Tetraglochin andina Ciald.: A medicinal plant from the Argentinean highlands with potential use in vaginal candidiasis

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): María Alejandra Moreno, Susana Córdoba, Iris Catiana Zampini, María Inés Mercado, Graciela Ponessa, María Rosa Alberto, M.E. Fatima Nader-Macias, Jorge Sayago, Alberto Burgos-Edwards, Guillermo Schmeda-Hirschmann, María Inés Isla
Ethnopharmacological relevanceThe Argentinean medicinal plant Tetraglochin andina Ciald, formerly classified as T. cristatum (Britton) Rothm is used in traditional medicine by inhabitants from Argentinean northwestern highlands (Puna) to treat candidiasis and as anti-inflammatory.Aim of the studyTo assess the potential of the crude drug as an anti-Candida agent with anti-inflammatory properties. The bioactivity and phytochemical composition of a dry extract of the plant was investigated.Material and methodsThe pharmacognostic description of the crude drug is carried out for the first time, including macroscopic and microscopic examinations of the different organs, physicochemical and extractive values (petroleum ether-, ethanol- and water-soluble). The dry extract from T. andina was evaluated as antifungal against pathogenic Candida sp. and Saccharomyces cerevisiae isolated from vaginal infections and reference strains, by the macrodilution and microdilution assays. The normal vaginal microbiome in women is characterized by the dominance of lactic acid-producing bacteria, mainly Lactobacillus spp. The effect of T. andina extract on Lactobacillus strains was also assayed. The inhibitory effect on proinflammatory enzymes (cyclooxygenase, lipoxygenase and phospholipase A2) and antioxidant capacity was studied. The chemical profile was analyzed by HPLC-ESI-MS.ResultsThe hydroalcoholic extract inhibited the growth of all yeasts with Minimal Inhibitory Concentration (MIC) values between 12.5 and 400 µg GAE/mL and the MIC values on Lactobacillus were higher than the MIC values against Candida isolates ( > 400 µg GAE/mL). These results indicate that the hydroalcoholic extract could be used without affecting the normal microbiota of vaginal fluid. The extract showed antioxidant activity and could modulate the inflammatory process by three pathways (sPLA2, COX-2, LOX). The plant extract contained high total phenolic levels (386.9±1.7 mg GAE/g dry extract) and flavonoid levels (260.4±2.7 mg GAE/g dry extract). Fifty phenolic compounds were identified by HPLC-ESI-MS. They were mainly hydrolysable and condensed tannins. The dry extract was chemically and biologically stable during one year at room temperature or 4 °C.ConclusionsThe presence of anti-Candida and anti-inflammatory activities in Tetraglochin andina extracts give support to their traditional use for treating conditions associated with microorganism infections and inflammatory process in humans. This plant preparation could be used to design phytopharmaceutical preparations to inhibit yeast growth and moderate the inflammatory and oxidative process.

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Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): Hee-Seon Park, Charith U.B. Wijerathne, Hye-Yun Jeong, Chang-Seob Seo, Hyekyung Ha, Hyo-Jung Kwun
Ethnopharmacological relevanceHelicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis.Aim of the studyThe emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model.Materials and methodsH. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis.ResultsOur in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1β, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB).ConclusionsOur findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.

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Ethnomedical uses and pharmacological activities of most prevalent species of genus Piper in Panama: A review

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Armando A. Durant-Archibold, Ana I. Santana, Mahabir P. Gupta
Ethnopharmacological relevancePiperaceae is the fifth largest family of plants in Panama. This review focuses on the ethnomedical uses of the most prevalent Panamanian species and biological activities of their extracts and/or constituents both in Panama and worldwide. Many species have a plethora of ethnomedical uses such as antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic, anti-Helicobacter pylori, antiulcer, antiprotozoal, estrogenic, insecticidal, local anesthetic, diuretic, and for women's health conditions.Aim of the reviewThe aim of this review is to compile all ethnomedical uses of most prevalent species of Piper in Panama, and their extracts or phytoconstituents worldwide, through a complete literature search, so that it may allow selection of potential unexplored Piper species for future research and development of phytotherapeuticals for important ailments.MethodologyThis review conducted a thorough search in books and databases such as Google Scholar, PubMed, Sci-Finder, Scopus, ACS publications, Science Direct, and Reaxys (Elsevier), until October of 2017. The information provided in this review is based on peer-reviewed papers only in English. The key words used to search were: "Piper", "Piperaceae", "Panama", "Pharmacological activity", "Chemistry," "Toxicity," and "Clinical studies". Scientific names of the plants were validated through www.tropicos.org. Potential full-texts of eligible papers, irrespective of database, were identified. Study selection and data extraction were conducted by one author (AIS) and confirmed by others (MPG, ADA). The extracted data were summarized in tabular form and a narrative description was used to provide a summary of updated information.ResultsThe ethnomedical uses of most prevalent 23 Panamanian species of Piper both in Panama as well in the world are provided. Of these species only Piper arboreum, Piper auritum, Piper cordulatum, Piper hispidum, Piper dariense, Piper multiplinervium and Piper umbellatum have ethnomedical uses in Panama. Some of the uses are by native Amerindians of Panama. These include ailments such as liver pains, common colds, skin infections, insecticidal, as a bath to alleviate colds, snakebites, different types of pains, skin ailments, wound healing, rheumatism, women's health, antipyretic, and anti-inflammatory. Other Panamanian species are widely used in many countries of the world. Of all the Piper species, P. aduncum has the most ethnomedical uses. Panamanian uses are different from the ones in other countries. A total of 61 compounds present in Piper species reported in this review have shown a variety of biological activities in vitro. These compounds belong to different chemical types, such as chromenes, amides, alkaloids, benzopyrans, benzoates, essential oils, pyrrolidines, flavokaines, chalcones, methylenedioxy propiophenones, cinnamates, monoterpenes, sesquiterpenes, phenols, among others. From this review it is evident that extracts and pure compounds isolated from Piper species have shown a wide array of mainly in vitro activity and some ethnomedical uses may be correlated with their activities reported.ConclusionsPlants of this genus have provided bioactive species, both from crude extracts and pure compounds thus substantiating their efficacy in traditional medicine. In vivo and toxicological studies are still limited, but the results of different activities of Piper reported point out the great potential of these species for obtaining bioactive principles that may be useful in treating diseases. However, a thorough investigation of Piper species relating to chemistry, in vivo pharmacological activities, with emphasis on their mechanism of action, safety and efficacy and toxicity is warranted.



