Pathological Structural Changes Research Articles

Cerebral Hemodynamics and Carotid Atherosclerosis in Patients With Subcortical Ischemic Vascular Dementia.

A growing body of evidence indicates that atherosclerosis is correlated with cerebral small vessel disease and contributes to cognitive decline. This study aimed to explore the characteristics and contributions of intracranial hemodynamics and carotid atherosclerosis to cognitive dysfunction in subjects with subcortical ischemic vascular dementia (SIVD). Notably, 44 patients with SIVD, 30 patients with Alzheimer’s disease (AD), and 30 healthy controls (HCs) were recruited from our longitudinal MRI study for AD and SIVD (ChiCTR1900027943). The cerebral mean flow velocity (MFV) and pulsatility index (PI) of both anterior and posterior circulations, artery plaque, and lumen diameter in carotid arteries were investigated using transcranial Doppler and carotid ultrasound, respectively. Their correlations with cognitive function were analyzed in patients with dementia. Decreased MFV and increased PI were found in patients with SIVD and AD. Patients with SIVD showed lower MFV and higher PI in the bilateral posterior cerebral arteries compared to patients with AD. Increases in lumen diameter, number of arteries with plaque, and total carotid plaque score were found in patients with SIVD. The Mini-Mental State Examination score was positively correlated with the MFV and negatively correlated with the PI of most major cerebral arteries, while it was negatively correlated with the lumen diameter of the common carotid artery, number of arteries with plaque, and total carotid plaque score in patients with dementia. There were also correlations between these parameters of some arteries and memory and executive function. Our results provide additional evidence suggesting that the pathological changes in macrovascular structure and function are correlated with cognitive impairment in dementia patients with SIVD and to a lesser extent AD.

Optical angiography for diabetes-induced pathological changes in microvascular structure and function: An overview

Diabetes mellitus (DM) is a kind of metabolic disorder characterized by chronic hyperglycemia and glucose intolerance due to absolute or relative lack of insulin, leading to chronic damage of vasculature within various organ systems. These detrimental effects on the vascular networks will result in the development of various diseases associated with microvascular injury. Modern optical imaging techniques provide essential tools for accurate evaluation of the structural and functional changes of blood vessels down to capillaries level, which can offer valuable insight on understanding the development of DM-associated complications and design of targeted therapy. This review will briefly introduce the DM-induced structural and functional alterations of vasculature within different organs such as skin, cerebrum and kidneys, as well as how novel optical imaging techniques facilitate the studies focusing on exploration of these pathological changes of vasculature caused by DM both in-vivo and ex-vivo.

Upregulation of autophagy in M2 macrophage by vitamin D alleviates crystalline silica-induced pulmonary inflammatory damage

Crystalline silica (CS) is a universal environmental pollutant, which causes a typical inflammatory lung injury. Vitamin D shows huge potential against particles-induced lung injury, while little known about the molecular mechanism involved in macrophage autophagy. In this study, we aim to identify the protective effects of vitamin D on CS caused lung inflammatory injury and clarify the detail mechanism. After exposure to CS (3 mg/mice in 50 μl PBS), wildtype and Atg7flox/flox Lyz2-cre mice were treated with or without vitamin D3 (40,000 IU/kg). The results indicated that exposure to CS caused an obvious lung injury, manifesting as pathological structural changes, macrophage-dominated inflammatory cell infiltration and increased pro-inflammatory cytokines. Remarkably, these damages were more serious in Atg7flox/flox Lyz2-cre mice. Vitamin D was found to inverse CS-induced inflammatory cell infiltration and restored anti-inflammatory M2 macrophages by inducing autophagy, which attenuated lung injury, as determined by decreased levels of apoptosis and inflammatory response. While, this effects of vitamin D were slashed in Atg7flox/flox Lyz2-cre mice. This study reveals the adverse effect of CS on lung tissue and the protective mechanism of vitamin D involved in M2 macrophages autophagy, which attenuates CS-caused lung injury.

