Targeting Tumor Cells with Nanoparticles for Enhanced Co-Drug Delivery in Cancer Treatment.

Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future.

ADP Induces Blood Glucose Through Direct and Indirect Mechanisms in Promotion of Hepatic Gluconeogenesis by Elevation of NADH.

Extracellular ADP, a derivative of ATP, interacts with the purinergic receptors in the cell membrane to regulate cellular activities. This signaling pathway remains unknown in the regulation of blood glucose in vivo. We investigated the acute activity of ADP in mice through a peritoneal injection. In the lean mice, in response to the ADP treatment, the blood glucose was elevated, and pyruvate tolerance was impaired. Hepatic gluconeogenesis was enhanced with elevated expression of glucogenic genes (G6pase and Pck1) in the liver. An elevation was observed in NADH, cAMP, AMP, GMP and citrate in the liver tissue in the targeted metabolomics assay. In the primary hepatocytes, ADP activated the cAMP/PKA/CREB signaling pathway, which was blocked by the antagonist (2211) of the ADP receptor P2Y13. In the circulation, gluconeogenic hormones including glucagon and corticosterone were elevated by ADP. Insulin and thyroid hormones (T3 and T4) were not altered in the blood. In the diet-induced obese (DIO) mice, NADH was elevated in the liver tissue to match the hepatic insulin resistance. Insulin resistance was intensified by ADP for further impairment in insulin tolerance. These data suggest that ADP induced the blood glucose through direct and indirect actions in liver. One of the potential pathways involves activation of the P2Y13/cAMP/PKA/CREB signaling pathway in hepatocytes and the indirect pathway may involve induction of the gluconeogenic hormones. NADH is a signal for gluconeogenesis in the liver of both DIO mice and lean mice.

Effects of Storage Time and Temperature on Antioxidants in Juice from Momordica charantia L. and Momordica charantia L. var. abbreviata Ser.

This study determined the antioxidant activities of juice from Momordica charantia L. (MC) and MC var. abbreviata Ser. (MCVAS) by analyzing 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, ferric reducing power (FRP), and total phenolic content (TPC). The effects of storage time and storage temperature on these antioxidant activities were investigated. Liquid chromatography-mass spectrometry was conducted to identify the major components of MC and MCVAS. The results revealed that the antioxidant activity of MCVAS was better than that of MC, possibly because of richer components of MCVAS. For MC and MCVAS, the scavenging concentrations of 50% DPPH were 3.33 and 1.19 mg/mL, respectively; moreover, the FRP values were 68.93 and 118.14 mg ascorbic acid equivalent/g dry weight, respectively; and the TPC values were 8.15 and 11.47 mg gallic acid equivalent/g dry weight, respectively. The antioxidant activities of MC and MCVAS decreased with storage time. High storage temperature decreased antioxidant activity more quickly than a low temperature. In addition, MC had exhibited a faster decline in DPPH scavenging ability and FRP than MCVAS during 24-day storage, but no difference was observed in TPC.

Antioxidant Ability and Stability Studies of 3-O-Ethyl Ascorbic Acid, a Cosmetic Tyrosinase Inhibitor.

3-O-ethyl ascorbic acid may be a good whitening ingredient in cosmetics. However, before it can be successfully used in cosmetics, its biofunctionality and stability need to be comprehensively investigated. The reduction and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability of this compound were analyzed to assess its antioxidant potential. In addition, the tyrosinase inhibitory ability was analyzed to show the whitening capacity of 3-O-ethyl ascorbic acid. Response surface methodology (RSM) was used to determine the optimal conditions for the ascorbic acid derivative in cosmetics. Based on the DPPH radical scavenging ability results, the half-inhibitory concentration (IC50) value of 3-O-ethyl ascorbic acid was 0.032 g/L. It also showed a good reducing ability at 1.5 g/L concentration. Based on the tyrosinase inhibition analysis, the IC50 value was 7.5 g/L. The optimal conditions to achieve the best stability were determined from the RSM as 36.3°C and pH 5.46.

