Therapeutic efficacy of the drug Simparica® for demodicosis in dogs in the Kamianets-Podilskyi, Ukraine

The purpose of our research was to test the therapeutic efficacy of the acaricide «Simparica®» in combination with the biostimulator «Catosal» and the hepatoprotector «Tioprotectin» for demodicosis in dogs in the conditions of veterinary clinics in the Kamianets-Podilskyi, Ukraine. The study has been performed on dogs of different genders, ages and breeds that had a generalized form of demodicosis (affected at least 6 areas on the body of animals), to test the effectiveness of this drug in different treatment schemes. Acarological studies of scrapings from the skin of experimental animals for the presence of live or dead mites Demodex canis or their eggs have been carried out by the vital method according to D.O. Pryselkova. As a result of the conducted researches the choice of acaricidal drugs and development of complex therapeutic measures for demodicosis of dogs has been experimentally substantiated. The drug «Simparica®» has proved to be quite effective against demodicosis of dogs, even with a single use. The dependence of the effectiveness of the use of prolonged acaricide «Simparica®» on clinical forms of demodicosis has been shown. The absolute therapeutic effect of acaricide is obtained in the scaly form of demodicosis. However, in pustular and mixed clinical forms of demodicosis, its effectiveness decreased to 71.4 and 57.1%, respectively. In combination with the drug of pathogenetic therapy «Catosal» for pustular and mixed forms of demodicosis, the therapeutic efficacy of the drug «Simparica®» increases to 85.7%. When added to the scheme of hepatoprotector “Thioprotectin”, it is possible to achieve 100% therapeutic effect in pustular forms of demodicosis. However, in severe mixed form of demodicosis, the effectiveness was not absolute and was only 85.7%. In case of generalized demodicosis of dogs, regardless of clinical forms, it is recommended to use the acaricide «Simparica®» in combination with the drug «Catosal» and in the combination of «Catosal» and «Thioprotectin».

Low-Molecular-Weight Heparin Enhanced Therapeutic Effects of Human Adipose-Derived Stem Cell Administration in a Mouse Model of Lupus Nephritis

BackgroundLupus nephritis is a life-threatening complication in systemic lupus erythematosus (SLE), but the efficiency of current therapies involving corticosteroids, immunosuppressants, and biological agents is limited. Adipose-derived mesenchymal stem cells (ASCs) are gaining attention as a novel treatment for inflammation in SLE. Low-molecular-weight heparin (LMWH) exhibits multiple functions including anti-inflammatory, anti-fibrotic, and cell function-promoting effects. LMWH stimulation is expected to increase the therapeutic effect of ASCs by promoting cellular functions. In this study, we investigated the effects of LMWH on ASC functions and the therapeutic effect of LMWH-activated human-ASCs (hep-hASCs) in an SLE mouse model.MethodsThe cellular functions of human-derived ASCs stimulated with different LMWH concentrations were observed, and the optimum LMWH dose was selected. The mice were assigned to control, human-ASC, and hep-hASC groups; treatments were performed on week 20. Twenty-six week-old mice were sacrificed, and urine protein score, serum blood urea nitrogen, creatinine (Cr), anti-ds DNA IgG antibody, and serum IL-6 levels were analyzed in each group. Mice kidneys were evaluated via histological examination, immunohistochemical staining, and gene expression levels.ResultsLMWH significantly promoted ASC migration and proliferation and hepatocyte growth factor production and upregulated immunomodulatory factors in vitro. Hep-hASC administration resulted in significant disease activity improvement including proteinuria, serum Cr and IL-6 levels, anti-ds DNA IgG antibody, glomerulonephritis, and immune complex in mice. Inflammation and fibrosis in kidneys was significantly suppressed in the hep-hASC group; the gene expression levels of TNF-alpha, TIMP-2, and MMP-2 was significantly downregulated in the hep-hASC group compared with the control group.ConclusionsHep-hASC exhibited higher anti-inflammatory and anti-fibrotic effects than hASCs and may be a candidate tool for SLE treatment in future.

Diosmin Alleviates Venous Injury and Muscle Damage in a Mouse Model of Iliac Vein Stenosis

Chronic venous disease (CVD) is a progressive inflammatory disease that increases in prevalence with age. Elucidating the underlying molecular mechanism of CVD development is essential for disease prevention and treatment. This study constructed a mouse model of iliac vein stenosis to explore the mechanism of the CVD disease progression, and diosmin was administered as a positive control (as recommended by clinical practice). The mouse model was established successfully with iliac vein stenosis, leading to the expansion of the intercellular space and venous leakage. Conversely, micronized diosmin showed a dose-dependent therapeutic effect for these manifestations. Concerning the mechanism, iliac vein stenosis caused an inflammatory response in veins, while diosmin suppressed this increase. Furthermore, RNA sequencing analysis indicated that diosmin significantly improved muscle function through actin filament organization and muscle contraction. These results indicated that the mouse model of iliac vein stenosis is a reliable model to study venous diseases. Furthermore, the dose-dependent therapeutic effect of diosmin on stenosis (without toxic side-effects) suggests greater protection against venous diseases at higher doses of diosmin.

Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Background: Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury.Objectives: This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models.Methods and Results: The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = −30.00 [−42.09 to −17.91], p < 0.00001), and serum creatinine (SCr) (20 studies, WMD = −0.91 [−1.17 to −0.66], p < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease.Conclusions: From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.

The Cumulative Therapeutic Effect of Acupuncture Treatment in Patients with Migraine without Aura: Evidence from Dynamic Alterations of Intrinsic Brain Activity and Effective Connectivity Analysis

We explored the dynamic alterations of intrinsic brain activity and effective connectivity after acupuncture treatment to investigate the underlying neurological mechanism of acupuncture treatment in patients with migraine without aura (MwoA). The fMRI scans were separately obtained at baseline, after the first and after the 12th acupuncture sessions in 40 patients with MwoA. Compared with HCs, patients with MwoA showed mostly decreased dynamic amplitude of low-frequency fluctuation (dALFF) variability in regions with differences. After acupuncture treatment, the decreased dALFF variability of the rostral ventromedial medulla (RVM), the superior lobe of left cerebellum (Cerebelum_Crus1_L), and the right precuneus (PCUN.R) progressively recovered. The RVM revealed gradually increased dynamic effective connectivity (DEC) variability outflow to the right middle frontal gyrus, the left insula, the right precentral gyrus, and the right supramarginal gyrus, and enhanced DEC variability from the right fusiform gyrus inflow to RVM. Furthermore, the increased DEC variability were found from Cerebelum_Crus1_L outflow to the left middle occipital gyrus and the left precentral gyrus, from PCUN.R outflow to the right thalamus. These dALFF variabilities were positive correlated with frequency of migraine attack and negative correlated with disease duration, dynamic GCA coefficients were positive correlated with Migraine-Specific Quality of Life Questionnaire score, negative correlated with frequency of migraine attack and visual analog scale score postacupuncture treatment. Our results provide insight into dynamic alterations from the perspective of dynamic local brain activity and effective connectivity for the understanding mechanisms of cumulative therapeutic effect of acupuncture in patients with MwoA.

Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease

Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 Mpro. In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betrixaban and Rivaroxaban to the SARS-CoV-2 Mpro with the use of the MicroScale Thermophoresis technique. Our results indicate that the experimentally measured binding affinity is weak and the therapeutic effect due to the SARS-CoV-2 Mpro inhibition is rather negligible.