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International Journal of Molecular... Jun 2022Specific antibody responses to subfornical organs, including Na antibody, have been reported in patients with adipsic hypernatremia of unknown etiology who do not have... (Review)
Review
Specific antibody responses to subfornical organs, including Na antibody, have been reported in patients with adipsic hypernatremia of unknown etiology who do not have structural lesions in the hypothalamic-pituitary gland. The subfornical organ, also referred to as the window of the brain, is a sensing site that monitors sodium and osmotic pressure levels. On the other hand, ROHHAD syndrome is a rare disease for which the etiology of the hypothalamic disorder is unknown, and there have been some reports in recent years describing its association with autoimmune mechanisms. In addition, abnormal Na levels, including hypernatremia, are likely to occur in this syndrome. When comparing the clinical features of adipsic hypernatremia due to autoimmune mechanisms and ROHHAD syndrome, there are similar hypothalamic-pituitary dysfunction symptoms in addition to abnormal Na levels. Since clinical diagnoses of autoimmunological adipsic hypernatremia and ROHAD syndrome might overlap, we need to understand the essential etiology and carry out precise assessments to accurately diagnose patients and provide effective treatment. In this review, I review the literature on the autoimmune mechanism reported in recent years and describe the findings obtained so far and future directions.
Topics: Autoimmunity; Autonomic Nervous System Diseases; Endocrine System Diseases; Humans; Hypernatremia; Hypothalamic Diseases; Rare Diseases; Respiration Disorders; Sodium; Syndrome
PubMed: 35805903
DOI: 10.3390/ijms23136899 -
Cold Spring Harbor Molecular Case... Jun 2023PPP2 syndrome type R5D, or Jordan's syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants in , a β-subunit of the Protein Phosphatase 2A...
PPP2 syndrome type R5D, or Jordan's syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants in , a β-subunit of the Protein Phosphatase 2A (PP2A). The condition is characterized by global developmental delays, seizures, macrocephaly, ophthalmological abnormalities, hypotonia, attention disorder, social and sensory challenges often associated with autism, disordered sleep, and feeding difficulties. Among affected individuals, there is a broad spectrum of severity, and each person only has a subset of all associated symptoms. Some, but not all, of the clinical variability is due to differences in the genotype. These suggested clinical care guidelines for the evaluation and treatment of individuals with PPP2 syndrome type R5D are based on data from 100 individuals reported in the literature and from an ongoing natural history study. As more data are available, particularly for adults and regarding treatment response, we anticipate that revisions to these guidelines will be made.
Topics: Adult; Humans; Intellectual Disability; Jordan; Neurodevelopmental Disorders; Autistic Disorder; Syndrome; Reference Standards; Protein Phosphatase 2
PubMed: 37339871
DOI: 10.1101/mcs.a006285 -
Trends in Genetics : TIG Dec 2020Single-cell multimodal omics (scMulti-omics) technologies have made it possible to trace cellular lineages during differentiation and to identify new cell types in... (Review)
Review
Single-cell multimodal omics (scMulti-omics) technologies have made it possible to trace cellular lineages during differentiation and to identify new cell types in heterogeneous cell populations. The derived information is especially promising for computing cell-type-specific biological networks encoded in complex diseases and improving our understanding of the underlying gene regulatory mechanisms. The integration of these networks could, therefore, give rise to a heterogeneous regulatory landscape (HRL) in support of disease diagnosis and drug therapeutics. In this review, we provide an overview of this field and pay particular attention to how diverse biological networks can be inferred in a specific cell type based on integrative methods. Then, we discuss how HRL can advance our understanding of regulatory mechanisms underlying complex diseases and aid in the prediction of prognosis and therapeutic responses. Finally, we outline challenges and future trends that will be central to bringing the field of HRL in complex diseases forward.
Topics: Animals; Computational Biology; Disease; Gene Regulatory Networks; Humans; Single-Cell Analysis
PubMed: 32868128
DOI: 10.1016/j.tig.2020.08.004 -
Expert Review of Endocrinology &... Sep 2019: Obesity affects about 40% of US adults and 18% of children. Its impact on the pulmonary system is best described for asthma. : We reviewed the literature on PubMed and... (Review)
Review
: Obesity affects about 40% of US adults and 18% of children. Its impact on the pulmonary system is best described for asthma. : We reviewed the literature on PubMed and Google Scholar databases and summarize the effect of obesity, its associated metabolic dysregulation and altered systemic immune responses, and that of weight gain and loss on pulmonary mechanics, asthma inception, and disease burden. We include a distinct approach for diagnosing and managing the disease, including pulmonary function deficits inherent to obesity-related asthma, in light of its poor response to current asthma medications. : Given the projected increase in obesity, obesity-related asthma needs to be addressed now. Research on the contribution of metabolic abnormalities and systemic immune responses, intricately linked with truncal adiposity, and that of lack of atopy, to asthma disease burden, and pulmonary function deficits among obese children is fairly consistent. Since current asthma medications are more effective for atopic asthma, investigation for atopy will guide management by distinguishing asthma responsive to current medications from the non-responsive disease. Future research is needed to elucidate mechanisms by which obesity-mediated metabolic abnormalities and immune responses cause medication non-responsive asthma, which will inform repurposing of medications and drug discovery.