New mechanism-based approaches to treating and evaluating the vasculopathy of scleroderma.

Utilizing recent insight into the vasculopathy of scleroderma (SSc), the review will highlight new opportunities for evaluating and treating the disease by promoting stabilization and protection of the microvasculature. Endothelial junctional signaling initiated by vascular endothelial-cadherin (VE-cadherin) and Tie2 receptors, which are fundamental to promoting vascular health and stability, are disrupted in SSc. This would be expected to not only diminish their protective activity, but also increase pathological processes that are normally restrained by these signaling mediators, resulting in pathological changes in vascular function and structure. Indeed, key features of SSc vasculopathy, from the earliest signs of edema and puffy fingers to pathological disruption of hemodynamics, nutritional blood flow, capillary structure and angiogenesis are all consistent with this altered endothelial signaling. It also likely contributes to further progression of the disease including tissue fibrosis, and organ and tissue injury. Restoring protective endothelial junctional signaling should combat the vasculopathy of SSc and prevent further deterioration in vascular and organ function. Indeed, this type of targeted approach has achieved remarkable results in preclinical models for other diseases. Furthermore, tracking this endothelial junctional signaling, for example by assessing vascular permeability, should facilitate insight into disease progression and its response to therapy.

The effect of subchronic cigarette smoke exposure on oxidative stress parameters and endothelial nitric oxide synthase in a rat aorta.

BACKGROUNDThe compounds in cigarette smoke are believed to cause oxidative stress, leading to endothelial dysfunction. Understanding the mechanism of endothelial dysfunction due to cigarette smoke is useful for the development of early and preventive therapy for cardiovascular diseases (CVDs) with smoking risk factors.METHODSIn this experimental study, a posttest-only control group design was used. 20 Wistar rats were divided into two groups: a smoking group (exposed to 40 cigarettes per day for 4 weeks) and a control group. After the exposure, the animals were sacrificed and aortas were removed for measurement of malondialdehyde (MDA), superoxide dismutase (SOD), endothelial nitric oxide synthase (eNOS), intima-media thickness (IMT), and for histological analysis.RESULTSExposure to cigarette smoke caused a significant decrease in SOD activity (24.28 ± 4.90; P = 0.027) and eNOS levels (50.81 ± 4.18; P = 0.014), but no significant effect on the level of MDA (17.08 ± 5.78; P = 0.551). Histological analysis showed an increase in IMT (13.27 ± 2.40; P = 0.000) and disorganization and vacuolation of smooth muscle cells in tunica media after exposure to cigarette smoke. The regression analysis showed a significant negative relationship between the eNOS level and IMT (β = -1.012, P = 0.009).CONCLUSIONSubchronic exposure to cigarette smoke caused a decrease in SOD activity and eNOS levels, but no significant change in MDA levels. This study also indicated that smoking causes IMT thickening and pathological structural changes in the aorta. Another finding indicated that a decrease in eNOS levels could cause an increase in the IMT of the aorta.

Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure.

This study investigated hepatic oxidative damage in rats following long-term manganese (Mn) exposure and clarified the underlying mechanisms. Forty-eight rats (SPF, male) were randomly assigned to receive low (10 mg/kg, n = 16) or high doses of Mn (50 mg/kg, n = 16) or sterilized distilled water (control group, n = 16). Rats were euthanized after 12 months, and liver Mn levels and histopathological changes were determined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver malondialdehyde (MDA), glutathione peroxidase (GSH-PX), nuclear factor E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinine oxidoreductase-1 (NQO1) levels were also determined. The Mn concentration and relative liver weights were significantly higher in the high-dose Mn group than in the control and low-dose Mn exposure groups. Low-dose Mn exposure resulted in mild expansion of hepatic sinuses and intact nuclei, whereas high-dose exposure led to pathological alterations in hepatocytes. High-dose Mn treatment significantly increased AST, ALT, and MDA activities and decreased GSH-PX activity. Additionally, liver Nrf2, HO-1, and NQO1 protein expression were markedly reduced by Mn exposure. Under the study conditions, long-term low-dose Mn exposure resulted in slight pathological changes in liver structure, but high-dose Mn exposure affected both liver structure and function, which might be related to the inhibition of Nrf2 expression, suppression of the transcription of its underlying antioxidant genes, and down regulation of the corresponding proteins. Consequently, the antioxidant capacity in the rat liver was weakened.

