Blood Features Associated with Viral Infection Severity: An Experience from COVID-19-Pandemic Patients Hospitalized in the Center of Iran, Yazd.

Pandemics such as coronavirus disease 2019 (COVID-19) can manifest as systemic infections that affect multiple organs and show laboratory manifestations. We aimed to analyze laboratory findings to understand possible mechanisms of organ dysfunction and risk stratification of hospitalized patients in these epidemics. Methods. This retrospective study was conducted among patients admitted to COVID-19 referral treatment center, Shahid Sadoughi Hospital, Yazd, Iran, from April 21 to November 21, 2021. It was the fifth peak of COVID-19 in Iran, and Delta (VOC-21APR-02; B.1-617.2) was the dominant and most concerning strain. All cases were positive for COVID-19 by RT-PCR test. Lab information of included patients and association of sex, age, and outcome were analyzed, on admission. Results. A total of 466 COVID-19 patients were included in the study, the majority of whom were women (68.9%). The average age of hospitalized patients in male and female patients was 57.68 and 41.32 years, respectively (p < 0.01). During hospitalization, abnormality in hematological and biochemical parameters was significant and was associated with the outcome of death in patients. There was incidence of lymphopenia, neutrophilia, anemia, and thrombocytopenia. The changes in neutrophil/lymphocyte (N/L) and hematocrit/albumin (Het/Alb) ratio and potassium and calcium levels were significant. Conclusion. Based on these results, new biochemical and hematological parameters can be used to predict the spread of infection and the underlying molecular mechanism. Viral infection may spread through blood cells and the immune system.

Designing the pH-sensitive indicator based on starch nanoparticle with bromocresol green for monitoring meat spoilage.

The starch nanoparticle, combined with bromocresol green (BCG), served as a pH-sensitive indicator to monitor meat quality throughout an 8-day refrigerated storage period. The meat samples were sealed in package which the pH-sensitive indicator attached to the interior part of packaging lid. The changes in meat quality were evaluated by total volatile base nitrogen (TVBN), pH, total viable count (TVC), sensory analysis, and color in interval of 0, 3, 5, 7, and 8-days storage at 4°C. Initial TVBN values were recorded at 19.6 mg/100 g, increased to 26.6 mg/100 g by the end of storage period. The pH value was significantly increased after 8 days storage at 4°C. The observed color variation in the indicator from yellow to blue was attributed to the concurrent increases in TVBN, TVC, and pH. The indicator color changes had significant correlation with analyzed chemical quality of stored meat. Therefore, the designed BCG pH-sensitive indicator could be effective in monitoring the meat spoilage during storage.

Combination of atorvastatin and gemfibrozil plus physical activity: an animal model of statin/fibrate-induced myopathy.

INTRODUCTION: Drug-induced myopathy is among the most common causes of muscle disease. Lipid-lowering drugs, primarily the statins as inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are a common cause of myopathy. Statin-fibrate combination potentially increases risk for myopathy and rhabdomyolysis. Blood levels of the enzymes creatine kinase (CK), aldolase and lactate dehydrogenase (LDH) increase during myopathy. Exercise may be a trigger for statin-associated muscle symptoms (SAMS). METHODS: In this study a model of myopathy induction was designed via combination of oral atorvastatin, gemfibrozil and exercise for ten days in rats. To maximise exercise, the rats were placed in a pool of water and allowed to swim before sinking in the last three days. Finally, the mean of swimming tolerance times and blood levels of creatine kinase, aldolase and lactate dehydrogenase were measured. RESULTS: The results showed a significantly (p < 0.05) decreased swimming tolerance time and elevated enzyme levels in rats receiving atorvastatin (ATV) and gemfibrozil (GMF) plus exercise compared with those rats in other groups. This animal model can be used to evaluate the effects of medication on reduction of statin/fibrate-induced myopathy.

Molecular identification and phylogenetic analysis of Dipetalonema evansi (LEWIS, 1882) in camels (Camelus dromedarius) of Iran.

Despite the economic importance of camels, the parasites that affect them have not received adequate attention so far and molecular studies are scarce compared to other livestock. In this study, we characterized peripheral blood microfilariae in 200 healthy one-humped camels (Camelus dromedarius) from south-east Iran by microscopy and molecular tools to receive a more detailed insight into prevalence and species that affect them. Moreover, adult specimens of the filarial nematode Dipetalonema evansi were collected from the carcass of an infected animal. Microscopic examination was performed on Giemsa-stained blood smears, and blood was also spotted on Whatman FTA(®) cards for DNA analysis. Genomic DNA was extracted, and PCR was carried out for the detection of filaroid helminths, followed by sequence analysis of positive samples. Four samples were positive for microfilariae by microscopy, while 16 animals (8 %) were positive by PCR. Sequence analysis revealed D. evansi in all cases. Phylogenetic analysis of a cytochrome C oxidase subunit I (COI) sequence of filaroid nematodes showed that most species in a single genus cluster in the same clade; however, D. evansi and D. gracile are not monophyletic and branch rather at the base of the tree. Further studies on the life cycle of D. evansi, specifically the identification of intermediate host(s), have become feasible with the provision of the first specific COI sequences in this study.

