The known,unknown,and unknown unknowns of cell-cell communication in planarian regeneration

Planarians represent the most primitive bilateral triploblastic animals.Most planarian species exhibit mechanisms for whole-body regeneration,exemplified by the regeneration of their cephalic ganglion after complete excision.Given their robust whole-body regeneration capacity,planarians have been model organisms in regenerative research for more than 240 years.Advancements in research tools and techniques have progressively elucidated the mechanisms underlying planarian regeneration.Accurate cell-cell communication is recognized as a fundamental requirement for regeneration.In recent decades,mechanisms associated with such communication have been revealed at the cellular level.Notably,stem cells(neoblasts)have been identified as the source of all new cells during planarian homeostasis and regeneration.The interplay between neoblasts and somatic cells affects the identities and proportions of various tissues during homeostasis and regeneration.Here,this review outlines key discoveries regarding communication between stem cell compartments and other cell types in planarians,as well as the impact of communication on planarian regeneration.Additionally,this review discusses the challenges and potential directions of future planarian research,emphasizing the sustained impact of this field on our understanding of animal regeneration.

Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway

BACKGROUND Mesenchymal stem cells(MSCs)exert anti-oncogenic effects via exosomes containing non-coding RNA(ncRNA),which play important roles in tumor biology.Our preliminary study identified the interaction of the ncRNA hsa_-circ_0000563(circ563)and the circ563-associated miR-148a-3p in exosomes,as miR-148a-3p and its target metal-regulatory transcription factor-1(MTF-1)are implicated in hepatocellular carcinoma(HCC)progression.AIM To identify the clinical significance,functional implications,and mechanisms of circ563 in HCC.METHODS The expression levels of miR-148a-3p and MTF-1 in exosomes derived from MSC and HCC cells were compared,and their effects on HCC cells were assessed.Using a dual-luciferase reporter assay,miR-148a-3p was identified as an associated microRNA of circ563,whose role in HCC regulation was assessed in vitro and in vivo.RESULTS The silencing of circ563 blocked the HCC cell proliferation and invasion and induced apoptosis.Co-culturing of HCC cells with MSC-derived exosomes following circ563 overexpression promoted cell proliferation and metastasis and elicited changes in miR-148a-3p and MTF-1 expression.The tumor-promoting effects of circ563 were partially suppressed by miR-148a-3p overexpression or MTF-1 depletion.Xenograft experiments performed in nude mice confirmed that circ563-enriched exosomes facilitated tumor growth by upregulating the expression of MTF-1.In HCC tissues,circ563 expression was negatively correlated with miR-148a-3p expression but positively correlated with MTF-1 levels.CONCLUSION MSCs may exhibit anti-HCC activity through the exosomal circ563/miR-148a-3p/MTF-1 pathway,while exosomes can transmit circ563 to promote oncogenic behavior by competitively binding to miR-148a-3p to activate MTF-1.

Influence of vascular endothelial growth factor and radiation on gap junctional intercellular communication in glioblastoma multiforme cell lines

Glioblastoma multiforme （GBM） is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor （VEGF）, an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients＇ prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains un- known, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junc- tional intercellular communication （GJIC）. Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF reocptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJ1C in pathologic brain tumor tissue.

Junctional communication of embryonic cells after induction

Cell couplings before and after neural induction in embryos of Cynops orientalis were studied by means of single cell injection of Lucifer Yellow.Differences both in incidence and the extent of cell couplings were demonstrated.Results of cell couplings were correlated with electron microscopic observations of freeze-etching replicas.

A Comprehensive Review of Exosomes with Therapeutic Potential in Cancer and Coeliac Disease

The aim of this review was to evaluate the therapeutic potential of exosomes, extracellular vesicles secreted by cells. They have emerged as potential therapeutic transporters for several diseases. This review provides an overview of exosomes’ therapeutic potential in cancer therapy and autoimmune conditions such as Coeliac Disease. The therapeutic effect is that the phospholipid-binding protein ANXA1 improves its anti-inflammatory properties. The review also analyzes the intricate processes of exosome production and composition ability to transport biomolecules such as proteins, microRNAs, and lipids, which promote intercellular communication and alter recipient cell behavior. Exosomes, linked to neurological disorders, cardiovascular disease, and cancer, present the means of targeted drug administration due to their innate specificity. Through genetic engineering and chemical modifications, exosomes can be tailored for specific purposes, demonstrating their versatility in targeted therapy. With ongoing research uncovering their therapeutic potential, exosomes present a promising frontier in novel medical treatments across various health conditions.

