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Background: The combination of sofosbuvir (SOF) and daclatasvir (DCV) has shown preliminary efficacy for patients with COVID-19 in five open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir and daclatasvir to standard care improved clinical endpoints in hospitalized patients with moderate or severe COVID-19. Methods: This was a placebo-controlled, randomized clinical trial in adults with moderate or severe COVID-19 admitted to 19 hospitals in Iran. Patients were randomized to SOF/DCV 400/60mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O 2 saturation

SARS-CoV-2 that causes Coronavirus disease 2019 (COVID-19) was first known in Wuhan, China, in December 2019. The aim of this study was to evaluate the level of common hepatic, renal, and cardiac diagnostic markers in hospitals in patients with severe COVID 19. In this study, 259 patients with symptoms of severe COVID-19 and a positive RT-PCR assay of nasopharyngeal samples were enrolled. Inclusion criteria are positive for COVID-19 patients at the diagnosis of an infectious disease physician. Diagnostic markers of liver, kidney, and heart were evaluated by age and gender. In this study, 48.3% of patients severe with COVID-19 were male, and 51.7% were female. The mean of markers such as LDH, Direct Bilirubin, SGOT, SGPT, D-dimer was higher than normal, which was observed in men more than women. The mean of CK-MB also was higher than normal, which was observed in women more than men. The highest mean of markers was seen in the older ages. The mean of BUN was observed in the age range of 55-64 years and above 65 years above normal. But the mean of CPK, creatinine, potassium and alkaline phosphatase were normal. The results of the present study showed an increase in the level of some of the most important diagnostic markers of hepatic, renal, and cardiac in patients with COVID 19. This increase was greater in some markers, including SGOT, SGPT, Direct bilirubin, LDH, D-dimer, in men than in women, and more in older patients.

Background and aims The current study was done to examine the efficacy of naproxen in the management of patients with COVID-19 infection. Methods This randomized, double-blind, placebo-controlled, clinical trial was done on hospitalized adult patients with confirmed COVID-19 infection. Patients were randomly assigned to receive either naproxen (two capsules per day each containing 500 mg naproxen sodium) or placebo (containing starch) for five days along with the routine treatment that was nationally recommended for COVID-19 infection. Clinical symptoms of COVID-19 infection, the time to clinical improvement, blood pressure, laboratory parameters, and death due to COVID-19 infection were considered as the outcome variables in the present study. Results Treatment with naproxen improved cough and shortness of breath in COVID-19 patients; such that, compared with placebo, naproxen intake was associated with 2.90 (95% CI: 1.10–7.66) and 2.82 (95% CI: 1.05–7.55) times more improvement in cough and shortness of breath, respectively. In addition, naproxen administration resulted in a significant increase in mean corpuscular volume (MCV) and had a preventive effect on the reduction of systolic blood pressure in COVID-19 patients. Conclusion Treatment with naproxen can improve cough and shortness of breath in COVID-19-infected patients. Further studies are required to confirm our findings.

The combination therapy of cytotoxic drugs and chemosensitizing agents encapsulated in nanoparticles has been highlighted as an effective treatment for various cancers. Combination therapy is promising to produce synergistic anticancer effects, to magnify the treatment effect and overcome multidrug resistance. In this investigation, we have studied augmentation of therapeutic efficacy upon c combinational treatment of paclitaxel (PCL) and curcumin (Cur), an inhibitor of nuclear factor kappa B (NF-κB), in OVCAR-3 cell. PCL and Cur were encapsulated in nanoniosome formulations. Then, the effects of nanoniosome formulations on cytotoxicity, expression profile of AKT-1 gene and NF-κB activity were evaluated. The findings showed that nanoniosomes were highly efficient in delivering the PCL and Cur drugs to OVCAR-3 cell. A 3-fold and 3.6-fold reduction in Cur and PCL concentration were measured, respectively, when the Cur and PCL were administered in nanoniosomes compared to free Cur and free PCL solutions in OVCAR-3 cell. Moreover, curcumin could significantly increase cell growth inhibition of paclitaxel so that, in presence of NioCur, the IC50 of NioPCL was diminished to ∼2.4 –fold. AKT-1 gene expression studies showed that co-administration of curcumin/paclitaxel nanoniosome formulations caused 91.2% reduction in AKT-1 gene expression compared to control group. On the other hand, this co-administration caused 79.42% reduction in the amount of NF-κB activity and a 4-fold reduction in the activity of the MDR protein pumps in cancer cells compared to the control group. Our findings demonstrate that the combination therapy of PCL with Cur using the nanoniosomes delivery is a promising strategy for breast cancer more effective therapy