Antioxidation and Melanogenesis Inhibition of Various Dendrobium tosaense Extracts.

This study investigated the polyphenol content, antioxidant activity, and inhibition ability of mushroom tyrosinase and melanogenesis of Dendrobium tosaense (DT) extract. Ground DT was extracted using deionized water (W) or 50% ethanol (50E) at room temperature (RT) or 50 °C (50T) for 20 min. The 50T + 50E extract exhibited the highest total phenol content 47.0 ± 4.0 mg gallic acid equivalent/g DT extract, the highest level of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) free-radical scavenging 66.0 ± 3.0 mg Trolox equivalent/g DT extract, and the highest reducing power 12.00 ± 0.50 mg vitamin C equivalent/g DT extract. The RT + W extract had the highest total flavonoid content 110.0 ± 3.0 mg quercetin equivalent/g DT extract. The RT + 50E extract had the lowest half maximal inhibitory concentration 1.30 ± 0.00 mg/mL for 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging, and the lowest half maximal inhibitory concentration 6.40 ± 0.30 mg/mL for mushroom tyrosinase inhibition activity. DT extracts, especially RT + W and 50T + W, exhibited potent inhibitory effects on melanogenesis of B16/F10 cells. These results demonstrated the application potential of DT extract for skincare.

Morphological features of complex congenital cardiovascular anomalies in fetuses: as evaluated by cast models.

Accurate prenatal diagnosis of complex congenital cardiovascular anomalies, vascular ones in particular, is still challenging. A fetal cardiovascular cast model can provide a copy of the cardiac chambers and great vessels with normal or pathological structures. This study was aimed to demonstrate three-dimensional anatomy of complex congenital cardiovascular anomalies in fetuses by means of corrosion casting. Twenty fetuses with prenatal-ultrasound-diagnosed complex cardiovascular anomalies were enrolled in this study (19 to 35 gestational weeks). Fetal cardiovascular cast models were made by a corrosion casting technique. The specimens were injected with casting material via the umbilical vein, and then immersed in strong acid after casting fluid was solidified, to disclose the geometries of cardiovascular cavities. Nineteen cast models were successfully made from 20 specimens. The casts distinctly showed the morphological malformations and spatial relationship between cardiac chambers and great vessels. One hundred and eleven abnormalities were revealed by casting in the 19 specimens, including 34 abnormalities located in the cardiac chambers (3, 4 and 27 anomalies in the atria, atrioventricular valves and ventricles, respectively), and 77 in the great vessels (28, 20, 24 and 5 anomalies in the aorta and its branches, the pulmonary artery, the ductus arteriosus and the major veins, respectively). Corrosion casting can display three-dimensional anatomy of fetal complex cardiovascular anomalies. This improves our understanding of related pathomorphology and prenatal diagnosis.

Kinetics of Tyrosinase Inhibitory Activity Using Vitis vinifera Leaf Extracts.

Natural medical plant is considered as a good source of tyrosinase inhibitors. Red vine leaf extract (RVLE) can be applied to a wide variety of medical disciplines, such as treatments for chronic venous insufficiency over many decades. This study investigated the tyrosinase inhibitory activity of RVLE containing gallic acid, chlorogenic acid, epicatechin, rutin, and resveratrol which are effective for skin hyperpigmentation. The five components contents are 1.03, 0.2, 18.55, 6.45, and 0.48 mg/g for gallic acid, chlorogenic acid, epicatechin, rutin, and resveratrol. The kinetic study showed the tyrosinase inhibitory of RVLE via a competitive reaction mechanism. RVLE solution has an IC50 (the half inhibitory concentration) value of 3.84 mg/mL for tyrosinase inhibition, that is, an effective tyrosinase inhibitory activity, and can be used as a whitening agent for cosmetic formulations in the future.