Local vibration induced vascular pathological structural changes and abnormal levels of vascular damage indicators

BackgroundThe vascular component of the hand-arm-vibration syndrome (HAVS) is often characterized by vibration-induced white fingers (VWF). Active substances secreted by the vascular endothelial cells (VEC) maintain a dynamic balance but damage to the blood vessels may occur when the equilibrium is altered, thus forming an important pathological basis for VWF. This study was aimed at investigating vascular damage indicators as a basis for an early detection of disorders caused by vibration, using the rat tail model. Methods and resultsExperiments were conducted using a control group of rats not exposed to vibration while two exposed groups having different exposure durations of 7 and 14 days were randomly formed. Following exposure, the structural changes of tail tissue samples in anesthetized rats were observed. Enzyme-linked immunosorbent assay (ELISA) was used for analyzing four vascular damage indicators myosin regulatory light chain (MLC2), endothelin-1 (ET-1), vinculin (VCL) and 5-hydroxytryptamine (5-HT) in tail blood samples. We found that both vascular smooth muscle and endothelial cells displayed changes in morphology characterized by vacuolization and swelling in the vibration-exposed group. The levels of vascular damage indicators were altered under the vibration. ConclusionThe degree of vascular pathology increased with the longer duration exposure. Furthermore, the levels of MLC2, ET-1 and 5-HT in rat plasma were associated with vascular injury caused by local vibration.

Assessment of children`s psychomotor development in the remote period after aortic arch reconstruction with antegrade cerebral perfusion

Objective. To evaluate the psychomotor development of children after aortic arch reconstruction in the conditions of selective antegrade cerebral perfusion.
 Materials and methods. The results of surgical treatment and psychomotor development of 48 children aged 1 to 3 years, who underwent reconstruction of the aortic arch in terms of artificial circulation and selective antegrade cerebral perfusion at the age of 1 year at the Amosov National Institute of Cardiovascular Surgery and the Scientific and Practical Medical Center of Pediatric Cardiology and Cardiac Surgery in the period from 2014 to 2019 were analyzed. To study the cognitive sphere and motor development of children we used the 2nd edition of the method "Bayley Scales of Infant Development - II". In analyzing the results in children with psychomotor developmental delay, the values of the mental index and the index of psychomotor development were taken into account.
 Results. 2 (3.7%) patients died after surgery. Postoperative mortality was connected with neurological complications and technique of cerebral perfusion. In the remote period no patient died. According to neurosonography in the postoperative period, no pathological structural changes in the brain were detected. In 16 (33.3%) children at the age of 1 year there was a slight delay in mental and / or psychomotor development. Evaluation of the results of the survey in the dynamics showed that at the age of 3 years, 9 (18.7%) children had a slight development delay. The average values of the mental index in 1 year were 81.2 ± 8.6, and in 3 years - 96.4 ± 12.7 (p <0.05), and the index of psychomotor development - respectively 83.3 ± 11.4 and 94.5 ± 10.2 (p <0.05). The difference between the indicators of mental and psychomotor indices in children with congenital heart disease at 1 year and 3 years is statistically significant.
 Conclusions. A delay in psychomotor development at the age of 1 year was revealed in 33.3% of children after the aortic arch reconstruction in the conditions of selective antegrade cerebral perfusion. This indicates the need for further research and monitoring. A statistically significant difference between the indicators of mental and psychomotor development of children aged 1 and 3 years after aortic arch reconstruction indicates a positive dynamics and recovery of psychomotor development with age in most of children.

