Enhancement of TRP Gene Expression and UV Absorption by Bioconverted Chestnut Inner Shell Extracts Using Lactiplantibacillus plantarum.

In this work, the suppression of tyrosinase-related genes, including an improvement in UV absorption effects of bioconverted CS extracts (BCS), was investigated to improve the skin-whitening effect. Total polyphenols and total flavonoids, which are bioactive components, increased 2.6- and 5.4-times in bioconversion using Lactiplantibacillus plantarum SM4, respectively, as compared to ultrasound-assisted extracts (UCS). The effect of BCS on radical scavenging activity, UV-A absorption, and tyrosinase activity inhibition, contributing to skin-whitening, were 1.3-, 1.2-, and 1.2-times higher than those of UCS, respectively. The main component identified in high-performance liquid chromatography (HPLC) was gallic acid in both UCS and BCS, which increased by 2.9-times following bioconversion. The gene expression of tyrosinase-related proteins, including TRP-1 and TRP-2 genes, was studied to confirm the suppression of melanin synthesis by BCS in order to identify the skin-whitening mechanism, and BCS decreased both genes' expression by 1.7- and 1.6-times, demonstrating that BCS effectively suppressed melanin synthesis. These findings imply that the chestnut inner shell can be employed as a cosmetic material by simultaneously inhibiting melanogenesis and enhancing UV-A absorption through bioconversion using L. plantarum SM4.

Production of Bioactive Substances to Alleviates Hangover and Ethanol-Induced Liver Damage through Fermentation of Oenanthe javanica Using Lactiplantibacillus plantarum.

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.

Development of Ultrasound-Assisted Extraction to Produce Skin-Whitening and Anti-Wrinkle Substances from Safflower Seed.

In this study, ultrasound-assisted extraction (UAE) was applied to extract bioactive substances with skin-whitening, anti-wrinkle, and antioxidant effects from safflower seeds, and the extraction conditions were optimized by a central composite design. The independent variables, including extraction time (5.0~55.0 min), extraction temperature (26.0~94.0 °C), and ethanol concentration (0.0~100%), were optimized to increase tyrosinase activity inhibitory (TAI), collagenase activity inhibitory (CAI), and radical scavenging activity (RSA), which are indicators of skin-whitening, anti-wrinkle, and antioxidant effects. An extraction time of 26.4 min, extraction temperature of 52.1 °C, and ethanol concentration of 50.7% were found to be optimum conditions of UAE, under which TAI, CAI, and RSA were 53.3%, 91.5%, and 27.7%, respectively. The extract produced by UAE was analyzed by LC-MS/MS, and maleic acid and levulinic acid were identified as the main substances. Therefore, UAE is evaluated as an effective process to extract skin-whitening, anti-wrinkle, and antioxidant substances from safflower seeds at lower temperatures and shorter extraction times compared to the conventional extraction methods. Overall, safflower seeds extract can be used as a material for value-added cosmetics, including maleic acid and levulinic acid, which have bioactive functions.

Application of the Trabecular Bone Score in Clinical Practice.

The trabecular bone score (TBS) was introduced as an indirect index of trabecular microarchitecture, complementary to bone mineral density (BMD), and is derived using the same dual energy X-ray absorptiometry images. Recently, it has been approved for clinical use in Korea. Therefore, we conducted a comprehensive review to optimize the use of TBS in clinical practice. The TBS is an independent predictor of osteoporotic fractures in postmenopausal women and men aged >50 years. The TBS is potentially useful in monitoring the skeletal effects of anabolic agents but not of antiresorptive agents. In postmenopausal women with type 2 diabetes mellitus, the TBS assesses osteoporotic fracture risk not captured by BMD. However, high body mass index and soft tissue thickness can cause underestimation of the TBS; however, this limitation has been improved in recent versions of the TBS software. However, a high precision error and low reproducibility limit the use of TBS. This review may provide information on the application of the TBS in clinical practice based on reliable evidence.

Transcription Factor TonEBP Stimulates Hyperosmolality-Dependent Arginine Vasopressin Gene Expression in the Mouse Hypothalamus.

