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Rheumatoid arthritis (RA) is a common autoimmune condition and chronic inflammatory disease, mostly affecting synovial joints. The complex pathogenesis of RA is supportive of high morbidity, disability, and mortality rates. Pathological changes a common characteristic in RA synovial tissue is attributed to the inadequacy of apoptotic pathways. In that regard, apoptotic pathways have been the center of attention in RA therapeutic approaches. As the regulators in the complex network of apoptosis, microRNAs (miRNAs) are found to be vital modulators in both intrinsic and extrinsic pathways through altering their regulatory genes. Indeed, miRNA, a member of the family of non-coding RNAs, are found to be an important player in not even apoptosis, but proliferation, gene expression, signaling pathways, and angiogenesis. Aberrant expression of miRNAs is implicated in attenuation and/or intensification of various apoptosis routes, resulting in culmination of human diseases including RA. Considering the need for more studies focused on the underlying mechanisms of RA in order to elevate the unsatisfactory clinical treatments, this study is aimed to delineate the importance of apoptosis in the pathophysiology of this disease. As well, this review is focused on the critical role of miRNAs in inducing or inhibiting apoptosis of RA-synovial fibroblasts and fibroblast-like synoviocytes and how this mechanism can be exerted for therapeutic purposes for RA.
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Apoptosis , Artritis Reumatoide , MicroARNs , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Membrana Sinovial/patología , Membrana Sinovial/metabolismo , Sinoviocitos/metabolismo , Sinoviocitos/patología , Transducción de Señal , Fibroblastos/metabolismo , Fibroblastos/patología , AnimalesRESUMEN
During the last decades, the ever-increasing incidence of diseases has led to high rates of mortality throughout the world. On the other hand, the inability and deficiencies of conventional approaches (such as chemotherapy) in the suppression of diseases remain challenging issues. As a result, there is a fundamental requirement to develop novel, biocompatible, bioavailable, and practical nanomaterials to prevent the incidence and mortality of diseases. Chitosan (CS) derivatives and their blends are outstandingly employed as promising drug delivery systems for disease therapy. These biopolymers are indicated more efficient performance against diseases compared with conventional modalities. The CS blends possess improved physicochemical properties, ease of preparation, high affordability, etc. characteristics compared with other biopolymers and even pure CS which result in efficient thermal, mechanical, biochemical, and biomedical features. Also, these blends can be administrated through different routes without a long-term treatment period. Due to the mentioned properties, numerous formulations of CS blends are developed for pharmaceutical sciences to treat diseases. This review article highlights the progressions in the development of CS-based blends as potential drug delivery systems against diseases.
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Quitosano , Sistemas de Liberación de Medicamentos , Quitosano/química , Humanos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , AnimalesRESUMEN
The two primary forms of inflammatory disorders of the small intestine andcolon that make up inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). While ulcerative colitis primarily affects the colon and the rectum, CD affects the small and large intestines, as well as the esophagus,mouth, anus, andstomach. Although the etiology of IBD is not completely clear, and there are many unknowns about it, the development, progression, and recurrence of IBD are significantly influenced by the activity of immune system cells, particularly lymphocytes, given that the disease is primarily caused by the immune system stimulation and activation against gastrointestinal (GI) tract components due to the inflammation caused by environmental factors such as viral or bacterial infections, etc. in genetically predisposed individuals. Maintaining homeostasis and the integrity of the mucosal barrier are critical in stopping the development of IBD. Specific immune system cells and the quantity of secretory mucus and microbiome are vital in maintaining this stability. Th22 cells are helper T lymphocyte subtypes that are particularly important for maintaining the integrity and equilibrium of the mucosal barrier. This review discusses the most recent research on these cells' biology, function, and evolution and their involvement in IBD.
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Enfermedades Inflamatorias del Intestino , Humanos , Animales , Enfermedades Inflamatorias del Intestino/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiologíaRESUMEN
Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.
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Although CAR-T cell therapy has emerged as a game-changer in cancer immunotherapy several bottlenecks limit its widespread use as a front-line therapy. Current protocols for the production of CAR-T cells rely mainly on the use of lentiviral/retroviral vectors. Nevertheless, according to the safety concerns around the use of viral vectors, there are several regulatory hurdles to their clinical use. Large-scale production of viral vectors under "Current Good Manufacturing Practice" (cGMP) involves rigorous quality control assessments and regulatory requirements that impose exorbitant costs on suppliers and as a result, lead to a significant increase in the cost of treatment. Pursuing an efficient non-viral method for genetic modification of immune cells is a hot topic in cell-based gene therapy. This study aims to investigate the current state-of-the-art in non-viral methods of CAR-T cell manufacturing. In the first part of this study, after reviewing the advantages and disadvantages of the clinical use of viral vectors, different non-viral vectors and the path of their clinical translation are discussed. These vectors include transposons (sleeping beauty, piggyBac, Tol2, and Tc Buster), programmable nucleases (ZFNs, TALENs, and CRISPR/Cas9), mRNA, plasmids, minicircles, and nanoplasmids. Afterward, various methods for efficient delivery of non-viral vectors into the cells are reviewed.
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Vectores Genéticos , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Animales , Linfocitos T/inmunología , Terapia Genética/métodos , Neoplasias/terapiaRESUMEN
Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs.
