Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 22, Issue 4, 2022

A wealth of information suggests that hyperglycemia plays a paramount role in diabetes- related chronic complications. Notably, in Type 2 Diabetes Mellitus (T2DM), a persistent condition of hyperglycemia and altered insulin signaling seems to account for a status of chronic low-grade inflammation. This systemic inflammatory condition, in turn, depends on the profound impairment of the immune machinery, especially in some corporeal districts such as the adipose tissue, pancreatic islets, endothelia, and circulating leukocytes. Interestingly, poor glycemic control has been associated with cardiac autoimmunity in patients with Type 1 Diabetes (T1DM), and cardiac autoantibody positivity is associated with an increased risk of Cardiovascular Diseases (CVD) decades later. This condition also suggests a role for autoimmune mechanisms in CVD development in patients with T1DM, possibly through inflammatory pathways. Evidence has been provided for an elevated release of cytokines, such as interleukin (IL)-1 beta and IL-6, as well as chemokines (C-C motif Ligand 2 and IL-8). Of note, these mediators are responsible for abnormal leukocyte trafficking into many tissues, contributing to insulin resistance, reduced insulin secretion, and vascular complications. In fact, hyperglycemia in individuals with diabetes mellitus is associated with higher circulating E-selectin, soluble Cell Adhesion Molecule (sCAM)-1, and vascular CAM-1 compared to normoglycemic healthy volunteers. Therefore, patients with diabetes mellitus exhibit an exaggerated adhesion of leukocytes to endothelia, and this phenomenon is related to hyperglycemia. The increased production of advanced glycosylation end products or AGEs activates a further cascade of noxious events with a massive generation of Reactive Oxygen Radicals (ROS) and enhanced expression of CAMs.

Background: The most common liver diseases are fibrosis, alcoholic liver disease, nonalcoholic fatty disease, viral hepatitis, and hepatocellular carcinoma. These liver diseases account for approximately 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of the worldwide burden. The most widely used liver function tests for diagnosis are alanine transaminase, aspartate transaminase, serum proteins, serum albumin, and serum globulins, whereas antivirals and corticosteroids have been proven to be useful for the treatment of liver diseases. A major disadvantage of these diagnostic measures is the lack of specificity to a particular tissue or cell type, as these enzymes are common to one or more tissues. The major adverse effect of current treatment methods is drug resistance. To overcome these issues, interleukins have been investigated. The balance of these interleukins determines the outcome of an immune response. Interleukins are considered interesting therapeutic targets for the treatment of liver diseases. In this review, we summarize the current state of knowledge regarding interleukins in the diagnosis, treatment, and pathogenesis of different acute and chronic liver diseases. Objective: To understand the role of interleukins in the assessment and treatment of different types of liver diseases. Methods: A literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: Interleukins, Acute Liver Failure, Alcoholic Liver Disease, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, Hepatocellular Carcinoma, Inflammation, Liver injury, Hepatoprotective effect. Clinical trial data on these interleukins have been searched on Clinicaltrials.gov. Results: Existing literature and preclinical and clinical trial data demonstrate that interleukins play a crucial role in the pathogenesis of liver diseases. Conclusion: Our findings indicate that IL-1, IL-6, IL-10, IL-17, IL-22, IL-35, and IL-37 are involved in the progression and control of various liver conditions via the regulation of cell signaling pathways. However, further investigation on the involvement of these interleukins is necessary for their use as a targeted therapy in liver diseases.

Background: World Health Organization (WHO) has increasingly improved the guidelines to tackle the spread of Coronavirus Disease 2019 (COVID-19) among the worldwide population. In this context, each country has introduced specific social, healthcare, political and macroeconomic measures to face COVID pandemic locally. Objective: The general aim of this comparative overview is to highlight the most significant effects of COVID-19 pandemic on the main healthcare systems. Also, we critically analyzed the macroeconomic variables and the most promising solutions to improve both healthcare system and its related risk management, taking into specific consideration the most industrialized countries. Methods: The main strategy has been built on a renewed concept of the hospital, rebuilding the old concepts of “triage” and “intensive care”. Recently, COVID-19 hospitals have allowed to cater the patients affected by COVID-19. Results: The reshaping of several healthcare policies and requirements has led to several positive effects, such as the recruitment of a huge number of human resources in the healthcare systems. Nevertheless, several negative effects have also impacted the communities mostly subjected to infections. Conclusion: Undoubtedly, the national healthcare systems have somehow addressed the people’s needs, trying not to neglect the social, healthcare, economic and political aspects. In our overview, we have reported how the different actions taken in the last months, have resulted in different outcomes.

