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Resveratrol, a dietary phytoalexin readily available in the diet, is reported to possess antitumorigenic properties in several cancers, including colorectal. However, the underlying mechanism(s) involved is not completely understood. In the present study, we investigated the effect of resveratrol treatment on gene modulation in human colorectal cancer cells and identified activating transcription factor 3 (ATF3) as the most highly induced gene after treatment. We confirmed that resveratrol upregulates ATF3 expression, both at the mRNA and protein level, and showed resveratrol involvement in ATF3 transcriptional regulation. Analysis of the ATF3 promoter revealed the importance of early growth response-1 (Egr-1; located at −245 to −236) and Krüppel-like factor 4 (KLF4; located at −178 to −174) putative binding sites in resveratrol-mediated ATF3 transactivation. Specificity of these sites to the Egr-1 and KLF4 protein was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. Resveratrol increased Egr-1 and KLF4 expression, which preceded ATF3 expression, and further suggests Egr-1 and KLF4 involvement in resveratrol-mediated activity. We provide evidence for Egr-1 and KLF4 interaction in the presence of resveratrol, which may facilitate ATF3 transcriptional regulation by this compound. Furthermore, we demonstrate that induction of apoptosis by resveratrol is mediated, in part, by increased ATF3 expression. Taken together, these results provide a novel mechanism by which resveratrol induces ATF3 expression and represent an additional explanation of how resveratrol exerts its antitumorigenic effects in human colorectal cancer cells. Cancer Prev Res; 4(1); 116–27. ©2011 AACR.

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PDF file - 135K, Figure S1. TA-induced cyclin D1 down-regulation is independent of proteasomal pathway. Figure S2. ubiquitination is not involved in TA-induced cyclin D1 down-regulation. Figure S3. ER stress mediated cyclin D1 down-regulation by TA.

