The mA writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N-adenosine methylation (mA) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how mA methyltransferases modulate mA levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an mA writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes.

Metformin Suppresses Both PD-L1 Expression in Cancer Cells and Cancer-Induced PD-1 Expression in Immune Cells to Promote Antitumor Immunity.

Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells.

Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay.

AMPK-HIF-1α signaling enhances glucose-derived de novo serine biosynthesis to promote glioblastoma growth.

Background: Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown.

Methods: We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo.

Disruption of phosphofructokinase activity and aerobic glycolysis in human bronchial epithelial cells by atmospheric ultrafine particulate matter.

Exposure to ambient ultrafine particulate matter (UPM) causes respiratory disorders; however, the underlying molecular mechanisms remain unclear. In this study, we synthesized simulated UPM (sUPM) with controlled physicochemical properties using the spark-discharge method. Subsequently, we investigated the biological effects of sUPM using BEAS-2B human bronchial epithelial cells (HBECs) and a mouse intratracheal instillation model.

Fabrication Procedure for a 3D Hollow Nanofibrous Bifurcated-Tubular Scaffold by Conformal Electrospinning.

Electrospinning has shown great potential for the fabrication of 3D nanofibrous tubular scaffolds for bifurcated vascular grafts. However, fabrication of complex 3D nanofibrous tubular scaffolds with bifurcated or patient-specific shapes remains limited. In this study, a 3D hollow nanofibrous bifurcated-tubular scaffold was fabricated by the uniform and conformal deposition of electrospun nanofibers via conformal electrospinning.

A Study on the Effective Ratio of Fat to Stromal Vascular Fraction for Cell-Assisted Lipotransfer.

Background: Fat grafting, used for soft tissue augmentation during aesthetic or reconstructive plastic surgery, has disadvantages of low efficiency and unpredictable resorption rate. As an alternative, cell-assisted lipotransfer (CAL) is widely used because of its simplicity and low fat resorption rate. However, relevant studies on optimal CAL parameters are still lacking.

Impact of Organic Manure on Growth, Nutrient Content and Yield of Chilli Pepper under Various Temperature Environments.

Expected climatic changes likely elicit serious challenges for crop production. Therefore, it is indispensable to investigate the response of crop growth parameters and yield under temperature variability environments. The current experiment on chilli pepper growth was conducted in a field, rain-shelter plastic house, and plastic greenhouse, with accumulated temperatures of 2832 °C, 2967 °C, and 3105 °C in 2017; and 2944 °C, 3091 °C, and 3168 °C in 2018 growing seasons.

Effects of δ-Catenin on APP by Its Interaction with Presenilin-1.

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. β-Amyloid (Aβ) peptide is the predominant proteinaceous component of senile plaques.

Yin Yang 1 is a multi-functional regulator of adipocyte differentiation in 3T3-L1 cells.

Yin Yang 1 (YY1) is an ubiquitously distributed transcription factor that belongs to the GLI-Kruppel class of zinc finger proteins. The mechanism by which YY1 regulates adipocyte differentiation remains unclear. In this study, we investigated the functional role of YY1 during adipocyte differentiation.

Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix.

E3 ubiquitin ligase Cbl-b and c-Cbl play important roles in bone formation and maintenance. Cbl-b and c-Cbl regulate the activity of various receptor tyrosine kinases and intracellular protein tyrosine kinases mainly by regulating the degradation of target proteins. However, the precise mechanisms of how Cbl-b and c-Cbl regulate osteoblast differentiation are not well known.

An early endosome regulator, Rab5b, is an LRRK2 kinase substrate.

Leucine-rich repeat kinase 2 (LRRK2) has been identified as a causative gene for Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, both of which provide critical intracellular signal-transduction functions. We showed previously that Rab5b, a small GTPase protein that regulates the motility and fusion of early endosomes, interacts with LRRK2 and co-regulates synaptic vesicle endocytosis.

Cbl regulates the activity of SIRT2.

SIRT2 is a member of the sirtuin family of NAD(+)-dependent protein deacetylases. It is involved in metabolic homeostasis and has been linked to the progression of age-related diseases. Casitas B-lineage lymphoma (Cbl) proteins regulate signal transduction through many pathways and, consequently, regulate cell function and development.

Src regulates the activity of SIRT2.

SIRT2 is a mammalian member of the Sirtuin family of NAD(+)-dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established.

Akt enhances Runx2 protein stability by regulating Smurf2 function during osteoblast differentiation.

