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RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 788-806页

作者： Ankit Srivastava Deeksha Rikhari Sameer Srivastava Department of biotechnology Motilal Nehru National Institute of TechnologyAllahabadUttar Pradesh 211004India

R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signaling,which has now been acknowledged in numerous in vitro and in vivo studies.Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer.Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks.Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types,particularly CRC.As a critical regulator of the Wnt pathway,it modulates several phenotypes of cells,such as cell proliferation,invasion,migration,and cancer stem cell properties.Recently,RSPO mutations,gene rearrangements,fusions,copy number alterations,and altered gene expression have also been identified in a variety of cancers,including CRC.In this review,we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC.In addition to the compelling physiological and biological roles in cellular fate and regulation,we propose that RSPO2 would be valuable as a potential biomarker for prognostic,diagnostic,and therapeutic use in CRC.

关键词： CRC Gene fusion R-Spondins RSPO2 Therapeutics Wnt signaling

Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus

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World Journal of Clinical Cases 2024年第3期12卷 525-537页

作者： Dharmsheel Shrivastav Desh Deepak Singh Amity institute of biotechnology Amity University RajasthanJaipur 303002India

BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Uncontrolled high sugar levels lead to advanced glycation end products(AGEs),which affects several metabolic pathways by its receptor of advanced glycation end products(RAGE)and causes diabetic complication.MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis,and target tissues,influencing health and disease processes.AIM To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications.METHODS We systematically searched the electronic database PubMed using keywords.We included free,full-length research articles that evaluate the role of miRNAs in T2DM and its complications,focusing on genetic and molecular disease mechanisms.After assessing the full-length papers of the shortlisted articles,we included 12 research articles.RESULTS Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications.miR-96-5p,miR-7-5p,miR-132,has_circ_0071106,miR-143,miR-21,miR-145-5p,and more are associated with various aspects of T2DM,including disease risk,diagnostic markers,complications,and gene regulation.CONCLUSION Targeting the AGE/RAGE axis,with a focus on miRNA regulation,holds promise for managing T2DM and its complications.MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE,potentially reducing inflammation,oxidative stress,and vascular complications.Additionally,miRNAs may serve as early diagnostic biomarkers for T2DM.Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.

关键词： Type 2 diabetes mellitus MicroRNAs Advanced glycation end products Receptor for advanced glycation end products

Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

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World Journal of Stem Cells 2024年第2期16卷 102-113页

作者： Pakkath Narayanan Arya Iyyappan Saranya Nagarajan Selvamurugan Department of biotechnology School of BioengineeringSRM Institute of Science and TechnologyKattankulathur 603203India

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

关键词： Bone Mesenchymal stem cells Osteogenic differentiation Wnt/β-catenin Bone morphogenetic proteins

Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

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Bio-Design and Manufacturing 2024年第1期7卷 57-73页

作者： Amit Kumar Singh Krishna Pramanik Amit Biswas Centre of Excellence in Tissue Engineering Department of Biotechnology and Medical EngineeringNational Institute of TechnologyRourkela 769008India

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.

关键词： Scaffold Biomaterial Sodium alginate Chitosan Gelatin 3D printing Tissue engineering

RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila

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Marine Life Science & Technology 2024年第2期6卷 183-197页

作者： Huijuan Hao Yinjie Lian Chenhui Ren Sitong Yang Min Zhao Tao Bo Jing Xu Wei Wang Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi Key Laboratory of biotechnology Taiyuan 030006China

Histone modification and nucleosome assembly play important roles in chromatin-related processes.Histone chaperones form different complexes and coordinate histone transportation and assembly.Various histone chaperone complexes have been identified in different organisms.The ciliate protozoa(ciliates)have various chromatin structures and different nuclear morphology.However,histone chaperone components and functions of different subunits remain unclear in ciliates.Tet-rahymema thermophila contains a transcriptionally active macronucleus(MAC)and a transcriptionally inactive micronu-cleus(MIC)which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages.Here,we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages.REBL1 knockdown inhibited cellular proliferation.The macronuclear morphology became bigger in growing mutants.The abnormal macronuclear structure also occurred in the starvation stage.Furthermore,micronuclear meiosis was disturbed during sexual development,leading to a failure to generate new gametic nuclei.RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages.REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription.Taken together,RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T.thermophila.

