Dysfunction of low-density neutrophils in peripheral circulation in patients with sepsis

Low-density neutrophils (LDNs) have been described in tumors and various autoimmune diseases, where they exhibit immune dysfunction and alter disease progression. Nevertheless, LDNs have been rarely reported in sepsis. We studied sepsis patients admitted to the intensive care unit. Wright-Giemsa stain assay and Transmission electron microscopy were performed to detect the morphology of neutrophils. Flow cytometry was used to analyze the number and function of LDNs. Concentration of cytokines was measured using ELISA. Neutrophil chemotaxis was examined using an under-agarose chemotaxis model. We found that LDNs were significantly elevated in patients with sepsis. Phenotypes and morphological characteristics suggest that LDNs may be formed by mixtures of neutrophils at various maturation stages. In vitro experiments showed that LDN formation was closely associated with neutrophil degranulation. We preliminarily discussed changes in immune function in LDNs. Compared with high-density neutrophils, expression levels of CXC chemokine receptor 4 on LDN surfaces were increased, phagocytotic capacity was decreased, and life span was prolonged. The chemotactic ability of LDNs was significantly reduced, possibly related to the increased expression of P2X1. These data suggest that LDNs are essential components of neutrophils in sepsis. To clarify the source and dysfunction mechanism of LDN in sepsis may be helpful for the diagnosis and treatment of sepsis in the future.

Balancing cholesterol in the brain: from synthesis to disposal

The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.

An evidence-based approach in the management of fatigue due to heart failure: breathing exercises

Fatigue is one of the common symptoms that adversely affect the quality of life of patients with heart failure. It has been reported that fatigue seen in heart failure is caused by conditions such as deterioration of peripheral circulation due to decrease in oxygen delivery, autonomic nervous system abnormalities and deterioration in the strength of the respiratory muscles. Breathing exercises are one of the integrative applications that can increase oxygen delivery due to the functional connection of the heart and lungs providing relief from fatigue. In the literature, breathing exercises have a wide range of breathing techniques that create changes in breathing form and rate. Many studies have found that breathing exercises reduce fatigue, and can have significant effects on patient care and clinical outcomes. Nurses have a major impact on patient outcomes such as reducing fatigue in heart failure patients and improving health-related quality of life. For this reason, it is very important to include breathing exercises in nursing practices. In this regard, the importance of breathing exercises in the management of fatigue due to heart failure has been addressed in this review.

EFFECT OF QUERСETIN AND CHLORHEXIDINE-DENT ON CHANGES IN PERIODONTIC TISSUES IN CHILDREN LIVING IN ENVIRONMENTALLY POLLUTED REGIONS OF PRECARPATHIAN REGIONS

The aim of the research is to increase the effectiveness of treatment of patients with chronic catarrhal gingivitis living in ecologically favorable conditions and in ecologically polluted regions of Precarpathian, by adding to the complex therapy of quercetin and chlorhexidine dent. The results of research by a number of scientists indicate that the use of quercetin in complex therapy helps to restore the antioxidant system, improve oxygen uptake by tissues and peripheral circulation, improve the rheological properties of the patient's blood. These properties of the drug were used by us in the research. We studied changes in periodontal tissues in children living in ecologically favorable conditions and in ecologically polluted regions of Precarpathian, conducted a comparative characterization of changes in periodontium and proposed a treatment plan for patients with chronic catarrhal gingivitis, supplemented with chlorhexidine dent and quercetin. We examined 60 children with chronic catarrhal gingivitis living in the contaminated areas of Precarpathian (Burshtyn) and 15 people with intact periodontium living in environmentally stable conditions. All patients underwent a full range of treatment measures, taking into account the removal of dental plaque and rehabilitation of the oral cavity. In 1 group of patients (30 people) patients were treated with chlorhexidine, calendula and chamomile infusion and 1% mefenamine paste. Patients of group 2 (30 people) - the drug quercetin on the mucous membrane of the gums under the individual gingival cap and chlorhexidine dent in the form of oral baths. In order to compare the two groups, an index assessment of the condition of periodontal tissues and a study of rheographic parameters of periodontal tissues were performed. The results of the research did not show a significant difference between clinical and laboratory parameters in patients 1 and 2 groups before treatment (p> 0.05), but they differed significantly from those in the comparison group (p <0.05), which indicates the fact that unfavorable environmental living conditions have an impact on the course of periodontal disease in children. We obtained a significant difference in the blood supply to periodontal tissues in patients with chronic catarrhal gingivitis compared with (p <0.05). The results of the research showed that the use of quercetin and 0.12% chlorhexidine solution in the complex treatment of patients with chronic catarrhal gingivitis provided a significant improvement in clinical parameters and laboratory characteristics of periodontal tissues in children living in different environmental conditions, and provided stabilization of these indicators in long-term observation. The use of the proposed scheme of treatment of patients with chronic catarrhal gingivitis stimulates metabolic processes in periodontal tissues, reduces cyanosis, edema of periodontal tissues according to the results of rheography of periodontal tissues. After treatment, we observe the normalization of the rheological characteristics of the gums, which indicates an improvement in blood circulation in the periodontal tissues in these patients (normalization of qualitative and quantitative characteristics of rheograms).

