Proteomics and Extracellular Vesicles as Novel Biomarker Sources in Peritoneal Dialysis in Children

Peritoneal dialysis (PD) represents the dialysis modality of choice for pediatric patients with end-stage kidney disease. Indeed, compared with hemodialysis (HD), it offers many advantages, including more flexibility, reduction of the risk of hospital-acquired infections, preservation of residual kidney function, and a better quality of life. However, despite these positive aspects, PD may be associated with several long-term complications that may impair both patient’s general health and PD adequacy. In this view, chronic inflammation, caused by different factors, has a detrimental impact on the structure and function of the peritoneal membrane, leading to sclerosis and consequent PD failure both in adults and children. Although several studies investigated the complex pathogenic pathways underlying peritoneal membrane alterations, these processes remain still to explore. Understanding these mechanisms may provide novel approaches to improve the clinical outcome of pediatric PD patients through the identification of subjects at high risk of complications and the implementation of personalized interventions. In this review, we discuss the main experimental and clinical experiences exploring the potentiality of the proteomic analysis of peritoneal fluids and extracellular vesicles as a source of novel biomarkers in pediatric peritoneal dialysis.     

First-Void Urine Microbiome in Women with Chlamydia trachomatis Infection

Background: Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide. Until now, little information is available about the microbial composition of urine samples during CT urethritis. Therefore, in this study, we characterized the microbiome and metabolome profiles of first-void urines in a cohort of women with CT urethral infection attending an STI clinic. Methods: Based on CT positivity by nucleic acid amplification techniques on urine samples, the enrolled women were divided into two groups, i.e., “CT-negative” (n = 21) and “CT-positive” (n = 11). Urine samples were employed for (i) the microbiome profile analysis by means of 16s rRNA gene sequencing and (ii) the metabolome analysis by ¹H-NMR. Results: Irrespective of CT infection, the microbiome of first-void urines was mainly dominated by Lactobacillus, L. iners and L. crispatus being the most represented species. CT-positive samples were characterized by reduced microbial biodiversity compared to the controls. Moreover, a significant reduction of the Mycoplasmataceae family—in particular, of the Ureaplasma parvum species—was observed during CT infection. The Chlamydia genus was positively correlated with urine hippurate and lactulose. Conclusions: These data can help elucidate the pathogenesis of chlamydial urogenital infections, as well as to set up innovative diagnostic and therapeutic approaches.     

ILB®, a Low Molecular Weight Dextran Sulphate,Restores Glutamate Homeostasis,Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury

In a previous study, we found that administration of ILB^®, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB^® administration (at the dose levels of 1, 5 and 15 mg/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB^®-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB^® significantly decreased whole brain glutamate (normalizing the glutamate/glutamine ratio), glycine, serine and γ-aminobutyric acid. Furthermore, ILB^® administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB^® were the relevant improvement in neurocognitive functions of the group of animals treated with ILB^® 5 mg/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB^® administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB^®-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB^® is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.     

State-of-the-Art on Wound Vitality Evaluation: A Systematic Review

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were “wound”, “lesion”, “vitality”, “evaluation”, “immunohistochemistry”, “proteins”, “electrolytes”, “mRNAs”, and “miRNAs” in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation.     

Functionalized Hydrogels for Cartilage Repair: The Value of Secretome-Instructive Signaling

Cartilage repair has been a challenge in the medical field for many years. Although treatments that alleviate pain and injury are available, none can effectively regenerate the cartilage. Currently, regenerative medicine and tissue engineering are among the developed strategies to treat cartilage injury. The use of stem cells, associated or not with scaffolds, has shown potential in cartilage regeneration. However, it is currently known that the effect of stem cells occurs mainly through the secretion of paracrine factors that act on local cells. In this review, we will address the use of the secretome—a set of bioactive factors (soluble factors and extracellular vesicles) secreted by the cells—of mesenchymal stem cells as a treatment for cartilage regeneration. We will also discuss methodologies for priming the secretome to enhance the chondroregenerative potential. In addition, considering the difficulty of delivering therapies to the injured cartilage site, we will address works that use hydrogels functionalized with growth factors and secretome components. We aim to show that secretome-functionalized hydrogels can be an exciting approach to cell-free cartilage repair therapy.     

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.     

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. We provide a comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting.