Natural Killer T (NKT) Cells in Autoimmune Hepatitis: Current Evidence from Basic and Clinical Research.

Natural killer T (NKT) cells are unconventional T cells that are activated by glycolipid antigens. They can produce a variety of inflammatory and regulatory cytokines and, therefore, modulate multiple aspects of the immune response in different pathological settings, including autoimmunity. NKT cells have also been implicated in the immunopathogenesis of autoimmune hepatitis, and in this review we summarize and analyze the main studies investigating the involvement and/or homeostasis of NKT cells in this disease. In detail, the evidence from both basic and clinical research has been specifically analyzed. Even though the experimental murine models supported a relevant role of NKT cells in immune-mediated hepatic injury, very few studies specifically investigated NKT cell homeostasis in patients with autoimmune hepatitis; however, these initial studies reported some alterations of NKT cells in these patients, which may also correlate with the disease activity to some extent. Further clinical studies are needed to investigate the potential role and use of NKT cell analysis as a disease marker of clinical relevance, and to better understand the precise cellular and molecular mechanisms by which NKT cells contribute to the pathogenesis of autoimmune hepatitis.

The antiproliferative potential and mechanism of action of metformin in MCF-7 cells.

Aim: The current study aimed to investigate the potential antiproliferative activity of metformin, the effective concentration range, and the mechanism of action. Materials & methods: Human breast cancer cells, MCF-7 were treated with a serial dilution of metformin (10-150 µM) for 24 and 48 h. Potential antiproliferative activity of metformin and its ability in inducing cellular apoptosis and autophagy were also investigated. Results: Metformin inhibited MCF-7 proliferation in a concentration and time dependent manner, with 80 µM as the most effective concentration. Compared with nontreated cells, metformin induced significant levels of autophagy and apoptosis, which were confirmed by the reduction of mTOR and BCL-2 protein expression. Conclusion: The study confirms the antiproliferative activity of metformin, which may likely occur through AMPK signaling pathway.

The antidiabetic drug, metformin is tested in this work for its possible ability to inhibit the growth of breast cancer cells. Using different concentrations of the drug over different time points, the results showed that the drug was able to inhibit cancer growth through different mechanisms. The results also showed that the drug inhibits cancer growth by stimulating program cell death (apoptosis), as well as autophagy, where the cell breaks old and abnormal cellular substances.

The impact of modular cardiac rehabilitation on quality of life and exercise tolerance in patients with myocardial infarction and COVID-19 infection.

Introduction: Acute myocardial infarction (AMI) remains one of the leading causes of death worldwide during cardiovascular diseases. An important step in the secondary prevention of recurrent myocardial infarction is cardiac rehabilitation (CR). However, with the onset of the global COVID-19 pandemic, the CR programs in many clinics were limited due to the quarantine measures. Knowledge about the effects of CR on quality of life and exercise tolerance in AMI patients with COVID is scarce. Aim: To evaluate the use of a modular CR program on quality of life and exercise tolerance among post-AMI patients with COVID-19 recovery, and in those with no history of COVID-19 infection. Material and methods: This study included 118 patients with or recovering from acute myocardial infarction. They were divided into 2 groups: the first group included 86 patients, who had slight "ground-glass opacity" changes on the computed tomography (CT) scans, and the second group comprised 32 patients, who had no history of coronavirus infection or no change on CT scan of the lungs during the pandemic. The CR program was modified due to the pandemic era. Results: Physical tolerance increased in both groups after CR 3.6 months as compared to before the CR program (duration of training in seconds (p < 0.05), a 6-minute walk test (p < 0.05), the maximal oxygen consumption (VO2max) (p < 0.05), and the metabolic equivalent of task (MET) (p < 0.05)). Similarly, quality of life measures improved in both groups. Treatment satisfaction was higher in the first group at the beginning and the end of CR. Conclusions: The modular CR program improves exercise capacity and quality of life with AMI and COVID-19 similar to that of patients without AMI. Patients after COVID-19 should undergo rehabilitation.

Population Health and Health Services: Old Challenges and New Realities in the COVID-19 Era.

(1) Background: Health services that were already under pressure before the COVID-19 pandemic to maximize its impact on population health, have not only the imperative to remain resilient and sustainable and be prepared for future waves of the virus, but to take advantage of the learnings from the pandemic to re-configure and support the greatest possible improvements. (2) Methods: A review of articles published by the Special Issue on Population Health and Health Services to identify main drivers for improving the contribution of health services on population health is conducted. (3) Health services have to focus not just on providing the best care to health problems but to improve its focus on health promotion and disease prevention. (4) Conclusions: Implementing innovative but complex solutions to address the problems can hardly be achieved without a multilevel and multisectoral deliberative debate. The CHRODIS PLUS policy dialog method can help standardize policy-making procedures and improve network governance, offering a proven method to strengthen the impact of health services on population health, which in the post-COVID era is more necessary than ever.

The Identification of Diabetes Mellitus Subtypes Applying Cluster Analysis Techniques: A Systematic Review.

Diabetes Mellitus is a chronic and lifelong disease that incurs a huge burden to healthcare systems. Its prevalence is on the rise worldwide. Diabetes is more complex than the classification of Type 1 and 2 may suggest. The purpose of this systematic review was to identify the research studies that tried to find new sub-groups of diabetes patients by using unsupervised learning methods. The search was conducted on Pubmed and Medline databases by two independent researchers. All time publications on cluster analysis of diabetes patients were selected and analysed. Among fourteen studies that were included in the final review, five studies found five identical clusters: Severe Autoimmune Diabetes; Severe Insulin-Deficient Diabetes; Severe Insulin-Resistant Diabetes; Mild Obesity-Related Diabetes; and Mild Age-Related Diabetes. In addition, two studies found the same clusters, except Severe Autoimmune Diabetes cluster. Results of other studies differed from one to another and were less consistent. Cluster analysis enabled finding non-classic heterogeneity in diabetes, but there is still a necessity to explore and validate the capabilities of cluster analysis in more diverse and wider populations.