vCPP2319 interacts with metastatic breast cancer extracellular vesicles (EVs) and transposes a human blood-brain barrier model.

Brain metastases (BM) are frequently found in cancer patients and, though their precise incidence is difficult to estimate, there is evidence for a correlation between BM and specific primary cancers, such as lung, breast, and skin (melanoma). Among all these, breast cancer is the most frequently diagnosed among women and, in this case, BM cause a critical reduction of the overall survival (OS), especially in triple negative breast cancer (TNBC) patients. The main challenge of BM treatment is the impermeable nature of the blood-brain barrier (BBB), which shields the central nervous systems (CNS) from chemotherapeutic drugs.

Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice.

Overall health relies on features of skeletal muscle that generally decline with age, partly due to mechanisms associated with mitochondrial redox imbalance and bioenergetic dysfunction. Previously, aged mice genetically devoid of the mitochondrial NAD(P) transhydrogenase (NNT, encoded by the nicotinamide nucleotide transhydrogenase gene), an enzyme involved in mitochondrial NADPH supply, were shown to exhibit deficits in locomotor behavior. Here, by using young, middle-aged, and older NNT-deficient (Nnt) mice and age-matched controls (Nnt), we aimed to investigate how muscle bioenergetic function and motor performance are affected by NNT expression and aging.

Development, characterization and evaluation of the ointment containing hyaluronic acid for potential wound healing applications.

Wound healing is a complex biological process. In this context, hyaluronic acid (HA) plays an important role in all phases of wound healing, from inflammation to the remodelling process. Nevertheless, its presence in adults decreases by 50% compared to newborns, which drastically reduces tissue regeneration.

Dichloroacetate reactivates pyruvate-supported peroxide removal by liver mitochondria and prevents NAFLD aggravation in NAD(P) transhydrogenase-null mice consuming a high-fat diet.

The mechanisms by which a high-fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunction and redox imbalance. The functional loss of the enzyme NAD(P) transhydrogenase, a main source of mitochondrial NADPH, results in impaired mitochondrial peroxide removal, pyruvate dehydrogenase inhibition by phosphorylation, and progression of NAFLD in HFD-fed mice. The present study aimed to investigate whether pharmacological reactivation of pyruvate dehydrogenase by dichloroacetate attenuates the mitochondrial redox dysfunction and the development of NAFLD in NAD(P) transhydrogenase-null (Nnt) mice fed an HFD (60% of total calories from fat).

The antimetastatic breast cancer activity of the viral protein-derived peptide vCPP2319 as revealed by cellular biomechanics.

The incidence of metastatic breast cancer (MBC) is increasing and the therapeutic arsenal available to fight it is insufficient. Brain metastases, in particular, represent a major challenge for chemotherapy as the impermeable nature of the blood-brain barrier (BBB) prevents most drugs from targeting cells in the brain. For their ability to transpose biological membranes and transport a broad spectrum of bioactive cargoes, cell-penetrating peptides (CPPs) have been hailed as ideal candidates to deliver drugs across biological barriers.

Climate regime shifts and biodiversity redistribution in the Bay of Biscay.

Global ocean warming, wave extreme events, and accelerating sea-level rise are challenges that coastal communities must address to anticipate damages in coming decades. The objective of this study is to undertake a time-series analysis of climate change (CC) indicators within the Bay of Biscay, including the Basque coast. We used an integrated and flexible methodology, based on Generalized Additive Mixed Models, to detect trends on 19 indicators (including marine physics, chemistry, atmosphere, hydrology, geomorphology, biodiversity, and commercial species).

NEW DEFINITIVE HOST RECORD FOR CHORDODES MORGANI (NEMATOMORPHA) IN NEBRASKA WITH NOTES ON ECOLOGY.

The life cycle and ecology of the horsehair worm Chordodes morgani (Nematomorpha) in Nebraska remain unknown. To identify its definitive host, we installed a series of pitfall traps along 3 first-order streams at 4 sites: Elk Creek, Upper Elk Creek, Maple Creek, and West Oak Creek, all located northwest of Lincoln, Nebraska. In addition, we opportunistically hand-collected insects at these sites, including wood cockroaches (Parcoblatta virginica), and maintained them in the lab until they passed adult worms.

Products and technologies for treating patients with evidence-based pressure ulcers.

Objective: to identify products/technologies for treating patients with pressure ulcers with an evidence level 1.

