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Indian Journal of Dermatology,... 2023For any biological response, transmission of extracellular signals to the nucleus is required for DNA transcription and gene expression. In that respect,... (Review)
Review
For any biological response, transmission of extracellular signals to the nucleus is required for DNA transcription and gene expression. In that respect, cytokines/chemokines are well-known inflammatory agents which play a critical role in signalling pathways by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signalling proteins (Janus kinase-signal transducers and activators of transcription) which are a group of intracellular kinase molecules. Cytokines are a category of small proteins (∼5-25 kDa) that play a major role in cell signalling and are major drivers of an autoimmune response. Here we will discuss the role of Janus kinase-signal transducers and activators of transcription kinase cascades in the inflammatory-proliferative cascades of autoimmune disease and about the recent progress in the development of oral synthetic Janus kinase inhibitors (JAKi) and their therapeutic efficacies in dermatologic and systemic autoimmune diseases. Therapeutic efficacy of Janus kinase inhibitors is now well established in the treatment of array of autoimmune and inflammatory disease: spondylarthritis with a special focus on psoriatic arthritis (PsA) and its dermatologic manifestations (psoriasis) and ankylosing spondylitis (AS), atopic dermatitis (AD), alopecia areata (AA), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In addition to the first-generation Janus kinase inhibitors several new-generation Janus kinase inhibitors are currently being evaluated. It is expected that these Janus kinase inhibitors likely have higher potency and less adverse effects as compared to their predecessors. Here we have discussed: (1) the functional significance of the Janus kinase-signal transducers and activators of transcription kinase cascades in the inflammatory-proliferative processes of autoimmune diseases and its cellular/molecular mechanisms and (2) progress in the development of oral synthetic Janus kinase inhibitors and their therapeutic efficacies in several systemic and cutaneous autoimmune diseases.
Topics: Humans; Janus Kinase Inhibitors; Arthritis, Psoriatic; Janus Kinases; Autoimmune Diseases; Cytokines
PubMed: 37609730
DOI: 10.25259/IJDVL_1152_2022 -
Cureus Jul 2023Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin, leading to red blood cell deformities and subsequent vaso-occlusive events.... (Review)
Review
Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin, leading to red blood cell deformities and subsequent vaso-occlusive events. Platelet activation and adhesion play a significant role in the pathophysiology of SCD, contributing to the development of complications such as vaso-occlusive events, stroke, acute chest syndrome, and other manifestations. Antiplatelet therapy has emerged as a potential strategy to mitigate these complications by modulating the platelet function and reducing thrombotic events. This review article provides an overview of antiplatelet therapy's role in managing SCD patients. It discusses the pathophysiological abnormalities in the platelet function in SCD, the rationale for antiplatelet therapy, and the evidence supporting its use in various clinical scenarios. The article explores aspirin as the primary antiplatelet agent in SCD, including its mechanism of action, dosing considerations, and efficacy and safety data. Additionally, it highlights other antiplatelet agents, such as clopidogrel, prasugrel, ticagrelor, and emerging therapies under investigation. Clinical applications of antiplatelet therapy in primary and secondary prevention and the management of acute chest syndrome and other SCD complications are also discussed. Safety considerations are emphasized, including bleeding risk assessment, monitoring, and patient selection for antiplatelet therapy. Finally, the review highlights future research and clinical practice directions, including the development of novel antiplatelet agents, combination therapies, and the integration of antiplatelet therapy with other SCD treatments. Overall, this review provides a comprehensive understanding of the current role of antiplatelet therapy in SCD management, the challenges faced, and future directions for improving patient outcomes.
PubMed: 37602132
DOI: 10.7759/cureus.42058 -
Biomedicine & Pharmacotherapy =... Sep 2023Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from... (Review)
Review
Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from bacteria and are important messengers for communication between bacteria and their environment. OMVs play multiple roles in bacterial survival and adaptation and can affect host physiological functions and disease development by acting on host cell membranes and altering host cell signaling pathways. This paper summarizes the mechanisms of OMV genesis and the multiple roles of OMVs in the tumor microenvironment. Also, this paper discusses the prospects of OMVs for a wide range of applications in drug delivery, tumor diagnosis, and therapy.