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Suppression of lung inflammation by the methanol extract of Spilanthes acmella Murray is related to differential regulation of NF-κB and Nrf2

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Kyun Ha Kim, Eun Jung Kim, Min Jung Kwun, Ji Yeon Lee, Tran The Bach, Sang Mi Eum, Jun Yong Choi, Sayeon Cho, Sang-Jun Kim, Seung-Il Jeong, Myungsoo Joo
Ethnopharmacological relevanceAlthough Spilanthes acmella has been used to relieve inflammation, fever, pain, or infection in traditional Asian medicine, experimental evidence supporting these functions is scarce. Here, we examined an anti-inflammatory function and a possible underlying mechanism of S. acmella Murray (SAM).Materials and methodThe methanol extract of SAM was fingerprinted by HPLC. C57BL/6 mice were administered with a single intratracheal (i.t.) LPS and 2 h later with a single i.t. SAM. The effect of SAM on lung inflammation was assessed by histology, semi-quantitative RT-PCR, and MPO assay of lung tissue. The effects of SAM on a pro-inflammatory factor NF-κB and an anti-inflammatory factor Nrf2 were analyzed by immunoblotting of nuclear proteins and by semi-quantitative RT-PCR analysis of mRNA of the genes governed by these transcription factors. V5-Nrf2 was precipitated by an anti-V5 antibody and the ubiquitinated V5-Nrf2 was revealed by immunoblotting of HA-tagged ubiquitin.ResultsThe i.t. SAM robustly diminished a neutrophilic lung inflammation induced by i.t. LPS treatment of mice. In RAW 264.7 cells, SAM suppressed the nuclear localization of NF-κB and the expression of NF-κB-dependent cytokine genes. SAM increased the level of Nrf2 in the nucleus and the expression of Nrf2-dependent genes while suppressing ubiquitination of Nrf2.ConclusionOur results suggest that SAM can suppress a neutrophilic inflammation in mouse lungs, which is associated with suppressed NF-κB and activated Nrf2. Our results provide experimental evidence supporting the anti-inflammatory function of S. acmella.

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Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide-induced animal model of Alzheimer's disease

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Yunlong Wang, Mengshi Wang, Kaiyue Fan, Tongde Li, Tingxu Yan, Bo Wu, Kaishun Bi, Ying Jia
Ethnopharmacological relevanceAlpinae Oxyphyllae Fructus (AOF) with warming and tonifying the kidney and spleen, anti-salivation, anti-polyuria and anti-diarrhea functions is the dried ripe fruits of Alpinia oxyphylla Miq. (Zingiberaceae). As a traditional Chinese medicine, its application history is very long.Aims of the studyThe purpose of our study is to investigate the effects of different solvent extracts from AOF on lipopolysaccharide (LPS)-induced animal model of Alzheimer's disease (AD) to elucidate the traditional medical theories with modern pharmacological methods and provide a reference for further clarifying its active components and mechanisms.Materials and methodsThe method of stepwise screening was adopted in this paper. The animals were divided into 9 groups, including control (CT) group, model (MD) group, donepezil (DPZ) group, total extract (TT) group, petroleum ether extract (PE) group, chloroform extract (CF) group, ethyl acetate extract (EA) group, n-butanol extract (NB) group and water extract (WT) group. The anti-amnesic effects of different solvent extracts from AOF were measured in LPS-induced memory deficits mice by Y maze test and Morris water maze (MWM) test. Hematoxylin eosin (HE) staining was applied to observe pathological changes in hippocampus and cerebral cortex tissue of different groups. Biochemical indicators including ionized calcium-binding adaptor molecule 1 (IBA-1), interleukin beta 1 (IL-1β), Aβ1–42 and hyperphosphorylated tau proteins (p-tau) in hippocampus and cortex after treatment with LPS were measured according to the manufacturer's instructions of ELISA kits. HPLC was used to evaluate the major components of different extracts.ResultsIt was found that successive intragastric administration of AOF (360 mg/kg) extracts for 14 days showed different degrees of improvement on LPS-induced AD model as measured by Y-maze test, Morris water maze test, and Histopathological examination. Moreover, the results of ELISA suggested petroleum ether (PE) extracts were worth recommending for inhibiting the high level of IBA-1, IL-1β, Aβ1–42 and p-tau in hippocampus and cortex after treatment with LPS.ConclusionsThe present study demonstrated for the first time that AOF attenuated LPS-induced learning and memory impairment, which may be associated with its inhibitory effect on neuroinflammation, amyloids-β (Aβ) deposition and p-tau. This research provided a theoretical basis for elucidating the traditional theory of AOF, and was also the stepping stone to the next step.

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Understanding cancer and its treatment in Thai traditional medicine: An ethnopharmacological-anthropological investigation

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): Natchagorn Lumlerdkij, Jaturapat Tantiwongse, Suksalin Booranasubkajorn, Ranida Boonrak, Pravit Akarasereenont, Tawee Laohapand, Michael Heinrich
Ethnopharmacological relevanceThai traditional medicine (TTM) is widely practiced in Thailand and continues to gain importance in cancer management, but little is known about the TTM practitioners' emic concepts and practice.Aim of the studyWith this study we firstly aim to document the practice of cancer treatment and prevention by TTM practitioners and, secondly, to evaluate how such traditional concepts and practices are correlated with biomedical ones. This in turn can form the basis for developing novel strategies for designing pharmacological experiments and longer term strategies to develop TTM practice.MethodsSemi-structured interviews with 33 TTM practitioners were performed in five provinces in different regions of Thailand. The following information were recorded; basic information of informants, descriptions of cancer (mareng in Thai), causes, diagnosis, treatment, and prevention. Plants used in the treatment and prevention of mareng were also collected.ResultsUsing an in depth ethnographic approach four representative case studies to assist in a better understanding of the characteristics of mareng, its diagnosis, treatment, and prevention are reported here. Five characteristics of mareng – waste accumulation (khong sia), chronic illnesses (krasai), inflammation (kan aksep), bad blood (luead) and lymph (namlueang), and the imbalance of four basic elements (dhātu si) – have been identified. Explanatory models of cancer in TTM were linked with biomedical concepts and relevant pharmacological actions. Traditional uses and available scientific evidence of medicinal plants mentioned in the case studies for the treatment or prevention of mareng are presented and discussed.ConclusionHere for the first time five main characteristics of cancer based on Thai traditional medical concepts are analysed. Our findings are relevant not only for the planning of clinical studies or pharmacological experiment in the search for novel compounds for cancer treatment and prevention, but also for the integration of Thai traditional medicine in cancer care.