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis.

The age-related senescence of adult tissues is associated with the decreased level of angiogenic capability and with the development of a degenerative disease such as atherosclerosis which thereafter result in the deteriorating function of multiple systems. Findings indicate that tissue senescence not only diminishes repair processes but also promotes atherogenesis, serving as a double-edged sword in the development and prognosis of ischaemia-associated diseases. Evidence evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in different tissues. Here, miRNAs would promote new potential targets for optimizing therapeutic methods in blood flow recovery to the ischaemic area. Effectively beginning an ischaemia therapy, a more characteristic of miRNA changes in adult tissues is prerequisite and in the forefront. It may also be a preliminary phase in treatment strategies by stem cell-based therapy.

Combined 1,25-Dihydroxy-vitamin D and Resveratrol: A Novel Therapeutic Approach to Ameliorate Ischemia Reperfusion-Induced Myocardial Injury.

The aim of this study was to assess the effect of combined 1,25-dihydroxyvitamin D (1,25 D) and resveratrol on cardiac arrhythmias, infarct size, and transcription of catalase, thioredoxin-1 and B-cell lymphoma 2 (Bcl-2), following myocardial ischemia-reperfusion (IR) in male rats. Ligation of coronary artery was performed in rats (n = 6 per group) without any treatment (IR group), pretreated with 0.1 µg/kg/day of 1,25 D (1,25 D + IR), 1 mg/kg/day of resveratrol (Res + IR) or a combination (1,25 D + Res + IR) for 14 days. Arrhythmias were analyzed according to the Lambeth conventions, and infarct size was measured by 2,3,5-triphenyl-2H-tetrazolium chloride staining. Expression of prosurvival genes was evaluated by real-time polymerase chain reaction. In the 1,25 D + Res + IR group the mean infarct size was 17.6 ± 3.5 %, which was significantly less than that in the IR, 1,25 D + IR, and Res + IR groups (p < 0.001). Although the single therapy of either 1,25 D or resveratrol did not change the incidence of arrhythmias significantly, a reduction in the number of ventricular ectopic beats was noted in group 1,25 D + Res + IR (179.19 ± 58.87, p < 0.001 vs IR; p < 0.05 vs Res + IR; p < 0.01 vs Vit D + IR). Combination of 1,25 D and resveratrol increased transcription of catalase by 119 ± 37 % (p < 0.001 vs IR, p < 0.01 vs Res + IR, p < 0.001 vs 1,25 D + IR). Our study showed that combination of a non-hypotensive dose of 1,25 D and resveratrol can be a novel and effective strategy for protecting against ischemia.

The Efficacy of Propofol vs. Subcutaneous Sumatriptan for Treatment of Acute Migraine Headaches in the Emergency Department: A Double-Blinded Clinical Trial.

BACKGROUND: In this double-blinded, randomized trial, we hypothesized that propofol is as effective as sumatriptan in treating acute migraine headaches, with better control of nausea and vomiting, and fewer side effects. METHODS: Ninety cases of acute migraine attack admitted to the emergency department were randomly allocated into two treatment groups: (1) 6 mg of sumatriptan subcutaneously or (2) propofol injected intravenously in 30 to 40 mg boluses, followed by 10 to 20 mg intermittent bolus doses to sedate the patients to Ramsey score of 3 to 4. Headache severity was assessed using an 11-point visual analog scale before treatment and 30 minutes, 1 hour, and 2 hours after treatment. Accompanying symptoms, improvement in headache, and the need for anti-emetic therapy were also assessed. RESULTS: A total of 91 patients were enrolled in this study. One patient in the sumatriptan group was excluded due to severe chest tightness, and 90 patients were included in the final analysis. Pain intensity was significantly lower in the propofol group 30 minutes after treatment (P = 0.001); however, after 1 and 2 hours, there were no significant differences between the groups. The need for anti-emetic therapy and the recurrence of symptoms were significantly lower in the propofol group (P = 0.045 and P = 0.001, respectively). CONCLUSION: Propofol is equally suitable as sumatriptan for the acute treatment of migraine headaches in an emergency department setting. Moreover, the use of propofol avoids some of the adverse side effects of sumatriptan while providing better control of nausea and vomiting.

