Recent Advances In Pathogenesis Research Articles

Recent Advances in Pathogenesis, Diagnostic Imaging, and Treatment of Sjögren’s Syndrome

It is our pleasure to present the Special Issue “Diagnosis and Treatment of Sjögren’s Syndrome” to the readers of the Journal of Clinical Medicine [...]

Recent advances in pathogenesis, diagnosis, and therapeutic approaches for digestive system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of large amounts of autoantibodies and immune complex formation. Because of their atypical clinical symptoms, SLE patients with digestive systeminvolvement may not be recognized or treated precisely and extensively. Clinicians should pay close attention to SLE with digestive system involvement, as these conditions can easily worsen the condition and possibly endanger the patient's life. In this review we summarized the pathogenesis, pathological characteristics, clinical manifestations, diagnosis, and therapies for digestive system involvement in SLE.

Case report: Interleukin-17 targeted biological therapy in netherton syndrome

Netherton syndrome (NS) is rare and multisystemic congenital skin disorder classically distinguied as a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata (TI), and an atopic diathesis. Recent advances in pathogenesis have explored the role of IL-23/Th17 pathway in NS. Herein, we present a 17 years old girl harbouring homozygous four base pair deletion in exon 26 of the SPINK5 gene, presented with pruritus, scaling, dry skin and generalized eczematous lesions. She was administered anti IL17A (subcutaneous secukinumab) therapy. The treatment was well tolerated and resulted in a favourable clinical response, reduction of the IL17A gene expression and CD4 + Th17 cell population after 6 months which revealed an abrogation of Th17-skewing during therapy.

Current trends and prospects of multiple sclerosis research in Arab countries.

Multiple sclerosis is a complex and intractable neurological disease associated with substantial morbidity, healthcare utilization, management cost, and loss of productivity. There has been an alarming increase in the number of multiple sclerosis cases in Arab countries in recent years, which has spurred an increase in local research. To analyse the multiple sclerosis research profile in Arab countries. A total of 781 publications focusing on multiple sclerosis research in Arab countries from 1983 to 2021 were extracted from the Web of Science database and analysed using bibliometric techniques. Publication on multiple sclerosis research increased sharply in the last decade, globally and in the Arab countries. However, Arab countries have only contributed 0.8% of the overall number of publications. Keyword pattern analysis showed that magnetic resonance imaging, optical coherence tomography, expanded disability status, demyelination, and epidemiology were the major themes of multiple sclerosis research in Arab countries. Case-control, cohort, and descriptive studies were the most prevalent study designs. However, there was a notable paucity of meta-analyses, randomized controlled trials, and clinical trials. Arab countries can improve their regional expertise and add a wealth of knowledge to global multiple sclerosis resources by diversifying their current research initiatives, and tracking recent advances in pathogenesis, diagnosis, and management of multiple sclerosis.

Diagnostic and therapeutic strategies for non-alcoholic fatty liver disease.

The global incidence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 25%. With the global increase in obesity and its associated metabolic syndromes, NAFLD has become an important cause of chronic liver disease in many countries. Despite recent advances in pathogenesis, diagnosis, and therapeutics, there are still challenges in its treatment. In this review, we briefly describe diagnostic methods, therapeutic targets, and drugs related to NAFLD. In particular, we focus on evaluating carbohydrate and lipid metabolism, lipotoxicity, cell death, inflammation, and fibrosis as potential therapeutic targets for NAFLD. We also summarized the clinical research progress in terms of drug development and combination therapy, thereby providing references for NAFLD drug development.

Arms Race between the Host and Pathogen Associated with Fusarium Head Blight of Wheat.

