Aging of hematopoietic stem cells (HSCs) is implicated in various aging phenotypes, including immune dysfunction, anemia, and malignancies. The role of HSC proliferation in driving these aging phenotypes, particularly under stress conditions, remains unclear. Therefore, we induced forced replications of HSCs in vivo by a cyclical treatment with low-dose fluorouracil (5FU) and examined the impact on HSC aging.
View Article and Find Full Text PDFDietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, a less restrictive diet that allows for cyclical periods of reduced calories mitigates aging phenotypes, yet the effects of such an intervention in a genetically heterogenous, higher-order mammal has not been examined. Here, using middle-aged rhesus macaques matched for age and sex, we show that a regimen of 4 days of low-calorie intake followed by 10 days of ad libitum feeding (4:10 diet) performed in repeating cycles over 12 weeks led to significant loss of weight and fat percentage, despite the free access to food for most of the study duration.
View Article and Find Full Text PDFTristetraprolin (TTP), encoded by Zfp36 in mice, is one of the best-characterized tandem zinc-finger mRNA binding proteins involved in mRNA deadenylation and decay. TTPΔARE mice lack an AU-rich motif in the 3'-untranslated regions of TTP mRNA, leading to increased TTP mRNA stability and more TTP protein, resulting in elevated mRNA decay rates of TTP targets. We examined the effect of TTP overexpression on the hematopoietic system in both young and middle-aged mice using TTPΔARE mice and found alterations in blood cell frequencies, with loss of platelets and B220 cells and gains of eosinophils and T cells.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, SCV2), which has resulted in higher morbidity and mortality rate than other respiratory viral infections, such as Influenza A virus (IAV) infection. Investigating the molecular mechanisms of SCV2-host infection vs IAV is vital in exploring antiviral drug targets against SCV2. We assessed differential gene expression in human nasal cells upon SCV2 or IAV infection using RNA sequencing.
View Article and Find Full Text PDFBackground: Electronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes.
View Article and Find Full Text PDF: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb.
View Article and Find Full Text PDFWe have recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancers also co-opt differentiation of these B-cell precursors to generate macrophage-like cells (termed B-MF). We link the transdifferentiation to a small subset of CSF1R Pax5 cells within BM pre-B and immature B cells responding to cancer-secreted M-CSF with downregulation of the transcription factor Pax5 via CSF1R signaling.
View Article and Find Full Text PDFMany age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from 3 to 27 months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25 CD4 population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions.
View Article and Find Full Text PDFUnlabelled: Melatonin is a hormone secreted by the pineal gland that is involved in the biorhythm of reproductive activities. The present study investigated the inhibitory effects of melatonin on osteoclastogenesis in RAW 264.7 cells according to changes in V-ATPase and the corresponding inhibition of the MAPK and NFATc1 signaling processes.
View Article and Find Full Text PDFMalignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery.
View Article and Find Full Text PDFAlthough various methods, such as surgery and chemotherapy, are applied to the treatment of OSCC, there are problems, such as functional and aesthetic limitations of the mouth and face, drug side effects, and lymph node metastasis. Many researchers are making efforts to develop new therapeutic agents from plant-derived substances to overcome the side effects that occur in oral cancer treatment. Polydatin is known as a natural precursor of resveratrol, and research on its efficacy is being actively conducted recently.
View Article and Find Full Text PDFNAD supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD precursor, improved lymphoid lineage potential during supplementation.
View Article and Find Full Text PDFSelf-adhesive resins (SARs) contain adhesives, which simplify the procedures of resin application, and primers, which provide sufficient bonding ability. In this study, mesoporous bioactive glass nanoparticles (MBN) were added to a SAR to easily improve the physical properties and remineralization ability. The experimental resins comprised 1%, 3%, and 5% MBN mixed in Ortho Connect Flow (GC Corp, Tokyo, Japan).
View Article and Find Full Text PDFParticulate matter ≤2.5μm (PM) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact of chronic exposure to PM alone, or with light at night exposure (LL) on metabolism.
View Article and Find Full Text PDFThe purpose of this study was to assess the effects in the dentin bond strength of dental adhesives (DAs) and biological effects using zinc (Zn)-doped mesoporous bioactive glass nanoparticles (MBN-Zn). Synthesized MBN and MBN-Zn were characterized by scanning electron microscopy (SEM), X-ray diffraction and the Brunauer, Emmett and Teller (BET) method. The matrix metalloproteinases (MMP) inhibition effects of DA-MBN and DA-MBN-Zn were analyzed.
View Article and Find Full Text PDFNuclear actin has been elusive due to the lack of knowledge about molecular mechanisms. From actin-containing chromatin remodeling complexes, we discovered an arginine mono-methylation mark on an evolutionarily conserved R256 residue of actin (R256me1). Actin R256 mutations in yeast affect nuclear functions and cause diseases in human.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFChronic exposure to particulate matter < 2.5µ (PM) has been linked to cardiopulmonary disease. Tissue-resident (TR) alveolar macrophages (AΦ) are long-lived, self-renew and critical to the health impact of inhalational insults.
View Article and Find Full Text PDFBiodegradable materials, including the widely used poly (lactic-co-glycolic acid) (PLGA) nanoparticles contained in slow-release drug formulations, scaffolds and implants, are ubiquitous in modern biomedicine and are considered inert or capable of being metabolized through intermediates such as lactate. However, in the presence of metabolic stress, such as in obesity, the resulting degradation products may play a detrimental role, which is still not well understood. We evaluated the effect of intravenously-administered PLGA nanoparticles on the gut-liver axis under conditions of caloric excess in C57BL/6 mice.
View Article and Find Full Text PDFAir pollution involving particulate matter smaller than 2.5 μm in size (PM2.5) is the world's leading environmental risk factor contributing to mortality through cardiometabolic pathways.
View Article and Find Full Text PDFPreterm birth (PTB) is a major public health challenge, and novel, sensitive approaches to predict PTB are still evolving. Epigenomic markers are being explored as biomarkers of PTB because of their molecular stability compared to gene expression. This approach is also relatively new compared to gene-based diagnostics, which relies on mutations or single nucleotide polymorphisms.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
May 2020
Air-liquid interface (ALI) cultures are ex vivo models that are used extensively to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient in vivo, and the degree to which this alters gene expression remains unclear. In this study we employed RNA sequencing to compare the transcriptome of fresh brushings of nasal epithelial cells with that of ALI-cultured epithelial cells from the same patients.
View Article and Find Full Text PDFThe purpose of this study was to investigate the effects of mesoporous bioactive glass nanoparticle (MBN)/graphene oxide (GO) composites on the mineralization ability and differentiation potential of human dental pulp stem cells (hDPSCs). MBN/GO composites were synthesized using the sol-gel method and colloidal processing to enhance the bioactivity and mechanical properties of MBN. Characterization using FESEM, XRD, FTIR, and Raman spectrometry showed that the composites were successfully synthesized.
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