Silver and gold nanostructures: antifungal property of different shapes of these nanostructures on Candida species.

The shape of nanoparticles is an important determinant of their physical and chemical properties, possibly including the little-explored area of their use as antifungal agents. Therefore, we evaluated the in vitro antifungal activities of three different shapes of silver and gold nanostructures, including nanocubes, nanospheres, and nanowires, on Candida albicans, C. glabrata and C. tropicalis, using the microdilution and disk diffusion methods as per the guidelines of the Clinical and Laboratory Standards Institute. We found that silver and gold nanocubes had higher antifungal properties against the test species than nanospheres and nanowires. While some isolates were resistant to silver and gold nanospheres and nanowires, none of the isolates were resistant to silver and gold nanocubes. The occurrence of resistance is a new finding which should be further explored.

The cytotoxicity of silver nanoparticles coated with different free fatty acids on the Balb/c macrophages: an in vitro study.

Nanoparticles (NPs) can adsorb different molecules, because of their high local charge density and specific surface area. The toxicity of NPs is changed after adsorption, which may be different from unbound or unbound NPs. In this study, unbound silver nanoparticles (Ag NPs) and Ag NPs coated with different free fatty acids (FFAs) including lauric acid, alpha linoleic acid, oleic acid, and palmitic acid were incubated with mouse macrophages for 24 hours at 37 °C. After incubation, their toxicities, reactive oxygen species (ROS) generation, and uptake were separately investigated. This study showed that FFA-coated Ag NPs had less toxicity, higher uptake, and less ROS generation than unbound Ag NPs. Based on the results, unbound Ag NPs aggregated in RPMI1640 medium, and their size distribution was near 100-1000 nm. But all FFA-coated Ag NPs had nano metric size (near 20--40 nm) without agglomeration.

Lectin coated MgO nanoparticle: its toxicity, antileishmanial activity, and macrophage activation.

The purpose of this research was to evaluate toxicity of uncoated magnesium oxide nanoparticles (MgO NPs), MgO NPs coated with Peanut agglutinin (PNA) lectin, and PNA alone on the promastigotes of Leishmania major (L. major) and macrophages of BALB/c mice. On the other hand, antileishmanial property of uncoated MgO NPs, lectin coated MgO NPs, and PNA lectin alone was evaluated, and also macrophage activation was investigated after treatment with these materials by measurement of nitrite, H2O2, and some interleukins. This study showed that PNA lectin and lectin coated MgO NPs had approximately no toxicity on L. major and macrophages, but some toxic effects were observed for uncoated MgO NPs, especially at concentration of 500 µg/mL. Interestingly, lectin coated MgO NPs had the highest antileishmanial activity and macrophage activation, compared with uncoated MgO NPs and PNA lectin.

Transposable elements, contributors in the evolution of organisms (from an arms race to a source of raw materials).

There is a concept proposing that the primitive lineages of prokaryotes, eukaryotes, and viruses emerged from the primordial pool of primitive genetic elements. In this genetic pool, transposable elements (TEs) became a source of raw material for primitive genomes, tools of genetic innovation, and ancestors of modern genes (e.g. ncRNAs, tRNAs, and rRNAs). TEs contributed directly to the genome evolution of three forms of life on the earth. TEs now appear as tools that were used to giving rise to sexual dimorphism and sex determination, lineage-specific expression of genes and tissue differentiation and finally genome stability and lifespan determination.

The Comparison of Clinical and Histopathological Effects of Topical Psyllium (Plantago ovata) Powder and Silver Sulfadiazine on Second-Degree Burn Wound Healing in Rats.

BACKGROUND: Burn wounds are a worldwide health problem, leading to physical and psychological disabilities in all age's groups. With regard to absorbent properties of Plantago ovata mucilage which can decrease wound moisture, we aimed to compare the effect of silver sulfadiazine (SSD) 1% and powdered P. ovata on second-degree burn wound healing in rats. METHODS: This experimental study was conducted on 30 male Wistar rats with second-degree burn in three groups. Group 1 (control) did not receive any treatment; group 2 and group 3 (treated groups) were dressed daily using SSD cream and P. ovata powder, respectively. The weight of rats, wound size (by applying ImageJ software) and percentage of wound healing on the 5th, 7th, 10th, 13th, 16th, 19th, and 22nd days (by diagnosing a plastic surgeon) and histological cutaneous changes at day 22 were evaluated. The Prism software was applied for data analysis. The Haematoxylin & Eosin as well as Masson's trichrome staining were performed on wound skin biopsies. RESULTS: On day 22nd, 20%, 50% and 60% of the rats had complete wound healing in the control, SSD and P. ovata groups, respectively. A significant decrease in wound size was shown in the treated groups compared to the control group (P<0.01), but no significant difference was shown between the treated groups (P>0.05). CONCLUSION: However, the wound healing in P. ovata group or SSD was better than the control group, and the significant difference was not found with the treated group.

