Gut microbiome a promising target for management of respiratory diseases

2020 ◽  
Vol 477 (14) ◽  
pp. 2679-2696
Author(s):  
Riddhi Trivedi ◽  
Kalyani Barve

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

2019 ◽  
Vol 1 (9) ◽  
pp. 38-46
Author(s):  
A. P. Babkin ◽  
A. A. Zuikova ◽  
O. N. Krasnorutskaya ◽  
Yu. A. Kotova ◽  
D. Yu. Bugrimov ◽  
...  

The widespread worldwide spread of acute respiratory diseases is an urgent problem in health care. Expressed polyetiology of respiratory diseases does not allow to limit the use of specific vaccine preparations and dictates the need to use to combat them a variety of non-specific means that stimulate the natural resistance of the human body. The main pharmacological action of sodium deoxyribonucleate is the stimulation of phagocytic activity of T-helpers and T-killers, increasing the functional activity of neutrophils and monocytes/ macrophages, providing regeneration and repair processes in the epithelial component of antiviral protection of the body. Based on the above, the study of the clinical efficacy of Derinat® in the form of spray in the treatment of acute respiratory viral infections is relevant.


2021 ◽  
Vol 22 (10) ◽  
pp. 5148
Author(s):  
Karin Enderle ◽  
Martin Dinkel ◽  
Eva-Maria Spath ◽  
Benjamin Schmid ◽  
Sebastian Zundler ◽  
...  

Intraepithelial lymphocytes (IEL) are widely distributed within the small intestinal epithelial cell (IEC) layer and represent one of the largest T cell pools of the body. While implicated in the pathogenesis of intestinal inflammation, detailed insight especially into the cellular cross-talk between IELs and IECs is largely missing in part due to lacking methodologies to monitor this interaction. To overcome this shortcoming, we employed and validated a murine IEL-IEC (organoids) ex vivo co-culture model system. Using livecell imaging we established a protocol to visualize and quantify the spatio-temporal migratory behavior of IELs within organoids over time. Applying this methodology, we found that IELs lacking CD103 (i.e., integrin alpha E, ITGAE) surface expression usually functioning as a retention receptor for IELs through binding to E-cadherin (CD324) expressing IECs displayed aberrant mobility and migration patterns. Specifically, CD103 deficiency affected the ability of IELs to migrate and reduced their speed during crawling within organoids. In summary, we report a new technology to monitor and quantitatively assess especially migratory characteristics of IELs communicating with IEC ex vivo. This approach is hence readily applicable to study the effects of targeted therapeutic interventions on IEL-IEC cross-talk.


Author(s):  
Anastasiya S. Kazitskaya ◽  
Oleg I. Bondarev ◽  
Maria S. Bugaeva ◽  
Anna G. Zhukova ◽  
Tatyana K. Yadykina

Introduction. The combined impact of unfavorable factors of the production environment in miners leads to the development of associated pathology of the bronchopulmonary and cardiovascular systems, the predisposition to which depends on the individual susceptibility of the body. In this regard, it is important to comprehensively study the pathogenetic mechanisms underlying the formation and course of occupational and work-related diseases for a personalized approach to the diagnosis, prevention and therapy of this pathology. The purpose of this study was to study the mechanisms of damage to the cardiovascular system in miners with dust lung pathology on the basis of morphological and genetic studies. Materials and methods. For genetic studies, venous blood drawing was conducted in 190 Kuzbass miners. The main group included 126 miners of the main professions with the previously proven diagnosis "dust lung pathology", the comparison group consisted of 64 workers without a proven diagnosis working in similar sanitary and hygienic conditions. Morphometric studies were carried out using autopsy material obtained during 80 forensic medical examinations of miners in the Kemerovo region. All the miners were divided into 4 groups depending on their underground work experience. The control group was formed from 20 cases of forensic medical examinations of men who died in road accidents and did not have organ pathology according to the results of autopsies. Results. The study of the autopsy material revealed the presence of morphostructural changes in the vascular walls of the miners’ hearts in the form of hypertrophy of the smooth muscle cells of the medial layers, thickening of the endothelial lining, and the development of fibroplastic changes in the perivascular zones. These changes began to form from the first years of work in the underground conditions and progressed with increasing work experience contributing to the "recalibration" of the heart vessels with the formation of the lumen "obstruction". One of the mechanisms of endothelial damage in miners was a change in the expression of the EDN1 gene, which regulates the synthesis of endothelin-1. The risk and resistance genotypes of the development of dust lung pathology for the rs5370 polymorphism of the EDN1 gene were identified. Morphostructural rearrangement of the endothelium in the combination with its pathological activation contributed to the occurrence of endothelial dysfunction in miners. Conclusions. The conducted studies of the parameters of the vascular endothelium indicate its key role in the pathogenesis of bronchopulmonary and cardiovascular pathology in miners of the main professions. Getting into the body of workers, particles of coal-rock dust lead to morphostructural rearrangement of the cells of the endothelial layer and its pathological activation. The contribution of molecular and genetic mechanisms to the development of occupational lung pathology and associated diseases of the circulatory system in miners is revealed. Ethics. The studies were carried out in compliance with the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, elaborated on the basis of the Helsinki Declaration of the World Medical Association "Ethical Principles for Conducting Human Scientific Medical Research" as amended in 2013 and the "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated 19.06.2003. All workers were informed about their participation in the molecular-genetic study and gave written consent to carry it out. The research of the dead miners was based on the secondary examination of blocks and ready-made histological micro-preparations of the material of the Bureau for Forensic Medical Expert Examination of the cities of Novokuznetsk, Osinniki, and Prokopyevsk. The study of pathomorphological material was carried out in accordance with the Federal Law of 21.11.2011, No. 323-FZ "On the Fundamentals of Health Protection of Citizens in the Russian Federation", in particular, with Article 67 "Carrying out pathological and anatomical autopsies", Federal Law of 12.01.1996, No. 8-FZ "On burial and funeral business" (Article 5, paragraphs 1, 2), as well as on the basis of the Order of the Ministry of Health of April 29, 1994, No. 82 "On the procedure for conducting pathological and anatomical autopsy" (Annex to the Order of the Ministry of Health and Medical Industry of 29.04.1994 No. 82), the Order of the Ministry of Health of Russia of 24.03.2016. No. 179n "On the rules for conducting pathological and anatomical examinations".


