Solute Stabilization Effects of Nanoparticles Containing Boronic Acids in the Absence of Binding Pairs.

Boronic acids are widely used in materials science because of their ability to reversibly bind with diol and catechol moieties through dynamic covalent interactions in a pH- and oxidative-dependent manner. Considerably fewer studies focus on property modulation of boronic acid-based materials in the absence of a biding pair. Herein, we discuss the effects of the boronic acid-containing polymer block length on solute release kinetics from nanoparticles in a stimuli-responsive manner for on-demand delivery. In this study, ABC-type linear amphiphiles of poly(d,l-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) containing a middle block functionalized with 3-aminophenylboronic acid were synthesized by a combination of ring-opening and controlled free radical polymerizations. Nile red-loaded nanoparticles were self-assembled using a multi-inlet vortex mixer in a well-controlled manner. Release was evaluated at pH above and below the pKa of the boronic acid and in the presence of hydrogen peroxide. Our results show that release kinetics from nanoparticles incorporating a boronic acid-functionalized interlayer were slower than those without it, and the rate could be modulated according to pH and oxidative conditions. These effects can be attributed to several factors, including the hydrophobicity of the boronic acid block as well as hydrogen bonding interactions existing between locally confined boronic acids. While boronic acids are generally utilized as boronic/boronate esters, their stabilizing effects in the absence of appropriate binding pairs are relevant and should be considered in the design of boronic acid-based technologies.

Thyroid-Stimulating Hormone as a Biomarker for Stress After Thyroid Surgery: A Prospective Cohort Study.

BACKGROUND Thyroid-stimulating hormone (TSH), which is regulated by the negative feedback of triiodothyronine (T3) and thyroxine (T4), is affected by cortisol (a stress hormone) and cytokines during allostasis. Thus, we assessed changes in TSH levels under stress and its potential as a stress marker in patients lacking T3 or T4 feedback after thyroid surgery. MATERIAL AND METHODS Three stress questionnaires (Korean version of the Daily Stress Inventory, Social Readjustment Rating Scale, and Stress Overload Scale-Short [SOSS]), an open-ended questionnaire (OQ), and thyroid function tests were administered twice to 106 patients enrolled from January 2019 to October 2020. RESULTS In a multiple generalized linear mixed-effect model (GLMM) involving 106 patients, the T3 and free T4 levels, OQ, body weight, extent of thyroidectomy, and preoperative TSH levels were significantly correlated with log-transformed TSH (lnTSH). The modified SOSS (category) based on recent stressors on OQ interview was significantly associated with lnTSH. In the GLMM with modified SOSS (category), the lnTSH increased by 2.3 and 0.56 in the unconscious high- and high-risk groups, respectively, compared to that in the low-risk group (P<0.05). The calculated power of this study was 0.92 based on alpha=0.05. CONCLUSIONS TSH had a significant relationship with stress and the extent of thyroidectomy. An OQ supported the SOSS to help detect unrecognized stressors. TSH has potential utility as a stress marker combined with the modified SOSS (category) with sufficient power. However, questionnaires on social environments and research on coping strategies for stress are necessary for future studies.

Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails.

Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region.

Recurrent neural network FPGA hardware accelerator for delay-tolerant indoor optical wireless communications.

The optical wireless communication (OWC) system has been widely studied as a promising solution for high-speed indoor applications. The transmitter diversity scheme has been proposed to improve the performance of high-speed OWC systems. However, the transmitter diversity is vulnerable to the delay of multiple channels. Recently neural networks have been studied to realize delay-tolerant indoor OWC systems, where long-short term memory (LSTM) and attention-augmented LSTM (ALSTM) recurrent neural networks (RNNs) have shown their capabilities. However, they have high computation complexity and long computation latency. In this paper, we propose a low complexity delay-tolerant RNN scheme for indoor OWC systems. In particular, an RNN with parallelized structure is proposed to reduce the computation cost. The proposed RNN schemes show comparable capability to the more complicated ALSTM, where a bit-error-rate (BER) performance within the forward-error-correction (FEC) limit is achieved for up to 5.5 symbol periods delays. In addition, previously studied LSTM/ALSTM schemes are implemented using high-end GPUs, which have high cost, high power consumption, and long processing latency. To solve these practical limitations, in this paper we further propose and demonstrate the FPGA-based RNN hardware accelerator for delay-tolerant indoor OWC systems. To optimize the processing latency and power consumption, we also propose two optimization methods: the parallel implementation with triple-phase clocking and the stream-in based computation with additive input data insertion. Results show that the FPGA-based RNN hardware accelerator with the proposed optimization methods achieves 96.75% effective latency reduction and 90.7% lower energy consumption per symbol compared with the FPGA-based RNN hardware accelerator without optimization. Compared to the GPU implementation, the latency is reduced by about 61% and the power consumption is reduced by about 58.1%.

