Component Of Various Diseases Research Articles

Микрочастицы клеток крови у больных COVID-19 как маркер активации системы гемостаза.

Введение. Наблюдения за больными COVID-19 показали развитие коагулопатии на фоне тяжелой инфекции, вызванной SARC–CoV-2. Патогенетические механизмы влияния SARC–CoV-2 на систему гемостаза в настоящее время активно исследуются, однако для практического здравоохранения крайне актуальным является поиск маркеров активации системы свертывания крови с целью ранней профилактики тромбоэмболических осложнений у пациентов с COVID-19. Цель исследования: определить количество микрочастиц, отделяющихся от клеток крови, у больных COVID-19 и здоровых индивидуумов и проанализировать корреляцию числа микрочастиц с лабораторными и клиническими характеристиками пациентов. Материалы и методы. Обследованы 10 пациентов с COVID-19, госпитализированных в ФГБОУ ВО СЗГМУ им. И. И. Мечникова Минздрава России в период июнь-июль 2020 г., контрольную группу составили 12 сотрудников ФГБОУ ВО СЗГМУ им. И.И. Мечникова Минздрава России без признаков острого респираторного заболевания, без сердечно-сосудистых и тромбоэмболических эпизодов в анамнезе. У всех обследованных выполнен клинический анализ крови, исследованы маркеры активации и воспаления, а также измерено количество внеклеточных микровезикул — экзосом на проточном цитометре. Результаты. У пациентов с COVID-19 по сравнению с контрольной группой наблюдалось увеличение относительного количества нейтрофилов и снижение тромбоцитов. Такие маркеры как фибриноген, С-реактивный белок, ферритин, интерлейкин-6 и лактатдегидрогеназа значительно превышали верхнюю границу референтных значений. При этом количество экзосом оказалось значимо выше у пациентов с COVID-19 по сравнению со здоровыми лицами (% позитивных событий) — 93,2 [88,7–96,5] против 56,2 [50,5–73,5] соответственно (p = 0,00001) и коррелировало с относительным уровнем нейтрофилов. Среди проанализированных экзосом преобладали микрочастицы тромбоцитарного и лейкоцитарного происхождения. Заключение. Увеличение количества внеклеточных микрочастиц у больных COVID-19 может быть использовано как маркер активации гемостаза и повышенного риска тромботических осложнений на фоне инфекционного заболевания. Background. The monitoring of COVID-19 patients showed the development of coagulopathy in the context of severe infection caused by SARC–CoV-2. The pathogenetic mechanisms of SARC–CoV-2 influence on hemostasis are currently being actively examined, but the search for markers of the blood-clotting system activation for early prevention of thromboembolic complications in patients with COVID-19 is highly relevant for the practical health care. Objectives: to analyze the number of microparticles that separate from blood cells due to the hemostasis activation in COVID-19 patients and in healthy donors and to analyze the correlation between microparticles number and laboratory and clinical characteristics of patients. Patients /Methods. The study included 10 patients with COVID-19 who were hospitalized in Mechnikov North- Western State Medical University in June- July 2020; the control group consisted of 12 employees of Mechnikov North- Western State Medical University without signs of acute respiratory disease, without cardiovascular and thromboembolic episodes in the history. All patients and individuals in the control group had their blood clinically tested on a 5-Diff hematological analyzer, markers for activation and inflammation were examined, and the number of extracellular microvesicles (exosomes) was measured on the flow cytometer. Results. Patients with COVID-19 had an increase in the relative amount of neutrophiles and a decrease in platelets compared to controls. Markers such as fibrinogen, C-reactive protein, ferritin, interleukine-6 and lactate dehydrogenase significantly exceeded the upper reference limit. The number of exosomes was significantly higher in patients with COVID-19 compared to healthy controls (% of positive events) — 93.2 [88.7–96.5] vs. 56.2 [50.5–73.5] respectively (p = 0.00001), and correlated with the relative level of neutrophiles. Among the exosomes analyzed, platelet and leukocyte microparticles prevailed. Conclusions. The increase of extracellular microparticles in COVID-19 patients can be used as a marker of hemostasis activation and increased risk of thrombotic complications in the context of severe infectious disease.

The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System.

Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape. The recently identified participation of the gut microbiota in the remodeling of the epigenome of immune cells has triggered a paradigm shift in our understanding of the etiology of various inflammatory diseases and opened new paths toward therapeutic strategies. In this review, we provide an overview of the contribution of the Th17/Treg balance in the development and progression of inflammatory bowel diseases and metabolic diseases. We discuss the involvement of epigenetic mechanisms in the regulation of T cell function in the particular context of dysbiosis. Finally, we examine the potential for nutritional interventions affecting the gut microbiota to reshape the T cell epigenome and address the inflammatory component of various diseases.

NLRP3 inflammasome: A therapeutic option for kidney disease?

To determine if considering inflammasome NLRP3 as a treatment option for kidney disease is possible. Literature review related to NLRP3 inflammasome structure, biological function and relationship with renal disease and others (hypertension, diabetes, gout, atherosclerosis, amyloidosis, Alzheimer's disease); the systematic review was made searching in the databases PubMed and SciELO for the following terms: "The NLRP3 inflammasome therapeutic for kidney disease", "NLRP3 nflammasome in kidney disease" in PubMed, and "Inflammasome" for Scielo. 146 documents were found, althoughonly 34 matched the working hypothesis concerning the NLRP3 inflammasome as a central component of various diseases in humans, with potential therapeutic use. The NLRP3 inflammasome is responsible for the maturation of inflammatory pro-interleukin IL-1 β and IL-18, which can be triggered by aggregated or crystalline materials (particles), and by various microorganisms and toxins derived from these; however, the way how activation mechanisms work is not completely clear. Research on new therapies that focus on removing or inhibiting inflammasome components, both individually and together, is proposed.

Clinical Relevance of Biomarkers of Oxidative Stress.

Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170.

In vivo microscopy of microvessel oxygenation and network connections

Abnormal or compromised microvascular function is a key component of various diseases. In vivo microscopy of microvessel function in preclinical models can be useful for the study of a disease state and effects of new treatments. Wide-field imaging of microvascular oxygenation via hemoglobin (Hb) saturation measurements has been applied in various applications alone and in combination with other measures of microvessel function, such as blood flow. However, most current combined imaging methods of microvessel function do not provide direct information on microvessel network connectivity or changes in connections and blood flow pathways. First-pass fluorescence (FPF) imaging of a systemically administered fluorescent contrast agent can be used to directly image blood flow pathways and connections relative to a local supplying arteriole in a quantitative manner through measurement of blood supply time (BST). Here, we demonstrate the utility of information produced by the combination of Hb saturation measurements via spectral imaging with BST measurements via FPF imaging for correlation of microvessel oxygenation with blood flow pathways and connections throughout a local network. Specifically, we show network pathway effects on oxygen transport in normal microvessels, dynamic changes associated with wound healing, and pathological effects of abnormal angiogenesis in tumor growth and development.

Microparticles: a component of various diseases

Microparticles (MPs) are phenotypically and functionally heterogeneous population of microvesicles. Although MP formation represents a physiological phenomenon. A multitude of pathologies, including inflammatory and autoimmune diseases, atherosclerosis, and malignancies, are associated with a considerable increase in circulating MPs. Elevated levels of platelet‑, endothelial cell‑, and monocyte‑derived MPs have been documented in a number of clinical conditions in which vascular dysfunction and inflammation are important pathophysiological mechanisms (e.g., coronary artery disease or thrombotic microangiopathies). Knowledge of the functional properties of MPs will contribute to a better understanding of the pathological mechanisms of communication between cells and of the causes of various diseases.

Functional Role of Intracellular Labile Zinc in Pulmonary Endothelium

After iron, zinc is the most abundant essential trace metal. Intracellular zinc ([Zn]i) is maintained across a wide range of cells and species in a tight quota (100 to 500 μM) by a dynamic process of transport, intracellular vesicular storage, and binding to a large number of proteins (estimated at 3-10% of human proteome). As such, zinc is an integral component of numerous metalloenzymes, structural proteins, and transcription factors. It is generally assumed that a vanishingly small component of [Zn]i, referred to as free or labile zinc, and operationally defined as the pool sensitive to chelation (by agents such as N, N, N’, N’-tetrakis [2-pyridylmethyl] ethylenediamine [TPEN]) and capable of detection by a variety of chemical and genetic sensors, participates in signal transduction pathways. Zinc deficiencies, per se, can arise from acquired (malnutrition, alcoholism) or genetic (mutations in molecules affecting zinc homeostasis, the informative and first example being acrodermatitis enteropathica) factors or as a component of various diseases (e.g., sickle cell disease, cystic fibrosis, sepsis). Hypozincemia has profound effects on developing humans, and all facets of physiological function (neuronal, endocrine, immunological) are affected, although considerably less is known regarding cardiovascular pathophysiology. In this review, we provide an update on current knowledge of molecular and cellular aspects of zinc homeostasis and then focus on implications of zinc signaling in pulmonary endothelium as it relates to programmed cell death, altered contractility, and septic and aseptic injury to this segment of the lung.