Morphological Features of Complex Congenital Cardiovascular Anomalies in Fetuses: as Evaluated by Cast Models / 华中科技大学学报（医学）（英德文版）

Accurate prenatal diagnosis of complex congenital cardiovascular anomalies,vascular ones in particular,is still challenging.A fetal cardiovascular cast model can provide a copy of the cardiac chambers and great vessels with normal or pathological structures.This study was aimed to demonstrate three-dimensional anatomy of complex congenital cardiovascular anomalies in fetuses by means of corrosion casting.Twenty fetuses with prenatal-ultrasound-diagnosed complex cardiovascular anomalies were enrolled in this study (19 to 35 gestational weeks).Fetal cardiovascular cast models were made by a corrosion casting technique.The specimens were injected with casting material via the umbilical vein,and then immersed in strong acid after casting fluid was solidified,to disclose the geometries of cardiovascular cavities.Nineteen cast models were successfully made from 20 specimens.The casts distinctly showed the morphological malformations and spatial relationship between cardiac chambers and great vessels.One hundred and eleven abnormalities were revealed by casting in the 19 specimens,including 34 abnormalities located in the cardiac chambers (3,4 and 27 anomalies in the atria,atrioventricular valves and ventricles,respectively),and 77 in the great vessels (28,20,24 and 5 anomalies in the aorta and its branches,the pulmonary artery,the ductus arteriosus and the major veins,respectively).Corrosion casting can display three-dimensional anatomy of fetal complex cardiovascular anomalies.This improves our understanding of related pathomorphology and prenatal diagnosis.

Nanoparticle Targeting CD44-Positive Cancer Cells for Site-Specific Drug Delivery in Prostate Cancer Therapy.

Prostate cancer is one of the leading causes of cancer death in adult men and is a multistage disease with therapeutic challenges of local recurrent advanced tumors and distant metastatic disease. CD44 is a multifunctional and multistructural cell surface glycoprotein that is involved in cell-cell interactions, cell proliferation, and cell migration. In the study, we produced negatively charged and biocompatible hyaluronic acid-based nanoparticles as a therapeutic system for targeting CD44-positive cancer cells. Subsequently, we confirmed the delivery of bioactive epigallocatechin-3-gallate and site-specific inhibition of prostate tumor growth. In this study, hyaluronic acid-based nanoparticles successfully encapsulated epigallocatechin-3-gallate and were efficiently internalized into cancer cells via CD44 ligand receptor recognition, induced cell cycle arrest at G2/M phase, and inhibited prostate cancer cell growth. Furthermore, in vivo assays indicated that these nanoparticles specifically bind CD44 receptors and increase apoptosis of cancer cells, leading to significant decreases in prostate tumor activity and tumor tissue inflammation.

N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability.

R-spondin 1 (Rspo1) plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1) domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER) quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1.

The first imported human case of Yersinia pseudotuberculosis serotype O1 septicemia presents with acute appendicitis-like syndrome in Taiwan.

Human nonplague yersiniosis occurs more commonly in temperate regions than in tropical or subtropical regions. In Taiwan, which is located in a subtropical region of Southeast Asia, only environmental isolates and human infection of Yersinia enterocolitica were reported, but a human case of Y. pseudotuberculosis infection had not been identified. We report the first person with Y. pseudotuberculosis serotype O1 septicemia who presented with acute appendicitis-like syndrome and who was probably contracted the infection via ingestion of raw foods in a barbecue restaurant in Japan.

Supercritical fluid extract of Lycium chinense Miller root inhibition of melanin production and its potential mechanisms of action.

