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Frontiers in Immunology 2023Graves' orbitopathy (GO) is an organ-specific autoimmune disease, but its pathogenesis remains unclear. There are few review articles on GO research from the perspective... (Review)
Review
Graves' orbitopathy (GO) is an organ-specific autoimmune disease, but its pathogenesis remains unclear. There are few review articles on GO research from the perspective of target cells and target antigens. A systematic search of PubMed was performed, focusing mainly on studies published after 2015 that involve the role of target cells, orbital fibroblasts (OFs) and orbital adipocytes (OAs), target antigens, thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R), and their corresponding antibodies, TSHR antibodies (TRAbs) and IGF-1R antibodies (IGF-1R Abs), in GO pathogenesis and the potentially effective therapies that target TSHR and IGF-1R. Based on the results, OFs may be derived from bone marrow-derived CD34+ fibrocytes. In addition to CD34+ OFs, CD34- OFs are important in the pathogenesis of GO and may be involved in hyaluronan formation. CD34- OFs expressing Slit2 suppress the phenotype of CD34+ OFs. β-arrestin 1 can be involved in TSHR/IGF-1R crosstalk as a scaffold. Research on TRAbs has gradually shifted to TSAbs, TBAbs and the titre of TRAbs. However, the existence and role of IGF-1R Abs are still unknown and deserve further study. Basic and clinical trials of TSHR-inhibiting therapies are increasing, and TSHR is an expected therapeutic target. Teprotumumab has become the latest second-line treatment for GO. This review aims to effectively describe the pathogenesis of GO from the perspective of target cells and target antigens and provide ideas for its fundamental treatment.
Topics: Humans; Graves Ophthalmopathy; Receptors, Thyrotropin; Signal Transduction; Receptors, G-Protein-Coupled; Phenotype
PubMed: 36742308
DOI: 10.3389/fimmu.2023.1062045 -
The Journal of Dermatology Mar 2021Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of... (Review)
Review
Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of melanocytes. Sustained recent efforts have resulted in a detailed understanding of the genetic architecture of vitiligo. About 80% of vitiligo risk is attributable to genetic factors; and the rest (20%) is attributable to the environment. Over the past decade, substantial progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Melanocytes from patients with vitiligo are more susceptible to oxidative stress which begets the release of exosomes and inflammatory cytokines that will lead to activation of the innate immune response and subsequently to adaptive immune response through activation of autoreactive cytotoxic CD8+ T cells. These produce interferon-γ (IFN-γ) which promotes disease progression through IFN-γ-induced chemokine secretion from surrounding keratinocytes to further recruit T cells to the skin through a positive feedback loop. CD8 tissue-resident memory T cells are in turn responsible for long-term maintenance and potential relapse of vitiligo in human patients through cytokine-mediated recruitment of T cells from the circulation. This review summarizes the current knowledge on vitiligo and attempt to give an overview of the future in vitiligo treatment.
Topics: Humans; Interferon-gamma; Keratinocytes; Melanocytes; Skin; Vitiligo
PubMed: 33404102
DOI: 10.1111/1346-8138.15743 -
International Journal of Molecular... Nov 2022The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced... (Review)
Review
The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.
Topics: Humans; Child; Adolescent; Cholelithiasis; Causality; Comorbidity; Genetic Predisposition to Disease
PubMed: 36362164
DOI: 10.3390/ijms232113376 -
International Journal of Molecular... Sep 2023Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the... (Review)
Review
Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast-myofibroblast transition, epithelial-mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.
Topics: Male; Animals; Humans; Female; Phosphatidylinositol 3-Kinases; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Risk Factors; Rheumatoid Factor
PubMed: 37833957
DOI: 10.3390/ijms241914509 -
Dermatologic Therapy Mar 2022Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence... (Review)
Review
Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation. Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.
Topics: Aged; Carcinoma, Merkel Cell; Humans; Merkel cell polyomavirus; Prognosis; Skin Neoplasms; Ultraviolet Rays
PubMed: 34967084
DOI: 10.1111/dth.15292 -
Annual Review of Pathology Jan 2020Malaria remains a major public health threat in tropical and subtropical regions across the world. Even though less than 1% of malaria infections are fatal, this leads... (Review)
Review
Malaria remains a major public health threat in tropical and subtropical regions across the world. Even though less than 1% of malaria infections are fatal, this leads to about 430,000 deaths per year, predominantly in young children in sub-Saharan Africa. Therefore, it is imperative to understand why a subset of infected individuals develop severe syndromes and some of them die and what differentiates these cases from the majority that recovers. Here, we discuss progress made during the past decade in our understanding of malaria pathogenesis, focusing on the major human parasite .
