Identification and Structure Prediction of Human Septin-4 as a Biomarker for Diagnosis of Asthenozoospermic Infertile Patients—Critical Finding Toward Personalized Medicine

Semen parameters are been found as a key factor to evaluate the count and morphology in the given semen sample. The deep knowledge of male infertility will unravel with semen parameters correlated with molecular and biochemical parameters. The current research study is to identify the motility associated protein and its structure through the in-silico approach. Semen samples were collected and initial analysis including semen parameters was analyzed by using the World Health Organization protocol. Semen biochemical parameters, namely, seminal plasma protein concentration, fructose content, and glucosidase content were calculated and evaluated for correlation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) were carried out for identification of Septin-4 presence in the semen sample. Mascot search was done for protein conformation and in-silico characterization of Septin-4 by structural modeling in Iterative Threading Assembly Refinement (I-TASSER). Twenty-five nanoseconds molecular dynamics (MD) simulations results showed the stable nature of Septin-4 in the dynamic system. Overall, our results showed the presence of motility-associated protein in normospermia and control samples and not in the case of asthenospermia and oligoasthenospermia. Molecular techniques characterized the presence of Septin-4 and as a novel biomarker for infertility diagnosis.

PBPK modelling of dexamethasone in patients with COVID-19 and liver disease

The aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to simulate 100 adult individuals aged 18-60 years. Physiological changes (e.g., plasma protein concentration, liver size, CP450 expression, hepatic blood flow) and portal vein shunt were incorporated into the LD model. The changes were implemented by using the Child-Pugh (CP) classification system. DEX was qualified using clinical data in healthy adults for both oral (PO) and intravenous (IV) administrations and similarly propranolol (PRO) and midazolam (MDZ) were qualified with PO and IV clinical data in healthy and LD adults. The qualified model was subsequently used to simulate a 6 mg PO and 20 mg IV dose of DEX in patients with varying degrees of LD, with and without shunting. The PBPK model was successfully qualified across DEX, MDZ and PRO. In contrast to healthy adults, the simulated systemic clearance of DEX decreased (35% - 60%) and the plasma concentrations increased (170% - 400%) in patients with LD. Moreover, at higher doses of DEX, the AUC ratio between healthy/LD individuals remained comparable to lower doses. The exposure of DEX in different stages of LD was predicted through PBPK modelling, providing a rational framework to predict PK in complex clinical scenarios related to COVID-19. Model simulations suggest dose adjustments of DEX in LD patients are not necessary considering the low dose administered in the COVID-19 protocol.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC). It is often clinically complicated by malignant diseases or severe infections. Research on the molecular mechanism of High PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate, Bombyx mori, to investigate the effect of HPPC on circulating blood cells. We showed that HPPC affected blood cell homeostasis and enhanced blood cell phagocytosis, leading to increased reactive oxygen species levels, and induced programmed cell death that depended on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the JAK/STAT signaling pathway. Supplementation with endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Herein, we reported a novel signaling pathway by which HPPC affected blood cell homeostasis, which was different from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early monitoring index for hyperproteinemia.

Immunomodulatory Effects of Gum Arabica in Goat Blood

Gastrointestinal nematodes and other pathogens pose a major problem for goat production by reducing animal performance and welfare. Plants such as Acacia Senegal are useful as dietary sources for natural prophylaxis. Gum Arabica (GA) from A. Sengal has antimicrobial, anti-inflammatory properties that need to be explored in goats. The objective of this study was to investigate the possible immunomodulatory effect of a water extract of GA in goat blood. Clinically healthy Boer and Spanish goats from the NCA&T Small ruminant unit were used. Goats were assigned randomly to two groups of ten (n = 20). Goats of one group were drenched daily with 10 mL of GA (treatment I) extract for 6 weeks. The second (control) group of goats received sterile water (treatment II). Blood was collected from the jugular vein in tubes containing acid-citrate-dextrose anticoagulant. Plasma was separated and the concentration of total protein was determined using Pierce BCA kit (Thermo Scientific Pierce, Rockford, IL). The white blood cell differential count was assessed on Wrights smeared stains. Data were analyzed using PROC GLM in SAS 9.4 (P < 0.05). Treatment with GA modulated total plasma protein concentration and the differential white blood cell counts. Treatment increased total plasma protein concentration and % lymphocytes, it decreased % neutrophils. Immunomodulation by GA may be advantageous in promoting health and wellness in goats. Further studies on the mechanism of action are warranted.

Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in Bombyx mori

Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, PPO1 and PPO2. High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.

A system for assessing the functional state of blood flow in the skin surface layers by the speckle structure of multiply scattered optical radiation

Assessment of the parameters of skin microcirculation is an urgent and important task of modern medicine in the development of methods for diagnosing diseases of the nervous system. The system for assessing the functional state of blood flow in the skin surface layers in the wavelength range from 400 to 850 nm has been improved based on the use of an extended mathematical model of the propagation of optical radiation in human skin by taking into account additional parameters: optical anisotropy of the skin, diameter and shape of erythrocytes in the dermis layer, blood pressure in the brachial artery in the range from 90/60 to 195/130 mm·Hg, plasma protein concentration in the blood (α1, α2, β1, β2, γ-globulins and fibrinogen, g/l), rheological properties of blood flow with a diameter of blood vessels from 4.5 to 500 microns in the skin surface layers, skin temperature from +35 to +41 °C. The developed system makes it possible to determine the severity of microhemodynamic shifts in relation to metabolic disorders, improve diagnosis and evaluate the treatment efficacy of a number of neurological disorders; it also made it possible to reduce the patient examination time and increase the accuracy of measuring the blood flow microcirculation parameters by 10 % (linear and volumetric blood flow velocities) to detect blood flow disturbances in the surface layers of the skin in the normal and abnormal condition of the nervous system.

In ovo Administration of Nucleosides Improved the Performance, Apparent Metabolizable Energy and Gut Development in Broiler Chickens

An in ovo study on the effect of the administration of a combination of nucleosides (25, 50, and 100 mg/egg) on hatchability, growth performance, energy metabolizability, and intestinal morphology in broilers was carried out. Four hundred eighty (480) fertile eggs were divided into four groups (in four replicates each having 30 eggs). On the 18th days of incubation of the eggs, candling was carried out and the fertile eggs were selected and given one of the four in ovo administrations. Group one served as control and was injected with phosphate-buffered saline (PBS). The other groups were given in ovo administration of nucleosides (25, 50, and 100 mg/egg) at 100 μl through the yolk sac route, and chicks of respective groups were hatched out. Among the experimental groups, the hatchability was comparable; however, the hatchability was affected in the group injected with a higher level of nucleosides at 100 mg/egg. The hatched out chicks from higher doses of nucleosides (50 and 100 mg) had higher body weight (BW) (P < 0.05) than the control. Higher energy metabolizability (%) was observed in nucleoside-injected groups. Plasma protein concentration was higher in groups administered with nucleosides (50 and 100 mg). Histologically, the intestinal villi length was maximum in 100 mg-injected group followed by 50 and 25 mg. Relative expression of homeobox (Cdx) in the jejunum was significantly (P < 0.05) upregulated in all the injected groups at 3, 7, and 14 days of age. Nucleoside-administered groups had better performance, energy metabolizability, and intestinal morphology. Among the experimental groups, the administration of nucleosides at 50 mg/egg resulted in higher growth performance, plasma protein, intestinal surface, and villi development in broiler chickens.

