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.     

Human papillomavirus (HPV)‐18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein

High‐risk human papillomavirus (HPV) infection is the principal risk factor for the development of cervical cancer. The HPV E6 oncoprotein has the ability to target and interfere with several PSD‐95/DLG/ZO‐1 (PDZ) domain‐containing proteins that are involved in the control of cell polarity. This function can be significant for E6 oncogenic activity because a deficiency in cell polarisation is a marker of tumour progression. The establishment and control of polarity in epithelial cells depend on the correct asymmetrical distribution of proteins and lipids at the cell borders and on specialised cell junctions. In this report, we have investigated the effects of HPV E6 protein on the polarity machinery, with a focus on the PDZ partitioning defective 3 (Par3) protein, which is a key component of tight junctions (TJ) and the polarity network. We demonstrate that E6 is able to bind and induce the mislocalisation of Par3 protein in a PDZ‐dependent manner without significant reduction in Par3 protein levels. In addition, the high‐risk HPV‐18 E6 protein promotes a delay in TJ formation when analysed by calcium switch assays. Taken together, the data presented in this study contribute to our understanding of the molecular mechanism by which HPVs induce the loss of cell polarity, with potential implications for the development and progression of HPV‐associated tumours.     

Lateral Left Ventricular Wall Rupture Following Acute Myocardial Infarction: Pathophysiological Interpretation by Multimodality Imaging Approach

Lateral left ventricular wall rupture (LVWR) is a rare complication following acute myocardial infarction (AMI) less than 1%. After cardiogenic shock, LVWR constitutes the most common cause of in‐hospital death in AMI patients. Around 40% of all LVWR occurred during the first 24 hours and 85% within the first week. In the present case, 76 hours following the intervention, LVWR was observed likely due to a small infarction at the lateral left ventricular wall possibly due to the marginal lesion. Our patient refused surgery and was followed clinically. Eighteen months later, real time three‐dimensional echocardiography showed a pseudoaneurysm.     

Androgen production by testes of Gallus domesticus during postembryonic development

Cock testes incubated with labeled pregnenolone or progesterone as substrates produced testosterone as the main compound. The formation of 17α-hydroxyprogesterone was greater with progesterone as precursor, but the production of radioactive 20β-dihydroprogesterone and androstenedione was similar with either substrate. Testes from 1-, 21-, and 40-day-old chicks incubated with progesterone as a substrate had a very low testosterone: androstenedione production ratio (0.05). In mature animals, however, more testosterone than androstenedione was produced from radioactive progesterone and the production ratio testosterone: androstenedione was 24.     

Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response

Clinical Rheumatology - Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic...     

Postinfectious onset in functional dyspepsia is a risk factor for weight loss

Journal of Gastroenterology - Functional dyspepsia (FD) is differentiated into two subgroups: the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acute gastroenteritis and...     

Differences in COVID-19 Preventive Behavior and Food Insecurity by HIV Status in Nigeria

AIDS and Behavior - The aim of the study was to assess if there were significant differences in the adoption of COVID-19 risk preventive behaviors and experience of food insecurity by people living...     

Comparison of careHPV and Hybrid Capture 2 Assays for Detection of High-Risk Human Papillomavirus DNA in Cervical Samples from HIV-1-Infected African Women

The careHPV and HC2 assays were compared for high-risk human papillomavirus (HR-HPV) DNA detection in cervical samples from 149 HIV-1-infected African women. The HR-HPV DNA detection rates were 37.6% and 34.9% for careHPV and HC2, respectively. Agreement between the two tests was 94.6% (95% confidence interval [CI], 89.7% to 97.7%) with a kappa value of 0.88 (95% CI, 0.81 to 0.96), indicating an excellent agreement. careHPV may be considered as suitable as HC2 for cervical cancer screening among HIV-infected African women.     

Results of Abductor Pollicis Longus Suspension Ligamentoplasty for Treatment of Advanced First Carpometacarpal Arthritis

Background

Suspension ligamentoplasty using abductor pollicis longus (APL) tendon without bone tunneling, was introduced as one of the techniques for treatment of advanced first carpometacarpal (CMC) arthritis. The purpose of this study was to evaluate the radiologic and clinical results of APL suspension ligamentoplasty.

Methods

The medical records of 19 patients who underwent APL suspension ligamentoplasty for advanced first CMC arthritis between January 2008 and May 2012 were reviewed retrospectively. The study included 13 female and 6 male patients, whose mean age was 62 years (range, 43 to 82 years). For clinical evaluation, we assessed the grip and pinch power, radial and volar abduction angle, thumb adduction (modified Kapandji index), including visual analogue scale (VAS) and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Radiologic evaluation was performed using simple radiographs.

Results

The mean follow-up was 36 months (range, 19 to 73.7 months). Mean power improved from 18.3 to 27 kg for grip power, from 2.8 to 3.5 kg for tip pinch, and from 4.3 to 5.4 kg for power pinch. All patients showed decreased VAS from 7.2 to 1.7. Radial abduction improved from 71° preoperatively to 82° postoperatively. The modified Kapandji index showed improvement from 6 to 7.3, and mean DASH was improved from 41 to 17.8. The height of the space decreased from 10.8 to 7.1 mm. Only one case had a complication involving temporary sensory loss of the first dorsal web space, which resolved spontaneously.

Conclusions

The APL suspension ligamentoplasty for treatment of advanced first CMC arthritis yielded satisfactory functional results.