Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy.

Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications.

Cancer is a disease caused by abnormal cell growth that spreads through other parts of the body and threatens life by destroying healthy tissues. Therefore, numerous techniques have been employed not only to diagnose and monitor the progress of cancer in a precise manner but also to develop appropriate therapeutic agents with enhanced efficacy and safety profiles. In this regard, molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for theragnostic approaches.

Plasmon Modulated Upconversion Biosensors.

Over the past two decades, lanthanide-based upconversion nanoparticles (UCNPs) have been fascinating scientists due to their ability to offer unprecedented prospects to upconvert tissue-penetrating near-infrared light into color-tailorable optical illumination inside biological matter. In particular, luminescent behavior UCNPs have been widely utilized for background-free biorecognition and biosensing. Currently, a paramount challenge exists on how to maximize NIR light harvesting and upconversion efficiencies for achieving faster response and better sensitivity without damaging the biological tissue upon laser assisted photoactivation.

Tranilast protects pancreatic β-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition.

Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1's role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure.

Upconversion nanomaterials and delivery systems for smart photonic medicines and healthcare devices.

In the past decade, upconversion (UC) nanomaterials have been extensively investigated for the applications to photomedicines with their unique features including biocompatibility, near-infrared (NIR) to visible conversion, photostability, controllable emission bands, and facile multi-functionality. These characteristics of UC nanomaterials enable versatile light delivery for deep tissue biophotonic applications. Among various stimuli-responsive delivery systems, the light-responsive delivery process has been greatly advantageous to develop spatiotemporally controllable on-demand "smart" photonic medicines.

Sodium salicylate induces browning of white adipocytes via M2 macrophage polarization by HO-1 upregulation.

Browning, a white to brown-like (beige) adipocyte conversion, offers a promising therapeutic strategy for the treatment of human obesity. In the present study, the effects of sodium salicylate, a nonsteroidal anti-inflammatory drug, on adipocyte browning were investigated. We found sodium salicylate altered the macrophage phenotype to M2 in RAW264.

Graphene-Based Nanomaterials as Drug Delivery Carriers.

Graphene and graphene-based materials have been attracted in the past few years for biomedical applications due to their physicochemical and biological properties such as large surface area, chemical and mechanical stability, excellent conductivity, and good biocompatibility. Graphene-based materials not only surface modified graphene-based materials like graphene oxide (GO) or reduced graphene oxide (rGO) but also other structural forms like fullerene, carbon nanotubes, and graphite have been applied to advanced drug delivery systems. In this chapter, we review on the application of graphene-based materials in the drug delivery system with their physicochemical properties, methods for the preparation of graphene-based carriers, followed by analysis about their biodistribution and biosafety whether they are suitable as drug delivery carriers.

Non-Invasive Topical Drug-Delivery System Using Hyaluronate Nanogels Crosslinked via Click Chemistry.

Hyaluronate (HA) has been widely investigated for noninvasive topical drug delivery of chemical drugs and biopharmaceuticals. However, previous noninvasive delivery systems have been facilitated mostly by chemical conjugation of drugs with HA, which can cause reduced therapeutic efficacy and safety issues in chemically modified drugs. Here, HA nanogels were synthesized by crosslinking via "click" chemistry for noninvasive topical delivery of a model drug without chemical modification.

Novel FoxO1 inhibitor, JY-2, ameliorates palmitic acid-induced lipotoxicity and gluconeogenesis in a murine model.

Forkhead transcription factor forkhead box O1 (FoxO1) plays an important role in glucose and lipid metabolism, contributing to the pathogenesis of metabolic disorders. This study aimed to discover a novel FoxO1 inhibitor as a potential new anti-diabetic drug candidate, and describes the biological effects of JY-2, 5-(2,4-dichlorophenyl)-3-(pyridin-2-yl)-1,2,4-oxadiazole in vitro and in vivo. JY-2 inhibited FoxO1 transcriptional activity in a concentration-dependent manner, with an IC value of 22 μM.

Author Correction: Telmisartan induces browning of fully differentiated white adipocytes via M2 macrophage polarization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Telmisartan induces browning of fully differentiated white adipocytes via M2 macrophage polarization.

Telmisartan is a well-known anti-hypertensive drug acting as an angiotensin 2 receptor blocker (ARB), but it also possesses partial PPARγ agonistic activity and induces insulin sensitivity. In the present study, we investigated the effects of telmisartan on macrophage polarization in association with its browning capacity, because PPARγ plays a key role in M2 polarization and in the browning of white adipocytes. Telmisartan induced M2 marker expression in murine macrophages concentration dependently, which was confirmed by flow cytometry.

Foenumoside B isolated from Lysimachia foenum-graecum extract suppresses LPS-induced inflammatory response via NF-κB/AP-1 inactivation in murine macrophages and in endotoxin-induced shock model.

Foenumoside B (FSB), a bioactive component isolated from the Lysimachia foenum-graecum extract (LFE), has been shown to possess anti-inflammatory effects, but the underlying molecular mechanisms involved have not been elucidated. Accordingly, the authors investigated the mechanisms responsible for the anti-inflammatory effects of FSB in murine macrophages activated by LPS. FSB suppressed the LPS-induced expressions of iNOS and COX-2 at protein and mRNA levels and consequently decreased NO and PGE2 production in RAW264.