A Meta-Analysis of Alterations in the Retina and Choroid in High Myopia Assessed by Optical Coherence Tomography Angiography

Background: High myopia (HM) is a risk factor for several pathological structural changes in retinal and choroidal thickness or vessel. To date, changes in retinal and choroidal microvasculature circulations in HM have yielded inconsistent results. Objectives: The objective of this article was to evaluate alterations in retinal and choroidal thickness, and capillary microvasculature using optical coherence tomography angiography (OCTA) in HM. Methods: PubMed, Embase, and the Cochrane Library databases were searched for relevant published studies. Primary outcomes were foveal avascular zone, vessel density, retinal nerve fiber layer (RNFL) thickness, foveal thickness, sub-foveal choroidal thickness, and chorio-capillary density. Alterations in outcomes were evaluated by standardized mean difference with a 95% confidence interval. Results: Eleven eligible articles were included for the meta-analysis. The whole superficial and deep vessel densities of macular and parapapillary superficial vessel density were lower in HM than in control eyes. The thickness of parafoveal RNFL, parapapillary RNFL, and sub-foveal choroid was significantly lower in HM eyes. Also, chorio-capillary density was shown to be lower in HM eyes. Conclusions: The retinal and choroidal vessel network change may be related to the axial elongation in the progression of myopia. Furthermore, OCTA is an effective and noninvasive technology for monitoring the progress of myopia eyes.

Fundus changes in high myopic Kashmiri population

Background: High myopia (defined as myopia of -6D or more) is one of the main causes of visual impairment worldwide. High myopia is always accompanied by pathological structural changes such as axial elongation, posterior staphyloma, lacquer crack formation, thinning of the retina and choroid, and choroidal neovascularization.
 Aims and Objectives: The purpose of this study was to examine the fundus changes in eyes with high myopia.
 Materials and Methods: All study participants underwent dilated fundus examination and fundus photography. Myopia-related macular (posterior staphyloma, lacquer cracks, Fuchs spot, myopic chorioretinal atrophy, and myopic choroidal neovascularization)and optic disc (optic nerve head tilt,optic disc dimensions, and peripapillary atrophy) changes were evaluated.
 Results: Statistical analysis was performed to evaluate fundus changes in eyes with high myopia. Data analysis included 107 eyes of 57 patients.Mean ± SE was 12.07 ± 3.184D in eyes with high myopia. Mean ± AL was 26.68± 1.577mm in eyes with high myopia. The mean age was 28.54 ± 9.44 years(14-50 years). Fundus changes were: Temporal crescent in 56 (52.33%) eyes, tessellated fundus appearance in 52(48.59%) eyes, lacquer cracks in 40 (37.38%) eyes, tilted disc in 30 (28%) eyes, lattice degeneration in 20(18.69%) eyes, posterior staphyloma in 20(18.69%) eyes, focal chorioretinal atrophy in 3 (2.8%) eyes. CNV in 2 (1.86%)eyes and retinal hole in 1(1%) eye.
 Conclusions: Tessellated fundus and temporal crescent were the most common fundus findings among Kashmiri population with high myopia. In this population, lacquer cracks and tilted disc were also common, while CNV and retinal holes were rare.

МЕТОДИЧЕСКИЕ ПОДХОДЫ К ОЦЕНКЕ ЭНТОМОПАТОГЕННОЙ АКТИВНОСТИ МИКРООРГАНИЗМОВ В ОТНОШЕНИИ НАСЕКОМЫХ-ВРЕДИТЕЛЕЙ IN VITRO (ОБЗОР)

