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Exosomes are membrane-bound vesicles secreted by diverse cell types, serving as crucial mediators in intercellular communication and significantly influencing cancer development. Exosomes facilitate complex signaling processes in the tumor microenvironment for immunomodulation, metastasis, angiogenesis, and treatment resistance. Notably, long non-coding RNAs (lncRNAs), a class of non-coding RNAs, engage with mRNA, DNA, proteins, and miRNAs to modulate gene expression through multiple mechanisms, including transcriptional, post-transcriptional, translational, and epigenetic pathways. The quantitative dynamics of exosomal lncRNAs show a consistent variation correlating with cancer progression and metastasis, suggesting their potential utility as biomarkers for cancer diagnosis and prognosis. Additionally, exosomal lncRNAs can yield critical insights into therapeutic responses in patients. The identification of exosomal lncRNAs as indicators for various cancer subtypes presents them not only as prognostic tools but also as promising therapeutic targets. Despite their potential, the precise functions of exosomal lncRNAs in the cancer biology landscape remain inadequately understood. This paper delves into the multifaceted roles of exosomal lncRNAs, particularly in the context of breast cancer, highlighting their promise for therapeutic applications. A thorough comprehension of exosomal lncRNAs is imperative for advancing our knowledge of the underlying mechanisms of breast cancer, ultimately paving the way for the development of more effective treatment strategies for patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammation and autoimmune diseases (AD) are common outcomes of an overactive immune system. Inflammation occurs due to the immune system reacting to damaging stimuli. Exosomes are being recognized as an advanced therapeutic approach for addressing an overactive immune system, positioning them as a promising option for treating AD. Mesenchymal stem cells (MSCs) release exosomes that have strong immunomodulatory effects, influenced by their cell of origin. MSCs-exosomes, being a cell-free therapy, exhibit less toxicity and provoke a diminished immune response compared to cell-based therapies. Exosomal non-coding RNAs (ncRNA), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are intricately linked to various biological and functional aspects of human health. Exosomal ncRNAs can lead to tissue malfunction, aging, and illnesses when they experience tissue-specific alterations as a result of various internal or external problems. In this study, we will examine current trends in exosomal ncRNA researches regarding AD. Then, therapeutic uses of MSCs-exosomal ncRNA will be outlined, with a particle focus on the underlying molecular mechanisms., Competing Interests: Compliance with Ethical Standards Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MicroRNAs (miRNAs) are conserved non-protein-coding RNAs that are naturally present in organisms and can control gene expression by suppressing the translation of mRNA or causing the degradation of mRNA. MicroRNAs are highly concentrated in the PI3K/AKT pathway, and abnormal activation of the PI3K/AKT pathway plays a role in cancer progression. The AKT/PI3K pathway is critical for cellular functions and can be stimulated by cytokines and in normal situations. It is involved in regulating various intracellular signal transduction, including development, differentiation, transcriptional regulation, protein, and synthesis. There is a growing body of evidence indicating that miRNAs, which are abundant in exosomes released by different cells, can control cellular biological activities via modulating the PI3K/AKT pathway, hence influencing cancer progression and drug resistance. This article provides an overview of the latest research progress regarding the function and medical use of the PI3K/AKT pathway and exosomal miRNA/AKT/PI3K axis in the behaviors of cancer cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The most prevalent inflammatory arthritis and a leading contributor to disability is rheumatoid arthritis (RA). Although it may not have arrived in Europe until the 17th century, it was present in early Native American communities several thousand years ago. Exosomes released by mesenchymal stem cells (MSCs) are highly immunomodulatory due to the origin of the cell. As a cell-free therapy, MSCs-exosomes are less toxic and elicit a weakened immune response than cell-based therapies. Exosomal noncoding RNAs (ncRNAs) are closely associated with a number of biological and functional facets of human health, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Various exo-miRNAs and lncRNAs such as HAND2-AS1, miR-150-5p, miRNA-124a, and miR-320a lodged with MSC could be appropriate therapeutic ways for RA treatment. These MSC-derived exosomes affect RA disorders via different molecular pathways such as NFK-β, MAPK, and Wnt. The purpose of this review is to review the research that has been conducted since 2020 so far in the field of RA disease treatment with MSC-loaded exo-miRNAs and exo-lncRNAs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident., (© 2024 John Wiley & Sons Ltd.)

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future., (© 2024 Wiley Periodicals LLC.)

Head and neck cancer (HNC) refers to the epithelial malignancies of the upper aerodigestive tract. HNCs have a constant yet slow-growing rate with an unsatisfactory overall survival rate globally. The development of new blood vessels from existing blood conduits is regarded as angiogenesis, which is implicated in the growth, progression, and metastasis of cancer. Aberrant angiogenesis is a known contributor to human cancer progression. Representing a promising therapeutic target, the blockade of angiogenesis aids in the reduction of the tumor cells oxygen and nutrient supplies. Despite the promise, the association of existing anti-angiogenic approaches with severe side effects, elevated cancer regrowth rates, and limited survival advantages is incontrovertible. Exosomes appear to have an essential contribution to the support of vascular proliferation, the regulation of tumor growth, tumor invasion, and metastasis, as they are a key mediator of information transfer between cells. In the exocrine region, various types of noncoding RNAs (ncRNAs) identified to be enriched and stable and contribute to the occurrence and progression of cancer. Mounting evidence suggest that exosome-derived ncRNAs are implicated in tumor angiogenesis. In this review, the characteristics of angiogenesis, particularly in HNC, and the impact of ncRNAs on HNC angiogenesis will be outlined. Besides, we aim to provide an insight on the regulatory role of exosomes and exosome-derived ncRNAs in angiogenesis in different types of HNC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors are thankful to the Deanship of Scientific Research, King Khalid University, Abha, Saudi Arabia, for financially supporting this work through the Large Research Group Project under Grant no. R.G.P.2/557/44., (Copyright © 2024. Published by Elsevier GmbH.)

The term acute respiratory disease encompasses a wide range of acute lung diseases, which in recent years have been ranked among the top three deadly diseases in the world. Since conventional treatment methods, including the use of anti-inflammatory drugs, have had no significant effect on the treatment process of these diseases, the attention of the medical community has been drawn to alternative methods. Mesenchymal stem cells (MSC) are multipotential stem/progenitor cells that have extensive immunomodulatory and anti-inflammatory properties and also play a critical role in the microenvironment of injured tissue. MSC secretomes (containing large extracellular vesicles, microvesicles, and exosomes) are a newly introduced option for cell-free therapies that can circumvent the hurdles of cell-based therapies while maintaining the therapeutic role of MSC themselves. The therapeutic capabilities of MSCs have been showed in many acute respiratory diseases, including chronic respiratory disease (CRD), novel coronavirus 2019 (COVID -19), and pneumonia. MSCs offer novel therapeutic approaches for chronic and acute lung diseases due to their anti-inflammatory and immunomodulatory properties. In this review, we summarize the current evidence on the efficacy and safety of MSC-derived products in preclinical models of lung diseases and highlight the biologically active compounds present in the MSC secretome and their mechanisms involved in anti-inflammatory activity and tissue regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)