Fusarium head blight (FHB), or scab, caused by Fusarium species, is an extremely destructive fungal disease in wheat worldwide. In recent decades, researchers have made unremitting efforts in genetic breeding and control technology related to FHB and have made great progress, especially in the exploration of germplasm resources resistant to FHB; identification and pathogenesis of pathogenic strains; discovery and identification of disease-resistant genes; biochemical control, and so on. However, FHB burst have not been effectively controlled and thereby pose increasingly severe threats to wheat productivity. This review focuses on recent advances in pathogenesis, resistance quantitative trait loci (QTLs)/genes, resistance mechanism, and signaling pathways. We identify two primary pathogenetic patterns of Fusarium species and three significant signaling pathways mediated by UGT, WRKY, and SnRK1, respectively; many publicly approved superstar QTLs and genes are fully summarized to illustrate the pathogenetic patterns of Fusarium species, signaling behavior of the major genes, and their sophisticated and dexterous crosstalk. Besides the research status of FHB resistance, breeding bottlenecks in resistant germplasm resources are also analyzed deeply. Finally, this review proposes that the maintenance of intracellular ROS (reactive oxygen species) homeostasis, regulated by several TaCERK-mediated theoretical patterns, may play an important role in plant response to FHB and puts forward some suggestions on resistant QTL/gene mining and molecular breeding in order to provide a valuable reference to contain FHB outbreaks in agricultural production and promote the sustainable development of green agriculture.

New insights on multigenic autoinflammatory diseases.

Autoinflammatory diseases are disorders of the innate immune system, which can be either monogenic due to a specific genetic mutation or complex multigenic due to the involvement of multiple genes. The aim of this review is to explore and summarize the recent advances in pathogenesis, diagnosis, and management of genetically complex autoinflammatory diseases, such as Schnitzler’s syndrome; adult-onset Still’s disease; synovitis, acne, pustulosis, hyperostosis, osteitis syndrome/chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis; Adamantiades-Behçet’s disease; Yao syndrome; and periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome. The PubMed database was screened for relevant articles using free text words and specific search strings. The search was limited to English-language articles, reporting the results of studies in humans, published through March 2021. Evidence from literature suggest that these rare multigenic autoinflammatory diseases can present with different clinical features and the diagnosis of these diseases can be challenging due to a combination of nonspecific manifestations that can be seen in a variety of other conditions. Diagnostic delays and disease complications may occur due to low disease awareness and the lack of pathognomonic markers. The pathogeneses of these diseases are complex and in some cases precise pathogenesis is not clearly understood. Conventional treatments are commonly used for the management of these conditions, but biologics have shown promising results. Biologics targeting proinflammatory cytokines including IL-1, IL-6, TNF-α, IL-17A and IL-18 have been shown to ameliorate signs and symptoms of different multigenic autoinflammatory diseases.

Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments.

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells by their antigen-presenting functions. Moreover, the activation of the classical complement pathway participates to platelet opsonization and also to their destruction by complement-dependent cytotoxicity. Platelet destruction is also mediated by a FcγR-independent pathway, involving platelet desialylation that favors their binding to the Ashwell-Morell receptor and their clearance in the liver. Cytotoxic T cells also contribute to ITP pathogenesis by mediating cytotoxicity against megakaryocytes and peripheral platelets. The deficient megakaryopoiesis resulting from both the humoral and the cytotoxic immune responses is sustained by inappropriate levels of thrombopoietin, the major growth factor of megakaryocytes. The better understanding of ITP pathogenesis has provided important therapeutic advances. B cell-targeting therapies and thrombopoietin-receptor agonists (TPO-RAs) have been used for years. New emerging therapeutic strategies that inhibit FcγR signaling, the neonatal Fc receptor or the classical complement pathway, will deeply modify the management of ITP in the near future.

Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer's Disease.

Background The only conclusive way to diagnose Alzheimer’s is to carry out brain autopsy of the patient’s brain tissue and ascertain whether the subject had Alzheimer’s or any other form of dementia. However, due to the non-feasibility of such methods, to diagnose and conclude the conditions, medical practitioners use tests that examine a patient’s mental ability.Objective Accurate diagnosis at an early stage is the need of the hour for initiation of therapy. The cause for most Alzheimer’s cases still remains unknown except where genetic distinctions have been observed. Thus, a standard drug regimen ensues in every Alzheimer’s patient, irrespective of the cause, which may not always be beneficial in halting or reversing the disease progression. To provide a better life to such patients by suppressing existing symptoms, early diagnosis, curative therapy, site-specific delivery of drugs, and application of hyphenated methods like artificial intelligence need to be brought into the main field of Alzheimer’s therapeutics.Methods In this review, we have compiled existing hypotheses to explain the cause of the disease, and highlighted gene therapy, immunotherapy, peptidomimetics, metal chelators, probiotics and quantum dots as advancements in the existing strategies to manage Alzheimer’s.Conclusion Biomarkers, brain-imaging, and theranostics, along with artificial intelligence, are understood to be the future of the management of Alzheimer’s.

