Tailored hydration with lactated Ringer's solution for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: A randomized controlled trial.

OBJECTIVES: Aggressive hydration using lactated Ringer's solution (LRS) prevents post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention. METHODS: In this prospective, multicenter, double-blinded, randomized trial conducted across three tertiary Korean hospitals, patients who underwent ERCP for the first-time were randomly assigned (1:1) to tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/h LRS during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/h during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 h after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 h. The primary endpoint was PEP development and was analyzed on an intention-to-treat analysis. RESULTS: A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, p = 0.03). No difference was identified between the two groups in terms of PEP severity (p = 0.80) and complications related to volume overload (p = 0.32). CONCLUSIONS: TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 h after ERCP is safe and prevents PEP development.

A Mesoporous Tungsten Oxynitride Nanofibers/Graphite Felt Composite Electrode with High Catalytic Activity for the Cathode in Zn-Br Flow Battery.

High electrochemical polarization during a redox reaction in the electrode of aqueous zinc-bromine flow batteries largely limits its practical implementation as an effective energy storage system. This study demonstrates a rationally-designed composite electrode that exhibits a lower electrochemical polarization by providing a higher number of catalytically-active sites for faster bromine reaction, compared to a conventional graphite felt cathode. The composite electrode is composed of electrically-conductive graphite felt (GF) and highly active mesoporous tungsten oxynitride nanofibers (mWONNFs) that are prepared by electrospinning and simple heat treatments. Addition of the 1D mWONNFs to porous GF produces a web-like structure that significantly facilitates the reaction kinetics and ion diffusion. The cell performance achieves in this study demonstrated high energy efficiencies of 89% and 80% at current densities of 20 and 80 mA cm-2 , respectively. Furthermore, the cell can also be operated at a very high current density of 160 mA cm-2 , demonstrating an energy efficiency of 62%. These results demonstrate the effectiveness of the mWONNF/GF composite as the electrode material in zinc-bromine flow batteries.

Albizia julibrissin Exerts Anti-Obesity Effects by Inducing the Browning of 3T3L1 White Adipocytes.

This study investigated the effects of the Albizia julibrissin Leaf extracts (AJLE) on adipocytes using 3T3-L1 cells. AJLE inhibited adipogenesis by reducing the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteins (C/EBPs) that regulate enzymes involved in fat synthesis and storage, and subsequently reduced intracellular lipid droplets, glycerol-3-phosphate dehydrogenase (GPDH), and triglyceride (TG). AJLE also increased the expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1), PR/SET domain 16 (PRDM16), and bone morphogenetic protein 7 (BMP7) by inducing the differentiation of brown adipocytes, as shown by a decrease in the lipid droplet sizes and increasing mitochondrial mass. AJLE increased the expression of transcription factor A, mitochondrial (TFAM), mitochondrial DNA (mtDNA) copy number, and UCP-1 protein expression, all of which are key factors in regulating mitochondrial biogenesis. AJLE-induced browning was shown to be regulated by the coordination of AMPK, p38, and SIRT1 signaling pathways. The ability of AJLE to inhibit adipogenesis and induce brown adipocyte differentiation may help treat obesity and related diseases.

Assessment of the anti-hair loss potential of Camellia japonica fruit shell extract in vitro.

OBJECTIVE: Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C. japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C. japonica fruit shell extract (CJFSE) for hair loss mitigation. METHODS: MTT assay, spheroid culture and quantitative RT-PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT-induced hair loss were confirmed by Dkk-1 ELISA, ß-galactosidase (ß-gal) and 5α-reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. RESULTS: CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF-A, Wnt-1, c-Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α-reductase activity and DHT-induced decrease in cell proliferation, Dkk-1 secretion and ß-gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide-induced ROS production and ß-gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. CONCLUSION: CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair.

