查看更多>>摘要：The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling paths.Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.
查看更多>>摘要：Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples.Metabolomics is emerging as a powerful tool generally for pre-cision medicine.Particularly,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease.However,metabo-lomics data are very complicated.Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis.In this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data transformation.We discuss the advantages and limitations of each method.The choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis method.We then provide the perspective of their applications in the microbiome and metabolome research.
查看更多>>摘要：Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and it plays an important role in gene regulation of pro-inflammatory,pro-thrombotic,pro-oxidative stress,and cell permeability.Many impor-tant endothelial cell mechanosensitive genes have been discovered,including KLK10,CCN gene family,NRP2,YAP,TAZ,HIF-1α,NF-κB,FOS,JUN,TFEB,KLF2/KLF4,NRF2,and ID1.Some of them have been intensively studied,whereas the relevant regulatory mechanism of other genes remains unclear.Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease.Thus,this article reviews the mechanosensitive genes affecting vascular endothelial cells,including classical pathways and some newly screened genes,and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights for anti-atherosclerosis.
查看更多>>摘要：Long COVID,also known for post-acute sequelae of COVID-19,describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase.Long COVID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with COVID-19 before could experience long-COVID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long COVID may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(GI)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models.Here,we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID,including the clinical GI symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long COVID.We highlight the potential mechanisms and possible treatment based on GI health and microbiome.Finally,we discuss challenges and future direction in the long COVID clinic and research.
查看更多>>摘要：Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological,cellular,and clinical levels.Rheumatologists have marked them as two entirely distinct arthropathies.Given recent dis-coveries in disease initiation and progression,potential mechanisms,cellular signaling path-ways,and ongoing clinical therapeutics,there are now more opportunities for discovering osteoarthritis drugs.This review summarized the osteoarthritis and psoriasis arthritis signaling pathways,crosstalk between BMP,WNT,TGF-β,VEGF,TLR,and FGF signaling pathways,bio-markers,and anatomical pathologies.Through bench research,we demonstrated that regen-erative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses,multiple signaling blockers,and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation.Furthermore,we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.
查看更多>>摘要：Fibroblast growth factor 21(FGF21)was originally identified as an important meta-bolic regulator which plays a crucial physiological role in regulating a variety of metabolic pa-rameters through the metabolic network.As a novel multifunctional endocrine growth factor,the role of FGF21 in the metabolic network warrants extensive exploration.This insight was obtained from the observation that the FGF21-dependent mechanism that regulates lipid metabolism,glycogen transformation,and biological effectiveness occurs through the coordi-nated participation of the liver,adipose tissue,central nervous system,and sympathetic nerves.This review focuses on the role of FGF21-uncoupling protein 1(UCP1)signaling in lipid metabolism and how FGF21 alleviates non-alcoholic fatty liver disease(NAFLD).Additionally,this review reveals the mechanism by which FGF21 governs glucolipid metabolism.Recent research on the role of FGF21 in the metabolic network has mostly focused on the crucial pathway of glucolipid metabolism.FGF21 has been shown to have multiple regulatory roles in the metabolic network.Since an adequate understanding of the concrete regulatory path-ways of FGF21 in the metabolic network has not been attained,this review sheds new light on the metabolic mechanisms of FGF21,explores how FGF21 engages different tissues and organs,and lays a theoretical foundation for future in-depth research on FGF21-targeted treatment of metabolic diseases.
查看更多>>摘要：Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum stress.The exact interplay between stress and liver diseases remains unclear.Autophagy plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver diseases.Once the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain homeostasis.In recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much attention.FGF21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to stress.Also,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal role.This review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clin-ical practice.
查看更多>>摘要：There are few tumor cell subpopulations with stem cell characteristics in tumor tis-sue,defined as cancer stem cells(CSCs)or cancer stem-like cells(CSLCs),which can recon-struct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation.The microenvironment that CSCs depend on consists of various cellular components and corresponding medium components.Among these factors existing at a variety of levels and forms,cytokine networks and numerous signal pathways play an important role in signaling transduction.These factors promote or maintain cancer cell stem-ness,and participate in cancer recurrence,metastasis,and resistance.This review aims to summarize the recent molecular data concerning the multilayered relationship between CSCs and CSC-favorable microenvironments.We also discuss the therapeutic implications of target-ing this synergistic interplay,hoping to give an insight into targeting cancer cell stemness for tumor therapy and prognosis.
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