Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 22, Issue 2, 2022

Type 1 Diabetes (T1D) is a complex autoimmune disorder which occurs as a result of an intricate series of pathologic interactions between pancreatic β-cells and a wide range of components of both the innate and the adaptive immune systems. Stem-cell therapy, a recently-emerged potentially therapeutic option for curative treatment of diabetes, is demonstrated to cause significant alternations to both different immune cells such as macrophages, natural killer (NK) cells, dendritic cells, T cells, and B cells and non-cellular elements, including serum cytokines and different components of the complement system. Although there exists overwhelming evidence indicating that the documented therapeutic effects of stem cells on patients with T1D are primarily due to their potential for immune regulation rather than pancreatic tissue regeneration, to date, the precise underlying mechanisms remain obscure. On the other hand, immune-mediated rejection of stem cells remains one of the main obstacles to regenerative medicine. Moreover, the consequences of efferocytosis of stem-cells by the recipients’ lung-resident macrophages have recently emerged as a mechanism responsible for some immune-mediated therapeutic effects of stem-cells. This review focuses on the nature of the interactions amongst different compartments of the immune systems which are involved in the pathogenesis of T1D and provides an explanation as to how stem cell- based interventions can influence immune system and maintain the physiologic equilibrium.

Knowledge of epidemiology, genetic etiopathogenesis, diagnostic criteria, and management of familial hypercholesterolemia have increased in the last two decades. Several population studies have shown that familial hypercholesterolemia is more frequent than previously thought, making this entity the most common metabolic disease with monogenic inheritance in the world. Identification of causal heterozygous pathogenic variants in LDLR, APOB, and PCSK9 genes has increased diagnostic accuracy of classical criteria (extreme hypercholesterolemia, personal / family history of premature coronary artery disease or other cardiovascular diseases). Genetic screening has been recently introduced in many European countries to detect patients with familial hypercholesterolemia, mainly affected pediatric subjects, asymptomatic or those at the beggining of their disease, to increase surveillance and avoid complications such as cardiovascular diseases. Cholesterol- lowering drugs should be started as soon as the diagnosis is made. Various combinations between drugs can be used when the goal is not achieved. New therapies, including small interference ribonucleic acids (siRNA) are being tested in different clinical trials.

Breast Cancer (BC) has the highest incidence among all forms of malignancies detected in women globally. The therapeutic approaches available for BC include chemotherapy, radiation therapy, hormonal therapy, and surgery. Recently, advanced immunology-based therapeutics with potential for BC treatment, including immune checkpoint blockades, vaccines, and combinations with other treatment strategies, have emerged. Although commonly used treatments such as trastuzumab/ pertuzumab for human epidermal growth factor receptor 2-positive BC and hormone therapy for estrogen receptor-positive and/or progesterone receptor-positive BC are specific, triple-negative BC cases remain a great challenge for treatment measures. Immune checkpoint inhibitors (anti- PD-1/anti-CTLA-4) and anti-cancer vaccines (NeuVax, MUC-1, AVX901, INO-1400, and CEA), either alone or in combination with other therapies, represent a new paradigm in cancer therapeutics. In this review, we highlight the current immunotherapeutic aspects and ongoing trials aimed at the development of better treatment regimens for BC.

Metabolic disorder affects normal homeostasis and can lead to the development of diseases. Diabetes mellitus is the most common metabolic disorder, and a cluster of metabolic conditions can lead to cardiovascular disease (CVD) development. Diabetes mellitus and CVD are closely related, with oxidative stress, playing a major role in the pathophysiology. Glutathione-S-Transferases (GST) potentially play an important role by reducing oxidative stress and is found to be the underlying pathophysiology in the development of diabetes, cardiovascular diseases (CVD), etc Background: In this review, the role of GST genetic variant in the development of diabetes mellitus, CVD and diabetic vascular complications has been focused. Objectives: Based on the literature, it is evident that the GST can act as an important biochemical tool providing significant evidence regarding oxidative stress predominant in the development of diseases. Analysis of GST gene status, particularly detection of GSTM1 and GSTT1 null mutations and GSTP1 polymorphism, have clinical importance. Results: The analysis of GST polymorphism may help identify the people at risk and provide proper medical management. Genotyping of GST gene would be a helpful biomarker for early diagnosis of CVD development in DM and also in CVD cases. More studies focusing on the association of GST polymorphism with CVD development in diabetic patients will help us determine the pathophysiology better.