OBJECTIF: Divers facteurs sont responsables de la perte de cheveux. Souvent, les conséquences de ces facteurs se superposent et s'intensifient. Actuellement, on étudie comment atténuer la perte de cheveux en faisant proliférer les cellules de la papille dermique (DPC) et en inhibant les facteurs délétères tels que la dihydrotestostérone (DHT) et le stress oxydatif sur la croissance des cheveux. La coque du fruit du Camélia du Japon (Camelia japonica) est habituellement rejetée. Son utilité biologique reste à élucider. Dans cette étude, nous avons étudié la capacité de l'extrait de la coque du fruit du Camélia du Japon (CJFSE) dans la mitigation de la perte de cheveux. MÉTHODES: Un test MTT, une culture de sphéroïdes et une RT-PCR Quantitative ont été effectués pour observer la prolifération de CJFSE sur les cellules de la papille dermique du follicule pileux (HFDPC). Les effets du CJFSE sur la perte de cheveux induite par la DHT ont été confirmés par Dkk-1 ELISA, ß-galactosidase (ß-gal) et 5α-réductase. De plus, les effets du CJFSE sur le stress oxydatif ont été confirmés par des tests de production de DPPH et de ROS. RÉSULTATS: Le CJFSE a augmenté la prolifération et la taille sphéroïde des HFDPC. Les niveaux d'expression de VEGF-A, Wnt-1, c-Myc et cycline D1 ont été régulés de manière efficace par le CJFSE. Le CJFSE a également supprimé l'activité de la 5α-réductase et a induit la réduction de la DHT et de la prolifération cellulaire, ainsi que de la sécrétion de Dkk-1 et de l'activité ß-gal. Le CJFSE a en outre montré une activité de capture du DPPH et amélioré la production de ROS induite par le peroxyde d'hydrogène et l'activité ß-gal. Pour finir, les acides gallique et protocatéchuique ont été observés dans le CJFSE après analyse des HPLC. CONCLUSION: Le CJFSE a le potentiel d'atténuer la perte de cheveux en favorisant la croissance des cellules ciliées et en supprimant les effets de la DHT et du stress oxydatif sur les cheveux.

The effect of Salix alba L. bark extract on dark circles in vitro and in vivo.

OBJECTIVE: Dark circles in the infraorbital area are a common cosmetic concern among individuals because they exhibit fatigue and are undesirable across all ages. Of the dark circle etiologies, blood stasis by poor-vascular integrity can cause darkening of the lower eyelid skin, which might be alleviated by reduced endothelial permeability. In this study, we investigated the effects of Salix alba bark extract (SABE) on the synthesis of hyaluronic acid (HA) in fibroblasts and vascular integrity protection from inflammatory cytokine. We also performed a clinical trial investigating the effect of SABE on dark circles. METHODS: To confirm the effect of SABE on HA synthesis in human dermal fibroblasts (HDFs), we performed ELISA and real-time PCR. We investigated the interaction HDF-secreted substance with vascular integrity, and human dermal microvascular endothelial cells (HMEC-1) were treated with conditioned medium (CM) from HDF treated with or without SABE. Subsequently, we conducted a clinical study on 29 subjects by having them apply SABE containing cream for 8 weeks. RESULTS: Salix alba bark extract treatment increased HA synthesis and regulated HMW-HA-related gene expressions in HDF. CM from SABE-treated HDF alleviated endothelial permeability and led to improved vascular integrity in HMEC-1 cells. Treatment with the cream containing 2% SABE for 8 weeks improved the parameters measuring dark circles, skin microcirculation and elasticity. CONCLUSION: Our results showed that SABE could protect against dark circles in vitro, and that topical treatment of SABE improved the clinical indexes of dark circles in a clinical study. Therefore, SABE can be used as an active ingredient for improving dark circles.

OBJECTIF: Les cernes dans la région infra-orbitaire sont un problème cosmétique fréquent chez les patients, car elles témoignent de la fatigue et sont indésirables à tout âge. Parmi les étiologies de cerne, la stase sanguine due à une mauvaise intégrité vasculaire peut entraîner un assombrissement de la peau de la paupière inférieure qui peut être atténué par une réduction de la perméabilité endothéliale. Dans cette étude, nous avons étudié les effets de l'extrait d'écorce de Salix alba sur la synthèse de l'acide hyaluronique (AH) dans les fibroblastes, et la protection de l'intégrité vasculaire contre les cytokines inflammatoires. Nous avons également réalisé une étude clinique portant sur l'effet de l'extrait d'écorce de Salix alba sur les cernes. MÉTHODES: Pour confirmer l'effet de l'extrait d'écorce de Salix alba sur la synthèse de l'AH dans les fibroblastes dermiques humains (Human Dermal Fibroblasts, HDF), nous avons réalisé un test ELISA et un test PCR en temps réel. Nous avons étudié l'interaction entre la substance sécrétée par les HDF et l'intégrité vasculaire, et les cellules endothéliales microvasculaires dermiques humaines (Human Dermal Microvascular Endothelial Cells, HDMEC-1) ont été traitées avec un milieu conditionné pour les HDF traité avec ou sans extrait d'écorce de Salix alba. Par la suite, nous avons mené une étude clinique auprès de 29 sujets en leur demandant d'appliquer une crème à base d'extrait d'écorce de Salix alba pendant 8 semaines. RÉSULTATS: Le traitement par extrait d'écorce de Salix alba a augmenté la synthèse de l'AH et régulé les expressions géniques liées à l'acide hyaluronique à haut poids moléculaire dans les HDF. Les milieux conditionnés pour les HDF traités par extrait d'écorce de Salix alba ont atténué la perméabilité endothéliale et ont permis une amélioration de l'intégrité vasculaire des cellules HMEC-1. Le traitement avec la crème contenant 2% d'extrait d'écorce de Salix alba pendant 8 semaines a amélioré les paramètres de mesure des cernes, la microcirculation cutanée et l'élasticité. CONCLUSION: Nos résultats ont montré que l'extrait d'écorce de Salix alba pouvait protéger contre les cernes in vitro, et que le traitement topique par extrait d'écorce de Salix alba améliorait les indices cliniques des cernes dans une étude clinique. L'extrait d'écorce de Salix alba peut donc être utilisé comme principe actif pour améliorer les cernes.