Excessive application of chemical insecticides in agriculture has led to some serious problems that threaten the environment and human health. One of the possible ways to overcome the situation is to shift to environmentally-friendly preparations based on entomopathogenic bioagents. The purpose of this review was to search for and systematize methodological approaches to determine the entomopathogenic activity of microorganisms of various taxonomic groups in laboratory conditions. The expediency of choosing the necessary method when studying a particular phenomenon or process is an important point both in the fundamental and applied field of research. The primary assessment of the entomopathogenic activity of microorganisms in vitro is the basis for expanding the spectrum of their action, introducing new strains into collections. It also contributes to the replenishment of knowledge about the already known properties of various types of microorganisms. All this, certainly, is connected with the further choice of them as biological agents. Each of the presented groups of entomopathogens has its distinctive features of the mechanisms of action determined by the target insect. Concerning the choice of methodological approaches for assessing the entomopathogenic effect of fungi, the authors relied on the physiological characteristics of the insect and its stage of harmfulness. The researchers were guided by methodological approaches of oral infection of insects using an infected food source to study the activity of bacterial strains. Pathological changes in the cellular structure, as well as deformations of intestinal elements, were noted. The most common way to assess the effect of entomopathogenic viruses in the laboratory is the method of surface infection of the food source of the tested insect, taking into account the high specialization of the agent. When studying the mechanisms of action of fungal, bacterial and viral agents, researchers injected a suspension of the pathogen into the insect’s body. The search and systematization of relevant methodological approaches to assess entomopathogenic microorganisms depending on the taxonomic affiliation is an important part of the work directly related to the development of a high-quality and effective bioinsecticide.

Морфологическая характеристика сперматогенеза у крыс после прицельного облучения разными дозами электронов

Introduction. Today, a primary concern of humanity is male infertility. Recent figures suggest that the disease affects 186 million people worldwide, and its prevalence increases as men get older. In literature the radiation therapy effect on the male reproductive system is debated. Over the past decade, scientific and technological progress has definitely accelerated the development of the radiation therapy methods, and as new devices have emerged, there is a need to carefully select new dosing regimens. The aim of the experimental study was to evaluate morphological spermatogenesis indicators after targeted irradiation with electrons of variable doses. Materials and methods. Wistar rats (n=70) were once subjected to targeted ionizing irradiation on a pulsed electron accelerator NOVAC 11 with doses of 2 Gy, 4 Gy, 6 Gy, 8 Gy, 10 Gy, and 12 Gy, and a week later spermatogenesis was assessed with light microscopy. Results. In the experimental groups, we revealed a decrease in the number of germ cells; signs of degenera-tive changes and lysis of spermatids and spermatozoa; the appearance of intense pyknotic nuclei in primary spermatocytes; and a sharp decrease in the number of spermatogonia and Sertoli and Leydig cells without change in their structure. In the irradiation groups of 8–12 Gy, there was the deepest damage to the tubules, up to spermatogenic epithelium aplasia, and extensive vacuolization. Conclusion. In the testes, we observed dose-dependent progressive pathological changes in tissue structure as well as a decrease in the number of spermatogonia and other germ cells on day 7 after irradiation with a pulsed electron accelerator NOVAC 11. Keywords: electron irradiation, male infertility, spermatogenesis, seminal globs

Alzheimer’s Disease-Associated Pathology in a Transgenic Mouse Model Results in Altered Voiding Function

Alzheimer’s disease (AD) is a devastating disorder primarily affecting older adults and is the most common neurodegenerative disease in the US. More than one in three AD patients experience AD-associated urinary dysfunction (ADUD), which directly contributes to their institutionalization. While ADUD has been clinically regarded as a result of poor cognitive control over urinary function, the physiology underlying loss of urinary control remains unknown. We hypothesize that beta-amyloidosis in the CNS results in pathologic changes in urinary structure and function. Male and female Tg-APP/PS1DE9 mice were used before plaque deposition (4-6 months) and after plaque accumulation (8-10 months) and compared to their WT littermates. Pressure-flow cystometry was conducted under urethane anesthesia to assess urinary performance at the level of the autonomic nervous system in the absence of cortical control. Pharmacomyography was performed on bladder strips to determine tissue-level changes in the absence of CNS input. In Tg-APP/PS1DE9 mice, plaque accumulation resulted in diminished volume sensitivity and decreased voiding efficiency. Pharmacologic studies showed aberrant drug responses, altered cholinergic signaling, and decreased resilience of tissue longevity after plaque accumulation. Based on our findings, we conclude that the AD-related pathology of Aβ accumulation results in a distinct urinary phenotype in our model, analogous to the ADUD observed in AD patients. Establishing and expanding models of ADUD to other mouse models of AD-associated pathology may improve the efficacy of treating ADUD and increase quality of life for patients and their caregivers.