MicroRNAs as Potential Biomarkers for Exercise-Based Cancer Rehabilitation in Cancer Survivors

Expression and functions of microRNAs (miRNAs) have been widely investigated in cancer treatment-induced complications and as a response to physical activity, respectively, but few studies focus on the application of miRNAs as biomarkers in exercise-based cancer rehabilitation. Research has shown that certain miRNA expression is altered substantially due to tissue damage caused by cancer treatment and chronic inflammation. MiRNAs are released from the damaged tissue and can be easily detected in blood plasma. Levels of the miRNA present in peripheral circulation can therefore be used to measure the extent of tissue damage. Moreover, damage to tissues such as cardiac and skeletal muscle significantly affects the individual’s health-related fitness, which can be determined using physiologic functional assessments. These physiologic parameters are a measure of tissue health and function and can therefore be correlated with the levels of circulating miRNAs. In this paper, we reviewed miRNAs whose expression is altered during cancer treatment and may correlate to physiological, physical, and psychological changes that significantly impact the quality of life of cancer survivors and their role in response to physical activity. We aim to identify potential miRNAs that can not only be used for monitoring changes that occur in health-related fitness during cancer treatment but can also be used to evaluate response to exercise-based rehabilitation and monitor individual progress through the rehabilitation programme.

Current Perspectives on “Off-The-Shelf” Allogeneic NK and CAR-NK Cell Therapies

Natural killer cells (NK cells) are the first line of the innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected and malignant cells through a balancing play of inhibitory and stimulatory receptors. In pre-clinical investigational studies, NK cells show promising anti-tumor effects and are used in adoptive transfer of activated and expanded cells, ex-vivo. NK cells express co-stimulatory molecules that are attractive targets for the immunotherapy of cancers. Recent clinical trials are investigating the use of CAR-NK for different cancers to determine the efficiency. Herein, we review NK cell therapy approaches (NK cell preparation from tissue sources, ways of expansion ex-vivo for “off-the-shelf” allogeneic cell-doses for therapies, and how different vector delivery systems are used to engineer NK cells with CARs) for cancer immunotherapy.

How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19

Aging is characterized by the dynamic remodeling of the immune system designated “immunosenescence,” and is associated with altered hematopoiesis, thymic involution, and lifelong immune stimulation by multitudinous chronic stressors, including the cytomegalovirus (CMV). Such alterations may contribute to a lowered proportion of naïve T-cells and to reduced diversity of the T-cell repertoire. In the peripheral circulation, a shift occurs towards accumulations of T and B-cell populations with memory phenotypes, and to accumulation of putatively senescent and exhausted immune cells. The aging-related accumulations of functionally exhausted memory T lymphocytes, commonly secreting pro-inflammatory cytokines, together with mediators and factors of the innate immune system, are considered to contribute to the low-grade inflammation (inflammaging) often observed in elderly people. These senescent immune cells not only secrete inflammatory mediators, but are also able to negatively modulate their environments. In this review, we give a short summary of the ways that immunosenescence, inflammaging, and CMV infection may cause insufficient immune responses, contribute to the establishment of the hyperinflammatory syndrome and impact the severity of the coronavirus disease 2019 (COVID-19) in elderly people.

Efficacy of Probucol on cognitive function in Alzheimers disease: Study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA Study)

Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid-beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimers disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromises the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function and suppressing neurovascular inflammation. Probucol has also been shown to protect cognitive function in dietary-induced amyloidogenic mice. This protocol details the Probucol in Alzheimers Study (PIA-study), a double-blind, randomised, placebo-controlled drug intervention trial investigating if Probucol attenuates cognitive decline in patients with mild-to-moderate AD. Objectives: The primary objective of the 104-week study is to assess whether Probucol supports cognitive function and delays brain atrophy in AD patients. A secondary objective is to determine whether Probucol treatment will reduce cerebral amyloid burden.

Detection and clinical significance of circulating tumor cells in colorectal cancer

Histopathological examination (biopsy) is the “gold standard” for the diagnosis of colorectal cancer (CRC). However, biopsy is an invasive method, and due to the temporal and spatial heterogeneity of the tumor, a single biopsy cannot reveal the comprehensive biological characteristics and dynamic changes of the tumor. Therefore, there is a need for new biomarkers to improve CRC diagnosis and to monitor and treat CRC patients. Numerous studies have shown that “liquid biopsy” is a promising minimally invasive method for early CRC detection. A liquid biopsy mainly samples circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA (miRNA) and extracellular vesicles (EVs). CTCs are malignant cells that are shed from the primary tumors and/or metastases into the peripheral circulation. CTCs carry information on both primary tumors and metastases that can reflect dynamic changes in tumors in a timely manner. As a promising biomarker, CTCs can be used for early disease detection, treatment response and disease progression evaluation, disease mechanism elucidation, and therapeutic target identification for drug development. This review will discuss currently available technologies for plasma CTC isolation and detection, their utility in the management of CRC patients and future research directions.