A comprehensive insight into the contribution of epigenetics in male infertility; focusing on immunological modifications.

Numerous recent studies have examined the impact epigenetics-including DNA methylation-has on spermatogenesis and male infertility. Differential methylation of several genes has been linked to compromised spermatogenesis and/or reproductive failure. Specifically, male infertility has been frequently associated with DNA methylation abnormalities of MEST and H19 inside imprinted genes and MTHFR within non-imprinted genes. Microbial infections mainly result in male infertility because of the immune response triggered by the bacteria' accumulation of immune cells, proinflammatory cytokines, and chemokines. Thus, bacterially produced epigenetic dysregulations may impact host cell function, supporting host defense or enabling pathogen persistence. So, it is possible to think of pathogenic bacteria as potential epimutagens that can alter the epigenome. It has been demonstrated that dysregulated levels of LncRNA correlate with motility and sperm count in ejaculated spermatozoa from infertile males. Therefore, a thorough understanding of the relationship between decreased reproductive capacity and sperm DNA methylation status should aid in creating new diagnostic instruments for this condition. To fully understand the mechanisms influencing sperm methylation and how they relate to male infertility, more research is required.

Highlighting the role of long non-coding RNA (LncRNA) in multiple myeloma (MM) pathogenesis and response to therapy.

Transcripts longer than 200 nucleotides that are not translated into proteins are known as long non-coding RNAs, or lncRNAs. Now, they are becoming more significant as important regulators of gene expression, and as a result, of many biological processes in both healthy and pathological circumstances, such as blood malignancies. Through controlling alternative splicing, transcription, and translation at the post-transcriptional level, lncRNAs have an impact on the expression of genes. In multiple myeloma (MM), the majority of lncRNAs is elevated and promotes the proliferation, adhesion, drug resistance and invasion of MM cells by blocking apoptosis and altering the tumor microenvironment (TME). To control mRNA splicing, stability, and translation, they either directly attach to the target mRNA or transfer RNA-binding proteins (RBPs). By expressing certain miRNA-binding sites that function as competitive endogenous RNAs (ceRNAs), most lncRNAs mimic the actions of miRNAs. Here, we highlight lncRNAs role in the MM pathogenesis with emphasize on their capacity to control the molecular mechanisms known as "hallmarks of cancer," which permit earlier tumor initiation and progression and malignant cell transformation.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.

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.

HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.

The Homeobox (HOX) gene family is essential to regulating cellular processes because it maintains the exact coordination required for tissue homeostasis, cellular differentiation, and embryonic development. The most distinctive feature of this class of genes is the presence of the highly conserved DNA region known as the homeobox, which is essential for controlling their regulatory activities. Important players in the intricate process of genetic regulation are the HOX genes. Many diseases, especially in the area of cancer, are linked to their aberrant functioning. Due to their distinctive functions in biomedical research-particularly in the complex process of tumor advancement-HOXA9 and HOXB9 have drawn particular attention. HOXA9 and HOXB9 are more significant than what is usually connected with HOX genes since they have roles in the intricate field of cancer and beyond embryonic processes. The framework for a focused study of the different effects of HOXA9 and HOXB9 in the context of tumor biology is established in this study.

Relationship between lncRNA MALAT1 and Chemo-radiotherapy Resistance of Cancer Cells: Uncovered Truths.

The advancement of novel technologies, coupled with bioinformatics, has led to the discovery of additional genes, such as long noncoding RNAs (lncRNAs), that are associated with drug resistance. LncRNAs are composed of over 200 nucleotides and do not possess any protein coding function. These lncRNAs exhibit lower conservation across species, are typically expressed at low levels, and often display high specificity towards specific tissues and developmental stages. The LncRNA MALAT1 plays crucial regulatory roles in various aspects of genome function, encompassing gene transcription, splicing, and epigenetics. Additionally, it is involved in biological processes related to the cell cycle, cell differentiation, development, and pluripotency. Recently, MALAT1 has emerged as a novel mechanism contributing to drug resistance or sensitivity, attracting significant attention in the field of cancer research. This review aims to explore the mechanisms through which MALAT1 confers resistance to chemotherapy and radiotherapy in cancer cells.

A comprehensive insight into the immunomodulatory role of MSCs-derived exosomes (MSC-Exos) through modulating pattern-recognition receptors (PRRs).

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.

New Therapeutic Strategies for the Inflammatory Rheumatoid Arthritis Disease: Emphasizing Mesenchymal Stem Cells and Associated exo-miRNA or exo-lncRNA.

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-ß, 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.