The hypothalamic neuroendocrine system is strongly implicated in body energy homeostasis. In particular, the degree of production and release of arginine vasopressin (AVP) in the hypothalamus is affected by plasma osmolality, and that hypothalamic AVP is responsible for thirst and osmolality-dependent water and metabolic balance. However, the osmolality-responsive intracellular mechanism within AVP cells that regulates AVP synthesis is not clearly understood. Here, we report a role for tonicity-responsive enhancer binding protein (TonEBP), a transcription factor sensitive to cellular tonicity, in regulating osmosensitive hypothalamic AVP gene transcription. Our immunohistochemical work shows that hypothalamic AVP cellular activity, as recognized by c-fos, was enhanced in parallel with an elevation in TonEBP expression within AVP cells following water deprivation. Interestingly, our in vitro investigations found a synchronized pattern of TonEBP and AVP gene expression in response to osmotic stress. Those results indicate a positive correlation between hypothalamic TonEBP and AVP production during dehydration. Promoter and chromatin immunoprecipitation assays confirmed that TonEBP can bind directly to conserved binding motifs in the 5'-flanking promoter regions of the AVP gene. Furthermore, dehydration- and TonEBP-mediated hypothalamic AVP gene activation was reduced in TonEBP haploinsufficiency mice, compared with wild TonEBP homozygote animals. Therefore, our result support the idea that TonEBP is directly necessary, at least in part, for the elevation of AVP transcription in dehydration conditions. Additionally, dehydration-induced reductions in body weight were rescued in TonEBP haploinsufficiency mice. Altogether, our results demonstrate an intracellular machinery within hypothalamic AVP cells that is responsible for dehydration-induced AVP synthesis.

Effects of a Mixture of Ivy Leaf Extract and Coptidis rhizome on Patients with Chronic Bronchitis and Bronchiectasis.

BACKGROUND: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. METHODS: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George's Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. RESULTS: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37-88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16; p < 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45; p < 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. CONCLUSIONS: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.

Skin-Whitening and Anti-Wrinkle Effects of Bioactive Compounds Isolated from Peanut Shell Using Ultrasound-Assisted Extraction.

Response surface methodology was employed to optimize the ultrasound-assisted extraction (UAE) conditions for simultaneous optimization of dependent variables, including DPPH radical scavenging activity (RSA), tyrosinase activity inhibition (TAI), and collagenase activity inhibition (CAI) of peanut shell extracts. The effects of the main variables including extraction time (5.0~55.0 min, X1), extraction temperature (26.0~94.0 °C, X2), and ethanol concentration (0.0%~99.5%, X3) were optimized. Based on experimental values from each condition, quadratic regression models were derived for the prediction of optimum conditions. The coefficient of determination (R2) of the independent variable was in the range of 0.89~0.96, which demonstrates that the regression model is suitable for the prediction. In predicting optimal UAE conditions based on the superimposing method, extraction time of 31.2 min, extraction temperature of 36.6 °C, and ethanol concentration of 93.2% were identified. Under these conditions, RSA of 74.9%, TAI of 50.6%, and CAI of 86.8% were predicted, showing good agreement with the experimental values. A reverse transcription polymerase chain reaction showed that peanut shell extract decreased mRNA levels of tyrosinase-related protein-1 and matrix metalloproteinase-3 genes in B16-F0 cell. Therefore, we identified the skin-whitening and anti-wrinkle effects of peanut shell extracts at protein as well as gene expression levels, and the results show that peanut shell is an effective cosmetic material for skin-whitening and anti-wrinkle effects. Based on this study, peanut shell, which was considered a byproduct, can be used for the development of healthy foods, medicines, and cosmetics.

Effects of Allium sativum Stem Extract on Growth and Migration in Melanoma Cells through Inhibition of VEGF, MMP-2, and MMP-9 Genes Expression.

The present study investigated the effects of Allium sativum stem extract (ASE) on B16-F0 cell growth and metastasis. Evaluation of the effects of ASE on B16-F0 cells' viability and migration showed that 0.5 mg/mL ASE inhibited B16-F0 cells' growth by 30.2% and migration by 38.5%, which indicates that the ASE has anticancer and antimetastatic effects on B16-F0 cells. To study the anticancer and antimetastatic mechanism, mRNA levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) expressions were evaluated with reverse transcription polymerase chain reaction, and 0.25 and 0.5 mg/mL ASE was found to exert significant inhibition on mRNA expressions of VEGF, MMP-2, and MMP-9 in B16-F0 cells. Thus, ASE reduce extracellular matrix degradation through inhibitions of expression of MMP-2 and MMP-9, and also showed an angiogenesis inhibitory effect through reduction of VEGF expression. High-performance liquid chromatography analysis showed that among various polyphenols, gallic acid (2.1 mg/g) was a major compound of ASE. Overall, our results demonstrated that ASE inhibited the growth and migration of B16-F0 cells through downregulation of the VEGF, MMP-2, and MMP-9 genes expression, which indicates ASE could be applied for the prevention and treatment of melanoma.

LB-9, Novel Probiotic Lactic Acid Bacteria, Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice by Inhibiting TNF-α-Mediated Apoptosis of Intestinal Epithelial Cells.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a group of chronic and relapsing inflammatory conditions within the gastrointestinal tract. An increase in intestinal epithelial cell (IEC) apoptosis is a major characteristic of UC. Tumor necrosis factor-α (TNF-α) plays an essential role in the regulation of apoptosis. Aberrant activation of the immune response to resident microflora contributes to overproduction of TNF-α in the mucosal tissue of the gastrointestinal tract; a hallmark of UC. There are no curative medications for IBD. Thus, establishment of novel strategies for the treatment of this disease is imperative. Lactic acid bacteria (LAB) have been characterized as probiotics that can alleviate imbalances in indigenous microflora in UC, exhibiting beneficial effects for the treatment and prevention of IBD. In this study, we elucidate the potential of LB-9, a novel probiotic LAB, to protect against colitis development using a dextran sodium sulfate (DSS)-induced mouse model of UC. Treatment using LB-9 reduced clinical symptoms of colitis. In addition, both colitis-induced and NF-κB-mediated IEC apoptosis was markedly reduced in mice treated with LB-9. Moreover, these results were closely associated with reduced TNF-α levels. Our study demonstrates that the LB-9 probiotic exhibits therapeutic potential for UC through suppression of TNF-α-mediated IEC apoptosis in a murine DSS-induced colitis model, with important biological implications for treatment of IBD in humans.

Plasma micoRNA-122 as a predictive marker for treatment response following transarterial chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Circulating microRNA (miR)-122 has recently been investigated as a potential biomarker of various hepatic diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). We investigated the association between plasma miR-122 levels and the treatment outcomes following transarterial chemoembolization (TACE) in HCC patients. METHODS: We included 177 HCC patients treated with TACE in the study; TACE refractoriness and liver transplantation-free survival were evaluated during follow up. Pretreatment plasma miR-122 levels were assessed using quantitative real-time polymerase chain reaction. Relative quantification of miR-122 expression (fold change) was determined using the 2(-ΔΔCt) method. MiR-16 was used as an internal control for the normalization of miRNA data. RESULTS: During the mean follow up of 22.4 (range, 1-79) months, 112 (69.5%) patients exhibited TACE refractoriness. Multivariate analyses showed that tumor number (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.43-4.41; P = 0.001) and tumor size (HR, 2.65; 95% CI, 1.62-4.32; P = 0.000) can independently predict overall TACE refractoriness. High miR-122 expression (> 100) was associated with early TACE refractoriness (within 1 year; HR, 2.77; 95% CI, 1.12-6.86; P = 0.028), together with tumor number (HR, 22.73; 95% CI, 2.74-188.66; P = 0.004) and tumor size (HR, 4.90; 95% CI, 1.99-12.06; P = 0.001). Univariate analyses showed that high miR-122 expression tends to be associated with poor liver transplantation-free survival (HR, 1.42; 95% CI, 0.95-2.11; P = 0.085). However, it was statistically insignificant in multivariate analysis. CONCLUSION: High expression levels of plasma miR-122 are associated with early TACE refractoriness in HCC patients treated with TACE.

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

Exogenous γ-tocotrienol promotes preimplantation development and improves the quality of porcine embryos.