Neural Mechanisms of Paroxysmal Kinesigenic Dyskinesia: Insights from Neuroimaging.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder of the nervoussystem, and little is known about its pathogenesis. Currently, the diagnosis of PKD is primarily based on clinical manifestations, with little objective evidence. Neuroimaging has been used to explore the pathological changes in cerebral structure and function associated with PKD. The current review highlights recent advances in neuroimaging to provide a better understanding of the neuralmechanisms and early diagnosis of this disorder. Several studies utilizing single-photon emission computed tomography (CT), positron emission tomography, and structural and functional magnetic resonance imaging have found significant localized abnormalities in the caudate nucleus, putamen, pallidum, thalamus, and frontoparietal cortex in PKD patients. These studies have also revealed alterations in interhemispheric functional connectivity between the brain regions of bilateral cerebral hemispheres such as the putamen, primary motor cortex, supplementary motor area, dorsal lateral prefrontal cortex, and primary somatosensory cortex in these patients. In addition, proline-rich transmembrane protein 2 gene mutations can affect the functional organization of the brain in PKD. These results suggest that the neural mechanisms of PKD are associated with the disruption of both structural and/or functional properties in basal ganglia-thalamo-cortical circuitry and interhemispheric functional connectivity. PKD can be considered a circuitry/network disorder and is not restricted to localized structural and/or functional abnormalities. Multimodal neuroimaging combined with gene analysis can provide additional valuable information for a better understanding of the pathogenesis and early diagnosis of this disorder.

Abstract 15006: Serotonin Transporter (SERT) Knockout Leads to Increased Myocardial and Mitral Valvular Fibrosis in a Murine Model

Introduction: Heart valve disease attributed to serotonin (5HT) has been observed with 5HT-secreting carcinoid tumors and with the diet drug, Dexfenfluoramine, a 5HT transporter (SLC6A4, also known as SERT) inhibitor and 5HT receptor (HTR) 2B agonist. 5HT/SLC6A4 mechanisms had not been investigated in mitral valve (MV) regurgitation. SLC6A4 internalizes 5HT, limiting HTR signaling. Selective 5HT reuptake inhibitor (SSRI) antidepressants target SLC6A4 to increase 5HT. We showed that SLC6A4 reduction in human MV influences MV regurgitation through enhanced HTR signaling. We further investigate the cardiac impact of SLC6A4 deficiency in a SERT -/- mouse reported to have cardiac abnormalities. Hypothesis: Absence of SERT leads to increased myocardial and MV fibrosis. Methods: SERT -/- and wild type (WT) C57BL/6J mice underwent echocardiography at 8 and 16 weeks (w) of age (N=5 / group). Collagen staining was performed with Masson’s trichrome. Markers of myocardial fibrosis α-smooth muscle actin (αSMA) and collagen type1, alpha 1 (COL1A1) were measured by PCR. Results: 8w and 16w SERT -/- mice showed increased epicardial fibrosis and MV sub-valvular fibrosis, particularly at leaflet attachment points, and in 16w SERT -/- mice MV leaflet fibrosis was also present. At 8w, posterior ventricular wall thickness was greater in SERT -/- mice vs. WT, both in systole (1.30 ± 0.09mm vs. 1.61 ± 0.2mm, p=0.003) and diastole (0.78 ± 0.11mm vs. 1.22 ± 0.29mm, p=0.001). At 16 w, ventricular dimensions were larger in SERT -/- mice vs. WT at end-systole (2.29 ± 0.54mm vs. 3.0 ± 0.47mm, p=0.008) and end-diastole (3.48 ± 0.45mm vs. 4.07 ± 0.35, p=0.006). Fractional shortening was reduced in 16w SERT -/- mice vs. WT (35.20 ± 7.66 vs. 26.74 ± 6.14, p=0.017) and vs. 8w SERT -/- mice (38.85 ± 4.57 vs. 26.74 ± 6.14, p=0.002). PCR showed increased fibrosis markers αSMA and COL1A1 in SERT -/- mice (8w and 16w) vs. WT (all p<0.05). Conclusions: SERT -/- mice show pathologic structural changes and fibrosis in both myocardium and MV, corresponding to functional differences that worsen with age. As inhibition of SLC6A4, combined with active HTR2A/B signaling would hypothetically increase MV remodeling and regurgitation, these animals could be ideal to test 5HT pharmacology.