Cold atmospheric microwave plasma (CAMP) is a promising therapeutic option for treating skin infections and wounds. Changes in biophysical skin parameters and the tolerability in dogs after applying CAMP is unknown.This study aimed to evaluate the in vivo effects of CAMP on skin biophysical parameters [hydration, transepidermal water loss (TEWL) and surface temperature] and tolerability in dogs.Twenty client-owned dogs with normal skin.Cold atmospheric microwave plasma treatment was performed for 30 s and 1, 2 and 4 min, respectively, at different sites of normal canine skin in the inguinal area. Hydration, TEWL and surface temperature were measured five, three and three times, respectively, before and after CAMP application. After treatment, pain and adverse effects were evaluated using a modified Melbourne Pain Scale and the modified short form Glasgow Composite Measure Pain Scale (modified CMPS-SF).Transepidermal water loss values significantly decreased with 4 min of treatment, and hydration decreased significantly with 2 min of treatment. Temperature increased significantly with increasing treatment time. For other parameters, no significant changes were observed. No significant pain response or adverse effects were observed in most dogs, aside from mild erythema in the treatment area after 4 min.Cold atmospheric microwave plasma treatment was well-tolerated and did not significantly change canine skin biophysical parameters. CAMP achieves basic recommendations for safe use and is a potential therapeutic option for various skin diseases in dogs.Contexte - Le CAMP (Cold Atmospheric Microwave Plasma) est une option thérapeutique prometteuse pour le traitement des infections cutanées et des plaies. Les modifications des paramètres biophysiques de la peau et la tolérance chez les chiens après l'application de CAMP sont inconnues. Objectif - Cette étude visait à évaluer les effets in vivo du CAMP sur les paramètres biophysiques de la peau [hydratation, perte d'eau transépidermique (TEWL) et température de surface] et la tolérance chez le chien. Animaux - Vingt chiens de propriétaires à peau normale. Matériels et méthodes - Le traitement CAMP a été effectué pendant 30 s et 1, 2 et 4 min, respectivement, sur différents sites de peau canine normale dans la région inguinale. L'hydratation, la TEWL et la température de surface ont été mesurées cinq, trois et trois fois, respectivement, avant et après l'application de CAMP. Après le traitement, la douleur et les effets indésirables ont été évalués à l'aide d'une échelle de douleur de Melbourne modifiée et de la forme courte modifiée de l'échelle de mesure de la douleur composite de Glasgow (CMPS-SF modifiée). Résultats - Les valeurs de TEWL ont diminué de manière significative après 4 minutes de traitement et l'hydratation a diminué de manière significative après 2 minutes de traitement. La température a augmenté de manière significative avec l'augmentation du temps de traitement. Pour les autres paramètres, aucun changement significatif n'a été observé. Aucune réponse significative à la douleur ni aucun effet indésirable n'ont été observés chez la plupart des chiens, à l'exception d'un léger érythème dans la zone de traitement après 4 minutes. Conclusion et signification clinique - Le traitement CAMP a été bien toléré et n'a pas modifié de manière significative les paramètres biophysiques de la peau canine. CAMP répond aux recommandations de base pour une utilisation sûre et constitue une option thérapeutique potentielle pour diverses maladies de la peau chez les chiens.Introducción- el plasma de microondas atmosférico frío (CAMP) es una opción terapéutica prometedora para el tratamiento de infecciones y heridas de la piel. Se desconocen los cambios en los parámetros biofísicos de la piel y la tolerabilidad en perros después de aplicar CAMP. Objetivo- este estudio tuvo como objetivo evaluar los efectos in vivo de CAMP en los parámetros biofísicos de la piel [hidratación, pérdida de agua transepidérmica (TEWL) y temperatura superficial] y la tolerabilidad en perros. Animales - Veinte perros de propietarios particulares con piel normal. Materiales y métodos - El tratamiento CAMP se realizó durante 30 s y 1, 2 y 4 min, respectivamente, en diferentes sitios de piel canina normal en el área inguinal. La hidratación, el TEWL y la temperatura superficial se midieron cinco, tres y tres veces, respectivamente, antes y después de la aplicación de CAMP. Después del tratamiento, el dolor y los efectos adversos se evaluaron mediante una escala de dolor de Melbourne modificada y la escala de dolor de medida compuesta de Glasgow de forma abreviada modificada (CMPS-SF modificada). Resultados- los valores de TEWL disminuyeron significativamente con 4 min de tratamiento y la hidratación disminuyó significativamente con 2 min de tratamiento. La temperatura aumentó significativamente con el aumento del tiempo de tratamiento. Para otros parámetros no se observaron cambios significativos. En la mayoría de los perros no se observaron reacciones significativas de dolor ni efectos adversos, aparte de un leve eritema en el área de tratamiento después de 4 min. Conclusión y significado clínico- el tratamiento con CAMP fue bien tolerado y no cambió significativamente los parámetros biofísicos de la piel canina. CAMP obtuvo recomendaciones básicas para un uso seguro y es una opción terapéutica potencial para diversas enfermedades de la piel en perros.Hintergrund - Kaltes atmosphärisches Mikrowellen Plasma (CAMP) ist eine vielversprechende therapeutische Option zur Behandlung von Hautinfektionen und Wunden. Veränderungen der biophysischen Hautparameter und der Toleranz bei Hunden nach Anwendung von CAMP ist bisher nicht bekannt. Ziel - Diese Studie zielte darauf ab, die in vivo Wirksamkeit von CAMP auf biophysische Parameter der Haut [Hydration, Transepidermaler Wasserverlust (TEWL) und die Oberflächentemperatur] und die Verträglichkeit bei Hunden zu evaluieren. Tiere - Es wurden zwanzig Hunde in Privatbesitz, alle mit normaler Haut, inkludiert. Materialien und Methoden - Eine CAMP Behandlung wurde für 30 s und 1, 2 bzw 4 Minuten an verschiedenen Stellen normaler Hundehaut in der Inguinalgegend durchgeführt. Hydration, TEWL und die Oberflächentemperatur wurde fünf, drei bzw dreimal vor und nach der CAMP Anwendung gemessen. Nach der Behandlung wurden Schmerz und Nebenwirkungen mittels modifizierter Melbourne Pain Scale sowie der modifizierten Kurzform der Glasgow Measure Pain Scale (modifizierte CMPS-SF) evaluiert. Ergebnisse - Die TEWL Werte nahmen nach 4 Minuten der Behandlung, die Hydration nach 2 Behandlungsminuten signifikant ab. Die Temperatur nahm mit zunehmender Behandlungsdauer signifikant zu. Für die anderen Parameter konnten keine signifikanten Veränderungen beobachtet werden. Es wurden bei den meisten Hunden keine signifikanten Schmerzreaktionen oder Nebenwirkungen beobachtet, außer einem geringen Erythem nach 4 Minuten in der behandelten Körperregion. Schlussfolgerungen und klinische Bedeutung - Die Behandlung mit CAMP wurde gut toleriert und veränderte die biophysischen Parameter der Hundehaut nicht signifikant. Daher kann die CAMP grundsätzlich zur sicheren Anwendung bei Hunden empfohlen werden und stellt eine potenzielle Therapieoption für verschiedene Hauterkrankungen bei Hunden dar.背景 - 低音大気圧マイクロ波プラズマ (CAMP) は、皮膚の感染症や創傷の治療法として有望である。イヌにCAMPを適用した場合の皮膚の生物物理学的パラメータの変化と忍容性は不明である。 目的 -本研究は、犬の皮膚の生物物理学的パラメータ (水和性、経皮水分蒸散量(TEWL) 、表面温度) および忍容性に及ぼすCAMPのin vivo効果を評価することを目的とした。 供試動物 - 正常な皮膚を持つオーナー所有犬20頭。 材料と方法 -正常なイヌの鼠径部皮膚の異なる部位に、CAMP処理を30秒、1分、2分、4分それぞれ実施した。水和性、TEWL、表面温度はCAMP塗布の前後にそれぞれ5回、3回、3回測定した。治療後、修正メルボルン疼痛尺度及び修正短形式グラスゴー複合測定疼痛尺度 (修正CMPS-SF) を用いて、疼痛および副作用を評価した。 結果 - TEWL値は4分間の治療で有意に減少し、水和性は2分間の治療で有意に減少した。表面温度は治療時間が長くなるにつれて有意に上昇した。その他のパラメータについては、有意な変化は認められなかった。4分後の治療部位の軽度の紅斑を除けば、ほとんどの犬で有意な疼痛反応や副作用は観察されなかった。 結論と臨床的意義 - CAMP治療は忍容性が高く、犬の皮膚の生物物理学的パラメータに有意な変化を与えなかった。CAMPは安全使用のための基本的な推奨事項を満たしており、犬の様々な皮膚疾患に対する潜在的な治療オプションであると考えられる。.背景-冷大气微波等离子体(CAMP)是治疗皮肤感染和伤口的一种有前景的治疗选择。尚不清楚应用CAMP后犬的生物物理皮肤参数变化和耐受性。 目的-本研究旨在评价CAMP对犬皮肤生物物理参数[水合作用、经表皮水分流失(TEWL)和表面温度]和耐受性的体内影响。 动物-20只皮肤正常的私家犬。 材料与方法-在腹股沟区正常犬皮肤不同部位分别进行CAMP治疗30s和1、2和4 min。应用CAMP前后分别测量5次、3次和3次水化、TEWL和表面温度。治疗后采用改良墨尔本疼痛量表和改良简明格拉斯哥综合测量疼痛量表(改良CMPS-SF)评价疼痛和不良反应。 结果-治疗4 min后,TEW L值显著下降,治疗2 min后, 水合作用显著下降。随着治疗时间的增加,温度显著增加。对于其他参数,未观察到显著变化。除4 min后治疗区域出现轻度红斑外,在大多数犬中未观察到显著的疼痛反应或不良反应。 结论和临床意义-CAMP治疗耐受性良好,未显著改变犬皮肤生物物理参数。CAMP实现了安全使用的基本建议,是犬各种皮肤病的潜在治疗选择.Contexto - O plasma frio atmosférico de micro-ondas (CAMP) é uma opção terapêutica promissora para o tratamento de infecções cutâneas e feridas. Não se sabe a respeito das alterações nos parâmetros biofísicos da pele e a tolerabilidade de cães após a aplicação de CAMP. Objetivo - Este estudo tem como objetivo avaliar os efeitos in vivo de CAMP nos parâmetros biofísicos da pele [hidratação, perda de água transepidérmica (TEWL) e temperatura da superfície] e a tolerabilidade em cães. Materiais e métodos - O tratamento com CAMP foi realizado por 30s e 1, 2 e 4 min, respectivamente, em diferentes locais da pele canina normal na região inguinal. Hidratação, TEWL e temperatura da superfície foram medidas cinco, três e três vezes, respectivamente, antes e após a aplicação do CAMP. Após o tratamento, a dor e os efeitos adversos foram avaliados usando uma escala de dor de Melbourne modificada e a escala de medida composta de dor de Glasgow modificada (CMPS-SF modificada). Resultados - Os valores de TEWL reduziram significativamente com o tratamento de 4 min, e a hidratação reduziu significativamente com dois minutos de tratamento. A temperatura aumentou significativamente com o aumento do tempo de tratamento. Não foram observadas alterações significativas para outros parâmetros. Não se observou uma resposta de dor significativa ou efeitos adversos na maioria dos cães, além de eritema leve na área tratada após 4 min. Conclusão e significância clínica - O tratamento com CAMP foi bem tolerado e não alterou significativamente os parâmetros biofísicos da pele canina. CAMP requer recomendações básicas de segurança na sua utilização e é uma opção terapêutica potencial para várias dermatopatias em cães.