The Alleviating Effect of Lagerstroemia indica Flower Extract on Stretch Marks through Regulation of Mast Cells.

Striae distensae (SD) or stretch marks are common linear scars of atrophic skin with disintegrating extracellular matrix (ECM) structures. Although fibroblasts contribute to the construction of ECM structure in SD, some studies have reported that mast cell degranulation causes the disruption of ECM in early SD lesions. Lagerstroemia indica flower (LIF) has traditionally been used in India as a diuretic. However, little is known about the effect and molecular action of Lagerstroemia indica flower extract (LIFE) on alleviating SD. This study evaluated the effects of LIFE on mast cell degranulation and the synthesis of ECM components in fibroblasts. LIFE inhibits the adhesion of rat basophilic leukemia (RBL) cells, RBL-2H3 on fibronectin (FN) and the expression of integrin, a receptor for FN, thereby reducing focal adhesion kinase (FAK) phosphorylation. In addition, LIFE attenuated the allergen-induced granules and cytokine interleukin 3 (IL-3) through the adhesion with FN. Moreover, the conditioned medium (CM) of activated mast cells decreases the synthesis of ECM components, and LIFE restores the abnormal expressions induced by activated mast cells. These results demonstrate that LIFE suppresses FN-induced mast cell activation and promotes the synthesis of ECM components in fibroblast, which indicates that LIFE may be a useful cosmetic agent for SD treatment.

Evaluating the Sun Protection Factor of Cosmetic Formulations Containing Afzelin.

Exposure to UV radiation damages the skin and increases the risk of skin cancer. Sunscreen is used to protect the skin from the harmful effects of UV radiation. However, the chemical UV filters used in sunscreen can show toxicity and cause allergic reactions. A safe sunscreen that includes a lower content of chemical UV filters and exerts an excellent effect on UV protection needs to be developed. The objective of this study was to investigate whether the addition of afzelin to sunscreen could improve the sun protection factor (SPF). A synergistic effect between afzelin and organic sunscreen agents including padimate O and oxybenzone was confirmed. Interestingly, 100% in vitro SPF-boosting was observed when afzelin (0.05%) was applied with a standard SPF formulation containing organic sunscreens while afzelin alone had no contribution to the SPF. In vivo SPF analysis of the standard SPF formulation showed an SPF value of 13.3 that increased to 20.1 when supplemented with afzelin (0.05%). Additionally, afzelin showed no skin irritation in a human trial. These results suggest that afzelin is useful as a natural additive in sunscreen formulations and provides an SPF-boosting effect. Afzelin supplementation to the formulation showed the potential to reduce the use of synthetic photoprotectors, which could minimize the risk of synthetic agent toxicity.

Isookanin Inhibits PGE2-Mediated Angiogenesis by Inducing Cell Arrest through Inhibiting the Phosphorylation of ERK1/2 and CREB in HMEC-1 Cells.

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts.

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-ß-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.

The Role of Processed Aloe vera Gel in Intestinal Tight Junction: An In Vivo and In Vitro Study.

Leaky gut is a condition of increased paracellular permeability of the intestine due to compromised tight junction barriers. In recent years, this affliction has drawn the attention of scientists from different fields, as a myriad of studies prosecuted it to be the silent culprit of various immune diseases. Due to various controversies surrounding its culpability in the clinic, approaches to leaky gut are restricted in maintaining a healthy lifestyle, avoiding irritating factors, and practicing alternative medicine, including the consumption of supplements. In the current study, we investigate the tight junction-modulating effects of processed Aloe vera gel (PAG), comprising 5-400-kD polysaccharides as the main components. Our results show that oral treatment of 143 mg/kg PAG daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, PAG treatment at dose 400 µg/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients.

