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Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients. [ABSTRACT FROM AUTHOR]

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches. [ABSTRACT FROM AUTHOR]

Background: The aim of the present paper is to construct an emulator of a complex biological system simulator using a machine learning approach. More specifically, the simulator is a patient-specific model that integrates metabolic, nutritional, and lifestyle data to predict the metabolic and inflammatory processes underlying the development of type-2 diabetes in absence of familiarity. Given the very high incidence of type-2 diabetes, the implementation of this predictive model on mobile devices could provide a useful instrument to assess the risk of the disease for aware individuals. The high computational cost of the developed model, being a mixture of agent-based and ordinary differential equations and providing a dynamic multivariate output, makes the simulator executable only on powerful workstations but not on mobile devices. Hence the need to implement an emulator with a reduced computational cost that can be executed on mobile devices to provide real-time self-monitoring. Results: Similarly to our previous work, we propose an emulator based on a machine learning algorithm but here we consider a different approach which turn out to have better performances, indeed in terms of root mean square error we have an improvement of two order magnitude. We tested the proposed emulator on samples containing different number of simulated trajectories, and it turned out that the fitted trajectories are able to predict with high accuracy the entire dynamics of the simulator output variables. We apply the emulator to control the level of inflammation while leveraging on the nutritional input. Conclusion: The proposed emulator can be implemented and executed on mobile health devices to perform quick-and-easy self-monitoring assessments. [ABSTRACT FROM AUTHOR]

Background: The aim of a recent research project was the investigation of the mechanisms involved in the onset of type 2 diabetes in the absence of familiarity. This has led to the development of a computational model that recapitulates the aetiology of the disease and simulates the immunological and metabolic alterations linked to type-2 diabetes subjected to clinical, physiological, and behavioural features of prototypical human individuals. Results: We analysed the time course of 46,170 virtual subjects, experiencing different lifestyle conditions. We then set up a statistical model able to recapitulate the simulated outcomes. Conclusions: The resulting machine learning model adequately predicts the synthetic dataset and can, therefore, be used as a computationally-cheaper version of the detailed mathematical model, ready to be implemented on mobile devices to allow self-assessment by informed and aware individuals. The computational model used to generate the dataset of this work is available as a web-service at the following address: http://kraken.iac.rm.cnr.it/T2DM. [ABSTRACT FROM AUTHOR]

Background: Screening programmes for cervical cancer, breast cancer and colorectal cancer have been implemented in many Western countries to reduce cancer incidence and mortality. Ethnic minority women are less likely to participate in cancer screening than the majority population. In worst case this can result in higher incidence rates, later diagnosis and treatment and ultimately inferior survival. In this paper we explored the perceptions about cancer and perceived barriers towards cancer screening participation among ethnic minority women in a deprived area in Denmark.Methods: Interview study with ethnic minority women in a deprived area in Denmark. The interviews were transcribed verbatim followed by an inductive content analysis.Results: Cancer was perceived as a deadly disease that could not be treated. Cancer screening was perceived as only relevant if the women had symptoms. Knowledge about cancer screening was fragmented, often due to inadequate Danish language skills and there was a general mistrust in the Danish healthcare system due to perceived low medical competences in Danish doctors. There was, however, a very positive and curious attitude regarding information about the Danish cancer screening programmes and a want for more information.Conclusion: Ethnic minority women did not have sufficient knowledge about cancer and the purpose of cancer screening. Perceptions about cancer screening were characterised by openness and the study showed positive and curious attitudes towards screening participation. The findings emphasise the importance of culturally adapted interventions for ethnic minority women in attempts to reduce inequality in screening participation. [ABSTRACT FROM AUTHOR]

Background: Glycosaminoglycans (GAGs), including hyaluronic acid (HA), dermatan sulfate (DS) and chondroitin sulfate (CS) are essential components of the bone and cartilage tissues. CS isolated from the cartilage tissue of various animals has found application in pharmaceuticals, cosmetics and food industries. In the first part of the present work, three methods were used and compared to extract and purify glycosaminoglycans (GAGs) from the cartilage powder of a local cartilaginous marine species «Scyliorhinus canicula». One of these GAGs, chondroitin sulfate (CS), will be exploited for the development of an anti-osteoarthritis generic at the request of a collaborative pharmaceutical industry. Thus this active ingredient must meet the requirements and tests described by the European Pharmacopoeia (Ph. Eur.). These tests are treated in the second part of this work. Results: Among the three methods that have been applied in the present work, in order to optimize the best process for GAGs preparation, enzymatic hydrolysis with papain followed by deproteinisation using trichloroacetic acid (TCA) was found the best one. The separation of the extracted GAGs using agarose gel electrophoresis, and the identification of bands by Fourier Transform Infrared (FT-IR) Spectroscopy, revealed that the cartilage GAGs of « Scyliorhinus canicula» are exclusively chondroitin sulfate (CS) and dermatane sulfate (DS), with proportions of 12.889 and 87.111% respectively, and that CS is of type C. The extraction technique with papain provides a product with GAGs content of around 90%. The TCA deproteinisation yielded the lowest level of protein (2.8%) in the extracted GAGs, less than 3%, which is the standard required by the European Pharmacopoeia (Ph. Eur.). Cetylpyridinium chloride (CPC) assay suggests that the titration technique, although is introduced by the Ph. Eur. for the determination of CS content, is not an accurate method, and that the values obtained by the optimized and validated HPLC method, described in this work, are more exact. Conclusion: The extracted and purified active ingredient is perfectly conform to the tests described by the Ph. Eur. The results suggest that the co-product of Scyliorhinus canicula would be a perfect source of molecules of pharmacological interest, obtained by a simple and non-agressive process. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant CRT may lead to significant tumor regression in patients with rectal cancer. Different CRT regimens with consolidation chemotherapy may lead to increased rates of complete tumor regression. The purpose of this study was to understand tumor metabolic activity following two different neoadjuvant CRT regimens using sequential PET/CT imaging in two different intervals following RT.Methods: Patients with cT2-4 N0-2 M0 rectal cancer treated by standard CRT (54Gy and 2 cycles of 5FU-based chemotherapy) or extended CRT (54Gy and 6 cycles of 5FU-based chemotherapy) underwent sequential PET/CT imaging at baseline, 6 weeks and 12 weeks from radiation completion.Results: 99 patients undergoing standard CRT were compared to 12 patients undergoing CRT with consolidation chemotherapy. Patients treated with consolidation CRT had increased rates of complete clinical or pathological response (66 % vs. 23 %; p < 0.001). SUVmax variation between baseline and 6 weeks (88 % vs. 63 %; p < 0.001) and between baseline and 12 weeks (90 % vs. 57 %; p < 0.001) were significantly more pronounced among patients undergoing extended CRT with consolidation chemotherapy. An increase in SUVmax between 6 and 12 weeks was observed in 51 % of patients undergoing standard and 18 % of patients undergoing consolidation CRT (p = 0.04).Conclusions: Most of the reduction in tumor metabolism after neoadjuvant CRT occurs within the first 6 weeks from RT completion. In patients undergoing CRT with consolidation chemotherapy, tumors are less likely to regain metabolic activity between 6 and 12 weeks. Therefore, assessment of tumor response may be safely postponed to 12 weeks in patients undergoing extended CRT with consolidation chemotherapy.Trial Registration: NCT00254683. [ABSTRACT FROM AUTHOR]