Topics: Humans; Bacterial Outer Membrane; Extracellular Vesicles; Gram-Negative Bacteria; Neoplasms; Tumor Microenvironment
PubMed: 37442066
DOI: 10.1016/j.biopha.2023.115120 -
Journal of Integrative Neuroscience Jan 2024Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of... (Review)
Review
Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of diseases such as cancer, cardiovascular disorders, and psychiatric disorders. Numerous studies suggest a connection between epigenetic changes and mood disorders. In this study, we performed a comprehensive search using PubMed and Google for the terms "epigenetics", "ageing", "miRNA", "schizophrenia", and "mood disorders" in the titles and abstracts of articles. Epigenetic changes during early life may play a crucial role in triggering severe mental disorders and shaping their clinical trajectory. Although these alterations can take place at any age, their impact may not be immediately evident or observable until later in life. Epigenetic modifications play a crucial role in the ageing process and challenge the prevailing belief that mutations are the primary driver of ageing. However, it is plausible that these epigenetic changes are a consequence of the disorder rather than its root cause. Moreover, both the disorder and the epigenetic alterations may be influenced by shared environmental or genetic factors. In the near future, we might be able to replace chronological age with biological age, based on the epigenetic clock, with the promise of providing greater therapeutic benefits. A wide range of epigenetic drugs are currently under development at various stages. Although their full effectiveness is yet to be realized, they show great potential in the treatment of cancer, psychiatric disorders, and other complex diseases.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Mental Disorders; Schizophrenia; MicroRNAs; Aging
PubMed: 38287856
DOI: 10.31083/j.jin2301013 -
Children (Basel, Switzerland) Jul 2023Every child, irrespective of socioeconomic status, ethnicity, or ability, deserves the fundamental right to experience play, which is a powerful and enriching activity...
Every child, irrespective of socioeconomic status, ethnicity, or ability, deserves the fundamental right to experience play, which is a powerful and enriching activity that fosters their physical and mental health. Regrettably, most public play spaces hinder the complete inclusion of children with disabilities, with the main reason being a lack of universal accessibility. This study identified existing international and Canadian policies and community best practices related to inclusive playgrounds, and gathered stakeholders' opinions on the present condition of playgrounds, including challenges faced by children with disabilities and recommendations to make playgrounds inclusive. The questionnaires were completed by 97 participants. In addition, 10 individual interviews and three focus groups were performed. Ten policy documents and five community best practices were found. Our investigation identified factors that influence the design and implementation of inclusive playgrounds, categorized into three main areas: physical, social, and political environments. The results indicate that children with disabilities lack opportunities to engage fully in the physical and social aspects of playgrounds and spontaneous play activities with their peers. Notably, children with multiple disabilities may not feel welcomed or included in existing public play spaces.
PubMed: 37628308
DOI: 10.3390/children10081308 -
Frontiers in Immunology 2023Nicotinamide adenine dinucleotide (NAD) is indispensable for various oxidation-reduction reactions in mammalian cells, particularly during energy production. Malignant... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is indispensable for various oxidation-reduction reactions in mammalian cells, particularly during energy production. Malignant cells increase the expression levels of NAD biosynthesis enzymes for rapid proliferation and biomass production. Furthermore, mounting proof has indicated that NAD-degrading enzymes (NADases) play a role in creating the immunosuppressive tumor microenvironment (TME). Interestingly, both inhibiting NAD synthesis and targeting NADase have positive implications for cancer treatment. Here we summarize the detrimental outcomes of increased NAD production, the functions of NAD metabolic enzymes in creating an immunosuppressive TME, and discuss the progress and clinical translational potential of inhibitors for NAD synthesis and therapies targeting NADase.
