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Genes & Diseases 2024年第2期11卷 727-746页

作者： Anna Gajos-Michniewicz Malgorzata Czyz department of molecular biology of Cancer Medical University of LodzLodz 92-215Poland

Hepatocellular carcinoma(HCC)is a liver cancer,highly heterogeneous both at the histopathological and molecular levels.It arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways,including canonical WNT/β-catenin,AKT/mTOR,MAPK pathways as well as signaling associated with telomere maintenance,p53/cell cycle regulation,epigenetic modifiers,and oxidative stress.The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established,whereas in development and progression of HCC is extensively studied.Herein,we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development,acquisition of stemness features,metastasis,and resistance to treatment.We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC.We discuss the pivotal roles of CTNNB1 mutations,aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.

关键词： Cancer stem cells CTNNB1 mutations Liver cancer Non-coding RNA Tumor heterogeneity

OsPDR20 is an ABCG metal transporter regulating cadmium accumulation in rice

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Journal of Environmental Sciences 2024年第2期136卷 21-34页

作者： He Li Chao Li Di Sun Zhi Min Yang department of Biochemistry and molecular biology College of Life SciencesNanjing Agricultural UniversityNanjing 210095China

Cadmium(Cd)is a non-essential toxic heavy metal,seriously posing high environmental risks to human health.Digging genetic resources relevant to functional genes is important for understanding the metal absorption and accumulation in crops and bioremediation of Cd-polluted environments.This study investigated a functionally uncharacterized ATP binding cassette transporter G family(ABCG)gene encoding a Pleiotropic Drug Resistance 20(PDR20)type metal transporter which is localized to the plasma membrane of rice.OsPDR20 was transcriptionally expressed in almost all tissues and organs in lifespan and was strongly induced in roots and shoots of young rice under Cd stress.Ectopic expression of OsPDR20 in a yeast mutant ycf1 sensitive to Cd conferred cellular tolerance with less Cd accumulation.Knockdown of OsPDR20 by RNA interference(RNAi)moderately attenuated root/shoot elongation and biomass,with reduced chlorophylls in rice grown under hydroponic medium with 2 and 10μmol/L Cd,but led to more Cd accumulation.A field trial of rice grown in a realistic Cd-contaminated soil(0.40 mg/kg)showed that RNAi plants growth and development were also compromised compared to wild-type(WT),with smaller panicles and lower spikelet fertility but little effect on yield of grains.However,OsPDR20 suppression resulted in unexpectedly higher levels of Cd accumulation in rice straw including lower leaves and culm and grain.These results suggest that OsPDR20 is actively involved in Cd accumulation and homeostasis in rice crops.The increased Cd accumulation in the RNAi plants has the potential application in phytoremediation of Cd-polluted wetland soils.

关键词： Rice ABCG transporter Cadmium accumulation Phytoremediation

Adverse effects of early-life stress:focus on the rodent neuroendocrine system

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Neural Regeneration Research 2024年第2期19卷 336-341页

作者： Seung Hyun Lee Eui-Man Jung department of molecular biology College of Natural SciencesPusan National UniversityBusanRepublic of Korea

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

关键词： early-life stress hypothalamic-pituitary-adrenergic axis maternal separation mental illness neurodevelopmental disorder neuroendocrine system neurotransmitter

Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans:an overview of recent findings

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Neural Regeneration Research 2024年第9期19卷 1908-1918页

作者： Marcello Serra Nicola Simola Alexia E.Pollack Giulia Costa department of biomedical Sciences Section of NeuroscienceUniversity of CagliariCagliariItaly department of biology University of Massachusetts-BostonBostonMAUSA

Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.

关键词： 3,4-methylenedioxymethamphetamine amphetamine caffeine cell cultures cocaine methamphetamine methylphenidate neurotoxicity nicotine

Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le Jung Hoon Lee Min Jae Lee department of Biochemistry and molecular biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the neurons.Tau has unique biophysical properties that make it both highly water-soluble and positively charged.Although tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental biology Department of Biology University of Patras Laboratory of Cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia

Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders

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Neural Regeneration Research 2024年第10期19卷 2099-2100页

作者： Michiko Shirane department of molecular biology Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan

Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).

关键词： esters ester cholesteryl

Potential of molecular chaperones for treating Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2343-2344页

作者： Gefei Chen Jan Johansson department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden department of Cell and molecular biology Uppsala UniversityUppsalaSweden

Alzheimer’s disease(AD)is the most prevalent form of dementia,i.e.,progressive memory loss and profound cognitive dysfunction,resulting in a considerable societal burden.At the neuropathological level,the brains of AD patients exhibit amyloid-β(Aβ)plaques,neurofibrillary tangles,and neuroinflammation(Sala Frigerio and De Strooper,2016).

关键词： Alzheimer inflammation Aβ

SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis

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Neural Regeneration Research 2024年第6期19卷 1201-1202页

作者： Ruben J.Cauchi Centre for molecular Medicine and Biobanking Biomedical Sciences BuildingDepartment of Physiology and Biochemistry Faculty of Medicine and Surgery University of Malta

Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons,resulting in muscle weakness and spasticity,eventually leading to death due to respiratory failure.Analyses by our group of a casecontrol cohort from an isolated island population have found that genetics plays a significant role in disease etiology(Farrugia Wismayer et al.,2023).

关键词： PROTEIN SLY1

Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine department of molecular and Cellular biology Section of Endocrinology Diabetes and Metabolism Department of Medicine Baylor College of Medicine Brain Glycemic and Metabolism Control department Pennington Biomedical Research Center Louisiana State University

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.Prolonged high blood glucose(i.e.,

关键词： HYPOGLYCEMIA