Search Results (26)

Background and Objectives: Radon is a known risk factor for lung cancer, and residential radon exposure is the leading cause of lung cancer in never smokers; however, in Italy, there is still a lack of public awareness regarding the risk caused by residential radon exposure. In this mortality study, which was carried out in an Italian Apulian town (Locorotondo) of the Bari province, we aimed to analyze lung cancer mortality and all-cause mortality in a population highly exposed to radon. Materials and Methods: The study period was 1998–2021. Local and Italian population and national mortality data were collected from the Italian National Institute of Statistics (ISTAT) website platform. Local mortality data were collected using copies of the Local Health Authority death certificates. Results: We identified 117 lung cancers in the studied period. The mortality data trends revealed a decrease in the all-causes standardized mortality ratios (SMRs), increases in the incidence rates of lung cancer and colorectal cancer in recent years, and a decrease in the incidence of noncancer diseases. We also found high SMRs for colorectal cancer until 2016 among older females. With respect to the cardio-circulatory system, only in 2014 did the male SMRs significantly influence the total SMR; after this period, a decreasing stable trend was observed. Conclusions: The natural balance of the population is decreasing, and mortality is decreasing for all causes. A future study will be needed to assess the associations between observed lung cancer cases and domestic radon exposure to drive radon mitigation and public health strategies. Full article

Acute respiratory distress syndrome (ARDS) is a critical illness in critically unwell patients, characterized by refractory hypoxemia and shock. This study evaluates an early detection tool and investigates the relationship between hypoxia and circulatory shock in ARDS, to improve diagnostic precision and therapy customization. We used a porcine model, inducing ARDS with mechanical ventilation and intratracheal plus intravenous lipopolysaccharide (LPS) injection. Hemodynamic changes were monitored using an Acumen IQ sensor and a ForeSight Elite sensor connected to the HemoSphere platform. We evaluated tissue damage, inflammatory response, and hypoxia-inducible factor (HIF) alterations using enzyme-linked immunosorbent assay and immunohistochemistry. The results showed severe hypotension and increased heart rates post-LPS exposure, with a notable rise in the hypotension prediction index (HPI) during acute lung injury (p = 0.024). Tissue oxygen saturation dropped considerably in the right brain region. Interestingly, post-injury HIF-2α levels were lower at the end of the experiment. Our findings imply that the HPI can effectively predict ARDS-related hypotension. HIF expression levels may serve as possible markers of rapid ARDS progression. Further research should be conducted on the clinical value of this novel approach in critical care, as well as the relationship between the HIF pathway and ARDS-associated hypotension. Full article

Preclinical testing of medical devices is an essential step in the product life cycle, whereas testing of cardiovascular implants requires specialised testbeds or numerical simulations using computer software Ansys 2016. Existing test setups used to evaluate physiological scenarios and test cardiac implants such as mock circulatory systems or isolated beating heart platforms are driven by sophisticated hardware which comes at a high cost or raises ethical concerns. On the other hand, computational methods used to simulate blood flow in the cardiovascular system may be simplified or computationally expensive. Therefore, there is a need for low-cost, relatively simple and efficient test beds that can provide realistic conditions to simulate physiological scenarios and evaluate cardiovascular devices. In this study, the concept design of a novel left ventricular simulator made of latex rubber and actuated by pneumatic artificial muscles is presented. The designed left ventricular simulator is geometrically similar to a native left ventricle, whereas the basal diameter and long axis length are within an anatomical range. Finite element simulations evaluating left ventricular twisting and shortening predicted that the designed left ventricular simulator rotates approximately 17 degrees at the apex and the long axis shortens around 11 mm. Experimental results showed that the twist angle is 18 degrees and the left ventricular simulator shortens 5 mm. Twist angles and long axis shortening as in a native left ventricle show it is capable of functioning like a native left ventricle and simulating a variety of scenarios, and therefore has the potential to be used as a test platform. Full article

Cortisol is a steroid hormone that regulates energy metabolism, stress reactions, and immune response. Cortisol is produced in the kidneys’ adrenal cortex. Its levels in the circulatory system are regulated by the neuroendocrine system with a negative feedback loop of the hypothalamic–pituitary–adrenal axis (HPA-axis) following circadian rhythm. Conditions associated with HPA-axis disruption cause deteriorative effects on human life quality in numerous ways. Psychiatric, cardiovascular, and metabolic disorders as well as a variety of inflammatory processes accompanying age-related, orphan, and many other conditions are associated with altered cortisol secretion rates and inadequate responses. Laboratory measurements of cortisol are well-developed and based mainly on the enzyme linked immunosorbent assay (ELISA). There is a great demand for a continuous real-time cortisol sensor that is yet to be developed. Recent advances in approaches that will eventually culminate in such sensors have been summarized in several reviews. This review compares different platforms for direct cortisol measurements in biological fluids. The ways to achieve continuous cortisol measurements are discussed. A cortisol monitoring device will be essential for personified pharmacological correction of the HPA-axis toward normal cortisol levels through a 24-h cycle. Full article