Pathophysiological Perspective of Osteoarthritis.

Osteoarthritis (OA) is the most well-known degenerative disease among the geriatric and is a main cause of significant disability in daily living. It has a multifactorial etiology and is characterized by pathological changes in the knee joint structure including cartilage erosion, synovial inflammation, and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA, and current therapy is broadly divided into pharmacological and nonpharmacological measures prior to surgical intervention. In this review, the significant risk factors and mediators, such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA are described. As the understanding of the mechanisms underlying OA improves, treatments are being developed that target specific mediators thought to promote the cartilage destruction that results from imbalanced catabolic and anabolic activity in the joint.

CLINICAL AND THERAPEUTIC VALUE OF ADIPOKINES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

This review is devoted to the analysis of the role of adipokines in formation of pathological changes in renal function and structure. The patients with chronic kidney disease have a high risk of cardiovascular disease. Currently, the role of systemic hormonal and metabolic factors in the pathogenesis of the kidneys is growing. A promising area of pathogenetic prevention and treatment of kidney disease is an interdisciplinary approach, whereat the adipokine imbalance is of particular interest. Adipose tissue and its messengers, adipokines, are known to be highly associated with kidney disease. Adipocytes are metabolically active cells, producing the signaling lipids, metabolites and protein factors, i.e. adipokines. The interaction of adipose tissue with the kidney is called the adipose kidney axis, being important for the normal functioning of the body, as well as its response to an injury. It has a strong therapeutic potential in respect of the growing rates of chronic kidney disease. Adipocyte hypertrophy is often accompanied by the development of tissue fibrosis, hypoxia, and secretion of pro−inflammatory cytokines (such as tumor necrosis factor or interleukin, which triggers the cell inflammation). Dysfunction of adipose tissue contributes to the development of cardiovascular disease at the local and systemic levels. Thus, for the early diagnosis of chronic kidney disease into the diagnostic program, in addition to the generally accepted indices, the determination of adipokines: for example, serum leptin, adiponectin, omentin, visfatin, microalbuminuria, blood lipid spectrum, intrarenal and functional status of the kidneys with the assessment of functional renal reserve is recommended to be included. Early detection of the disease, new approaches to its diagnosis and treatment can help in reducing the risk of a high incidence and mortality from renal disease. Key words: chronic kidney disease, nephropathy, adipokines, leptin, resistin, adiponectin, visfatin, omentin.

Fufang Xueshuantong alleviates diabetic retinopathy by activating the PPAR signalling pathway and complement and coagulation cascades