1. Recent Advances in Pathogenesis and Treatment of Inflammatory Bowel Diseases

1. Recent Advances in Pathogenesis and Treatment of Inflammatory Bowel Diseases

Langerhans cell histiocytosis in children - a disease with many faces. Recent advances in pathogenesis, diagnostic examinations and treatment.

Langerhans cell histiocytosis is a rare clonal disease characterized by the proliferation of CD1a-positive immature dendritic cells. The purpose of this article was to present an updated review of recent advances in the pathogenesis, clinical features, imaging and treatment of this disease. The discovery of oncogenic BRAF mutations and the presence of proinflammatory cytokines and chemokines confirmed the unusual characteristics of this disease. Currently, children with organ involvement who do not have a good response to chemotherapy and have neurodegeneration or diabetes insipidus are the most problematic patients. Further research is needed to improve the results of treatment.

Cytokine profile: recent advances in pathogenesis of inflammatory bowel diseases

Inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, remain an urgent problem of clinical gastroenterology. Although the etiology of both diseases is still unknown, in recent years progress has been made in studying of pathogenesis of inflammatory processes in patients with inflammatory bowel diseases. In particular, recent data from the foreign literature on the immune dysregulation demonstrate the important roles of novel IL-1 family and the IL-6 family in the inflammatory bowel diseases development, which can determine their diagnostic value and the personalized therapeutic strategy in such patients in the future.

HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment.

HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the “gold standard” of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND. Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS) has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.

Allergic Aspergillus Rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid rhinosinusitis usually in atopic individuals, characterized by presence of eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into surrounding mucosa. It has emerged as an important disease involving a large population across the world with geographic variation in incidence and epidemiology. The disease is surrounded by controversies regarding its definition and etiopathogenesis. A working group on “Fungal Sinusitis” under the International Society for Human and Animal Mycology (ISHAM) addressed some of those issues, but many questions remain unanswered. The descriptions of “eosinophilic fungal rhinosinusitis” (EFRS), “eosinophilic mucin rhinosinusitis” (EMRS) and mucosal invasion by hyphae in few patients have increased the problem to delineate the disease. Various hypotheses exist for etiopathogenesis of AFRS with considerable overlap, though recent extensive studies have made certain in depth understanding. The diagnosis of AFRS is a multi-disciplinary approach including the imaging, histopathology, mycology and immunological investigations. Though there is no uniform management protocol for AFRS, surgical clearing of the sinuses with steroid therapy are commonly practiced. The role of antifungal agents, leukotriene antagonists and immunomodulators is still questionable. The present review covers the controversies, recent advances in pathogenesis, diagnosis, and management of AFRS.

Recent advances in pathogenesis, assessment, and treatment of atherosclerosis.

In recent years, there have been a number of advances in the pathogenesis and treatment of atherosclerosis and in assessing prognosis in carotid atherosclerosis. Risk stratification to improve vascular prevention by identifying patients most likely to benefit from intensive therapy is much improved by measuring carotid plaque burden. In patients with asymptomatic carotid stenosis, a number of modalities can be used to identify the 10-15% who could benefit from endarterectomy or stenting. Transcranial Doppler embolus detection, echolucency and ulceration on 3D ultrasound, intraplaque hemorrhage on magnetic resonance imaging (MRI), and reduced cerebrovascular reserve are useful already; new approaches including plaque texture on ultrasound and imaging of plaque inflammation and early calcification on positron emission tomography/computed tomography (PET/CT) are in development. The discovery that the intestinal microbiome produces vasculotoxic metabolites from dietary constituents such as carnitine in meat (particularly red meat) and phosphatidylcholine from egg yolk and other sources has revolutionized nutritional aspects of vascular prevention. Because many of these vasculotoxic metabolites are removed by the kidney, it is particularly important in patients with renal failure to limit their intake of red meat and egg yolk. A new approach to lowering low-density lipoprotein (LDL) cholesterol by blocking the action of an enzyme that destroys LDL receptors promises to revolutionize vascular prevention once less costly treatments are developed, and a new approach to vascular prevention—“treating arteries instead of risk factors”—shows promise but requires randomized trials. These advances all promise to help in the quest to prevent strokes in high-risk patients.

Autoimmune inflammatory neuropathies: updates in pathogenesis, diagnosis, and treatment.