BACKGROUND: The mode of action of Lycium chinense Miller root extract in skin care has never been explored. In the present study, Lycium chinense Miller root was extracted by the supercritical fluid CO2 extraction method. METHODS: In the present study, the components of the root extract were analyzed by HPLC. The effects of the extract on tyrosinase activity and melanin content were determined spectrophotometrically; the expression of melanogenesis-related proteins was determined by Western blotting; the possible signaling pathways involved in the root extract-mediated depigmentation were also investigated using specific inhibitors. RESULTS: The results revealed that the SFE of Lycium chinense Miller root (2.37-7.11 mg/mL) effectively suppressed intracellular tyrosinase activity and decreased the melanin content in B16F10 cells. The root extract also effectively decreased intracellular reactive oxygen species (ROS) levels. Furthermore, the root extract decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related protein-1 (TRP-1) and then inhibited melanogenesis in B16F10 cells. The root extract also showed antioxidant capacities and depleted cellular ROS. CONCLUSIONS: Our results indicate that the SFE of Lycium chinense Miller root inhibited melanogenesis in B16F10 cells by down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties.

Potent antioxidative and UVB protective effect of water extract of Eclipta prostrata L.

Oxidative stress, including Ultraviolet (UV) irradiation-induced skin damage, is involved in numerous diseases. This study demonstrates that water extract of Eclipta prostrata L. (WEP) has a potent effect in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radicals, and chelating ferrous ion, exhibiting IC50 values of 0.23 mg/mL, 0.48 mg/mL, and 1.25 mg/mL, respectively. The WEP total phenol content was 176.45 mg gallic acid equivalents (GAE)/g sample. Chlorogenic acid, a component of the plant's active ingredients, was determined by HPLC and antioxidative assay. However, no caffeic acid, stigmasterol, or wedelolactone was present in WEP. WEP absorbs both UVA and UVB irradiation, and furthermore, the extract shows a dose-dependent response in the protection of HaCaT human keratinocytes and mouse fibroblasts 3T3 cells against UVB-induced cytotoxicity, which may result from a synergistic effect between chlorogenic acid and other active components present in WEP.

Effects of water quality on dissolution of yerba mate extract powders.

Yerba mate tea is known as one of the most popular nonalcoholic beverages favoured by South Americans due to its nutrition facts and medicinal properties. The processing of yerba mate tea is found to affect the properties of its final forms. This study presents an investigation into the effects of water sources on the dissolution of yerba mate extract powders. Comparisons were conducted between yerba mate teas prepared by dissolving yerba mate extract powders into tap water and deionized water. Topics to be explored in this work are the major compositions and antioxidant activities, including total phenol content, reducing power, DPPH scavenging activity, and ABTS(+)• scavenging capacity. It is indicated that there is little difference for antioxidant activities and major constituents of yerba mate teas between both water sources. However, a deeper color is seen in the tap water case, resulting from the reaction between tannic acid and ions. This research finding can be treated as a way to benefit the yerba mate tea processing for applications.

Applications of Lactobacillus rhamnosus spent culture supernatant in cosmetic antioxidation, whitening and moisture retention applications.

This study was aimed at investigating the antioxidant, whitening, and moisture-retention properties of Lactobacillus rhamnosus spent culture supernatant (Lr-SCS) in cosmetic applications. Results reveal that Lr-SCS effectively and gradually scavenges 1,1-diphenyl-2-picrylhydrazyl as well as 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cations, and increases reducing power in a dose-dependent manner. Additionally, Lr-SCS can also suppress tyrosinase activity in vitro and effectively promote moisture retention. Heat treatment at 100 °C for 30 min does not influence the functions of Lr-SCS. We conclude that Lr-SCS can be used effectively in skin care cosmetics.

Effects of water solutions on extracting green tea leaves.

This study investigates the effects of water solutions on the antioxidant content of green tea leaf extracts. Green teas prepared with tap water and distilled water were compared with respect to four antioxidant assays: total phenol content, reducing power, DMPD assay, and trolox equivalent antioxidant capacity assay. The results indicate that green tea prepared with distilled water exhibits higher antioxidant activity than that made with tap water. The high performance liquid chromatography showed that major constituents of green tea were found in higher concentrations in tea made with distilled water than in that made with tap water. This could be due to less calcium fixation in leaves and small water clusters. Water solutions composed of less mineralisation are more effective in promoting the quality of green tea leaf extracts.

