A regulatory miRNA–mRNA network is associated with transplantation response in acute kidney injury

Background Acute kidney injury (AKI) is a life-threatening complication characterized by rapid decline in renal function, which frequently occurs after transplantation surgery. However, the molecular mechanism underlying the development of post-transplant (post-Tx) AKI still remains unknown. An increasing number of studies have demonstrated that certain microRNAs (miRNAs) exert crucial functions in AKI. The present study sought to elucidate the molecular mechanisms in post-Tx AKI by constructing a regulatory miRNA–mRNA network. Results Based on two datasets (GSE53771 and GSE53769), three key modules, which contained 55 mRNAs, 76 mRNAs, and 151 miRNAs, were identified by performing weighted gene co-expression network analysis (WGCNA). The miRDIP v4.1 was applied to predict the interactions of key module mRNAs and miRNAs, and the miRNA–mRNA pairs with confidence of more than 0.2 were selected to construct a regulatory miRNA–mRNA network by Cytoscape. The miRNA–mRNA network consisted of 82 nodes (48 mRNAs and 34 miRNAs) and 125 edges. Two miRNAs (miR-203a-3p and miR-205-5p) and ERBB4 with higher node degrees compared with other nodes might play a central role in post-Tx AKI. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that this network was mainly involved in kidney-/renal-related functions and PI3K–Akt/HIF-1/Ras/MAPK signaling pathways. Conclusion We constructed a regulatory miRNA–mRNA network to provide novel insights into post-Tx AKI development, which might help discover new biomarkers or therapeutic drugs for enhancing the ability for early prediction and intervention and decreasing mortality rate of AKI after transplantation.

A new humanized antibody is effective against pathogenic fungi in vitro

Invasive fungal infections mainly affect patients undergoing transplantation, surgery, neoplastic disease, immunocompromised subjects and premature infants, and cause over 1.5 million deaths every year. The most common fungi isolated in invasive diseases are Candida spp., Cryptococcus spp., and Aspergillus spp. and even if four classes of antifungals are available (Azoles, Echinocandins, Polyenes and Pyrimidine analogues), the side effects of drugs and fungal acquired and innate resistance represent the major hurdles to be overcome. Monoclonal antibodies are powerful tools currently used as diagnostic and therapeutic agents in different clinical contexts but not yet developed for the treatment of invasive fungal infections. In this paper we report the development of the first humanized monoclonal antibody specific for β-1,3 glucans, a vital component of several pathogenic fungi. H5K1 has been tested on C. auris, one of the most urgent threats and resulted efficient both alone and in combination with Caspofungin and Amphotericin B showing an enhancement effect. Our results support further preclinical and clinical developments for the use of H5K1 in the treatment of patients in need.

Enxertos ósseos em odontologia – uma revisão integrativa da literatura

A exodontia de unidades permanentes, assim como doença periodontal e trauma bucal, estão muitas vezes relacionados ao processo de reabsorção alveolar, o que culminam na perda óssea tanto em espessura quanto em altura, sendo esse principal impasse para reabilitação oral por meio de prótese sobre implantes. Cerca de 50% dos sítios para instalação de implantes não apresentam volume ósseo suficiente para sua instalação, o leva a necessidade de utilizar biomateriais para o processo de regeneração óssea guiada. Diante da necessidade de aumentar tecido ósseo em volume e espessura, diversos biomateriais foram desenvolvidos, sendo eles classificados em enxertos do tipo autógeno, alógeno, xenógeno e aloplástico. Para realização desse estudo foi realizada uma busca completa nas bases de dados: PubMed, Scielo, Lilacs e Google Scholar, utilizando as palavras-chave “dentistry bone transplantation, surgery oral, biocompatible materials and bone regeneration”, inseridas nas buscas de maneira cruzada adotando a expressão boolena "and”. Afim de selecionar os artigos a serem analisados foram elencados critérios de inclusão e exclusão. A utilização de enxertos ósseos tem mostrado resultados promissores no ganho de osso vertical e horizontal. A associação de biomaterias permite que as melhores propriedades de cada tipo de enxerto sejam usadas de forma integrada, o que leva a resultados favoráveis tanto histologicamente como funcionalmente.

