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.

Neutrophil elastase:From mechanisms to therapeutic potential

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases

In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.

Analysis on Therapeutic Potential and Action Mechanism of Folium Pyrrosiae Based on Biolabel Pattern

[Objectives]The therapeutic potential and action mechanism of Folium Pyrrosiae were analyzed based on the biolabel pattern.[Methods]The chemical components of Folium Pyrrosiae were analyzed by liquid chromatography-mass spectrometry(LC-MS).Ten databases,including Pubchem,CTD,BindingDB,HERB,TCMIP,ETCM,SwissTargetPrediction,SuperPred webserver,TargetNet and SEA,were used in turn to retrieve the targets of related components,and key components were obtained according to the enrichment degree of targets.The obtained targets were imported into the STRING database to obtain PPI information and screen out core targets.The DAVID database was employed to analyze KEGG pathways of core targets and obtain key pathways.A key component-core target-key pathway network of Folium Pyrrosiae was constructed by Cytoscape3.10.1 software.The obtained KEGG pathways were input into the CTD database to predict corresponding diseases,and discussion and analysis were carried out.[Results]Ten key components,30 potential targets and 10 key pathways were screened out,and they participated in many diseases,of which five diseases were mainly analyzed.[Conclusions]Folium Pyrrosiae had the characteristic of multi-component,multi-target and multi-pathway synergistic effect in the treatment of lung cancer,type 2 diabetes,atherosclerosis,liver cancer,prostate cancer and other diseases,and the therapeutic potential and action mechanism of Folium Pyrrosiae were analyzed through the biolabel pattern.This study provides a research basis for further developing new functions of Folium Pyrrosiae.

The therapeutic potential of mesenchymal stem cells in Alzheimer's disease:converging mechanisms

Mesenchymal stem cells （MSCS） are pluripotent stem cells isolated from various tissues, but mostly from bone marrow, adipose tissue, and umbilical cord blood. Well known for their mesenchymal lineages differentiation （e.g., bone, cartilage and fat tissues）, it was suggested that MSCs possess plasticity prop- erties enabling them to differentiate into non-mesenchymal lineages. Indeed, several protocols claimed for differentiating MSCs to neurons in vitro, but concern was raised for the ef- fectiveness and in vivo relevance of such differentiation. Thus, though their neurogenic differentiation properties are still in debate, they were nevertheless, suggested as candidates for treat- ing neurodegenerative disorders such as Parkinson＇s diseases, multiple sclerosis and Alzheimer＇s disease （AD）.

Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis:therapeutic potential for endogenous pulp regeneration

Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

Relevance and therapeutic potential of Cyp A targeting to block apoptosis inducing factor-mediated neuronal cell death

Programmed cell death （PCD） signaling pathways are import- ant contributors to acute neurological insults such as hypox- ic-ischemic brain damage, traumatic brain injury, stroke etc. The pathogenesis of all these diseases is closely linked with ab- erration of apoptotic cell death pathways. Mitochondria play a crucial role during PCD, acting as both sensors of death signals, and as initiators of biochemical path- ways, which cause cell death （Bras et al., 2005）. Cytochrome c was the firstly identified apoptogenic factor released from mitochondria into the cytosol, where it induces apoptosome formation through the activation of caspases. Other proteins, such as apoptosis inducing factor （AIF）, have been subsequently identified as mitochondrial released factors. AIF contributes to apoptotic nuclear DNA damage （Bras et al., 2005）. in a caspase-independent way

Therapeutic Potential of Anti-HIV RNA-loaded Exosomes

Highly active antiretroviral therapy（HAART）is used globally and has significantly reduced the morbidity,mortality,and transmission of human immunodeficiency virus（HIV）-related illness.However,the attendant shortcomings such as toxic side effects,necessity of life-long therapy that is expensive, and inefficiency in eradicating latent viral infections have greatly limited the application of HAART.

Therapeutic potential of N-acetyl cysteine during COVID-19 epoch

N-acetyl cysteine(NAC)is a promising drug for prophylaxis and treatment of coronavirus disease 2019(COVID-19)based on antioxidant and anti-inflammatory mechanisms.Further studies with cautious approach are needed to establish the benefits and risks before considering NAC as an adjuvant treatment for COVID-19.

Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

The pharmacology, toxicology and therapeutic potential of anthraquinone derivative emodin

Emodin(1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.

SOX2 in cancer stemness: tumor malignancy and therapeutic potentials

Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.

Mortalin/Hspa9 involvement and therapeutic perspective in Parkinson's disease

By controlling the proper folding of proteins imported into mitochondria and ensuring crosstalk between the reticulum and mitochondria to modulate intra cellular calcium fluxes.Mortalin is a chaperone protein that plays crucial roles in neuronal homeostasis and activity.Howeve r,its expression and stability are strongly modified in response to cellular stresses,in particular upon alte red oxidative conditions during neurodegeneration.Here,we report and discuss the abundant literature that has highlighted its contribution to the pathophysiology of Parkinson's disease,as well as its therapeutic and prognostic potential in this still incurable pathology.

Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage

Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.

Programmed cell death and natural killer cells in multiple sclerosis: new potential therapeutic targets?

Multiple sclerosis（MS）is a chronic,severe and complex disease of still uncertain etiopathogenesis,with lesions in the cerebral white matter and spinal cord.The disease is heterogeneous,but is characterized by neuroinflammatory and neurodegenerative processes,usually associated with altered activation of the immune system following presumable stimulation by still unknown autoantigens.

The Olfactory Receptor Pseudo-pseudogene: A Potential Therapeutic Target in Human Diseases

Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.

Potential therapeutic benefits stemming from the thermal nature of irreversible electropora tion of solid cancers

To the Editor：Irreversible electroporation （IRE） is a CE- and FDA- approved treatment modality for pancreatic and liver tumors that is based on the site-confined destruction of tumor tissue by multiple short, high-intensity electrical pulses.

Consequences of hepatic damage after traumatic brain injury: current outlook and potential therapeutic targets

Traumatic brain injury（TBI）triggers liver inflammation：TBI is a serious pathology affecting around 10 million people annually,being a persistent public health and medical problem Forceful impact while playing sports,falls,physical assault,or traffic accidents are common causes of head injury.

MicroRNA-216a: a potential therapeutic target for drug resistance and recurrent of liver cancer

The Editor welcomes submissions for possible publication in the Letters to the Editor section.Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published.Authors of the article being commented on will be given an opportunity to offer a timely response to the letter.Authors of letters will be notified that the letter has been received.Unpublished letters cannot be returned.

Potential therapeutic effects of thymoquinone on treatment of amphetamine abuse

Dear Editor,The prevalence of drug abuse has diverted from traditional drugs such as opioid and cannabis to modern,synthetic and psychoactive drugs such as amphetamine groups,the amphetamine(AT)and methamphetamine[1].Amphetamine is used medically to treat several disorders such as attention deficit hyperactivity disorder,narcolepsy,depression and minor obesity[2].However,AT has also gained