The Effect of Denosumab in Elderly Patients Regarding Bone Density and Fracture Risk.

Background: With an aging population, the importance of treating and diagnosing osteoporosis is increasing. Osteoporosis, previously known as a resorptive change primarily related to endocrinological mechanisms, is also being approached as a phenomenon of senile change. Denosumab is gaining popularity among osteoporosis medications due to its ability to increase bone mineral density (BMD) and the economic benefit arising from the 6-month cycle.

Regulation of the Ca Channel Ca1.2 Supports Spatial Memory and Its Flexibility and LTD.

Widespread release of norepinephrine (NE) throughout the forebrain fosters learning and memory via adrenergic receptor (AR) signaling, but the molecular mechanisms are largely unknown. The β AR and its downstream effectors, the trimeric stimulatory G-protein, adenylyl cyclase (AC), and the cAMP-dependent protein kinase A (PKA), form a unique signaling complex with the L-type Ca channel (LTCC) Ca1.2.

α-Adrenergic receptor-PKC-Pyk2-Src signaling boosts L-type Ca channel Ca1.2 activity and long-term potentiation in rodents.

The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca channel (LTCC) Ca1.2 as a principal target for G-coupled α-adrenergic receptors (ARs).

Sensitive label-free imaging of brain samples using FxClear-based tissue clearing technique.

Optical clearing has emerged as a powerful tool for volume imaging. Although volume imaging with immunostaining have been successful in many protocols, yet obtaining homogeneously stained thick samples remains challenging. Here, we propose a method for label-free imaging of brain slices by enhancing the regional heterogeneity of the optical properties using the tissue clearing principle.

Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus.

In the hippocampus, locations associated with salient features are represented by a disproportionately large number of neurons, but the cellular and molecular mechanisms underlying this over-representation remain elusive. Using longitudinal calcium imaging in mice learning to navigate in virtual reality, we find that the over-representation of reward and landmark locations are mediated by persistent and separable subsets of neurons, with distinct time courses of emergence and differing underlying molecular mechanisms. Strikingly, we find that in mice lacking Shank2, an autism spectrum disorder (ASD)-linked gene encoding an excitatory postsynaptic scaffold protein, the learning-induced over-representation of landmarks was absent whereas the over-representation of rewards was substantially increased, as was goal-directed behavior.

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models.

Key Points: Right heart catheterization data from clinical records of heart transplant patients are used to identify patient-specific models of the cardiovascular system. These patient-specific cardiovascular models represent a snapshot of cardiovascular function at a given post-transplant recovery time point. This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time.

MUL1 E3 ligase regulates the antitumor effects of metformin in chemoresistant ovarian cancer cells via AKT degradation.

Chemoresistance is one of most critical clinical problems encountered when treating patients with ovarian cancer, due to the fact that the disease is usually diagnosed at advanced stages. Metformin is used as a first‑line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP‑activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug‑resistant cancer cells. The current study revealed that the novel antitumor mechanism of metformin is mediated by regulation of mitochondrial E3 ubiquitin protein ligase 1 (MUL1) expression that negatively regulates AKT.

Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity.

Many postsynaptic proteins undergo palmitoylation, the reversible attachment of the fatty acid palmitate to cysteine residues, which influences trafficking, localization, and protein interaction dynamics. Both palmitoylation by palmitoyl acyl transferases (PAT) and depalmitoylation by palmitoyl-protein thioesterases (PPT) is regulated in an activity-dependent, localized fashion. Recently, palmitoylation has received attention for its pivotal contribution to various forms of synaptic plasticity, the dynamic modulation of synaptic strength in response to neuronal activity.

Ursolic Acid Induces Apoptosis in Colorectal Cancer Cells Partially via Upregulation of MicroRNA-4500 and Inhibition of JAK2/STAT3 Phosphorylation.

Though ursolic acid (UA) isolated from was known to exhibit anti-cancer, anti-inflammatory, and anti-obesity effects, the underlying antitumor mechanism of ursolic acid was not fully understood to date. Thus, in the present study, the apoptotic mechanism of ursolic acid was elucidated in HCT116 and HT29 colorectal cancer cells in association with STAT3 and microRNA-4500 (miR-4500) by MTT assay, Terminal deoxynucleotidyl transferase-dT-mediated dUTP nick end labelling (TUNEL) assay, cell cycle analysis, immunofluorescence, and Western blotting. Ursolic acid significantly exerted cytotoxicity, increased TUNEL positive cells and sub-G1 apoptotic portion, induced cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) and caspase 3 in HCT116 and HT29 cells.

Autophosphorylation of F-actin binding domain of CaMKIIβ is required for fear learning.

CaMKII is a pivotal kinase that plays essential roles in synaptic plasticity. Apart from its signaling function, the structural function of CaMKII is becoming clear. CaMKII - F-actin interaction stabilizes actin cytoskeleton in a dendritic spine.

SemGen: a tool for semantics-based annotation and composition of biosimulation models.

Summary: As the number and complexity of biosimulation models grows, so do demands for tools that can help users understand models and compose more comprehensive and accurate systems from existing models. SemGen is a tool for semantics-based annotation and composition of biosimulation models designed to address this demand. A key SemGen capability is to decompose and then integrate models across existing model exchange formats including SBML and CellML.

Less Invasive Anterior Iliac Approach and Compression Osteosynthesis for the Treatment of High Anterior Column Fractures of the Acetabulum.

Background: Displaced anterior column fractures have increasingly been treated surgically by the ilioinguinal approach and fixation with lag screws and a buttress plate on the pelvic brim. However, a major disadvantage of the ilioinguinal approach is possible damage to the neurovascular bundle and the lymphatic structures in the intermediate part of the approach. This study aims to present a novel surgical technique of the less invasive anterior iliac approach and compression osteosynthesis for high anterior column fractures of the acetabulum.

Comparison of the expression of cluster of differentiation (CD)39 and CD73 between propofol- and sevoflurane-based anaesthesia during open heart surgery.

High expression of cluster of differentiation (CD)39 and CD73 has cardio-protective effects. We hypothesised that the expression of CD39 and CD73 would differ between propofol- and volatile anaesthetic-based anaesthesia in patients undergoing open heart surgery (OHS). The objective of this prospective randomized trial was to compare the changes in CD39 and CD73 levels in CD4 T cells between propofol- and sevoflurane-based anaesthesia during OHS.

Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells.

Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways.

Packing of metalized polymer nanofibers for aneurysm embolization.

Aneurysmal subarachnoid hemorrhage (SAH) is the extravasation of blood into the subarachnoid space and is fatal in most cases. Platinum coils have been used to fill the hemorrhage site and prevent the extravasation of blood. Here we explored the use of Pt-coated polymer nanofibers (NF) to prevent blood extravasation and were able to achieve improved results in vitro.

α-Actinin Anchors PSD-95 at Postsynaptic Sites.

Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95.

Isoflurane's Effect on Intraoperative Systolic Left Ventricular Performance in Cardiac Valve Surgery Patients.

Background: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S') in patients undergoing cardiac surgery.

Methods: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S' at each isoflurane dose increment (1.

Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner.

Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34 cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period. Accordingly, this study aimed to examine whether NPGP genes were expressed on the way to eosinophil terminal differentiation stage and to compare their expression kinetics with that of genes encoding eosinophil-specific granule proteins (ESGPs).

Arctiin regulates collagen type 1α chain 1 mRNA expression in human dermal fibroblasts via the miR‑378b‑SIRT6 axis.

Arctiin, a lignin isolated from Arctium lappa, exhibits a variety of biological effects, including anti‑viral, anti‑inflammatory, and anti‑proliferative actions, in mammalian cells. In a previous study, arctiin was demonstrated to induce procollagen type I synthesis and exhibited protective effects against ultraviolet B (UVB) radiation in normal human dermal fibroblasts (nHDFs). However, the underlying molecular mechanism of arctiin‑mediated collagen synthesis remains unknown.

MicroRNA‑378b regulates α‑1‑type 1 collagen expression via sirtuin 6 interference.

Ultraviolet (UV) light mediates skin aging and induces destruction of the dermis by modulating the expression levels of extracellular matrix‑associated genes, including collagen and matrix metalloproteinases. Sirtuin 6 (SIRT6), a member of the sirtuin family of proteins, regulates collagen metabolism and is an established anti‑aging protein. However, the exact underlying mechanism by which SIRT6 expression is regulated in dermal fibroblasts during the aging process is unclear.

Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells.

Background: We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model.

Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo.

Apigenin (4',5,7-trihydroxyflavone) is a flavone that has been reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties. In this study, we investigated the protective effects of apigenin on skin and found that, in experiments using cells, apigenin restored the viability of normal human dermal fibroblasts (nHDFs), which had been decreased by exposure to ultraviolet (UV) radiation in the UVA range. Using a senescence-associated (SA)-β-gal assay, we also demonstrate that apigenin protects against the UVA-induced senescence of nHDFs.

Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5α-Dihydrotestosterone-Treated Human Dermal Papilla Cells.

Background: Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level.

Biological effects of rutin on skin aging.

Rutin, a quercetin glycoside is a member of the bioflavonoid family which is known to possess antioxidant properties. In the present study, we aimed to confirm the anti‑aging effects of rutin on human dermal fibroblasts (HDFs) and human skin. We examined the effects of rutin using a cell viability assay, senescence-associated-β-galactosidase assay, reverse transcription-quantitative polymerase chain reaction, and by measuring reactive oxygen species (ROS) scavenging activity in vitro.

Interplay of enzymatic and structural functions of CaMKII in long-term potentiation.

Since the discovery of long-term potentiation (LTP) about a half-century ago, Ca /CaM-dependent protein kinase II (CaMKII) has been one of the most extensively studied components of the molecular machinery that regulate plasticity. This unique dodecameric kinase complex plays pivotal roles in LTP by phosphorylating substrates through elaborate regulatory mechanisms, and is known to be both necessary and sufficient for LTP. In addition to acting as a kinase, CaMKII has been postulated to have structural roles because of its extraordinary abundance and diverse interacting partners.