Method: this is an integrative literature review. A survey of studies was carried out using the United States National Library of Medicine Portal, Scientific Electronic Library Online, Virtual Health Library, National Library of Medicine(®), The Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean in Health Sciences, Nursing Database.

The Impact of the Use of C-Arm Cone-Beam CT During Chemoembolization for Hepatocellular Carcinoma.

Objective: The objective of the study was to investigate the consequences of using CArm Cone-Beam computed Tomography (CBCT) on super-selective catheterization of Hepatic Artery (HA) branches during chemoembolization of hepatocellular carcinoma.

Methods: Two groups of patients were created according to the dates of their treatment sessions. Group A and Group B included patients who had their treatment sessions in 2004 - 2005 and 2008 - 2010, respectively.

Mitochondrial NAD(P) Transhydrogenase: From Molecular Features to Physiology and Disease.

Proton-translocating NAD(P) transhydrogenase, also known as nicotinamide nucleotide transhydrogenase (NNT), catalyzes a reversible reaction coupling the protonmotive force across the inner mitochondrial membrane and hydride (H, a proton plus two electrons) transfer between the mitochondrial pools of NAD(H) and NADP(H). The forward NNT reaction is a source of NADPH in the mitochondrial matrix, fueling antioxidant and biosynthetic pathways with reductive potential. Despite the greater emphasis given to the net forward reaction, the reverse NNT reaction that oxidizes NADPH also occurs in physiological and pathological conditions.

NADPH supply and the contribution of NAD(P) transhydrogenase (NNT) to HO balance in skeletal muscle mitochondria.

HO is endogenously generated and its removal in the matrix of skeletal muscle mitochondria (SMM) is dependent on NADPH likely provided by NAD(P) transhydrogenase (NNT) and isocitrate dehydrogenase (IDH2). Importantly, NNT activity is linked to mitochondrial protonmotive force. Here, we demonstrate the presence of NNT function in detergent-solubilized and intact functional SMM isolated from rats and wild type (Nnt) mice, but not in SMM from congenic mice carrying a mutated NNT gene (Nnt).

Anti-HIV-1 Activity of pepRF1, a Proteolysis-Resistant CXCR4 Antagonist Derived from Dengue Virus Capsid Protein.

There is an urgent need for the development of new anti-HIV drugs that can complement existing medicines to be used against resistant strains. Here, we report the anti-HIV-1 peptide pepRF1, a human serum-resistant peptide derived from the Dengue virus capsid protein. , pepRF1 shows a 50% inhibitory concentration of 1.

Mitochondrial NAD(P) Transhydrogenase is Unevenly Distributed in Different Brain Regions, and its Loss Causes Depressive-like Behavior and Motor Dysfunction in Mice.

NAD(P) transhydrogenase (NNT) links redox states of the mitochondrial NAD(H) and NADP(H) via a reaction coupled to proton-motive force across the inner mitochondrial membrane. NNT is believed to be ubiquitously present in mammalian cells, but its expression may vary substantially in different tissues. The present study investigated the tissue distribution and possible roles of NNT in the mouse brain.

Enfuvirtide-Protoporphyrin IX Dual-Loaded Liposomes: In Vitro Evidence of Synergy against HIV-1 Entry into Cells.

We have developed a nanocarrier consisting of large unilamellar vesicles (LUVs) for combined delivery of two human immunodeficiency virus type 1 (HIV-1) entry inhibitors, enfuvirtide (ENF) and protoporphyrin IX (PPIX). The intrinsic lipophilicity of ENF and PPIX, a fusion inhibitor and an attachment inhibitor, respectively, leads to their spontaneous incorporation into the lipid bilayer of the LUVs nanocarrier. Both entry inhibitors partition significantly toward LUVs composed of 1-palmitoyl-2-oleoyl--glycero-3-phosphocholine (POPC) and a 9:1 mixture of POPC:1,2-dipalmitoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DPPE-PEG), representative of conventional and immune-evasive drug delivery formulations, respectively.

Plant defensin PvD modulates the membrane composition of breast tumour-derived exosomes.

One of the most important causes of failure in tumour treatment is the development of resistance to therapy. Cancer cells can develop the ability to lose sensitivity to anti-neoplastic drugs during reciprocal crosstalk between cells and their interaction with the tumour microenvironment (TME). Cell-to-cell communication regulates a cascade of interdependent events essential for disease development and progression and can be mediated by several signalling pathways.