Incorporating lipophilic phytochemicals with anti-cancer activities in functional beverages requires an appropriate nanoencapsulation technology. The present objective was to encapsulate apigenin with whey protein isolate (WPI) utilizing a pH-cycle method and subsequently characterize physicochemical properties, the in vitro anticancer activities against human colorectal HCT-116 and HT-29 cancer cells, and the in vivo bioavailability. Up to 2.0 mg/mL of apigenin was nanoencapsulated with 1.0 mg/mL WPI, with an encapsulation efficiency of up to 98.15% and loading capacity of up to 196.21 mg/g-WPI. Nanodispersions were stable during storage, and apigenin became amorphous after encapsulation. Nanoencapsulation and in vitro digestion did not reduce the anti-proliferative activity of apigenin. Nanoencapsulation of apigenin enhanced the cellular uptake, the pro-apoptotic effects, and the bioavailability in the mice’s blood and colon mucosa when comparing to the unencapsulated apigenin. Therefore, the present work may be significant to incorporate lipophilic phytochemicals in functional beverages for disease prevention.

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Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1 splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type (TSP1W), as identified by in vivo and in vitro. These activities of TSP1V caused by inhibiting p-Smad and p-FAK. RT-PCR and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs (NSAIDs) enhanced IR. We further found that RNA binding motif protein 5 (RBM5) suppressed IR, induced by sulindac sulfide treatment. Sulindac sulfide also reduced p-RBM5 in a time dependent manner. On the other hand, trans-chalcone demethylated TSP1V, thereby preventing MeCP2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with DTC, but not in those with BTN, indicating its potential application as a diagnostic biomarker in tumor progression.

Despite technological advances in cancer treatment, the survival rate of patients with head and neck cancer (HNC) has not improved significantly. Many studies have shown that endoplasmic reticulum (ER) stress-related signals are associated with mitochondrial damage and that these signals determine whether cells maintain homeostasis or activate cell death programs. The unfolded protein response (UPR) is regulated by ER membrane proteins such as double-stranded RNA-activated protein kinase R(PKR)-like ER kinase (PERK), which directly activate transcription of chaperones or genes that function in redox homeostasis, protein secretion, or cell death programs. In this study, we focused on the role of mitophagy and ER stress-mediated cell death induced by DIM-C-pPhtBu in HNC cancer. We found that DIM-C-pPhtBu, a compound that activates ER stress in many cancers, induced lysosomal dysfunction, excessive mitophagy, and cell death in HNC cells. Moreover, DIM-C-pPhtBu strongly inhibited HNC progression in a xenograft model by altering mitophagy related protein expression. Taken together, the results demonstrate that DIM-C-pPhtBu induces excessive mitophagy and eventually UPR-mediated cell death in HNC cells, suggesting that new anti-cancer drugs could be developed based on the connection between mitophagy and cancer cell death.

Despite intensive research efforts in recent decades, cancer remains a leading cause of death worldwide. The chalcone family is a promising group of phytochemicals for therapeutic use against cancer development. Naturally-occurring chalcones, as well as synthetic chalcone analogues, have shown many beneficial biological properties, including anti-inflammatory, antioxidant, and anti-cancer activities. In this report, trans-chalcone (TChal) was found to increase cell death in breast cancer cells, assessed using high content screening. Subsequently, using antibody array analysis, TChal was found to increase heme oxygenase-1 (HO-1) expression in TChal-treated breast cancer cells. Blocking of HO-1 by siRNA in breast cancer cells diminished the effect of TChal on cell growth inhibition. TChal-fed mice also showed less tumor growth compared to vehicle-fed mice. Overall, we found that TChal increases HO-1 expression in breast cancer cells, thereby enhancing anti-tumorigenesis. Our results suggest that HO-1 expression could be a potential new target of TChal for anti-tumorigenesis in breast cancer.

Growth Differentiation Factor 15 (GDF15), also known as NSAID activated gene-1 (NAG-1), is associated with a large number of biological processes and diseases, including cancer and obesity. GDF15 is synthesized as pro-GDF15, is dimerized, and is cleaved and secreted into the circulation as a mature dimer GDF15. Both the intracellular GDF15 and the circulating mature GDF15 are implicated in biological processes, such as energy homeostasis and body weight regulation. Although there have been many studies on GDF15, GFRAL, a member of the glial-derived neurotropic factor receptor α family, has only been recently identified as a receptor for mature GDF15. In this review, we focused on cancer and energy homeostasis along with obesity and body weight, and the effect of the identification of the GDF15 receptor in these investigations. In addition, the therapeutic potential of GDF15 as a pharmacological agent in obesity and other metabolic diseases was discussed.

Bisphenol A (BPA) has been reported to have neurotoxic properties that may increase the risk of neurodegenerative diseases by inducing neuroinflammation. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced inflammation of BV2 microglial cells were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 microglia by reducing microglial activation and the expression of pro-inflammatory cytokines. These anti-inflammatory effects were regulated by the NF-κB signaling pathway. In addition, APH and APE exhibited antioxidative effects by increasing the activity of the SOD-1 enzyme and restoring the accumulation of reactive oxygen species (ROS) in BPA-induced BV2 cells. Moreover, the conditioned medium prepared using BPA-induced BV2 cells demonstrated that the presence of APH or APE could attenuate ROS production in HT-22 cells. Further, ergosterol was isolated from APE and also showed anti-inflammatory and antioxidative activities. In conclusion, AP extracts and ergosterol attenuated neuroinflammation against BPA induction in BV2 microglial cells through the NF-κB signaling pathway.

