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Open Biology Sep 2020Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. Derangement... (Review)
Review
Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. Derangement in wound-linked cellular behaviours, as occurs with diabetes and ageing, can lead to healing impairment and the formation of chronic, non-healing wounds. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence. Thus, there is an urgent requirement for the improved biological and clinical understanding of the mechanisms that underpin wound repair. Here, we review the cellular basis of tissue repair and discuss how current and emerging understanding of wound pathology could inform future development of efficacious wound therapies.
Topics: Acute Disease; Animals; Chronic Disease; Disease Susceptibility; Humans; Translational Research, Biomedical; Wound Healing; Wounds and Injuries
PubMed: 32993416
DOI: 10.1098/rsob.200223 -
Genes & Development Dec 2020Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive... (Review)
Review
Cellular senescence is a stress response that elicits a permanent cell cycle arrest and triggers profound phenotypic changes such as the production of a bioactive secretome, referred to as the senescence-associated secretory phenotype (SASP). Acute senescence induction protects against cancer and limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting senescent cells to delay aging and limit dysfunction, known as "senotherapy," is gaining momentum. While drugs that selectively kill senescent cells, termed "senolytics" are a major focus, SASP-centered approaches are emerging as alternatives to target senescence-associated diseases. Here, we summarize the regulation and functions of the SASP and highlight the therapeutic potential of SASP modulation as complimentary or an alternative to current senolytic approaches.
Topics: Aging; Cellular Senescence; Disease Susceptibility; Drug Development; Drug Therapy; Epigenesis, Genetic; Gene Expression Regulation; Humans; Pharmaceutical Preparations; Secretory Pathway; Signal Transduction
PubMed: 33262144
DOI: 10.1101/gad.343129.120 -
Journal of Immunology Research 2019Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.
Topics: Animals; Disease Susceptibility; Environment; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases
PubMed: 31886308
DOI: 10.1155/2019/7247238 -
International Journal of Molecular... Jan 2022Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic... (Review)
Review
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.
Topics: Animals; Arthritis, Rheumatoid; Biomarkers; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Immune System; Molecular Diagnostic Techniques; Prognosis; Treatment Outcome
PubMed: 35055087
DOI: 10.3390/ijms23020905 -
Frontiers in Neuroendocrinology Jul 2019Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of... (Review)
Review
Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models. Finally, we provide evidence that 5-HT is a critical factor linking dysregulation of the circadian system and mood. Determining how these two systems interact may provide novel therapeutic targets for depression.
Topics: Animals; Circadian Rhythm; Depression; Depressive Disorder; Disease Susceptibility; Humans; Serotonin; Stress, Psychological
PubMed: 31002895
DOI: 10.1016/j.yfrne.2019.04.003 -
Immunity Nov 2021Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. This recently implemented definition does not capture... (Review)
Review
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. This recently implemented definition does not capture the heterogeneity or the underlying pathophysiology of the syndrome, which is characterized by concurrent unbalanced hyperinflammation and immune suppression. Here, we review current knowledge of aberrant immune responses during sepsis and recent initiatives to stratify patients with sepsis into subgroups that are more alike from a clinical and/or pathobiological perspective, which could be key for identification of patients who are more likely to benefit from specific immune interventions.
Topics: Disease Susceptibility; Host-Pathogen Interactions; Humans; Immunity; Sepsis
PubMed: 34758337
DOI: 10.1016/j.immuni.2021.10.012 -
Journal of Immunology Research 2019Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically... (Review)
Review
Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically applying diagnostic scores; however, the heterotopic disease phenotype often makes a rapid determination of disease challenging. AIH responds favorably to steroids and pharmacologic immunosuppression, and liver transplantation is only necessary in cases with acute liver failure or end-stage liver cirrhosis. Recurrence or development of de novo AIH after transplantation is possible, and treatment is similar to standard AIH therapy. Current experimental investigations of T cell-mediated autoimmune pathways and analysis of changes within the intestinal microbiome might advance our knowledge on the pathogenesis of AIH and trigger a spark of hope for novel therapeutic strategies.
Topics: Animals; Autoimmunity; Biomarkers; Combined Modality Therapy; Disease Susceptibility; Hepatitis, Autoimmune; Humans; Risk Factors; Severity of Illness Index; Treatment Outcome
PubMed: 31886312
DOI: 10.1155/2019/9437043 -
Trends in Cancer Jul 2019Cancer immunotherapy aims to arm patients with cancer-fighting immunity. Many new cancer-specific immunotherapeutic drugs have gained approval in the past several years,... (Review)
Review
Cancer immunotherapy aims to arm patients with cancer-fighting immunity. Many new cancer-specific immunotherapeutic drugs have gained approval in the past several years, demonstrating immunotherapy's efficacy and promise as an anticancer modality. Despite these successes, several outstanding questions remain for cancer immunotherapy, including how to make immunotherapy more efficacious in a broader range of cancer types and patients, and how to predict which patients will respond or not respond to therapy. We present a case for integrative systems approaches that will answer these questions. This involves applying mechanistic and statistical modeling, establishing consistent and widely adopted experimental tools to generate systems-level data, and creating sustained mechanisms of support. If implemented, these approaches will lead to major advances in cancer treatment.
Topics: Combined Modality Therapy; Computational Biology; Disease Susceptibility; Humans; Immunotherapy; Immunotherapy, Adoptive; Machine Learning; Models, Theoretical; Neoplasms; Research Design; Treatment Outcome
PubMed: 31311655
DOI: 10.1016/j.trecan.2019.05.010 -
Pediatric Blood & Cancer Jul 2020Oncologists and cancer biologists are frequently confronted by the question of what causes cancer? This is particularly vexing for cancers affecting children and young... (Review)
Review
Oncologists and cancer biologists are frequently confronted by the question of what causes cancer? This is particularly vexing for cancers affecting children and young adults who have had limited exposure to environmental mutagens and the effects of aging. Here, I focus on a general framework of the causes of early-onset cancer development in children and young adults by relating inherited and constitutional cancer predisposition, oncogenic pathogens, and developmental mutations. This framework has implications not only for mechanistic investigation of young cancers, but should also clarify improved strategies for their treatment, screening, and potential prevention.
Topics: Adolescent; Carcinogens, Environmental; Child; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Medical Oncology; Mutagens; Mutation; Neoplasms; Neoplastic Syndromes, Hereditary; Oncogenic Viruses; Pediatrics; Young Adult
PubMed: 32391946
DOI: 10.1002/pbc.28335 -
Circulation Aug 2021Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a... (Review)
Review
Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.
Topics: Animals; Biopsy; Child; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Multimodal Imaging; Myocarditis; Prognosis; Symptom Assessment; Treatment Outcome
PubMed: 34229446
DOI: 10.1161/CIR.0000000000001001