Mutant p53 affects the mitochondrial proteome, promoting mitochondrial fragmentation and OXPHOS in pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer marked by poor prognosis and frequent gain-of-function mutations in the TP53 tumor suppressor gene. Given the crucial role of mutant p53 in the context of metabolic reprogramming and aggressive tumor behavior, we explored its role on mitochondria, which may present a valuable therapeutic target. In this study, we characterized the unique mitochondrial proteome observed in PDAC cells harboring the gain-of-function TP53 mutation and discovered a strong mutant p53-dependent upregulation of myosin heavy chain 14 (MYH14), a nonmuscle myosin, implicated in mitochondrial dynamics.

Aging in the Skeletal Muscle Revealed by Molecular Immunohistochemical Imaging.

The skeletal muscle is a complex organ mainly composed of multinucleated fibres responsible for contractile activity, but it also contains postnatal myogenic stem cells (i.e., satellite cells), connective cells and nervous cells.

A Fluid Dynamic In Vitro System to Study the Effect of Hyaluronic Acid Administration on Collagen Organization in Human Skin Explants.

Hyaluronic acid (HA) is an unbranched polysaccharide particularly abundant in the extracellular matrix (ECM) of soft connective tissues. In humans, about 50% of the total HA in the organism is localized in the skin. HA plays an essential role in the hydration of the ECM, in the regulation of tissue homeostasis, in the resistance to mechanical stimuli/forces, and in the modulation of tissue regeneration.

Low ozone concentrations do not exert cytoprotective effects on tamoxifen-treated breast cancer cells .

Medical treatment with low ozone concentrations proved to exert therapeutic effects in various diseases by inducing a cytoprotective antioxidant response through the nuclear factor erythroid derived-like 2 (Nrf2) transcription factor pathway. Low ozone doses are increasingly administered to oncological patients as a complementary treatment to mitigate some adverse side-effects of antitumor treatments. However, a widespread concern exists about the possibility that the cytoprotective effect of Nrf2 activation may confer drug resistance to cancer cells or at least reduce the efficacy of antitumor agents.

Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging.

Aging is accompanied by a progressive loss of skeletal muscle mass and strength. The mechanisms underlying this phenomenon are certainly multifactorial and still remain to be fully elucidated. Changes in the cell nucleus structure and function have been considered among the possible contributing causes.

Modifications of Blood Molecular Components after Treatment with Low Ozone Concentrations.

The ex vivo treatment of a limited volume of blood with gaseous oxygen-ozone (O-O) mixtures and its rapid reinfusion into the patient is a widespread medical procedure. O instantly reacts with the blood's antioxidant systems, disappearing before reinfusion, although the molecules formed act as messengers in the organism, inducing multiple antioxidant and anti-inflammatory responses. An appropriate dose of O is obviously essential to ensure both safety and therapeutic efficacy, and in recent years, the low-dose O concept has led to a significant reduction in the administered O concentrations.

Aged gastrocnemius muscle of mice positively responds to a late onset adapted physical training.

A regular physical training is known to contribute to preserve muscle mass and strength, maintaining structure and function of neural and vascular compartments and preventing muscle insulin resistance and inflammation. However, physical activity is progressively reduced during aging causing mobility limitations and poor quality of life. Although physical exercise for rehabilitation purposes ( after fractures or cardiovascular events) or simply aiming to counteract the development of sarcopenia is frequently advised by physicians, nevertheless few data are available on the targets and the global effects on the muscle organ of adapted exercise especially if started at old age.

Ozone and procaine increase secretion of platelet-derived factors in platelet-rich plasma.

Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes.

Human Mutated and Genes Cause a Myopathic Phenotype in Zebrafish.

Myofibrillar myopathies (MFMs) are a group of hereditary neuromuscular disorders sharing common histological features, such as myofibrillar derangement, Z-disk disintegration, and the accumulation of degradation products into protein aggregates. They are caused by mutations in several genes that encode either structural proteins or molecular chaperones. Nevertheless, the mechanisms by which mutated genes result in protein aggregation are still unknown.

Physical Training Chronically Stimulates the Motor Neuron Cell Nucleus in the Ts65Dn Mouse, a Model of Down Syndrome.

Down syndrome (DS) is a genetically-based disease based on the trisomy of chromosome 21 (Hsa21). DS is characterized by intellectual disability in association with several pathological traits among which early aging and altered motor coordination are prominent. Physical training or passive exercise were found to be useful in counteracting motor impairment in DS subjects.

Mitochondrial Features of Mouse Myoblasts Are Finely Tuned by Low Doses of Ozone: The Evidence In Vitro.