Cold atmospheric plasma (CAP) is a new generation medical therapeutic option for bacterial infections. CAP causes physical cell wall rupture and DNA damage, therefore making it highly useful in the treatment of various conditions such as skin infections.The antimicrobial activity of cold atmospheric microwave plasma (CAMP) against major strains in canine skin infections was tested and the difference in antimicrobial activity between the antibiotic-resistant and antibiotic-susceptible strains of Staphylococcus pseudintermedius was evaluated.American Type Culture Collection (ATCC) strains (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) and clinical isolates identified as methicillin-resistant S. pseudintermedius (n = 27) and methicillin-susceptible S. pseudintermedius (n = 13) were exposed to CAMP for 10 s, 30 s and 60 s. Afterwards, the bacterial survival rate was confirmed.Gram-negative bacteria (P. aeruginosa and E. coli) were more susceptible than Gram-positive bacteria (S. aureus and S. pseudintermedius) for the same duration of CAMP exposure. Only the Gram-negative bacteria were completely killed after 60 s exposure. In S. pseudintermedius isolates, CAMP exposure had similar antibacterial effects regardless of antibiotic resistance.CAMP has sufficient antimicrobial activity against major bacterial strains that cause pyoderma and otitis externa in dogs, and may be an alternative therapeutic option for S. pseudintermedius skin infections, for which antibiotics often are ineffective because of antimicrobial resistance in clinical veterinary medicine.Le CAP (Cold atmospheric plasma) est une nouvelle génération de traitement pour les infections bactériennes. CAP cause une rupture physique de la paroi et endommage l’ADN, le rendant ainsi hautement utile pour le traitement d’atteintes variées telles que les infections bactériennes. HYPOTHÈSES/OBJECTIFS: L’activité antimicrobienne de CAMP (cold atmospheric microwave plasma) contre des souches majeures des infections cutanées canines a été testée et la différence d’activité antimicrobienne entre les souches résistances ou sensibles aux antibiotiques de Staphylococcus pseudintermedius a été évaluée. MATÉRIELS ET MÉTHODES: Les souches ATCC (American Type Culture Collection) (Staphylococcus aureus, Pseudomonas aeruginosa et Escherichia coli) et les souches cliniques isolées de S. pseudintermedius identifiées comme résistantes à la méticiline (n = 27) S. pseudintermedius sensibles à la méticiline (n = 13) ont été exposées à CAMP pendant 10 s, 30 s et 60 s. Ensuite, le taux de survie bactérien a été confirmé. RÉSULTATS: Les bactéries Gram-négatives (P. aeruginosa et E. coli) étaient plus sensibles que les bactéries Gram-positives (S. aureus et S. pseudintermedius) pour la même durée d’exposition au CAMP. Seules les bactéries Gram-négatives étaient complètement tuées après 60s d’exposition. Dans les souches de S. pseudintermedius, l’exposition à CAMP avait des effets antibactériens similaires au regard de la résistance antibiotique.Le CAMP a une activité antimicrobienne suffisante contre les souches bactériennes majeures causant pyodermite et otite externe chez le chien et peut être une option thérapeutique alternative pour les infections cutanées à S. pseudintermedius pour laquelle les antibiotiques sont souvent inefficaces en raison de résistances antimicrobiennes en médecine vétérinaire clinique.INTRODUCCIÓN: el plasma atmosférico frío (CAP) es una opción terapéutica médica de nueva generación para las infecciones bacterianas. El CAP provoca la ruptura física de la pared celular y el daño al DNA, por lo que es muy útil en el tratamiento de diversas afecciones, como las infecciones de la piel. HIPÓTESIS/OBJETIVOS: se probó la actividad antimicrobiana del plasma de microondas atmosférico frío (CAMP) contra las principales cepas en las infecciones cutáneas caninas y se evaluó la diferencia en la actividad antimicrobiana entre las cepas resistentes y sensibles a los antibióticos de Staphylococcus pseudintermedius. MÉTODOS Y MATERIALES: cepas de la American Type Culture Collection (ATCC) (Staphylococcus aureus, Pseudomonas aeruginosa y Escherichia coli) y aislados clínicos identificados como S. pseudintermedius resistente a meticilina (n = 27) y S. pseudintermedius sensible a meticilina (n = 13) fueron expuestos a CAMP durante 10 s, 30 s y 60 s. Posteriormente, se valoró la tasa de supervivencia bacteriana. RESULTADOS: las bacterias Gram negativas (P. aeruginosa y E. coli) fueron más susceptibles que las bacterias Gram positivas (S. aureus y S. pseudintermedius) durante la misma duración de exposición a CAMP. Solo las bacterias Gram negativas murieron por completo después de 60 s de exposición. En los aislados de S. pseudintermedius, la exposición a CAMP tuvo efectos antibacterianos similares independientemente de la resistencia a los antibióticos. CONCLUSIONES E IMPORTANCIA CLÍNICA: CAMP tiene suficiente actividad antimicrobiana contra las principales cepas bacterianas que causan pioderma y otitis externa en perros, y puede ser una opción terapéutica alternativa para las infecciones cutáneas por S. pseudintermedius, para las cuales los antibióticos a menudo son ineficaces debido a la resistencia a los antimicrobianos en medicina veterinaria.Kaltes atmosphärisches Plasma (CAP) zählt zu einer neuen Generation an medizinischen Behandlungsoptionen für bakterielle Infektionen. CAP verursacht eine physische Zellwandruptur und eine DNA Schädigung, was es in der Folge bei der Behandlung verschiedener Erkrankungen wie Hautinfektionen sehr wirkungsvoll macht.Die antimikrobielle Wirksamkeit von kaltem atmosphärischem Mikrowellenplasma (CAMP) wurde gegenüber wichtigen Stämmen bei Hautinfektionen des Hundes getestet und der Unterschied der antimikrobiellen Aktivität zwischen den Antibiotika-resistenten und den Antibiotika-empfindlichen Stämmen von Staphylococcus pseudintermedius evaluiert.Stämme (Staphylococcus aureus, Pseudomonas aeruginosa und Escherichia coli) aus der American Type Culture Collection (ATCC) und klinische Isolate, die als Methicillin-resistente S. pseudintermedius (n = 27) und Methicillin-empfindliche S. pseudintermedius (n = 13) isoliert worden waren, wurden CAMP für 10 s, 30 s und 60 s ausgesetzt. Danach wurde die bakterielle Überlebensrate bestätigt.Gram-negative Bakterien (P. aeruginosa und E. coli) waren empfindlicher als Gram-positive Bakterien (S. aureus und S. pseudintermedius) bei gleich langer Dauer der Exposition zu CAMP. Nur die Gram-negativen Bakterien waren nach einer 60 s dauernden Exponierung völlig abgetötet. In S. pseudintermedius Isolaten zeigte die Exponierung unabhängig von der antibiotischen Resistenz zu CAMP eine ähnliche antibakterielle Wirkung.CAMP zeigt eine ausreichende antimikrobielle Aktivität gegenüber bakteriellen Stämmen, die eine Pyodermie und eine Otitis externa bei Hunden verursachen und könnte eine alternative therapeutische Option für Hautinfektionen durch S. pseudintermedius darstellen, für die Antibiotika aufgrund der antimikrobiellen Resistenz in der klinischen Veterinärmedizin oft unwirksam sind.背景: 低温大気圧プラズマ (CAP) は、細菌感染症に対する新世代の治療法として注目されている。CAPは、物理的な細胞壁破壊とDNAの損傷を引き起こすため、皮膚感染症などの様々な症状の治療に非常に有用である。 仮説・目的: 本研究の目的は、犬の皮膚感染症における主要な菌株に対する低温マイクロ波プラズマ (CAMP) の抗菌活性を試験し、Staphylococcus pseudintermediusの抗生物質耐性菌株および抗生物質感受性菌株間の抗菌活性の違いを評価することであった。 材料・方法: American Type Culture Collection(ATCC) 株 (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli)と、メチシリン耐性S. pseudintermedius(n = 27)およびメチシリン感受性S. pseudintermedius(n = 13)と同定された臨床分離株をCAMPに10秒、30秒、60秒曝露し、その後、細菌の生存率を確認した。 結果: グラム陰性菌 (P. aeruginosaおよびE. coli) は、同じCAMP曝露時間でもグラム陽性菌 (S. aureusおよびS. pseudintermedius) よりも感受性が高かった。60秒の曝露で完全に死滅したのはグラム陰性菌のみであった。S. pseudintermedius分離菌では、CAMP曝露は抗生物質耐性にかかわらず同様の抗菌効果を示した。 結論および臨床上の重要性: CAMPは犬膿皮症および外耳炎の原因となる主要な細菌株に対して十分な抗菌活性を有しており、臨床獣医学では抗菌剤耐性のために抗生物質が効かないことが多いS. pseudintermedius皮膚感染症の代替治療法となる可能性がある。.背景: 大气低温等离子体(CAP)是新一代细菌感染的药物治疗选择。CAP引起物理性细胞壁破裂和DNA损伤, 因此使其在皮肤感染等多种疾病的治疗中非常有用。 假设/目的: 检测了大气低温微波等离子体(CAMP)对犬皮肤感染中主要菌株的抗菌活性, 并评价了假中间型葡萄球菌的抗生素耐药性和抗生素敏感性菌株之间的抗菌活性差异。 方法和材料: 将美国典型培养物保藏中心(ATCC)菌株 (金黄色葡萄球菌、铜绿假单胞菌和大肠埃希菌) 和鉴定为耐甲氧西林假中间型链球菌(n = 27)和甲氧西林敏感假中间型链球菌(n = 13)的临床分离株暴露于CAMP 10s、30s和60s后, 证实了细菌存活率。 结果: 在相同的CAMP暴露时间内, 革兰氏阴性菌 (铜绿假单胞菌和大肠埃希菌) 比革兰氏阳性菌 (金黄色葡萄球菌和假中间型链球菌) 更敏感。暴露60s后仅完全杀灭革兰氏阴性菌。在假中间型链球菌分离株中, 无论抗生素耐药性如何, CAMP暴露均具有相似的抗菌作用。 结论和临床重要性: CAMP对引起犬脓皮病和外耳炎的主要细菌菌株具有足够的抗菌活性, 可能是假中间型葡萄球菌皮肤感染的替代治疗选择, 在临床兽药中, 由于抗菌药物耐药性, 抗生素通常无效。.O plasma atmosférico frio (PAF) é uma opção terapêutica de nova geração para infecções bacterianas. O PAF causa ruptura física da parede celular e danos ao DNA, sendo, portanto, altamente útil no tratamento de várias condições, como infecções de pele. HIPÓTESE/OBJETIVOS: A atividade antimicrobiana do plasma atmosférico frio de microondas (PAFM) contra as principais cepas em infecções cutâneas caninas foi testada e a diferença na atividade antimicrobiana entre as cepas de Staphylococcus pseudintermedius resistentes a antibióticos e suscetíveis a antibióticos foi avaliada. MÉTODOS E MATERIAIS: Cepas da American Type Culture Collection (ATCC) (Staphylococcus aureus, Pseudomonas aeruginosa e Escherichia coli) e isolados clínicos identificados como S. pseudintermedius resistente à meticilina (n = 27) e S. pseudintermedius sensível à meticilina (n = 13) foram expostos ao PAFM por 10 s, 30 s e 60 s. Posteriormente, a taxa de sobrevivência bacteriana foi confirmada.As bactérias Gram-negativas (P. aeruginosa e E. coli) foram mais suscetíveis do que as bactérias Gram-positivas (S. aureus e S. pseudintermedius) para a mesma duração da exposição PAFM. Apenas as bactérias Gram-negativas foram completamente mortas após 60 s de exposição. Nos isolados de S. pseudintermedius, a exposição ao PAFM teve efeitos antibacterianos semelhantes, independentemente da resistência aos antibióticos. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: PAFM tem atividade antimicrobiana suficiente contra as principais cepas bacterianas que causam piodermite e otite externa em cães, e pode ser uma opção terapêutica alternativa para infecções cutâneas por S. pseudintermedius, para as quais os antibióticos muitas vezes são ineficazes devido à resistência antimicrobiana na medicina veterinária.