Incorporation of immunotherapies and nanomedicine to better normalize angiogenesis-based cancer treatment.

Neoadjuvant targeting of tumor angiogenesis has been developed and approved for the treatment of malignant tumors. However, vascular disruption leads to tumor hypoxia, which exacerbates the treatment process and causes drug resistance. In addition, successful delivery of therapeutic agents and efficacy of radiotherapy require normal vascular networks and sufficient oxygen, which complete tumor vasculopathy hinders their efficacy. In view of this controversy, an optimal dose of FDA-approved anti-angiogenic agents and combination with other therapies, such as immunotherapy and the use of nanocarrier-mediated targeted therapy, could improve therapeutic regimens, reduce the need for administration of high doses of chemotherapeutic agents and subsequently reduce side effects. Here, we review the mechanism of anti-angiogenic agents, highlight the challenges of existing therapies, and present how the combination of immunotherapies and nanomedicine could improve angiogenesis-based tumor treatment.

Exploring the detailed role of interleukins in cancer: A comprehensive review of literature.

The cancer cells that are not normal can grow into tumors, invade surrounding tissues, and travel to other parts of the body via the lymphatic or circulatory systems. Interleukins, a vital class of signaling proteins, facilitate cell-to-cell contact within the immune system. A type of non-coding RNA known as lncRNAs mediates its actions by regulating miRNA-mRNA roles (Interleukins). Because of their dual function in controlling the growth of tumors and altering the immune system's response to cancer cells, interleukins have been extensively studied concerning cancer. Understanding the complex relationships between interleukins, the immune system, the tumor microenvironment, and the components of interleukin signaling pathways that impact the miRNA-mRNA axis, including lncRNAs, has advanced significantly in cancer research. Due to the significant and all-encompassing influence of interleukins on the immune system and the development and advancement of cancers, lncRNAs play a crucial role in cancer research by modulating interleukins. Their diverse effects on immune system regulation, tumor growth encouragement, and tumor inhibition make them appealing candidates for potential cancer treatments and diagnostics. A deeper understanding of the relationship between the biology of interleukin and lncRNAs will likely result in more effective immunotherapy strategies and individualized cancer treatments.

Critical role of exosome, exosomal non-coding RNAs and non-coding RNAs in head and neck cancer angiogenesis.

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.

A comprehensive review of lncRNA CRNDE in cancer progression and pathology, with a specific glance at the epithelial-mesenchymal transition (EMT) process.

It has been suggested that the long non-coding RNAs (lncRNAs), such as colorectal neoplasia differentially expressed (CRNDE), may contribute to the formation of human cancer. It is yet unknown, though, what therapeutic significance CRNDE expression has for different forms of cancer. CRNDE has recently been proposed as a possible diagnostic biomarker and prognostic pred for excellent specificity and sensitivity in cancer tissues and plasma. To provide the groundwork for potential future therapeutic uses of CRNDE, we briefly overview its biological action and related cancer-related pathways. Next, we mainly address the impact of CRNDE on the epithelial-mesenchymal transition (EMT). The epithelial-mesenchymal transition, or EMT, is an essential biological mechanism involved in the spread of cancer.

Nucleic acid-based vaccine for ovarian cancer cells; bench to bedside.

Ovarian cancer continues to be a difficult medical issue that affects millions of individuals worldwide. Important platforms for cancer immunotherapy include checkpoint inhibitors, chimeric antigen receptor T cells, bispecific antibodies, cancer vaccines, and other cell-based treatments. To avoid numerous infectious illnesses, conventional vaccinations based on synthetic peptides, recombinant subunit vaccines, and live attenuated and inactivated pathogens are frequently utilized. Vaccine manufacturing processes, however, are not entirely safe and carry a significant danger of contaminating living microorganisms. As a result, the creation of substitute vaccinations is required for both viral and noninfectious illnesses, including cancer. Recently, there has been testing of nucleic acid vaccines, or NAVs, as a cancer therapeutic. Tumor antigens (TAs) are genetically encoded by DNA and mRNA vaccines, which the host uses to trigger immune responses against ovarian cancer cells that exhibit the TAs. Despite being straightforward, safe, and easy to produce, NAVs are not currently thought to be an ideal replacement for peptide vaccines. Some obstacles to this strategy include selecting the appropriate therapeutic agents (TAs), inadequate immunogenicity, and the immunosuppressive characteristic of ovarian cancer. We focus on strategies that have been employed to increase NAVs' effectiveness in the fight against ovarian cancer in this review.

The interaction between lncRNAs and transcription factors regulating autophagy in human cancers: A comprehensive and therapeutical survey.