Stimuli-Responsive Conformational Transformation of Peptides for Tunable Cytotoxicity.

The stimuli-responsive conformational transformation of peptides possessing a constrained form triggered by specific biological microenvironment would provide an effective strategy for the development of highly specific peptide therapeutics. Here, we developed a peptide containing a cytotoxic helical KLA sequence with therapeutic specificity through the use of stimuli-responsive conformational transformation. The KLA peptide is modified to form a cyclic structure to allow for constrained helicity that confers low cytotoxicity. The modified KLA peptide is electrostatically complexed to hyaluronic acid to facilitate enhanced endocytosis into the cancer cells. After endocytosis, the peptide is released from the complex into the cellular cytoplasm by hyaluronidases on the surface of the cellular membrane. Specific intracellular stimuli then trigger the release of the strain that suppresses peptide helicity, and the inherent helical conformation of the KLA peptide is restored. Therefore, the stimuli-responsive conformational transformation of a peptide from low to high helicity selectively induces cell death by disruption of the plasma and mitochondrial membrane.

FPGA-based neural network accelerators for millimeter-wave radio-over-fiber systems.

With rapidly developing high-speed wireless communications, the 60 GHz millimeter-wave (mm-wave) frequency range has attracted extensive interests, and radio-over-fiber (RoF) systems have been widely investigated as a promising solution to deliver mm-wave signals. Neural networks have been proposed and studied to improve the mm-wave RoF system performances at the receiver side by suppressing both linear and nonlinear impairments. However, previous studies of neural networks in mm-wave RoF systems all focus on the use of off-line processing with high-end GPUs or CPUs, which are not practical for low power-consumption, low-cost and limited computation platform applications. To solve this issue, in this paper we investigate neural network hardware accelerator implementations for mm-wave RoF systems for the first time using the field programmable gate array (FPGA), taking advantage of the low power consumption, parallel computation, and reconfigurablity features of FPGA. Both the convolutional neural network (CNN) and binary convolutional neural network (BCNN) hardware accelerators are demonstrated. In addition, to satisfy the low-latency requirement in mm-wave RoF systems and to enable the use of low-cost compact FPGA devices, a novel inner parallel computation optimization method for implementing CNN and BCNN on FPGA is proposed. It is shown that compared with the popular embedded processor (ARM Cortex A9) execution latency, the proposed FPGA-based hardware accelerator reduces the processing delay in mm-wave RoF systems by about 99.45% and 92.79% for CNN and BCNN, respectively. Compared with non-optimized FPGA implementations, results show that the proposed inner parallel computation method reduces the processing latency by about 44.93% and 45.85% for CNN and BCNN, respectively. In addition, compared with the GPU implementation, the latency of CNN implementation with the proposed optimization method is reduced by 85.49%, while the power consumption is reduced by 86.91%. Although the latency of BCNN implementation with the proposed optimization method is larger compared with the GPU implementation, the power consumption is reduced by 86.14%. The demonstrated FPGA-based neural network hardware accelerators provide a promising solution for mm-wave RoF systems.

Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches.

A series of diarylurea derivatives comprising 2,4-diarylpyrimidines were synthesized based on a combination of postulated molecular hybridization design and failed-ligands repurposing approaches, which enabled the discovery of novel potential antiproliferative agents. Towards credible biological evaluation, an in vitro anticancer activity assay was conducted employing a library of 60 cancer cell lines constituting nine panels representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. The results revealed high effectiveness and broad-spectrum anticancer activity of compounds 4m and 4g. Five-dose assay of compounds 4m and 4g proved their high potency that surpassed that of four standard kinase inhibitors FDA-approved anticancer drugs against many cancer cells. Towards the identification of their molecular target, screening of kinase inhibitory profile employing a panel of 51 kinases involved in cancer revealed inhibition of several kinases from the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) kinase family, which might mediate, at least in part, the antiproliferative activity. Molecular docking of 4g into the crystal structure of the Feline McDonough Sarcoma (FMS) kinase predicted that it binds to a pocket formed by the juxtamembrane domain, the catalytic loop, and the αE helix, thus stabilizing the inhibited conformation of the kinase. Flow cytometric study of the cytotoxic effects of compound 4g in A549 cells showed it induces dose- and time-dependent apoptotic events leading to cell death. Collectively, this work presents compound 4g as a potential broad-spectrum anticancer agent against multiple cancer types.

