miR-23b-3p, miR-126-3p and GAS5 delivered by extracellular vesicles inhibit breast cancer xenografts in zebrafish.

Background: Extracellular vesicles (EVs) are a group of nanoscale cell-derived membranous structures secreted by all cell types, containing molecular cargoes involved in intercellular communication. EVs can be used to mimic "nature's delivery system" to transport nucleic acids, peptides, lipids, and metabolites to target recipient cells. EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches that can be used in different diseases, including cancer.

Optimal Operation of Cryogenic Calorimeters Through Deep Reinforcement Learning.

Cryogenic phonon detectors with transition-edge sensors achieve the best sensitivity to sub-GeV/c dark matter interactions with nuclei in current direct detection experiments. In such devices, the temperature of the thermometer and the bias current in its readout circuit need careful optimization to achieve optimal detector performance. This task is not trivial and is typically done manually by an expert.

Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions.

Mitophagy is the intracellular recycling system that disposes damaged/inefficient mitochondria and allows biogenesis of new organelles to ensure mitochondrial quality is optimized. Dysfunctional mitophagy has been implicated in human aging and diseases. Multiple evolutionarily selected, redundant mechanisms of mitophagy have been identified, but their specific roles in human health and their potential exploitation as therapeutic targets are unclear.

Characterization of Chemoresistance in Pancreatic Cancer: A Look at MDR-1 Polymorphisms and Expression in Cancer Cells and Patients.

Pancreatic malignancy is the fourth cause of cancer-related death in Western countries and is predicted to become the second leading cause of cancer-related mortality by 2030. The standard therapies (FOLFIRINOX and gemcitabine with nab-paclitaxel) are not resolutive because this type of cancer is also characterized by a high chemoresistance, due in part to the activity of the ATP Binding Cassette (ABC) pumps accounting for the reduction in the intracellular concentration of the drugs. In this work, we analyze the occurrence of single-nucleotide polymorphisms (SNPs) in the MDR-1 gene, in different pancreatic cancer cell lines, and in tissues from pancreatic cancer patients by DNA sequencing, as well as the expression levels of MDR-1 mRNA and protein, by qRT-PCR and Western Blot analysis.

Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task.

In silico evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19.

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.

Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?

Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC.

Esophageal food bolus impaction in pediatric age.

Objectives: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children.

Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells.

Background: Among the mechanisms of mitochondrial quality control (MQC), generation of mitochondria-derived vesicles (MDVs) is a process to avoid complete failure of mitochondria determining lysosomal degradation of mitochondrial damaged proteins. In this context, RAB7, a late endocytic small GTPase, controls delivery of MDVs to late endosomes for subsequent lysosomal degradation. We previously demonstrated that RAB7 has a pivotal role in response to cisplatin (CDDP) regulating resistance to the drug by extracellular vesicle (EVs) secretion.

Deciphering the impact of decabromodiphenyl ether (BDE-209) on benthic foraminiferal communities: Insights from Cell-Tracker Green staining and eDNA metabarcoding.

This study investigates the ecotoxicological effects of BDE-209, a persistent organic pollutant (POP) prevalent in Kuwait's coastal-industrial areas, on benthic foraminiferal communities. We conducted a mesocosm experiment in which we exposed benthic foraminiferal communities sampled from the coastal-industrial areas of Kuwait to a gradient of BDE-209 concentrations (0.01 to 20 mg/kg).

Erratum: Measurement of the 2νββ Decay Half-Life of ^{130}Te with CUORE [Phys. Rev. Lett. 126, 171801 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.

The interaction of patients' physical status and time to endoscopy on mortality risk in patients with upper gastrointestinal bleeding: A national prospective cohort study.

Background And Aim: The correct time to perform an upper endoscopy is decisive in acutely GI bleeding patients. However, patients' physical status may affect mortality. We speculated that the physical status and procedural time could be the principal factors accountable for death-risk.

Measurement of the 2νββ Decay Half-Life of ^{82}Se with the Global CUPID-0 Background Model.

We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82  kg×yr of ^{82}Se. We identify with improved precision the background sources within the 3 MeV energy region, where neutrinoless double β decay of ^{82}Se and ^{100}Mo is expected, making more solid the foundations for the background budget of the next-generation CUPID experiment.

Magnetic foreign body ingestion in pediatric age.

Objectives: To assess the clinical complications reported after the ingestion of magnetic foreign bodies (FBs) in pediatric age, along with their incidence among all FB ingestions and clinical presentation.

Study Design: We've consecutively recruited all children aged 0-14 years who were admitted for single or multiple magnet ingestion from May 2015 to December 2022. Patient demographics, admission sources and discharge status were accurately recorded, along with their clinical management and outcomes.

Antisense therapy: a potential breakthrough in the treatment of neurodegenerative diseases.

Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system. Currently, there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide. Therefore, it is necessary to find new therapeutic approaches, and antisense therapies offer this possibility, having the great advantage of not modifying cellular genome and potentially being safer.

Mitochondrial-Derived Vesicles: The Good, the Bad, and the Ugly.

Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal-lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal.

An aqueous olive leaf extract (OLE) ameliorates parameters of oxidative stress associated with lipid accumulation and induces lipophagy in human hepatic cells.

Fatty liver is a disease characterized by a buildup of lipids in the liver, often resulting from excessive consumption of high-fat-containing foods. Fatty liver can degenerate, over time, into more severe forms of liver diseases, especially when oxidative stress occurs. Olive leaf extract (OLE) is a reliable source of polyphenols with antioxidant and hypolipidemic properties that have been successfully used in medicine, cosmetics, and pharmaceutical products.

The contribution of mitochondrial DNA alterations to aging, cancer, and neurodegeneration.

Mitochondrial DNA (mtDNA) is as a double-stranded molecule existing in hundreds to thousands copies in cells depending on cell metabolism and exposure to endogenous and/or environmental stressors. The coordination of mtDNA replication and transcription regulates the pace of mitochondrial biogenesis to guarantee the minimum number of organelles per cell. mtDNA inheritance follows a maternal lineage, although bi-parental inheritance has been reported in some species and in the case of mitochondrial diseases in humans.

Defining Time in Acute Upper Gastrointestinal Bleeding: When Should We Start the Clock?

Introduction: The execution of upper endoscopy at the proper time is key to correctly managing patients with upper gastrointestinal bleeding (UGIB). Nonetheless, the definition of "time" for endoscopic examinations in UGIB patients is imprecise. The primary aim of this study was to verify whether the different definitions of "time" (i.

Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis.

Odevixibat, an ileal bile acid transporter (IBAT) inhibitor, is effective for the treatment of pruritus in children diagnosed with progressive familial intrahepatic cholestasis (PFIC) type 1 and 2. There are no studies showing the efficacy of Odevixibat in children with different subtypes of PFIC. We describe the case of a 6-year-old girl with chronic cholestatic jaundice.