Melatonin increases collagen content accumulation and Fibroblast Growth Factor-2 secretion in cultured human cardiac fibroblasts.

BACKGROUND: The extracellular matrix serves as a scaffold for cardiomyocytes, allowing them to work in accord. In rats, collagen metabolism within a myocardial infarction scar is regulated by melatonin. The present study determines whether melatonin influences matrix metabolism within human cardiac fibroblast cultures and examines the underlying mechanism. METHODS: The experiments were performed on cultures of cardiac fibroblasts. The Woessner method, 1,9-dimethylmethylene blue assay, enzyme-linked immunosorbent assay and quantitative PCR were used in the study. RESULTS: Melatonin treatment lowered the total cell count within the culture, elevated necrotic and apoptotic cell count as well as augmented cardiac fibroblast proliferation, and increased total, intracellular, and extracellular collagen within the fibroblast culture; it also elevated type III procollagen α1 chain expression, without increasing procollagen type I mRNA production. The pineal hormone did not influence matrix metalloproteinase-2 (MMP-2) release or glycosaminoglycan accumulation by cardiac fibroblasts. Melatonin increased the release of Fibroblast Growth Factor-2 (FGF-2) by human cardiac fibroblasts, but cardiotrophin release was not influenced. CONCLUSION: Within human cardiac fibroblast culture, collagen metabolism is regulated by melatonin. The profibrotic effect of melatonin depends on the elevation of procollagen type III gene expression, and this could be modified by FGF-2. Two parallel processes, viz., cell elimination and proliferation, induced by melatonin, lead to excessive replacement of cardiac fibroblasts.

Case Report: Sequential Liver After Kidney Transplantation in a Patient With Sensenbrenner Syndrome (Cranioectodermal Dysplasia).

Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a rare ciliopathy clinically characterized by congenital craniofacial, skeletal, and ectodermal defects. Chronic kidney and liver insufficiency are also present in this disorder. Cranioectodermal dysplasia is an autosomal recessive and heterogeneous genetic disease. Six genes (IFT122, WDR35, IFT140, IFT43, IFT52, and WDR19) are known to be associated with this syndrome. Until 2021 more than 70 patients have been reported with CED, however, an orthotopic liver transplantation has been reported only in one case. Here, we present a case report of sequential liver-after-kidney transplantation in a male patient affected by CED. The kidney and liver transplantation was performed at the age of 7 and 12 years, respectively. Patients with Sensenbrenner syndrome require a multidisciplinary medical management and should regularly be followed-up by hepatologists and nephrologists, as the liver and kidney diseases are the major cause of morbidity and mortality.

Successful Treatment with Corticosteroids in an 11-Year-Old Patient with Crohn's Disease and Myopericarditis-Case Report.

Extraintestinal manifestations (EIMs) are observed in 15-20% of patients with inflammatory bowel disease (IBD). One of the rare EIMs is myocarditis, the incidence of which is estimated at around 1%. The main cause of myocarditis is a viral infection. Other causes include autoimmune diseases and drug complications (sulfasalazine, mesalazine). We present the case of an 11-year-old girl with Crohn's disease (CD) with EIMs, manifested as hip joint inflammation and erythema nodosum. At the same time, the symptoms of myopericarditis appeared with changes in electrocardiogram (ECG), echocardiography and high troponin I concentration. Therapy with corticosteroids resulted in the resolution of skin lesions and cardiological symptoms. Systemic connective tissue diseases, viral and bacterial infections were excluded in the differential diagnosis. The suspicion of mesalazine-induced EIMs was also ruled out as the symptoms resolved despite continued therapy with mesalazine. No further recurrences of myopericarditis were observed.

The role of chemerin in the pathogenesis of cholelithiasis in children and adolescents.

BACKGROUND AND AIM: Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis. METHODS: The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays. RESULTS: The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls. CONCLUSION: Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents.