Vascular calcification and cellular signaling pathways as potential therapeutic targets.

Increased vascular calcification (VC) is observed in patients with cardiovascular diseases such as atherosclerosis, diabetes, and chronic kidney disease. VC is divided into three types according to its location: intimal, medial, and valvular. Various cellular signaling pathways are associated with VC, including the Wnt, mitogen-activated protein kinase, phosphatidylinositol-3 kinase/Akt, cyclic nucleotide-dependent protein kinase, protein kinase C, calcium/calmodulin-dependent kinase II, adenosine monophosphate-activated protein kinase/mammalian target of rapamycin, Ras homologous GTPase, apoptosis, Notch, and cytokine signaling pathways.

Macrophages are primed to transdifferentiate into fibroblasts in malignant ascites and pleural effusions.

Cancer-associated fibroblasts (CAFs) play an important role in cancer progression. However, the origin of CAFs remains unclear. This study shows that macrophages in malignant ascites and pleural effusions (cavity fluid-associated macrophages: CAMs) transdifferentiate into fibroblast-like cells.

Bioinspired macrophage-targeted anti-inflammatory nanomedicine: A therapeutic option for the treatment of myocarditis.

Myocarditis is a disease characterized by inflammation of the heart muscle, which increases the risk of dilated cardiomyopathy and heart failure. Macrophage migration is a major histopathological hallmark of myocarditis, making macrophages a potential therapeutic target for the management of this disease. In the present study, we synthesized a bioinspired anti-inflammatory nanomedicine conjugated with protein G (PSL-G) that could target macrophages and induce macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.

Identification of Activated Protein Kinase Cα (PKCα) in the Urine of Orthotopic Bladder Cancer Xenograft Model as a Potential Biomarker for the Diagnosis of Bladder Cancer.

Bladder cancer has a high recurrence rate; therefore, frequent and effective monitoring is essential for disease management. Cystoscopy is considered the gold standard for the diagnosis and continuous monitoring of bladder cancer. However, cystoscopy is invasive and relatively expensive.

Protein Nanoparticles Modified with PDGF-B as a Novel Therapy After Acute Cerebral Infarction.

Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs (HSPNPs) to examine its therapeutic effect in cerebral infarction.

Reflectance spectra analysis for mucous assessment.

This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology.

Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells.

Background: Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage.

Methods: Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle.

Sodium thiosulfate prevents doxorubicin-induced DNA damage and apoptosis in cardiomyocytes in mice.

Aim: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy.

Main Methods: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later.

Design of substrates and inhibitors of G protein-coupled receptor kinase 2 (GRK2) based on its phosphorylation reaction.

The G protein-coupled receptor kinase (GRK) family consists of seven cytosolic serine/threonine (Ser/Thr) protein kinases, and among them, GRK2 is involved in the regulation of an enormous range of both G protein-coupled receptors (GPCRs) and non-GPCR substrates that participate in or regulate many critical cellular processes. GRK2 dysfunction is associated with multiple diseases, including cancers, brain diseases, cardiovascular and metabolic diseases, and therefore GRK2-specific substrates/inhibitors are needed not only for studies of GRK2-mediated cellular functions but also for GRK2-targeted drug development. Here, we first review the structure, regulation and functions of GRK2, and its synthetic substrates and inhibitors.

Effect of Fetal Bovine Serum Concentration on Lysophosphatidylcholine-mediated Proliferation and Apoptosis of Human Aortic Smooth Muscle Cells.

Lysophosphatidylcholine (lysoPtdCho) is produced by the phospholipase A-mediated hydrolysis of phosphatidylcholine and can stimulate proliferation and apoptosis of vascular smooth muscle cells. We examined the influence of fetal bovine serum (FBS) concentration in the culture medium on lysoPtdCho-mediated apoptosis and proliferation of human aortic smooth muscle cells (HASMCs) as well as on the activation of extracellular signal-regulated kinases (ERK)1/2. In the presence of 1% FBS, HASMC viability increased after lysoPtdCho treatment at 1 and 10 μM but decreased at 25 and 50 μM.

Suppression of Lysophosphatidylcholine-Induced Human Aortic Smooth Muscle Cell Calcification by Protein Kinase A Inhibition.

Lysophosphatidylcholine (lysoPtdCho) is produced mainly by the phospholipase A2-dependent hydrolysis of phosphatidylcholine (PtdCho) and can induce inflammatory activation and osteogenic gene expression in vascular smooth muscle cells. However, the mechanisms mediating these processes have not been fully elucidated. In this study, we investigated whether inhibition of protein kinase A (PKA) signaling suppressed lysoPtdCho-induced calcification of human aortic smooth muscle cells (HASMC).