Effects of Aloe vera Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies.

Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis. Aloe vera, a miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the Aloe vera flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with Aloe vera flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of Aloe vera flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the Aloe vera flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies.

Anti-Inflammatory Activity and Mechanism of Isookanin, Isolated by Bioassay-Guided Fractionation from Bidens pilosa L.

Bidens pilosa L. (Asteraceae) has been used historically in traditional Asian medicine and is known to have a variety of biological effects. However, the specific active compounds responsible for the individual pharmacological effects of Bidens pilosa L. (B. pilosa) extract have not yet been made clear. This study aimed to investigate the anti-inflammatory phytochemicals obtained from B. pilosa. We isolated a flavonoids-type phytochemical, isookanin, from B. pilosa through bioassay-guided fractionation based on its capacity to inhibit inflammation. Some of isookanin's biological properties have been reported; however, the anti-inflammatory mechanism of isookanin has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of isookanin using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that isookanin reduces the production of proinflammatory mediators (nitric oxide, prostaglandin E2) by inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Isookanin also inhibited the expression of activator protein 1 (AP-1) and downregulated the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun NH2-terminal kinase (JNK) in the MAPK signaling pathway. Additionally, isookanin inhibited proinflammatory cytokines (tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß)) in LPS-induced THP-1 cells. These results demonstrate that isookanin could be a potential therapeutic candidate for inflammatory disease.

The Axin2-snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma.

BACKGROUND: In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC. METHODS: The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo. RESULTS: Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model. CONCLUSIONS: Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.

Correction to: A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic extension of pyogenic liver abscess.

An amendment to this paper has been published and can be accessed via the original article.

A prospective, randomized, multicenter clinical trial comparing 25-gauge and 20-gauge biopsy needles for endoscopic ultrasound-guided sampling of solid pancreatic lesions.

BACKGROUND: Various core biopsy needles have previously been developed for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). However, the properties of needle gauge in the diagnostic outcomes of solid pancreatic lesions remain unknown. This trial compared the procurement rates of histologic cores from solid pancreatic lesions with EUS-FNB using 20- and 25-gauge (G) FNB needles. METHODS: In a prospective randomized multicenter clinical trial, patients with solid pancreatic lesions underwent EUS-FNB with either a 20-gauge or a 25-gauge FNB needle. The rates of histologic core procurement, overall diagnostic accuracy, and adverse events were compared between the two groups (20-gauge or 25-gauge FNB needle). RESULTS: In total, 88 patients (48 men, 40 women, mean age 65.7 years) were enrolled. No significant differences were found in the demographic characteristics between the two groups (20-gauge or 25-gauge FNB needle). The procurement rate of histologic cores in the 20-guage FNB needle group (41/45, 91.1%) was significantly higher than that in the 25-guage FNB needle group (32/43, 74.4%, P = 0.037). However, no significant differences were found in the overall diagnostic accuracy between 20-guage FNB needle (40/45, 88.9%) and 25-guage FNB needle (34/43, 79.1%, P = 0.208). No procedure-related adverse events were observed in either group. CONCLUSIONS: Although both FNB needles provided high overall diagnostic accuracy, the reliability of the 20-guage FNB needle is better than the 25-guage FNB needle when retrieving samples for histological analysis.

TGF-ß Pathway in Salivary Gland Fibrosis.

Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-ß) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-ß superfamily members, TGF-ß1 and 2 are pro-fibrotic ligands, whereas TGF-ß3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-ß1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren's syndrome. Potential therapeutic strategies that target multiple levels in the TGF-ß pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-ß signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

Coptis chinensis Franch Directly Inhibits Proteolytic Activation of Kallikrein 5 and Cathelicidin Associated with Rosacea in Epidermal Keratinocytes.

