bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK inhibition with tofacitinib suppresses arthritic joint structural damage through decreased RANKL production
Authors: LaBranche Timothy P. , Jesson Michael I. , Radi Zaher A. , Storer Chad E. , Guzova Julia A. , Bonar Sheri L. , Thompson Janice M. , Happa Fernando A. , Stewart Zachary S. , Zhan Yutian , Bollinger Chris S. , Bansal Prashant N. , Wellen Jeremy W. , Wilkie Dean P. , Bailey Steven A. , Symanowicz Peter T. , Hegen Martin , Head Richard D. , Kishore Nandini , Mbalaviele Gabriel , Meyer Debra M. 
Published: August 2012

AbstractObjectiveThe mechanistic link between Janus kinase (JAK) signaling and structural damage to arthritic joints in rheumatoid arthritis (RA) is poorly understood. This study was undertaken to investigate how selective inhibition of JAK with tofacitinib (CP‐690,550) affects osteoclast‐mediated bone resorption in a rat adjuvant‐induced arthritis (AIA) model, as well as human T lymphocyte RANKL production and human osteoclast differentiation and function.MethodsHind paw edema, inflammatory cell infiltration, and osteoclast‐mediated bone resorption in rat AIA were assessed using plethysmography, histopathologic analysis, and immunohistochemistry; plasma and hind paw tissue levels of cytokines and chemokines (including RANKL) were also assessed. In vitro RANKL production by activated human T lymphocytes was evaluated by immunoassay, while human osteoclast differentiation and function were assessed via quantitative tartrate‐resistant acid phosphatase staining and degradation of human bone collagen, respectively.ResultsEdema, inflammation, and osteoclast‐mediated bone resorption in rats with AIA were dramatically reduced after 7 days of treatment with the JAK inhibitor, which correlated with reduced numbers of CD68/ED‐1+, CD3+, and RANKL+ cells in the paws; interleukin‐6 (transcript and protein) levels were rapidly reduced in paw tissue within 4 hours of the first dose, whereas it took 4–7 days of therapy for RANKL levels to decrease. Tofacitinib did not impact human osteoclast differentiation or function, but did decrease human T lymphocyte RANKL production in a concentration‐dependent manner.ConclusionThese results suggest that the JAK inhibitor tofacitinib suppresses osteoclast‐mediated structural damage to arthritic joints, and this effect is secondary to decreased RANKL production.
A novel patchwork model used in lecture and laboratory to teach the three‐dimensional organization of mesenteries
Authors: Noël Geoffroy P.J.C. 
Published: August 2012

AbstractAnatomy teaching is seeing a decline in both lecture and laboratory hours across many medical schools in North America. New strategies are therefore needed to not only make anatomy teaching more clinically integrated, but also to implement new interactive teaching techniques to help students more efficiently grasp the complex organization of the human body. Among the difficult anatomical concepts that students struggle to understand, the anatomy of the peritoneal cavity with its complex projections of peritoneum could benefit strongly from new learning aids. In this report, an innovative teaching tool is presented to engage students during both lecture and laboratory, and help them build three‐dimensional (3D) mental maps of peritoneal cavity. The model consists of a patchwork of mesenteries and gut made from colored cloth stitched together onto a T‐shirt to denote the origin and outflow of each peritoneum projection. As the lecturer wears the life‐size model, the students can appreciate the 3D organization of the peritoneal cavity on a living body. In addition, the T‐shirt model can be used in parallel with dissection to ensure a strong reinforcement of the spatial understanding of the peritoneal cavity. Anat Sci Educ. © 2012 American Association of Anatomists.
In vitro and in vivo evaluation of a primaquine prodrug without red blood cell membrane destabilization property
Authors: Davanço Marcelo Gomes , Campos Michel Leandro , Nogueira Marco Antonio , Campos Silvio Lopes , Marques Ricardo Vian , dos Santos Jean Leandro , Chin Chung Man , da Fonseca Luiz Marcos , Peccinini Rosângela Gonçalves 
Published: August 2012