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A rich source of potential bioactive compounds with anticancer activities by Catharanthus roseus cambium meristematic stem cell cultures

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): So Hyun Moon, Muthuraman Pandurangan, Doo Hwan Kim, Jelli Venkatesh, Rahul V. Patel, Bhupendra M. Mistry
Ethnopharmacological importanceCatharanthus roseus (L.) G. Don. is an important medicinal plant with rich sources of remarkable health benefits consisting more than 100 alkaloids and significant amounts of bioactive compounds, which have been widely used as a folk medicine for treatment of several pathologies.The aim of the studyIn the present study, we isolated and cultured innately undifferentiated cambium meristematic cells (CMCs), which were observed stable cell growth, enhancement of bioactive compounds from C.roseus.Materials and methodsWe attempted to determine the effect of association between time-course growth rates, bioactive compounds and terpenoids indole alkaloid (TIA) contents as well as antioxidant and anticancer efficacies of C. roseus CMC suspension culture treated by UV-C.ResultsThe bioactive compounds, vincristine contents, and antioxidant power were noticed significantly higher in 60 min exposure at 5 cm distances and with the directly collected sample (T7). A similar trend has also been noticed from the anticancer activity. Demonstration of TIA accumulation was found higher at 5 min exposure, at 20 cm distances and 48 h of incubation (T21) and the result of TIA contents had the highest correlation effects of anticancer activities.ConclusionIn the current study, we demonstrated that UV-C light could enhance the production of the essential compounds and bioactivities in the CMCs of C. roseus, and thus, C. roseus CMCs have the potential to serve as an industrial platform for the production of bioactive alkaloids and antioxidant, anticancer activity. Moreover, additional efforts should be made to irradiate CMC suspension cultures from C. roseus with UV-C to achieve better pharmacological profiles.

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Anticancer effect of petroleum ether extract from Bidens pilosa L and its constituent's analysis by GC-MS

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Yiwei Shen, Zhouliang Sun, Peiying Shi, Gang Wang, Youjia Wu, Shaoguang Li, Yanjie Zheng, Liying Huang, Liqing Lin, Xinhua Lin, Hong Yao
Ethnopharmacological relevanceBidens pilosa L, belonging to the family of Acanthaceae, has been used as an anticancer medicine in folk in China. In our preliminary experiments, the petroleum ether extract from B. pilosa showed good cytotoxic activity to human lung cancer A549 cell. However, to date, it's lack of the further study on antitumor effect, mechanism and active substances composition of the petroleum ether extract of B. pilosa.Aim of the studyThe study aimed to evaluate the anti-lung cancer efficacy of the petroleum ether extract from B. pilosa (PEEBP) in vitro and in vivo, explore the possible anticancer mechanisms, and further disclose the chemical composition of the extract.Materials and methodsB. pilosa was extracted with 75% ethanol (v/v), followed by extracted with petroleum ether to obtain the objective fraction. Antiproliferation effect of the petroleum ether extract in HepG2, A549, CNE and B16 cells was evaluated by MTT assay. The in vivo anticancer effect was examined by A549 cells nude mice xenograft tumor model. The possible effect mechanism was studied by western blot assay. The chemical constituents of the extract was analyzed by GC-MS.ResultsThe petroleum ether extract showed favorable antiproliferation activity against the four human cancer cell lines, especially for A549 cells with an IC50 of 49.11 ± 2.72 μg/mL. The extract inhibited the growth of A549 cell in mice with the inhibitory rates of 24.76%, 35.85% and 53.07% for 90, 180 and 360 mg/kg oral dosages, respectively. The B. pilosa extract could significantly down-regulate the expression of apoptosis-related protein Bcl-2 and up-regulate the protein expression of Bax and Caspase-3. 138 compounds were identified by GC-MS in the extract and the main chemical components were triterpenes, including 4,22-cholestadien-3-one (4.82%), stigmasterol (4.56%), friedelan-3-one (3.28%), etc.ConclusionThe PEEBP is abundant of triterpenes and has significant anti-tumor activities against human A549 cells in vitro and in vivo, indicating it a potential anticancer agent.

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Development of an in vitro screening method of acute cytotoxicity of the pyrrolizidine alkaloid lasiocarpine in human and rodent hepatic cell lines by increasing susceptibility

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Kristina Forsch, Verena Schöning, Lucia Disch, Beate Siewert, Matthias Unger, Jürgen Drewe
Ethnopharmacological relevancePyrrolizidine alkaloids (PAs) are secondary plant ingredients formed in many plant species to protect against predators. PAs are generally considered acutely hepatotoxic, genotoxic and carcinogenic. Up to now, only few in vitro and in vivo investigations were performed to evaluate their relative toxic potential.Aim of the studyThe aim was to develop an in vitro screening method of their cytotoxicity.Materials and methodsHuman and rodent hepatocyte cell lines (HepG2 and H-4-II-E) were used to assess cytotoxicity of the PA lasiocarpine. At concentrations of 25 µM up to even 2400 µM, no toxic effects in neither cell line was observed with standard cell culture media. Therefore, different approaches were investigated to enhance the susceptibility of cells to PA toxicity (using high-glucose or galactose-based media, induction of toxifying cytochromes, inhibition of metabolic carboxylesterases, and inhibition of glutathione-mediated detoxification).ResultsGalactose-based culture medium (11.1 mM) increased cell susceptibility in both cell-lines. Cytochrome P450-induction by rifampicin showed no effect. Inhibition of carboxylesterase-mediated PA detoxification by specific carboxylesterase 2 inhibitor loperamide (2.5 µM) enhanced lasiocarpine toxicity, whereas the unspecific carboxylesterase inhibitor bis(4-nitrophenyl)phosphate (BNPP, 100 µM)) had a weaker effect. Finally, the inhibition of glutathione-mediated detoxification by buthionine sulphoximine (BSO, 100 µM) strongly enhanced lasiocarpine toxicity in H-4-II-E cells in low and medium, but not in high concentrations.ConclusionsIf no toxicity is observed under standard conditions, susceptibility enhancement by using galactose-based media, loperamide, and BSO may be useful to assess relative acute cytotoxicity of PAs in different cell lines.