5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and insulin resistance via AMPK activation in murine myotubes.

Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production.

6-(3,4-Dihydro-1H-isoquinoline-2-yl)-N-(6-methoxypyridine-2-yl) nicotinamide-26 (DIMN-26) decreases cell proliferation by induction of apoptosis and downregulation of androgen receptor signaling in human prostate cancer cells.

Previously, we reported that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl) nicotinamide (DIMN) analogues inhibited the growth of prostate cancer cells as an anti-androgenic compound. In the present study, we evaluated cytotoxic effects of these DIMN derivatives and found that DIMN-26 most potently inhibited the proliferation of the LNCap-LN3 androgen-dependent and DU145 androgen-independent prostate cancer cells through induction of G/M phase cell cycle arrest and subsequent apoptosis. The G/M phase arrest was found due to increases in the activation of cdc2 (also known as cyclin-dependent kinase 1, CDK1)/cyclin B1 complex.

Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages.

Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects; however, the underlying mechanisms responsible for its actions are poorly understood. In the present study, we investigated the inhibitory effects of berberine and the molecular mechanisms involved in lipopolysaccharide (LPS)-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice.

Suppression of Adipocyte Differentiation by Foenumoside B from Lysimachia foenum-graecum Is Mediated by PPARγ Antagonism.

Lysimachia foenum-graecum extract (LFE) and its active component foenumoside B (FSB) have been shown to inhibit adipocyte differentiation, but their mechanisms were poorly defined. Here, we investigated the molecular mechanisms responsible for their anti-adipogenic effects. Both LFE and FSB inhibited the differentiation of 3T3-L1 preadipocytes induced by peroxisome proliferator-activated receptor-γ (PPARγ) agonists, accompanied by reductions in the expressions of the lipogenic genes aP2, CD36, and FAS.

Bortezomib attenuates palmitic acid-induced ER stress, inflammation and insulin resistance in myotubes via AMPK dependent mechanism.

Bortezomib is an anti-cancer agent that induces ER stress by inhibiting proteasomal degradation. However, the effects of bortezomib appear to be dependent on its concentration and cellular context. Since ER stress is closely related to type 2 diabetes, the authors examined the effects of bortezomib on palmitic acid (PA)-induced ER stress in C2C12 murine myotubes.

Involvement of Prolyl Hydroxylase Domain Protein in the Rosiglitazone-Induced Suppression of Osteoblast Differentiation.

Rosiglitazone is a well-known anti-diabetic drug that increases insulin sensitivity via peroxisome proliferator-activated receptor γ (PPARγ) activation, but unfortunately it causes bone loss in animals and humans. A previous study showed that prolyl hydroxylase domain protein (PHD) plays a role in rosiglitazone-induced adipocyte differentiation. Based on the inverse relationship between adipocyte and osteoblast differentiation, we investigated whether PHD is involved in the effects of rosiglitazone on osteoblast differentiation.

Resveratrol analogue (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline induces G₂/M cell cycle arrest through the activation of ATM/ATR in human cervical carcinoma HeLa cells.

Styrylquinazolines are synthetic analogues of resveratrol and have been suggested to cause anti-inflammatory activity by modulating prostaglandin E₂ (PGE₂) production. In the present study, we evaluated cytotoxic effects of various styrylquinazoline derivatives and found that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ) most potently inhibited the proliferation of the human cervical carcinoma HeLa cells. Exploring the growth-inhibitory mechanisms of 8-ADEQ, we found that it causes a cell cycle arrest at the G₂/M phase by DNA flow cytometric analysis, which was accompanied by upregulation of cyclin B1 expression and cyclin-dependent protein kinase 1 (Cdk1) phosphorylation.

Anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile, a synthetic arvelexin derivative, on the macrophages through destabilizing mPGES-1 mRNA and suppressing NF-κB activation.

We previously demonstrated that 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin, showed the strong inhibitory effects on LPS-induced NO and PGE2 production in macrophages. In this study, we focused on elucidating the anti-inflammatory properties of 7-HMIA and the mechanisms involved using in vitro and in vivo experimental models. In LPS-induced RAW 264.

Chemopreventive effects of standardized ethanol extract from the aerial parts of Artemisia princeps Pampanini cv. Sajabal via NF-κB inactivation on colitis-associated colon tumorigenesis in mice.

Chronic inflammation is an underlying risk factor of colon cancer, and NF-κB plays a critical role in the development of inflammation-associated colon cancer in an AOM/DSS mouse model. The aim of this study was to determine whether the standardized ethanol extract obtained from the aerial parts of Artemisia princeps Pampanini cv. Sajabal (EAPP) is effective at preventing inflammation-associated colon cancer, and if so, to identify the signaling pathways involved.

Anti-inflammatory effect of a standardized triterpenoid-rich fraction isolated from Rubus coreanus on dextran sodium sulfate-induced acute colitis in mice and LPS-induced macrophages.

Ethnopharmacological Relevance: Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.