Background MicroRNA expression signature and reactive oxygen species (ROS) production have been associated with the development of cardiovascular diseases (CVDs). This study aimed to evaluate oxidative stress, inflammation, apoptosis, and the expression of miRNA-208a and miRNA-1 in cardiovascular patients. Methods The study population included four types of patients (acute coronary syndromes (ACS), myocardial infarction (MI), arrhythmia, and heart failure (HF)), with 10 people in each group, as well as a control group. Quantitative real-time PCR was performed to measure mir-208 and miR-1 expression, the mRNAs of inflammatory mediators (TNFα, iNOS/eNOS), and apoptotic factors (Bax and Bcl2). XOX, MDA, and antioxidant enzymes (CAT, SOD, and GPx) were measured by ZellBio GmbH kits by an ELISA Reader. Results The results showed significant decreases in the activity of antioxidant enzymes (CAT, SOD, and Gpx) and a significant increase in the activity of the MDA and XOX in cardiovascular patients. Significant increases in IL-10, iNos, iNOS / eNOS, and TNF-α in cardiovascular patients were also observed. Also, a significant increase in the expression of miR-208 (HF> arrhythmia> ACS> MI) and a significant decrease in the expression of miR-1 (ACS> arrhythmia> HF> MI) were found in all four groups in cardiovascular patients. Conclusion The results showed increases in oxidative stress, inflammation, apoptotic factors, and in the expression of miR-208a in a variety of cardiovascular patients (ACS, MI, arrhythmia, and HF). It is suggested that future studies determine the relationships that miR-1, miR-208, and oxidative stress indices have with inflammation and apoptosis.

BACKGROUND: The effect of total suspended particulate matter (TSP) was investigated on the expression of inflammatory and apoptotic factors in diabetic rats, and the effect of crocin and insulin was examined on these factors. METHODS: Fifty-four adult male wistar rats were divided into nine experimental groups: control group, crocin group (received crocin, 50 mg/kg), diabetic group (received a single dose of alloxan at 120 mg/kg, IP), TSP group (5 mg/kg TSP instilled intratracheally), diabetic-crocin group (received crocin at 50 mg/kg after the induction of diabetes by alloxan (120 mg/kg)), diabetic-insulin group (received regular insulin (5 U/kg), crocin-TSP group (received crocin at 50 mg/kg, IP, and then 5 mg/kg TSP was instilled intratracheally), diabetic-TSP-insulin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose (5 U/kg) of regular insulin), and diabetic-TSP-crocin group (after receiving alloxan (120 mg/kg) and instilling TSP (5 mg/kg, intratracheally), a single dose of crocin (50 mg/kg, IP)). Quantitative real-time PCR was performed to measure the expression of the mRNAs of apoptotic (Bax and Bcl2) and inflammatory mediators (TNFα, COX2, iNOS/eNOS) in Wistar rats. RESULTS: In diabetic and TSP groups the inflammatory factors and BAX/Bcl2 ratio significantly increased compared to the control group. In diabetic-TSP-insulin and diabetic-TSP-crocin, a significant decrease was observed in the rate of inflammatory factors and BAX/Bcl2 ratio. CONCLUSION: The results suggested that diabetes and exposure to TSP increase the rate of apoptosis and inflammation, and also demonstrated the anti-apoptotic and anti-inflammation role of insulin and crocin.

Objectives Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. Methods Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT–PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. Results Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04–0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1–12.1, P Conclusions Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.