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Enhanced anticancer effects of Scutellaria barbata D. Don in combination with traditional Chinese medicine components on non-small cell lung cancer cells

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
Ethnopharmacological relevanceExperience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, 莲甲散结方 in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells.Materials and methodsFour different NSCLC cell lines (A549, H460, H1650, and H1975) were used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein expression were analyzed by MTT assay, soft agar assay, real-time PCR, and Western blots, respectively.ResultsAmong the 14 components in LJSJF, SB was the only one to possess cytotoxic effects at its pharmacologically relevant doses. Additionally, we observed synergistically dose-dependent cytotoxic effects of SB in combination with other LJSJF components. After SB or LJSJF treatment, significant reductions in colony number and/or size were observed in A549 and H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and H1650; significant downregulation in EGFR and its downstream signaling targets mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were significantly increased while survivin, cyclin D1, and MDM2 were significantly decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73 was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct apoptotic pathways in different NSCLC cells.ConclusionLJSJF exerts more pronounced cytotoxic effects against NSCLC cells than SB does by synergistically regulating the underlining molecular mechanisms including EGFR and/or p53 signaling pathways.

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Restoring Th17/Treg balance via modulation of STAT3 and STAT5 activation contributes to the amelioration of chronic obstructive pulmonary disease by Bufei Yishen formula

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Peng Zhao, Jiansheng Li, Yange Tian, Jing Mao, Xuefang Liu, Suxiang Feng, Junzi Li, Qingqing Bian, Huige Ji, Lanxi Zhang
Ethnopharmacology relevanceBufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), has been extensively applied in clinical treatment of chronic obstructive pulmonary disease (COPD) and provides an effective treatment strategy for the syndrome of lung-kidney qi deficiency in COPD patients. Here, we investigated its anti-COPD mechanism in COPD rats in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells.MethodsRat model of cigarette smoke- and bacterial infection-induced COPD was established, and orally treated with BYF for 12 consecutive weeks. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were collected to evaluate the Th17 and Treg cells.ResultsOral treatment of BYF markedly suppressed the disease progression and alleviated the pathological changes of COPD. It also decreased the bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and Th17-related IL-17A, and induced a significant increase in Treg-related IL-10. Furthermore, BYF treatment obviously decreased the proportion of CD4⁺RORγt⁺ T (Th17) cell and increased the proportion of CD4⁺CD25⁺Foxp3⁺ T (Treg) cell, leading to restore the Th17/Treg balance. BYF treated groups also decreased RORγt and increased Foxp3 expression in the spleens and MLNs. BYF further inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and boosted the phosphorylation of STAT5, that were critical transcription factors for TH17 and Treg differentiation.Conclusionthese results demonstrated that BYF exerted its anti-COPD efficacy by restoring Th17/Treg balance via reciprocally modulating the activities of STAT3 and STAT5 in COPD rats, which may help to elucidate the underlying immunomodulatory mode of BYF on COPD treatment.

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Ethnobotanical and ethnomedicinal studies in Baluchi tribes: A case study in Mt. Taftan, southeastern Iran

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Tahereh Maleki, Hossein Akhani
Ethnobotanical relevanceFrom ancient times, the applied use of herbs has been common among indigenous people throughout the world. The present survey is a regional ethnobotanical study of Baluchi tribes living in the Mt. Taftan area, Sistan and Baluchistan Province, southeastern Iran. The aim of this study was to document all traditional knowledge and analyze the medicinal plants used in area and also to identify significant plant species for future pharmacological study.Materials and methodsLocal knowledge was obtained through semi structured and open interviews, in which 51 informants were interviewed. Data were analyzed with Informant Agreement Relative (IAR) and Frequency of Citation (FC) indices.ResultsA total number of 106 taxa of medicinal plants were collected from ten villages from the surrounding plains and highlands of Mt. Taftan, out of 446 plant taxa collected or reported as native in the area. Most plants belong to the Irano-Turanian phytogeographical region in which Asteraceae (15%), Lamiaceae (11%), Fabaceae (8%), Rosaceae (7%), Apiaceae (7%) and Brassicaceae (5%) are those predominantly used. The regression analysis shows that families Apiaceae, Lamiaceae, Solanaceae and Rosaceae are more highly used as medicinal than species rich families such as Asteraceae and Fabaceae, which are the richest families in the Iranian flora. The highest FC was recorded for Artemisia spp. (41) and Berberis integerrima (40). The highest IAR Index was obtained for stings (0.86), followed by disorders in the circulatory system (0.7), dental problems (0.70) and injuries (0.69). Comparing our data with major ethnobotanical references in Iran revealed that medicinal applications of 34 taxa have not been cited, including Hyoscyamus malekianus, a local endemic plant using for ailments of toothache and worms. The toxicity of the endemic Semenovia suffruticosa is also reported.ConclusionAs a result of this study we conclude that Taftan area harbours many plant species for which indigenous knowledge provides a background of medicinal importance. The high percentage of medicinal plants proportional to the native flora is 23.8%, compared to the world percentage of 17.1%, is an indication of the rich knowledge and relationship of isolated Baluchi tribes living in Mt. Taftan to the local flora growing in their surroundings. This rich knowledge should be highly regarded as a cultural and ethnobotanical heritage. Furthermore, ethnobotanical results show some weak interrelation between Baluchi tribes living in Iran and Pakistan, probably because of a different flora and/or unfavourable environmental conditions and perhaps local conflicts which might have reduced active cultural exchange.