The Association Between Chronic Lymphocytic Thyroiditis and the Progress of Papillary Thyroid Cancer.

BACKGROUND: Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. METHODS: Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. RESULTS: In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. CONCLUSIONS: The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.

Development and Validation of an LC-MS/MS Assay to Quantitate 2',4',6'-Trihydroxyacetophenone in Rat and Dog Plasma and its Application to a Pharmacokinetic Study.

In the present study, a simple, rapid, and reliable bioanalytical method was developed using liquid chromatography with tandem-mass spectrometry (LC-MS/MS) to quantify 2',4',6'-trihydroxyacetophenone (THAP) in rat and dog plasma with 2',4',6'-trihydroxybenzaldehyde as an internal standard (IS). The LC-MS/MS instrument was operated in the multiple reaction monitoring (MRM) mode to detect THAP at m/z transition 166.89 > 82.8 and IS at 152.89 > 82.8, respectively. A simple, one-step protein precipitation (PP) method was employed with acetonitrile for sample preparation. Utilizing a Gemini C18 column, THAP and IS were separated with an isocratic mobile phase consisting of 10 mM ammonium acetate and methanol (10:90, v/v) at a flow rate of 0.2 mL/min. Total chromatographic run time was 2.5 min per sample injection. The standard calibration curve for THAP was linear (r2 ≥ 0.9987) over the concentration range of 0.1 to 100 µg/mL with the lower limit of quantitation (LLOQ) of 0.1 µg/mL (S/N ratio > 10). According to the regulatory guidelines from the U.S. Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS), our newly developed biomedical analytical method was fully and adequately validated in terms of selectivity, sensitivity, linearity, intra- and inter-day precision and accuracy, recovery, matrix effect, stability, and dilution integrity. Our validated assay was successfully utilized in a nonclinical pharmacokinetic study of THAP in rats and dogs.

Incidence of hemi-diaphragmatic paresis after ultrasound-guided intermediate cervical plexus block: a prospective observational study.

PURPOSE: An intermediate cervical plexus block (CPB) targets the posterior cervical space between the sternocleidomastoid muscle and the prevertebral fascia. The phrenic nerve descends obliquely on the surface of the anterior scalene muscle beneath the prevertebral fascia after originating from the C3-C5 ventral rami. Therefore, the phrenic nerve can be affected by a local anesthetic during an intermediate CPB, depending on the permeability characteristics of the prevertebral fascia. This study investigated whether an intermediate CPB affects the phrenic nerve, inducing hemidiaphragmatic paresis. METHODS: In this prospective observational study, 20 patients undergoing single-incision transaxillary robot-assisted right thyroidectomy were enrolled. The intermediate CPB (0.25% ropivacaine 0.2 ml/kg) was performed at the C4-5 intervertebral level carefully, without penetrating the prevertebral fascia, before the patient emerged from general anesthesia. Diaphragmatic motions of the block side were measured by M-mode ultrasonography at three time points: before anesthesia (baseline) and at 30 and 60 min after the intermediate CPB. Hemidiaphragmatic paresis was divided into three grades, depending on the percentage of diaphragm movement compared to the baseline: none (> 75%), partial paresis (25-75%), and complete paresis (< 25%). RESULTS: No patient showed any partial or complete ipsilateral hemidiaphragmatic paresis within 60 min after the intermediate CPB. CONCLUSION: Intermediate CPB using 0.2 ml/kg of 0.25% ropivacaine at the C4-5 intervertebral level did not cause ipsilateral hemidiaphragmatic paresis. This may imply that the effect of the intermediate CPB on the phrenic nerve is not significant.

Recurrent neural network (RNN) for delay-tolerant repetition-coded (RC) indoor optical wireless communication systems.

