Breast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to ...that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1-HIFα pathway.
In this study, we develop a bio-based and bioactive nanofibrous patch based on bacterial cellulose (BC) and chitin nanofibrils (CNs) using an ionic liquid as a solvent for BC, aimed at tympanic ...membrane (TM) repair. Electrospun BC nanofiber meshes were produced via electrospinning, and surface-modified with CNs using electrospray. The rheology of the BC/ionic liquid system was investigated. The obtained CN/BC meshes underwent comprehensive morphological, physicochemical, and mechanical characterization. Cytotoxicity tests were conducted using L929 mouse fibroblasts, revealing a cell viability of 97.8%.
tests on rabbit skin demonstrated that the patches were nonirritating. Furthermore, the CN/BC fiber meshes were tested
using human dermal keratinocytes (HaCaT cells) and human umbilical vein endothelial cells as model cells for TM perforation healing. Both cell types demonstrated successful growth on these scaffolds. The presence of CNs resulted in improved indirect antimicrobial activity of the electrospun fiber meshes. HaCaT cells exhibited an upregulated mRNA expression at 6 and 24 h of key proinflammatory cytokines crucial for the wound healing process, indicating the potential benefits of CNs in the healing response. Overall, this study presents a natural and eco-sustainable fiber mesh with great promise for applications in TM repair, leveraging the synergistic effects of BC and CNs to possibly enhance tissue regeneration and healing. Impact statement Repair of tympanic membrane perforations following chronic otitis media is a main clinical issue in otologic surgery, where the underlying infection obstacles self-healing. To address this challenge, our study proposes a bio-based patch made of nanoscale carbohydrate materials (i.e., bacterial cellulose electrospun fibers and chitin nanofibrils) processed via green solvents. The scaffold is nonirritating
, and cytocompatible with fibroblasts, endothelial cells, and keratinocytes. In epithelial cells, it stimulates the expression of the antimicrobial peptide human beta defensin 2, with a pathway of cytokine expression compatible with the wound healing process. Therefore, it could be applied with unsolved infective pathology.
Converging evidence shows that hand-actions are controlled at the level of synergies and not single muscles. One intriguing aspect of synergy-based action-representation is that it may be ...intrinsically sparse and the same synergies can be shared across several distinct types of hand-actions. Here, adopting a normative angle, we consider three hypotheses for hand-action optimal-control: sparse-combination hypothesis (SC) - sparsity in the mapping between synergies and actions - i.e., actions implemented using a sparse combination of synergies; sparse-elements hypothesis (SE) - sparsity in synergy representation - i.e., the mapping between degrees-of-freedom (DoF) and synergies is sparse; double-sparsity hypothesis (DS) - a novel view combining both SC and SE - i.e., both the mapping between DoF and synergies and between synergies and actions are sparse, each action implementing a sparse combination of synergies (as in SC), each using a limited set of DoFs (as in SE). We evaluate these hypotheses using hand kinematic data from six human subjects performing nine different types of reach-to-grasp actions. Our results support DS, suggesting that the best action representation is based on a relatively large set of synergies, each involving a reduced number of degrees-of-freedom, and that distinct sets of synergies may be involved in distinct tasks.
Hydrothermal venting is rather prevalent in many marine areas around the world, and marine shallow vents are relatively abundant in the Mediterranean Sea, especially around Italy. However, ...investigations focusing on the characterization of meiofaunal organisms inhabiting shallow vent sediments are still scant compared to that on macrofauna. In the present study, we investigated the meiobenthic assemblages and nematode diversity inhabiting the Secca delle Fumose (SdF), a shallow water vent area located in the Gulf of Naples (Italy). In this area, characterized by a rapid change in the environmental conditions on a relative small spatial scale (i.e., 100 m), we selected four sampling sites: one diffusive emission site (H); one geyser site (G) and two inactive sites (CN, CS). Total meiofauna abundance did not vary significantly between active and inactive sites and between surface and deeper sediment layers due to a high inter-replicate variability, suggesting a pronounced spatial-scale patchiness in distribution of meiofauna. Nematofauna at site H presented the typical features of deep-sea vents with low structural and functional diversity, high biomass and dominance of few genera (i.e.,
Oncholaimus
;
Daptonema
) while from site G we reported diversity values comparable to that of the inactive sites. We hypothesized that site G presented a condition of “intermediate disturbance” that could maintain a high nematode diversity. Environmental features such as sediment temperature, pH, total organic carbon and interstitial waters ions were found to be key factors influencing patterns of meiofauna and nematofauna assemblages at SdF. Even though the general theory is that nematodes inhabiting shallow vent areas include a subset of species that live in background sediments, this was not the case for SdF vent area. Due to a marked change in nematode composition between all sites and to the presence of many exclusive species, every single investigated site was characterized by a distinct nematofauna reflecting the high spatial heterogeneity of SdF.