A high-affinity peptide substrate for G protein-coupled receptor kinase 2 (GRK2).

We synthesized a previously identified β-tubulin-derived G protein-coupled receptor kinase 2 (GKR2) peptide (GR-11-1; DEMEFTEAESNMN) and its amino-terminal extension (GR-11-1-N; GEGMDEMEFTEAESNMN) and carboxyl-terminal extension (GR-11-1-C; DEMEFTEAESNMNDLVSEYQ) peptides with the aim of finding a high-affinity peptide substrate for GRK2. GR-11-1-C showed high affinity for GRK2, but very low affinity for GKR5. Its specificity and sensitivity for GKR2 were greater than those of GR-11-1 and GR-11-1-N.

Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate.

Aims: Smooth muscle cells (SMCs) play a role in medial vascular calcification, which can be stimulated by high levels of serum phosphate and inflammatory mediators. The aim of this study was to investigate whether mitogen-activated protein kinases (MAPKs) (p38 MAPK, ERK1/2, and JNK) and protein kinase A (PKA) can participate in inorganic phosphate (Pi)- and inflammation response-stimulated SMC calcification.

Main Methods: We examined the change of Pi- and/or inflammation-stimulated human aortic smooth muscle cell (HASMC) calcification in the presence and absence of inhibitors or small interfering RNAs.

Increased hepatic inflammation in a normal-weight mouse after long-term high-fat diet feeding.

Among five C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, one mouse showed a body weight (BW) similar to normal diet (ND)-fed mice. We compared obesity-related parameters of three groups (ND-fed mice, one HFD-fed normal-weight mouse, and HFD-fed overweight mice), including visceral fat weight, serum levels of total cholesterol (TC), glucose, and aminotransferases (AST and ALT), adipocyte size, percentage of crown-like structures, severity of hepatic steatosis, and number of inflammatory foci. Compared to ND-fed mice, the HFD-fed normal-weight mouse exhibited a similar visceral fat weight, similar serum levels of glucose and aminotransferases, and a similar percentage of crown-like structures.

Ligand-Mediated Coating of Liposomes with Human Serum Albumin.

Coating liposome surfaces with human serum albumin (HSA) can improve the colloidal stability and prevent opsonization. HSA coating via specific binding with alkyl ligands is promising because although the ligand-mediated coating is relatively stable it can spontaneously exchange with fresh HSA. However, to achieve surface coating with HSA, multiple hydrophobic ligands must be exposed to an aqueous medium prior to binding with HSA.

Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage-based targeted contrast agent.

Contrast agents with greater specificity and sensitivity are required for the diagnosis of pancreatic cancers by magnetic resonance imaging (MRI). In this study, small heat shock protein 16.5 (Hsp16.

Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice.

Obesity is associated with chronic inflammation and is known as a major risk factor for several diseases including chronic kidney disease, diabetes, and cardiovascular diseases. Macrophages play a critical role in the development of obesity-induced inflammation. Efficient delivery of therapeutic anti-inflammatory molecules, such as interleukin (IL)-10, to macrophages can dramatically improve therapeutic efficacy of obesity treatments.

Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2).

A series of amino acid substitutions was made in a previously identified β-tubulin-derived GRK2 substrate peptide (DEMEFTEAESNMN) to examine the role of amino acid residues surrounding the phosphorylation site. Anionic amino acid residues surrounding the phosphorylation site played an important role in the affinity for GRK2. Compared to the original peptide, a modified peptide (Ac-EEMEFSEAEANMN-NH) exhibited markedly higher affinity for GRK2, but very low affinity for GRK5, suggesting that it can be a sensitive and selective peptide for GRK2.

Noninvasive mapping of the redox status of dimethylnitrosamine-induced hepatic fibrosis using in vivo dynamic nuclear polarization-magnetic resonance imaging.

Hepatic fibrosis is a chronic disorder caused by viral infection and/or metabolic, genetic and cholestatic disorders. A noninvasive procedure that enables the detection of liver fibrosis based on redox status would be useful for disease identification and monitoring, and the development of treatments. However, an appropriate technique has not been reported.

Förster Resonance Energy Transfer-Based Self-Assembled Nanoprobe for Rapid and Sensitive Detection of Postoperative Pancreatic Fistula.

Postoperative pancreatic fistula (POPF) is the most serious and challenging complication following gastroenterological surgery. Activated pancreatic juice leaking from the organ remnant contains proteases that attack the surrounding tissue, potentially leading to severe inflammation, tissue necrosis, and fistula formation. However, it is difficult to observe pancreatic leakage during surgery and to evaluate the protease activity of leaked fluid at the patient's bedside.