Manganese transporter SLC30A10 and iron transporters SLC40A1 and SLC11A2 impact dietary manganese absorption.

SLC30A10 deficiency is a disease of severe manganese excess attributed to loss of SLC30A10-dependent manganese excretion via the gastrointestinal tract. Patients develop dystonia, cirrhosis, and polycythemia. They are treated with chelators but also respond to oral iron, suggesting that iron can outcompete manganese for absorption in this disease.

(,)-Bromido-(-{4-methyl-1-[(4-methyl-phenyl)sul-fan-yl]-pentan-2-yl}--(pyridin-2-yl)imidazol-2-yl-idene)palladium(II) bromide.

The mol-ecule of the title NCS pincer -heterocyclic carbene palladium(II) complex, [PdBr(CHNS)]Br, exhibits a slightly distorted square-planar coordination at the palladium(II) atom, with the five-membered chelate ring nearly planar. The six-membered chelate ring adopts an envelope conformation. Upon chelation, the sulfur atom becomes a stereogenic centre with an configuration induced by the chiral carbon of the precursor imidazolium salt.

Combination of a TGF-β ligand trap (RAP-GRL) and TMPRSS6-ASO is superior for correcting β-thalassemia.

A recently approved drug that induces erythroid cell maturation (luspatercept) has been shown to improve anemia and reduce the need for blood transfusion in non-transfusion-dependent as well as transfusion-dependent β-thalassemia (BT) patients. Although these results were predominantly positive, not all the patients showed the expected increase in hemoglobin (Hb) levels or transfusion burden reduction. Additional studies indicated that administration of luspatercept in transfusion-dependent BT was associated with increased erythropoietic markers, decreased hepcidin levels, and increased liver iron content.

Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract.

ROS-Induced Gingival Fibroblast Senescence: Implications in Exacerbating Inflammatory Responses in Periodontal Disease.

Periodontal disease is the pathological outcome of the overwhelming inflammation in periodontal tissue. Cellular senescence has been associated with chronic inflammation in several diseases. However, the role of cellular senescence in the pathogenesis of periodontal disease remained unclear.

Comparison of the osteogenic potential of fibroblasts from different sources.

Objective: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior.

Design: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization.

A functional interplay between the two BMP-SMAD pathway inhibitors TMPRSS6 and FKBP12 regulates expression in vivo.

The Activin A Receptor type I (ALK2) is a critical component of BMP-SMAD signaling that, in the presence of ligands, phosphorylates cytosolic SMAD1/5/8 and modulates important biological processes, including bone formation and iron metabolism. In hepatocytes, the BMP-SMAD pathway controls the expression of , the liver peptide hormone that regulates body iron homeostasis via the BMP receptors ALK2 and ALK3, and the hemochromatosis proteins. The main negative regulator of the pathway in the liver is transmembrane serine protease 6 (TMPRSS6), which downregulates by cleaving the BMP coreceptor hemojuvelin.

Coordinated inositide lipid-phosphatase activities of synaptojanin modulates actin cytoskeleton organization.

Synaptojanin proteins are evolutionarily conserved regulators of vesicle transport and membrane homeostasis. Disruption of synaptojanin function has been implicated in a wide range of neurological disorders. Synaptojanins act as dual-functional lipid phosphatases capable of hydrolyzing a variety of phosphoinositides (PIPs) through autonomous SAC1-like PIP 4-phosphatase and PIP 5-phosphatase domains.

Oligomeric β-Amyloid Suppresses Hippocampal γ-Oscillations through Activation of the mTOR/S6K1 Pathway.

Neuronal synchronization at gamma frequency (30-100 Hz: γ) is impaired in early-stage Alzheimer's disease (AD) patients and AD models. Oligomeric Aβ caused a concentration-dependent reduction of γ-oscillation strength and regularity while increasing its frequency. The mTOR1 inhibitor rapamycin prevented the Aβ-induced suppression of γ-oscillations, whereas the mTOR activator leucine mimicked the Aβ-induced suppression.

Mediator1 involved in functional integration of Smad3 and Notch1 promoting enamel mineralization.

Enamel hypoplasia is a tooth development defection due to the disruption of enamel matrix mineralization, manifesting as chalky white phenotype. Multiple genes may be involved in this tooth agenesis. It has been proved that ablation of coactivator Mediator1 (Med1) switches the cell fate of dental epithelia, resulting in abnormal tooth development via Notch1 signaling.

Heat Shock Proteins in Tooth Development and Injury Repair.

Heat shock proteins (HSPs) are a class of molecular chaperones with expression increased in response to heat or other stresses. HSPs regulate cell homeostasis by modulating the folding and maturation of intracellular proteins. Tooth development is a complex process that involves many cell activities.

A single approach to targeting transferrin receptor 2 corrects iron and erythropoietic defects in murine models of anemia of inflammation and chronic kidney disease.