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Eugenia brasiliensis leaves extract attenuates visceral and somatic inflammatory pain in mice

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Róli R. Simões, Scheila I. Kraus, Igor S. Coelho, Daniela Dal-Secco, Diogo A. Siebert, Gustavo A. Micke, Michele D. Alberton, Adair R.S. Santos
Ethnopharmacological relevanceEugenia brasiliensis Lam. (Myrtaceae) is a Brazilian tree distributed throughout Atlantic rain forest, since Bahia until Santa Catarina state, and is popularly known as "grumixaba, grumixameira, cumbixaba, ibaporoiti, and cereja-brasileira". The bark and leaves of Eugenia brasiliensis are used in folk medicine as adstringent, diuretic, energizing, anti-rheumatic and anti-inflammatory. This study aimed at investigating the chemical composition, antinociceptive and anti-inflammatory effect of the hydroalcoholic extract of Eugenia brasiliensis (HEEb).Material and methodsChemical composition of the HEEb was determined by High Performance Liquid Chromatography/ESI-Mass Spectrometry (HPLC-ESI-MS/MS). The antinociceptive and anti-inflammatory effects of HEEb (30–300 mg/kg) was verified in mice after oral administration by intra-gastric gavage (i.g.) 60 min prior to experimentation. It was investigated whether HEEb decreases visceral pain and leukocyte migration induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also evaluated whether HEEb decreases nociceptive behavior induced by formalin (including paw edema and temperature), prostaglandin E2 (PGE2), histamine, and compound 48/80. Finally, we evaluated the effect of HEEb in the chronic inflammatory (mechanical and thermal hypersensitivity) pain induced by complete Freund's adjuvant (CFA), as well as quantifying the concentration of the pro-inflammatory cytokines TNF-α and IL-6 in the paw by ELISA method.ResultsSeven polyphenols were identified in HEEb by HPLC-ESI-MS/MS analysis. HEEb treatment alleviated nocifensive behavior and leukocyte migration caused by acetic acid. Moreover, HEEb also reduced the inflammatory pain and paw temperature induced by formalin, as well as it decreased nociceptive behavior induced by histamine and compound 48/80. Finally, acute and repeated treatment of animals with HEEb (100 mg/kg, i.g.) markedly reduced the mechanical and thermal (heat) hypersensitivity, besides decrease paw edema and temperature induced by CFA, and this effect was evident until the day 7. Moreover, repeated treatment with HEEb (100 mg/kg, i.g.) significantly reduced the levels of IL-6 and TNF-α in the paw when compared to the CFA group.ConclusionsThis is the first report showing that HEEb presents antinociceptive and anti-inflammatory effects in the visceral and somatic inflammatory pain in mice, possibly involving the inhibition of histamine receptors and pro-inflammatory cytokines activated pathways. Our results are of interest because they support the use of Eugenia brasiliensis as a potential source of phytomedicine for inflammatory diseases and pain.

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An overview of anti-diabetic plants used in Gabon: Pharmacology and toxicology

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): B. Bading Taika, M. Bouckandou, A. Souza, H.P. Bourobou Bourobou, L.S. MacKenzie, L. Lione
Ethnopharmacological relevanceThe management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed.Materials and methodsEthnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including 'Diabetes', 'Gabon', 'Toxicity', 'Constituents', 'hyperglycaemia' were used.ResultsA total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver.ConclusionAn in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.



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Antinociceptive and anti-inflammatory activities of a standardizedextract of bis-iridoids from Pterocephalus hookeri

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): Yinglan Chen, Hui Yu, Fujiang Guo, Yingchun Wu, Yiming Li
Ethnopharmacological relevancePterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before.Aim of the studyThis study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis.Materials and methodsThe analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied.ResultsBCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter.ConclusionThe results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Graphical abstract

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Active principles of Tetradenia riparia. IV. Anthelmintic activity of 8(14),15-sandaracopimaradiene-7α,18-diol

Publication date: 24 April 2018
Source:Journal of Ethnopharmacology, Volume 216
Author(s): Luc Van Puyvelde, Maoxuan Liu, Cedrick Veryser, Wim M. De Borggraeve, Joseph Mungarulire, Marie Jeanne Mukazayire, Walter Luyten
Ethnopharmacological relevanceTetradenia (T.) riparia (Hochst.) Codd (Lamiaceae), formerly known as Iboza riparia (Hochst.) N.E.Br., is one of the most frequently used medicinal plants in traditional Rwandese medicine. It was used as a remedy against a wide range of diseases including malaria, angina, yaws, dental abscesses, headache, worm infections and several kinds of fevers and aches.Aim of the studyThis study aims to identify the compounds active against helminths from Tetradenia riparia.MethodsA bioassay-guided isolation of anthelmintic compounds from the leaves of Tetradenia riparia was performed using a Caenorhabditis elegans (C. elegans) testing model.ResultsThe bioassay-guided isolation led to one active compound, i.e. 8(14),15-sandaracopimaradiene-7α,18-diol. Its IC50 value was 5.4 ± 0.9 µg/mL (17.8 ± 2.9 µM).ConclusionsWe identified the bioactive compound from Tetradenia riparia responsible for its anthelmintic activity: 8(14),15-sandaracopimaradiene-7α,18-diol. Although the compound and several of its bioactivities have been described before, this is the first report of its anthelmintic effect.



http://ift.tt/2sNdcQz

Adsorption and desorption of potentially toxic metals on modified biosorbents through new green grafting process

