Clinical Safety and Efficacy Evaluation of a Dissolving Microneedle Patch Having Dual Anti-Wrinkle Effects With Safe and Long-Term Activities.

Background: Anti-aging products are widely used, but the desire for safe and more efficient anti-aging products continues to increase. Dissolving microneedle patches (MNPs) have provided a more efficient transdermal drug delivery solution. MNP is a promising candidate for developing better anti-aging products.

Biomarkers of angiogenesis as prognostic factors in myelodysplastic syndrome patients treated with hypomethylating agents.

Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS.

Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation.

When in the closed form, the substrate translocation channel of the proteasome core particle (CP) is blocked by the convergent N termini of α-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of α3; the resulting α3ΔN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquitinated proteins. Cells expressing the hyperactive proteasomes show markedly elevated degradation of many established proteasome substrates and resistance to oxidative stress.

Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals.

Hypoxia and infiltration of tumor-associated macrophages (TAM) are intrinsic features of the tumor microenvironment. Tumor cells that remain viable in hypoxic conditions often possess an increased survival potential and tend to grow aggressively. TAM also respond to a variety of signals in the hypoxic tumor microenvironment and express a more M2-like phenotype.

Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding.

We show that ATE1-encoded Arg-transfer RNA transferase (R-transferase) of the N-end rule pathway mediates N-terminal arginylation of multiple endoplasmic reticulum (ER)-residing chaperones, leading to their cytosolic relocalization and turnover. N-terminal arginylation of BiP (also known as GRP78), protein disulphide isomerase and calreticulin is co-induced with autophagy during innate immune responses to cytosolic foreign DNA or proteasomal inhibition, associated with increased ubiquitylation. Arginylated BiP (R-BiP) is induced by and associated with cytosolic misfolded proteins destined for p62 (also known as sequestosome 1, SQSTM1) bodies.

Direct cellular delivery of human proteasomes to delay tau aggregation.

The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial to prevent the accumulation of protein aggregates. Here we show that purified proteasomes can be directly transported into cells through mesoporous silica nanoparticle-mediated endocytosis.

A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway.

In the arginylation branch of the N-end rule pathway, unacetylated N-terminal destabilizing residues function as essential determinants of protein degradation signals (N-degron). Here, we show that a neurostimulant, para-chloroamphetamine (PCA), specifically inhibits the Arg/N-end rule pathway, delaying the degradation of its artificial and physiological substrates, including regulators of G protein signaling 4 (RGS4), in vitro and in cultured cells. In silico computational analysis indicated that PCA strongly interacts with both UBR box and ClpS box, which bind to type 1 and type 2 N-degrons, respectively.

A case of midazolam anaphylaxis.

Midazolam is a type of anesthetic agent frequently used for conscious sedation during a variety of medical procedures. Anaphylactic reactions to midazolam are rarely reported. However, we observed a case of midazolam hypersensitivity in which emergency measures were required to ensure patient recovery after administration of midazolam as a sedative.

Targeting estrogen receptors for the treatment of Alzheimer's disease.

The significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to loss of estrogen and a variety of related mechanisms at the molecular, cellular, and hormonal levels, which subsequently elucidate neuroprotective roles of estrogen against AD-related pathology. Recent studies have proposed that beneficial effects of estrogen on AD are directly linked to its ability to reduce amyloid-β peptides and tau aggregates, two hallmark lesions of AD. Despite high expectations, large clinical trials with postmenopausal women indicated that the beneficial effects of estrogen therapies were insignificant and, in fact, elicited adverse effects.

Molecular characteristics of cancer stem-like cells derived from human breast cancer cells.

We characterized the cellular properties of cancer stem-like cells (CSLCs) isolated from immortalized MDA-MB453 human breast cancer cells in culture. We showed that although the expression of Octamer-binding transcription factor-4 (OCT4) correlates to stemness in these CSLCs, OCT4 knockdown does not induce their differentiation. Our results suggest that the differentiation program in MDA-MB453 CSLCs is blocked at a step upstream of the transcription of the OCT4 promoter, allowing CSLCs to maintain their population through asymmetric cell division during many repeated passages.

UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells.

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I.

A case of partial trisomy 3p syndrome with rare clinical manifestations.

Partial trisomy 3p results from either unbalanced translocation or de novo duplication. Common clinical features consist of dysmorphic facial features, congenital heart defects, psychomotor and mental retardation, abnormal muscle tone, and hypoplastic genitalia. In this paper, we report a case of partial trisomy 3p with rare clinical manifestations.

Partners in crime: ubiquitin-mediated degradation and autophagy.

Recent focus on autophagy research has led to new insights on the involvement of ubiquitin (Ub)-mediated signaling as a selectivity factor in autophagy, which is generally considered a nonselective global degradation system. Emerging reports have demonstrated active crosstalk between the Ub-dependent proteolytic system and autophagy. This article highlights recent reports describing Ub-mediated selective autophagy regulated by the Toll-like receptor 4-induced immune response.

Synthesis of copper nanoparticles by solid-state plasma-induced dewetting.

Copper nanoparticles were prepared by the plasma treatment of Cu thin films without extra heating. The Cu nanoparticles were formed through a solid-state dewetting process at temperatures of less than 450 K. The particle sizes, from 10 to 80 nm, were controlled by changing the thickness of the Cu film; the particle size increased linearly with the film thickness.

Lysophosphatidic acid induces upregulation of Mcl-1 and protects apoptosis in a PTX-dependent manner in H19-7 cells.

Lysophosphatidic acid (LPA) is a lipid growth factor known to regulate diverse cell functions, including cell proliferation, survival, and apoptosis. Tight regulation of cell survival in neuronal precursor is essential during neurogenesis in both developing and adult brain. Increasing data show that diverse external factors including LPA play roles in controlling cell survival and apoptosis in early developing neurons.

Anti-proliferative and apoptosis induction activity of green tea polyphenols on human promyelocytic leukemia HL-60 cells.

Background: Anti-proliferation and apoptosis inducing effects of green tea polyphenols (GTPs) were studied against human promyeolcytic leukemia HL-60 cells.

Materials And Methods: Anti-proliferation activity of GTPs against HL-60 cells and cytotoxicity against normal cells, V79-4 were measured with the MTT assay. Nuclear fragmentation of GTP-treated cells was observed with a fluorescence microscope and flow-cytometric analysis was performed to observe the appearance of apoptotic bodies.

Difference in growth suppression and apoptosis induction of EGCG and EGC on human promyelocytic leukemia HL-60 cells.

Growth suppression and apoptosis inducing effect of (-)-epigallocatechin 3-gallate (EGCG) and (-)-epigallocatechin (EGC) were studied against human promyeolcytic leukemia, HL-60 cells. EGCG showed higher growth suppression against HL-60 cells than EGC. IC(50) values for EGCG were 60.

Antioxidant and apoptosis-inducing activities of ellagic acid.

Background: Antioxidant, antiproliferative and apoptosis inducing activities of a natural polyphenolic compound, ellagic acid, were studied.

Materials And Methods: DPPH radical scavenging and lipid peroxidation inhibitory activities were observed. Activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were measured in ellagic acid-treated V79-4 cells.

Inhibition of proliferation and induction of apoptosis by EGCG in human osteogenic sarcoma (HOS) cells.

EGCG [(-)-epigallocatechin-3-gallate], a major component of green tea has been considered as a major antioxidant constituent. In addition to having been considered for cancer treatment as a chemopreventive and chemotherapeutic agent, EGCG has recently been attributed an anti-proliferative effect. We re-examined the latter finding in this study and added specific focus on the ability of EGCG to induce apoptosis in human osteogenic sarcoma (HOS) cells.