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) has a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower bodyweight and fasting blood glucose and insulin levels than wildtype (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were three times lower than those of WT mice. Hematoxylin and eosin staining demonstrated that NAG-1 Tg mice exhibited a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas, compared to WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. The adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the IRS1/PI3K/AKT signaling pathway, especially Foxo1, which regulates gluconeogenesis in the muscle and WAT, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted As160 (AKT substrate of 160 kDa) expression in both muscles and adipocytes and the mRNA levels of the Nlrp3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.

Background A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

Pueraria lobata (Wild.) Ohwi. (P. lobata) flowers known as ‘Kudzu flower’ contain isoflavonoids and essential oil components. They have a wide range of biological and pharmacological activities, including protective effects against non-alcoholic fatty liver disease, hyperglycemia, and hypolipidemia, anti-mutagenic effects, and benefits for weight loss. However, the molecular mechanism of these effects remains unclear. Our study aimed to systematically examine the effects of flos puerariae crude extract (FPE) as an anti-diabetic agent using in vitro assays. The cytotoxicity of FPE was evaluated using MTS assay in L6 rat myocyte and 3T3-L1 murine fibroblast cell lines. PPARγ binding activity and adipogenesis were examined using dual-luciferase and differentiation assays, respectively. For investigating the anti-diabetic activity, glucose utilization, including GLUT4 protein expression, glucose uptake assay, and GLUT4 translocation using immunofluorescence microscopy were conducted in L6 cells. Furthermore, we assessed the antioxidant and anti-inflammatory activities of FPE. Our results demonstrated the ability to augment glucose uptake in L6 cells and enhance glucose utilization activity by increasing the expression of glucose transporter type 4 (GLUT4). In summary, our findings suggest that FPE may be a potential anti-diabetic substance for the treatment of diabetic patients and can prevent inflammatory or oxidation-related diseases.

Osteosarcoma is known to be one of the frequently occurring cancers in dogs. Its prognosis is usually very poor, with a high incidence of lung metastasis. Although radiation therapy has become a major therapeutic choice for canine osteosarcoma, the high costs and unexpected side effects prevent some patients from considering this treatment. Cold atmospheric plasma (CAP) is an ionized gas with high energy at low temperatures, and it produces reactive oxygen species that mediate many signaling pathways. Although many researchers have used CAP as an anticancer therapeutic approach in humans, its importance has been neglected in veterinary medicine. In this study, D-17 and DSN canine osteosarcoma cell lines were treated with CAP to observe its anticancer activity. By high-content screening and flow cytometry, CAP-treated cells showed growth arrest and apoptosis induction. Moreover, the osteosarcoma cells exhibited reduced migration and invasion activity when treated with CAP. Overall, CAP exerted an anticancer effect on canine osteosarcoma cell lines. CAP may have the potential to be used as a novel modality for treating cancer in veterinary medicine.

