Modern lifestyle diseases remain a persistent challenge in healthcare. Currently, about 422 million people worldwide are affected by diabetes, while 1 in 8 people are living with obesity. The development of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has marked a significant milestone in treating these conditions. Interest in GLP-1RAs has grown due to evidence that, beyond their established role in diabetes management, these drugs influence other metabolic disorders. This is attributed to the fact that GLP-1 receptors are found in various healthy human tissues. However, a potential cause for concern is the expression of GLP-1 receptors in certain cancers. This review focuses on the most recent findings concerning the actions of GLP-1RAs, detailing their documented impact on the thyroid gland and pancreas. It addresses concerns about the long-term use of GLP-1RAs in relation to the development of pancreatitis, pancreatic cancer, and thyroid neoplasms by exploring the mechanisms and long-term effects in different patient subgroups and including data not discussed previously. This review was conducted through an examination of the literature available in the MedLine (PubMed) database, covering publications from 1978 to 10 May 2024. The collected articles were selected based on their relevance to studies of GLP-1 agonists and their effects on the pancreas and thyroid and assessed to meet the established inclusion criteria. The revised papers suggest that prolonged use of GLP-1RA could contribute to the formation of thyroid tumors and may increase the risk of acute inflammatory conditions such as pancreatitis, particularly in high-risk patients. Therefore, physicians should advise patients on the need for more frequent and detailed follow-ups.

This review focuses on the role of metalloproteinases in the pathogenesis of myocardial injury in various disease entities. It reveals how the expression and serum levels of metalloproteinases and their inhibitors change in many disease states. At the same time, the study offers a review of the impact of immunosuppressive treatment on this relationship. Modern immunosuppressive treatment is based mainly on the use of calcineurin inhibitors, including cyclosporine A and tacrolimus. The use of these drugs may carry a number of side effects, specifically to the cardiovascular system. The scale and degree of long-term influence on the organism remains unclear, but a significant risk of complications for transplant recipients who take immunosuppressive drugs as part of their daily treatment is to be expected. Therefore, the knowledge on this subject should be expanded and the negative effects of post-transplant therapy minimized. Immunosuppressive therapy plays an important role in the expression and activation of tissue metalloproteinases and their specific inhibitors, which leads to many tissue changes. The presented study is a collection of research results on the effects of calcineurin inhibitors on the heart, with particular emphasis placed on the participation of MMP-2 and MMP-9. It is also an analysis of the effects of specific heart diseases on myocardial remodeling through inductive or inhibitory effects on matrix metalloproteinases and their inhibitors.

Immunosuppressive drugs are widely and chronically used to avoid graft rejection in transplant recipients. However, they are also known to have organotoxic effects and can exert numerous side effects. The aim of this study was to assess whether the chronic treatment of rats with the most commonly used clinical immunosuppressive regimens in organ recipients had an effect on the morphology and function of the aorta. The rats were divided into five groups and each group was chronically treated with different sets of three immunosuppressive drugs (TRG, CRG, MRG, CMG, TMG) for 6 months. The changes were most profound in calcineurin inhibitor-based protocols. TMG protocol treatment was characterized by the most numerous alterations such as morphological changes, changes in the thickness of the tunic media, wider distances between elastic lamellae, an increase in the number of vSMCs and changes in collagen deposition. We concluded that the morphological changes were connected with MMP-2 and MMP-9/TIMP-2 and TIMP-1 imbalances, which was also determined and noticed.

Physical dependence is associated with the formation of neuroadaptive changes in the central nervous system (CNS), both at the molecular and cellular levels. Various studies have demonstrated the immunomodulatory and proinflammatory properties of morphine. The resulting neuroinflammation in drug dependence exacerbates substance abuse-related behaviors and increases morphine tolerance. Studies prove that fluoride exposure may also contribute to the development of neuroinflammation and neurodegenerative changes. Morphine addiction is a major social problem. Neuroinflammation increases tolerance to morphine, and neurodegenerative effects caused by fluoride in structures related to the development of dependence may impair the functioning of neuronal pathways, change the concentration of neurotransmitters, and cause memory and learning disorders, which implies this element influences the development of dependence. Therefore, our study aimed to evaluate the inflammatory state of selected brain structures in morphine-dependent rats pre-exposed to fluoride, including changes in cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression as well as microglial and astroglial activity via the evaluation of Iba1 and GFAP expression. We provide evidence that both morphine administration and fluoride exposure have an impact on the inflammatory response by altering the expression of COX-1, COX-2, ionized calcium-binding adapter molecule (Iba1), and glial fibrillary acidic protein (GFAP) in brain structures involved in dependence development, such as the prefrontal cortex, striatum, hippocampus, and cerebellum. We observed that the expression of COX-1 and COX-2 in morphine-dependent rats is influenced by prior fluoride exposure, and these changes vary depending on the specific brain region. Additionally, we observed active astrogliosis, as indicated by increased GFAP expression, in all brain structures of morphine-dependent rats, regardless of fluoride exposure. Furthermore, the effect of morphine on Iba1 expression varied across different brain regions, and fluoride pre-exposure may influence microglial activation. However, it remains unclear whether these changes are a result of the direct or indirect actions of morphine and fluoride on the factors analyzed.

The current study focuses on the role of MMPs in the pathogenesis of the vascular damage and at the same time it offers the review referring to the influence of the immunosuppressive treatment on this interdependence. Contemporary immunosuppressive treatment constitutes of four groups of medications, such as: calcineurin inhibitors including cyclosporine A and tacrolimus; inhibitors of the inosine monophosphate dehydrogenase - the only agent from this group currently used in transplantation is mycophenalate mofetil (MMF); mTOR inhibitors, consisting of everolimus and glucocorticosteroids. Due to the fact that the properties of immunosuppressive drugs still remain unclear and transplant recipients need to use these medicines every day, knowledge of this should be further expanded. The deceases of the patients with the functioning graft who were diagnosed with the cardiovascular system diseases, constitute 50% of all renal transplant recipients. Immunosuppressive treatment leads to many pathological alterations within the organs and tissues and additionally they undoubtedly affect the activity of MMPs in the wall of the vessels.

Using different three-drug immunosuppressive treatment regimens in a rat model, we aimed to determine the effects of long-term therapy on metalloproteinase-2 and metalloproteinase-9 activity and the expression of their inhibitors, as well as to assess the morphology of the animals’ cardiac tissue. Our results suggest that chronic use of immunosuppressive drugs disrupts the balance between the activity of MMPs and TIMPs. Depending on the type of drug regimen used, this leads to abnormalities in the cardiac structure, collagen fiber accumulation, or cardiomyocyte hypertrophy. The information obtained in the present study allows us to conclude that the chronic treatment of rats with the most common clinical immunosuppressive regimens may contribute to abnormalities in the myocardial structure and function. The results presented in this study may serve as a prelude to more in-depth analyses and additional research into the optimal selection of an immunosuppressive treatment with the lowest possible risk of cardiovascular complications for patients receiving organ transplants.