Runx2 plays essential roles in bone formation and chondrocyte maturation. Akt promotes osteoblast differentiation induced by the bone morphogenetic proteins BMP2 and enhances the function and transcriptional activity of Runx2. However, the precise molecular mechanism underlying the relationship between Runx2 and Akt is not well understood.

Dexamethasone induces the expression of LRRK2 and α-synuclein, two genes that when mutated cause Parkinson's disease in an autosomal dominant manner.

LRRK2 (leucine-rich repeat kinase 2) has been identified as a gene corresponding to PARK8, an autosomal-dominant gene for familial Parkinson's disease (PD). LRRK2 pathogenic-specific mutants induce neurotoxicity and shorten neurites. To elucidate the mechanism underlying LRRK2 expression, we constructed the LRRK2-promoter-luciferase reporter and used it for promoter analysis.

LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25.

Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes autosomal-dominant familial Parkinson's disease (PD). Yeast two-hybrid screening revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein, interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is phosphorylated by LRRK2.

ERK1/2 regulates SIRT2 deacetylase activity.

SIRT2 is a mammalian member of the Sirtuin family of NAD-dependent protein deacetylases. The function of SIRT2 can be modulated by post-translational modification. However, the precise molecular signaling mechanisms of SIRT2 and extracellular signal-regulated kinase (ERK)1/2 have not been correlated.

PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function.

Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation.

Inhibition of osteoblastic differentiation by warfarin and 18-α-glycyrrhetinic acid.

Anticoagulation therapy with vitamin K antagonists such as warfarin is widely used to prevent and treat stroke in patients with chronic atrial fibrillation or mechanical heart valves. Because vitamin K is an essential factor for ggg-carboxylation of osteocalcin, vitamin K antagonists might cause bone loss. Although the association between warfarin use and bone metabolism is still controversial, several studies show that bone mineral density is decreased and fracture risk is increased with warfarin therapy.

Akt phosphorylates and regulates the osteogenic activity of Osterix.

Osterix (Osx), a zinc-finger transcription factor is required for osteoblast differentiation and new bone formation during embryonic development. Akt is a member of the serine/threonine-specific protein kinase and plays important roles in osteoblast differentiation. The function of Osterix can be also modulated by post-translational modification.

Akt phosphorylates and regulates the function of Dlx5.

Akt, a phosphoinositide-dependent serine/threonine protein kinase, acts as a key regulator in bone formation. Akt can be activated by several osteogenic signaling molecules, but its precise function and downstream targets in bone development are unknown. Dlx5 transcription factor plays important roles during bone development and osteoblast differentiation.

Xanthohumol from the hop plant stimulates osteoblast differentiation by RUNX2 activation.

Xanthohumol (XN), the principal prenylated flavonoid from the hop plant, an additive that contributes bitterness and flavor to beer, is known to be a potent phytoestrogen. Although XN has been identified as a chemopreventive agent and as an anti-infective agent, its effects on bone are unknown. In the present study, the effects of XN on osteoblast differentiation and function were determined by analyzing the activity of alkaline phosphatase (ALP), an osteoblast marker, and the regulation of RUNX2, a master gene of osteoblast differentiation, in a mesenchymal stem cell line.

Protein kinase A phosphorylates and regulates the osteogenic activity of Dlx5.

Dlx5 transcription factor plays important roles in osteoblast differentiation and its transcription is regulated by many osteogenic signals including BMP-2. Recent studies suggest that the function of Dlx5 is also regulated post-translationally by protein kinases such as p38 and CaMKII. Protein kinase A (PKA) is involved in several steps of osteoblast differentiation and its activity has been shown necessary, yet not sufficient, for BMP-induced osteoblast differentiation.

Calmodulin-dependent kinase II regulates Dlx5 during osteoblast differentiation.

Calmodulin-dependent kinase II (CaMKII) acts as a key regulator of osteoblast differentiation. CaMKII is a Ca(2+)-activated serine/threonine kinase and it regulates the activity of target proteins by phosphorylation. Dlx5 transcription factor plays crucial roles in osteoblast differentiation.

Acetylation of histone deacetylase 6 by p300 attenuates its deacetylase activity.

Protein acetyltransferases and deacetylases affect the activities of each other. This is well documented by the acetylation and inhibition of HDAC1 by p300, a transcriptional co-activator with protein acetyltransferase activity. However, the relationship between HDAC6 and p300 is poorly understood.