Indoor optical wireless communications have been widely studied to provide high-speed connections to users, where the use of repetition-coded (RC) multiple transmitters has been proposed to improve both the system robustness and capacity. To exploit the benefits of the RC system, the multiple signals received after transmission need to be precisely synchronized, which is challenging in high-speed wireless communications. To overcome this limit, we propose and demonstrate a recurrent neural network (RNN)-based symbol decision scheme to enable a delay-tolerant RC indoor optical wireless communication system. The experiments show that the proposed RNN can improve the bit-error-rate by about one order of magnitude, and the improvement is larger for longer delays. The results also show that the RNN outperforms previously studied fully connected neural network schemes.

Engineered Polymeric Micelles for Combinational Oxidation Anticancer Therapy through Concurrent HO-1 Inhibition and ROS Generation.

Cancer cells have a large amount of ROS (reactive oxygen species) because of disturbed ROS homeostasis. Cancer cells therefore undertake redox adaptation to drive proliferation in tumor environments and even survive during anticancer treatment by upregulating endogenous antioxidants. As one of antioxidant defense systems, heme oxygenase-1 (HO-1) acts as an essential role in tumor development by offering antioxidant bilirubin to protect cancer cells under stress conditions. It can be therefore reasoned that the combination of ROS generation and HO-1 inhibition would exert synergistic anticancer effects through the amplification of oxidative stress and provide a new opportunity for targeted anticancer therapy. To establish targeted anticancer therapy based on amplified oxidative stress, we developed molecularly engineered polymer, termed CZP, which incorporates ROS generating CA (cinnamaldehyde) and HO-1 inhibiting ZnPP (zinc protoporphyrin) in its backbone and could form stable micelles in aqueous solutions. CZP micelles not only elevated oxidative stress but also suppressed the expression of antioxidant HO-1, leading to apoptotic cell death. CZP micelles could also significantly suppress the tumor growth without body weight loss, tumor recurrence, and noticeable toxicity in organs. This study demonstrates that a combination of ROS generation and HO-1inhibition synergistically magnifies oxidative stress to kill cancer cells and oxidative stress amplifying CZP micelles may provide a promising strategy in anticancer treatment.

A novel mPGES-1 inhibitor alleviates inflammatory responses by downregulating PGE2 in experimental models.

We previously reported the strong inhibitory potency of N-phenyl-N'-(4- benzyloxyphenoxycarbonyl)-4-chlorophenylsulfonyl hydrazide (PBCH) on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production in macrophages. Herein, we characterized PBCH as a microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor and evaluated its anti-inflammatory effects using in vivo experimental models. PBCH inhibited PGE2 production in various activated cells in addition to inhibiting the mPGES-1 activity. In the ear edema and paw edema rat models, PBCH significantly reduced ear thickness and paw swelling, respectively. Besides, in adjuvant-induced arthritis (AIA) rat model, PBCH decreased paw swelling, plasma rheumatoid factor (RF), and receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. Furthermore, while PBCH reduced the plasma prostaglandin E metabolite (PGEM) levels, it did not affect the plasma levels of prostacyclin (PGI2) and thromboxane A2 (TXA2). Our data suggest that PBCH downregulates PGE2 production by interfering with the mPGES-1 activity, thus reducing edema and arthritis in rat models.

ß-Caryophyllene in the Essential Oil from Chrysanthemum Boreale Induces G1 Phase Cell Cycle Arrest in Human Lung Cancer Cells.

Chrysanthemum boreale is a plant widespread in East Asia, used in folk medicine to treat various disorders, such as pneumonia, colitis, stomatitis, and carbuncle. Whether the essential oil from C. boreale (ECB) and its active constituents have anti-proliferative activities in lung cancer is unknown. Therefore, we investigated the cytotoxic effects of ECB in A549 and NCI-H358 human lung cancer cells. Culture of A549 and NCI-H358 cells with ECB induced apoptotic cell death, as revealed by an increase in annexin V staining. ECB treatment reduced mitochondrial membrane potential (MMP), disrupted the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins, and activated caspase-8, -9, and -3, as assessed by western blot analysis. Interestingly, pretreatment with a broad-spectrum caspase inhibitor (z-VAD-fmk) significantly attenuated ECB-induced apoptosis. Furthermore, gas chromatography-mass spectrometry (GC/MS) analysis of ECB identified six compounds. Among them, ß-caryophyllene exhibited a potent anti-proliferative effect, and thus was identified as the major active compound. ß- Caryophyllene induced G1 cell cycle arrest by downregulating cyclin D1, cyclin E, cyclin-dependent protein kinase (CDK) -2, -4, and -6, and RB phosphorylation, and by upregulating p21CIP1/WAF1 and p27KIP1. These results indicate that ß-caryophyllene exerts cytotoxic activity in lung cancer cells through induction of cell cycle arrest.

