查看更多>>摘要：As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs,N6-methyladenosine(m6A)post-transcriptionally regulates the processing and meta-bolism of mRNAs involved in diverse biological processes.m6A modification is regulated by m6A writers,erasers,and readers.Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells.Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for under-standing early embryonic development,which is also the premise for the application of embry-onic stem cells in regenerative medicine.This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.
查看更多>>摘要：The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their prognosis.However,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of life.TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance.Now,the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs.However,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations.Therefore,finding new therapeutic targets to over-come TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a focus.The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes.In recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma.In CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem cells.Some of these molecules may help overcome TKI resistance and treat CML.In this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.
查看更多>>摘要：Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques.Sonogenetics,a method that uses genetic engi-neering to produce ultrasound-sensitive proteins in target cells,is gaining prominence along with optogenetics,electrogenetics,and magnetogenetics.Upon stimulation with ultrasound,these proteins trigger a cascade of cellular activities and functions.Unlike traditional ultra-sound modalities,sonogenetics offers enhanced spatial selectivity,improving precision and safety in disease treatment.This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications,including neuromodula-tion,oncologic treatments,stem cell therapy,and beyond.Although current literature pre-dominantly emphasizes ultrasonic neuromodulation,this review offers a comprehensive exploration of sonogenetics.We discuss ultrasound properties,the specific ultrasound-sensi-tive proteins employed in sonogenetics,and the technique's potential in managing conditions such as neurological disorders,cancer,and ophthalmic diseases,and in stem cell therapies.Our objective is to stimulate fresh perspectives for further research in this promising field.
查看更多>>摘要：A long noncoding RNA(lncRNA)is longer than 200 bp.It regulates various biological processes mainly by interacting with DNA,RNA,or protein in multiple kinds of biological pro-cesses.Adenosine monophosphate-activated protein kinase(AMPK)is activated during nutrient starvation,especially glucose starvation and oxygen deficiency(hypoxia),and exposure to toxins that inhibit mitochondrial respiratory chain complex function.AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes,including lipid and glucose metabolism,thereby maintaining intracellular energy homeostasis by activating catab-olism and inhibiting anabolism.The AMPK signalling pathway consists of AMPK and its upstream and downstream targets.AMPK upstream targets include proteins such as the transforming growth factor β-activated kinase 1(TAK1),liver kinase B1(LKB1),and calcium/calmodulin-dependent protein kinase β(CaMKKβ),and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin(mTOR)complex 1(mTORC1),hepatocyte nuclear factor 4α(HNF4α),and silencing information regulatory 1(SIRT1).In general,proteins function relatively independently and cooperate.In this article,a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the reg-ulatory mechanisms involved in human ageing and age-related diseases are provided.
查看更多>>摘要：Mechanical stimulation is the key physical factor in cell environment.Mechano-transduction acts as a fundamental regulator of cell behavior,regulating cell proliferation,dif-ferentiation,apoptosis,and exhibiting specific signature alterations during the pathological process.As research continues,the role of epigenetic science in mechanotransduction is at-tracting attention.However,the molecular mechanism of the synergistic effect between me-chanotransduction and epigenetics in physiological and pathological processes has not been clarified.We focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease progression.Specifically,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling pathways.Mechanotransduction and epigenetic changes could be potential markers and therapeutic targets in clinical practice.
查看更多>>摘要：Protein lysine crotonylation(Kcr)is one conserved form of posttranslational modi-fications of proteins,which plays an important role in a series of cellular physiological and pathological processes.Lysine ε-amino groups are the primary sites of such modification,re-sulting in four-carbon planar lysine crotonylation that is structurally and functionally distinct from the acetylation of these residues.High levels of Kcr modifications have been identified on both histone and non-histone proteins.The present review offers an update on the research progression regarding protein Kcr modifications in biomedical contexts and provides a discus-sion of the mechanisms whereby Kcr modification governs a range of biological processes.In addition,given the importance of protein Kcr modification in disease onset and progression,the potential viability of Kcr regulators as therapeutic targets is elucidated.
查看更多>>摘要：RNA N6-methyladenosine(m6A)methylation is the most abundant and conserved RNA modification in eukaryotes.It participates in the regulation of RNA metabolism and vanous pathophysiological processes.Non-coding RNAs(ncRNAs)are defined as small or long transcripts which do not encode proteins and display numerous biological regulatory functions.Similar to mRNAs,m6A deposition is observed in ncRNAs.Studying RNA m6A modifications on ncRNAs is of great importance specifically to deepen our understanding of their biological roles and clinical implications.In this review,we summarized the recent research findings regarding the mutual regulation between RNA m6A modification and ncRNAs(with a specific focus on mi-croRNAs,long non-coding RNAs,and circular RNAs)and their functions.We also discussed the challenges of m6A-containing ncRNAs and RNA m6A as therapeutic targets in human diseases and their future perspective in translational roles.
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