ABSTRACTPrimaquine is an important therapeutic resource for malaria treatment and it has wide activity against several pathogens. The haematotoxicity of primaquine is the major problem for its therapeutic application. This effect is aggravated by repeated use at high doses and by the wide fluctuation of plasma levels after administration. The primaquine prodrug (Phe‐Ala‐PQ) was planned in order to modify the pharmacokinetics and toxicity of primaquine. The in vitro conversion of Phe‐Ala‐PQ to primaquine, and the primaquine pharmacokinetics were evaluated in four groups of rats: two groups that received a single dose of Phe‐Ala‐PQ, one by intravenous and the other by gavage route, and two other groups that received primaquine diphosphate, by intravenous and gavage routes. In addition, the erythrocyte osmotic fragility was compared in two groups of rats that received multiple doses of primaquine diphosphate or Phe‐Ala‐PQ, as a parameter of haematotoxicity. The in vitro conversion of Phe‐Ala‐PQ to primaquine by plasma enzyme action was observed. The pharmacokinetic profile of primaquine from Phe‐Ala‐PQ was more favourable due to the lower fluctuation of plasma concentrations. Haematotoxicity was not evidenced in the prodrug administration. The results reinforce the need for further studies with this prodrug, promising an alternative in the therapeutic use of primaquine. Copyright © 2012 John Wiley & Sons, Ltd.
Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5
Authors: Arakawa Hiroshi , Shirasaka Yoshiyuki , Haga Makoto , Nakanishi Takeo , Tamai Ikumi 
Published: August 2012

ABSTRACTFluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier‐mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco‐2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8‐benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P‐glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5‐mediated uptake of ciprofloxacin was saturable with a Km value of 140 µm, and naringin inhibited the uptake with an IC50 value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal‐to‐serosal side, with an IC50 value of 7.5 µm by the Ussing‐type chamber method. The estimated IC50 values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P‐gp and Bcrp. Copyright © 2012 John Wiley & Sons, Ltd.
Recovery of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) from Ralstonia eutropha cultures with non‐halogenated solvents
Authors: Riedel Sebastian L. , Brigham Christopher J. , Budde Charles F. , Bader Johannes , Rha ChoKyun , Stahl Ulf , Sinskey Anthony J. 
Published: August 2012

AbstractReduced downstream costs, together with high purity recovery of polyhydroxyalkanoate (PHA), will accelerate the commercialization of high quality PHA‐based products. In this work, a process was designed for effective recovery of the copolymer poly(hydroxybutyrate‐co‐hydroxyhexanoate) (P(HB‐co‐HHx)) containing high levels of HHx (>15 mol%) from Ralstonia eutropha biomass using non‐halogenated solvents. Several non‐halogenated solvents (methyl isobutyl ketone, methyl ethyl ketone, and butyl acetate and ethyl acetate) were found to effectively dissolve the polymer. Isoamyl alcohol was found to be not suitable for extraction of polymer. All PHA extractions were performed from both dry and wet cells at volumes ranging from 2 mL to 3 L using a PHA to solvent ratio of 2% (w/v). Ethyl acetate showed both high recovery levels and high product purities (up to 99%) when using dry cells as starting material. Recovery from wet cells, however, eliminates a biomass drying step during the downstream process, potentially saving time and cost. When wet cells were used, methyl isobutyl ketone (MIBK) was shown to be the most favorable solvent for PHA recovery. Purities of up to 99% and total recovery yields of up to 84% from wet cells were reached. During polymer recovery with either MIBK or butyl acetate, fractionation of the extracted PHA occurred, based on the HHx content of the polymer. PHA with higher HHx content (17–30 mol%) remained completely in solution, while polymer with a lower HHx content (11–16 mol%) formed a gel‐like phase. All PHA in solution could be precipitated by addition of threefold volumes of n‐hexane or n‐heptane to unfiltered PHA solutions. Effective recycling of the solvents in this system is predicted due to the large differences in the boiling points between solvent and precipitant. Our findings show that two non‐halogenated solvents are good candidates to replace halogenated solvents like chloroform for recovery of high quality PHA. Biotechnol. Bioeng. 2013; 110: 461–470. © 2012 Wiley Periodicals, Inc.
Chemical Constituents of Saniculiphyllum guangxiense
Authors: Geng Chang‐An , Huang Xiao‐Yan , Lei Li‐Gong , Zhang Xue‐Mei , Chen Ji‐Jun 
Published: August 2012