Topics: Asthma; Child; Exercise Therapy; Humans; Hypersensitivity, Immediate; Lung Diseases; Metabolic Syndrome; Nutrition Therapy; Pediatric Obesity; Weight Loss
PubMed: 31241375
DOI: 10.1080/17446651.2019.1635007 -
Frontiers in Immunology 2022Almost all solid tumors display hypoxic areas in the tumor microenvironment associated with therapeutic failure. It is now well established that the abnormal growth of... (Review)
Review
Almost all solid tumors display hypoxic areas in the tumor microenvironment associated with therapeutic failure. It is now well established that the abnormal growth of malignant solid tumors exacerbates their susceptibility to hypoxia. Therefore, targeting hypoxia remains an attractive strategy to sensitize tumors to various therapies. Tumor cell adaptions to hypoxia are primarily mediated by hypoxia-inducible factor-1 alpha (HIF-1α). Sensing hypoxia by HIF-1α impairs the apoptotic potential of tumor cells, thus increasing their proliferative capacity and contributing to the development of a chaotic vasculature in the tumor microenvironment. Therefore, in addition to the negative impact of hypoxia on tumor response to chemo- and radio-therapies, hypoxia has also been described as a major hijacker of the tumor response by impairing the tumor cell susceptibility to immune cell killing. This review is not intended to provide a comprehensive overview of the work published by several groups on the multiple mechanisms by which hypoxia impairs the anti-tumor immunity and establishes the immunosuppressive tumor microenvironment. There are several excellent reviews highlighting the value of targeting hypoxia to improve the benefit of immunotherapy. Here, we first provide a brief overview of the mechanisms involved in the establishment of hypoxic stress in the tumor microenvironment. We then discuss our recently published data on how targeting hypoxia, by deleting a critical domain in HIF-1α, contributes to the improvement of the anti-tumor immune response. Our aim is to support the current dogma about the relevance of targeting hypoxia in cancer immunotherapy.
Topics: Humans; Hypoxia; Immunosuppressive Agents; Immunotherapy; Neoplasms; Syndrome; Tumor Microenvironment
PubMed: 35795658
DOI: 10.3389/fimmu.2022.880810 -
Biomedicine & Pharmacotherapy =... Jul 2021miR-379 is a miRNA transcribed from the MIR379 locus on 14q32.31. This miRNA is located in an evolutionarily conserved miRNA cluster in an imprinted region that contains... (Review)
Review
miR-379 is a miRNA transcribed from the MIR379 locus on 14q32.31. This miRNA is located in an evolutionarily conserved miRNA cluster in an imprinted region that contains DLK1 and DIO3 genes. The mouse homolog of this miRNA has been shown to be under-expressed in response to glucocorticoid receptor deficiency. Moreover, miR-379 has a tumor-suppressive role in a wide variety of tissues including the brain, breast, lung, and liver. In addition to restraining cell proliferation and migration, miR-379 can suppress the epithelial-mesenchymal transition process. Abnormal expression of this miRNA implies the pathogenesis of Duchene muscular dystrophy, spinal cord injury, diabetic nephropathy, acute myocardial infarction, and premature ovarian failure. This review aims to the summarization of the role of miR-379 in neoplastic and non-neoplastic conditions.
Topics: Animals; Biomarkers; Disease; Humans; MicroRNAs; Neoplasms
PubMed: 33845370
DOI: 10.1016/j.biopha.2021.111553 -
Nutrients Jul 2022Young children's growth is influenced by food and feeding behavior. Responsive feeding has been shown to promote healthy growth and development, to prevent under- and...
Young children's growth is influenced by food and feeding behavior. Responsive feeding has been shown to promote healthy growth and development, to prevent under- and overfeeding, and to encourage children's self-regulation. However, most measures of responsive feeding do not incorporate bidirectional mother-infant responsivity or early learning principles and have not been validated against observations. To overcome these gaps, we laid the groundwork for a responsive feeding measure based on a community sample of 67 mothers and their 6-18-month-old children in Bangladesh. Children were weighed and measured. Mothers reported on their child's dietary intake and responded to a 38-item responsive feeding questionnaire developed through a 2-phase Delphi procedure. Based on a video-recorded feeding observation, mother-child dyads were categorized into proximal (43%) and distal (57%) responsivity groups. Using stepwise logistic regression, a 9-item model from the responsive feeding questionnaire had excellent fit (AUC = 0.93), sensitivity (90%), specificity (89%), positive predictive value (87%), and negative predictive value (93%). Proximal responsivity was characterized by maternal concerns about children's dietary intake. Distal responsivity was characterized by maternal perception of children's happy mood during feeding. Findings support responsive feeding as modulating between proximal and distal responsivity, promoting autonomy, self-regulation, and enabling children to acquire and practice healthy eating behaviors.