Panaxydol Derived from Panax ginseng Inhibits G1 Cell Cycle Progression in Non-small Cell Lung Cancer via Upregulation of Intracellular Ca2+ Levels.

Panaxydol, a polyacetylenic compound derived from Panax ginseng has been reported to suppress the growth of cancer cells. However, the molecular mechanisms underlying cell cycle arrest by this compound in non-small cell lung cancer (NSCLC) are unknown. Our study found that panaxydol treatment induced cell cycle arrest at G1 phase in NSCLC cells. The cell cycle arrest was accompanied by down-regulation of the protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E, and decrease in the phosphorylation of retinoblastoma (Rb) protein. Furthermore, up-regulation of cyclin-dependent kinase inhibitor (CDKI) p21CIP1/WAF1 and p27KIP1 was observed in panaxydol-treated NSCLC cells. In addition, panaxydol also induced accumulation of intracellular Ca2+ ([Ca2+]i). (Acetyloxy)methyl 2-({2-[(acetyloxy)methoxy]-2-oxoethyl}[2-(2-{2-[bis({2-[(acetyloxy)methoxy]-2-oxoethyl})amino]phenoxy}ethoxy)phenyl]amino)acetate (BAPTA-AM), the Ca2+ chelator, attenuated not only panaxydol-induced accumulation of [Ca2+]i, but also G1 cell cycle arrest and decrease of CDK6 and cyclin D1 protein expression level. These results demonstrated that the anti-proliferative effects of panaxydol were caused by cell cycle arrest, which is closely linked to the up-regulation of [Ca2+]i and represents a promising approach for the treatment of lung cancer.

Novel Rhodanine Derivative, 5-[4-(4-Fluorophenoxy) phenyl]methylene-3-{4-[3-(4-methylpiperazin-1-yl) propoxy]phenyl}-2-thioxo-4-thiazolidinone dihydrochloride, Induces Apoptosis via Mitochondria Dysfunction and Endoplasmic Reticulum Stress in Human Colon Cancer Cells.

We previously reported that 5-[4-(4-fluorophenoxy) phenyl] methylene-3-{4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}-2-thioxo-4-thiazolidinone dihydrochloride (KSK05104) has potent, selective and metabolically stable IKKß inhibitory activities. However, the apoptosis-inducing of KSK05104 and its underlying mechanism have not yet been elucidated in human colon cancer cells. We show that KSK05104 triggered apoptosis, as indicated by externalization of Annexin V-targeted phosphatidylserine residues in HT-29 and HCT-116 cells. KSK05104 induced the activation of caspase-8, -9, and -3, and the cleavage of poly (ADP ribose) polymerase-1 (PARP-1). KSK05104-induced apoptosis was significantly suppressed by pretreatment with z-VAD-fmk (a broad caspase inhibitor). KSK05104 also induced release of cytochrome c (Cyt c), apoptosis inducing factor (AIF), and endonuclease G (Endo G) by damaging mitochondria, resulting in caspase-dependent and -independent apoptotic cell death. KSK05104 triggered endoplasmic reticulum (ER) stress and changed the intracellular calcium level ([Ca2+]i). Interestingly, treatment with KSK05104 activated not only ER stress marker proteins including inositol-requiring enzyme 1-alpha (IRE-1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), but also µ-calpain, and caspase-12 in a time-dependent manner. KSK05104-induced apoptosis substantially decreased in the presence of BAPTA/AM (an intracellular calcium chelator). Taken together, these results suggest that mitochondrial dysfunction and ER stress contribute to KSK05104-induced apoptosis in human colon cancer cells.

23-Hydroxyursolic Acid Isolated from the Stem Bark of Cussonia bancoensis Induces Apoptosis through Fas/Caspase-8-Dependent Pathway in HL-60 Human Promyelocytic Leukemia Cells.