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.

A therapeutical insight into the correlation between circRNAs and signaling pathways involved in cancer pathogenesis.

Pre-messenger RNA molecules are back-spliced to create circular RNAs, which are non-coding RNA molecules. After a thorough investigation, it was discovered that these circRNAs have critical biological roles. CircRNAs have a variety of biological functions, including their ability to operate as microRNA sponges, interact with proteins to alter their stabilities and activities, and provide templates for the translation of proteins. Evidence supports a link between the emergence of numerous diseases, including various cancer types, and dysregulated circRNA expression. It is commonly known that a significant contributing element to cancer development is the disruption of numerous molecular pathways essential for preserving cellular and tissue homeostasis. The dysregulation of multiple biological processes is one of the hallmarks of cancer, and the molecular pathways linked to these processes are thought to be promising targets for therapeutic intervention. The biological and carcinogenic effects of circRNAs in the context of cancer are thoroughly reviewed in this article. Specifically, we highlight circRNAs' involvement in signal transduction pathways and their possible use as novel biomarkers for the early identification and prognosis of human cancer.

Long non-coding RNA (lncRNA) PVT1 in drug resistance of cancers: Focus on pathological mechanisms.

According to estimates, cancer will be the leading cause of death globally in 2022, accounting for 9.6 million deaths. At present, the three main therapeutic modalities utilized to treat cancer are radiation therapy, chemotherapy, and surgery. However, during treatment, tumor cells resistant to chemotherapy may arise. Drug resistance remains a major oppose since it often leads to therapeutic failure. Furthermore, the term "acquired drug resistance" describes the situation where tumor cells already display drug resistance before undergoing chemotherapy. However, little is still known about the basic mechanisms underlying chemotherapy-induced drug resistance. The development of new technologies and bioinformatics has led to the discovery of additional genes associated with drug resistance. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been linked to an increased risk of cancer, according to a growing body of research. Apart from biological functions associated with cell division, development, pluripotency, and cell cycle, lncRNA PVT1 contributes significantly to the regulation of various aspects of genome function, such as transcription, splicing, and epigenetics. The article will address the mechanism by which lncRNA PVT1 influences drug resistance in cancer cells.

Role of genetically engineered mesenchymal stem cell exosomes and LncRNAs in respiratory diseases treatment.

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.

Getting to know ovarian cancer: Focusing on the effect of LncRNAs in this cancer and the effective signaling pathways.

This article undertakes a comprehensive investigation of ovarian cancer, examining the complex nature of this challenging disease. The main focus is on understanding the role of long non-coding RNAs (lncRNAs) in the context of ovarian cancer (OC), and their regulatory functions in disease progression. Through extensive research, the article identifies specific lncRNAs that play significant roles in the intricate molecular processes of OC. Furthermore, the study examines the signaling pathways involved in the development of OC, providing a detailed comprehension of the underlying molecular mechanisms. By connecting lncRNA dynamics with signaling pathways, this exploration not only advances our understanding of ovarian cancer but also reveals potential targets for therapeutic interventions. The findings open up opportunities for targeted treatments, highlighting the importance of personalized approaches in addressing this complex disease and driving progress in ovarian cancer research and treatment strategies.

Bilosomes as Nanocarriers for the Drug and Vaccine Delivery against Gastrointestinal Infections: Opportunities and Challenges.

The gastrointestinal tract (GIT) environment has an intricate and complex nature, limiting drugs' stability, oral bioavailability, and adsorption. Additionally, due to the drugs' toxicity and side effects, renders are continuously seeking novel delivery systems. Lipid-based drug delivery vesicles have shown various loading capacities and high stability levels within the GIT. Indeed, most vesicular platforms fail to efficiently deliver drugs toward this route. Notably, the stability of vesicular constructs is different based on the different ingredients added. A low GIT stability of liposomes and niosomes and a low loading capacity of exosomes in drug delivery have been described in the literature. Bilosomes are nonionic, amphiphilic, flexible surfactant vehicles that contain bile salts for the improvement of drug and vaccine delivery. The bilosomes' stability and plasticity in the GIT facilitate the efficient carriage of drugs (such as antimicrobial, antiparasitic, and antifungal drugs), vaccines, and bioactive compounds to treat infectious agents. Considering the intricate and harsh nature of the GIT, bilosomal formulations of oral substances have a remarkably enhanced delivery efficiency, overcoming these conditions. This review aimed to evaluate the potential of bilosomes as drug delivery platforms for antimicrobial, antiviral, antifungal, and antiparasitic GIT-associated drugs and vaccines.