Topics: Africa South of the Sahara; Child; Child, Preschool; Disease Susceptibility; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Severity of Illness Index
PubMed: 31648610
DOI: 10.1146/annurev-pathmechdis-012419-032640 -
Critical Reviews in Oncology/hematology Jan 2020Cancer and chemotherapy-induced anemia (CIA) is commonly encountered among patients undergoing active chemotherapy with or without radiation therapy. Its pathogenesis is... (Review)
Review
Cancer and chemotherapy-induced anemia (CIA) is commonly encountered among patients undergoing active chemotherapy with or without radiation therapy. Its pathogenesis is complex and is often difficult to identify. Symptoms related to CIA may have a negative impact on quality of life and may influence treatment efficacy, disease progression and even survival. The recent major setback of erythropoietin-stimulating agents (ESAs) and the reluctance to transfuse cancer patients with mild and even moderate anemia, had resulted in significant under-treatment of CIA. The discovery of hepcidin and its role in iron homeostasis has revolutionized our understanding of the pathogenesis of iron deficiency and iron overload states. In the present review we examine the multifactorial pathogenesis of CIA, addressing the main mechanisms by which the tumor and immune system affect anemia. Additionally, we discuss the treatment options with more focus on the utilization of the new intravenous iron formulations for this indication.
Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life
PubMed: 31830663
DOI: 10.1016/j.critrevonc.2019.102837 -
Advances in Experimental Medicine and... 2020In the past decade, research focusing on the gut microbiota has attracted a growing number of scientists. We increasingly realize that the gut microbiota plays a key...
In the past decade, research focusing on the gut microbiota has attracted a growing number of scientists. We increasingly realize that the gut microbiota plays a key role in both maintaining host homeostasis and affecting the progression of multiple diseases, which means that the microorganisms living in the intestines would not only influence the gastrointestinal tract but also impact other important organs such as the liver, brain, kidney, and lung. The underlying modulatory mechanism is complicated; however, we can expand the existing insight on the development of organ damage pathogenesis and discover novel therapeutic targets for organ injury-related diseases by investigating this "hot-topic". In this chapter, we will present a broad overview of the gut microbiota and organ injury, as well as the latest research achievements regarding the linkage between them.
Topics: Brain Diseases; Dysbiosis; Gastrointestinal Microbiome; Homeostasis; Humans; Kidney Diseases; Liver Diseases; Lung Diseases
PubMed: 32323176
DOI: 10.1007/978-981-15-2385-4_1 -
Immunopharmacology and Immunotoxicology Apr 2021Atopic dermatitis (AD) is the long-lasting chronic inflammatory skin condition associated with cutaneous hyper-reactivity and triggered by environmental factors. The... (Review)
Review
Atopic dermatitis (AD) is the long-lasting chronic inflammatory skin condition associated with cutaneous hyper-reactivity and triggered by environmental factors. The attributes of AD include dry skin, pruritus, lichenification and frequent eczematous abrasions. This has a strong heritable aspect and typically occurs with asthma and allergic rhinitis. The complex pathological mechanism behind AD etiology is epidermal barrier destruction resulting in the lack of filaggrin protein that can induce inflammation and T-cell infiltration. T-helper 2 cell-mediated pathways also bear the responsibility of damage to the epidermal barrier. Certain causative factors for AD include microbial imbalance of skin microbiota, immunoglobulin-E-induced sensitization and neuro-inflammation. Numerous beneficial topical and oral treatments have been available to patients and there are even more drugs in the pipeline for the treatment of AD. Topical moisturizers, corticosteroids, anti-inflammatory agents such as calcineurin inhibitors, phototherapy, cAMP-specific 3, 5 half-cyclic phosphodiesterase 4 inhibitors and systemic immunosuppressants are widely available for AD treatments. Different positions and pathways inside the immune system including JAK-STAT, phosphodiesterase 4, aryl hydrocarbon receptor and T-helper 2 cytokines are targeted by above-mentioned drug treatments. Instead of the severe side effects of topical steroids and oral antihistamines, herbal plants and their derived phytoconstituents are commonly used for the treatment of AD. A clear understanding of AD's cellular and molecular pathogenesis through substantial advancement in genetics, skin immunology and psychological factors resulted in advancement of AD management. Therefore, the review highlights the recent advancements in the understanding of clinical features, etiology, pathogenesis, treatment and management and non-adherence to AD treatment.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents; Biological Products; Dermatitis, Atopic; Environmental Exposure; Filaggrin Proteins; Humans; Immunosuppressive Agents; Phosphodiesterase 4 Inhibitors
PubMed: 33645388
DOI: 10.1080/08923973.2021.1889583 -
Seminars in Liver Disease Feb 2020Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The... (Review)
Review
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.
Topics: Animals; Apoptosis; Environmental Exposure; Epithelial Cells; Female; Genetic Predisposition to Disease; Humans; Liver Cirrhosis, Biliary; Male; Mitochondria
PubMed: 31537031
DOI: 10.1055/s-0039-1697617