Anemia is a common complication of systemic inflammation. Proinflammatory cytokines both decrease erythroblast sensitivity to erythropoietin (EPO) and increase the levels of the hepatic hormone hepcidin, sequestering iron in stores and causing functional iron deficiency. Anemia of chronic kidney disease (CKD) is a peculiar form of anemia of inflammation, characterized by impaired EPO production paralleling progressive kidney damage.

Hypoxia-inducible factor 2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane transport protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract.

[Dietary micronutrient intake of children aged 2-5 years in China in 2019-2021].

Objective: To describe dietary intake of calcium, iron, zinc, selenium, vitamin A, vitamin B_1, vitamin B_2 and vitamin C and compare the intake between urban and rural areas among preschool children aged 2-5 years based on the data from the National Nutrition and Health Systematic Survey for Children 0-17 Years of Age in China.

Methods: Children from 14 provinces were selected by multi-stage stratified random cluster sampling, and the dietary data of preschool children aged 2-5 years were recorded using the 3 day 24-hour weighted food records method. SAS 9.

Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection.

Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)-short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression.

MED1 Ablation Promotes Oral Mucosal Wound Healing via JNK Signaling Pathway.

Mediator complex subunit 1 (MED1) is a coactivator of multiple transcription factors and plays a key role in regulating epidermal homeostasis as well as skin wound healing. It is unknown, however, whether it plays a role in healing oral mucosal wounds. In this study, we investigate MED1's functional effects on oral mucosal wound healing and its underlying mechanism.

[Relationship between sugary food intake and myopia in 11-14 years old Chinese children in 2019-2021].

Objective: To investigate the relationship between the intake of sugary foods and the occurrence and development of myopia in children aged 11-14 in China.

Methods: In the 28 urban and rural survey sites in 14 provinces that implemented the "China Children's Nutrition and Health System Survey and Application for 0-18 Years Old" project, a multi-stage stratified random cluster sampling method was adopted, and finally 12 397 adolescent children aged 11 to 14 were selected in the analysis. Demographic characteristics, myopia information and the intake of sugary food(cakes, preserved fruits, candies, chocolates and ice cream) were collected through questionnaires.

N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging.

Background: Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration.

The PD-1 with PD-L1 Axis Is Pertinent with the Immune Modulation of Atrial Fibrillation by Regulating T Cell Excitation and Promoting the Secretion of Inflammatory Factors.

Objective: To analyze the role of PD-1/PD-L1 signaling pathway in regulating T cell activation and secretion of proinflammatory factors in atrial fibrillation.

Methods: Forty-five patients with atrial fibrillation admitted to the cardiology department of our hospital from July 2019 to March 2021 were selected to be included in the atrial fibrillation group, and another 45 healthy volunteers were selected as the control group to compare the changes of T cell CD69 and human leukocyte antigen-DR (HLA-DR) expression in the peripheral blood of the two study groups; compare the changes of programmed death factor-1 on CD4+ and CD8+ lymphocytes in the peripheral blood of the two groups (PD-1) expression changes and PD-L1 and PD-L2 expression changes on peripheral blood myeloid dendritic cells (mDCs) cells; compare the changes of interleukin-2, interleukin-6, interleukin-10, and interleukin-17A (IL-2, IL-6, IL-10, and IL-17), tumor necrosis factor (TNF), and interferon gamma (IFN-) concentrations on peripheral blood inflammatory factors in the two groups; and isolate the two groups of peripheral blood mDCs cells; interferon upregulated PD-L1 expression in the cells and analyzed the effect of PD-L1 expression on the ability of mDCs to stimulate T cells to secrete cytokines.

Results: The positive expression rates of CD69 and HLA-DR on peripheral blood CD3+ T lymphocytes were significantly higher in patients in the atrial fibrillation group than in the control group, and the differences were statistically significant ( < 0.

CFTR mRNAs with nonsense codons are degraded by the SMG6-mediated endonucleolytic decay pathway.

Approximately 10% of cystic fibrosis patients harbor nonsense mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which can generate nonsense codons in the CFTR mRNA and subsequently activate the nonsense-mediated decay (NMD) pathway resulting in rapid mRNA degradation. However, it is not known which NMD branches govern the decay of CFTR mRNAs containing nonsense codons. Here we utilize antisense oligonucleotides targeting NMD factors to evaluate the regulation of nonsense codon-containing CFTR mRNAs by the NMD pathway.

Heterogeneity affects the differentiation potential of dental follicle stem cells through the TGF-β signaling pathway.

Adult mesenchymal stem cells play an important role in maintaining organ homeostasis owing to their unique ability to generate more specialized cell populations in a coordinated manner. Adult mesenchymal stem cells are heterogeneous, a feature that is essential for their functions. However, studies have not elucidated how heterogeneity of mesenchymal stem cells affects their differentiation capacity.