2019 ◽  
Vol 60 (4) ◽  
pp. 442-450 ◽  
Author(s):  
Yu Zhao ◽  
Junling Zhang ◽  
Xiaodan Han ◽  
Saijun Fan

Abstract Radiation can induce senescence in many organs and tissues; however, it is still unclear how radiation stimulates senescence in mouse small intestine. In this study, we use the bone marrow transplantation mouse model to explore the late effects of total body irradiation on small intestine. Our results showed that almost all of the body hairs of the irradiated mice were white (which is an indication of aging) 10 months after the exposure to radiation. Furthermore, compared with the age-matched control mice, there were more SA-β-galactosidase (SA-β-gal)–positive cells and an upregulation of p16 and p21 in 8 Gy–irradiated mice intestinal crypts, indicating that radiation induced senescence in the small intestine. Intestinal bacterial flora profile analysis showed that the diversity of the intestinal bacterial flora decreased in irradiated mice; in addition it showed that the principal components of the irradiated and control mice differed: there was increased abundance of Bacteroidia and a decreased abundance of Clostridia in irradiated mice. To explore the underlying mechanism, an RNA-sequence was executed; the results suggested that pancreatic secretion, and the digestion and absorption of proteins, carbohydrates, fats and vitamins were damaged in irradiated mice, which may be responsible for the body weight loss observed in irradiated mice. In summary, our study suggested that total body irradiation may induce senescence in the small intestine and damage the health status of the irradiated mice.


Author(s):  
Yidan Pang ◽  
Changqing Zhang ◽  
Junjie Gao

Macrophages are a group of heterogeneous cells widely present throughout the body. Under the influence of their specific environments, via both contact and noncontact signals, macrophages integrate into host tissues and contribute to their development and the functions of their constituent cells. Mitochondria are essential organelles that perform intercellular transfers to regulate cell homeostasis. Our review focuses on newly discovered roles of mitochondrial transfers between macrophages and surrounding cells and summarizes emerging functions of macrophages in transmitophagy, metabolic regulation, and immune defense. We also discuss the negative influence of mitochondrial transfers on macrophages, as well as current therapies targeting mitochondria in macrophages. Regulation of macrophages through mitochondrial transfers between macrophages and their surrounding cells is a promising therapy for various diseases, including cardiovascular diseases, inflammatory diseases, obesity, and cancer.


Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1106
Author(s):  
Di Wang ◽  
Ye Cong ◽  
Quanfeng Deng ◽  
Xiahe Han ◽  
Suonan Zhang ◽  
...  

The pathogenesis of respiratory diseases is complex, and its occurrence and development also involve a series of pathological processes. The present research methods are have difficulty simulating the natural developing state of the disease in the body, and the results cannot reflect the real growth state and function in vivo. The development of microfluidic chip technology provides a technical platform for better research on respiratory diseases. The size of its microchannel can be similar to the space for cell growth in vivo. In addition, organ-on-a-chip can achieve long-term co-cultivation of multiple cells and produce precisely controllable fluid shear force, periodically changing mechanical force, and perfusate with varying solute concentration gradient. To sum up, the chip can be used to analyze the specific pathophysiological changes of organs meticulously, and it is widely used in scientific research on respiratory diseases. The focus of this review is to describe and discuss current studies of artificial respiratory systems based on organ-on-a-chip technology and to summarize their applications in the real world.