γ-tocotrienol (GTT), an isomer of vitamin E, has been the subject of increasing interest due to its strong anti-oxidant effects. Therefore, in this study, the effects of GTT on blastocyst development, expression levels of reactive oxygen species (ROS) and apoptotic index were investigated in preimplantation porcine embryos. After in vitro maturation and fertilisation, porcine embryos were cultured for 6 days in porcine zygote medium 3 supplemented with or without GTT (200µM) under oxidative stress conditions (200µM hydrogen peroxide (H2O2)). Blastocyst development was significantly improved in the GTT-treated group when compared with the H2O2-treated group (P<0.05). Subsequent evaluation of the intracellular levels of ROS and numbers of apoptotic nuclei in GTT-treated blastocysts revealed that ROS levels of GTT-treated porcine blastocysts were decreased (P<0.05) and the numbers of apoptotic nuclei were reduced by GTT treatment in porcine embryos. Moreover, the total cell numbers of blastocysts were significantly increased in the GTT-treated group relative to the untreated group under H2O2-induced oxidative stress (P<0.05). The expression levels of apoptosis-related genes (BCL-XL, BAX) in GTT-treated blastocysts were then investigated using real-time reverse transcription polymerase chain reaction. Expression of the anti-apoptotic BCL-XL gene was shown to be increased in the GTT-treated blastocyst group, whereas expression of the pro-apoptotic BAX gene was decreased. Taken together, these results suggest that GTT (200µM) under H2O2-induced oxidative stress, thereby improving the developmental competence of porcine embryos via modulation of intracellular levels of ROS and the apoptotic index during the preimplantation stage.

Efficacy and safety of Korean red ginseng for cold hypersensitivity in the hands and feet: a randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: In Korean medicine, the steamed root of Panax ginseng C.A. Meyer, known as Korean red ginseng (KRG), is used to invigorate the body, enhance qi, and improve blood flow. It is a potential treatment for cold hypersensitivity in the hands and feet (CHHF), a common complaint among Asians, especially women. However, few studies of its efficacy and safety for CHHF have been conducted. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial included 80 female patients with CHHF at Kyung Hee University Hospital at Gangdong, Seoul, Korea. The participants took six capsules of 500-mg KRG powder or placebo twice daily for 8 weeks and were followed up for 4 weeks. The primary outcome measure was change in skin temperature of the hands. The secondary outcome measures included change in skin temperature of the feet, visual analog scale (VAS) scores of CHHF severity, recovered temperature (RT) of the hands after cold stress test, distal-dorsal difference (DDD) in temperature of the hands, power variables of heart rate variability (HRV), and 36-item Short-Form Health Survey (SF-36) scores. RESULTS: The KRG group had significantly higher skin temperature of the hands and feet, lower VAS scores, higher RT of the right 5th finger, and less parasympathetic activity than the placebo group at 8 weeks. No significant differences were noted in DDD of the hands and SF-36 scores. No serious adverse events were reported during the study. CONCLUSIONS: Peripheral vasodilation by KRG may alleviate CHHF. Further controlled studies are required to elucidate the effects of KRG on the autonomic nervous system.

Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution.

Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such "stealth" CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering.

Effects of adjunctive daily phototherapy on chronic periodontitis: a randomized single-blind controlled trial.

PURPOSE: The purpose of this randomized single-blind controlled trial was to elucidate the clinical and antimicrobial effects of daily phototherapy (PT) as an adjunct to scaling and root planing (SRP) in patients with chronic periodontitis. METHODS: The study was conducted from December 2013 to May 2014 at Ewha Womans University Mokdong Hospital, Seoul, Korea. Forty-one patients with mild to moderate chronic periodontitis were randomly divided into two therapeutic groups in a 1:1 ratio: SRP+PT and SRP (control) groups. All participants underwent full-mouth SRP. PT was performed thrice a day for a month by using electric toothbrushes with embedded light-emitting diodes. Plaque index, gingival index, probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing were assessed before (baseline) and four weeks after (follow-up) the treatment. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Parvimonas micra, Campylobacter rectus, Eikenella corrodens, Streptococcus mutans, and Streptococcus sobrinus levels were detected by a real-time polymerase chain reaction at the same points in time. RESULTS: The clinical parameters improved in both the groups. At the follow-up assessment, PPD was significantly decreased in the SRP+PT group (P=0.00). Further, PPD and CAL showed significantly greater changes in the SRP+PT group than in the SRP group (PPD, P=0.03; CAL, P=0.04). P. gingivalis and T. forsythia levels decreased in this group, but no significant intergroup differences were noted. CONCLUSIONS: Adjunctive PT seems to have clinical benefits, but evidence of its antimicrobial effects is not sufficient. Long-term studies are necessary to develop the most effective PT protocol and compare the effectiveness of PT with and without exogenous photosensitizers.

Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity. METHODS/DESIGN: This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey. DISCUSSION: This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF. TRIAL REGISTRATION: CliniacalTrials.gov NCT01664156.

Selective pathogen targeting and macrophage evading carbon nanotubes through dextran sulfate coating and PEGylation for photothermal theranostics.

Single-walled carbon nanotubes (SWNTs) have shown promise as in vivo contrast nanoagents for medical theranostics, in particular photoacoustic and photothermal imaging and therapy, as well as targeted drug delivery systems. However, SWNTs have not proved able to evade biological obstacles, such as opsonization and phagocytosis by macrophage and nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. Here, we demonstrate the stealth character of dextran sulfate (DS) coated SWNTs (DS-SWNTs) towards human macrophages and other biological barriers using Staphylococcus aureus, a bacterial pathogen, as a model. DS-SWNTs were compared to PEGylated SWNTs, a commonly accepted standard for rendering nanoparticles immune to opsonization. Also a new site-specific conjugation strategy was developed to functionalize antibody (Ab) on DS-SWNT in an upright way, enhancing their targeting efficiency. DS coating was proved to be resistant to opsonins and bacterial cells, demonstrating its potential to provide considerable stealth.character to SWNTs with excellent immunity versus macrophages and other biological barriers, and achieve prolonged blood circulation times. Moreover, the hybrid nanoagents could not only selectively bind to target pathogenic cells upon the controlled Ab attachment but also effectively eradicate pathogens after near-infrared laser irradiation.

Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics.

Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action.

In vivo magnetic enrichment, photoacoustic diagnosis, and photothermal purging of infected blood using multifunctional gold and magnetic nanoparticles.

Bacterial infections are a primary cause of morbidity and mortality worldwide. Bacteremia is a particular concern owing to the possibility of septic shock and the development of metastatic infections. Treatment of bacteremia is increasingly compromised by the emergence of antibiotic resistant strains, creating an urgent need for alternative therapy. Here, we introduce a method for in vivo photoacoustic (PA) detection and photothermal (PT) eradication of Staphylococcus aureus in tissue and blood. We show that this method could be applicable for label-free diagnosis and treatment of in the bloodstream using intrinsic near-infrared absorption of endogenous carotenoids with nonlinear PA and PT contrast enhancement. To improve sensitivity and specificity for detection of circulating bacteria cells (CBCs), two-color gold and multilayer magnetic nanoparticles with giant amplifications of PA and PT contrasts were functionalized with an antibody cocktail for molecular targeting of S. aureus surface-associated markers such as protein A and lipoprotein. With a murine model, the utility of this approach was demonstrated for ultrasensitive detection of CBCs with threshold sensitivity as low as 0.5 CBCs/mL, in vivo magnetic enrichment of CBCs, PT eradication of CBCs, and real-time monitoring of therapeutic efficacy by CBC counting. Our PA-PT nano-theranostic platform, which integrates in vivo multiplex targeting, magnetic enrichment, signal amplification, multicolor recognition, and feedback control, could be used as a biological tool to gain insights on dissemination pathways of CBCs, infection progression by bacteria re-seeding, and sepsis development and treatment, and could potentially be feasible in humans, especially using bypass schematic.

Endobronchial mass developing 19 years after total thyroidectomy due to follicular thyroid carcinoma.

Endobronchial metastasis from thyroid follicular carcinoma is a rare manifestation. We describe a case of 62-year-old woman who underwent total thyroidectomy due to thyroid follicular carcinoma 19 years previously. Computerized tomography and bronchoscopy suggested an endobronchial enhancing nodule in the right bronchus intermedius, resulting in right middle lobe (RML) and right lower lobe (RLL) collapse. A biopsy specimen showed thyroid follicular carcinoma identical to that taken from a specimen previously. She underwent metastectomy and high-dose radioactive iodine ablation therapy. To our knowledge, this patient represents the first case of endobronchial metastasis with a long past history of thyroid follicular carcinoma.