AbstractThe first phytochemical investigation on Saniculiphyllum guangxiense resulted in the isolation of two new triterpenoids, 16β‐hydroxybryodulcosigenin (3) and 3α‐O‐feruloylolean‐12‐en‐27‐oic acid (6), together with six known compounds, menisdaurin (1), purshianin (2), oleanolic acid (4), 3β‐hydroxyolean‐12‐en‐27‐oic acid (5), β‐sitosterol (7), and daucosterol (8), which were characterized by extensive spectroscopic analyses and in one case by X‐ray diffraction. According to this primary investigation, S. guangxiense is rich in nitrile glucosides and triterpenoids, of which menisdaurin (1; 0.06%) and purshianin (2; 0.015%) are the main constituents. Compounds 1–6 were assayed for their anti‐hepatitis B virus (HBV) activities against the secretion of HBsAg and HBeAg, as well as HBV DNA replication on Hep G 2.2.15 cell line in vitro. The most active compound, menisdaurin (1), inhibits HBV DNA replication with an IC50 value of 0.32 mM (SI>11.97).
Essential Oil of Azorella cryptantha Collected in Two Different Locations from San Juan Province, Argentina: Chemical Variability and Anti‐Insect and Antimicrobial Activities
Authors: López Sandra , Lima Beatriz , Aragón Liliana , Espinar Luis Ariza , Tapia Alejandro , Zacchino Susana , Zygadlo Julio , Feresin Gabriela Egly , López María Liza 
Published: August 2012

AbstractThe essential oils (EOs) of two populations of Azorella cryptantha (Clos) Reiche, a native species from San Juan Province, were obtained by hydrodistillation in a Clevenger‐type apparatus and characterized by GC‐FID and GC/MS analyses. The compounds identified amounted to 92.3 and 88.7% of the total oil composition for A. cryptantha from Bauchaceta (Ac‐BAU) and Agua Negra (Ac‐AN), respectively. The EO composition for the two populations was similar, although with differences in the identity and content of the main compounds and also in the identity of minor components. The main compounds of the Ac‐BAU EO were α‐pinene, α‐thujene, sabinene, δ‐cadinene, δ‐cadinol, trans‐β‐guaiene, and τ‐muurolol, while α‐pinene, α‐thujene, β‐pinene, γ‐cadinene, τ‐cadinol, δ‐cadinene, τ‐muurolol, and a not identified compound were the main constituents of the Ac‐AN EO, which also contained 3.0% of oxygenated monoterpenes. The repellent activity on Triatoma infestans nymphs was 100 and 92% for the Ac‐AN and Ac‐BAU EOs, respectively. Regarding the toxic effects on Ceratitis capitata, the EOs were very active with LD50 values lower than 11 μg/fly. The dermatophytes Microsporum gypseum, Trichophyton rubrum, and T. mentagrophytes and the bacterial strains Escherichia coli LM1, E. coli LM2, and Yersinia enterocolitica PI were more sensitive toward the Ac‐AN EO (MIC 125 μg/ml) than toward the Ac‐BAU EO. This is the first report on the composition of A. cryptantha EO and its anti‐insect and antimicrobial properties.
Chemical Properties and Antioxidant and Antimicrobial Activities of Slovenian Propolis
Authors: Mavri Ana , Abramovič Helena , Polak Tomaž , Bertoncelj Jasna , Jamnik Polona , Smole Možina Sonja , Jeršek Barbara 
Published: August 2012

AbstractThe chemical composition as well as the antioxidant and antimicrobial activities of two EtOH extracts of propolis (PEEs) from Slovenia were determined. EtOH was used as extracting solvent at 70 and 96%, providing the extracts PEE70 and PEE96, respectively. The extraction with 70% EtOH was more efficient than that with 96% EtOH, as the PEE70 was richer in total phenolic compounds than the PEE96. The Slovenian propolis was characterized by different phenolic acids and flavonoids. The PEE96 was slightly richer in three specific compounds, i.e., caffeic acid, ferulic acid, and luteolin, while all other substances detected showed higher contents in the PEE70. The PEE70 showed a stronger reducing power and ability to scavenge free radicals and metal ions than the PEE96. Both PEEs were in the main more effective against Gram‐positive bacteria than against fungi and Gram‐negative bacteria like Salmonella and Escherichia coli, with the exception of Campylobacter. The PEE96 decreased the intracellular oxidation in Saccharomyces cerevisiae in a dose‐dependent manner. The antimicrobial activities and antioxidant properties were related to the total phenolic contents. The two PEEs have the potential for use as natural antimicrobial and antioxidant additives in foods.
Essential Oils of Three Taxa of the Nepeta argolica Aggregate from Greece
Authors: Hanlidou Effie , Karousou Regina , Lazari Diamanto 
Published: August 2012