Aortic disease has a significant impact on quality of life. The involvement of the aortic arch requires the preservation of blood supply to the brain during surgery. Deep hypothermic circulatory arrest is an established technique for this purpose, although neurological injury remains high. Additional techniques have been used to reduce risk, although controversy still remains. A three-way cannulation approach, including both carotid arteries and the femoral artery or the ascending aorta, has been used successfully for aortic arch replacement and redo procedures. We developed circuits of the circulation to simulate blood flow during this type of cannulation set up. The CARDIOSIM© cardiovascular simulation platform was used to analyse the effect on haemodynamic and energetic parameters and the benefit derived in terms of organ perfusion pressure and flow. Our simulation approach based on lumped-parameter modelling, pressure–volume analysis and modified time-varying elastance provides a theoretical background to a three-way cannulation strategy for aortic arch surgery with correlation to the observed clinical practice. Full article

Aptamer–drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, Sgc8-paclitaxel by conjugation and Sgc8-gemcitabine, by automated solid-phase synthesis. In vitro experiments showed that F-base-modified ApDCs retain the specificity of the aptamer to target cells and the biological stability is improved. In vivo studies demonstrated that the circulatory time is increased by up to 55 h or longer, as the incorporated F base leads to a stable ApDC-albumin complex as the formulation for targeted delivery. Moreover, conjugated drug molecules were released efficiently and the drug (paclitaxel) concentration in the tumor site was improved. The results demonstrate that an F-base-directed ApDC-albumin complex is a potential platform for drug delivery and targeted cancer therapy. Full article

Severe acute respiratory syndrome–Coronavirus 2 (SARS-CoV-2) can infect various human organs, including the respiratory, circulatory, nervous, and gastrointestinal ones. The virus is internalized into human cells by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor through its spike protein (S-glycoprotein). As S-glycoprotein is required for the attachment and entry into the human target cells, it is the primary mediator of SARS-CoV-2 infectivity. Currently, this glycoprotein has received considerable attention as a key component for the development of antiviral vaccines or biologics against SARS-CoV-2. Moreover, since the ACE2 receptor constitutes the main entry route for the SARS-CoV-2 virus, its soluble form could be considered as a promising approach for the treatment of coronavirus disease 2019 infection (COVID-19). Both S-glycoprotein and ACE2 are highly glycosylated molecules containing 22 and 7 consensus N-glycosylation sites, respectively. The N-glycan structures attached to these specific sites are required for the folding, conformation, recycling, and biological activity of both glycoproteins. Thus far, recombinant S-glycoprotein and ACE2 have been produced primarily in mammalian cells, which is an expensive process. Therefore, benefiting from a cheaper cell-based biofactory would be a good value added to the development of cost-effective recombinant vaccines and biopharmaceuticals directed against COVID-19. To this end, efficient protein synthesis machinery and the ability to properly impose post-translational modifications make microalgae an eco-friendly platform for the production of pharmaceutical glycoproteins. Notably, several microalgae (e.g., Chlamydomonas reinhardtii, Dunaliella bardawil, and Chlorella species) are already approved by the U.S. Food and Drug Administration (FDA) as safe human food. Because microalgal cells contain a rigid cell wall that could act as a natural encapsulation to protect the recombinant proteins from the aggressive environment of the stomach, this feature could be used for the rapid production and edible targeted delivery of S-glycoprotein and soluble ACE2 for the treatment/inhibition of SARS-CoV-2. Herein, we have reviewed the pathogenesis mechanism of SARS-CoV-2 and then highlighted the potential of microalgae for the treatment/inhibition of COVID-19 infection. Full article

Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted. Full article

This review is devoted to presenting the history of the CARDIOSIM^© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory systems. The first version of CARDIOSIM^© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on a PC with a disk operating system (MS-DOS) and was developed using the Turbo Basic language. The latest version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce the most important pathophysiological conditions. One or more zero-dimensional (0-D) modules have been implemented in the platform for each section. The different modules can be assembled to reproduce part or the whole circulation according to Starling’s law of the heart. Different mechanical ventilatory and circulatory devices have been implemented in the platform, including thoracic artificial lungs, ECMO, IABPs, pulsatile and continuous right and left ventricular assist devices, biventricular pacemakers and biventricular assist devices. CARDIOSIM^© is used in clinical and educational environments. Full article

