Lipidomic profile of human nasal mucosa and associations with circulating fatty acids and olfactory deficiency

The nasal mucosa (NM) contains olfactory mucosa which contributes to the detection of odorant molecules and the transmission of olfactory information to the brain. To date, the lipid composition of the human NM has not been adequately characterized. Using gas chromatography, liquid chromatography coupled to mass spectrometry and thin layer chromatography, we analyzed the fatty acids and the phospholipid and ceramide molecular species in adult human nasal and blood biopsies. Saturated and polyunsaturated fatty acids (PUFAs) accounted for 45% and 29% of the nasal total fatty acids, respectively. Fatty acids of the n-6 family were predominant in the PUFA subgroup. Linoleic acid and arachidonic acid (AA) were incorporated in the main nasal phospholipid classes. Correlation analysis revealed that the nasal AA level might be positively associated with olfactory deficiency. In addition, a strong positive association between the AA levels in the NM and in plasma cholesteryl esters suggested that this blood fraction might be used as an indicator of the nasal AA level. The most abundant species of ceramides and their glycosylated derivatives detected in NM contained palmitic acid and long-chain fatty acids. Overall, this study provides new insight into lipid species that potentially contribute to the maintenance of NM homeostasis and demonstrates that circulating biomarkers might be used to predict nasal fatty acid content.

Comparative Evaluation of Wound Healing Effect of Cord Blood Low Molecular Weight Fraction (Below 5 kDa) and Actovegin Drug in Skin Cryolesions

This paper presents the results of comparative studies of the impact of the low molecular weight (below 5 kDa) cattle cord blood fraction (CBF) and the comparator drug Actovegin on tissue regeneration after skin cryoablation in rats. Here, a local contact cryoexposure was shown to result not only in destruction of all skin layers, but secondary ischemic damage to deeper and adjacent tissues as well. The use of an injection solution of CBF as a therapy for simulated cryolesion proved its pronounced wound healing effect, manifested in accelerated reparation, improved trophicity in an injured area due to hypervascularization and prevention of sclerotic processes. The introduction of CBF and Actovegin to rats accelerated the normalization of clinical blood parameters (RBC and WBC counts, alkaline phosphatase activity) in shorter terms as compared with the control. The obtained effect may be compared with Actovegin action.

Convalescent Plasma to Limit Coronavirus Associated Complications: A Proof of Concept Phase-2 Clinical Study at a designated COVID-19 hospital in Mumbai city

Objective: With few treatment options available to manage coronavirus disease 2019 (COVID-19), health systems devised strategies to manage covid-19 using repurposed drugs and revisiting older strategies, such as convalescent plasma. This study was planned to evaluate safety and efficacy of Anti-SARS-CoV-2 convalescent plasma in hospitalized subjects with COVID-19. Method: An open label, single centre, two arm, prospective, randomised, controlled exploratory phase 2 study was conducted at a covid-19 designated center. 20 subjects (≥18 years) were admitted to hospital (screened 15 June to 27 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/ fraction of inspired oxygen (PaO2/FiO2) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 10 subjects were assigned to convalescent plasma with standard treatment (test arm) and 10 subjects to standard treatment only (control arm). Subjects in the test arm received either single or two doses of convalescent plasma 24 hours apart based on their clinical condition as per investigator’s discretion. Results: Subjects in test arm showed earlier resolution of symptoms of fever, shortness of breath and cough and the mean duration for RT-PCR test turning negative was better in the test arm. One subject in the control arm progressed to severe ARDS, while none in test arm progressed to severe ARDS. There was no difference in the use of respiratory support (invasive and non-invasive ventilation) between the 2 arms. There was no mortality observed in the study and no serious adverse reaction observed with the transfusion of convalescent plasma in the study. Conclusion: This was an exploratory proof of concept study to explore the effectiveness of convalescent plasma in COVID-19 subjects and sample size was not large enough to detect a statistically significant difference however subjects in test arm of this study showed better outcomes in few of the efficacy parameters as compared to subjects in control arm. The use of convalescent plasma transfusion was also observed to be safe.

Monosomy 3 Influences Epithelial-Mesenchymal Transition Gene Expression in Uveal Melanoma Patients; Consequences for Liquid Biopsy

Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCβ4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions.

Serum Heme Oxygenase-1 Measurement is Useful for Evaluating Disease Activity and Outcomes in Patients With Acute Respiratory Distress Syndrome and Acute Exacerbation of Interstitial Lung Disease

Background: Oxidative stress plays an important role in acute lung injury, which is associated with the development and progression of acute respiratory failure. Here, we investigated whether the degree of oxidative stress as indicated by serum heme oxygenase-1 (HO-1) is clinically useful for the patients with acute lung injury including ARDS and AE-ILDs.Methods: Serum HO-1 levels of newly diagnosed or untreated ARDS and AE-ILD patients were measured at diagnosis. Relationships between serum HO-1 and other clinical parameters and 1-month mortality were evaluated. Results: Fifty-five ARDS (n = 22) and AE-ILD (n = 33) patients were assessed. Serum HO-1 level at diagnosis was significantly higher in ARDS patients than AE-ILD patients (87.8 ± 60.0 ng/mL vs. 52.5 ± 36.3 ng/mL, P < 0.001). Serum HO-1 correlated with serum T-bil (R = 0.454, P < 0.001) and serum LDH (R = 0.500, P < 0.001). Serum HO-1 level significantly decreased from diagnosis to 2 weeks after diagnosis (81.1 ± 9.3 ng/mL vs. 60.9 ± 52.4 ng/mL, P = 0.016), however normalized. Composite parameters including serum HO-1, diagnosis, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and sex for prediction of 1-month mortality showed a higher AUC (0.932) than did AUCs of a single predictor or combination of two or three predictors. Conclusion: Oxidative stress assessed by serum HO-1 is persistently high in patients with acute lung injury against intensive treatment. Also, serum HO-1 measurement could be clinically useful for evaluating disease activity and prognosis in patients with ARDS and AE-ILDs.