Incorporating lipophilic phytochemicals with anti-cancer activities in functional beverages requires an appropriate nanoencapsulation technology. The present objective was to encapsulate apigenin with whey protein isolate (WPI) utilizing a pH-cycle method and subsequently characterize physicochemical properties, the in vitro anticancer activities against human colorectal HCT-116 and HT-29 cancer cells, and the in vivo bioavailability. Up to 2.0 mg/mL of apigenin was nanoencapsulated with 1.0 mg/mL WPI, with an encapsulation efficiency of up to 98.15% and loading capacity of up to 196.21 mg/g-WPI. Nanodispersions were stable during storage, and apigenin became amorphous after encapsulation. Nanoencapsulation and in vitro digestion did not reduce the anti-proliferative activity of apigenin. Nanoencapsulation of apigenin enhanced the cellular uptake, the pro-apoptotic effects, and the bioavailability in the mice's blood and colon mucosa when comparing to the unencapsulated apigenin. Therefore, the present work may be significant to incorporate lipophilic phytochemicals in functional beverages for disease prevention.

Caffeic acid phenethyl ester (CAPE) has high cytotoxicity against various cancer cells but has low water solubility and poor bioavailability. The objective of this work was to study a fully-dilutable oil-in-water microemulsion as a delivery vehicle of CAPE and the impacts on cellular uptake and expression of relevant proteins. Up to 3.30% w/w CAPE was dissolved in the microemulsion with droplets smaller than 20 nm and stable in 180 days. CAPE in the microemulsion had the significantly increased anti-proliferative activity against human HCT-116 colorectal and MCF-7 breast cancer cells than that in dimethyl sulfoxide. Dissolving CAPE in the microemulsion enhanced the cellular uptake according to fluorescence microscopy, flow cytometry, and HPLC. Subsequently, cyclin D1 was suppressed and p53 was induced, which regulated cell cycle and apoptosis, respectively, thereby enhancing anti-cancer activity. Findings from the present work suggest the potential of the studied microemulsion as a vehicle of CAPE for development of cancer intervention strategies.

Dietary polyphenols including quercetin are secondary plant metabolites that have been reported to prevent many chronic diseases; however, the high hydrophobicity of quercetin results in low water solubility and bioavailability, which limits the therapeutic efficacy and impedes further applications in aqueous systems. Encapsulation may be a potential solution to the aforementioned problems. Some polysaccharides, including soluble soybean polysaccharides (SSPS) and chitosan, were widely used as polymeric backbones for the formation of nanoparticles. We investigated the physicochemical property of encapsulated quercetin in SSPS with chitosan. Encapsulation of quercetin was confirmed using Dynamic light scattering, Zeta potential, Fourier-transform infrared spectroscopy, Differential scanning calorimetry, and Transmission electron microscopy. The biological activity of this nanoparticle showed that encapsulated quercetin exhibits better biological activity compared to free quercetin. Alongside the enhanced solubility of quercetin in an aqueous solution, our results illustrate the improved utility of this nanoparticle in the biomedical and food industry.

