A new approach for the pleiotropic effect of metformin use in type 2 diabetes mellitus

Objectives Metformin is the first choice for type 2 diabetes mellitus (T2DM) treatment in the guidelines and is used in combination with many drugs. Growth arrest-specific protein 6 (Gas6)/Axl signaling plays a role in many metabolic disorders. This study aims to investigate the effects of metformin and metformin-insulin combination used in patients with T2DM on Gas6, Axl, and soluble Axl (sAxl) levels. Materials and methods A total of 71 patients diagnosed with T2DM and 21 healthy subjects were divided into 4 groups control, diet and exercises recommended (DER), metformin, and metformin + insulin. Diabetic patients were treated with metformin only or with a metformin-insulin combination and monitored for six months. Gas6, Axl, and sAxl levels of subjects' sera obtained from their baseline and post-therapeutic sixth month blood samples were measured by ELISA methods. Results Compared to baseline, the sixth month Gas6 and Axl levels of Metformin and Metformin + Insulin groups significantly decreased (p<0.05). However, there was no statistically significant difference in sAxl values for these two groups of patients. Discussion The use of metformin in diabetic patients may be beneficial for inhibiting the Gas6/Axl pathway. This study presents a new aspect of the pleiotropic effects of metformin. This study will be clinically useful for designing therapeutic approaches targeting Gas6/Axl

Therapeutic approaches on the interaction between SARS-CoV2 and ACE2: a biochemical perspective

The current conditions in the progression of the SARS-CoV2 pandemic changed the current scientific paradigm, and we now observe a novel rhythm and way of evaluating the collected information. Previous experiences in epidemics with similar viruses (viz., SARS-CoV1, and MERS-CoV) and collected information about the viral transmission and replication can be used to overcome the SARS-CoV2 pandemic. Although SARS-CoV2 emerged very recently, there are plenty of scientific studies about similar viruses to comment on the current situation. Inhibition of SARS-CoV2 spike protein activation, inhibition of virus endocytosis, using a soluble form of ACE2, peptide or non-peptide analogs of ACE2, and sustaining ACE2/Angiotensin-(1-7)/Mas receptor pathway activation can be proposed for use in therapeutic studies. In this review, the biochemical mechanism of SARS-CoV2 and ACE2 binding, virus-cell membrane fusion, and endocytosis of virus to host cells are discussed according to the currently available literature. The significant contribution of this review may be to provide useful information to researchers into the SARS-CoV2 outbreak

Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 ageand sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer

Chromosomal and oxidative DNA damage in non-functioning pituitary adenomas

Introduction: Clinically non-functioning pituitary adenomas (NFPA) are common tumours of the pituitary gland and are mainly considered as benign. The primary aim of this study was to research the effects of NFPA on genome instability in patients with non-functioning pituitary adenoma by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay and 8-hydroxy- 2’-deoxyguanosine (8-OHdG) assay. The second objective of this study was to assess whether there is a relationship between age, pituitary adenoma diameters, 8-OHDG levels, CBMN site assay parameters, and tumour aggressiveness. Material and methods: The study was performed on 30 patients who had been diagnosed with NFPA and were admitted to the Department of Endocrinology and Metabolism, and 20 healthy subjects of similar age and sex. Results: Micronucleus (MN), nucleoplasmic bridges (NPBs), nuclear bud (NBUD) frequencies, and apoptotic and necrotic cell frequencies in patients with NFPA were found to be significantly higher than in control subjects, and plasma 8-OHdG levels in patients with NFPA were statistically significantly lower than control subjects in this study. Conclusions: It is believed that this is the first study to evaluate the aggressiveness of tumour with chromosome/oxidative DNA damage in patients with NFPA. However, further studies are needed in order to understand the cause of NFPA aggression and to evaluate these patients in terms of risk of cancer.

Measurement of serial serum total and acylated ghrelin levels in critically ill patients: A prospective and observational pilot study

© 2021 American Society for Parenteral and Enteral NutritionBackground: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. Methods: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. Results: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651–3995), 3485.20 (1379–4071), 3359 (1167–3919), and 3355 pg/ml (2207–3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0–673), 50 (0–730), 73 (0–808), and 125 pg/ml (0–689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P >.05). ICU mortality was 30%. Conclusion: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality