Equisetum arvense standardized dried extract hinders age-related osteosarcopenia.

Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties. Thus, considering that a chronic low-grade inflammatory state predisposes to both osteoporosis and sarcopenia, we tested a standardized hydroalcoholic extract of EQ in in vitro models of muscle atrophy [C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ), excess glucocorticoids (dexamethasone), or the osteokine, receptor activator of nuclear factor kappa-B ligand (RANKL)] and osteoclastogenesis (RAW 264.7 cells treated with RANKL). We found that EQ counteracted myotube atrophy, blunting the activity of several pathways depending on the applied stimulus, and reduced osteoclast formation and activity. By in silico target fishing, IKKB-dependent nuclear factor kappa-B (NF-κB) inhibition emerges as a potential common mechanism underlying EQ's anti-atrophic effects. Consumption of EQ (500 mg/kg/day) by pre-geriatric C57BL/6 mice for 3 months translated into: i) maintenance of muscle mass and performance; ii) restrained myofiber oxidative shift; iii) slowed down age-related modifications in osteoporotic bone, significantly preserving trabecular connectivity density; iv) reduced muscle- and spleen-related inflammation. EQ can preserve muscle functionality and bone remodeling during aging, potentially valuable as a natural treatment for osteosarcopenia.

Clonal dynamics and copy number variants by single-cell analysis in leukemic evolution of myeloproliferative neoplasms.

Transformation from chronic (CP) to blast phase (BP) in myeloproliferative neoplasm (MPN) remains poorly characterized, and no specific mutation pattern has been highlighted. BP-MPN represents an unmet need, due to its refractoriness to treatment and dismal outcome. Taking advantage of the granularity provided by single-cell sequencing (SCS), we analyzed paired samples of CP and BP in 10 patients to map clonal trajectories and interrogate target copy number variants (CNVs). Already at diagnosis, MPN present as oligoclonal diseases with varying ratio of mutated and wild-type cells, including cases where normal hematopoiesis was entirely surmised by mutated clones. BP originated from increasing clonal complexity, either on top or independent of a driver mutation, through acquisition of novel mutations as well as accumulation of clones harboring multiple mutations, that were detected at CP by SCS but were missed by bulk sequencing. There were progressive copy-number imbalances from CP to BP, that configured distinct clonal profiles and identified recurrences in genes including NF1, TET2, and BCOR, suggesting an additional level of complexity and contribution to leukemic transformation. EZH2 emerged as the gene most frequently affected by single nucleotide and CNVs, that might result in EZH2/PRC2-mediated transcriptional deregulation, as supported by combined scATAC-seq and snRNA-seq analysis of the leukemic clone in a representative case. Overall, findings provided insights into the pathogenesis of MPN-BP, identified CNVs as a hitherto poorly characterized mechanism and point to EZH2 dysregulation as target. Serial assessment of clonal dynamics might potentially allow early detection of impending disease transformation, with therapeutic implications.

Efficacy and safety of a new peeling formulated with a pool of PHAs for the treatment of all skin types, even sensitive.

BACKGROUND: Actually, the use of chemical peels in cosmetics and dermatology continues to grow due to their versatility, clinical endpoint-directed predictability, and favorable risk profile in comparison to lasers. The chemical peel is a generally safe method for treatment of some skin disorders and to refresh and rejuvenate the skin. The major challenge of chemical peels is the tolerability, that is because of sensitive skin which is one of the most common skin disorders. AIM: The aim of this study was to evaluate the effectiveness of the new Miamo Renewal Peel Serum formulated with a pool of new generation acids (ELPA25™) on sensitive skin with respect to mandelic acid serum only and with respect to placebo comparison. MATERIALS AND METHODS: The "in vivo" study following the half-face experimental protocol active versus placebo involved 30 healthy Caucasian female volunteers between 25 and 64 years, with sensitive skin, who were divided into two different groups. ELPA25™ serum was applied in one group three times a week for 8 weeks. The other group, with the same protocol, applied an active serum containing mandelic acid, as control, versus placebo. In particular, skin moisturizing, skin viscoelastic properties, skin surface smoothness, wrinkle reduction, and stratum corneum renewal were evaluated. RESULTS: Renewal Peel Serum was very well tolerated from sensitive skin. A significant decrease in skin roughness and wrinkle breadth, and an improvement in firmness and in skin elasticity, was observed after 2 months of treatment with respect both to mandelic acid serum and to placebo comparison. CONCLUSIONS: Scientific protocol using self-controlled study methodology and noninvasive skin bioengineering techniques with adequate statistical methods were able to evaluate both the safety and the efficacy of the new Miamo Renewal Peel Serum. This study highlighted that the Miamo Renewal Peel Serum formulated with a patent-pending mixture of new generation acids (ELPA25™) exerts many beneficial effects and it can be successfully employed for sensitive skin.

KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK.

The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized Withania somnifera, Silybum marianum and Trigonella foenum-graecum herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. Withania somnifera appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or Withania somnifera-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.

Impact of capped and uncapped abandoned leads on the heating of an MR-conditional pacemaker implant.

PURPOSE: To assess the risk of radiofrequency (RF)-induced heating in patients with MR-conditional pacemaker (PM) systems, in the presence of another lead abandoned from a previous implant. METHODS: Four commercial pacemaker leads were placed beside a MR-conditional PM system, inside a human trunk simulator. The phantom has been exposed to the RF generated by a 64 MHz body bird-cage coil (whole-body specific absorption rate [SAR] = 1 W/kg) and the induced heating was measured at the tip of the abandoned lead and of the MR-conditional implant. Configurations that maximize the coupling between the RF field and the leads have been tested, as well as realistic implant positions. RESULTS: Abandoned leads showed heating behaviors that strongly depend on the termination condition (abandoned-capped or saline exposed) and on the lead path (left or right positioning). Given a whole-body SAR = 1 W/kg, a maximum temperature rise of 17.6°C was observed. The presence of the abandoned lead modifies the RF-heating profile of the MR-conditional implant: either an increase or a decrease in the induced heating at its lead tip can occur, mainly depending on the relative position of the two leads. Variations ranging from -63% to +69% with respect to the MR-conditional system alone were observed. CONCLUSION: These findings provide experimental evidence that the presence of an abandoned lead poses an additional risk for the patient implanted with a MR-conditional PM system. Our results support the current PM manufacturers' policy of conditioning the MR compatibility of their systems to the absence of abandoned leads (including leads from MR-conditional implants). From a clinical point of view, in such cases, the decision whether to perform the exam shall be based upon a risk/benefit evaluation, as in the case of conventional PM systems.