Reviews & Analysis

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  • Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with no curative therapy. Liquid-liquid phase separation (LLPS) is a biophysical phenomenon in which a homogeneous mixture of solutions separates into two phases. Recently LLPS has gained attention in ALS research because many ALS-causing proteins undergo LLPS, which eventually contribute to protein aggregates. This review summarizes the molecular mechanisms underlying the LLPS of ALS-causing proteins and discusses strategies to develop therapeutics targeting LLPS.

    • Kohsuke Kanekura
    • Masahiko Kuroda
    Review Article
  • Pleomorphic xanthoastrocytomas (PXAs) are rare tumors having a heterogenous morphology and biological behavior. Recent genomic advances have discovered BRAFp.V600E mutations, CDKN2A/B deletions and TERTp mutations to be the most frequent alterations in PXAs. These tumors can present a diagnostic challenge as they share overlapping histopathological, genomic as well as methylation profile with various other tumor types. This review provides the spectrum of evolution of PXAs from their genesis to recent molecular insights and attempts to review pathogenesis and relationship to other tumors that they mimic.

    • Swati Mahajan
    • Iman Dandapath
    • Chitra Sarkar
    Review Article
  • Recent progress on the biological functions of exosome-derived noncoding RNAs (exo-ncRNAs) in liver diseases is discussed in this review. Exo-ncRNAs are involved in the initiation and progression of liver diseases by regulating hepatic lipid metabolism, internal immunity, viral infection, fibrosis, biliary atresia and cancer. Exo-ncRNAs have clinical implications as promising biomarkers and therapeutic targets, especially for non-invasive diagnosis.

    • Zhe Wen Zhou
    • Wei Zheng
    • Ke Yang Xu
    Review Article
  • Neuroendocrine prostate cancer (NEPC) is an aggressive prostate cancer (PCa) variant. The exact mechanism underlying PCa development remains unclear due to the limited availability of NEPC models. In this review, the authors summarize strategies for NEPC model development and methods for model evaluation; discuss the origin of NEPC and the neuroendocrine transformation mechanism; and propose the challenges associated with research on NEPC. This study provides valuable insights into NEPC development and reveals potential therapeutic targets for NEPC.

    • Xue Shui
    • Rong Xu
    • Changhong Shi
    Review Article
  • Cell-free DNA (cfDNA) profiling as liquid biopsy is of clinical utility in carcinomas of adult-onset. However, its application in childhood cancers, including brain tumors, has not been as extensively studied. In this article, we review the current status of applying cfDNA analysis for pediatric central nervous system neoplasms. Technical challenges, evidence for utility based on current literature, and potential future developments are discussed.

    • Anthony Pak-Yin Liu
    • Paul A. Northcott
    • Amar Gajjar
    Review Article
  • Vitamin D has recently emerged as a neurosteroid and a regulator of various physiological functions. It has been widely reported to promote tumor-suppressive effects, however this proposal remains controversial. This article reviews the anti-tumoral mechanisms of vitamin D in glioblastoma, current evidence of its therapeutic application as a supplement to standard chemotherapy, and its potential applications for cancer prevention; it endeavors to offer insight into new means of overcoming chemoresistance and improving glioma patient survival.

    • Carmen Sze-Ching Lo
    • Karrie Mei-Yee Kiang
    • Gilberto Ka-Kit Leung
    Review Article
  • The 5th edition of WHO Classification of Tumors of the Central Nervous System adopted new molecular markers into the revised grading criteria of IDH-mutant and -wild-type astrocytoma, i.e., the CDKN2A/B homozygous deletion for IDH-mutant astrocytoma and the following three criteria for IDH-wild-type astrocytoma: the concurrent gain of whole chromosome 7 and loss of whole chromosome 10, TERT promoter mutations, and EGFR amplification, as independent molecular markers of the highest grade.

    • Takashi Komori
    Review Article
  • During the COVID-19 pandemics, sensitive and reliable assays for SARS-CoV-2 detection are essential for screening the population, identifying asymptomatic individuals, making diagnoses, monitoring treatment responses, and determining viral clearance. This review summarizes the principles, advantages, disadvantages, and specific applications of currently available assays for detection of the viral nucleotide, genome or proteins, as well as host antibody responses, and provide overall guidelines for selection of optimal assays for specific usage.

