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American Journal of Medical Genetics.... Dec 2019Congenital hyperinsulinism (HI) is the most frequent cause of persistent hypoglycemia in infants and children. Delays in diagnosis and initiation of appropriate... (Review)
Review
Congenital hyperinsulinism (HI) is the most frequent cause of persistent hypoglycemia in infants and children. Delays in diagnosis and initiation of appropriate treatment contribute to a high risk of neurocognitive impairment. HI represents a heterogeneous group of disorders characterized by dysregulated insulin secretion by the pancreatic beta cells, which in utero, may result in somatic overgrowth. There are at least nine known monogenic forms of HI as well as several syndromic forms. Molecular diagnosis allows for prediction of responsiveness to medical treatment and likelihood of surgically-curable focal hyperinsulinism. Timely genetic mutation analysis has thus become standard of care. However, despite significant advances in our understanding of the molecular basis of this disorder, the number of patients without an identified genetic diagnosis remains high, suggesting that there are likely additional genetic loci that have yet to be discovered.
Topics: Child; Congenital Hyperinsulinism; Epigenesis, Genetic; Genetic Testing; Humans; Infant; Mutation; Philadelphia; Syndrome
PubMed: 31414570
DOI: 10.1002/ajmg.c.31737 -
Physiological Research Dec 2021Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could... (Review)
Review
Aspiration is a common condition affecting healthy or sick patients which could create an acute or chronic inflammatory reaction in the lungs. Aspiration syndromes could be categorized according to a content entering the respiratory system into bacterial aspiration pneumonia with the gastric or oropharyngeal bacteria entering, aspiration chemical pneumonitis with bacteria-freegastric acid aspiration, or aspiration of a foreign body which causes an acute pulmonary emergency. There are differences in the clinical presentation of volume-dependent aspirations (microaspiration and macroaspiration): the higher is the volume of aspiration, the greater is the injury to the patient and more serious are the health consequences (with 70 % mortality rate for hospitalized patients). Aspiration syndromes can affect both the airways and pulmonary parenchyma, leading to acute lung injury, increased hospitalization rate and worse outcomes in critically ill patients. Impaired alveolar-capillary permeability, oedema formation, neutrophilic inflammatory response and pulmonary surfactant inactivation lead to reduced lung compliance and loss of aerated lung tissue and give rise to hypoxemia and respiratory failure. This review discusses the effect of aspiration events on the pulmonary tissue. The main focus is to distinguish the differences between bacterial and chemical pneumonia, their clinical presentation and symptoms, risk factors of developing the changes, possibilities of diagnostics and management as well as prevention of aspirations. Because of a risk of serious lung damage after the aspiration, pathophysiology and processes leading to lung tissue injury are discussed in detail. Data sources represent a systematic literature search using relevant medical subject headings.
Topics: Acute Lung Injury; Humans; Incidence; Lung; Pneumonia, Aspiration; Syndrome
PubMed: 35199544
DOI: 10.33549/physiolres.934767 -
Molecules (Basel, Switzerland) Nov 2020Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation,... (Review)
Review
Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in targeting for inflammatory biomarkers and multiple signaling pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3, have been described. Furthermore, the applications of anti-inflammatory effects of astaxanthin in neurological diseases, diabetes, gastrointestinal diseases, hepatic and renal diseases, eye and skin disorders, are highlighted. In addition to the protective effects of astaxanthin in various chronic and acute diseases, we also summarize recent advances for the inconsistent roles of astaxanthin in infectious diseases, and give our view that the exact function of astaxanthin in response to different pathogen infection and the potential protective effects of astaxanthin in viral infectious diseases should be important research directions in the future.
Topics: Animals; Anti-Inflammatory Agents; Disease; Humans; Inflammation; Xanthophylls
PubMed: 33207669
DOI: 10.3390/molecules25225342 -
Biochimica Et Biophysica Acta.... Oct 2020One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in... (Review)
Review
One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in differentiation and activation processes of immune cells. Upon activation, immune cells have a high need for energy. Immune cells have different strategies to generate this energy. In pro-inflammatory cells, such as activated monocytes and activated T and B cells, the energy is generated by increasing glycolysis, while in regulatory cells, such as regulatory T cells or M2 macrophages, energy is generated by increasing mitochondrial function and beta-oxidation. Except for being important for energy supply during activation, mitochondria also induce immune responses. During an infection, they release mitochondrial danger associated molecules (DAMPs) that resemble structures of bacterial derived pathogen associated molecular patterns (PAMPs). Such mitochondrial DAMPS are for instance mitochondrial DNA with hypomethylated CpG motifs or a specific lipid that is only present in prokaryotic bacteria and mitochondria, i.e. cardiolipin. Via release of such DAMPs, mitochondria guide the immune response towards an inflammatory response against pathogens. This is an important mechanism in early detection of an infection and in stimulating and sustaining immune responses to fight infections. However, mitochondrial DAMPs may also have a negative impact. If mitochondrial DAMPs are released by damaged cells, without the presence of an infection, such as after a trauma, mitochondrial DAMPs may induce an undesired inflammatory response, resulting in tissue damage and organ dysfunction. Thus, immune cells have developed mechanisms to prevent such undesired immune activation by mitochondrial components. In the present narrative review, we will describe the current view of mitochondria in regulation of immune responses. We will also discuss the current knowledge on disturbed mitochondrial function in immune cells in various immunological diseases.