The mild oxidative stress induced by low doses of gaseous ozone (O) activates the antioxidant cell response through the nuclear factor erythroid 2-related factor 2 (Nrf2), thus inducing beneficial effects without cell damage. Mitochondria are sensitive to mild oxidative stress and represent a susceptible O target. In this in vitro study, we investigated the mitochondrial response to low O doses in the immortalized, non-tumoral muscle C2C12 cells; a multimodal approach including fluorescence microscopy, transmission electron microscopy and biochemistry was used.

Cellular and Molecular Mechanisms of Ozone Therapy: Present Knowledge and Prospective Applications.

As a complementary, adjuvant or palliative cure, ozone therapy has increasingly been used globally on a wide variety of diseases [...

Slow Evolution toward "Super-Aggregation" of the Oligomers Formed through the Swapping of RNase A N-Termini: A Wish for Amyloidosis?

Natively monomeric RNase A can oligomerize upon lyophilization from 40% acetic acid solutions or when it is heated at high concentrations in various solvents. In this way, it produces many dimeric or oligomeric conformers through the three-dimensional domain swapping (3D-DS) mechanism involving both RNase A N- or/and C-termini. Here, we found many of these oligomers evolving toward not negligible amounts of large derivatives after being stored for up to 15 months at 4 °C in phosphate buffer.

Uranyl-Free Staining as a Suitable Contrasting Technique for Nuclear Structures at Transmission Electron Microscopy.

Uranyl acetate solution has widely been used as staining reagent for samples processed for ultrastructural morphology, cytochemistry, and immunocytochemistry. Although uranyl acetate guarantees high performance as a staining reagent, the radioactive uranyl salts make its use and purchase severely restricted. In this view, we used a non-radioactive lanthanide mix solution as contrasting dye for both nucleoplasmic and nucleolar ribonucleoprotein-containing components.

Ozone at low concentration modulates microglial activity in vitro: A multimodal microscopy and biomolecular study.

Oxygen-ozone (O -O ) therapy is an adjuvant/complementary treatment based on the activation of antioxidant and cytoprotective pathways driven by the nuclear factor erythroid 2-related factor 2 (Nrf2). Many drugs, including dimethyl fumarate (DMF), that are used to reduce inflammation in oxidative-stress-related neurodegenerative diseases, act through the Nrf2-pathway. The scope of the present investigation was to get a deeper insight into the mechanisms responsible for the beneficial result of O -O treatment in some neurodegenerative diseases.

Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem cells (CSCs). CSCs present a heterogeneous metabolic profile that might be supported by an adaptation of mitochondrial function; however, the role of this organelle in the development and maintenance of CSCs remains controversial.

Quantitative magnetic resonance characterization of the effect of physical training on skeletal muscle of the Ts65Dn mice, a model of Down syndrome.

Down syndrome (DS) is characterized by muscle hypotonia and low muscle strength associated with motor dysfunction. Elucidation of the determinants of muscle weakness in DS would be relevant for therapeutic approaches aimed at treating/mitigating a physical disability with a strong impact on the quality of life in persons with DS. The Ts65Dn mice is a recognized mouse model of DS, with trisomic mice presenting gross motor and muscle phenotypes.

Age-Related Changes in the Matrisome of the Mouse Skeletal Muscle.

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e.

A computational approach to quantitatively define sarcomere dimensions and arrangement in skeletal muscle.

Background And Objective: The skeletal muscle is composed of integrated tissues mainly composed of myofibers i.e., long, cylindrical syncytia, whose cytoplasm is mostly occupied by parallel myofibrils.

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro.

Oxygen-ozone (O-O) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines.

Ultrastructural immunocytochemistry shows impairment of RNA pathways in skeletal muscle nuclei of old mice: A link to sarcopenia?

During aging, skeletal muscle is affected by sarcopenia, a progressive decline in muscle mass, strength and endurance that leads to loss of function and disability. Cell nucleus dysfunction is a possible factor contributing to sarcopenia because aging-associated alterations in mRNA and rRNA transcription/maturation machinery have been shown in several cell types including muscle cells. In this study, the distribution and density of key molecular factors involved in RNA pathways namely, nuclear actin (a motor protein and regulator of RNA transcription), 5-methyl cytosine (an epigenetic regulator of gene transcription), and ribonuclease A (an RNA degrading enzyme) were compared in different nuclear compartments of late adult and old mice myonuclei by means of ultrastructural immunocytochemistry.

Nanoparticles exhibiting self-regulating temperature as innovative agents for Magnetic Fluid Hyperthermia.

During the last few years, for therapeutic purposes in oncology, considerable attention has been focused on a method called magnetic fluid hyperthermia (MFH) based on local heating of tumor cells. In this paper, an innovative, promising nanomaterial, M48 composed of iron oxide-based phases has been tested. M48 shows self-regulating temperature due to the observable second order magnetic phase transition from ferromagnetic to paramagnetic state.