Author(s):  
Vikram Aggarwal ◽  
Yoonju Cho ◽  
Aniruddha Chatterjee ◽  
Dickson Cheung

Central venous pressure (CVP) is a measure of the mean pressure within the thoracic vena cava, which is the largest vein in the body and responsible for returning blood from the systemic circulation to the heart. CVP is a major determinant of the filling pressure and cardiac preload, and like any fluid pump, the heart depends on an adequate preload to function effectively. Low venous return translates into a lower preload and a drop in overall cardiac output, a relationship described by the Frank-Starling Mechanism. CVP is an important physiological parameter, the correct measure of which is a clinically relevant diagnostic tool for heart failure patients. In addition to other vitals such as heart rate and mean arterial pressure, accurate measures of central venous pressure through simple diagnostic instrumentation would provide physicians with a clear picture of cardiac functionality, and allow for more targeted treatment. Recent literature has also shown that measuring CVP can be an important hemodynamic indicator for the early identification and treatment of more widespread conditions, such as sepsis (Rivers, Nguyen, Havstad, & Ressler, 2001). With over five million patients (American Heart Association, http://www.americanheart.org/presenter. jhtml) in the U.S. presenting with heart failure-like symptoms annually, a current challenge for physicians is to obtain a quick and accurate measure of a patient’s central venous pressure in a manner that poses minimum discomfort.


Author(s):  
Laura Nicholson ◽  
Olivia Lin ◽  
Edward Shim

A new technology using an intelligent bed sheet made of fabric sensors is described as a novel advancement that supports wireless and continuous monitoring of vital signs without requiring wire attachments to the body. The intelligent bed sheet developed by Studio 1 Labs Inc. (Studio 1 Labs), can be used to support three distinct groups: i) healthcare institutions with human resource constraints, ii) caregivers who provide care for seniors, infants and children at home, and iii) independent seniors who prefer to age in place. This article describes two complementary research phases using the intelligent bed sheet to detect heart rate, respiratory rate, and respiratory effort. The first phase explores sensor validation from the intelligent bed sheet with preset respiratory conditions from high technology mannequins. The second phase involves a use case with healthy young adults comparing between physiological signals from the bed sheet with standard nursing protocols of manual counts and a pulse oximeter approved by Health Canada.


Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 216 ◽  
Author(s):  
Sayeh Ezzikouri ◽  
Mohammad Enamul Hoque Kayesh ◽  
Soumaya Benjelloun ◽  
Michinori Kohara ◽  
Kyoko Tsukiyama-Kohara

Despite the availability of an effective preventive vaccine for hepatitis B virus (HBV) for over 38 years, chronic HBV (CHB) infection remains a global health burden with around 257 million patients. The ideal treatment goal for CHB infection would be to achieve complete cure; however, current therapies such as peg-interferon and nucleos(t)ide analogs are unable to achieve the functional cure, the newly set target for HBV chronic infection. Considering the fact functional cure has been accepted as an endpoint in the treatment of chronic hepatitis B by scientific committee, the development of alternative therapeutic strategies is urgently needed to functionally cure CHB infection. A promising target for future therapeutic strategies is immune modulation to restore dysfunctional HBV-specific immunity. In this review, we provide an overview of the progress in alternative therapeutic strategies, including immune-based therapeutic approaches that enhance host innate and adaptive immunity to achieve and increase the functional cure from CHB infection.


2016 ◽  
Vol 78 (7-5) ◽  
Author(s):  
Kui Lin Kam ◽  
Tze Weng Ow ◽  
Wan Yong Chia ◽  
Rabia Bakhteri ◽  
Norhafizah Ramli ◽  
...  

Arrhythmia is an irregular heartbeat where the blood may not be delivered effectively throughout the body and cause sudden cardiac arrest (SCA). Immediate treatment is required to prevent SCA. However, most of the existing electrocardiogram (ECG) monitoring devices are bulky, cost expensive and lack arrhythmia detection and classification system. This paper proposes a front-end on-board graphical interface design of System-on-Chip (SoC) based arrhythmia detector which can be used as a first screening device for cardiac disease patient. The system consists of a knowledge-based arrhythmia classifier which is able to identify three types of arrhythmias which are ventricular fibrillation (VF), premature ventricular contractions (PVCs) and second-degree atrioventricular (AV) block. The system has been evaluated and benchmarked with ECG data from MIT-BIH arrhythmia database. The results show that its accuracy is up to 99.25% with a computation time of 6.385 seconds. It is highly portable and relatively inexpensive for installation in small clinics and home monitoring.  


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