Interleukin-18, Functional IL-18 Receptor and IL-18 Binding Protein Expression in Active and Latent Tuberculosis

A thorough understanding of the processes modulating the innate and acquired immune response to Mycobacterium tuberculosis (M.tb) infection in the context of gene expression is still a scientific and diagnostic problem. The study was aimed to assess IL-18, IL-18 binding protein (IL-18BP), IL-18R, IFN-γ, and IL-37 mRNA expression in patients with active tuberculosis (ATB) and healthy volunteers with latent M.tb-infection (LTB) or M.tb-uninfected healthy controls (Control). The relative mRNA expression was assessed in the buffy coat blood fraction using the qPCR method. In total, 97 BCG-vaccinated Polish adults were enrolled in the study. The relative expression of IL-18 and IL-18BP mRNA was significantly elevated in the ATB and LTB groups. In ATB, but not LTB individuals, the overexpression of IL-18 and IL-18BP, as well as a significant increase in IFN-γ mRNA expression, might be considered as a manifestation of active tuberculosis disease. No statistically significant differences were observed in the IL-37 mRNA expression among the studied groups. Particularly noteworthy is the outstanding reduction in the relative expression of IL-18R mRNA in the LTB group as compared to the ATB and Control group. Reduced expression of IL-18R in LTB group may, at least partially, prevent the development of a pathological inflammatory reaction and promote the maintenance of homeostatic conditions between host immunity and M.tb.

Incorporation of Fatty Acids as a Biomarker of Dietary Intake and Source is Fatty Acid and Blood Fraction Specific in CD-1 Mice

Objectives Accurate biomarkers of fatty acid (FA) intake and source (e.g., diet-derived FA) are an important assessment tool to study the role of dietary fat quality on metabolic health. The purpose of this study was to assess the incorporation of unique, dietary FA from fish oil, echium oil, and dairy fat into the red blood cell membranes (RBCM), plasma phospholipids (PPL), and plasma cholesterol esters (PCE) of genetically-outbred CD-1 mice. Methods At one month of age, mice were assigned to one of four isocaloric diets consisting either of a control fat blend or the control fat blend supplemented (30%) with fish oil, echium oil, or dairy fat (n = 10/diet/sex). After 52 weeks of feeding, cardiac blood was collected for FA analysis of RBCM, PPL, and PCE using gas-liquid chromatography. Results Expectedly, a higher proportion of fish-derived FA (eicosapentaenoic acid and docosahexaenoic acid) was observed in the RBCM and PCE of fish oil-fed mice (P &lt; 0.0001). Accordingly, a greater proportion of echium oil-derived γ-linolenic acid was incorporated into all blood fractions of echium oil-fed mice (P &lt; 0.0001). Yet, stearidonic acid, specific to echium oil, was not detected in the RBCM of mice, and no differences in the proportion of stearidonic acid were found in the PPL and PCE. Odd-chain FA (pentadecanoic acid and heptadecanoic acid) were not exclusively enriched in the blood fractions of dairy-fed mice. Conversely, trans-palmitoleic acid, vaccenic acid, rumenic acid, and branched-chain FA were differentially incorporated into the PPL and PCE, while not detected in the RBCM. Conclusions In summary, unique, diet-derived FA are differentially incorporated into the blood fractions of mice, indicating that the incorporation of dietary FA into blood fractions is highly dependent upon the FA species. Therefore, diet-derived FA cannot be used universally as a reliable biomarker to validate dietary FA source in mice, rather, the specific FA and blood fraction must be carefully considered. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1,006,628).

Characteristics of the productive-economic indicators of cows of Yaroslavl breed of different genotypes

Aim. The study of the influence of crossbriding on the growth and development of heifers and subsequent productive and reproductive qualities of cows on the first lactation. Methods. Using statistical methods, correlation analysis and ANOVA for evaluated genetic indicators of economic-valuable traits of dairy cattle. In particular was studied live weight of heifers from birth to 18 months, first insemination age and first fecundation age, live weight at fecundation, frequency of insemination, first calving age, days open, live weight at first lactation, milk yield for 305 days (kg), fat (%, kg) and protein (%, kg) in milk. Results. Relationship between productive indicators and the genotype of the animal is established. When assessing the strength of the influence of the factor «blood on the Holstein breed» it was found that the greatest impact can be traced at the age of 6 and 18 months, and is respectively 12.7 % and 17.1 %.The reproductive qualities of the first-calf cows decreased with the increase percent of blood in the Holstein breed. Evaluation of the impact of crossbreeding on milk production at first lactation has revealed significant strong influence on milk yield for 305 days of first lactation, and related signs the amount of milk fat and protein. According to qualitative indicators, the low influence of the Holstein blood fraction was found, while to a greater extent on the fat content than on the protein content in milk. Evaluation of phenotypic and genotypic correlations of milk yield and quality components of milk revealed average negative phenotypic and low negative genotypic correlation in all groups. The exception was in heifers of Yaroslavl breed with percent of Holstein blood less than 50 %, in which the relationship of yield x protein was positive. The relationship between milk yield and fat and protein content in milk has the opposite moderate character and strength. Practical significance. Studies was established that breeding of animals of Holstein and Yaroslavl breeds in one herd allows to receive an optimum ratio of milk production with optimal percentage fat and protein. For this herd among animals of the improved genotypes of the Yaroslavl breed, the use of genotypes with a percent of blood in the Holstein breed from 75.1 % to 87.6 % is optimal, which should be taken into account when selecting bulls to the breeding program.