Pseudomonas aeruginosa is an opportunist pathogen that causes purulent inflammation in the skin and in the ears of dogs. Among the various virulence factors of P. aeruginosa, biofilms have been reported to result in antibiotic resistance, leading to therapeutic limitations. Cold atmospheric microwave plasma (CAMP) is known to have a high antimicrobial effect, which causes physical cell wall rupture and DNA damage.The objective of this study was to evaluate the antibacterial and antibiofilm effects of CAMP against planktonic bacteria and the biofilm of P. aeruginosa.The antibacterial effect of CAMP against P. aeruginosa ATCC10145 and clinical isolates (n = 30) was evaluated using the colony count method. We also assessed the effect of CAMP on biofilm of P. aeruginosa ATCC strain by the colony count method, water-soluble tetrazolium salt (WST) assay and confocal laser scanning microscopy (CLSM).The complete eradication of P. aeruginosa (ATCC strain and clinical isolates) was achieved within 120 s at 50 W, and clinical isolates required 60 s shorter than the ATCC strain for complete eradication at 50 W. We also confirmed the time-dependent bactericidal effect of CAMP at 50 W against ATCC strain biofilm.CAMP was effective against both planktonic bacteria and biofilm formation of P. aeruginosa. However, further studies on in vivo efficacy and safety in canine skin and ears are necessary to fully validate its clinical application.背景-铜绿假单胞菌是一种条件致病菌, 可引起犬皮肤和耳部化脓性炎症。在铜绿假单胞菌的各种毒力因子中, 有报道生物膜导致抗生素耐药, 限制了疗效。已知冷大气微波等离子体(CAMP)具有较高的抗菌作用, 从而引起物理细胞壁破裂和DNA损伤。 假设/目的-本研究的目的是评价CAMP对浮游细菌和铜绿假单胞菌生物膜的抗菌和抗生物膜作用。 方法和材料-使用菌落计数法评价CAMP对铜绿假单胞菌ATCC10145和临床分离株(n = 30)的抗菌作用。我们还通过菌落计数法、水溶性四唑盐(WST)试验和激光共聚焦显微镜(CLSM)评估了CAMP对铜绿假单胞菌ATCC菌株生物膜的影响。 结果-铜绿假单胞菌 (ATCC菌株和临床分离株) 在50 W下120 s内完全根除, 在50 W下,临床分离株完全根除所需时间比ATCC菌株短60 s。我们还证实了50 WCAMP对ATCC菌株生物膜的时间依赖性杀菌作用。 结论和临床重要性-CAMP对抑制浮游细菌和铜绿假单胞菌生物膜形成均有效。但有必要对犬皮肤和耳部的体内疗效和安全性进行进一步研究, 以充分验证其临床应用。.Pseudomonas aeruginosa est un pathogène opportuniste qui provoque une inflammation purulente de la peau et des oreilles des chiens. Parmi les différents facteurs de virulence de P. aeruginosa, il a été rapporté que les biofilms entraînent une résistance aux antibiotiques, entraînant des limitations thérapeutiques. Le CAMP (Cold atmospheric microwave plasma) est connu pour avoir un effet antimicrobien élevé, ce qui provoque une rupture physique de la paroi cellulaire et des dommages à l'ADN. HYPOTHÈSE/OBJECTIFS: L'objectif de cette étude était d'évaluer les effets antibactériens et antibiofilm du CAMP contre les bactéries planctoniques et le biofilm de P. aeruginosa. MÉTHODES ET MATÉRIEL: L'effet antibactérien du CAMP contre P. aeruginosa ATCC10145 et les isolats cliniques (n = 30) a été évalué à l'aide de la méthode de comptage des colonies. Nous avons également évalué l'effet du CAMP sur le biofilm de la souche ATCC de P. aeruginosa par la méthode de comptage des colonies, le dosage du sel de tétrazolium hydrosoluble (WST) et la microscopie confocale à balayage laser (CLSM). RÉSULTATS: L'éradication complète de P. aeruginosa (souche ATCC et isolats cliniques) a été réalisée en 120 s à 50 W, et les isolats cliniques ont nécessité 60 s de moins que la souche ATCC pour une éradication complète à 50 W. Nous avons également confirmé l’effet bactéricide temps dépendant du CAMP à 50 W contre le biofilm de la souche ATCC.CAMP était efficace contre les bactéries planctoniques et la formation de biofilm de P. aeruginosa. Cependant, d'autres études sur l'efficacité et l'innocuité in vivo dans la peau et les oreilles canines sont nécessaires pour valider pleinement son application clinique.Pseudomonas aeruginosa ist ein opportunistisches Pathogen, welches eine eitrige Entzündung in der Haut und in den Ohren von Hunden verursacht. Unter den verschiedenen Virulenzfaktoren von P. aeruginosa wird ein Biofilm beschrieben, welcher zu antibiotischer Resistenz führt, was wiederum zu therapeutischen Limitierungen führt. Kaltes atmosphärisches Mikrowellenplasma (CAMP) ist bekannt für eine starke antimikrobielle Wirkung, die eine physische Zellwandruptur und eine Schädigung der DNA verursacht.Das Ziel dieser Studie war eine Evaluierung der antibakteriellen und Antibiofilm Wirksamkeiten von CAMP gegenüber planktonischen Bakterien und dem Biofilm von P. aeruginosa.Die antibakterielle Wirkung von CAMP gegenüber P. aeruginosa ATCC10145 und klinischen Isolaten (n = 30) wurde mittels Koloniezählungsmethode evaluiert. Wir untersuchten auch die Auswirkung von CAMP auf den Biofilm von P. aeruginosa ATCC Stamm mittels Koloniezählungsmethode, wasserlöslichem Tetrazolium Salz (WST) Assay und konfokaler Laserscanmikroskopie (CLSM).Die gänzliche Auslöschung von P. aeruginosa (ATCC Stamm und klinische Isolate) wurde innerhalb von 120s bei 50 W erzielt, klinische Isolate benötigten 60s weniger als die ATCC Stämme für eine komplette Auslöschung bei 50 W. Wir bestätigten auch eine Zeit-abhängige bakterizide Wirkung von CAMP bei 50 W gegenüber dem Biofilm von ATCC Stämmen.CAMP war gegenüber planktonischen Bakterien sowie Biofilmbildung von P. aeruginosa wirksam. Es sind jedoch weitere Studien nötig, um die in vivo Wirksamkeit und Sicherheit auf der Haut und in den Ohren des Hundes zu untersuchen, um die klinische Applikation vollständig zu validieren.背景-Pseudomonas aeruginosaは、犬の皮膚や耳に膿性の炎症を引き起こす日和見病原体である。P. aeruginosaの様々な病原因子の中でも、バイオフィルムは抗生物質耐性をもたらすことが報告されており、治療の限界につながっている。冷気マイクロ波プラズマ (CAMP) は高い抗菌効果を持つことが知られており、物理的な細胞壁の破壊及びDNAの損傷を引き起こす。 仮説・目的-本研究の目的は、浮遊性細菌およびP. aeruginosaのバイオフィルムに対するCAMPの抗菌・抗バイオフィルム効果を評価することであった。 材料と方法 - P. aeruginosa ATCC10145および臨床分離株 (n = 30) に対するCAMPの抗菌効果をコロニーカウント法で評価した。また、P. aeruginosa ATCC株のバイオフィルムに対するCAMPの効果をコロニーカウント法、水溶性テトラゾリウム塩 (WST) アッセイ法、共焦点レーザー走査型顕微鏡 (CLSM) で評価した。 結果 - P. aeruginosa(ATCC株および臨床分離株) の完全な根絶は50Wで120秒以内に達成され、臨床分離株は50Wでの完全な根絶にATCC株よりも60秒短い時間を必要とした。また、ATCC株のバイオフィルムに対するCAMPの50Wでの時間依存的な殺菌効果を確認した。 結論と臨床上の重要性 - CAMPは、浮遊性細菌及びP. aeruginosaのバイオフィルム形成の両方に対して有効であった。しかし、その臨床応用を完全に検証するためには、犬の皮膚や耳におけるin vivoの有効性及び安全性に関するさらなる研究が必要である。.Pseudomonas aeruginosa é um patógeno oportunista que causa inflamação purulenta na pele e orelhas de cães. Dentre os fatores de virulência de P. aeruginosa, os biofilmes têm sido relatados como causadores de resistência a antimicrobianos, levando a limitações terapêuticas. O plasma atmosférico frio (CAMP) é conhecido por apresentar elevada ação antimicrobiana, que causa ruptura física da parede celular e dano ao DNA. HIPÓTESE/OBJETIVOS: O objetivo deste estudo foi avaliar os efeitos antibacterianos e antibiofilme do CAMP contra bactérias P. aeruginosa nas formas planctônica e biofilme. MÉTODOS E MATERIAIS: O efeito antibacteriano de CAMP contra P. aeruginosa ATCC10145 e isolados clínicos (n = 30) foi avaliado utilizando o método de contagem de colônias. Nós também avaliamos o efeito de CAMP no biofilme de P. aeruginosa cepa ATCC pelo método de contagem de colônias, ensaio de sal de tetrazólio solúvel em água (WST) e microscopia confocal de varredura a laser (CLSM).A erradicação completa de P. aeruginosa (cepa ATCC e isolados clínicos) foi obtida dentro de 120 s a 50 W, e os isolados clínicos precisaram de 60 s a menos que a cepa ATCC para completar a erradicação a 50 W. Nós também confirmamos o efeito bactericida tempo-dependente do CAMP a 50 W contra o biofilme da cepa ATCC. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: O CAMP foi eficaz contra bactérias planctônicas e formação de biofilme de P. aeruginosa. Entretanto, mais estudos sobre a eficácia in vivo e a segurança na pele canina e orelhas são necessários para validar a sua aplicação clínica.INTRODUCCIÓN: Pseudomonas aeruginosa es un patógeno oportunista que causa inflamación purulenta en la piel y en los oídos de los perros. Entre los diversos factores de virulencia de P. aeruginosa, se ha informado que la formación de biopelículas da lugar a resistencia a los antibióticos, lo que genera limitaciones terapéuticas. Se sabe que el plasma de microondas atmosférico frío (CAMP) tiene un alto efecto antimicrobiano, que provoca la ruptura física de la pared celular y daño al DNA bacteriano. HIPÓTESIS/OBJETIVOS: El objetivo de este estudio fue evaluar los efectos antibacterianos y antipelículas biológicas de CAMP contra bacterias planctónicas y el biofilm de P. aeruginosa. MÉTODOS Y MATERIALES: Se evaluó el efecto antibacteriano de CAMP contra P. aeruginosa ATCC10145 y aislados clínicos (n = 30) utilizando el método de recuento de colonias. También evaluamos el efecto de CAMP sobre la biopelícula de la cepa ATCC de P. aeruginosa mediante el método de recuento de colonias, el ensayo de sal de tetrazolio soluble en agua (WST) y la microscopía de barrido láser confocal (CLSM). RESULTADOS: la eleiminación completa de P. aeruginosa (cepa ATCC y aislados clínicos) se logró con 120s a 50 W, y los aislados clínicos requirieron 60s menos que la cepa ATCC para la eliminación completa a 50 W. También confirmamos efecto bactericida dependiente de tiempo de CAMP a 50 W contra la biopelícula de la cepa ATCC. CONCLUSIONES E IMPORTANCIA CLÍNICA: CAMP fue eficaz tanto contra las bacterias planctónicas como contra la formación de biopelículas de P. aeruginosa. Sin embargo, son necesarios más estudios sobre la eficacia y seguridad in vivo en piel y oídos caninos para validar completamente su aplicación clínica. CONCLUSIONS AND CLINICAL IMPORTANCE: CAMP was effective against both planktonic bacteria and biofilm formation of P. aeruginosa. However, further studies on in vivo efficacy and safety in canine skin and ears are necessary to fully validate its clinical application.

