Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases.

Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases.

Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.     

PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes

Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m², glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease.     

Influence of Some Psychosocial Factors on Mobbing and its Consequences Among Employees Working with People with Intellectual Disabilities

Background The problem of mobbing has attracted a great deal of attention over the past few years. This concern has increased the study of the phenomena, which has resulted in many scientific publications. Mobbing has been characterized as an emerging risk at work. The aim of this study was to analyse the influence of some psychosocial factors at work – role clarity, interpersonal conflicts and social support – on mobbing and its consequences – that is, inclination towards absenteeism and psychosomatic disorders. Materials and methods The sample included 422 employees working with people with intellectual disabilities. Structural equation modelling (SEM) was used to test the hypotheses. Results The Hypothesized model showed an adequate fit to data, and all hypothesized relationships were significant. Conclusions The results of this study provide support for the mediator role of mobbing in the relationship between high role ambiguity, low social support and high interpersonal conflicts and psychosomatic disorders and inclination towards absenteeism.     

Impact of macrolide therapy on mortality of HIV-infected patients with community-acquired pneumonia in a tertiary teaching hospital

BackgroundBacterial pneumonia is one of the main causes of morbidity and mortality in patients infected by the human immunodeficiency virus (HIV). The main objective of this study was to evaluate the effect of macrolide therapy in combination with a beta-lactam based empiric regimen for inpatients with community-acquired pneumonia and HIV.MethodsThis is a retrospective cohort study of hospitalized patients. Adult patients who had received treatment with ceftriaxone or ceftriaxone plus clarithromycin were included.Results76 patients met the inclusion criteria. Among baseline characteristics analyzed, only respiratory rate showed significant difference: patients who had received clarithromycin were more likely to have a respiratory rate > 30/min than patients who received only ceftriaxone (64% versus 36%, p = 0.03). ICU admission was the only outcome that showed a significant difference, more frequent in the ceftriaxone plus clarithromycin group (45% versus 20%, p = 0.03).ConclusionsThis study does not support the addition of a macrolide to a beta-lactam based regimen in HIV-infected patients. This is probably related to the patients’ immunodeficiency status, which impairs the immunomodulatory properties of the macrolides.