Introduction: Asthma is defined as a chronic inflammatory airway disease. Recent studies have shown the association between metabolic syndrome and deterioration of lung functions in patients with asthma. The aim of this study was to evaluate the relationship between metabolic syndrome and asthma status. Methods: In this prospective cross-sectional study, 160 asthmatic patients attending Razi hospital in Guilan province were divided equally into two groups of 80 patients. The case group comprised asthmatic patient with metabolic syndrome and the control group involved asthmatic patient without metabolic syndrome. Blood pressure, height, weight, waist circumferences, fasting blood glucose and lipid profiles were measured by standard methods. Asthma severity was determined based on clinical symptoms and GINA criteria. To evaluate pulmonary function parameters, spirometry was performed for the patients. Results: Pulmonary function tests including FEF, FVC and FEV1 were significantly lower in the case group compared to the control group (P < 0.05). Also, a significant negative correlation was found between waist circumference, cardiovascular risk factors (including diabetes, hypertriglyceridemia, hypertension) with spirometric indices (P < 0.05). Conclusion: Metabolic syndrome causes major declines of pulmonary parameters in asthma patients; thus controlling metabolic syndrome might improve symptoms of asthma.

Background: Asparagus contains different bioactive and volatile components including pyrazines, sulphur-containing compounds, and polyphenols. Asparagus juice is a new low-calorie LAB-containing natural juice product, the usage of which is expanding. Pyrazines and sulphur-containing compounds are degraded by bacteria on one hand, but on the other hand, dietary polyphenols prevent human colorectal diseases as modulators of the composition and/or activity of gut microbiota. However, the utility of these asparagus compounds for reversal of age-associated microbial dysbiosis and the immunometabolic disorders that dysbiosis incites body inflammatory reactions was not much explored so far. Hence, using middle-aged mice, we conducted the current study to verify the effect of freshly squeezed domestic white asparagus juice on the biomarkers reflecting immuno-metabolic pathways linking age-related dysbiosis and metabolic events. Materials and Methods: Thirty-two conventional Harlan Laboratories C57BL/6 mice aged between 11-12 months were randomly divided into two groups (n=16). Mice in control group 1 received sterile tap water. Animals in group 2 had 60 days ad libitum free-choice access to sterile tap water supplemented with 5% (v/v) freshly squeezed domestic white asparagus juice. Clinical signs of general health, hydration, and inflammation were monitored daily. Caecal content samples were analysed by qPCR for microbial composition. Histology of relevant organs was carried out on day 60 after sacrificing the mice. Universal markers of metabolic- and liver function were determined in serum samples. Caecal SCFAs contents were measured using HPLC. Results: Overall, no significant differences in general health or clinical signs of inflammation between the two groups were observed. The liver to body weight ratio in asparagus juice-drank mice was lowered. The qPCR quantification showed that asparagus juice significantly decreased the caecal Clostridium coccoides group while causing an enhancement in Clostridium leptum, Firmicutes, and bifidobacterial groups as well as total caecal bacterial count. Asparagus juice significantly elevated the caecal contents of SCFAs. Enhanced SCFAs (acetate, butyrate, and propionate) in mice receiving asparagus juice, however, did coincide with altered lipid levels in plasma or changes in the abundance of relevant bacteria for acetate-, butyrate-, and propionate production. Discussion: To the best of our knowledge, this is the first study aiming at evaluating the effect of freshly squeezed German domestic white asparagus juice on universal markers of metabolic- and liver function in middle- aged mice and the role of gut microbiota in this regard. The effectiveness of asparagus juice to improve metabolism in middle-aged mice was associated with alterations in intestinal microbiota but maybe also due to uptake of higher amounts of SCFAs. Conclusion: Hence, the key signal pathways corresponding to improved immune-metabolic homeostasis will be an important research scheme in the future.