Cellular prion protein: on the road for functions

Cellular prion (PrPc) is a plasma membrane glycosyphosphatidylinositol-anchored protein present in neurons but also in other cell types. Protein conservation among species suggests that PrPc may have important physiological roles. Cellular and molecular approaches have established several novel features of the regulation of PrPc expression, cellular trafficking as well as its participation in copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling and cell survival. It is therefore likely that PrPc plays pleiotropic roles in neuronal and non-neuronal cells, and as such the loss of function of PrPc may be an important component of various diseases.

The case for routine determination of chorionicity and zygosity in multiple pregnancy

Twin pregnancy has a disproportionate effect on perinatal mortality, being six times higher than for singleton gestations. The major threats to perinatal survival are from two very different pathological processes: spontaneous preterm delivery, and the interlacing clinical complications of monochorionicity. With the realization that perinatal loss/handicap is higher in monochorionic than dichorionic twins, attempts have been made in the last decade to assign chorionicity ultrasonographically, using single or composite parameters, such as number of placental masses, fetal sex, septal thickness and twin peak signs. Such knowledge will allow (a) risk stratification of twin gestations, (b) appropriate selection of prenatal screening and diagnostic methods, (c) vigilant monitoring for early diagnosis of twin–twin transfusion syndrome and growth restriction, and (d) management of preterm labour, congenital malformation, single intra-uterine death and polyhydramnios. By contrast, prospective knowlege of zygosity is unlikely to influence perinatal outcome, since approximately 25 per cent of monozygous conceptions have dichorionic placentation. Postnatal determination of zygosity in like sex twin pairs with dichorionic placenta is important for the future consideration of organ transplantation compatibility and to evaluate the genetic component of various diseases. © 1997 by John Wiley & Sons, Ltd.

The case for routine determination of chorionicity and zygosity in multiple pregnancy

Twin pregnancy has a disproportionate effect on perinatal mortality, being six times higher than for singleton gestations. The major threats to perinatal survival are from two very different pathological processes: spontaneous preterm delivery, and the interlacing clinical complications of monochorionicity. With the realization that perinatal loss/handicap is higher in monochorionic than dichorionic twins, attempts have been made in the last decade to assign chorionicity ultrasonographically, using single or composite parameters, such as number of placental masses, fetal sex, septal thickness and twin peak signs. Such knowledge will allow (a) risk stratification of twin gestations, (b) appropriate selection of prenatal screening and diagnostic methods, (c) vigilant monitoring for early diagnosis of twin-twin transfusion syndrome and growth restriction, and (d) management of preterm labour, congenital malformation, single intra-uterine death and polyhydramnios. By contrast, prospective knowledge of zygosity is unlikely to influence perinatal outcome, since approximately 25 per cent of monozygous conceptions have dichorionic placentation. Postnatal determination of zygosity in like sex twin pairs with dichorionic placenta is important for the future consideration of organ transplantation compatibility and to evaluate the genetic component of various diseases.

The disease complex of the gypsy moth: I. Major components

A study was undertaken to elucidate the impact of the various components of disease on natural populations of the gypsy moth, Porthetria dispar. Diseased larvae from both sparse and dense populations were examined and categorized on the basis of etiologic and nonetiologic mortality factors. Results indicated a significantly higher incidence of parasitoid involvement—but virtual nonexistence of polyhedral viroses—in the relatively stable sparse populations. Nuclear polyhedrosis probably represented the primary mortality factor in the dense populations. Many insects examined from both population types revealed no infectious agent or overt cause of disease, a fact that may indicate a major regulatory role of noninfectious disease in natural populations. Variation in the disease complex within the populations that have been studied indicates that minor causes of disease in one may well predominate in others. Thus, to fully understand this complex, it must be studied across a number of years within a series of populations from different geographical areas.