Modulatory Effect of Probiotics on Proinflammatory Cytokine Levels in Acrylamide-Treated Rats.

The aims of this study are to investigate the effect of acrylamide on the level of proinflammatory cytokines in the blood of acrylamide-treated rats and to find the modulatory impact of probiotics on those cytokines. Thirty-two rats were divided into four groups: rats which received 20 mg acrylamide, acrylamide with 20 mg probiotics, acrylamide with 200 mg probiotics, and standard water and food (groups 1-4, respectively). The serum levels of cytokines were measured on days 0, 15, and 30. Group 1 showed an increased serum level of IL-1ß, IL-6, and TNF-α after 15 days, and they decreased in day 30. Serum IL-6 level was significantly decreased on days 15 and 30 in rats in group 2 compared to the controls. TNF-α and IL-1ß levels were not statistically different after treated with probiotics. The exposure of rats to acrylamide led to increased systemic inflammation as evidenced by higher levels of proinflammatory cytokines, and probiotics can modulate this inflammation.

Ascorbic Acid Significantly Decreases Creatine Kinase Plasma Levels in an Animal Model of Statin/Fibrate-Induced Myopathy.

BACKGROUND: Myopathy is one of the side effects of lipid-lowering drugs, especially statins and particularly when combined with a fibrate. To diagnose myopathy and determine its severity, the plasma levels of three enzymes, creatine kinase (CK), aldolase, and lactate dehydrogenase (LDH), are routinely measured. Physical exercise can aggravate the statin-associated muscular disease. The question is whether antioxidants like ascorbic acid (Vit. C) can prevent such myopathy. METHODS: In this experiment, a combination of atorvastatin (ATV, 80 mg/kg/day) and gemfibrozil (GMF, 1000 mg/kg/day) orally for 10 days as well as exercise as forced swimming on days 8, 9, and 10 were used to induce myopathy. Ascorbic acid (50 mg/kg/day, orally) was added to ATV/GMF plus exercise regimen throughout the 10 days in the treatment group. Mean blood levels of CK, aldolase, and LDH were measured in addition to swimming tolerance times. RESULTS: There was a significantly higher swimming tolerance time (P < 0.05) and lower CK levels (P < 0.01) in rats receiving ATV/GMF/Vit. C plus exercise compared with rats not taking Vit. C. LDH and aldolase did not decrease significantly. CONCLUSION: The results of this study showed that Vit. C can be effective in preventing myopathy caused by fat-lowering drugs.

Ginger Extract Increases GLUT-4 Expression Preferentially Through AMPK Than PI3K Signalling Pathways in C2C12 Muscle Cells.

PURPOSE: There are two signal transduction pathways related to glucose metabolism in C2C12 mouse myoblast cells; one through AMP-activated protein kinase (AMPK), and the other through phosphoinositide 3-kinase (PI3K). Ginger is reported to have hypoglycemic effects. The aim of this study was to determine the exact mechanism of action of ginger in those pathways. METHODS: C2C12 cells were seeded to four separate experimental groups; Control: treated with 50 µg/mL DMSO in the absence of any inhibitor; Treatment 1: treated with 50 µg/mL ethyl acetate ginger extract without any inhibitor; Treatment 2: treated with 50 µg/mL extract in the presence of 20 µM AMPK inhibitor; Treatment 3: treated with 50 µg/mL extract in the presence of 25 µM PI3K inhibitor. The amount of GLUT-4 protein (an important glucose transporter) was determined in cytosolic and membrane fractions using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. RESULTS: GLUT-4 concentration was significantly higher in the membrane fraction of cells treated with ethyl acetate ginger extract in the absence of any inhibitor in comparison with cells treated with this extract in the presence of each of the inhibitors (P-value < 0.05). GLUT-4 quantity in the membrane fractions in all groups was more than cytosolic fractions. The amount of GLUT-4 in membrane fraction of treated cells in the presence of PI3K inhibitor was higher than in the cells treated with this extract in the presence of AMPK inhibitor (P-value < 0.05). CONCLUSION: Ethyl acetate ginger extract affects the amount of GLUT-4 protein in membrane and cytosolic fractions of C2C12 myoblast cells mostly through AMPK pathway but less via PI3K.