What Are the Effects of Irreversible Electroporation on a Staphylococcus aureus Rabbit Model of Osteomyelitis?

Background: The treatment of osteomyelitis can be challenging because of poor antibiotic penetration into the infected bone and toxicities associated with prolonged antibiotic regimens to control infection. Irreversible electroporation (IRE), a percutaneous image-guided ablation technology in which the targeted delivery of high-voltage electrical pulses permanently damages the cell membrane, has been shown to effectively control bacterial growth in various settings. However, IRE for the management of bone infections has yet to be evaluated.

Nicotinamide nucleotide transhydrogenase is required for brain mitochondrial redox balance under hampered energy substrate metabolism and high-fat diet.

Among mitochondrial NADP-reducing enzymes, nicotinamide nucleotide transhydrogenase (NNT) establishes an elevated matrix NADPH/NADP by catalyzing the reduction of NADP at the expense of NADH oxidation coupled to inward proton translocation across the inner mitochondrial membrane. Here, we characterize NNT activity and mitochondrial redox balance in the brain using a congenic mouse model carrying the mutated Nnt gene from the C57BL/6J strain. The absence of NNT activity resulted in lower total NADPH sources activity in the brain mitochondria of young mice, an effect that was partially compensated in aged mice.

Structure-Stability-Function Mechanistic Links in the Anti-Measles Virus Action of Tocopherol-Derivatized Peptide Nanoparticles.

Measles remains one of the leading causes of child mortality worldwide and is re-emerging in some countries due to poor vaccine coverage, concomitant with importation of measles virus (MV) from endemic areas. The lack of specific chemotherapy contributes to negative outcomes, especially in infants or immunodeficient individuals. Fusion inhibitor peptides derived from the MV Fusion protein C-terminal Heptad Repeat (HRC) targeting MV envelope fusion glycoproteins block infection at the stage of entry into host cells, thus preventing viral multiplication.

Mitochondrial calcium transport and the redox nature of the calcium-induced membrane permeability transition.

Mitochondria possess a Ca transport system composed of separate Ca influx and efflux pathways. Intramitochondrial Ca concentrations regulate oxidative phosphorylation, required for cell function and survival, and mitochondrial redox balance, that participates in a myriad of signaling and damaging pathways. The interaction between Ca accumulation and redox imbalance regulates opening and closing of a highly regulated inner membrane pore, the membrane permeability transition pore (PTP).

Effective in Vivo Targeting of Influenza Virus through a Cell-Penetrating/Fusion Inhibitor Tandem Peptide Anchored to the Plasma Membrane.

The impact of influenza virus infection is felt each year on a global scale when approximately 5-10% of adults and 20-30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs.

Fusion Inhibitory Lipopeptides Engineered for Prophylaxis of Nipah Virus in Primates.

Background: The emerging zoonotic paramyxovirus Nipah virus (NiV) causes severe respiratory and neurological disease in humans, with high fatality rates. Nipah virus can be transmitted via person-to-person contact, posing a high risk for epidemic outbreaks. However, a broadly applicable approach for human NiV outbreaks in field settings is lacking.

Facilitation of Ca -induced opening of the mitochondrial permeability transition pore either by nicotinamide nucleotide transhydrogenase deficiency or statins treatment.

Mitochondrial redox imbalance and high Ca uptake induce the opening of the permeability transition pore (PTP) that leads to disruption of energy-linked mitochondrial functions and triggers cell death in many disease states. In this review, we discuss the major results from our studies investigating the consequences of NAD(P)-transhydrogenase (NNT) deficiency, and of statins treatment for mitochondrial functions and susceptibility to Ca -induced PTP. We highlight the aggravation of high fat diet-induced fatty liver disease in the context of NNT deficiency and the role of antioxidants in the prevention of statins toxicity to mitochondria.

Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes.

The causative agent of malaria, Plasmodium, replicates inside a membrane-bound parasitophorous vacuole (PV), which shields this intracellular parasite from the cytosol of the host cell . One common threat for intracellular pathogens is the homeostatic process of autophagy, through which cells capture unwanted intracellular material for lysosomal degradation . During the liver stage of a malaria infection, Plasmodium parasites are targeted by the autophagy machinery of the host cell, and the PV membrane (PVM) becomes decorated with several autophagy markers, including LC3 (microtubule-associated protein 1 light chain 3) .