Abstract

Six lignocellulosic waste-derived biosorbents [cantaloupe peel (CAN), pine cone (PC), litchi fruit peel (LP), annona squamosal (AS), bamboo shoot (BS), and sugarcane bagasse (SB)] were selected as low-cost and renewable materials to prepare chemically modified biosorbent. The modified biosorbent was prepared through a newer carboxyl groups-grafting process onto the biosorbent's surface using acrylic acid. The results showed that the cation exchange capacity (CEC) of biosorbents increased by approximately 66.3–104% after modified. The modified biosorbent exhibited significantly higher adsorption capacity of Pb²⁺, Cu²⁺, and Cd²⁺ ions than the pristine biosorbent. The maximum Langmuir adsorption capacity (Q^o_max) of both pristine and modified biosorbents toward three metal ions (Pb²⁺, Cu²⁺, and Cd²⁺) followed the decreasing order: CAN > PC > LP > AS > BS > SB. The preference ranking of three metal ions on the pristine and modified biosorbents (mmol/kg) was generally in the order: Pb²⁺ > Cu²⁺ > Cd²⁺. Among these biosorbents, cantaloupe peel exhibited an excellent adsorption affinity to metal cations compared to the five others. The Q^o_max values of modified and pristine cantaloupe peels were ordered as follows: 143.2 and 81.1 mg/g for Pb²⁺ adsorption, > 45.4 and 30.4 mg/g for Cd²⁺ adsorption, > 33.1 and 23.5 mg/g for Cu²⁺ adsorption. After five adsorption–desorption cycles, the removal efficiency of Pb²⁺ by modified CAN was maintained at around 70%. The ion exchange played a determining role in adsorption mechanism. It can be concluded that modified cantaloupe peel can serve as a newer and promising biosorbent with a high adsorption capacity to various potentially toxic metals.

http://ift.tt/2omespf

Performance of sorghum cultivars for biomass quality and biomethane yield grown in semi-arid area of Pakistan

Abstract

Biomass is a promising renewable energy source and its significance is escalating in the context of climate change and depletion of fossil foils. This study was conducted for two consecutive years 2016 and 2017, using five sorghum cultivars, i.e., JS-263, Jawar-2011, Hagari, JS-2002, and YS-2016, in order to determine the best cultivars in terms of dry matter yield, chemical composition, and biomethane yield grown under semi-arid conditions in Pakistan. The results revealed that sorghum cultivars responded differently in terms of growth, biomass yield, chemical composition, and methane yield. Cultivars Jawar-2011 produced maximum leaf area index, leaf area duration, crop growth rate, plant height, and leaves per plant, however, they were comparable with Sorghum-2016, whereas cultivar JS-2002 performed poorly among the tested cultivars. Similarly, cultivar Jawar-2011 produced maximum dry matter yield (16.37 t ha⁻¹) similar to that of YS-2016, further cultivar JS-2002 performed poorly and gave lower dry matter yield (12.87 t ha⁻¹). The maximum protein concentration (10.95), neutral detergent fibers (61.20), and lignin contents (5.55) found in Jawar-2011 were comparable with those in YS-2016, while the lowest neutral detergent fiber and lignin contents were found in JS-2002. Although JS-2002 produced the highest specific methane yield per kilogram of volatile solids, it was overcompensated by Jawar-2011 owing to higher dry matter yield per hectare. These results suggested that cultivar Jawar-2011 can be grown successfully in semi-arid conditions of Pakistan in order to get good biomass yield along with higher methane yield.

http://ift.tt/2oqTwfZ

Terminal Arbors of Callosal Axons Undergo Plastic Changes in Early-Amputated Rats

Abstract

Sensory information is processed in specific brain regions, and shared between the cerebral hemispheres by axons that cross the midline through the corpus callosum. However, sensory deprivation usually causes sensory losses and/or functional changes. This is the case of people who suffered limb amputation and show changes of body map organization within the somatosensory cortex (S1) of the deafferented cerebral hemisphere (contralateral to the amputated limb), as well as in the afferented hemisphere (ipsilateral to the amputated limb). Although several studies have approached these functional changes, the possible finer morphological alterations, such as those occurring in callosal axons, still remain unknown. The present work combined histochemistry, single-axon tracing and 3D microscopy to analyze the fine morphological changes that occur in callosal axons of the forepaw representation in early amputated rats. We showed that the forepaw representation in S1 was reduced in the deafferented hemisphere and expanded in the afferented side. Accordingly, after amputation, callosal axons originating from the deafferented cortex undergo an expansion of their terminal arbors with increased number of terminal boutons within the homotopic representation at the afferented cerebral hemisphere. Similar microscale structural changes may underpin the macroscale morphological and functional phenomena that characterize limb amputation in humans.

http://ift.tt/2EZqEWl

Low-Intensity Pulsed Ultrasound Attenuates LPS-Induced Neuroinflammation and Memory Impairment by Modulation of TLR4/NF-κB Signaling and CREB/BDNF Expression

Abstract

The purpose of this study was to investigate the restorative role of low-intensity pulsed ultrasound (LIPUS) against lipopolysaccharide (LPS)-induced neuroinflammation and memory impairments in a simulation of Alzheimer's disease. Mice subjected to LPS administration (250 μg/kg, i.p.) were treated with LIPUS daily for 7 days. The levels of brain-derived neurotrophic factor (BDNF) and inflammatory markers were estimated in brain tissue using western blot. After LIPUS treatment, the neuroprotective effects of LIPUS in mice were assessed by behavioral tests. LPS plus LIPUS-treated mice exhibited a significant increase in the average time spent in the target quadrant compared to the LPS-treated group. Compared with the LPS-treated group, LPS plus LIPUS-treated mice revealed a preference for the novel object. LIPUS treatment significantly attenuated LPS-induced increases in the expression of amyloid-beta (Aβ) and amyloid precursor protein (APP) in the hippocampus region of LPS-treated mice. Furthermore, LIPUS significantly reduced the protein levels of TNF-α, IL-1β, and IL-6 in the mice brain induced by LPS. LIPUS treatment induces neuroprotection by inhibiting the LPS-induced activation of TLR4/NF-κB inflammatory signaling and by enhancing the associated CREB/BDNF expression in LPS-treated mice. Our data showed that LIPUS attenuated LPS-induced memory impairment as well as amyloidogenesis via the suppression of neuroinflammatory activity and BDNF decline.