关键词： Gametogenesis Histone chaperone Macronuclear structure RebL1 Tetrahymena thermophilaIntroduction

GeMemiOM: the curated database on genes, putative methylation study targets, and microRNA targets for otitis media

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Journal of Genetics and Genomics 2024年第2期51卷 260-263页

作者： Kondyarpu Abhishek Bineet Kumar Mohanta Pratima Kumari Anshuman Dixit Puppala Venkat Ramchander institute of Life Sciences Nalco SquareChandrasekharpurBhubaneswarIndia Regional Center for biotechnology FaridabadHaryanaIndia

Otitis media(OM),the most underrated middle ear disease,often onsets during childhood and gets complicated in susceptible patients.Inflammation of the middle ear(ME)leads to its degradation and abnormal physiological functions.Prolonged ME inflammation sometimes results in lethal secondary complications(Penido et al.,2016).OM is a corroboration of multiple facets that leads to disabling hearing loss and associated complications.Some of the facets constituted are genetic,epigenetic,immunogenetic,anatomical.

关键词： inflammation media

Commercial genetically modified corn and soybean are poised following pilot planting in China

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Molecular Plant 2024年第4期17卷 519-521页

作者： Mei Sun Suzhen Li Wenzhu Yang Bowen Zhao Youhua Wang Xiaoqing Liu biotechnology Research institute Chinese Academy of Agricultural ScienceBeijing 100081China Farmers'Daily Beijing 100025China

"Who will feed China?"This was a question raised by Lester Brown,the director of the World Watch institute in the United States,in 1994.He predicted that China's grain production would decrease from 340 million tons in 1990 to 272 million tons by 2030,a 20%decrease,while China's population would reach 1.6 billion(Brown,1995).If the dietary structure was not improved,China would need to import 200-369 million tons of grain,equivalent to the global grain trade at the time.He projected the high possibility of a food crisis in China,which might further trigger a global food crisis.However,with the joint efforts of national agricultural researchers,represented by Yuan Longping,and the Chinese government,China's grain production has achieved 18 consecutive increases from 2004 to 2021.In 2022,grain production in China reached 633 million tons(NBS and Statistics,2022),while the population remained stable at 1.4 billion.As a result,China has achieved complete self-sufficiency in its staple food supply and has demonstrated to the international community through practical actions that the Chinese people can feed themselves.

关键词： planting soybean raised

Effects of different doses of glucose and fructose on central metabolic pathways and intercellular wireless communication networks in humans

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Food Science and Human Wellness 2024年第4期13卷 1906-1916页

作者： Dingqiang Lu Yujiao Liu Miao Zhao Shuai Yuan Danyang Liu Xinqian Wang Yixuan Liu Yifei Zhang Ming Li Yufeng Lü Guangchang Pang Ruijuan Ren College of biotechnology&Food Science Tianjin University of CommerceTianjin Key Laboratory of Food BiotechnologyTianjin 300314China Tianjin institute for Food Safety Inspection Technology Tianjin 300134China

Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.

关键词： Fructose Glucose Central carbon metabolic pathway Metabolic enzymes Cytokine network

Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors

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Animal Models and Experimental Medicine 2024年第2期7卷 189-193页

作者： Savani Anbalagan Faculty of Biology Institute of Molecular Biology and BiotechnologyAdam Mickiewicz UniversityPoznańPoland

The current restrictive criteria for gasotransmitters exclude oxygen(O_(2))as a gasotransmitter in vertebrates.In this manuscript,I propose a revision of gasotransmitter criteria to include O_(2) per se as a signaling molecule and'essential gasotransmitter'for vertebrates.This revision would enable us to search for protein-based O_(2)-binding sensors(gasoreceptors)in all cells in the brain or other tissues rather than specialized tissues such as the carotid body or gills.If microorganisms have protein-based O_(2)-binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains,then eukaryotic cells must also have O_(2)-binding sensors or gasoreceptors.Just as there are proteinbased receptor(s)for nitric oxide(GUCY1A,GUCY1B,CLOCK,NR1D2)in cells of diverse tissues,it is reasonable to consider that there are protein-based receptors for O_(2) in cells of diverse tissues as well.In mammals,O_(2) must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O_(2).Accepting O_(2) as an essential gasotransmitter will enable us to search for gasoreceptors not only for O_(2) but also for other nonessential gasotransmitters such as hydrogen sulfide,ammonia,methane,and ethylene.It will also allow us to investigate the role of environment-derived metal ions in acute gas(or solute)sensing within and between organisms.Finally,accepting O_(2) per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.

关键词： essential gasotransmitter gasocrine gasoreceptor gasocrinology