Topics: Animals; Autoimmune Diseases; B-Lymphocytes; DNA, Mitochondrial; Disease; Health; Humans; Immunity; Infections; Inflammation; Lymphocytes; Macrophages; Mitochondria; Monocytes; Pathogen-Associated Molecular Pattern Molecules; T-Lymphocytes
PubMed: 32473386
DOI: 10.1016/j.bbadis.2020.165845 -
Acta Bio-medica : Atenei Parmensis Nov 2021Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy (FA) characterized by delayed and severe gastrointestinal symptoms that typically... (Review)
Review
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy (FA) characterized by delayed and severe gastrointestinal symptoms that typically occurs within the first year of life. Many aspects of this pathology are currently unclear. FPIES is classified as a non-IgE immune-mediated FA in which the immune response is thought to act mainly through cell-mediated mechanisms. In patients with FPIES, the symptom pattern is determined by the frequency and dose of food allergen in the diet. Diagnosis of FPIES may be difficult, mainly due to the lack of specific biomarkers to confirm or exclude the diagnosis. FPIES is a clinical diagnosis, mainly based on clinical features which, although not specific, are reproducible every time the patient takes the food. Different diagnostic criteria of FPIES were published over time in the literature. The present narrative review aims to analyze the current clinical evidence in epidemiology, pathophysiology, diagnosis, and management of this condition.
Topics: Allergens; Biomarkers; Enterocolitis; Food Hypersensitivity; Humans; Infant; Syndrome
PubMed: 34842596
DOI: 10.23750/abm.v92iS7.12394 -
Microbiome Jul 2022Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human...
BACKGROUND
Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human health. Microbiota plays an essential role in regulating immunity and autoimmunity in the host organism, but the influence of host-microbiota interactions on disease resistance phenotypes remains unclear. Here, multiomics analysis was performed to identify potential regulatory mechanisms of disease resistance at both the microbiome and host levels in two pig breeds.
RESULTS
Acute colitis models were established in Min pigs and Yorkshire pigs, and control and diseased individuals were compared. Compared with Yorkshire pigs under the same nutritional and management conditions, Min pigs exhibited strong disease resistance, as indicated by a low disease activity index (DAI) and a low histological activity index (HAI). Microbiota sequencing analysis showed that potentially harmful microbes Desulfovibrio, Bacteroides and Streptococcus were enriched in diseased individuals of the two breeds. Notably, potentially beneficial microbes, such as Lactobacillus, Clostridia and Eubacterium, and several genera belonging to Ruminococcaceae and Christensenellaceae were enriched in diseased Min pigs and were found to be positively associated with the microbial metabolites related to intestinal barrier function. Specifically, the concentrations of indole derivatives and short-chain fatty acids were increased in diseased Min pigs, suggesting beneficial action in protecting intestinal barrier. In addition, lower concentrations of bile acid metabolites and short-chain fatty acids were observed in diseased Yorkshire pigs, which were associated with increased potentially harmful microbes, such as Bilophila and Alistipes. Concerning enrichment of the immune response, the increase in CD4 T cells in the lamina propria improved supervision of the host immunity response in diseased Min pigs, contributing to the maintenance of Th2-type immune superiority and immune tolerance patterns and control of excessive inflammation with the help of potentially beneficial microbes. In diseased Yorkshire pigs, more terms belonging to biological processes of immunity were enriched, including Toll-like receptors signalling, NF-κB signalling and Th1 and Th17-type immune responses, along with the increases of potentially harmful microbes and damaged intestinal barrier.
CONCLUSIONS
Cumulatively, the results for the two pig breeds highlight that host-microbiota crosstalk promotes a disease resistance phenotype in three ways: by maintaining partial PRR nonactivation, maintaining Th2-type immune superiority and immunological tolerance patterns and recovering gut barrier function to protect against colonic diseases. Video abstract.
