Non-alcoholic steatohepatitis patients exhibit reduced CD47, and increased sphingosine, cholesterol and MCP1 levels in the erythrocyte membranes

Non-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF-α release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by ELISA, and cholesterol and sphingosine with thin-layer chromatography. 18 patients (8 men, 10 women aged 56.7+/-11.5 years) and 14 healthy controls (7 men, 7 women aged 39.3+/-15.5 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NASH patients (844+/-409 pg/ml) compared to healthy controls (2969+/-1936 pg/ml) with P(Healthy>NAFLD)=99.1%, while the levels of MCP1 were increased in NASH patients (389+/-255 pg/ml), compared to healthy controls (230+/-117 pg/ml) with P(Healthy<NAFLD)=88.9%. Moreover, in erythrocyte membranes there was a statistically significant accumulation of sphingosine and cholesterol in NASH patients, compared to healthy controls. Our results imply that erythrocytes release chemotactic (find me signals) MCP1, while containing reduced (do not eat me signals) CD47. These molecules can lead to erythrophagocytosis. Next, increased (goodbye signals) sphingosine and cholesterol could augment inflammation by metabolic reprogramming.

Healthcare of the Netherlands

The Netherlands is a state located in Western Europe bordering Germany and Belgium. The population of the country is just over 17million people. In terms of GDP, theNetherlands is among the twenty richest countries in the world, and in terms of exports, it is in the top ten. The average life expectancy in theNetherlands is 81.4 years; in the structure ofmortality, malignant neoplasms come out on top, which distinguishes the state from other European countries, where the main cause of deaths is cardiovascular diseases. The compulsory health insurance system was introduced in the country in 2006 after the medical reform. A distinctive feature of the Dutch healthcare system is its relative autonomy from the state, which performs only the function of an external controller, and all other powers belong to the municipal authorities. As a result, several private insurance companies have been admitted to health insurance in the Netherlands, which create healthy competition among themselves, thereby contributing to better quality and more affordable healthcare.

Remote Arrhythmia Detection for Eldercare in Malaysia

Cardiovascular disease continues to be one of the most prevalent medical conditions in modern society, especially among elderly citizens. As the leading cause of deaths worldwide, further improvements to the early detection and prevention of these cardiovascular diseases is of the utmost importance for reducing the death toll. In particular, the remote and continuous monitoring of vital signs such as electrocardiograms are critical for improving the detection rates and speed of abnormalities while improving accessibility for elderly individuals. In this paper, we consider the design and deployment characteristics of a remote patient monitoring system for arrhythmia detection in elderly individuals. Thus, we developed a scalable system architecture to support remote streaming of ECG signals at near real-time. Additionally, a two-phase classification scheme is proposed to improve the performance of existing ECG classification algorithms. A prototype of the system was deployed at the Sarawak General Hospital, remotely collecting data from 27 unique patients. Evaluations indicate that the two-phase classification scheme improves algorithm performance when applied to the MIT-BIH Arrhythmia Database and the remotely collected single-lead ECG recordings.

A Statistical Analysis of Forensic Autopsies Performed in the Jungbu Province of Korea in 2020

We analyzed the manner and cause of death in 945 forensic autopsies from the Jungbu province (Central part of South Korea) conducted by the National Forensic Service Daejeon institute in 2020. Analysis of the manner of death revealed that 43.6% (412/945 cases) were natural deaths, 41.6% (393/945 cases) were unnatural deaths, and 14.8% (140/945 cases) deaths were unknown. Among the unnatural deaths, the major manner of death (40.7%, 160/393 cases) were by accidents, 29.5% (116/393 cases) were by suicide, 21.6% (85/393 cases) were undetermined, and 8.1% (32/393 cases) were by homicide. Among the unnatural deaths, the major cause of death (42.7%, 168/393 cases) were by trauma, 19.3% (76/393 cases) were by poisoning, and 16.5% (65/393 cases) were by asphyxia. Falling was the major cause of death by trauma (42.9%, 72/168 cases) and strangulation was the major cause of death by asphyxia (72.3%, 47/65 cases). Among natural deaths, heart disease was the major cause (43.7%, 180/412 cases), followed by vascular disease (18.9%, 78/412 cases). This study is the first statistical analysis of the manner and cause of deaths in the Jungbu province. A time-series statistical analysis of the manner and cause of deaths in this province might allow more advanced interpretations about both public safety and healthcare in the future.

The Role of Ferroptosis in Cardiovascular Disease and Its Therapeutic Significance

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide with regulated cell death playing an important role in cardiac pathophysiology. However, the classical mode of cell death cannot fully explain the occurrence and development of heart disease. In recent years, much research has been performed on ferroptosis, a new type of cell death that causes cell damage and contributes to the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In this review, we discuss the role of different organelles in ferroptosis and also focus on the relationship between autophagy and ferroptosis. Additionally, we describe the specific mechanism by which ferroptosis contributes to the development of CVD. Finally, we summarize the current research on ferroptosis-related pathway inhibitors and the applications of clinically beneficial cardiovascular drugs.

