SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways

SMYD3 is a member of the SMYD lysine methylase family and plays an important role in the methylation of various histone and non-histone targets. Aberrant SMYD3 expression contributes to carcinogenesis and SMYD3 upregulation was proposed as a prognostic marker in various solid cancers. Here we summarize SMYD3-mediated regulatory mechanisms, which are implicated in the pathophysiology of cancer, as drivers of distinct oncogenic pathways. We describe SMYD3-dependent mechanisms affecting cancer progression, highlighting SMYD3 interplay with proteins and RNAs involved in the regulation of cancer cell proliferation, migration and invasion. We also address the effectiveness and mechanisms of action for the currently available SMYD3 inhibitors. The findings analyzed herein demonstrate that a complex network of SMYD3-mediated cytoplasmic and nuclear interactions promote oncogenesis across different cancer types. These evidences depict SMYD3 as a modulator of the transcriptional response and of key signaling pathways, orchestrating multiple oncogenic inputs and ultimately, promoting transcriptional reprogramming and tumor transformation. Further insights into the oncogenic role of SMYD3 and its targeting of different synergistic oncogenic signals may be beneficial for effective cancer treatment

Consensus on the use of the fixed combination calcipotriol/betamethasone dipropionate in the treatment of plaque psoriasis.

Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination a

An IoT Measurement System Based on LoRaWAN for Additive Manufacturing

The Industrial Internet of Things (IIoT) paradigm represents a significant leap forward for sensor networks, potentially enabling wide-area and innovative measurement systems. In this scenario, smart sensors might be equipped with novel low-power and long range communication technologies to realize a so-called low-power wide-area network (LPWAN). One of the most popular representative cases is the LoRaWAN (Long Range WAN) network, where nodes are based on the widespread LoRa physical layer, generally optimized to minimize energy consumption, while guaranteeing long-range coverage and low-cost deployment. Additive manufacturing is a further pillar of the IIoT paradigm, and advanced measurement capabilities may be required to monitor significant parameters during the production of artifacts, as well as to evaluate environmental indicators in the deployment site. To this end, this study addresses some specific LoRa-based smart sensors embedded within artifacts during the early stage of the production phase, as well as their behavior once they have been deployed in the final location. An experimental evaluation was carried out considering two different LoRa end-nodes, namely, the Microchip RN2483 LoRa Mote and the Tinovi PM-IO-5-SM LoRaWAN IO Module. The final goal of this research was to assess the effectiveness of the LoRa-based sensor network design, both in terms of suitability for the aforementioned application and, specifically, in terms of energy consumption and long-range operation capabilities. Energy optimization, battery life prediction, and connectivity range evaluation are key aspects in this application context, since, once the sensors are embedded into artifacts, they will no longer be accessible

P-440 Impact of electrospun scaffold topology on the performance of in-vitro Folliculogenesis applied to preantral ovine follicles

Study question How to improve in-vitro Folliculogenesis (ivF) protocols to address the enlarged demand of fertility preservation? Summary answer Tissue engineering-based approach opens new frontiers for ivF improving 3D-technologies addressed to support immature-ovarian-follicle-growth to obtain an increased number of competent oocytes enrolled in Assisted-Reproductive-Technology. What is known already ivF is a promising Assisted-Reproductive-Technology (ART) for preserving and restoring fertility. This technology potentially reproduces the early stages of folliculogenesis and oogenesis in-vitro allowing to move a large amount of oocyte on individual basis towards the validated protocol of in-vitro maturation/in-vitro fertilization (IVM/IVF). The current availability of biocompatible-supporting materials offers the challenging opportunity to mimic the native organ stroma in order to better reproduce the 3D environmental conditions leading to synergic follicles-oocyte development in-vitro with the aim to improve the performance of ivF in translational large sized mammal models. Study design, size, duration The present research aimed to compare preantral (PA) follicles culture on two different typologies of scaffolds fabricated using PCL(poly(epsilon caprolactone)), respectively made with patterned and randomly aligned fibers (PCL-Patterned/PCL-Randomic) with a standardized-single-follicle scaffold-free-method (3D-oil), widely validated on ovine model (Cecconi et al., 2004). The culture outcomes are compared analyzing follicle/oocyte growth, percentage of antrum differentiation and the incidence of meiotic competence, by exposing ivF growing oocytes to IVM protocol. Participants/materials, setting, methods PA follicles (mean size diameter: 250±4μm), mechanically isolated from slaughterhoused lamb ovaries, were individually cultured on electrospun PCL scaffolds (patterned vs randomic) or using the 3D-oil method. ivF were cultured alphaMEM-Fetal Bovine Serum free medium (5% Knockout Serum Replacement) supplemented with 4 IU/mL of equine Chorionic Gonadotropin (Di Berardino et al., 2021). At the end of ivF (14-days) the fully-grown oocytes isolated from early-antral follicles were tested on IVM. Main results and the role of chance PCL-Patterned electrospun scaffolds were able to strongly support a synergic oocyte and follicular growth. The 3D culture on Patterned electrospun scaffold supported the highest viability of follicles (87.5% vs 63% under 3D-oil conditions). On the contrary, the highest incidence of degenerated follicles was observed in cultures performed using PCL-Randomic materials (55 vs 37% vs 12.5% for PCL-Randomic vs 3D-oil vs PCL-Patterned, respectively; p <0.0004). The greatest follicle diameter increment (74.7±1 vs 70±0.4 vs 60.9±2%, for PCL-Patterned vs 3D-oil vs PCL-Randomic, respectively p <0.0007) and rate of antrum differentiation (87.5% vs 45% and vs 63%, for PCL-Patterned vs 3D-oil vs PCL-Randomic, for both p <0.0001) were observed in PA ovine follicles cultured on PCL-Patterned scaffolds. Furthermore, PCL-Patterned electrospun scaffolds supported a complete functional development of the oocyte compartment. More in detail, the majority of fully grown oocytes isolated from early- antral follicles grown on PCL-Patterned materials reached the metaphase-II stage (MII 80%) at the end of IVM in comparison to the significant lower percentage in 3D-oil (MII 68%, p =0.04) and PCL-Randomic (MII 18%, p <0.0001) protocols, respectively. Limitations, reasons for caution - Wider implications of the findings Tissue engineering scaffold-based approach represents a valid strategy generating a multi-organ in-vitro system, where different compartments may cooperate generating the complexity of paracrine-mechanism controlling early-follicles outcomes. Scaffold topology is essential to control early-follicles development. Indeed, exclusively PCL-Patterned can preserve long-term follicle 3D-microarchitecture supporting in-vitro oogenesis up to a complete meiotic-competence-acquisition. Trial registration number not applicabl