http://ift.tt/2sQg8Me

Preterm Birth Changes Networks of Newborn Cortical Activity

Abstract

Preterm birth is the greatest risk factor for lifelong neurocognitive deficits, globally. The effect of prematurity on early cortical network function has, however, remained poorly understood. Here, we developed a novel methodology that allows reliable assessment of functional connectivity in neonatal brain activity at millisecond and multisecond scales in terms of cortical phase and amplitude correlations, respectively. We measured scalp electroencephalography at term-equivalent age in infants exposed to very early prematurity as well as in healthy controls. We found that newborn cortical activity organizes into multiplex networks that differ significantly between vigilance states. As compared with healthy control infants, prematurity was found to cause frequency-specific patterns of dysconnectivity in cortical network, changes that were distinct for networks of phase and amplitude correlations. Neuroanatomically, the most prominent markers of prematurity were found in connections involving the frontal regions. Phase synchrony in frontally connected networks was correlated with newborn neurological performance, suggesting the first measure of cortical functional coupling that correlates with neurological performance in human infant.

http://ift.tt/2EX1J5U

GSK3β Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels

Abstract

Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K⁺ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K⁺ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3β influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K⁺ currents. Collectively, these results identify the functional interaction between GSK3β and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3β role in synaptic plasticity.

http://ift.tt/2sP68CY

Antioxidant action and protective and reparative effects of lentinan on oxidative damage in HaCaT cells

Summary

Background

Lentinus edodes is one of the largest edible fungi. Lentinan, extracted from its fruiting body has clinically significant anticancer, antibacterial, antiviral, and anticoagulant effects; however, its preventive effects on skin oxidative damage are unclear.

Aims

We aimed to evaluate the in vitro antioxidation capability of lentinan and its protective and reparative effects on a model of cell oxidative damage.

Methods

We evaluated the in vitro antioxidant potential of lentinan by assessing its free-radical quenching ability using DPPH and ABTS and superoxide anions. Using the HaCaT cell line as the experimental system, we tested the protective and reparative effects of lentinan on a model of H₂O₂-induced cellular oxidative damage through assessment of cell survival rate, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity.

Results

Lentinan displayed high antioxidant potential: DDPH and ABTS quenching rates were above 60%; superoxide anions, approximately 18%. Furthermore, lentinan could dose-dependently prevent the reduction of activity in HaCaT cells by H₂O₂, reduce MDA formation, and increase SOD activity. Moreover, lentinan showed not only a protective effect against oxidative damage but also reparative effects to a certain extent, in HaCaT cells.

Conclusions

Our findings demonstrated the ability of lentinan to enhance cellular tolerance to oxidative damage, stress resistance, and to have protective and reparative effects on damaged cells. Therefore, with L. edodes as a source for antiaging substances, cosmetics with homology to foods have great potential clinical applications.

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Seven novel COL7A1 mutations identified in patients with recessive dystrophic epidermolysis bullosa from Mexico

Summary

Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the most devastating subtypes of epidermolysis bullosa, a group of skin and mucous membrane blistering disorders often associated with extracutaneous manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII collagen (C7), and to date over 700 different mutations in the 8835 nucleotides constituting the open reading frame or adjacent exon–intron boundaries of COL7A1 have been described. We used targeted next-generation sequencing to identify seven previously unreported mutations in a cohort of 17 Mexican patients who were diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our study expands the spectrum of mutations identified in this cohort, including those suitable for emerging therapies reliant on precise genotyping.

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Pigmented onychomatricoma: a rare mimic of subungual melanoma

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CD30-positive primary cutaneous anaplastic large cell lymphoma with coexistent pseudocarcinomatous hyperplasia

Summary

CD30-positive primary cutaneous anaplastic large cell lymphoma (C-ALCL) is an indolent type of cutaneous lymphoma with favourable clinical prognosis. Pseudocarcinomatous hyperplasia (PCH) is a rare benign epithelial condition that can resemble invasive squamous cell carcinoma both clinically and histopathologically. PCH predominantly occurs in CD30-positive lymphoproliferative disorders. We report a 75-year-old woman with PCH in a multifocal C-ALCL located on the scalp and right retroauricular area, which rapidly responded to treatment with psoralen ultraviolet A photochemotherapy. Comprehensive virological analyses for potential oncogenic viruses, including Epstein–Barr virus, human herpesvirus-8, human papillomaviruses, the recently discovered cutavirus and nine different human polyomaviruses, were negative.

http://ift.tt/2EZE4kZ

Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation

Publication date: Available online 22 February 2018
Source:Cell Stem Cell
Author(s): Luca Peruzzotti-Jametti, Joshua D. Bernstock, Nunzio Vicario, Ana S.H. Costa, Chee Keong Kwok, Tommaso Leonardi, Lee M. Booty, Iacopo Bicci, Beatrice Balzarotti, Giulio Volpe, Giulia Mallucci, Giulia Manferrari, Matteo Donegà, Nunzio Iraci, Alice Braga, John M. Hallenbeck, Michael P. Murphy, Frank Edenhofer, Christian Frezza, Stefano Pluchino
Neural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the CNS. Metabolites, such as succinate, modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here, we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage. Inflammatory MPs release succinate, which activates succinate receptor 1 (SUCNR1)/GPR91 on NSCs, leading them to secrete prostaglandin E2 and scavenge extracellular succinate with consequential anti-inflammatory effects. Thus, our work reveals an unexpected role for the succinate-SUCNR1 axis in somatic and directly induced NSCs, which controls the response of stem cells to inflammatory metabolic signals released by type 1 MPs in the chronically inflamed brain.

Graphical abstract

Teaser

Peruzzotti-Jametti et al. demonstrate that somatic and directly induced brain stem cells injected into the cerebrospinal fluid of mice with experimental multiple sclerosis ameliorate chronic neuroinflammation. Grafted stem cells use SUCNR1 to decrease the inflammatory metabolite succinate, thus inducing a metabolic switch in endogenous macrophages and microglia toward an anti-inflammatory phenotype.


