Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD).
View Article and Find Full Text PDFHaploinsufficiency of the transcription factor interferon-regulatory factor 4 (IRF4) prevents the onset of spontaneous diabetes in NOD mice. However, the immunological mechanisms of the IRF4-mediated disease regulation remain unclear. This study aims to investigate the role of IRF4 in the pathogenesis of autoimmune diabetes by conducting adoptive transfer experiments using donor IRF4 gene-deficient CD4+ T cells from BDC2.
View Article and Find Full Text PDFγδ T cells facilitate the CD4 T helper 1 (Th1) cell response against infection by activating conventional dendritic cells (cDCs), although the underlying mechanism remains elusive. Our study revealed that γδ T cells promote the complete maturation and production of interleukin-12 and CXCR3-ligands specifically in type 1 cDCs (cDC1), with minimal impact on cDC2 and monocyte derived DCs (Mo-DCs). During the initial infection phase, γδ T cell activation and temporal accumulation in the splenic white pulp, alongside cDC1, occur via CCR7-signaling.
View Article and Find Full Text PDFThe generation and maintenance of memory T cells are regulated by various factors, including cytokines. Previous studies have shown that IL-27 is produced during the early acute phase of Plasmodium chabaudi chabaudi AS (Pcc) infection and inhibits the development of Th1-type memory CD4+ T cells. However, whether IL-27 acts directly on its receptor on Plasmodium-specific CD4+ T cells or indirectly via its receptor on other immune cells remains unclear.
View Article and Find Full Text PDFDiabetes causes arteriosclerosis, primarily due to persistent hyperglycemia, subsequently leading to various cardiovascular events. No method has been established for directly detecting and evaluating arteriosclerotic lesions from blood samples of diabetic patients, as the mechanism of arteriosclerotic lesion formation, which involves complex molecular biological processes, has not been elucidated. "NMR modal analysis" is a technology that enables visualization of specific nuclear magnetic resonance (NMR) signal properties of blood samples.
View Article and Find Full Text PDFObjective: To evaluate the effect of a Nisin-based dentin pretreatment solution on microtensile bond strength, antibacterial activity, and matrix metalloproteinase (MMP) activity of the adhesive interface.
Materials And Methods: 100 human molars were sectioned to expose dentin. The teeth were assigned to five groups (n = 20), according to the dentin pretreatment: 0.
The association between the lipid peroxidation product malondialdehyde (MDA)-modified low-density lipoprotein (MDA-LDL) and the pathophysiology of autism spectrum disorder (ASD) is unclear. This association was studied in 17 children with ASD and seven age-matched controls regarding autistic behaviors. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC).
View Article and Find Full Text PDFMalaria infection elicits both protective and pathogenic immune responses, and IL-27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4 T cell responses that is targeted by IL-27. Neutralization of IL-27 during acute infection with Plasmodium chabaudi expanded specific CD4 T cells, which were maintained at high levels thereafter.
View Article and Find Full Text PDFPolyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls.
View Article and Find Full Text PDFMalaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria.
View Article and Find Full Text PDFBackground: The health benefits of n-3 (ω-3) PUFAs are well studied. A self-emulsifying drug delivery system (SEDDS) is expected to improve n-3 PUFA absorption.
Objectives: The present study investigated how a single ingestion of a new SEDDS containing the triglyceride (TG) form of DHA (22:6n-3) (DHA/TG) would affect the plasma DHA concentration in healthy participants.
The signaling pathways associated with lipid metabolism contribute to the pathophysiology of autism spectrum disorder (ASD) and provide insights for devising new therapeutic strategies. Prostaglandin E2 is a membrane-derived lipid molecule that contributes to developing ASD associated with canonical Wnt signaling. Cyclooxygenase-2 plays a key role in neuroinflammation and is implicated in the pathogenesis of neurodevelopmental diseases, such as ASD.
View Article and Find Full Text PDFThe marine polyclad flatworm Planocera multitentaculata is known to possess high levels of tetrodotoxin (TTX), but the presence of TTX analogues in the species has been unexplored. In this study, TTX and several analogues such as 5,6,11-trideoxyTTX, monodeoxyTTXs, dideoxyTTXs, and 11-norTTX-6(S)-ol were identified in three adults and egg plates of P. multitentaculata using high resolution liquid chromatography-mass spectrometry (HR-LC/MS) for the first time.
View Article and Find Full Text PDFThorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of -derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4 T cells specific for an MHC class II (I-A)-restricted epitope and is responsive to both sporozoites and blood-stage .
View Article and Find Full Text PDFLipomas of the cerebellopontine angle (CPA) and internal auditory canal (IAC) are relatively rare tumors. Acoustic neurinoma is the most common tumor in this location, which often causes hearing loss, vertigo, and tinnitus. Occasionally, this tumor compresses the brainstem, prompting surgical resection.
View Article and Find Full Text PDFPlasmodium parasites that infect humans are highly polymorphic, and induce various infections ranging from an asymptomatic state to life-threatening diseases. However, how the differences between the parasites affect host immune responses during blood-stage infection remains largely unknown. We investigated the CD4+ T-cell immune responses in mice infected with P.
View Article and Find Full Text PDFThe balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems.
View Article and Find Full Text PDFBackground Lipid metabolism has been associated with the development of autism. The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) readily undergo lipid peroxidation and conversion to malondialdehyde (MDA). MDA-modified low-density lipoprotein (MDA-LDL) is a marker of lipid peroxidation.
View Article and Find Full Text PDFUpon activation, specific CD4+ T cells up-regulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4+ T cells. However, using T-cell receptor transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4+ T cells develop not only to CD11ahiCD49dhi cells, but also to CD11ahiCD49dlo cells during acute Plasmodium infection. CD49dhi PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet and produced IFN-γ, indicating that they were type 1 helper T (Th1)-type cells.
View Article and Find Full Text PDFBackground: This study aimed to evaluate surface treatments, adhesives and composites for repairing silorane based restorations.
Material And Methods: One hundred and twenty truncated cones (2 mm smaller diameter and 4 mm larger diameter) made of silorane composite were divided in 12 groups according with the surface treatment (diamond bur and oxide aluminum abrasion), the adhesive (Adper Scothbond Multipurpose (3M ESPE), Ecusit (Voco) and Filtek P90 Adhesive (3M ESPE)). Each group was subdivided in two according with the composite used for repair (methacrylate and silorane).
To evaluate the effects of 25-hydroxyvitamin D (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 μg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage.
View Article and Find Full Text PDFA 51-year-old man had a 1-year history of numbness on the ulnar side of the 4th finger, the 5th finger, and the ulnar side of the forearm, and weakness of the right hand. The Spurling sign was negative, and cervical radiography and magnetic resonance imaging revealed no abnormality. The Tinel-like signs at the Guyon's canal and cubital tunnel were positive.
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