Glycyrrhizic acid ameliorates submandibular gland oxidative stress, autophagy and vascular dysfunction in rat model of type 1 diabetes

The burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

Antiplatelet and Antithrombotic Therapy in Type I Diabetes Mellitus: Update on Current Data.

Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors.The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.

Hidradenitis Suppurativa and Comorbid Disorder Biomarkers, Druggable Genes, New Drugs and Drug Repurposing—A Molecular Meta-Analysis

Chronic inflammation and dysregulated epithelial differentiation, especially of hair follicle keratinocytes, have been suggested as the major pathogenetic pathways of hidradenitis suppurativa/acne inversa (HS). On the other hand, obesity and metabolic syndrome have additionally been considered as an important risk factor. With adalimumab, a drug has already been approved and numerous other compounds are in advanced-stage clinical studies. A systematic review was conducted to detect and corroborate HS pathogenetic mechanisms at the molecular level and identify HS molecular markers. The obtained data were used to confirm studied and off-label administered drugs and to identify additional compounds for drug repurposing. A robust, strongly associated group of HS biomarkers was detected. The triad of HS pathogenesis, namely upregulated inflammation, altered epithelial differentiation and dysregulated metabolism/hormone signaling was confirmed, the molecular association of HS with certain comorbid disorders, such as inflammatory bowel disease, arthritis, type I diabetes mellitus and lipids/atherosclerosis/adipogenesis was verified and common biomarkers were identified. The molecular suitability of compounds in clinical studies was confirmed and 31 potential HS repurposing drugs, among them 10 drugs already launched for other disorders, were detected. This systematic review provides evidence for the importance of molecular studies to advance the knowledge regarding pathogenesis, future treatment and biomarker-supported clinical course follow-up in HS.

Fracture of the Bone Inducing Its Necrosis as the End Point in the Evolution of Untreated Neuroarthropathy

We describe here the case of a female patient with type I diabetes who developed active Charcot neuroarthropathy in the foot. Due to therapeutic noncompliance, talus necrosis was discovered 2 years after the presentation of neuroarthropathy. The impact of untreated neuroarthropathy on the bone is commonly described as fracture and joint dislocation, but we describe the complete disappearance of the bony structure and its necrosis associated with active neuroarthropathy in a patient who refused offloading.

Xanthogranulomatous hypophysitis: a different rare presentation in a young patient

Hypophysitis is a rare inflammatory condition that may present both clinically and radiologically as a neoplastic lesion. Xanthogranulomas are rare intracranial lesions with controversial etiology. Here, we report a clinical case of histologically confirmed xanthogranuloma in a young female with type I diabetes mellitus and hypothyroidism.

Type I Diabetes Mellitus and Insulin Therapy on Bone Microarchitecture, Composition and Mechanical Properties

Background: The aim of this study was to evaluate the microarchitecture, composition and mechanical properties of cortical bone of rats with type I diabetes mellitus (TIDM) and submitted to insulin therapy (IT). Methods: Thirty rats were divided into three groups (n=10): non-diabetic, diabetic and diabetic+insulin. TIDM was induced by intravenous injection of streptozotocin. In diabetic+insulin group, 4IU insulin was administered twice per day (1IU at 7am and 3IU at 7pm). The animals were euthanized five weeks after TIDM induction; the tibiae were removed and submitted to microcomputed tomography (micro-CT, 8µm), fourier transform infrared spectroscopy (FTIR) and dynamic microhardness indentation. Results: Micro-CT analysis showed that diabetic group had lower bone surface/tissue volume ratio (BS/BV) (p=0.018), cortical thickness (Ct.Th) (p<0.001) and degree of anisotropy (Ct.DA) (p=0.034) values compared to non-diabetic group. The diabetic group showed lower Ct.Th than diabetic + insulin group (p=0.018). The non-diabetic group had lower fractal dimension (Ct.FD) values compared to diabetic groups (p<0.001). The ATR-FTIR analyses showed lower values for all measured parameters in the diabetic group than non-diabetic group (amide I ratio: p=0.046; crystallinity index: p=0.038; matrix:mineral ratios - M:MI: p=0.006; M:MIII: p=0.028). The diabetic+insulin group showed a lower crystallinity index (p=0.022) and M:MI ratio (p=0.002) than non-diabetic and diabetic groups, respectively. The diabetic group showed lower Vickers hardness values than non-diabetic (p<0.001) and diabetic+insulin (p=0.003) groups. Conclusion: TIDM negatively affect bone microarchitecture, collagen maturation, mineralization and bone microhardness. Moreover, insulin minimized the effect of TIDM on cortical thickness and organic/mineral matrix.