DNMT3B in vitro knocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS

Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition

BACKGROUND: Rhabdomyosarcoma (RMS) is the most commonly diagnosed malignant soft tissue tumour in children and adolescents. Aberrant expression of Anaplastic Lymphoma Kinase (ALK) and MET gene has been implicated in the malignant progression of RMS, especially in the alveolar subtype. This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied. METHODS: RH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays. Multiple approaches, including flow cytometry, immunofluorescence, western blotting and siRNA-based knock-down, were used in order to investigate possible molecular mechanisms linked to crizotinib activity. RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival. Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2. Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively. The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells. Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential. CONCLUSIONS: These results provide a further insight into the molecular mechanisms affected by crizotinib in ARMS cells inferring that it could be a useful therapeutic tool in ARMS cancer treatment

Assessment on different tools used for Simulation of routing for Low power and lossy Networks(RPL)

RPL is the iIPv6 routing protocol for low-power and lossy networks, standardized by IETF in i2012 as iRFC6550. specifically, RPL is designed to be a simple and inter-operable networking protocol for resource-constrained devices in industrial, home, and urban environments intended to support the division of the internet of things with thousands of devices interconnected through multihop mesh networks. More than four years have passed science the standardization of RPL, and we believe that it iis time to examine and understand its current state. In this paper, we review the history of research efforts in RPL; what aspects have been (and have not been) iinves-litigated and evaluated, how they have been studied, what was (and was not) implemented, and what remains for future investigation. We reviewed over i97 [41] iRPL-related academic research papers published by major academic publishers and present a topic-oriented survey for these research efforts. Our survey shows that only 40.2% of the papers evaluate RPL through experiments using implementations ion real embedded devices, ContikiOS and TinyOS are ithe two most popular implementations i(92.3%), and iTelosB was ithe most frequently used hardware platform i(69%) ion testbeds that have average and median size of i49.4 and i30.5 inodes, respectively. furthermore, unfortunately, despite it being approximately four years since its initial standardization, we are yet to see wide adoption of RPL as part of real-world systems and applications. We present our observations on the reasons behind this and suggest directions ion which RPL should evolve. &nbsp

Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype, induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells

EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines

Survey on Mobile Social Cloud Computing (MSCC)

Due to enhancement in technology the use of mobile devices increases with time. Now mobile devices (mobiles, PDA, Laptops etc.) became an essential part of mankind’s life. With the ease of Internet the popularity of Social Networking Services (SNS) among people increases. With the sharp drops in the prices, the working of mobile devices including smart phones and laptops is rising steadily. So due to this, mobile devices are now used as a provider of computing resources and services instead of requester. For this concept of Cloud Computing (CC) is merged with the mobile computing and SNS which is known as MSCC. MSCC is technology of future and it enables users/consumers to access the services in a fast and efficient manner. MSCC is the integration of three different technologies 1) Mobile Computing 2) SNS 3) Cloud Computing. Here mobile devices are (those have moments) using SNS (Both as a provider or requester) in Cloud Computing (CC) environment. In such environment, a user through mobile devices canparticipate in a social network through relationships which are based on trust. Units of the identical or alike social network can share services or data of cloud with other users of that social network without any authentication by using their mobile device as they be members of the identical social network. Various techniques are revised and improved to achieve good performance in a cloud computing network environment. In this work, there is a detailed survey of existing social cloud and mobile cloud techniques and their application areas. The comparative survey tables can be used as a guideline to select a technique suitable for different applications at hand. This survey paper reports the results of a survey of Mobile Social Cloud Computing (MSCC) regarding the importance of security of MSCC. Here we compare the works of different researcher in the field of MSCC on the basis of some essential features like security algorithm used, Qos and Fault tolerant strategy used, ease of proposed algorithm, space complexity etc. Considering all the limitations of the existing social cloud and mobile cloud techniques, an adaptive MSCC framework of Fault tolerance for future research is proposed

Confounding variables affecting long term results of standard two screw cephalomedullary nail in intertrochanteric fractures of femur