Changes in gap junctional intercellular communication in rabbits lens epithelial cells induced by low power density microwave radiation

OBJECTIVE: To demonstrate the changes in gap junctional intercellular communication (GJIC) mediated by low power density microwave radiation in rabbits lens epithelial cells (LECs) and its mechanisms. METHODS: Rabbits' eyes were exposed to 5 mW/cm(2) and 10 mW/cm(2) power densities of microwave radiation for 3 hours. The fluorescence-recovery-after-photobleaching (FRAP) method was used to determine the GJIC. The localization and function of connexin 43 in LECs was detected by laser scanning confocal microscopy. RESULTS: The GJIC of rabbits LECs was inhibited by microwave radiation especially in the 10 mW/cm(2) irradiated samples. A decrease in connexin 43-positive staining was seen in 5 mW/cm(2) x 3 h treated LECs. Intracellular space accumulation and cytoplasmic internalization were clearly demonstrated in 10 mW/cm(2) group. CONCLUSIONS: Low power densities microwave radiation (5 mW/cm(2) and 10 mW/cm(2)) induces damage to connexin 43 and inhibits the GJIC of rabbits LECs. These changes result in an osmotic imbalance within the lens and induce early cataract. 5 mW/cm(2) or 10 mW/cm(2) microwave radiation is cataractogenic.

Membrane nanotubes:Novel communication between distant cells

The many kinds of cell structures involved in cell-cell communication include tight junction,adherens junction and gap junction,but almost all are between adjacent cells.Recently,a general and dynamic membrane tether,termed tunneling nanotubes or membrane nanotubes(MNTs),was discovered to be involved in communication between distant cells.By facilitating intercellular communication,MNTs contribute to many biological functions and pathologic changes in cells.Many works have revealed the structure,formation and functional properties of MNTs.However,as novel structures,further research is needed.

How functional foods play critical roles in human health

How do functional foods affect human health?To answer this question it is important to understand what happens when food is digested and taken up by the gastrointestinal(GI)tract.The gut is a selective nutrient absorption system and the most important signal transduction and information exchange system within the body.It acts as a signal transducer,a neuroendocrine sensor,and an immunological recognition and presentation system.It is also a complex information exchange system comprising a number of signaling networks involving GI cells and cells immobilized in organs or transported in blood.The bioactivity of functional foods in vivo may be due to their effects on such networks,but this raises the question of what signaling pathways are used by non-nutrients that cannot be absorbed by the gut.The purpose of this review is to describe intestinal nutrient transportation,identify a number of widely expressed receptors and signal transduction pathways,and outline our current understanding of the mechanisms involved in health and disease.At the end of the review,a method for developing a cell communication network is described.This network is convenient for investigating the effects of oral administration of experimental medicines,drugs,or functional foods on cytokines of interest.Because cytokines and chemokines are transported via the circulatory system,a simple 2–3 mL blood sample from a volunteer is a rich source of information.This method may become the gold standard for evaluating the effects of functional foods or medicines in vivo.©2012 Production and hosting by Elsevier B.V.on behalf of Beijing Academy of Food Sciences.

Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology,from the invention of the microscope 350 years ago to the recent emergence of single-cell sequencing,by which the scientific community has been able to visualize life at an unprecedented resolution.Most recently,the Spatially Resolved Transcriptomics(SRT)technologies have filled the gap in probing the spatial or even three-dimensional organization of the molecular foundation behind the molecular mysteries of life,including the origin of different cellular populations developed from totipotent cells and human diseases.In this review,we introduce recent progresses and challenges on SRT from the perspectives of technologies and bioinformatic tools,as well as the representative SRT applications.With the currently fast-moving progress of the SRT technologies and promising results from early adopted research projects,we can foresee the bright future of such new tools in understanding life at the most profound analytical level.

Nitric Oxide： A Multitasked Signaling Gas in Plants

Nitric oxide （NO） is a gaseous reactive oxygen species （ROS） that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological sce- narios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca^2＋ pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell-cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress.

Moving RNA moves RNA forward

Cell communication affects all aspects of cell structure and behavior,such as cell proliferation,differentiation,division,and coordination of various physiological functions.The moving RNA in plants and mammalian cells indicates that nucleic acid could be one of the various types of messengers for cell communication.The microvesicle is a critical pathway that mediates RNA moving and keeps moving RNA stable in body fluids.When moving miRNA enters the target cell,it functions by altering the gene expression profile and significantly inhibiting mRNA translation in recipient cells.Thus,moving RNA may act as a long-range modulator during development,organogenesis,and tumor metastasis.

Role of gap junctions between keratinocyte and melanocyte in melanogenesis

The process ofmelanogenesis in melanocytes and the transport of melanin in the form ofmelanosomes to the neighboring keratinocytes are the key steps in human skin pigmentation. Keratinocytes and melanocytes interact in intricate manner to maintain the homeostasis. The present study was designed to understand the role of cell-cell interaction through the gap junctions between melanocytes and keratinocytes on melanogenesis. We show that, inhibition of the gap junctional activity between human keratinocytes and melanocytes in a coculture system using gap junction blocker lowers the expression of key regulatory genes of melanogenesis such as tyrosinase and microphthalmia- associated transcription factor （MITF）. This was followed by concurrent decrease in tyrosinase protein levels and activity. Our results show the preliminary evidence for the regulation of melanogenesis in melanocytes through direct gap junctional communication by keratinocytes. Deciphering the mechanism and factors involved in the process would uncover the significance of gap junctions in melanogenesis.