Current Protein and Peptide Science - Volume 23, Issue 7, 2022

Physical inactivity is a major cause of chronic diseases. It shortens the health span by lowering the age of the first chronic disease onset, which leads to decreased quality of life and increased mortality risk. On the other hand, physical exercise is considered a miracle cure in the primary prevention of at least 35 chronic diseases, including obesity, insulin resistance, and type 2 diabetes. However, despite many scientific attempts to unveil the health benefits conferred by regular exercise, the underlying molecular mechanisms driving such benefits are not fully explored. Recent research shows that exercise-induced bioactive molecules, named exerkines, might play a critical role in the regulation of metabolic homeostasis and thus prevent metabolic diseases. Here we summarize the current understanding of the health-promoting effects of exerkines secreted from skeletal muscle, adipose tissue, bone, and liver, including MOTS-c, BDNF, miR-1, 12,13-diHOME, irisin, SPX, OC, GDF15, and FGF21 on obesity, insulin resistance, and type 2 diabetes. Identifying the systemic health benefits of exerkines may open a new area for the discovery of new pharmacological strategies for the prevention and management of metabolic diseases.

Prostate cancer (PCa) is the most frequent cancer of the male genitourinary system and the second most common cancer in men worldwide. PCa has become one of the leading diseases endangering men's health in Asia in recent years, with a large increase in morbidity and mortality. MTA1 (metastasis-associated antigen-1), a transcriptional coregulator involved in histone deacetylation and nucleosome remodeling, is a member of the MTA family. MTA1 is involved in cell signaling, chromosomal remodeling, and transcriptional activities, all of which are important for epithelial cell progression, invasion, and growth. MTA1 has been demonstrated to play a significant role in the formation, progression, and metastasis of PCa, and MTA1 expression is specifically linked to PCa bone metastases. Therefore, MTA1 may be a potential target for PCa prevention and treatment. Here, we reviewed the structure, function, and expression of MTA1 in PCa as well as drugs that target MTA1 to highlight a potential new treatment for PCa.

In Covid-19, the pathological effect of SARS-CoV-2 infection is arbitrated through direct viral toxicity, unusual immune response, endothelial dysfunction, deregulated renin-angiotensin system [RAS], and thrombo-inflammation, leading to acute lung injury (ALI), with a succession of acute respiratory distress syndrome (ARDS) in critical conditions. C1 esterase inhibitor (C1INH) is a protease inhibitor that inhibits the spontaneous activation of complement and contact systems and kinin pathway, clotting, and fibrinolytic systems. Therefore, targeting the complement system through activation of C1INH might be a novel therapeutic modality in the treatment of Covid-19. Therefore, this study aims to illustrate the potential nexus between C1INH and the pathophysiology of SARS-CoV-2 infection. C1INH is highly dysregulated in Covid-19 due to inflammatory and coagulation disorders. C1INH is up-regulated in Covid-19 and sepsis as an acute phase response, but this increase is insufficient to block the activated complement system. In addition, the C1INH serum level predicts the development of ARDS in Covid-19 patients, as its up-regulation is associated with the development of cytokine storm. In Covid-19, C1INH might be inhibited or dysregulated by SARS-CoV-2, leading to propagation of complement system activation with subsequent uncontrolled immunological stimulation due to activation of bradykinin and FXII with sequential activation of coagulation cascades and polymerization of fibrin. Thus, suppression of C1INH by SARS-CoV-2 infection leads to thrombosis and excessive inflammation due to uncontrolled activation of complements and contact systems.

Background: In-silico mapping of epitopes by immune-informatics has simplified the efforts towards understanding antigen-antibody interactions. The knowledge of allergen epitopes may help in advancing the diagnosis and therapy of allergic diseases. Objective: This study was intended to identify B and T cell epitopes of cysteine protease allergen of Phaseolus vulgaris. Methods: Modeller 9v20 software was used for the generation of three-dimensional model of cysteine protease and quality assessment was performed using SAVES webserver and other in silico software. Linear and conformational B and T cell epitopes were predicted via immuno-informatics based computational servers. Epitopes were synthesized and their immunoreactivity was analyzed using specific IgE ELISA with food allergy positive patient’s sera. Cellular immune response of peptides was determined through basophil activation assay. Consurf and SDAP (property distance) were used to examine the evolutionary conservancy and potential cross-reactivity of predicted epitopes. MSA based positional conservancy between HDM allergen epitopes and predicted peptides was also established using IEDB epitope database. Finally, population coverage for each promiscuous T cell epitope was predicted using IEDB population coverage analysis tool. Results: Cysteine protease structure was derived by homology modeling and combination of bioinformatic tools predicted three B- and three T-cell peptides by consensus method and validated computationally. ELISA with kidney bean sensitive patient’s sera showed higher IgE binding of B-cell peptides as compared to T-cell or control peptides. Epitope conservancy revealed B-cell epitopes being upto 95% conserved in comparison to variable T-cell epitopes (upto 69%). B-cell peptides were crossreactive with homologous allergens based on PD values. Structural comparison of cysteine protease with Der p 1 and Der f 1 showed similar epitopic regions, validating the prediction accuracy of epitopes. Promiscuous T-cell epitopes binding to broad-spectrum class-II MHC alleles demonstrated the distribution of T-cell peptides world-wide (30-98%) and in Asian population (99%). Conclusion: The current approach can be applied for identification of epitopes. Analysis of crossreactive and widely-distributed specific epitopes of allergen and knowledge about their interactive surfaces will help in understanding of food allergy and related immune responses.

Background: Screening of critical variables, including formulation and process variables, in the development of various dosage forms facilitates the identification of the most influencing parameters, which modulate the responses, thereby helping in building the strong quality target product profile. Objective: The objective of the present work was to screen out the most influential and critical variables for the development of an anabolic peptide encapsulated lipid nanovesicles (PTH-LNVs). Methods: PTH-LNVs were prepared by the ethanol injection method. Taguchi standard orthogonal array L8 design was employed to assess the effect of formulation and processing variables on different response variables. Independent variables considered were drug concentration, lipid concentration, cholesterol concentration, stirring rate, and rate of injection, whereas dependent variables studied were particle size, PDI, zeta potential, % entrapment efficiency, and % drug loading. Particle size, PDI, and zeta potential were evaluated by a zeta sizer. Drug loading efficiency and % entrapment efficiency were determined by HPLC analysis. Results: The ethanol injection method was employed to formulate PTH-LNVs using Taguchi standard orthogonal array L8 design. From the half-normal plot and Pareto ranking analysis, it was found that drug, lipid, and cholesterol concentration have a significant effect on responses of formulation and are hence considered critical variables during the formulation development. Conclusion: The presented work demonstrates the feasibility of Taguchi orthogonal array design in the screening of potential independent factors in the development of peptide encapsulated nanoformulations.