Nanotechnology-Assisted Cell Tracking

The usefulness of nanoparticles (NPs) in the diagnostic and/or therapeutic sector is derived from their aptitude for navigating intra-and extracellular barriers successfully and to be spatiotemporally targeted. In this context, the optimization of NP delivery platforms is technologically related to the exploitation of the mechanisms involved in the NP–cell interaction. This review provides a detailed overview of the available technologies focusing on cell–NP interaction/detection by describing their applications in the fields of cancer and regenerative medicine. Specifically, a literature survey has been performed to analyze the key nanocarrier-impacting elements, such as NP typology and functionalization, the ability to tune cell interaction mechanisms under in vitro and in vivo conditions by framing, and at the same time, the imaging devices supporting NP delivery assessment, and consideration of their specificity and sensitivity. Although the large amount of literature information on the designs and applications of cell membrane-coated NPs has reached the extent at which it could be considered a mature branch of nanomedicine ready to be translated to the clinic, the technology applied to the biomimetic functionalization strategy of the design of NPs for directing cell labelling and intracellular retention appears less advanced. These approaches, if properly scaled up, will present diverse biomedical applications and make a positive impact on human health

quality of life assessment of patients with scalp dermatitis using the italian version of the scalpdex

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Targeted therapy against chemoresistant colorectal cancers: Inhibition of p38α modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FoxO3A

Chemoresistance is a major obstacle to effective therapy against colorectal cancer (CRC) and may lead to deadly consequences. The metabolism of CRC cells depends highly on the p38 MAPK pathway, whose involvement in maintaining a chemoresistant behavior is currently being investigated. Our previous studies revealed that p38a is the main p38 isoform in CRC cells. Here we show that p38a pharmacolog- ical inhibition combined with cisplatin administration decreases colony formation and viability of cancer cells and strongly increases Bax-dependent apoptotic cell death by activating the tumor suppressor pro- tein FoxO3A. Our results indicate that FoxO3A activation up-regulates transcription of its target genes (p21, PTEN, Bim and GADD45), which forces both chemosensitive and chemoresistant CRC cells to undergo apoptosis. Additionally, we found that FoxO3A is required for apoptotic cell death induction, as confirmed by RNA interference experiments. In animal models xenografted with chemoresistant HT29 cells, we further confirmed that the p38-targeted dual therapy strategy produced an increase in apoptosis in cancer tissue leading to tumor regression. Our study uncovers a major role for the p38- FoxO3A axis in chemoresistance, thereby suggesting a new therapeutic approach for CRC treatment; moreover, our results indicate that Bax status may be used as a predictive biomarker

Health-related quality of life in psoriasis: an analysis of Psocare project patients

Psoriasis is a common, chronic, immune-mediated skin disorder that may be complicated by psoriatic arthritis in up to one-third of patients. Psoriasis treatments are increasingly effective, yet more expensive, thus requiring rational decision-making on interventional priorities. The ability to perform cost-utility analyses is hindered by the lack of algorithms that allow the inference of utility measures, like QALY, from specific dermatological health-related qualityof- life (HR-QoL) measures (e.g. Dermatology Life Quality Index [DLQI]). This study aimed to assess whether psoriasisrelated HR-QoL data (DLQI) could be used to obtain utility measures for use in economic analyses

Health-related quality of life in psoriasis: an analysis of Psocare project patients

Psoriasis is a common, chronic, immune-mediated skin disorder that may be complicated by psoriatic arthritis in up to one-third of patients. Psoriasis treatments are increasingly effective, yet more expensive, thus requiring rational decision-making on interventional priorities. The ability to perform cost-utility analyses is hindered by the lack of algorithms that allow the inference of utility measures, like QALY, from specific dermatological health-related qualityof- life (HR-QoL) measures (e.g. Dermatology Life Quality Index [DLQI]). This study aimed to assess whether psoriasisrelated HR-QoL data (DLQI) could be used to obtain utility measures for use in economic analyses