Stability studies of ascorbic acid 2-glucoside in cosmetic lotion using surface response methodology.

Ascorbic acid 2-glucoside (AA-2G) has been widely used in cream and lotion types of cosmetic products. Thus, the degradation of AA-2G caused by the temperature change and pH variation was very critical for determining the bio-functionality of cosmetics. Response surface methodology (RSM) was introduced to study the influence of temperature and pH on the stability of AA-2G. The optimal condition of retaining AA-2G with the highest stability was determined to be 55.3°C and pH 6.4. The antioxidative activities of AA-2G including DPPH and ABTS free radical scavenging activities, metal chelating activity, and reducing ability were also determined. AA-2G was a good ascorbic acid derivative which could be used in cosmetic products as an active ingredient.

Development of fibroblast culture in three-dimensional activated carbon fiber-based scaffold for wound healing.

This work developed a novel bi-layer wound dressing composed of 3D activated carbon fibers that allows facilitates fibroblast cell growth and migration to a wound site for tissue reconstruction, and the gentamicin is incorporated into a poly(γ-glutamic acid)/gelatin membrane to prevent bacterial infection. In an in vitro, field emission scanning electron microscopy shows that rat skin fibroblasts appeared and spread on the surface of activated carbon fibers, and penetrated the interior and exterior of the 3D activated carbon fiber construct to a depth of roughly 200 µm. An in vivo analysis shows that fibroblast cells containing the proposed 3D scaffold had the potential of a biologically functionalized dressing to accelerate wound closure. Additionally, fibroblasts migrated to the wound site in a bi-layer wound dressing containing fibroblasts, enhancing fibronectin and type I collagen expression, resulting in faster skin regeneration than that achieved with a Tegaderm™ hydrocolloid dressing or gauze.

Danggui Buxue Tang attenuates eosinophil infiltration and airway hyperresponsiveness in asthmatic mice.

BACKGROUND: Danggui Buxue Tang (DBT), an herbal formula containing Angelica sinensis (AS) and Astragalus membranaceus (AM) (AS:AM = 1:5, designated as DBT1 here), has been used in Chinese medicine to enhance qi and blood circulation. In addition, DBT has served as a treatment for atopic dermatitis in dogs in Taiwan. It also may improve fibrosis in a rat model of pulmonary fibrosis. OBJECTIVE: In this study, we evaluated the effect of oral administration of DBT1 in asthma in ovalbumin (OVA)-sensitized mice. METHODS: Female BALB/c mice were sensitized and challenged with OVA and fed with DBT1 or modified formulas of DBT1, designated as DBT2 (AS:AM = 1:1) and DBT3 (AS:AM = 5:1), from days 21 to 27. RESULTS: DBT1 suppressed airway hyperresponsiveness and eosinophil infiltration in bronchoalveolar lavage fluid (BALF) and lung, and Th2-associated cytokines and chemokines were inhibited in BALF. In addition, levels of OVA-immunoglobulin E (IgE) also were suppressed in serum. However, treatment with DBT2 or DBT3 showed no improved effects relative to DBT1 in treating asthmatic symptoms. CONCLUSIONS: These results suggest that orally administered DBT (DBT1) can reduce allergic reactions in OVA-sensitized mice.

Antimelanogenic and antioxidative properties of Bifidobacterium bifidum.

Various skin hyperpigmentation disorders consist in accumulation and overproduction of melanin. In this report, we investigated the melanogenesis inhibitory and antioxidant effects of Bifidobacterium bifidum culture filtrate. The results revealed that B. bifidum culture filtrate effectively suppresses murine tyrosinase activity and decreases the amount of intracellular melanin in a dose-dependent manner. Additionally, the bacterial culture filtrate-scavenged DPPH and ABTS radicals, and shows potent-reducing power in a dose-dependent pattern. Our results expand the application of B. bifidum culture filtrate in the development and research of skin-whitening ingredients.