Topics: Bangladesh; Child; Child Behavior; Child, Preschool; Diet, Healthy; Eating; Feeding Behavior; Female; Humans; Infant; Mother-Child Relations; Mothers; Surveys and Questionnaires
PubMed: 35956330
DOI: 10.3390/nu14153156 -
The Journal of Experimental Medicine May 2024NLRP3-associated autoinflammatory disease is a heterogenous group of monogenic conditions caused by NLRP3 gain-of-function mutations. The poor functional...
NLRP3-associated autoinflammatory disease is a heterogenous group of monogenic conditions caused by NLRP3 gain-of-function mutations. The poor functional characterization of most NLRP3 variants hinders diagnosis despite efficient anti-IL-1 treatments. Additionally, while NLRP3 is controlled by priming and activation signals, gain-of-functions have only been investigated in response to priming. Here, we characterize 34 NLRP3 variants in vitro, evaluating their activity upon induction, priming, and/or activation signals, and their sensitivity to four inhibitors. We highlight the functional diversity of the gain-of-function mutants and describe four groups based on the signals governing their activation, correlating partly with the symptom severity. We identify a new group of NLRP3 mutants responding to the activation signal without priming, associated with frequent misdiagnoses. Our results identify key NLRP3 residues controlling inflammasome activity and sensitivity to inhibitors, and antagonistic mechanisms with broader efficacy for therapeutic strategies. They provide new insights into NLRP3 activation, an explanatory mechanism for NLRP3-AID heterogeneity, and original tools for NLRP3-AID diagnosis and drug development.
Topics: Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Gain of Function Mutation; Inflammasomes; Drug Development; Syndrome
PubMed: 38530241
DOI: 10.1084/jem.20231200 -
Cephalalgia : An International Journal... Feb 2023Background Accumulating evidence suggests various specific triggers may lead to new daily persistent headache (NDPH)-like presentations, suggesting that new daily... (Review)
Review
Background Accumulating evidence suggests various specific triggers may lead to new daily persistent headache (NDPH)-like presentations, suggesting that new daily persistent headache is a heterogenous syndrome, and challenging the concept that new daily persistent headache is a primary headache disorder.Method We searched the PubMed database up to August 2022 for keywords including persistent daily headache with both primary and secondary etiologies. We summarized the literature and provided a narrative review of the clinical presentation, diagnostic work-ups, possible pathophysiology, treatment response, and clinical outcomes.Results and conclusion New daily persistent headache is a controversial but clinically important topic. New daily persistent headache is likely not a single entity but a syndrome with different etiologies. The issue with past studies of new daily persistent headache is that patients with different etiologies/subtypes were pooled together. Different studies may investigate distinct subsets of patients, which renders the inter-study comparison, both positive and negative results, difficult. The identification (and removal) of a specific trigger might provide the opportunity for clinical improvement in certain patients, even when the disease has lasted for months or years. Nonetheless, if there is a specific trigger, it remains unknown or unidentified for a great proportion of the patients. We need to continue to study this unique headache population to better understand underlying pathogenesis and, most importantly, to establish effective treatment strategies that hopefully resolve the continuous cycle of pain.
Topics: Humans; Headache Disorders; Headache; Treatment Outcome; Syndrome; Databases, Factual
PubMed: 36759317
DOI: 10.1177/03331024221146314 -
Cell Calcium Jan 2020Inositol 1,4,5 trisphosphate receptors (ITPRs) are a family of endoplasmic reticulum Ca channels essential for the control of intracellular Ca levels in virtually every... (Review)
Review
Inositol 1,4,5 trisphosphate receptors (ITPRs) are a family of endoplasmic reticulum Ca channels essential for the control of intracellular Ca levels in virtually every mammalian cell type. The three isoforms (ITPR1, ITPR2 and ITPR3) are highly homologous in amino acid sequence, but they differ considerably in terms of biophysical properties, subcellular localization, and tissue distribution. Such differences underscore the variety of cellular responses triggered by each isoform and suggest that the expression/activity of specific isoforms might be linked to particular pathophysiological states. Indeed, recent findings demonstrate that changes in expression of ITPR isoforms are associated with a number of human diseases ranging from fatty liver disease to cancer. ITPR3 is emerging as the isoform that is particularly important in the pathogenesis of various human diseases. Here we review the physiological and pathophysiological roles of ITPR3 in various tissues and the mechanisms by which the expression of this isoform is modulated in health and disease.
Topics: Animals; Biophysical Phenomena; Calcium Channels; Disease; Endoplasmic Reticulum; Humans; Inositol 1,4,5-Trisphosphate Receptors; Mitochondria; Models, Biological
PubMed: 31790953
DOI: 10.1016/j.ceca.2019.102132