Background: Corticobasal Degeneration (CBD) is a rare neurological disease caused by the pathological accumulation of tau protein. The primary pathological features of CBD include progressive neurodegenerative processes resulting in remarkable frontoparietal and basal ganglia atrophy. Objective: Like in many other neurodegenerative disorders, there is still no effective disease-modifying drug therapy in CBD. Therefore, the development of new treatment methods is of great importance. In this study, we aimed to assess the stimulating effects of high-frequency DLPFC rTMS on the motor, cognitive and behavioral disturbances in four CBD patients. Methods: Four (three females, one male) CBD patients who had been diagnosed as CBD were enrolled in this study. Patients were evaluated before and after the rTMS procedure regarding the motor, neuropsychometric and behavioral tests. The results of statistical analysis of behavioral and neuropsychometric evaluation were assessed via SPSS 18.0 package program. Data are expressed as mean, standard deviation. Before and after values of the groups were compared with the Wilcoxon sign rank test, and p<0.05 was considered significant. Results: We have provided strong preliminary evidence that the improvement in clinical parameters was associated with the normalizations of the theta activity and glucose metabolism. Conclusion: Our current results are consistent with some previous trials showing a strong association between DLPFC targeted rTMS and electrophysiological normalizations in the left DLPFC.

Background: Syphilis is a chronic infectious disease caused by Treponema pallidum (Tp) infection, which causes local inflammation in the host. TpF1 is an oligomeric protein expressed by the Tp-infected host that can induce the host immune response. There are few studies regarding the role of TpF1 in macrophage activation and the subsequent release of cytokines. Objective: The objective of this study is to elucidate the effects of TpF1 on the pathological process of Syphilis. In addition, we explored how purinergic 2X7 (P2X7R) induced NOD-like receptor family protein 3 (NLRP3) -dependent release of interleukin-1β (IL-1β) and the underlying mechanisms. Methods: We explored the influence of TpF1 on cytokine release by macrophages using qRT-PCR and ELISA. The specific phenotype of activated macrophages was determined by flow cytometry. Results: TpF1 was able to activate macrophages and induce the M1 macrophage phenotype. Moreover, TpF1 activated the NLRP3 inflammasome in macrophages, which was mediated by P2X7R. Conclusion: The Tp-induced protein TpF1 is able to induce macrophage activation and P2X7R-induced NLRP3-dependent release of IL-1β. Our findings provide a theoretical basis for clarifying the clinical symptoms and pathogenesis of syphilis.

Background: Hypercholesterolemia is one of the principal causes of the development of cardiovascular diseases. Recently, probiotics consumption has also been proposed as a non-pharmacological intervention to control cholesterol concentrations. Objective: To evaluate in vitro assimilation of cholesterol by Bifidobacterium animalis subsp. lactis (BPL1) under simulated intestinal environment in anaerobic conditions and to review and discuss potential physiological mechanisms in this context. Methods: Bacterial viability and cholesterol assimilation were evaluated in both standard MRS and Stimulated Intestinal Fluid (SIF) medium under anaerobic conditions and in the presence or absence of cholesterol. For assimilation assays, cholesterol concentrations in the different suspensions, containing the probiotic or not, were determined by chromatography coupled to mass spectrometry. Results: The results showed that the growth of B. lactis BPL1 under intestinal conditions is favored when cholesterol is present in the culture medium. In addition, cholesterol assimilation of up to 44.4% under intestinal and anaerobic conditions was observed. Conclusion: Taking into account the revised literature and the experimental results presented herein, the administration of functional foodstuffs together with probiotic bacteria, such as B. lactis BPL1, could be a potentially effective option to decrease hypercholesterolemia, thus preventing the development of cardiovascular diseases. Nevertheless, further studies on mechanisms of effectiveness in animals and clinical trials are still needed.

Background: Cardiovascular diseases (CVDs) are crucial cause of death and hospitalization all over the world including India. The CVDs including the coronary artery disease (CAD) are developed by the interaction of genetic and environmental factors. Hyperlipidemia is a traditional risk factor for CVD. Aim: The aim of this study was to study the clinical correlations of lipid profiles with the age and gender in the Coronary Artery Disease Patients: Methods: In this study, we have investigated the effect of age and sex on in lipid profile in 3878 (1171 females and 2707 males) CAD patients from India. Results: The plasma TG was higher in males than in females regardless of the age. Results showed that CAD female patients had significantly increased HDL-C than their aged matched males. Moreover, the plasma TC and LDL-C were significantly higher in males than females until age 40 years. Then after the age of 40 years, TC and LDL-C become significantly higher in females than in males. In addition, we found that more than 85% of CAD cases were <55 years old, and about 30% of CAD cases had normal lipid profile. Conclusion: We conclude that elderly females are at a greater risk for CAD than males. Moreover, there were no significant differences in CVDs causes between nonelderly and elderly females. In addition, a higher percentage of cases were premature CAD, and 30% of CAD may be caused by loci that are not related to lipid metabolism.