Adrenocortical carcinoma (ACC) is a rare endocrine malignancy arising from the adrenal cortex often with unexpected biological behavior. It can occur at any age, with two peaks of incidence: in the ...first and between fifth and seventh decades of life. Although ACC are mostly hormonally active, precursors and metabolites, rather than end products of steroidogenesis are produced by dedifferentiated and immature malignant cells. Distinguishing the etiology of adrenal mass, between benign adenomas, which are quite frequent in general population, and malignant carcinomas with dismal prognosis is often unfeasible. Even after pathohistological analysis, diagnosis of adrenocortical carcinomas is not always straightforward and represents a great challenge for experienced and multidisciplinary expert teams. No single imaging method, hormonal work-up or immunohistochemical labelling can definitively prove the diagnosis of ACC. Over several decades' great efforts have been made in finding novel reliable and available diagnostic and prognostic factors including steroid metabolome profiling or target gene identification. Despite these achievements, the 5-year mortality rate still accounts for approximately 75% to 90%, ACC is frequently diagnosed in advanced stages and therapeutic options are unfortunately limited. Therefore, imperative is to identify new biological markers that can predict patient prognosis and provide new therapeutic options.
With poor outcomes and an immense financial burden, acute coronary syndrome (ACS) and its ischemic repercussions still present a major global health problem. Unfavorable outcomes seem to be mainly ...due to adverse cardiac remodeling. Since the inflammatory response takes an important role in remodeling secondary to myocardial infarction (MI), and as inflammation in this manner has not been completely elucidated, we attempted to give rise to a further understanding of ACS pathophysiology. Hence, in this review, we integrated current knowledge of complex communication networks between natural killer (NK) cells and immune and resident heart cells in the context of ACS. Based on available data, the role of NK cells seems to be important in the infarcted myocardium, where it affects heart remodeling. On the other hand, in atherosclerotic plaque, NK cells seem to be mere passers-by, except in the case of chronic infections by atherogenic pathogens. In that case, NK cells seem to support proinflammatory milieu. NK cell research is challenging due to ethical reasons, convergent evolution, and phenotypic diversity among individuals. Therefore, we argue that further research of NK cells in ACS is valuable, given their therapeutic potential in improving postischemic heart remodeling.
Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to ...prevent further deterioration of kidney function and to delay adverse outcomes. However, the paucity of early, predictive and noninvasive biomarkers has undermined our ability to promptly detect and treat this common clinical condition which affects more than 10% of the population worldwide. Despite all limitations, kidney function is still measured by serum creatinine, cystatin C, and albuminuria, as well as estimating glomerular filtration rate using different equations. This review aims to provide comprehensive insight into diagnostic methods available for early detection of CKD. In the review, we discuss the following topics: (i) markers of glomerular injury; (ii) markers of tubulointerstitial injury; (iii) the role of omics; (iv) the role of microbiota; (v) and finally, the role of microRNA in the early detection of CKD. Despite all novel findings, none of these biomarkers have met the criteria of an ideal early marker. Since the central role in CKD progression is the proximal tubule (PT), most data from the literature have analyzed biomarkers of PT injury, such as KIM-1 (kidney injury molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), and L-FABP (liver fatty acid-binding protein).
The aim of this study was to determine plasma adropin concentration and parameters of insulin resistance in obese male type 2 diabetes mellitus (T2DM) patients before and after 3-month liraglutide ...treatment. In this interventional study, we enrolled 15 obese male T2DM patients with body mass index (BMI) >35 kg/m
, uncontrolled disease and HbA
>7.5%, having previously taken taking two oral antidiabetic drugs. We modified their therapy to metformin and liraglutide for the next three months. After three months of liraglutide treatment, we observed significant decrease in body weight (from 111.5±18.7 kg to 109.2±17.5 kg, p=0.016) and BMI (from 40.9±7.3 to 40.1±7.0 kg/m
, p=0.021). Plasma adropin concentration increased significantly (p=0.003) compared with baseline. Fasting plasma insulin level decreased from 17.79±6.53 to 13.38±3.51 mU/L (p=0.002), fasting plasma glucose level decreased from 8.66±3.07 to 7.41±2.21 mmol/L (p=0.004) and HbA
decreased from 7.98±0.70% to 7.26±0.36% (p=0.003). Insulin resistance presented as HOMA-IR decreased significantly from 7.30±5.19 to 4.52±2.61 (p=0.002). Systolic blood pressure, lipid status, liver and kidney function improved, but not reaching statistical significance. Treating obese male T2DM patients with liraglutide resulted in a significantly higher plasma adropin concentration, significant weight loss and improved parameters of insulin resistance, i.e. decreased fasting plasma insulin, plasma glucose levels and HOMA-IR.