The myosin light chain phosphatase target subunit 1 (MYPT1), encoded by the PPP1R12A gene, is a key component of the myosin light chain phosphatase (MLCP) protein complex. MYPT1 isoforms have been described as products of the cassette-type alternative splicing of exons E13, E14, E22, and E24. Through in silico analysis of the publicly available EST and mRNA databases, we established that PPP1R12A contains 32 exons (6 more than the 26 previously reported), of which 29 are used in 11 protein-coding transcripts. An in silico analysis of publicly available RNAseq data combined with validation by reverse transcription (RT)-PCR allowed us to determine the relative abundance of each transcript in three cell types of the circulatory system where MYPT1 plays important roles: human umbilical vein endothelial cells (HUVEC), human saphenous vein smooth muscle cells (HSVSMC), and platelets. All three cell types express up to 10 transcripts at variable frequencies. HUVECs and HSVSMCs predominantly express the full-length variant (58.3% and 64.3%, respectively) followed by the variant skipping E13 (33.7% and 23.1%, respectively), whereas in platelets the predominant variants are those skipping E14 (51.4%) and E13 (19.9%), followed by the full-length variant (14.4%). Variants including E24 account for 5.4% of transcripts in platelets but are rare (<1%) in HUVECs and HSVSMCs. Complex transcriptional profiles were also found across organs using in silico analysis of RNAseq data from the GTEx project. Our findings provide a platform for future studies investigating the specific (patho)physiological roles of understudied MYPT1 isoforms. Full article

Skin cancer, which includes the most frequent malignant non-melanoma carcinomas (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC), along with the difficult to treat cutaneous melanoma (CM), pose important worldwide issues for the health care system. Despite the improved anti-cancer armamentarium and the latest scientific achievements, many skin cancer patients fail to respond to therapies, due to the remarkable heterogeneity of cutaneous tumors, calling for even more sophisticated biomarker discovery and patient monitoring approaches. Droplet digital polymerase chain reaction (ddPCR), a robust method for detecting and quantifying low-abundance nucleic acids, has recently emerged as a powerful technology for skin cancer analysis in tissue and liquid biopsies (LBs). The ddPCR method, being capable of analyzing various biological samples, has proved to be efficient in studying variations in gene sequences, including copy number variations (CNVs) and point mutations, DNA methylation, circulatory miRNome, and transcriptome dynamics. Moreover, ddPCR can be designed as a dynamic platform for individualized cancer detection and monitoring therapy efficacy. Here, we present the latest scientific studies applying ddPCR in dermato-oncology, highlighting the potential of this technology for skin cancer biomarker discovery and validation in the context of personalized medicine. The benefits and challenges associated with ddPCR implementation in the clinical setting, mainly when analyzing LBs, are also discussed. Full article

The use of secondary hospital-based clinical data and electronical health records (EHR) represent a cost-efficient alternative to investigate chronic conditions. We present the Clinical Network Big Data and Personalised Health project, which collects EHRs for patients accessing hospitals in Central-Southern Italy, through an integrated digital platform to create a digital hub for the collection, management and analysis of personal, clinical and environmental information for patients, associated with a biobank to perform multi-omic analyses. A total of 12,864 participants (61.7% women, mean age 52.6 ± 17.6 years) signed a written informed consent to allow access to their EHRs. The majority of hospital access was in obstetrics and gynaecology (36.3%), while the main reason for hospitalization was represented by diseases of the circulatory system (21.2%). Participants had a secondary education (63.5%), were mostly retired (25.45%), reported low levels of physical activity (59.6%), had low adherence to the Mediterranean diet and were smokers (30.2%). A large percentage (35.8%) were overweight and the prevalence of hypertension, diabetes and hyperlipidemia was 36.4%, 11.1% and 19.6%, respectively. Blood samples were retrieved for 8686 patients (67.5%). This project is aimed at creating a digital hub for the collection, management and analysis of personal, clinical, diagnostic and environmental information for patients, and is associated with a biobank to perform multi-omic analyses. Full article

Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury. Full article

Breast cancer (BC) is the second most common cancer in women globally after lung cancer. Presently, the most important approach for BC treatment consists of surgery, followed by radiotherapy and chemotherapy. The latter therapeutic methods are often unsuccessful in the treatment of BC because of their various side effects and the damage incurred to healthy tissues and organs. Currently, numerous nanoparticles (NPs) have been identified and synthesized to selectively target BC cells without causing any impairments to the adjacent normal tissues or organs. Based on an exploratory study, this comprehensive review aims to provide information on engineered NPs and their payloads as promising tools in the treatment of BC. Therapeutic drugs or natural bioactive compounds generally incorporate engineered NPs of ideal sizes and shapes to enhance their solubility, circulatory half-life, and biodistribution, while reducing their side effects and immunogenicity. Furthermore, ligands such as peptides, antibodies, and nucleic acids on the surface of NPs precisely target BC cells. Studies on the synthesis of engineered NPs and their impact on BC were obtained from PubMed, Science Direct, and Google Scholar. This review provides insights on the importance of engineered NPs and their methodology for validation as a next-generation platform with preventive and therapeutic effects against BC. Full article

Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyte^TM Cytefinder II platform. The Lin− and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK (“classic” CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions. Full article