AbstractThe essential‐oil composition of three not previously studied taxa belonging to the Nepeta argolica aggregate was examined. The oils of N. argolica ssp. malacotrichos and N. argolica ssp. vourinensis (both Greek endemics) are rich in 1,8‐cineole (30.9–55.6% of the total oil composition), while those of the Balkan endemic N. spruneri are rich in either sesquiterpenes (mainly caryophyllene oxide, 14.6–19.8%) or in 4aα,7α,7aβ‐ and 4aα,7α,7aα‐nepetalactones (total content 17.5–40.5%), accompanied by caryophyllene oxide (11.5–11.7%) and 1,8‐cineole (up to 16.5%). The comparison of our results with published information concerning the related taxa of the N. argolica aggregate showed that while oils with as main components nepetalactones or 1,8‐cineole are common, sesquiterpene‐rich oils are reported for the first time within the aggregate.
Isolation and Characterization of Two Novel Antibacterial Cyclic Hexapeptides from Streptomyces alboflavus 313
Authors: Ji Zhiqin , Qiao Gang , Wei Shaopeng , Fan Lixia , Wu Wenjun 
Published: August 2012

AbstractTwo novel cyclic hexapeptides, designated NW‐G08 (1) and NW‐G09 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their structures were elucidated on the basis of extensive spectroscopic analysis, MS experiments, and chemical analysis. Their antibacterial activities against several strains of bacteria were evaluated by micro‐broth dilution method. NW‐G08 (1) and NW‐G09 (2) were highly antibacterial against Gram‐positive but not active against Gram‐negative bactaria. The minimum inhibitory concentrations (MICs) of 1 against Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus were 6.25, 6.25, and 1.56 μg/ml, respectively. It is worth noting that 1 and 2 exhibited much higher activities against methicillin‐resistant Staphylococcus aureus (MRSA) than ampicillin, which implies that they might be potential candidates for the development of novel drugs against resistant pathogenic bacteria.
Studies on Chemical Structure Modification and StructureActivity Relationship of Derivatives of Gambogic Acid at C(39)
Authors: Sun Hao‐Peng , Liu Zong‐Liang , Xue Xin , Gao Yuan , Zhang Lei , Wang Jin‐Xin , Guo Qing‐Long , You Qi‐Dong 
Published: August 2012

AbstractThe natural product gambogic acid exhibits high potency in inhibiting cancer cell lines. Rational medicinal modifications on gambogic acid will improve its physicochemical properties and drug‐like characters. To investigate the structureactivity relationship of gambogic acid and also to find rational modification position on its chemical skeleton, we designed, synthesized, and characterized 16 derivatives of gambogic acid that were modified at C(39). The structureactivity relationships (SARs) were discussed. The anti‐proliferation data were accquired through MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assays of A549, BGC823, U251, HepG2, and MDA‐MB‐231 cancer cell lines. Most of the synthesized compounds showed strong inhibitory effects. The SAR study revealed that derivatives with aliphatic amino moieties at C(39) were more potent than those with other substituents. The C(39) position can undergo different kinds of chemical modifications without leading to loss of activity. Compounds 4 and 6 can serve as potential lead compounds for further development of new anticancer drugs.
Fatty‐Acid Profile of Total and Polar Lipids in Cultured Rainbow Trout (Oncorhynchus mykiss) Raised in Freshwater and Seawater (Croatia) Determined by Transmethylation Method
Authors: Staver Mladenka Malenica , Jerković Igor , Giacometti Jasminka , Malenica Ante , Marijanović Zvonimir 
Published: August 2012