Particulate matter (PM) inhalation is an established trigger of cardiovascular events such as cardiac arrhythmias that occur within hours to days after exposure. Higher daily PM levels are related to acute increases in systemic arterial blood pressure (BP). The aim of the present study was to evaluate the effects of PM10 on electrocardiogram (ECG) parameters, blood pressure, lipid peroxidation (MDA), xanthine oxidase, and antioxidant enzyme in healthy rats and also to examine the protective effects of vanillic acid (VA) in this respect. Eighty male Wistar rats were divided into eight groups (n = 10), namely control (normal saline, gavage), VAc (10 mg/kg), sham (normal saline, intratracheal instillation), VA (10 mg/kg VA, 10 days gavage +0.1 ml normal saline, intratracheal instillation), PM1 (0.5 mg/kg), PM2 (2.5 mg/kg), PM3 (5 mg/kg), PM3 + VA (5 mg/kg, intratracheal instillation + 10 mg/kg VA, 10 days, gavage) groups. The rats were anesthetized and 0.1 ml of saline as well as a certain concentration of PM10 was instilled into the trachea and it was repeated after 48 h, then 30 min after that, PR interval, QTc, and systolic blood pressure were measured. The activities of antioxidant enzymes, xanthine oxidase (XOX), and malondialdehyde (MDA) were measured in plasma by special Kits. A significant increase in blood pressure (BP), PR interval, QTc, MDA, and XOX and a significant decrease in antioxidant enzyme (CAT, SOD, and GPx) occurred in PM10 groups. Vanillic acid ameliorated blood pressure, QTc, PR interval, XOX, MDA, and increased antioxidant enzymes (SOD, CAT, and GPx) significantly. In the present study, it was shown that PM10 had devastating effects on the heart and blood pressure, probably due to the increased oxidative stress in healthy rats. Vanillic acid could improve the symptoms of PM10 exposure and can be used as an antioxidant agent against the harmful effects of PM10.

Myocardial infarction is the acute condition of myocardial necrosis that occurs as a result of imbalance between coronary blood supply and myocardial demand. Air pollution increases the risk of death from cardiovascular diseases (CVDs). The aim of this study was to investigate the effects of particulate matter (PM) on oxidative stress, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) level induced by ischemia-reperfusion injury, and the protective effects of vanillic acid (VA) in the isolated rat heart. Male Wistar rats were randomly divided into eight groups (n = 10), namely control, VAc, sham, VA, PMa (0.5 mg/kg), PMb (2.5 mg/kg), PMc (5 mg/kg), and PMc + VA groups. Particles with an aerodynamic diameter

Air pollution related damage to the Central Nervous System (CNS) has been widely neglected in studies of air pollution and adverse health outcomes. The aim of this study was to evaluate hospital admissions in Abadan, Iran for several neurological diseases including cerebral ischemic attack, epilepsy, and various types of headache on days with polluted air compared with clean days. Abadan is a city in Khuzestan Province that is located in southwestern Iran and experiences many sand and dust storms. The sampling station was located on the roof of the Department of Environment (DoE) in Abadan. Sampling was conducted over four years (from March 2012 to July 2016). Hospital admissions of patients with cerebral ischemic attack, epilepsy, and headache types from March 2012 to July 2016 were obtained from the Hospital Information System (HIS). This study showed that hospital admissions for patients with cerebral ischemic attack, epilepsy, and patients with types of headaches on dusty days increased significantly compared to hospital admissions on clean days. Also hospital admissions of these patients significantly increased with increased concentrations of coarse particulate matter (PM10). Ambient PM10 concentrations in Abadan were relatively high. Significant increases in hospital admissions in this study were related to high PM10 concentrations. Elderly and women were susceptible subpopulations showing more sensitivity to dust compared with the rest of the population. Staying indoors and using facial respirators under these emergency conditions could be effective in protecting these sensitive subjects against dust.

Epidemiological studies show that particulate matter (PM) is the principal instigator of some adverse clinical symptoms involving cardiovascular diseases. PM exposure can increase experimental infarct size and potentiate myocardial ischemia and arrhythmias in experimental MI models such as ischemia-reperfusion (I/R) injury.The present study was aimed to evaluate the effects of particulate matter (PM10) on ischemia- reperfusion induced arrhythmias with emphasis on the protective role of VA as an antioxidant on them. Male Wistar rats were divided into 8 groups (n=10): Control, VAc, Sham, VA, PM1 (0.5 mg/kg), PM2 (2.5 mg/kg), PM3 group (5 mg/kg), PM3 + VA group. Within 48 hours, PM10 was instilled into trachea in two stages. Then the hearts were isolated, transferred to a Langendorff apparatus, and subjected to global ischemia (30 minutes) followed by reperfusion (60 minutes). The ischemia- reperfusion induced ventricular arrhythmias were assessed according to the Lambeth conventions.In the present study,the number, incidence and duration of arrhythmiasduring30 minutes ischemia were demonstrated to be more than those in the reperfusion stage. PM exposure increased significantly the number, incidence and duration of arrhythmias in the ischemia and reperfusion duration. Vanillic acid reduced significantly the number, incidence and duration of arrhythmias during the ischemia and reperfusion period.In summary, the results of this study demonstrated that the protective and dysrhythmic effects of VA in the PM exposure rats in I/R model are probably related to its antioxidant properties.