    • Yuan Zhou
    • Li Zhang
    • Jian Wu
    Review Article
  • Data processing and learning has become a spearhead for the advancement of medicine. Computational pathology is burgeoning subspecialty that promises a better-integrated solution to whole-slide images, multi-omics data and clinical informatics as innovative approach for patient care. This review describes clinical perspectives and discusses the statistical methods, clinical applications, potential obstacles, and future directions of computational pathology.

    • Miao Cui
    • David Y. Zhang
    Review Article
  • Disorders involving injury to tissue stem cells may show unusually devastating clinical consequences. In acute graft-versus-host disease (aGVHD) relatively few cytotoxic immune cells target skin stem cells to produce significant morbidity and mortality. By analogy, SARS-CoV-2 initially homes to pulmonary stem cells that preferentially express the ACE2 receptor, thus potentially incurring similarly robust pathological consequences. As with aGVHD, lung stem cell targeting is a potential co-factor in explaining age-related severity of COVID-19 infection.

    • George F. Murphy
    Mini Review
  • Tandem mass spectrometry can reveal metabolite positional labeling and improve the performance of metabolic flux analysis as long as daughter ions are carefully inspected. When calculating the fluxes, the tandem mass isotopomer distributions as well as the mass isotopomer distributions of parent and daughter ions should all be used to constrain the fluxes in order to achieve the best performance.

    • Yujue Wang
    • Sheng Hui
    • Xiaoyang Su
    Mini Review
  • This mini-review summarizes the role of βcysteine 93 in oxidative stability of hemoglobin in human blood. βCys93 has been recognized as an end point for radicals originating from heme during oxidative stress and therefore it may be an important biological marker of oxidative stability of hemoglobin within red blood cells intended for transfusion or in hemoglobinopathies.

    • Abdu I. Alayash
    Mini Review
  • The authors review the data which describe how the deletion of TRPV4 evokes abnormal behavior in mice. These studies demonstrate that the maintenance of body temperature and the sensory system for detecting body temperature, such as via TRPV4, are critical components for normal cellular function.

    • Koji Shibasaki
    Review Article
  • Transient receptor potential vanilloid 2 (TRPV2) plays a significant role in the onset and progression of heart failure. In this review, the authors summarize the recent findings on TRPV2 in cardiomyocytes and immune cells involved in the development of heart failure and discuss the current progress of drug development that is aimed at treating heart failure through targeting TRPV2.

    • Yuko Iwata
    • Shin Ito
    • Masafumi Kitakaze
    Review Article
  • Transient receptor potential cation channel subfamily V (TRPV) can be overexpressed in breast cancer. TRPV channels play important roles in breast cancer cell proliferation, migration, and cell death as well as the tumor microenvironment and cancer-associated pain. This review provides an overview of TRPV channels in the context of breast cancer.

    • Choon Leng So
    • Michael J. G. Milevskiy
    • Gregory R. Monteith
    Review Article
  • Transient receptor ion channels have emerged as critical channels/receptors in numerous physiological and pathological conditions. In this paper the authors discuss our current understanding of the role of macrophage transient receptor potential channel subfamily V member 4 (TRPV4) in various inflammatory conditions.

    • Bidisha Dutta
    • Rakesh K. Arya
    • Shaik O. Rahaman
    Review Article
  • More than 40 different neurological diseases are caused by microsatellite repeat expansions. Repeat-associated non-AUG (RAN) proteins are translated from different types of nucleotide repeat expansions. The authors review the pathological and molecular aspects of RAN protein accumulation for each RAN translation disorder, the correlation between disease pathology, the available in vivo models and the common features shared by some of the newly discovered RAN proteins.

    • Monica Banez-Coronel
    • Laura P. W. Ranum
    Review Article
  • Increasing lines of evidence have shown beneficial effects of physical exercise against or delay neurodegeneration. However, the mechanisms of their beneficial effects are confusing because it involves the connection between the brain and muscles. This review summarizes these findings and discusses the differential and common effects of aerobic versus resistance exercises.

    • Yan Liu
    • Tim Yan
    • Raymond Chuen-Chung Chang
    Review Article