differences were observed when participants were grouped according to their clinical experience and qualifications, where participants with longer clinical experience displayed higher mean scores for the use of protective devices score (P = 0.024), disposal of sharps score (P = 0.003), and total CSPS score (P = 0.006). Conclusions: Clinical experience and educational qualifications are key factors that impact nurses' compliance with infection control practices. Nurses should receive up-to-date evidence-based educational and practical sessions that link theory to clinical practice and elucidate the importance of accurate implementation of proper infection prevention and control practices.

Associations between Nutrigenomic Effects and Incidences of Microbial Resistance against Novel Antibiotics.

Nutrigenomics is the study of the impact of diets or nutrients on gene expression and phenotypes using high-throughput technologies such as transcriptomics, proteomics, metabolomics, etc. The bioactive components of diets and nutrients, as an environmental factor, transmit information through altered gene expression and hence the overall function and traits of the organism. Dietary components and nutrients not only serve as a source of energy but also, through their interactions with genes, regulate gut microbiome composition, the production of metabolites, various biological processes, and finally, health and disease. Antimicrobial resistance in pathogenic and probiotic microorganisms has emerged as a major public health concern due to the presence of antimicrobial resistance genes in various food products. Recent evidence suggests a correlation between the regulation of genes and two-component and other signaling systems that drive antibiotic resistance in response to diets and nutrients. Therefore, diets and nutrients may be alternatively used to overcome antibiotic resistance against novel antibiotics. However, little progress has been made in this direction. In this review, we discuss the possible implementations of nutrigenomics in antibiotic resistance against novel antibiotics.

COVID-19 Vaccination in Pediatrics: Was It Valuable and Successful?

BACKGROUND: The mass vaccination of children against coronavirus 2019 disease (COVID-19) has been frequently debated. The risk-benefit assessment of COVID-19 vaccination versus infection in children has also been debated. AIM: This systematic review looked for answers to the question "was the vaccination of our children valuable and successful?". METHODS: The search strategy of different articles in the literature was based on medical subject headings. Screening and selection were based on inclusion/exclusion criteria. RESULTS AND DISCUSSION: The search results revealed that the majority of the reported adverse events after COVID-19 vaccination in pediatrics were mild to moderate, with few being severe. Injection site discomfort, fever, headache, cough, lethargy, and muscular aches and pains were the most prevalent side effects. Few clinical studies recorded significant side effects, although the majority of these adverse events had nothing to do with vaccination. In terms of efficacy, COVID-19 disease protection was achieved in 90-95% of cases for mRNA vaccines, in 50-80% of cases for inactivated vaccines, and in 58-92% of cases for adenoviral-based vaccines in children and adolescents. CONCLUSIONS: Based on available data, COVID-19 immunizations appear to be safe for children and adolescents. Furthermore, multiple studies have proven that different types of vaccines can provide excellent protection against COVID-19 in pediatric populations. The efficacy of vaccines against new SARS-CoV-2 variants and the reduction in vaccine-related long-term adverse events are crucial for risk-benefit and cost-effectiveness assessments; therefore, additional safety studies are required to confirm the long-term safety and effectiveness of vaccinations in children.

COVID-19 signalome: Potential therapeutic interventions.

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development.

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.

Evaluation of the combination effect of rutin and vitamin C supplementation on the oxidative stress and inflammation in hemodialysis patients.

Background: Hemodialysis (HD) patients are at risk of malnutrition, cardiovascular complications, and all-cause mortality due to oxidative stress and inflammation. Some studies have demonstrated that rutin attenuates oxidative stress and inflammation in CKD rats, but its effects in HD patients are unknown to date. Aim: The aim of this study was to evaluate the effect of rutin and vitamin C versus vitamin C alone on oxidative stress and inflammation in HD patients. Methods: A prospective randomized, open-label, controlled trial enrolled on hundred and five HD patients divided into three groups as follows: patients in group 1 were given a rutin/vitamin C combination (Ruta C group as the combination trade name is known as Ruta C 60 tablets), patients in group 2 were given vitamin C (1 g) (vitamin C group), and group 3 was the control group; the study period was 16 weeks. The following were assessed at baseline and at the end of the study: serum malondialdehyde (MDA), glutathione peroxidase (GPx), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), lipid profile levels, and erythrocyte sedimentation rate. Results: It was found that vitamin C significantly increased serum GPx in group 2 (p = 0.001) compared to a non-significant result in both group 1 and 3; in addition, serum MDA and TNF-α values had decreased significantly in the three groups compared to their baselines; however, a non-significant difference was seen among the studied groups at the end of the study. On the other hand, MDA levels were reduced by 50% in interventional groups compared to 28% in the control group, while the Ruta C group showed an 80% reduction in the level of TNF α compared to the 78% reduction observed in the vitamin C group, and finally, the interventional drugs showed a significant improvement in the lipid profile. Conclusion: Vitamin C supplementation alone for 16 weeks had a potential effect on the antioxidant's GPx activity. Moreover, it was reported that both vitamin C alone or the rutin/vitamin C combination (Ruta C) showed a protective role against lipid peroxidation, evidenced by the reduced levels of MDA. Finally, rutin had a favorable synergistic effect with vitamin C in reducing TG and TNF-α levels and increasing HDL-C level.

Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial.

Background: Critically ill patients have an increased requirement for vitamin C in sepsis and these patients have low levels of vitamin C. The researchers validated the efficacy of high-dose vitamin C intravenous infusion (IVI) in patients with sepsis requiring mechanical ventilation. Methods: Forty patients were randomly assigned to 2 groups (20 each) in a 1 : 1 ratio in accordance with the vitamin C treatment regimen: Group I (GI): patients received 1.5 g/6 h vitamin C in 50 ml of dextrose 5% in water (D5W) IVI over 30 minutes for 4 consecutive days; Group II (GII): patients received 100 mg vitamin C/day as a first single dose in 50 ml of D5W IVI over 30 minutes and the other three subsequent doses were 50 ml of plain D5W IVI over 30 minutes for 4 consecutive days. Primary outcomes were the change in sequential organ failure assessment (SOFA) score at day 7, the incidence of ventilator-associated pneumonia (VAP), and the plasma vitamin C level. The glutathione peroxidase (GPX) activity, C-reactive protein (CRP) level, duration of vasopressor therapy, and 28-day mortality were secondary outcomes. Results: The change in SOFA score at day 7 showed a significant difference between GI and GII (p < 0.001). The incidence of early VAP was significantly lower in GI (p=0.044). Vitamin C levels showed a significant rise in GI at day 1 and day 4 (p < 0.001 and p < 0.001, respectively). GPX activity of day 4 and day 7 was significantly higher in GI (p=0.005 and p=0.014, respectively). CRP levels of day 4 and day 7 were significantly higher in GII (p < 0.001 and p < 0.001, respectively). There was a significant difference in 28-day mortality (p=0.038) and duration of vasopressor therapy (p=0.033) in GI compared to GII. Conclusion: The early use of high-dose vitamin C intravenous infusion in patients with sepsis requiring mechanical ventilation in combination with the standard treatment for sepsis lowered the incidence of VAP, increased the antioxidant status, and improved the illness severity. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier (NCT04029675).