The present review aims at discussing the recent advances in pathogenesis, diagnosis, and treatment of major subtypes of autoimmune inflammatory neuropathies. Concerning pathogenesis, further evidence has proved that antibodies to nodal proteins are pathogenic in inflammatory neuropathies. The presence of these antibodies is related to distinctive clinical features. Disruption of blood-nerve barrier mediated by cytokines and chemokines also plays an important role in the pathogenesis. The new terminology of 'nodopathies' describes immune-mediated attack beginning and limited to the nodal region, and this phenomenon can be found in both acute and chronic inflammatory neuropathies. Recent trials comparing intravenous and subcutaneous immunoglobulin confirm that subcutaneous immunoglobulin is not only cost-effective, but also improves patients' satisfaction and quality of life compared to intravenous immunoglobulin. Although immunotherapies are effective in most of the inflammatory neuropathies, accurate predictors and biomarkers of treatment response are lacking. Moreover, some patients do not respond to current immunotherapies and continue to relapse after discontinuation of treatment. More studies are required to understand the exact antigenic targets and mechanism in inflammatory neuropathies, so as to develop more novel immunotherapies.

Antiphospholipid syndrome: an update.

Antiphospholipid syndrome (APS) or 'Hughes syndrome' is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). More than three decades have passed, and experts are still uncovering new pieces of this disease complex pathogenesis and management. We searched in literature using MEDLINE and PubMed databases focusing on the latest development on disease pathogenesis, risk assessment of thrombosis and treatment of APS. The phosphatidylinositol 3-kinase (PI3K)-AKT-mTORC pathway was most recently identified to have a crucial role in activating inflammation among endothelial vessel wall causing vascular lesions in APS. Additionally, new variables are being implemented to assess the risk of thrombosis in patients with APS. Global APS Score (GAPSS) utilizes cardiovascular risk factors and new autoimmune antibodies as part of the score assessment and is the most valid so far. It can be a promising tool in the future for prediction of thrombosis. Anticoagulation remains the cornerstone in APS; however, many new potential therapeutic agents are developing and are currently under investigation. The most recent advances in pathogenesis, risk stratification and treatment provide a platform for high yield studies with the ultimate goal of providing the optimal management to patients with APS.

Management of hepatic adenomatosis.

Hepatic adenomatosis (HeAs) is a rare clinical entity defined by the presence of 10 or more hepatic adenomas (HA) within the background of an otherwise normal liver parenchyma, in the absence of glycogen storage disease or anabolic steroid use. HA is a benign tumor associated with oral contraceptive use. Recent advances in pathogenesis and classification of HA have questioned the distinction between these two diseases. HA are currently classified into four different subtypes with genotypic and phenotypic correlation: HNF-1a inactivated HA, B-catenin activated HA, inflammatory HA, and undetermined subtype. The clinical presentation of HA depends on the lesion size and the subtype. MRI using hepatospecific contrast agents is helpful in diagnosing the most common subtypes. When diagnosis is uncertain, biopsy with immunohistochemistry is used to diagnose and classify the lesions. Management is governed by the molecular subtype and tumor size. Pregnancy is not routinely discouraged but management is individualized.

Recent advances in pathogenesis and management of pruritus in cholestatic liver disease

Recent advances in pathogenesis and management of pruritus in cholestatic liver disease

Autoimmune pancreatitis: pathogenesis, latest developments and clinical guidance.

Recently, autoimmune pancreatitis has been classified into two subtypes. Type 1 is related to immunoglobulin G4 and type 2 is related to granulocytic epithelial lesions, but pathogenetic mechanisms in both still remain unclear. Apart from type 2 autoimmune pancreatitis, the pathological features of type 1 autoimmune pancreatitis with increased serum immunoglobulin G4/immunoglobulin E levels, abundant infiltration of immunoglobulin G4+plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive of abnormal immunity such as allergy or autoimmunity. Although pathophysiological conditions seem to be different in each, both respond well to steroid drugs. After remission, the patients with type 1 autoimmune pancreatitis show high relapse rates (30-50% within 6-12 months), whereas those with type 2 autoimmune pancreatitis seldom relapse. After remission, the steroid maintenance therapy and therapeutic strategy for relapsing patients with type 1 is different among local expertise. In this paper, recent advances in pathogenesis and clinical guidance for therapy are discussed.