Background: Neonatal Respiratory Distress Syndrome (RDS) is a dangerous disease in neonates and is accompanied by neonatal complications and death. Objective: The aim of this study was the early determination of neonatal serum vitamin A levels as a possible novel predictor for neonatal RDS. Patients and Methods: A case-control study with the identification number TCTR20210206001, was performed on 100 neonates who were admitted to the Neonatal Intensive Care Unit (NICU) of Tanta University Hospital (TUH) suffering from RDS (patient group) and 100 healthy neonates (control group). Estimation of serum vitamin A (retinol) was made for all neonates of this study within the first four hours after birth before any nutrition or therapies. Results: The results showed no significant difference between serums retinol (RT) levels in grade 1 & 2 RDS neonates (patient group) and the serum RT levels in the control group, while there was a significant difference between serums retinol levels in grade 3 & 4 RDS neonates (patient group) and the serum retinol levels in the control group where the P-value was 0.006 and 0.002 respectively. Conclusion: Serum vitamin A levels in neonates were found to be decreased in RDS neonates and could be used as a predictor for the development and severity of RDS. Recommendation: It is recommended to carry out routine estimation of serum vitamin A levels in neonates as a novel predictor for neonatal RDS.

Background: Exertional heat stroke (EHS) is a life-threatening illness that can lead to multiple organ damage in the early stage. Objective: This study aimed to investigate the relationship between 24-hour indicators and mortality in patients with EHS. Methods: The records of EHS patients hospitalized were collected and divided into the death group and the survival group. We then analyzed the demographic characteristics and APACHE II scores and laboratory results of the participants in the blood within the first 24 h after hospitalization, and assessed whether these candidate indicators differed between the death group and the survival group. Cox regression analysis of the survival data was performed to explore the relationship between early indicators and prognosis. Results: The levels of plasma PT, APTT, TT, and INR were significantly higher in the death group than in the survival group. The blood PLT count and the levels of PTA and Fb were significantly lower in the death group than in the survival group, while the levels of BU, SCr, ALT, AST, TBil, and DBil were significantly higher in the death group than in the survival group. Furthermore, the levels of Mb, LDH, TNI, and NT-proBNP were significantly higher in the death group than in the survival group, while there was no significant difference in CK levels between the two groups. Conclusion: Patients with EHS often had multiple organ injuries in the early stage (within 24 h), while those cases in the death group were more severe.

Background: Bibliometric analysis can analyze development trends and predict research hotspots. We used these analyses to better understand the pregnancy-related implications of thyroid diseases. Methods: Publications on thyroid diseases during pregnancy from 1926 to hitherto were retrieved based on the Web of Science database. The publications and references, the institutions and countries, the journals, the keywords and citations were analyzed by utilizing VOSviewer, CiteSpace and Cit- NetExplorer. Results: A total of 3310 publications were retrieved and were cited 87913 times. The United States took the dominant position in outputs and collaborations. Harvard University had the most articles 86, which also had the highest h-index 30. Thyroid ranked first with 201 publications and Journal of Clinical Endocrinology Metabolism had the highest h-index 67. Among the 49 burst keywords, "antibody" had the longest burst period from 1991 to 2012, "thyroxine" had the strongest burst strength 16.7026, "hypothyroxinemia" appeared most recently in 2018. The most frequent keyword was "pregnancy" which occurred 1324 times. All the top 98 frequent keywords were clustered into 4 clusters. The citation network visualization was grouped into 8 groups. Conclusion: The research focus of thyroid diseases in pregnancy ranged from clinical thyroid dysfunction to milder thyroid dysfunction. Guidelines published by the American Thyroid Association enacted a crucial purpose in the treatment and development of thyroid diseases during pregnancy. Some randomized controlled studies of unresolved problems and long-term follow-up of offspring may be the direction of future research. In the meantime, bibliometric methods can help scholars choose journals, track research hotspots, and identify the direction or focus of future research.