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Enfermedades Autoinmunes , Inmunoterapia Adoptiva , Células Asesinas Naturales , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Receptores Quiméricos de Antígenos/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/inmunología , Inmunoterapia Adoptiva/métodos , AnimalesRESUMEN
Long noncoding RNAs (lncRNAs) are a category of noncoding RNAs characterized by their length, often exceeding 200 nucleotides. There is a growing body of data that indicate the significant involvement of lncRNAs in a wide range of disorders, including cancer. lncRNA H19 was among the initial lncRNAs to be identified and is transcribed from the H19 gene. The H19 lncRNA exhibits significant upregulation in a diverse range of human malignancies, such as breast, colorectal, pancreatic, glioma, and gastric cancer. Moreover, the overexpression of H19 is frequently associated with a worse prognosis among individuals diagnosed with cancer. H19 has been shown to have a role in facilitating several cellular processes, including cell proliferation, invasion, migration, epithelial-mesenchymal transition, metastasis, and apoptosis. This article summarizes the aberrant upregulation of H19 in human malignancies, indicating promising avenues for future investigations on cancer diagnostics and therapeutic interventions.
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Neoplasias , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Transición Epitelial-Mesenquimal/genética , Proliferación Celular , Apoptosis , Regulación Neoplásica de la Expresión Génica , Movimiento CelularRESUMEN
Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.
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Isquemia Encefálica , Precondicionamiento Isquémico , Accidente Cerebrovascular Isquémico , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Precondicionamiento Isquémico/métodos , Células Madre Mesenquimatosas/metabolismoRESUMEN
Nucleic acid vaccines (NAVs) have the potential to be economical, safe, and efficacious. Furthermore, just the chosen antigen in the pathogen is the target of the immune responses brought on by NAVs. Triple-negative breast cancer (TNBC) treatment shows great promise for nucleic acid-based vaccines, such as DNA (as plasmids) and RNA (as messenger RNA [mRNA]). Moreover, cancer vaccines offer a compelling approach that can elicit targeted and long-lasting immune responses against tumor antigens. Bacterial plasmids that encode antigens and immunostimulatory molecules serve as the foundation for DNA vaccines. In the 1990s, plasmid DNA encoding the influenza A nucleoprotein triggered a protective and targeted cytotoxic T lymphocyte (CTL) response, marking the first instance of DNA vaccine-mediated immunity. Similarly, in vitro transcribed mRNA was first successfully used in animals in 1990. At that point, mice were given an injection of the gene encoding the mRNA sequence, and the researchers saw the production of a protein. We begin this review by summarizing our existing knowledge of NAVs. Next, we addressed NAV delivery, emphasizing the need to increase efficacy in TNBC.
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Neoplasias de la Mama Triple Negativas , Vacunas de ADN , Humanos , Ratones , Animales , Vacunación Basada en Ácidos Nucleicos , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/patología , Inmunoterapia , ADN , ARN Mensajero/genéticaRESUMEN
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.
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ARN Largo no Codificante , Humanos , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Procesos Neoplásicos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
In this review, we intend to summarize the most important discoveries in the deborylative (thio-/seleno-) cyanation of aryl boronic acids from 2006 to the end of 2023. Thus, the review is divided into three parts. The first section focuses exclusively on cyanation of aryl boronic acids into aryl nitriles. The second section covers the available literature on the synthesis of aryl thiocyanates through thiocyanation of respective aryl boronic acids. The third will discuss selenocyanation of aryl boronic acids into aryl selenocyanates.
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Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis. Sesquiterpene lactones are one of the large and diverse groups of planet-derived phytochemicals that can be used as sources for a variety of drugs. Some sesquiterpene lactones possess many biological activities such as anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic. This review article briefly overviews the intrinsic and extrinsic pathways of apoptosis and the interactions between the modulators of both pathways. Also, the present review summarizes the potential effects of sesquiterpene lactones on different modulators of the intrinsic and extrinsic pathways of apoptosis in a variety of cancer cell lines and animal models. The main purpose of the present review is to give a clear picture of the current knowledge about the pro-apoptotic effects of sesquiterpene lactones on various cancers to provide future direction in cancer therapeutics.
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The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.
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Neoplasias , Vacunas , Humanos , ARN Mensajero/genética , Vacunas/uso terapéutico , Vacunación/métodos , Neoplasias/tratamiento farmacológicoRESUMEN
Metastatic cancer, which accounts for the majority of cancer fatalities, is a difficult illness to treat. Currently used cancer treatments include radiation therapy, chemotherapy, surgery, and targeted treatment (immune, gene, and hormonal). The disadvantages of these treatments include a high risk of tumor recurrence and surgical complications that may result in permanent deformities. On the other hand, most chemotherapy drugs are small molecules, which usually have unfavorable side effects, low absorption, poor selectivity, and multi-drug resistance. Anticancer drugs can be delivered precisely to the cancer spot by encapsulating them to reduce side effects. Stimuli-responsive nanocarriers can be used for drug release at cancer sites and provide target-specific delivery. As previously stated, metastasis is the primary cause of cancer-related mortality. We have evaluated the usage of nano-medications in the treatment of some metastatic tumors.
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Antineoplásicos , Neoplasias , Humanos , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Resistencia a Múltiples MedicamentosRESUMEN
Having been involved in complex cellular regulatory networks and cell-to-cell communications, non-coding RNAs (lncRNAs) have become functional carriers that transmit information between cells and tissues, modulate tumor microenvironments, encourage angiogenesis and invasion, and make tumor cells more resistant to drugs. Immune cells' exosomal lncRNAs may be introduced into tumor cells to influence the tumor's course and the treatment's effectiveness. Research has focused on determining if non-coding RNAs affect many target genes to mediate regulating recipient cells. The tumor microenvironment's immune and cancer cells are influenced by lncRNAs, which may impact a treatment's efficacy. The lncRNA-mediated interaction between cancer cells and immune cells invading the tumor microenvironment has been the subject of numerous recent studies. On the other hand, tumor-derived lncRNAs' control over the immune system has not gotten much attention and is still a relatively new area of study. Tumor-derived lncRNAs are recognized to contribute to tumor immunity, while the exact mechanism is unclear.