I have been thinking and writing Ipermodernità (Hypermodernity) for the past ten years; it took a long time to circumscribe and to define the object of my inquiry. It's not a militant book properly, ...but it contains the traces of the many discussions that stimulated me during the composition of this book.
The tuna fish processing industry produces more than 50% of waste and by-products (scales, head, viscera, etc.) that are usually discarded or used to produce low added value products such as fish ...meals. However, these waste materials still contain molecules essential for the human diet, such as essential metals, vitamins, omega-3 fatty acids, amino acids, and proteins of high nutritional value. The re-use of such wastes for the production of dietary supplements for human consumption would perfectly fit with the concept of Blue Economy, defined as the sustainable use of ocean resources for economic growth, improved livelihoods, and jobs while preserving the health of the ocean ecosystem. Moreover, waste product revenue will be a key factor in maintaining long-term profitability of industrial food processing. In this work, the yellowfin tuna (
Thunnus albacares
) was used as a model for fish processing by-products, as it is a large epipelagic species widely distributed in the tropical and subtropical waters of the major oceans. The determination of heavy metals and histamine is an essential control point for the re-utilization of the wastes. Then, they must be monitored in all the processes leading to the formulation of new high-quality products. Inductively coupled plasma–mass spectrometry and a fast gas chromatographic–mass spectrometry methods were validated and applied for the determination of metals and histamine and amino acids, respectively. In particular, both essential and heavy metals and histamine and amino acids were quantified in tuna fish by-products. The presence of essential metals and essential amino acids in the analyzed samples represents the strength point of the proposed model, which aims to valorize by-products and reduce the disposal of wastes.
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, ...but this relation is not yet fully elucidated. Pro‐inflammatory cytokines, such as IL‐33, OPN, IL‐17, and TNF‐α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL‐33, OPN, IL‐17, and TNF‐α induced the release of a wide range of pro‐osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts. The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely deplete osteoclast formation, suggesting that skin produced several additional pro‐osteoclastogenic mediators, which could act in a RANKL‐independent manner. Moreover, we have found that RANKL serum levels as well as osteoclast number and activity in psoriatic patients with and without arthritis, was influenced by severity of cutaneous disease. Our data demonstrate that psoriatic cutaneous inflammation contributes to bone damage.
We suggest the possibility of a “pro‐osteoclastogenic march” that starts from psoriatic plaque and reaches the bone: in this route, cutaneous pro‐osteclastogenic factors induce osteoclast differentiation, contributing to bone erosions. “We have highlighted a new mechanism through which psoriasis interrelates with psoriatic arthritis.”
Objectives
The aim of the present randomized clinical trial (RCT) with a parallel arm design was to evaluate the clinical and microbiological efficacy of repeated ICG-aPDT as an adjunct to full-mouth ...subgingival debridement in the treatment of periodontitis.
Materials and methods
Twenty-four periodontitis patients were treated with full-mouth ultrasonic subgingival debridement (FMUD). Initial sites with probing depth (PD) > 4 mm were randomly assigned to receive the test (ICG-aPDT with an 810 nm diode laser) or the control treatment (off-mode aPDT) one and four weeks after FMUD. Clinical parameters were registered after 3 and 6 months. The presence of the main periodontal pathogens in subgingival samples was assessed with real-time PCR.
Results
Both treatment modalities resulted in significant clinical improvements at 3 and 6 months. The only significant differences in favour of the test group were found at 6 months for a higher PD reduction in initial deep pockets (PD ≥ 6 mm) and a higher percentage of closed pockets (PD ≤ 4 mm/no bleeding on probing). Limited microbiological changes were observed in both groups after treatment with no inter-group difference, except for a more significant reduction in
Aggregatibacter actinomycetemcomitans
and
Parvimonas micra
levels in the test group at 3 months.
Conclusion
The combination of repeated ICG-aPDT and FMUD provided no benefits except for selective clinical and microbiological improvements compared to FMUD alone.
Clinical relevance
Based on the obtained results, only limited adjunctive effects could be found for the combined use of ICG-aPDT and FMUD. Further, well-designed RCT with larger sample sizes are required to confirm these findings.
Trial registration
ClinicalTrials.gov
NCT04671394.
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