The interplay among MAP3K1 and SOX2 regulated metastasis by MAPK signaling pathway through interaction with KLF4 in triple-negative breast cancer

BackgroundTumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC. MethodsThe expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation. ResultCompared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited. ConclusionsIt is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .

The Application of Single-Cell Technologies in Cardiovascular Research

Cardiovascular diseases (CVDs) are the leading cause of deaths in the world. The intricacies of the cellular composition and tissue microenvironment in heart and vasculature complicate the dissection of molecular mechanisms of CVDs. Over the past decade, the rapid development of single-cell omics technologies generated vast quantities of information at various biological levels, which have shed light on the cellular and molecular dynamics in cardiovascular development, homeostasis and diseases. Here, we summarize the latest single-cell omics techniques, and show how they have facilitated our understanding of cardiovascular biology. We also briefly discuss the clinical value and future outlook of single-cell applications in the field.

A review on Coumarin derivatives as potent anti-Tuberculosis agent

Background: : Tuberculosis (TB) is an acute or chronic infectious disease caused by several species of Myco-bacterium, collectively called as tubercle bacilli or Mycobacterium tuberculosis complex. Around 10 million people get sick with tuberculosis (TB) each year. TB is the second leading cause of deaths today after HIV/AIDS. A serious problem in the context of MDR-TB, is the extensively drug-resistant TB which is an im-portant reason for the restricted chemotherapy in TB. Therefore, there is a need to explore new antitubercular (anti-TB) agents. Coumarin is an oxygen-containing heterocyclic compound and can be widely found in many natural products, and many of them display diverse biological activities.The wide spectrum of activities of coumarin molecules have intrigued the scientists to explore the natural coumarins and their synthetic deriva-tives for their potential as anti-TB drugs. Objective: The objective of this review is to emphasize on important coumarin analogs with anti-TB activities and their structure-activity relationships (SAR) for designing better anti-TB agents. Method: Latest, authentic and published reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being thoroughly studied and analyzed. The structural requirements of coumarins as anti-TB drugs have also been studied. Results : Collection and compilation of reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being done. Conclusion: The study provides latest report on coumarin derivatives synthesized as anti-TB agent and wheth-er their activity depends on structural changes or not.

Early Diagnosis of Lung Cancer in the United Arab Emirates: Challenges and Strategic Recommendations

In the United Arab Emirates (UAE), lung cancer (LC) was the third leading cause of deaths due to cancer in 2017. Around 80% of the patients in the UAE are diagnosed at a late stage, rendering the treatment less effective in improving survival outcomes. Lack of awareness of disease symptomatology, deficient screening initiatives, misdiagnosis, and delayed referral to the specialist are contributing factors for delayed diagnosis. Effective screening at a primary care setting can be crucial for early diagnosis, referral to specialists, and enhancing patient outcomes. It is important to establish screening and referral guidelines through which each suspected case can be identified and provided timely intervention. Although the international screening and referral pathway framework are comprehensive, several regional barriers need to be addressed before they can be adapted at the national level. A group of LC experts from the UAE deliberated on issues like delayed diagnosis of LC and strategic recommendations for overcoming the challenges. The discussion was based on the review of the published evidence, international and regional guidelines for screening and early diagnosis of LC. Herein, we present a guideline, endorsed by the esteemed panel of experts, for aiding early diagnosis and optimizing the management of LC in the UAE.

Causes of death in patients with tuberculosis and human immunodeficiency virus co-infection

Objectives. The aim of the study was to investigate the cause of death of tuberculosis patients infected with the human immunodeficiency virus (HIV). Many researchers and experts note the urgency of the problem of tuberculosis combined with HIV infection in the world and in Russia. One of the main criteria for assessing the effectiveness of medical care for tuberculosis patients infected with the human immunodeficiency virus is the mortality rate.Materials and methods. For a detailed study of the causes of death of patients with tuberculosis in combination with HIV infection, we analyzed the causes of death of this contingent of patients in 5 regions of the Russian Federation.Results. The social characteristics of patients, the forms and course of the disease, the main and immediate causes of death of 223 patients with co-infection with HIV and tuberculosis were studied.Conclusion. Half of the deaths of tuberculosis patients infected with human im­munodeficiency virus were not associated with tuberculosis. Among these cases, there was either the presence of several infections at the same time, equally leading to death, or separate opportunistic infections (candidiasis, Pneumocystis pneumonia, toxoplasmosis), or cancer. In addition, the lifestyle of patients often became the cause of deaths, namely: drug poisoning and accidents, or cirrhosis of the liver, which develops as a result of alcoholism or hepatitis C infection which occurred during intravenous administration of drugs.