The hemodynamic effects of intravenous paracetamol (acetaminophen) in patients with chronic liver disease undergoing liver transplantation: a pilot study

Objective We performed a single-center double-blinded, randomized trial to investigate the hemodynamic effects of IV paracetamol in patients with chronic liver disease (CLD) undergoing liver transplantation surgery. Patients with CLD are particularly susceptible to hemodynamic derangements given their low systemic vascular resistance state. Accordingly, hypotension is common in this setting. The hemodynamic effects of IV paracetamol in patients undergoing elective liver transplantation are unknown, therefore we evaluated whether the intraoperative administration of IV paracetamol in patients with chronic liver disease undergoing liver transplantation results in adverse hemodynamic effects. The primary end point was a change in systolic blood pressure 30-min after the preoperative infusion. Results Twenty-four participants undergoing liver transplantation surgery were randomly assigned to receive a single bolus of IV paracetamol (1 g paracetamol + 3.91 g mannitol per 100 mL) (n = 12) or placebo (0.9% Saline 100 mL) (n = 12). All participants completed their study intervention, and there were no breaches or violations of the trial protocol. Baseline characteristics were similar in both groups. There were no significant differences regarding surgical duration, intraoperative use of fluids, and intraoperative noradrenaline use. After the administration of paracetamol there were no significant differences observed in blood pressure or other hemodynamic parameters when compared to placebo.

Qualitative Assessment of YouTube Videos as a Source of Patient Information for Corneal Transplant Surgery

Purpose: Healthcare information is easily accessible on YouTube, however it is unregulated and the quality may vary considerably. This study characterised and evaluated the content on YouTube regarding corneal transplantation surgery.Methods: YouTube was searched using ‘corneal transplant’ and the variations for penetrating and lamellar transplants. The results were deduplicated and screened for inclusion by two independent reviewers. A modified DISCERN tool was used to evaluate the quality of each video by two observers independently. Discrepancies were resolved through discussion and a third adjudicator where necessary.Results: 53 videos were included in this study and the mean overall DISCERN score was 1.91 out of 5 (SD = 0.90). Videos scored highest in relevance to corneal transplant (mean 3.89) and lowest in explaining which patients are unsuitable (mean 1.00) and offering sources of information (mean 1.11). The video with the highest viewer engagement (VPI) was a patient vlogging their experience of the procedure. Conclusion: Quality of YouTube content is variable and the lack of clarity over subtypes of corneal transplant can be confusing for patients. There is considerable scope to improve the use of visual aids, animations and diagrams within videos in order to supplement verbal information in clinic. Essential components needed to make an informed decision about corneal transplant are lacking in many videos, meaning videos may be a useful supplement but should not be relied on for comprehensive material.

Novel Cell Culture Paradigm Prolongs Mouse Corneal Epithelial Cell Proliferative Activity in vitro and in vivo

It has been a long-standing challenge to obtain from cell cultures adequate amounts of mouse corneal epithelial cells (mCEC) to perform transplantation surgery. This limitation is attributable to the passage dependent declines in their proliferative activity. We describe here development of a novel 6C medium that contains six different modulators of different signaling pathways, which control proliferative mCEC activity. Its usage shortens the time and effort required to obtain epithelial sheets for hastening healing of an epithelial wound in an experimental animal model. This serum-free 6C medium contains:Y27632, forskolin, SB431542, DAPT, IWP-2, LDN-193189 and also DermaLife K keratinocyte calcium. Their inclusion inhibits rises in four specific markers of epithelial mesenchymal transdifferentiation:ZEB1/2, Snail, β-catenin and α-SMA. This medium is applied in a feeder-free air-lifted system to obtain sufficient populations of epithelial progenitor cells whose procurement is facilitated due to suppression of progenitor epithelial cell transdifferentiation into epithelial-mesenchymal cells. Diminution of this decline in transdifferentiation was confirmed based on the invariance of P63, K14, Pax6, and K12 gene expression levels. This cell culture technique is expected to facilitate ex vivo characterization of mechanisms underlying cell fate determination. Furthermore, its implementation will improve yields of progenitor mouse corneal epithelial cells, which increases the likelihood of using these cells as a source to generate epithelial sheets for performing transplantation surgery to treat limbal stem cell deficiency in a clinical setting. In addition, the novel insight obtainable from such studies is expected to improve the outcomes of corneal regenerative medicine.

Pathophysiology of exercise capacity after heart transplantation

Heart transplantation is a life-saving treatment option for patients with end-stage heart failure. The improvement in exercise capacity of patients can vary to a great extent following transplant surgery. This review outlines the pathophysiology behind the changes in exercise capacity after heart transplantation. Reasons for exercise intolerance can be classified as central (cardiac) and peripheral (vascular and skeletal muscle). Cardiac mechanisms that limit exercise capacity are chronotropic incompetence due to denervation of the heart and diastolic dysfunction. Peripheral mechanisms are endothelial dysfunction and morphological alterations in the skeletal muscle. Some of the pathophysiological changes can be recovered with exercise therapy after the transplantation surgery. Research should be directed to reveal the safest and most effective exercise prescription to heart transplant recipients, targeting all of the mechanisms that contribute to exercise intolerance in a holistic approach.