Genetic Characterization and Risk Stratification of Acute Myeloid Leukemia.

The most common acute leukemia in adults is acute myeloid leukemia (AML). The pathophysiology of the disease associates with cytogenetic abnormalities, gene mutations and aberrant gene expressions. At the molecular level, the disease manifests as changes in both epigenetic and genetic signatures. At the clinical level, two aspects of AML should be taken into account. First, the molecular changes occurring in the disease are important prognostic and predictive markers of AML. Second, use of novel therapies targeting these molecular changes. Currently, cytogenetic abnormalities and molecular alterations are the common biomarkers for the prognosis and choice of treatment for AML. Finding a panel of multiple biomarkers is a crucial diagnostic step for patient classification and serves as a prerequisite for individualized treatment strategies. Furthermore, the most important way of identifying relevant targets for new treatment approaches is defining specific patterns or a spectrum of driver gene mutations occurring in AML. Then, an algorithm can be established by the use of several biomarkers, to be used for personalized medicine. This review deals with molecular alterations, risk stratification, and relevant therapeutic decision-making in AML.

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabolites impart unique properties in the interaction with each of the intracellular targets and metabolic enzymes whereby resulting in unique clinical activity. To date, most of the combinations have used a targeted agent combined with standard agents such as anthracyclines, cytarabine, or hypomethylating agents to improve the outcome. Rational combinations of DNA damage-inducing therapies with DNA methyltransferase and histone deacetylase inhibitors synergistically enhance the DNA damage, growth inhibition and apoptosis of myeloid cells. This review makes a thorough look at current antineoplastic agents for AML with emphasis on its genetics and molecular mechanisms of action and the role of combination regimens.

Application of essential oil of Pistacia atlantica Gum, polypropylene and silica nanoparticles as a new milk packaging.

The aim of current study was to investigate the antimicrobial effect of gum essential oil of Pistacia atlantica (wild pistachio) tree (GEO) and design a new film based on polypropylene polymer coated with silica nanoparticles and GEO. The antimicrobial activity of the packaging film was evaluated with or without milk on Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Listeria monocytogenes during 35 days. The results showed that GEO has significant antibacterial properties. It was most effective on Salmonella enterica, while its effect on Listeria monocytogenes was the weakest. Antimicrobial activity of the film without milk showed no significant differences among the different sizes of nanoparticles used (0.05, 0.025, and 0.051 g) (p ≥ .05). It can be concluded that polypropylene incorporated with GEO and silica nanoparticles active film had antimicrobial properties up to 35 days, while using with milk or without milk. Therefore, this type of packaging is effective to enhance the shelf life of milk.

Gelatin hydrogel containing cerium oxide nanoparticles covered by interleukin-17 aptamar as an anti- inflammatory agent for brain inflammation.

The purpose of this study was to evaluate the anti-inflammatory property of gelatin hydrogel containing cerium oxide nanoparticles coated with interleukin-17 Aptemer ([CeON@IL-17]). Here, the brain inflammation model was induced by both proteolipid protein (PLP) and parathion. Then, the expression of some inflammatory genes and the serum level of related interleukins were evaluated. This study showed that the expression of IL-17, IL-10, and IL-6 genes and their serum levels were significantly decreased (P < .05) by administration of gelatin hydrogel containing [CeON@IL-17].

Vector-borne bacteria in blood of camels in Iran: New data and literature review.

Despite close association between camels and humans, molecular based studies on vector-borne pathogens infecting camels are scarce compared to other animals in Iran. The current study was carried out to investigate the occurrence of vector-borne bacteria in the blood of dromedaries by molecular tools. A total of 200 peripheral blood samples were collected from apparently healthy animals. Microscopic examination was performed on Giemsa-stained blood smears, and drops of blood were spotted on Whatman FTA® cards for molecular analyses. Genomic DNA was extracted from the cards, and PCR amplification followed by sequencing of positive samples was carried out for the detection of Anaplasmataceae, spotted fever group (SFG) rickettsiae, Bartonella spp. and Borrelia spp. Intra-cytic forms of any blood pathogens could not be detected by light microscopy. PCR results revealed 30 animals (15%) to be infected with Anaplasmataceae bacteria. Analyses of sequences revealed a strain of Anaplasma sp. identical to Candidatus Anaplasma camelii isolated from camels, cattle and deer in Asia and Africa. Neither SFG rickettsiae, nor Borrelia or Bartonella species were found. Further studies for determining epidemiological role of camels and its zoonotic potential are recommended. This paper reviews the current knowledge on camels' tickborne bacteria including microscopy, serology and molecular studies.