PSX-15 Fall grazing of annual forages with fall born lambs may improve animal growth and total protein concentrations when compared to stockpiled pastures

There is a consistent demand for grass-fed livestock products in the domestic market. Alternative grazing strategies should be considered to sustain the year-round production of grass-fed products that meet consumer demand and support animal health and performance. The objective of this study was to evaluate the effect of annual forages on the growth and parasite resilience of growing lambs. We hypothesized that lambs grazing annual forages would increase their body weight at a greater rate when compared to lambs grazing stockpiled pasture. A total of 54, 60-day-old lambs (24 kg ± 4.9 kg) were stratified by weight, sex, and randomly assigned to one of three grazing treatments: 1) oats (O); 2) turnips (T); and 3) stockpiled tall fescue pasture (F). Lamb body weight and indices of parasitism were measured every 14 days. Data were analyzed using PROC MIXED in SAS. There was a treatment × day effect for body weight such that T lambs were heavier on days 42 and 56 than O and F lambs (P < 0.03). Furthermore, there was a treatment × day effect for average daily gain (ADG) whereas T lambs had a greater ADG on days 28 and 42 than O and F lambs (P < 0.0001). In addition, on day 42, F lambs had a greater ADG when compared to O lambs (P < 0.003). For the indices of parasitism, T lambs demonstrated lesser total plasma protein concentration on days 28 and 42 when compared with O lambs (P < 0.05). Forage type plays a critical role in lamb resilience to gastrointestinal parasites and body weight gain whereas T lambs showed a greater liveweight gain. However, T lambs also demonstrated lesser concentrations of total plasma protein when compared to O lambs. Under these conditions, annual forages adequately sustained the growth of fall grazing lambs.

43 Effect of Mushroom Probiotic (Coriolus Versicolor) on Galectin Gene Secretion in Goat Blood

Galectins (GAL) constitute an evolutionarily conserved family of β-galactoside-binding proteins that are secreted. They are involved in the regulation of homeostasis, innate and adaptive immune responses to infectious challenge. The mushroom Coriolus versicolor (CV) has been reported to boost suppressed immune function, extending the survival rate and improving quality of life in man. The objective of this study was to evaluate the effect of mushroom probiotics on the secretion of Galectins in goat blood. Ten BoerXSpanish female goats (5 weeks of age) were used for this study. Powdered CV was soaked in cold water and sterile filtered. Following initial screening for infection, goats were assigned to two groups of five (n = 10). Goats were drenched daily with 10 mL cold (treatment I) extract for 4 weeks. A control group of five age-matched goats received sterile water (treatment II). Blood samples were collected on a weekly basis. The concentration plasma protein was determined by using Pierce BCA kit (Thermo Scientific Pierce, Rockford, IL). Galectins-1, -3, -8, -9 and -12 concentration was detected by using a commercial ELISA kits (ABclonal Biotechnology, Woburn, MA). There was an effect of treatment in total plasma protein concentration when compared to the control group (P < 0.02). Galectins tested were secreted in both control and treatment groups. Treatment with CV decreased the concentration of Gal-1, 8 and 9 and increased the concentration of Gal-3 and -12 (P < 0.05). Results from this study indicate that mushroom probiotics can modulate the secretion of GAL.

Comparative Plasma Endocrine, Metabolic and Mineral Profile of Cyclic, Acyclic, Endometritic and Pregnant Buffaloes

Circulating concentrations of hormones, metabolites, and minerals reflect the physio-pathological status of reproduction in animals. This study was carried out on infertile (anestrus, endometritic), normal healthy cyclic and pregnant buffaloes to evaluate the comparative plasma progesterone (P4) and estrogen (E2) hormones, plasma total protein, total cholesterol, calcium, and phosphorus profile. The study showed higher mean plasma E2 and lower P4 levels in the follicular phase of estrous cycle in buffaloes. Significantly (p less than 0.05) higher mean plasma P4 level and lower E2 levels were recorded during the luteal phase and in endometritic and pregnant buffaloes. Total plasma protein concentration was non-significantly higher in normal cyclic than acyclic and endometritic buffaloes. It was also comparatively lower in buffalo with 9 months of pregnancy than 3 and 6 months of pregnancy. The mean plasma total cholesterol level was significantly (p less than 0.05) higher in pregnant than acyclic and endometritic buffaloes. Cyclic buffaloes had significantly (p less than 0.05) higher mean plasma calcium levels than acyclic buffaloes. Plasma phosphorus concentration, however, did not show any significant difference between different stages of the reproductive cycle.