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The complex role of Wnt ligands in type 2 diabetes mellitus and related complications
Type 2 diabetes mellitus (T2DM) is one of the major chronic diseases, whose prevalence is increasing dramatically worldwide and can lead to a range of serious complications. Wnt ligands (Wnts) and their activating Wnt signalling pathways are closely involved in the regulation of various processes that are important for the occurrence and progression of T2DM and related complications. However, our understanding of their roles in these diseases is quite rudimentary due to the numerous family members of Wnts and conflicting effects via activating the canonical and/or non‐canonical Wnt signalling pathways. In this review, we summarize the current findings on the expression pattern and exact role of each human Wnt in T2DM and related complications, including Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt7a, Wnt7b, Wnt8a, Wnt8b, Wnt9a, Wnt9b, Wnt10a, Wnt10b, Wnt11 and Wnt16. Moreover, the role of main antagonists (sFRPs and WIF‐1) and coreceptor (LRP6) of Wnts in T2DM and related complications and main challenges in designing Wnt‐based therapeutic approaches for these diseases are discussed. We hope a deep understanding of the mechanistic links between Wnt signalling pathways and diabetic‐related diseases will ultimately result in a better management of these diseases.
Journal Article
Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches
Nuclear factor-κB (NF-κB) is a transcription factor that plays a crucial role in various biological processes, including immune response, inflammation, cell growth and survival, and development. NF-κB is critical for human health, and aberrant NF-κB activation contributes to development of various autoimmune, inflammatory and malignant disorders including rheumatoid arthritis, atherosclerosis, inflammatory bowel diseases, multiple sclerosis and malignant tumors. Thus, inhibiting NF-κB signaling has potential therapeutic applications in cancer and inflammatory diseases.
Journal Article
Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease
The Hh/GLI signaling pathway was originally discovered in Drosophila as a major regulator of segment patterning in development. This pathway consists of a series of ligands (Shh, Ihh, and Dhh), transmembrane receptors (Ptch1 and Ptch2), transcription factors (GLI1–3), and signaling regulators (SMO, HHIP, SUFU, PKA, CK1, GSK3β, etc.) that work in concert to repress (Ptch1, Ptch2, SUFU, PKA, CK1, GSK3β) or activate (Shh, Ihh, Dhh, SMO, GLI1–3) the signaling cascade. Not long after the initial discovery, dysregulation of the Hh/GLI signaling pathway was implicated in human disease. Activation of this signaling pathway is observed in many types of cancer, including basal cell carcinoma, medulloblastoma, colorectal, prostate, pancreatic, and many more. Most often, the activation of the Hh/GLI pathway in cancer occurs through a ligand-independent mechanism. However, in benign disease, this activation is mostly ligand-dependent. The upstream signaling component of the receptor complex, SMO, is bypassed, and the GLI family of transcription factors can be activated regardless of ligand binding. Additional mechanisms of pathway activation exist whereby the entirety of the downstream signaling pathway is bypassed, and PTCH1 promotes cell cycle progression and prevents caspase-mediated apoptosis. Throughout this review, we summarize each component of the signaling cascade, non-canonical modes of pathway activation, and the implications in human disease, including cancer.
Journal Article
The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.
Journal Article
A Robust and Accurate Indoor Localization Using Learning-Based Fusion of Wi-Fi RTT and RSSI
Great attention has been paid to indoor localization due to its wide range of associated applications and services. Fingerprinting and time-based localization techniques are among the most popular approaches in the field due to their promising performance. However, fingerprinting techniques usually suffer from signal fluctuations and interference, which yields unstable localization performance. On the other hand, the accuracy of time-based techniques is highly affected by multipath propagation errors and non-line-of-sight transmissions. To combat these challenges, this paper presents a hybrid deep-learning-based indoor localization system called RRLoc which fuses fingerprinting and time-based techniques with a view of combining their advantages. RRLoc leverages a novel approach for fusing received signal strength indication (RSSI) and round-trip time (RTT) measurements and extracting high-level features using deep canonical correlation analysis. The extracted features are then used in training a localization model for facilitating the location estimation process. Different modules are incorporated to improve the deep model’s generalization against overtraining and noise. The experimental results obtained at two different indoor environments show that RRLoc improves localization accuracy by at least 267% and 496% compared to the state-of-the-art fingerprinting and ranging-based-multilateration techniques, respectively.
Journal Article
A highlight on Sonic hedgehog pathway
Hedgehog (Hh) signaling pathway plays an essential role during vertebrate embryonic development and tumorigenesis. It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors. Most of the brain tumors are resistant to chemotherapeutic drugs, consequently, they have a poor prognosis. So, a better knowledge of the Shh pathway opens an opportunity for targeted therapies against brain tumors considering a multi-factorial molecular overview. Therefore, emerging studies are being conducted in order to find new inhibitors for Shh signaling pathway, which could be safely used in clinical trials. Shh can signal through a canonical and non-canonical way, and it also has important points of interaction with other pathways during brain tumorigenesis. So, a better knowledge of Shh signaling pathway opens an avenue of possibilities for the treatment of not only for brain tumors but also for other types of cancers. In this review, we will also highlight some clinical trials that use the Shh pathway as a target for treating brain cancer.
Journal Article
Enhanced Oscillation Criteria for Non-Canonical Second-Order Advanced Dynamic Equations on Time Scales
This study aims to establish novel iterative oscillation criteria for second-order half-linear advanced dynamic equations in non-canonical form. The results extend and enhance recently established criteria for this type of equation by various authors and also encompass the classical criteria for related ordinary differential equations. Our methodology involves transforming the non-canonical equation into its corresponding canonical form. The inherent symmetry of these canonical forms plays a pivotal role in deriving our new criteria. By employing techniques from the theory of symmetric differential equations and utilizing symmetric functions, we establish precise conditions for oscillation. Several illustrative examples highlight the accuracy, applicability, and versatility of our results.
Journal Article
Deep learning for early warning signals of tipping points
Many natural systems exhibit tipping points where slowly changing environmental conditions spark a sudden shift to a new and sometimes very different state. As the tipping point is approached, the dynamics of complex and varied systems simplify down to a limited number of possible “normal forms” that determine qualitative aspects of the new state that lies beyond the tipping point, such as whether it will oscillate or be stable. In several of those forms, indicators like increasing lag-1 autocorrelation and variance provide generic early warning signals (EWS) of the tipping point by detecting how dynamics slow down near the transition. But they do not predict the nature of the new state. Here we develop a deep learning algorithm that provides EWS in systems it was not explicitly trained on, by exploiting information about normal forms and scaling behavior of dynamics near tipping points that are common to many dynamical systems. The algorithm provides EWS in 268 empirical and model time series from ecology, thermoacoustics, climatology, and epidemiology with much greater sensitivity and specificity than generic EWS. It can also predict the normal form that characterizes the oncoming tipping point, thus providing qualitative information on certain aspects of the new state. Such approaches can help humans better prepare for, or avoid, undesirable state transitions. The algorithm also illustrates how a universe of possible models can be mined to recognize naturally occurring tipping points.
Journal Article
The windowed linear canonical Fourier-Jacobi transform and the related uncertainty principles
The main objective of this work is to introduce the windowed linear canonical Fourier-Jacobi transform and to study its properties. In particular, Parseval and inversion formulas are given and proved for this transform. Heisenberg uncertainty inequalities for the LCFJ-transform and the windowed LCFJ-transform are proved. The Donoho-Stark and Lieb uncertainty principles are also discussed and established for the proposed integral transform.
Journal Article