Rosacea is a common and chronic inflammatory skin disease that is characterized by dysfunction of the immune and vascular system. The excessive production and activation of kallikerin 5 (KLK5) and cathelicidin have been implicated in the pathogenesis of rosacea. Coptis chinensis Franch (CC) has been used as a medicinal herb in traditional oriental medicine. However, little is known about the efficacy and mechanism of action of CC in rosacea. In this study, we evaluate the effect of CC and its molecular mechanism on rosacea in human epidermal keratinocytes. CC has the capacity to downregulate the expression of KLK5 and cathelicidin, and also inhibits KLK5 protease activity, which leads to reduced processing of inactive cathelicidin into active LL-37. It was determined that CC ameliorates the expression of pro-inflammatory cytokines through the inhibition of LL-37 processing. In addition, it was confirmed that chitin, an exoskeleton of Demodex mites, mediates an immune response through TLR2 activation, and CC inhibits TLR2 expression and downstream signal transduction. Furthermore, CC was shown to inhibit the proliferation of human microvascular endothelial cells induced by LL-37, the cause of erythematous rosacea. These results demonstrate that CC improved rosacea by regulating the immune response and angiogenesis, and revealed its mechanism of action, indicating that CC may be a useful therapeutic agent for rosacea.

Inclusion complexes of cysteinyl ß-cyclodextrin with baicalein restore collagen synthesis in fibroblast cells following ultraviolet exposure.

Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl ß-cyclodextrin (ß-CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl ß-CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV-exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized ß-CDs were found to promote baicalein-induced collagen synthesis. Inclusion complexes of cysteinyl ß-CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl ß-CDs with baicalein also downregulated matrix metalloproteinase -1 and -3, and α-smooth muscle actin expression. In addition, inclusion complexes of cysteinyl ß-CDs with baicalein attenuated the expression of caveolin-1, but this treatment enhanced the UV-induced phosphorylation of Smad in the transforming growth factor-ß pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.

nc886, a non-coding RNA, inhibits UVB-induced MMP-9 and COX-2 expression via the PKR pathway in human keratinocytes.

nc886, a long non-coding RNA (ncRNA) of 101 nucleotides in length, is known as a vault RNA or microRNA precursor. Despite the recent discovery that ncRNAs in the nucleus play a crucial role in regulating chromosomal transformation and transcription, only a few studies have focused on the function of ncRNAs in the cytoplasm, such as nc886. Several studies have investigated the function of nc886 as a suppressor of carcinogenesis and inflammation in different cancer cell types; however, its role in the skin has yet to be clearly elucidated. The two RNA binding sites for protein kinase RNA-activated (PKR) are located in the central region of the stable structure of nc886, which competes with other double-stranded RNA species. Successful binding results in decreased PKR activity. Among changes in skin cells induced by ultraviolet B (UVB) radiation, nc886 expression decreases, whereas PKR phosphorylation via mitogen-activated protein kinases (MAPKs) increases. Reduced nc886 expression leads to uncontrolled PKR activity and increases in the expression of inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), type IV collagenase, and cyclooxygenase (COX-2), which ultimately accelerate inflammatory responses and skin aging. The present study investigated the regulatory mechanism associated with PKR activity and nc886-PKR binding in skin cell aging and inflammation. These results suggest a role for nc886 in controlling photoaging and inflammation in skin cells.

Ga-Doped Pt-Ni Octahedral Nanoparticles as a Highly Active and Durable Electrocatalyst for Oxygen Reduction Reaction.

Bimetallic PtNi nanoparticles have been considered as a promising electrocatalyst for oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells (PEMFCs) owing to their high catalytic activity. However, under typical fuel cell operating conditions, Ni atoms easily dissolve into the electrolyte, resulting in degradation of the catalyst and the membrane-electrode assembly (MEA). Here, we report gallium-doped PtNi octahedral nanoparticles on a carbon support (Ga-PtNi/C). The Ga-PtNi/C shows high ORR activity, marking an 11.7-fold improvement in the mass activity (1.24 A mgPt-1) and a 17.3-fold improvement in the specific activity (2.53 mA cm-2) compared to the commercial Pt/C (0.106 A mgPt-1 and 0.146 mA cm-2). Density functional theory calculations demonstrate that addition of Ga to octahedral PtNi can cause an increase in the oxygen intermediate binding energy, leading to the enhanced catalytic activity toward ORR. In a voltage-cycling test, the Ga-PtNi/C exhibits superior stability to PtNi/C and the commercial Pt/C, maintaining the initial Ni concentration and octahedral shape of the nanoparticles. Single cell using the Ga-PtNi/C exhibits higher initial performance and durability than those using the PtNi/C and the commercial Pt/C. The majority of the Ga-PtNi nanoparticles well maintain the octahedral shape without agglomeration after the single cell durability test (30,000 cycles). This work demonstrates that the octahedral Ga-PtNi/C can be utilized as a highly active and durable ORR catalyst in practical fuel cell applications.