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Journal of the American Academy of... Jan 2022Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and... (Review)
Review
Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via 2 main receptor families: G protein-coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines, such as interleukin-4, interleukin-13, interleukin-31, and thymic stromal lymphopoietin, are particularly important mediators that signal through shared Janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires that treatment approaches be tailored to specific etiologic itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this 2-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.
Topics: Analgesics, Opioid; Humans; Pruritus; Skin
PubMed: 34648873
DOI: 10.1016/j.jaad.2021.07.078 -
International Journal of Molecular... Mar 2023Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis,... (Review)
Review
Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated with uveitis and inflammatory bowel disease (Crohn's disease and ulcerative colitis). To capture these manifestations as well as the associated comorbidities, and to recognize their underlining common pathogenesis, the name of psoriatic disease was coined. The pathogenesis of PsA is complex and multifaceted, with an interplay of genetic predisposition, triggering environmental factors, and activation of the innate and adaptive immune system, although autoinflammation has also been implicated. Research has identified several immune-inflammatory pathways defined by cytokines (IL-23/IL-17, TNF), leading to the development of efficacious therapeutic targets. However, heterogeneous responses to these drugs occur in different patients and in the different tissues involved, resulting in a challenge to the global management of the disease. Therefore, more translational research is necessary in order to identify new targets and improve current disease outcomes. Hopefully, this may become a reality through the integration of different omics technologies that allow better understanding of the relevant cellular and molecular players of the different tissues and manifestations of the disease. In this narrative review, we aim to provide an updated overview of the pathophysiology, including the latest findings from multiomics studies, and to describe current targeted therapies.
Topics: Humans; Arthritis, Psoriatic; Comorbidity; Cytokines; Psoriasis
PubMed: 36902329
DOI: 10.3390/ijms24054901 -
Seminars in Reproductive Medicine May 2020Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is... (Review)
Review
Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial-myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.
Topics: Adenomyosis; Animals; Cell Movement; Dysmenorrhea; Endometrium; Female; Humans; Infertility, Female; Menorrhagia; Myometrium
PubMed: 33032339
DOI: 10.1055/s-0040-1716687 -
Chinese Medical Journal Feb 2020Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear.... (Review)
Review
Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear. To gain an insight into AIS pathogenesis, this review searched PubMed database up to June 2019, using key words or medical subject headings terms including "adolescent idiopathic scoliosis," "scoliosis," "pathogenesis," "etiology," "genetics," "mesenchymal stem cells," and their combinations, summarized existing literatures and categorized the theories or hypothesis into nine aspects. These aspects include bone marrow mesenchymal stem cell studies, genetic studies, tissue analysis, spine biomechanics measurements, neurologic analysis, hormone studies, biochemical analysis, environmental factor analysis, and lifestyle explorations. These categories could be a guidance for further etiology or treatment researches to gain inspiration.
Topics: Adolescent; Biomechanical Phenomena; Bone Density; Cerebellum; Chromosome Aberrations; Epigenesis, Genetic; Humans; Melatonin; Scoliosis; Vestibular Nuclei
PubMed: 31972723
DOI: 10.1097/CM9.0000000000000652 -
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 -
BJU International Apr 2021To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies. (Review)
Review
OBJECTIVES
To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies.
METHODS
The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined.
RESULTS
In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40 years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies.
CONCLUSION
BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.
Topics: Humans; Male; Prostatic Hyperplasia
PubMed: 32893964
DOI: 10.1111/bju.15229 -
Dermatology (Basel, Switzerland) 2020Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of... (Review)
Review
Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of melanocytes which results in typical nonscaly, chalky-white macules. In recent years, considerable progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Vitiligo is often dismissed as a cosmetic problem, although its effects can be psychologically devastating, often with a considerable burden on daily life. In 2011, an international consensus classified segmental vitiligo separately from all other forms of vitiligo, and the term vitiligo was defined to designate all forms of nonsegmental vitiligo. This review summarizes the current knowledge on vitiligo and attempts to give an overview of the future in vitiligo treatment.
Topics: Humans; Oxidative Stress; Quality of Life; Vitiligo
PubMed: 32155629
DOI: 10.1159/000506103 -
Frontiers in Immunology 2021Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune... (Review)
Review
Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.
Topics: Animals; Environment; Humans; IgA Vasculitis
PubMed: 34858429
DOI: 10.3389/fimmu.2021.771619 -
International Journal of Molecular... Dec 2022Alzheimer's disease (AD) is the most common type of dementia, accounting for 60% to 80% of all cases [...].
Alzheimer's disease (AD) is the most common type of dementia, accounting for 60% to 80% of all cases [...].
Topics: Humans; Alzheimer Disease
PubMed: 36613544
DOI: 10.3390/ijms24010107 -
International Journal of Molecular... Jun 2021Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as... (Review)
Review
Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.
Topics: Animals; Genetic Predisposition to Disease; Humans; Melanoma; Risk Factors; Signal Transduction; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 34203771
DOI: 10.3390/ijms22126395