Human somatostatin receptor specificity of backbone-cyclic analogues containing novel sulfur building units

Somatostatin-14 (somatostatin) and its clinically available analogues octreotide, lanreotide, and vapreotide are potent inhibitors of growth hormone, insulin, and glucagon release. Recently, a novel backbone cyclic somatostatin analogue c(GABA-Phe-Trp-(D)Trp-Lys-Thr-Phe-GlyC3-NH(2)) (analogue 1, PTR 3173) that possesses in vivo endocrine selectivity was described. This long-acting octapeptide exhibits high affinity to human recombinant somatostatin receptors (hsst) hsst2, hsst4, and hsst5. Its novel binding profile resulted in potent in vivo inhibition of growth hormone but not of insulin release. We report the synthesis, bioactivity, and structure-activity relationship studies of compounds related to 1. In these analogues, the lactam bridge of 1 was replaced by a backbone disulfide bridge. We present a novel approach for conformational constraint of peptides by utilizing sulfur-containing building units for on-resin backbone cyclization. These disulfide backbone cyclic analogues of 1 showed significant metabolic stability as tested in various enzyme mixtures. Receptor binding assays revealed different receptor selectivity profiles for these analogues in comparison to their prototype. It was found that analogues of 1, bearing a disulfide bridge, had increased selectivity to hsst2 and hsst5; however, they exhibited weaker affinity to hsst4 as compared to 1. These studies imply that ring chemistry, ring size, and ring position of the peptide template may affect the receptor binding selectivity.     

Hypertension: Constraining the Expression of ACE-II by Adopting Optimal Macronutrients Diet Predicted via Support Vector Machine

The recent elevation of cases infected from novel COVID-19 has placed the human life in trepidation mode, especially for those suffering from comorbidities. Most of the studies in the last few months have undeniably raised concerns for hypertensive patients that face greater risk of fatality from COVID-19. Furthermore, one of the recent WHO reports has estimated a total of 1.13 billion people are at a risk of hypertension of which two-thirds live in low and middle income countries. The gradual escalation of the hypertension problem andthe sudden rise of COVID-19 cases have placed an increasingly higher number of human lives at risk in low and middle income countries. To lower the risk of hypertension, most physicians recommend drugs that have angiotensin-converting enzyme (ACE) inhibitors. However, prolonged use of such drugs is not recommended due to metabolic risks and the increase in the expression of ACE-II which could facilitate COVID-19 infection. In contrast, the intake of optimal macronutrients is one of the possible alternatives to naturally control hypertension. In the present study, a nontrivial feature selection and machine learning algorithm is adopted to intelligently predict the food-derived antihypertensive peptide. The proposed idea of the paper lies in reducing the computational power while retaining the performance of the support vector machine (SVM) by estimating the dominant pattern in the features space through feature filtering. The proposed feature filtering algorithm has reported a trade-off performance by reducing the chances of Type I error, which is desirable when recommending a dietary food to patients suffering from hypertension. The maximum achievable accuracy of the best performing SVM models through feature selection are 86.17% and 85.61%, respectively.     

The impact of cognitive behavioral therapy on IL-6 levels in unmedicated women experiencing the first episode of depression: A pilot study

A group of 11 women (18–29 years old) in the first episode of depression was evaluated before and after cognitive behavioral therapy (CBT). Depressive scores, assessed by Hamilton Rating Scale (HRSD), and serum IL-6 levels significantly decreased after the seventh session. These results suggest that CBT reduced both depressive symptoms and the inflammatory state in women.     

Muscle damage, fluid ingestion, and energy supplementation during recreational alpine skiing

This study examined energy and fluid supplementation on indices of muscle damage during alpine skiing. Skiers were assigned to a carbohydrate-protein (CP), placebo (PL), or no fluid (NF) group. CP and PL ingested 1.62 L during and after skiing. Myoglobin did not change from pre-skiing (PS) to 2 h post-skiing (2PS) for CP (24.8 +/- 1.4 and 25.6 +/- 1.6 ng/mL), but rose significantly from 26.4 +/- 1.3 to 40.0 +/- 2.8 ng/mL for PL and from 29.0 +/- 1.3 to 82.9 +/- 3.6 ng/mL for NF. Creatine kinase was maintained from PRE to 2 PS for CP, but increased significantly from 117 +/- 7.2 to 174 +/- 43.4 U/L for PL and from 126 +/- 23.2 to 243 +/- 34.3 U/L for NF. This study demonstrates that ingestion of a CP beverage minimized muscle damage indices during skiing compared to PL and NF and that ingesting fluids may also minimize muscle damage compared to a NF condition.