Topics: Animals; NAD; NAD+ Nucleosidase; Mammals; Neoplasms
PubMed: 38116009
DOI: 10.3389/fimmu.2023.1269896 -
Molecular and Cellular Neurosciences Sep 2023Mitochondrial dysfunction can arise from genetic defects or environmental exposures and impact a wide range of biological processes. Among these are metabolic pathways... (Review)
Review
Mitochondrial dysfunction can arise from genetic defects or environmental exposures and impact a wide range of biological processes. Among these are metabolic pathways involved in glutamine catabolism, anabolism, and glutamine-glutamate cycling. In recent years, altered glutamine metabolism has been found to play important roles in the pathologic consequences of mitochondrial dysfunction. Glutamine is a pleiotropic molecule, not only providing an alternate carbon source to glucose in certain conditions, but also playing unique roles in cellular communication in neurons and astrocytes. Glutamine consumption and catabolic flux can be significantly altered in settings of genetic mitochondrial defects or exposure to mitochondrial toxins, and alterations to glutamine metabolism appears to play a particularly significant role in neurodegenerative diseases. These include primary mitochondrial diseases like Leigh syndrome (subacute necrotizing encephalopathy) and MELAS (mitochondrial myopathy with encephalopathy, lactic acidosis, and stroke-like episodes), as well as complex age-related neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Pharmacologic interventions targeting glutamine metabolizing and catabolizing pathways appear to provide some benefits in cell and animal models of these diseases, indicating glutamine metabolism may be a clinically relevant target. In this review, we discuss glutamine metabolism, mitochondrial disease, the impact of mitochondrial dysfunction on glutamine metabolic processes, glutamine in neurodegeneration, and candidate targets for therapeutic intervention.
Topics: Animals; Glutamine; MELAS Syndrome; Mitochondria; Neurodegenerative Diseases; Mitochondrial Diseases
PubMed: 37586651
DOI: 10.1016/j.mcn.2023.103887 -
Clinical Medicine (London, England) Nov 2023Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to...
Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.
Topics: Humans; Crohn Disease; Quality of Life; Immunosuppressive Agents; Remission Induction
PubMed: 38065612
DOI: 10.7861/clinmed.2023-0493 -
Cancers Jul 2023Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States. Among newly diagnosed patients with CRC, 20% will present with... (Review)
Review
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States. Among newly diagnosed patients with CRC, 20% will present with metastatic disease and another 25% will develop metastases. The surgical resection of the primary tumor and metastatic disease sites confers the best chance at long-term survival. Unfortunately, many patients will recur after resection or present with unresectable disease. As such, metastatic CRC is commonly treated with a combination of surgery, systemic therapy, and/or liver-directed therapies. Despite best efforts, 5-year survival for unresectable metastatic CRC is only about 20%. CRC is a heterogeneous disease and the underlying genetic differences inform behavior, treatment strategy, and prognosis. Given the limitations of cytotoxic chemotherapy and the growing role of molecular profiling, research has focused on identifying and developing targeted therapies. We herein review how genetic profiling informs prognosis, crucial cell-signaling pathways that play a role in CRC carcinogenesis, and currently approved targeted therapies for metastatic CRC.
PubMed: 37444625
DOI: 10.3390/cancers15133513 -
Cureus Jan 2024Folliculitis decalvans (FD) is a rare disease that causes inflammation on the scalp, leading to scarring alopecia. It commonly affects young and middle-aged men and is...
Folliculitis decalvans (FD) is a rare disease that causes inflammation on the scalp, leading to scarring alopecia. It commonly affects young and middle-aged men and is characterized by pustules, papules, scarring, hemorrhagic crusts, and erosions. The exact cause of FD is not fully understood, but it is believed that may play a role in its development. The condition is thought to be influenced by a combination of genetic, allergic, infectious, and immunological factors. This report describes a 20-year-old male patient who experienced painful pustules on his scalp for six months. The pustules first appeared on the occipital region and then spread to the crown. The patient was diagnosed with FD after a thorough clinical and pus culture examination. Treatment involved a month-long prescription of doxycycline (100 mg BD) and topical ozenoxacin (2%), which led to successful remission of the lesions.
PubMed: 38406166
DOI: 10.7759/cureus.52881