Ethnopharmacological relevanceFufang Xueshuantong (FXST) is a traditional Chinese patent medicine composed of Panax notoginseng (Burkill) F.H.Chen (Araliaceae), Salvia miltiorrhiza Bunge (Lamiaceae), Astragalus propinquus Schischkin (Leguminosae), and Scrophularia ningpoensis Hemsl. (Scrophulariaceae). It has been widely used for the treatment of diabetic retinopathy (DR) and exerts a positive clinical therapeutic effect. Aim of the studyThe aim of this study was to observe the effect of FXST on diabetic rat retinas and investigate its pharmacological mechanism for improving DR. MethodsThe diabetic rat model was established by intraperitoneal injection of streptozotocin. The rats were divided into a normal group, diabetic group, and FXST group. The rats in the FXST group were treated with FXST by intragastric administration for 12 weeks while other rats were given the same volume of normal saline. The haemodynamic parameters of the central retinal artery in the rats were measured by ultrasound. Haematoxylin-eosin staining was utilised to observe the pathological structural changes in the retina. The apoptosis of retinal nerve cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling. RNA sequencing was used to screen the differentially expressed genes (DEGs), and enrichment analyses were performed. The DEGs were validated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). ResultsThe peak systolic velocity, end diastolic velocity, and mean velocity decreased while the resistance index and pulsatility index increased in the diabetic rat retinas. FXST also improved haemodynamics. In contrast with the diabetic group, FXST allayed the disorder and oedema of the retinal structure in addition to reversing the reductions in retinal thickness and retinal ganglion cell number. It also decreased the apoptosis index of retinal cells. A total of 1134 DEGs were identified by RNA sequencing in the FXST group compared to the diabetic group, including 814 upregulated genes and 320 downregulated genes. These genes were enriched in the complement and coagulation cascades as well as the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Several DEGs, including PPAR gamma, perilipin 4, acyl-CoA dehydrogenase long chain, CD55 molecule, and plasminogen activator urokinase, were identified by qRT-PCR, and the results were consistent with the RNA sequencing data. ConclusionsFXST alleviates DR by improving the haemodynamics and morphological alterations of diabetic rat retinas, which are mediated by complement and coagulation cascades and the PPAR signalling pathway.

Reorganization of motor modules for standing reactive balance recovery following pyridoxine-induced large-fiber peripheral sensory neuropathy in cats.

Task-level goals such as maintaining standing balance are achieved through coordinated muscle activity. Consistent and individualized groupings of synchronously activated muscles can be estimated from muscle recordings in terms of motor modules or muscle synergies, independent of their temporal activation. The structure of motor modules can change with motor training, neurological disorders, and rehabilitation, but the central and peripheral mechanisms underlying motor module structure remain unclear. To assess the role of peripheral somatosensory input on motor module structure, we evaluated changes in the structure of motor modules for reactive balance recovery following pyridoxine-induced large-fiber peripheral somatosensory neuropathy in previously collected data in four adult cats. Somatosensory fiber loss, quantified by postmortem histology, varied from mild to severe across cats. Reactive balance recovery was assessed using multidirectional translational support-surface perturbations over days to weeks throughout initial impairment and subsequent recovery of balance ability. Motor modules within each cat were quantified by non-negative matrix factorization and compared in structure over time. All cats exhibited changes in the structure of motor modules for reactive balance recovery after somatosensory loss, providing evidence that somatosensory inputs influence motor module structure. The impact of the somatosensory disturbance on the structure of motor modules in well-trained adult cats indicates that somatosensory mechanisms contribute to motor module structure, and therefore may contribute to some of the pathological changes in motor module structure in neurological disorders. These results further suggest that somatosensory nerves could be targeted during rehabilitation to influence pathological motor modules for rehabilitation.NEW & NOTEWORTHY Stable motor modules for reactive balance recovery in well-trained adult cats were disrupted following pyridoxine-induced peripheral somatosensory neuropathy, suggesting somatosensory inputs contribute to motor module structure. Furthermore, the motor module structure continued to change as the animals regained the ability to maintain standing balance, but the modules generally did not recover pre-pyridoxine patterns. These results suggest changes in somatosensory input and subsequent learning may contribute to changes in motor module structure in pathological conditions.

Cohort profile: the Oxford Parkinson’s Disease Centre Discovery Cohort MRI substudy (OPDC-MRI)

PurposeThe Oxford Parkinson’s Disease Centre (OPDC) Discovery Cohort MRI substudy (OPDC-MRI) collects high-quality multimodal brain MRI together with deep longitudinal clinical phenotyping in patients with Parkinson’s, at-risk individuals and healthy...