Obstructive sleep apnoea (OSA) and components of metabolic syndrome (MetS) are inextricably connected. Considering the increasing burden of MetS and OSA, in the present review, we aimed to collate ...and summarise the potential pathophysiological mechanisms linking these pathologies. In short, obesity appears to promote OSA development via multiple pathways, some of which are not directly related to mass but rather to metabolic complications of obesity. Simultaneously, OSA promotes weight gain through central mechanisms. On the other hand, diabetes mellitus contributes to OSA pathophysiology mainly through effects on peripheral nerves and carotid body desensitization, while intermittent hypoxia and sleep fragmentation are the principal culprits in OSA-mediated diabetes. Apart from a bidirectional pathophysiological relationship, obesity and diabetes mellitus together additively increase cardiovascular risk in OSA patients. Additionally, the emergence of new drugs targeting obesity and unequivocal results of the available studies underscore the need for further exploration of the mechanisms linking MetS and OSA, all with the aim of improving outcomes in these patients.
Since the initial coronavirus disease 2019 (COVID-19) outbreak in China in December 2019, the infection has now become the biggest medical issue of modern medicine. Two major contributors that ...amplified the impact of the disease and subsequently increased the burden on health care systems were high mortality among patients with multiple co-morbidities and overcapacity of intensive care units. Within the gastroenterology-related community, particular concern was raised with respect to patients with inflammatory bowel disease (IBD), as those patients are prone to opportunistic infections mainly owing to their immunosuppressive-based therapies. Hence, we sought to summarize current knowledge regarding COVID-19 infection in patients with IBD. Overall, it seems that IBD is not a comorbidity that poses an increased risk for COVID-19 acquisition, except in patients treated with 5-aminosalicylates. Furthermore, outcomes of the infected patients are largely dependent on therapeutic modality by which they are treated, as some worsen the clinical course of COVID-19 infection, whereas others seem to dampen the detrimental effects of COVID-19. Finally, we discussed the present and the future impact of COVID-19 pandemic and concomitantly increased health care burden on IBD-management.
Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of ...different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.
Affecting more than 26 million people worldwide and with rising prevalence, heart failure (HF) represents a major global health problem. Hence, further research is needed in order to abate poor HF ...outcomes and mitigate significant expenses that burden health care systems. Based on available data, experts agree that there is an urgent need for a cost-effective prognostic biomarker in HF. Although a significant number of biomarkers have already been investigated in this setting, the clinical utility of adding biomarker evaluation to routine HF care still remains ambiguous. Specifically, in this review we focused on uric acid (UA), a purine metabolism detriment whose role as cardiovascular risk factor has been exhaustingly debated for decades. Multiple large population studies indicate that UA is an independent predictor of mortality in acute and chronic HF, making it a significant prognostic factor in both settings. High serum levels have been also associated with an increased incidence of HF, thus expanding the clinical utility of UA. Importantly, emerging data suggests that UA is also implicated in the pathogenesis of HF, which sheds light on UA as a feasible therapeutic target. Although to date clinical studies have not been able to prove the benefits of xanthine oxidase in HF patients, we discuss the putative role of UA and xanthine oxidase in the pathophysiology of HF as a therapeutic target.
With the rising global burden of inflammatory bowel disease (IBD) and the rising costs of novel biological drugs, there is an increasing need for dietary approaches and functional foods that could ...modulate the course of IBD. The Mediterranean diet has proven to be efficacious in managing chronic inflammatory diseases, and recent studies have also shown its benefits in the setting of IBD. Since olive oil and its compounds have been shown to provide a considerable anti-inflammatory effect, in this review, we aim to discuss the latest evidence concerning the impact of olive oil and its bioactive compounds on IBD. Numerous preclinical studies have exhibited solid evidence on the mechanisms by which polyphenol-rich extra-virgin olive oil (EVOO) or specific polyphenols like hydroxytyrosol (HT) provide their anti-inflammatory, antioxidative, antitumour, and microbiota-modulation effects. Accordingly, several human studies that explored the effects of olive oil on patients with IBD further confirmed the evidence brought forward by preclinical studies. Nevertheless, there is a need for larger-scale, multicentric, randomized control trials that would finally elucidate olive oil's level of efficacy in modulating the course of IBD.
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