Simple Summary Thyroid cancer is one of the most common cancers worldwide, and its incidence has increased over the last few decades. It is difficult to diagnose different types of thyroid cancer. Tumor tissues from papillary thyroid cancer patient showed higher expression of mature NAG-1, whereas adjacent normal tissues showed higher expression of pro-NAG-1. Several anti-cancer compounds increased pro-NAG-1 expression in thyroid cancer cell line. Quercetin (3,3’,4’,5,7-pentahydroxyflavone) is a flavonoid that is a major component of various plants, including raspberries, grapes, and onions. Quercetin induced apoptosis by inducing only pro-NAG-1 expression, but not mature NAG-1, mediated by the transcription factor C/EBP. This study indicates that pro-NAG-1 could be used as a useful biomarker for thyroid cancer and also provides a potential therapeutic target for the treatment of thyroid cancer with quercetin. Abstract Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.

Damnacanthal (Dam) is a phytochemical with many pharmacological properties including anticancer activity. However, its hydrophobicity, poor bioavailability and stability limit its application in many biological approaches. In this study, Dam nanomicelles as an emerging platform were developed to overcome limitations. The deoxycholic and poly(ethylene glycol) methyl ether grafted chitosan (DCA-CS-mPEG) was synthesized and characterized by FTIR and 1 H NMR and the degree of substitution (DS) was determined by elemental analysis (EA). This polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 37.2 μg/mL. Dam-loaded polymeric micelles were prepared by dialysis method and characterized by DLS, TEM, FTIR, DSC and HPLC. The mean particle size of Dam-loaded micelles was about 200 nm with spherical shape. The drug entrapment efficiency was up to 57.7%. FTIR and DSC analysis revealed that Dam was entrapped in the micelles in the amorphous state. The in vitro release profiles of Dam from micelles were sustained release and pH-sensitive behavior. Cytotoxic studies exhibited the comparable efficacy and safety of this delivery system. Overall these results indicate the possible utilization of DCA-CS-mPEG micelles as a promising carrier for hydrophobic compounds like Dam.

Ischemia reperfusion (I/R) injury which inevitably occurs during heart transplantation is the major factor leading to organ failure and graft rejection. In order to develop new therapies to prevent I/R injury, we used both a murine heart transplantation model with 24 hour cold I/R and an in vitro cell culture system to determine whether growth differentiation factor 15 (GDF15) is a protective factor in preventing I/R injury in heart transplantation and to further investigate underlying mechanisms of I/R injury. We found that cold I/R caused severe damage to the endocardium, epicardium and myocardium of heart grafts from wild type C57BL/6 mice, whereas grafts from GDF15 transgenic (TG) mice showed less damage as demonstrated by decreased cell apoptosis/death, decreased neutrophils infiltration and the preservation of the normal structure of the heart. Over-expression of GDF15 reduced expression of phosphorylated RelA p65, pre-inflammatory and pro-apoptotic genes while it enhanced Foxo3a phosphorylation in vitro and in vivo. Over-expression of GDF15 inhibited cell apoptosis/death and reduced neutrophil infiltration. In conclusion, this study, for the first time, demonstrates that GDF15 is a promising target for preventing cold I/R injury in heart transplantation. This study also shows that the resultant protective effects are mediated by the Foxo3 and NFκB signaling pathways.

Non-steroidal anti-inflammatory drug activated gene-1 (NAG-1), also known as growth differentiation factor 15 (GDF15), is a TGF-β (transforming growth factor beta) superfamily protein with a distinctive secretion pathway. NAG-1 is associated with multiple diseases including cancer, wherein it plays a role in both pro- and anti-cancer activities. We previously reported that NAG-1 is translocated to different subcellular compartments and its activity depends on its localization. In this paper, we report that the transfection of a novel peptide corresponding to the nuclear localization signal (NLS) of NAG-1 blocks its translocation to the nucleus. Further, accumulation of NAG-1 in the cytoplasm decreased mitochondrial membrane potential, thus implying apoptosis induction as a consequence. Overall, our results indicate that the novel peptide derived from NAG-1 NLS sequence is a promising tool for enhancing the anti-tumorigenic activity of NAG-1.

Background/aim Plasma medicine is a new field that provides great potential for the treatment of human diseases including cancer in addition to sterilizing the surface of skin and facilitating wound healing. Recently, non-thermal atmospheric plasma (or cold atmospheric plasma, CAP) was introduced, not only for denaturing cells and tissues, but also for operating under the threshold of thermal damage and for chemically inducing a specific response or modification. Materials and methods Microwave-mediated CAP was used in this study. Results CAP increased high-mobility group box 1 protein (HMGB1) expression, thereby increasing HMGB-1 secretion. In addition, we observed that the calreticulin (CRT) protein was concentrated at the cellular membrane when plasma was treated, representing immunogenic cell death. Conclusion Overall, plasma treatment induces apoptosis via immunogenic cell death in cancer cells, implying a potential application to human cancer therapy and for the treatment of other human diseases.