The natural product 23-hydroxyursolic acid (23-HUA) is a derivative of ursolic acid, which is known to induce cancer cell apoptosis. However, apoptotic effects and mechanisms of 23-HUA have not been well characterized yet. Herein, we investigated the molecular mechanisms of 23-HUA-induced apoptosis in HL-60 human promyelocytic leukemia cells. 23-HUA-treated HL-60 cells showed apoptotic features including internucleosomal DNA condensation and fragmentation as well as externalization of phosphatidylserine residues. 23-HUA induced a series of mitochondrial events including disruption of mitochondrial membrane potential (ΔΨm), cytochrome c and Smac/DIABLO release and loss of balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins in HL-60 cells. In addition, 23-HUA activated caspase-8, caspase-9 and caspase-3. Pretreatment with a broad caspase inhibitor (z-VAD-fmk), a caspase-3 inhibitor (z-DEVD-fmk), and a caspase-8 inhibitor (z-IETD-fmk) significantly attenuated 23-HUA-induced DNA fragmentation. After 23-HUA-induced apoptosis, proteins expression levels of FasL, Fas and FADD constituting the death-inducing signaling complex (DISC) were upregulated in HL-60 cells. Moreover, transfection with Fas or FADD siRNA significantly blocked 23-HUA-induced DNA fragmentation and caspases activation. Taken together, these findings indicate that 23-HUA induces apoptosis in HL-60 human promyelocytic leukemia cells through formation of DISC and caspase-8 activation leading to loss of ΔΨm and caspase-3 activation.

Mesoporous Silica Nanocarriers with Cyclic Peptide Gatekeeper: Specific Targeting of Aminopeptidase†N and Triggered Drug Release by Stimuli-Responsive Conformational Transformation.

Utilizing stimuli-responsive conformational transformation of a cyclic peptide as a gatekeeper for mesoporous nanocarriers has several advantages such as facile introduction of targeting capabilities, low enzymatic degradation during blood circulation and enhanced specific binding to selected cells. In this report, a Asn-Gly-Arg (NGR)-containing dual-functional cyclic peptide gatekeeper on the surface of mesoporous nanocarrier is prepared not only for active targeting of the aminopeptidase N (APN) expressed on cancer cells but also stimuli-responsive intracellular drug release triggered by a glutathione (GSH)-induced conformational transformation of the peptide gatekeeper. The peptide gatekeeper on the surface of nanocarriers exhibits on-off gatekeeping by conformational transformation triggered by intracellular glutathione of the cancer cells. H1299 cells (high APN expression) showed greater uptake of the nanocarrier by endocytosis and higher apoptosis than A549 cells (low APN expression).

Nanotubular self-organization of amide dendrons with focal ß-sheet forming peptide units.

To develop rational design principles for a self-organized structure using dendron-peptide conjugates, a ß-sheet forming short peptide (VVLL) was introduced to the focal point of a second-generation amide dendron (2G-VVLL) and its self-organization characteristics were investigated. 2G-VVLL self-organized into a nanotubular structure in the aqueous phase. The twisted ß-sheet structure of the focal peptide unit was essential for the construction of the nanotubular structure. The design principle could be applied to another dendron-peptide conjugate (2G-AAVV). These findings are expected to assist in the construction of novel precisely controlled nanoarchitectures using amide dendrons with focal peptide units.

Prevention of Thyroidectomy Scars in Asian Adults With Low-Level Light Therapy.

BACKGROUND: Abnormal wound-healing after thyroidectomy with a resulting scar is a common dermatologic consultation. Despite many medical and surgical approaches, prevention of postoperative scars is challenging. OBJECTIVE: This study validated the efficacy and safety of low-level light therapy (LLLT) using an 830/590 nm light-emitting diode (LED)-based device for prevention of thyroidectomy scars. METHODS AND MATERIALS: Thirty-five patients with linear surgical suture lines after thyroidectomy were treated with 830/590 nm LED-LLLT. Daily application of 60 J/cm (11 minutes) for 1 week starting on postoperative day 1 was followed by treatment 3 times per week for 3 additional weeks. The control group (n = 15) remained untreated. Scar-prevention effects were evaluated 1 and 3 months after thyroidectomy with colorimetric evaluation using a tristimulus-color analyzer. The Vancouver Scar Scale (VSS) score, global assessment, and a subjective satisfaction score (range: 1-4) were also determined. RESULTS: Lightness (L*) and chrome values (a*) decreased significantly at the 3-month follow-up visit in the treatment group compared with those of controls. The average VSS and GAS scores were lower in the treatment group, whereas the subjective score was not significantly different. CONCLUSION: Light-emitting diode based LLLT treatment suppressed the formation of scars after thyroidectomy and could be safely used without noticeable adverse effects.