Background: Inter trochanteric fractures of femur are common fractures in the elderly. The aim of the study was to assess the long-term functional outcome of patients treated with trochanteric fixation nail (TFN) for inter trochanteric femur fractures and to determine variables which affect the final outcome of surgery at the end of five years.Methods: The study was done at tertiary centre in central India with 152 patients who sustained intertrochanteric femur fracture. The patients were followed up at 6 weeks, 6 months, 1 year, 2 years and 5 years after the surgery. The assessment of pain, functional activity, walking ability and range of motion were assessed by Harris hip score at 6 months, 1 year, 2 years and 5 years.Results: The good/excellent outcome at the end of 5 years was found in 84% of cases. Patients with age less than 65 years and male patients had better outcome at the end of five years. Some of the complications encountered with this type of implant were z effect, delayed union, screw back-out/breakage, varus collapse which affected the final outcome.Conclusions: TFN is effective treatment technique for inter trochanteric fractures of femur worldwide. There are some complications which can occur with this type of implant in early post-operative period but still long-term follow-up of patients suggested that the fracture pattern, preoperative mobility status, timing of surgery, post op mobilization also plays a key role in determining functional outcome of patients

Evaluation of functional outcome of tibial plateau fractures managed by different surgical modalities

Background: Tibial plateau makes up one of the most important weight bearing surface. Its fractures are commonly faced entity encompassing a wide spectrum of injuries of variable fracture morphology. Due to in-crease in incidence of high velocity trauma and higher functional demands of patients, surgery is warranted in most of the cases. Although, there is advancement in fracture fixation methods, apt treatment of tibial plateau fractures still remains controversial.Methods: In our series, we analyzed the functional outcomes of 58 of surgically treated tibial plateau fractures. Fractures were classified with Schatzker’s classification. Various fixation modalities of fixation were employed. Functional outcome was evaluated with modified Rasmussen’s criteria.Results: Most of the patient’s belonged to younger age groups (58.62%) and males (79.31%) were predominately involved. Road traffic accidents were the most common etiological factor (70.69%). Schatzker types I (29.31%) and II (27.59%) were the most common observed fracture type. The majority of the patients had a complication free recovery (81.03%). Infection was reported in only one case (1.72%). Similarly, malunion was noticed in only in one case (1.72%). None of the patients had complications like nonunion or neurovascular damage. The functional outcome assessment according to Modified Rasmussen’s criteria at the end of 12 months showed the excellent functional outcome in 41 (70.68%), good in eight (13.79%), fair in five (10.34%) and poor in four (6.9%) patients.Conclusions: Surgical treatment of tibial plateau fractures is challenging, yet it helps in achieving excellent anatomical restoration and rigid fracture fixation enabling in the restoration of articular congruity and facilitation of early knee motion thus achieving optimal knee function

Tridosha Paradigm in Cancer pathogenesis: Integrating Ayurvedic Principles with Modern Oncology

Whole medical systems typically rely on foundational texts and constitute comprehensive frameworks of theory and practice that have developed alongside biomedicine.[1] Ayurveda, an ancient system of medicine, posits that health results from a balance of three fundamental energies, or Doshas: Vata, Pitta, and Kapha. Cancer remains a formidable challenge in modern medicine, characterized by uncontrolled cell growth and proliferation. While contemporary approaches focus on molecular and genetic mechanisms, traditional medical systems like Ayurveda offer holistic perspectives. In the human body, Doshas govern physiological and psychological functions, and their imbalance is considered pivotal in disease manifestation, including cancer. Ayurvedic principles emphasize personalized therapies aimed at restoring Dosha equilibrium through diet, lifestyle modifications, herbal remedies, and detoxification procedures. Integrating Ayurvedic insights with conventional cancer treatments holds promise for comprehensive patient care, potentially enhancing therapeutic outcomes and quality of life. The study aimed to establish the interface between cancer biology and Ayurvedic concepts, highlighting opportunities for synergistic approaches in combating this multifaceted disease. This paper explores the theoretical framework of Ayurveda and its potential implications for understanding the etiology, progression, and treatment of cancer (Arbuda). The three primary ancient texts are the Charaka Samhita, which focuses on the fundamental principles of Ayurveda and internal medicine,[2] the Sushruta Samhitas, which cover surgical techniques and medical concepts,[3] and the Ashtanga Hridaya, a condensed and poetic summary of the first two texts.[4] Drawing from both ancient wisdom and modern scientific insights, this review synthesizes existing research to elucidate the interplay between cancer and the concept of Tridosha