-
Roberson Silverman posted an update 6 hours, 49 minutes ago
This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.RNA-binding proteins are frequently dysregulated in human cancer and able to modulate tumor cell proliferation as well as tumor metastasis through post-transcriptional regulation on target genes. Abnormal DNA damage response and repair mechanism are closely related to genome instability and cell transformation. Here, we explore the function of the RNA-binding protein muscleblind-like splicing regulator 2 (MBNL2) on tumor cell proliferation and DNA damage response. Transcriptome and gene expression analysis show that the PI3K/AKT pathway is enriched in MBNL2-depleted cells, and the expression of cyclin-dependent kinase inhibitor 1A (p21CDKN1A) is significantly affected after MBNL2 depletion. MBNL2 modulates the mRNA and protein levels of p21, which is independent of its canonical transcription factor p53. Moreover, depletion of MBNL2 increases the phosphorylation levels of checkpoint kinase 1 (Chk1) serine 345 (S345) and DNA damage response, and the effect of MBNL2 on DNA damage response is p21-dependent. MBNL2 would further alter tumor cell fate after DNA damage, MBNL2 knockdown inhibiting DNA damage repair and DNA damage-induced senescence, but promoting DNA damage-induced apoptosis.Immunotherapy of cancer with CD3-bispecific antibodies is an approved therapeutic option for some hematological malignancies and is under clinical investigation for solid cancers. However, the treatment of solid tumors faces more pronounced hurdles, such as increased on-target off-tumor toxicities, sparse T-cell infiltration and impaired T-cell quality due to the presence of an immunosuppressive tumor microenvironment, which affect the safety and limit efficacy of CD3-bispecific antibody therapy. In this review, we provide a brief status update of the CD3-bispecific antibody therapy field and identify intrinsic hurdles in solid cancers. Furthermore, we describe potential combinatorial approaches to overcome these challenges in order to generate selective and more effective responses.Blueberries are consumed as healthy fruits that provide a variety of benefits to the nervous system. Scientists have found that blueberries can be used as a daily edible source for supplementation to prevent and minimize complexities of age-related diseases as well as to improve learning and memory in children. Anthocyanins are the most mentioned compounds among the components in blueberries, as they play a major role in providing the health benefits of this fruit. However, while they are highly active in impeding biological impairment in neuronal functions, they have poor bioavailability. This review focuses on neurological investigations of blueberries from in vitro cell studies to in vivo studies, including animal and human studies, with respect to their positive outcomes of neuroprotection and intervention in neurodegenerative conditions. Readers will also find information on the bioavailability of anthocyanins and the considerable factors affecting them so that they can make informed decisions regarding the daily consumption of blueberries. read more In this context, the ways in which blueberries or blueberry supplementation forms are consumed and which of these forms is best for maximizing the health benefits of blueberries should be considered important decision-making factors in the consumption of blueberries; all of these aspects are covered in this review. Finally, we discuss recent technologies that have been employed to improve the bioavailability of blueberry anthocyanins in the development of effective delivery vehicles supporting brain health.This paper proposes a novel identity management framework for Internet of Things (IoT) and cloud computing-based personalized healthcare systems. The proposed framework uses multimodal encrypted biometric traits to perform authentication. It employs a combination of centralized and federated identity access techniques along with biometric based continuous authentication. The framework uses a fusion of electrocardiogram (ECG) and photoplethysmogram (PPG) signals when performing authentication. In addition to relying on the unique identification characteristics of the users’ biometric traits, the security of the framework is empowered by the use of Homomorphic Encryption (HE). The use of HE allows patients’ data to stay encrypted when being processed or analyzed in the cloud. Thus, providing not only a fast and reliable authentication mechanism, but also closing the door to many traditional security attacks. The framework’s performance was evaluated and validated using a machine learning (ML) model that tested the framework using a dataset of 25 users in seating positions. Compared to using just ECG or PPG signals, the results of using the proposed fused-based biometric framework showed that it was successful in identifying and authenticating all 25 users with 100% accuracy. Hence, offering some significant improvements to the overall security and privacy of personalized healthcare systems.Plants adapt to environmental changes by regulating their development and growth. As an important interface between plants and their environment, leaf morphogenesis varies between species, populations, or even shows plasticity within individuals. Leaf growth is dependent on many environmental factors, such as light, temperature, and submergence. Phytohormones play key functions in leaf development and can act as molecular regulatory elements in response to environmental signals. In this review, we discuss the current knowledge on the effects of different environmental factors and phytohormone pathways on morphological plasticity and intend to summarize the advances in leaf development. In addition, we detail the molecular mechanisms of heterophylly, the representative of leaf plasticity, providing novel insights into phytohormones and the environmental adaptation in plants.Wnt/β-catenin signaling controls many biological processes for the generation and sustainability of proper tissue size, organization and function during development and homeostasis. Consequently, mutations in the Wnt pathway components and modulators cause diseases, including genetic disorders and cancers. Targeted treatment of pathway-associated diseases entails detailed understanding of the regulatory mechanisms that fine-tune Wnt signaling. Here, we identify the neurotrophin receptor-associated death domain (Nradd), a homolog of p75 neurotrophin receptor (p75NTR), as a negative regulator of Wnt/β-catenin signaling in zebrafish embryos and in mammalian cells. Nradd significantly suppresses Wnt8-mediated patterning of the mesoderm and neuroectoderm during zebrafish gastrulation. Nradd is localized at the plasma membrane, physically interacts with the Wnt receptor complex and enhances apoptosis in cooperation with Wnt/β-catenin signaling. Our functional analyses indicate that the N-glycosylated N-terminus and the death domain-containing C-terminus regions are necessary for both the inhibition of Wnt signaling and apoptosis.