Identification of the serum metabolites associated with cow milk consumption in Chinese Peri-/Postmenopausal women.

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations.

Metagenomic study of the gut microbiota associated with cow milk consumption in Chinese peri-/postmenopausal women.

Cow milk consumption (CMC) and alterations of gut bacterial composition are proposed to be closely related to human health and disease. Our research aims to investigate the changes in human gut microbial composition in Chinese peri-/postmenopausal women with different CMC habits. A total of 517 subjects were recruited and questionnaires about their CMC status were collected; 394 subjects were included in the final analyses.

Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions.

Gasdermin B (GSDMB) belongs to a large family of pore-forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the IpaH7.

Long-term dental intervention and laboratory examination in a patient with Vitamin D-dependent rickets type I: A case report.

Rationale: Vitamin D-dependent rickets type I (VDDR-I) is a rare form of rickets, which is an autosomal recessive disease caused by 1α-hydroxylase enzyme deficiency. However, long-term dental management and microscopic morphology of teeth remain largely unclear.

Patient Concerns: We report the case of a 10-year-old Chinese boy complaining of yellowish-brown teeth with extensive caries.

Analysis of Continuous Mutation and Evolution on Circulating SARS-CoV-2.

Monitoring the mutation and evolution of the virus is important for tracing its ongoing transmission and facilitating effective vaccine development. A total of 342 complete genomic sequences of SARS-CoV-2 were analyzed in this study. Compared to the reference genome reported in December 2019, 465 mutations were found, among which, 347 occurred in only 1 sequence, while 26 occurred in more than 5 sequences.

Mechanosensing by Gli1 cells contributes to the orthodontic force-induced bone remodelling.

Objectives: Gli1 cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1 cells respond to force and contribute to bone remodelling.

Materials And Methods: We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force.

Oxysterols provide innate immunity to bacterial infection by mobilizing cell surface accessible cholesterol.

Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene that converts cholesterol to the oxysterol 25-hydroxycholesterol (25HC). Circulating 25HC modulates essential immunological processes including antiviral immunity, inflammasome activation and antibody class switching; and dysregulation of CH25H may contribute to chronic inflammatory disease and cancer. Although 25HC is a potent regulator of cholesterol storage, uptake, efflux and biosynthesis, how these metabolic activities reprogram the immunological state of target cells remains poorly understood.

Sensory nerve-deficient microenvironment impairs tooth homeostasis by inducing apoptosis of dental pulp stem cells.

Objectives: The aim of this study is to investigate the role of sensory nerve in tooth homeostasis and its effect on mesenchymal stromal/stem cells (MSCs) in dental pulp.

Materials And Methods: We established the rat denervated incisor models to identify the morphological and histological changes of tooth. The groups were as follows: IANx (inferior alveolar nerve section), SCGx (superior cervical ganglion removal), IANx + SCGx and Sham group.

Installation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9.

Background: Chromosomal translocation-induced expression of the chromatin modifying oncofusion protein MLL-AF9 promotes acute myelocytic leukemia (AML). Whereas WNT/β-catenin signaling has previously been shown to support MLL-AF9-driven leukemogenesis, the mechanism underlying this relationship remains unclear.

Methods: We used two novel small molecules targeting WNT signaling as well as a genetically modified mouse model that allow targeted deletion of the WNT protein chaperone Wntless (WLS) to evaluate the role of WNT signaling in AML progression.

Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration.

Periodontal disease is a widespread disease, which without proper treatment, may lead to tooth loss in adults. Because stem cells from the inflammatory microenvironment created by periodontal disease exhibit impaired regeneration potential even under favorable conditions, it is difficult to obtain satisfactory therapeutic outcomes using traditional treatments, which only focus on the control of inflammation. Therefore, a new stem cell-based therapy known as cell aggregates/cell sheets technology has emerged.

Chemical Modulation of WNT Signaling in Cancer.

Genetically based observations stemming from defects in development and in regeneration form the foundation of our understanding regarding how the secreted WNT proteins control coordinated cell fate decision-making in adult tissues. At the same time, our anticipation of potential benefits and unwanted toxicities associated with candidate anticancer agents targeting WNT signal transduction are also reliant upon this blueprint of WNT-associated physiology. Despite the long established role of WNT signaling in cancer, the emergence of WNT signaling as a suppressor of immunological attack in melanoma reveals an unanticipated anticancer potential in targeting WNT signaling.

Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor.

Direct interactions between pro- and anti-apoptotic BCL-2 family members form the basis of cell death decision-making at the outer mitochondrial membrane (OMM). Here we report that three anti-apoptotic BCL-2 proteins (MCL-1, BCL-2 and BCL-XL) found untethered from the OMM function as transcriptional regulators of a prosurvival and growth program. Anti-apoptotic BCL-2 proteins engage a BCL-2 homology (BH) domain sequence found in SUFU (suppressor of fused), a tumour suppressor and antagonist of the GLI DNA-binding proteins.

Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist.

The secreted Wnt signaling molecules are essential to the coordination of cell-fate decision making in multicellular organisms. In adult animals, the secreted Wnt proteins are critical for tissue regeneration and frequently contribute to cancer. Small molecules that disable the Wnt acyltransferase Porcupine (Porcn) are candidate anticancer agents in clinical testing.

Mass spectrometry based proteomics profiling of human monocytes.

Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study.

Delivery of the Porcupine Inhibitor WNT974 in Mice.

We describe here a technique for delivering the porcupine inhibitor WNT974 (formerly LGK974) in mice. The protocol entails once-a-day oral delivery of WNT974 for up to 3 months at a concentration sufficient to achieve systemic Wnt pathway inhibition with limited toxicity as measured by weight change. This route of delivery enables extended durations of Wnt signaling inhibition in a mammalian model organism.

Quantitative proteomics and integrative network analysis identified novel genes and pathways related to osteoporosis.

Unlabelled: Osteoporosis is mainly characterized by low bone mineral density (BMD), and can be attributed to excessive bone resorption by osteoclasts. Migration of circulating monocytes from blood to bone is important for subsequent osteoclast differentiation and bone resorption. Identification of those genes and pathways related to osteoclastogenesis and BMD will contribute to a better understanding of the pathophysiological mechanisms of osteoporosis.

Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-β42 to amyloid-β40 ratio.

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.

Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study.

Bone and muscle, two major tissue types of musculoskeletal system, have strong genetic determination. Abnormality in bone and/or muscle may cause musculoskeletal diseases such as osteoporosis and sarcopenia. Bone size phenotypes (BSPs), such as hip bone size (HBS), appendicular bone size (ABS), are genetically correlated with body lean mass (mainly muscle mass).

Diverse chemical scaffolds support direct inhibition of the membrane-bound O-acyltransferase porcupine.

Secreted Wnt proteins constitute one of the largest families of intercellular signaling molecules in vertebrates with essential roles in embryonic development and adult tissue homeostasis. The functional redundancy of Wnt genes and the many forms of cellular responses they elicit, including some utilizing the transcriptional co-activator β-catenin, has limited the ability of classical genetic strategies to uncover their roles in vivo. We had previously identified a chemical compound class termed Inhibitor of Wnt Production (or IWP) that targets Porcupine (Porcn), an acyltransferase catalyzing the addition of fatty acid adducts onto Wnt proteins.

Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans.

Low bone mineral density (BMD) is a risk factor of osteoporosis and has strong genetic determination. Genes influencing BMD and fundamental mechanisms leading to osteoporosis have yet to be fully determined. Peripheral blood monocytes (PBM) are potential osteoclast precursors, which could access to bone resorption surfaces and differentiate into osteoclasts to resorb bone.