AbstractFatty acids from total lipids and polar lipids in cultured rainbow trout (Oncorhynchus mykiss) raised in seawater (SW) and freshwater (FW) were identified and quantified from the muscle samples in January, April, and July. The highest total lipid and polar lipid amounts were found in April. July contents of total lipids were low, but percent of the polyunsaturated fatty acids (PUFAs) was high in SW and FW environment (particularly n‐3 PUFAs). Variety of 17 fatty acids was identified by GC‐FID after transmethylation. The predominant fatty acids in rainbow trout from SW and FW were: docosahexaenoic acid among n‐3 PUFAs, palmitic acid among saturated fatty acids (SFAs), and oleic acid among monounsaturated fatty acids (MUFAs). Appreciably higher n‐3/n‐6 ratio was found in total lipids in April (6.40, FW fish) and in polar lipids in July (18.76; SW fish). High n‐3/n‐6 ratio in total lipids and polar lipids of rainbow trout from SW and FW, besides beneficial n‐3/n‐6 ratio in the commercial fish food, could be characteristic for the local environmental conditions (Croatia).
Melanogenesis‐Inhibitory and Cytotoxic Activities of Diarylheptanoids from Acer nikoense Bark and Their Derivatives
Authors: Akihisa Toshihiro , Takeda Ayano , Akazawa Hiroyuki , Kikuchi Takashi , Yokokawa Satoru , Ukiya Motohiko , Fukatsu Makoto , Watanabe Kensuke 
Published: August 2012

AbstractNine cyclic diarylheptanoids, 1–9, including two new compounds, i.e., 9‐oxoacerogenin A (8) and 9‐O‐β‐D‐glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10–12, and four phenolic compounds, 13–16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D‐glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)‐acerogenin B (5), were converted to their ether and ester derivatives, 18–24 and 27–33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1–16 and 18–35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2–4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24–61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88–106% of cell viability at 100 μM). In addition, when compounds 1–16 and 18–35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18–22 and 27–31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC50 8.1–19.3 μM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC50 10.1–18.4 μM).
Melanogenesis Inhibitory Activity of Monoterpene Glycosides from Gardeniae Fructus
Authors: Akihisa Toshihiro , Watanabe Kensuke , Yamamoto Ayako , Zhang Jie , Matsumoto Masahiro , Fukatsu Makoto 
Published: August 2012

AbstractA new iridoid glycoside, 10‐O‐(4″‐O‐methylsuccinoyl)geniposide (7), and two new pyronane glycosides, jasminosides Q and R (13 and 14, resp.), along with nine known iridoid glycosides, 1–6 and 8–10, and two known pyronane glycosides, 11 and 12, were isolated from a MeOH extract of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides (Rubiaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1–14 on the melanogenesis in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), three compounds, i.e., 6‐O‐p‐coumaroylgeniposide (3), 7, and 6′‐O‐sinapoyljasminoside (12), exhibited inhibitory effects with 21.6–41.0 and 37.5–47.7% reduction of melanin content at 30 and 50 μM, respectively, with almost no toxicity to the cells (83.7–106.1% of cell viability at 50 μM).
Diversity of Unavailable Polysaccharides and Dietary Fiber in Domesticated Nopalito and Cactus Pear Fruit (Opuntia spp.)
Authors: Peña‐Valdivia Cecilia Beatriz , Trejo Carlos , Arroyo‐Peña V. Baruch , Sánchez Urdaneta Adriana Beatriz , Balois Morales Rosendo 
Published: August 2012

AbstractThe aim of this study was to quantify mucilages, pectins, hemicelluloses, and cellulose of nopalitos (edible, as vegetable, young cladodes of flat‐stemmed spiny cacti) of most consumed Mexican cultivars, and sweet and acid cactus pear fruits of Opuntia spp. The hypothesis is that, regardless of their unavailable polysaccharides diversity, nopalitos and cactus pear fruits are rich sources of soluble and insoluble dietary fiber. Twelve cultivars of Opuntia spp. were used. Nopalitos had a significant variation in structural polysaccharides among the cultivars: mucilages (from 3.8 to 8.6% dry matter (DM)) averaged near a half of pectins content (from 6.1 to 14.2% DM) and tightly bound hemicelluloses (from 2.2 to 4.7% DM), which were the less abundant polysaccharides, amounted 50% of the loosely bound hemicelluloses (from 4.3 to 10.7% DM). Acid fruits (or ‘xoconostle’) had significantly higher unavailable polysaccharides content than sweet fruit, and contain similar proportions than nopalitos. Unavailable polysaccharides represent a high proportion of dry tissues of nopalitos and cactus pear fruits, composition of both of these soluble and insoluble polysaccharides (total dietary fiber) widely vary among cultivars without an evident pattern. Nopalitos and cactus pear fruit can be considered an excellent source of dietary fiber.