Topics: Animals; Colitis; Disease Resistance; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Microbiota; Swine
PubMed: 35907917
DOI: 10.1186/s40168-022-01303-1 -
Journal of Pediatric Oncology Nursing :... 2019Children and adolescents receiving treatment for cancer experience multiple symptoms as a consequence of their disease and its treatment that interfere with the child's... (Review)
Review
Children and adolescents receiving treatment for cancer experience multiple symptoms as a consequence of their disease and its treatment that interfere with the child's quality of life. Understanding of symptom assessment in children with cancer is foundational to the work of the Children's Oncology Group Nursing Discipline, whose research aims are to address knowledge gaps including understanding illness-related distress. This article is the second of a two-part summary of current evidence addressing the assessment of symptoms frequently reported by children and adolescents receiving treatment for cancer. Studies reporting assessment of pain, sadness, and symptom clusters published between January 2008 and May 2018 were included. Forty-three publications addressed pain. Pain was highly prevalent and distressing, varied in its trajectory across a cycle of chemotherapy and across multiple cycles of treatment, and correlated with biomarkers associated with the pain response. Consequences of pain were poorer functional status and emotional health. Twenty publications addressed sadness. Sadness was the most prevalent psychosocial symptom. Its prevalence decreased over the course of treatment and over a cycle of chemotherapy. Persistent sadness was of greater severity and distress. Eight publications addressed symptom clusters. These studies identified both groups of co-occurring symptoms and groups of patients with common symptom profiles. This two-article series provides evidence for the distressing nature of symptoms among children receiving cancer treatment. Efforts to support clinicians in routine symptom assessment are needed. Additional research directed at alleviating symptoms and building resilience among the child experiencing symptoms is needed.
Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Neoplasms; Pain; Quality of Life; Sadness; Syndrome
PubMed: 31307323
DOI: 10.1177/1043454219849578 -
Nature Medicine Jun 2023Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the...
Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2- rs671 and ADH1B- rs1229984 , with >1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Among men, alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related, such as cataract (n = 2,028; hazard ratio 1.21; 95% confidence interval 1.09-1.33, per 280 g per week) and gout (n = 402; 1.57, 1.33-1.86). Genotype-predicted mean alcohol intake was positively associated with established (n = 28,564; 1.14, 1.09-1.20) and new alcohol-associated (n = 16,138; 1.06, 1.01-1.12) diseases, and with specific diseases such as liver cirrhosis (n = 499; 2.30, 1.58-3.35), stroke (n = 12,176; 1.38, 1.27-1.49) and gout (n = 338; 2.33, 1.49-3.62), but not ischemic heart disease (n = 8,408; 1.04, 0.94-1.14). Among women, 2% drank alcohol resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects. Among Chinese men, alcohol consumption increased multiple disease risks, highlighting the need to strengthen preventive measures to reduce alcohol intake.
Topics: Adult; Female; Humans; Male; Alcohol Drinking; Aldehyde Dehydrogenase, Mitochondrial; East Asian People; Ethanol; Genotype; Gout; Risk Factors; Disease; China
PubMed: 37291211
DOI: 10.1038/s41591-023-02383-8 -
Pediatric Rheumatology Online Journal Apr 2020Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable...
Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group.
BACKGROUND
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA.
METHODS
The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement.
RESULTS
The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study.
CONCLUSION
The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.
Topics: Adrenal Cortex Hormones; Advisory Committees; Antipyretics; Child; Child, Preschool; Cimetidine; Colchicine; Fever; Histamine H2 Antagonists; Humans; Lymphadenitis; Neck; Pharyngitis; Stomatitis, Aphthous; Syndrome; Tonsillectomy; Tubulin Modulators
PubMed: 32293478
DOI: 10.1186/s12969-020-00424-x -
International Journal of Molecular... Dec 2021Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the... (Review)
Review
Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the pathophysiology of the disease. Pyroptosis has been recently suggested as one of the pathways of exacerbated inflammation of periodontal tissues. Hence, this focused review aims to discuss pyroptosis as a pathological mechanism in the cause of periodontitis. The included articles presented similarities regarding methods, type of cells applied, and cell stimulation, as the outcomes also point to the same direction considering the cellular events. The collected data indicate that virulence factors present in the diseased periodontal tissues initiate the inflammasome route of tissue destruction with caspase activation, cleavage of gasdermin D, and secretion of interleukins IL-1β and IL-18. Consequently, removing periopathogens' virulence factors that trigger pyroptosis is a potential strategy to combat periodontal disease and regain tissue homeostasis.
Topics: Animals; Apoptosis; Humans; Inflammasomes; Periodontal Diseases; Pyroptosis; Virulence Factors
PubMed: 35008798
DOI: 10.3390/ijms23010372