http://ift.tt/2CeZdXE

Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS

Publication date: Available online 22 February 2018
Source:Cancer Cell
Author(s): Takuji Yamauchi, Takeshi Masuda, Matthew C. Canver, Michael Seiler, Yuichiro Semba, Mohammad Shboul, Mohammed Al-Raqad, Manami Maeda, Vivien A.C. Schoonenberg, Mitchel A. Cole, Claudio Macias-Trevino, Yuichi Ishikawa, Qiuming Yao, Michitaka Nakano, Fumio Arai, Stuart H. Orkin, Bruno Reversade, Silvia Buonamici, Luca Pinello, Koichi Akashi, Daniel E. Bauer, Takahiro Maeda
To identify novel targets for acute myeloid leukemia (AML) therapy, we performed genome-wide CRISPR-Cas9 screening using AML cell lines, followed by a second screen in vivo. Here, we show that the mRNA decapping enzyme scavenger (DCPS) gene is essential for AML cell survival. The DCPS enzyme interacted with components of pre-mRNA metabolic pathways, including spliceosomes, as revealed by mass spectrometry. RG3039, a DCPS inhibitor originally developed to treat spinal muscular atrophy, exhibited anti-leukemic activity via inducing pre-mRNA mis-splicing. Humans harboring germline biallelic DCPS loss-of-function mutations do not exhibit aberrant hematologic phenotypes, indicating that DCPS is dispensable for human hematopoiesis. Our findings shed light on a pre-mRNA metabolic pathway and identify DCPS as a target for AML therapy.

Graphical abstract

Teaser

Yamauchi et al. perform in vitro and in vivo CRISPR-Cas9 genetic screening of p53 WT AML to identify potential therapeutic targets. They find that AML relies on the DCPS decapping enzyme, and a DCPS inhibitor shows anti-leukemia activity in tumor models without impacting normal hematopoiesis.


http://ift.tt/2GDNXlw

Family environmental and dietary implications for low-level prenatal lead exposure in Wujiang City, China

Abstract

To explore the potential environmental and dietary factors during pregnancy affecting low-level prenatal lead exposure, we conducted a longitudinal study in Wujiang City, China. A total of 1976 mother-infant pairs were included from 2009 to 2010. An interviewed questionnaire was conducted and cord blood samples were collected. The geometric means of cord blood lead level was 30.3 μg/L (95% CI, 29.8–30.8) with 99.24% below 100 μg/L. Maternal age, passive smoking, and living in the countryside were significantly associated with cord blood lead concentrations. Multiple logistic models showed that some family environmental factors including using firewood and electricity as kitchen fuel were positively correlated with increased cord blood lead levels. Among dietary sources recorded in this study, meat consumption (> 3 times/week), fish consumption (1–3 times/week), vegetables consumption (> 1 times/day), and fruit intake (> 1 times/day) had inverse relationship with cord blood lead levels. In general, our findings may have important implications for family environmental and dietary direction during pregnancy to decrease prenatal lead exposure.

http://ift.tt/2EZbX5t

Effects of soil pyrene contamination on growth and phenolics in Norway spruce ( Picea abies ) are modified by elevated temperature and CO 2

Abstract

With the constant accumulation of polycyclic aromatic hydrocarbons (PAHs) in soil and increasing temperature and CO₂ levels, plants will inevitably be exposed to combined stress. Studies on the effects of such combined stresses are needed to develop mitigation and adaptation measures. Here, we investigated the effects of soil pyrene contamination (50 mg kg⁻¹) on growth and phenolics of 1-year-old Norway spruce seedlings from five different origins in Finland at elevated temperature (+ 2 °C) and CO₂ (+ 360 ppm). Pyrene significantly decreased spruce height growth (0–48%), needle biomass (0–44%), stem biomass (0–43%), and total phenolic concentrations in needles (2–13%) and stems (1–19%) compared to control plants. Elevated temperature alone did not affect growth but led to lower concentrations of total phenolics in needles (5–29%) and stems (5–18%) in both soil treatments. By contrast, elevated CO₂ led to higher needle biomass (0–39%) in pyrene-spiked soils and higher concentrations of stem phenolics (0–18%) in pyrene-spiked and control soils compared to ambient treatments. The decrease in height growth and phenolic concentrations caused by pyrene was greater at elevated temperature, while elevated CO₂ only marginally modified the response. Seedlings from different origins showed different responses to the combined environmental stressors. The changes in growth and in the quantity and quality of phenolics in this study suggest that future climate changes will aggravate the negative influence of soil pyrene pollution on northern conifer forest ecosystems.

http://ift.tt/2sNazy3

Treatment of post-burn and post-traumatic atrophic scars with fractional CO 2 laser: experience at a tertiary care centre

Abstract

Scars are abnormal wound responses in predisposed individuals. They occur after any kind of wound and skin inflammation in predisposed individuals. Despite their benign nature, they can be aesthetically disabling. Although several approaches have been tried in their management, most of them have produced poor results. This study aims to assess the efficacy and safety of fractional CO₂ laser treatment in the management of post-burn and post-traumatic scars. One hundred consecutive patients (77 females and 23 males) affected by post-burn scars as well as post-traumatic atrophic scars were treated with monthly sessions of fractional CO₂ laser treatment. Patient's response to treatment was assessed clinically as well as improvement of scars by comparing the photographs taken before treatment with those taken 6 months after the last treatment session. Changes in skin texture, surface irregularity and pigmentation were assessed on a quartile grading scale and scored individually from 0 to 4. A mean of the three individual scores was calculated and the response was labelled as 'excellent' if the mean score achieved was > 3. A score of 2–3 was labelled as good response while a score below 1 was labelled as 'poor' response. A mean of six treatments per scar were required and all patients, followed up for 1 year after the last treatment, had optimum results and no recurrence. Response to treatment was excellent in 53.75%, good in 16.25% patients, and poor in 30% patients. Fractional CO₂ laser gives a very good result in the management of patients with post-burn scars as well as post-traumatic scars with minimal adverse effects.

http://ift.tt/2F2fKyW

The effects of exercise training associated with low-level laser therapy on biomarkers of adipose tissue transdifferentiation in obese women

Abstract

Investigations suggest the benefits of low-level laser therapy (LLLT) to improve noninvasive body contouring treatments, inflammation, insulin resistance and to reduce body fat. However, the mechanism for such potential effects in association with exercise training (ET) and possible implications in browning adiposity processes remains unclear. Forty-nine obese women were involved, aged between 20 and 40 years with a body mass index (BMI) of 30–40 kg/m². The volunteers were divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of exercise training and phototherapy applications post exercise for 4 months, with three sessions/week. Body composition, lipid profile, insulin resistance, atrial natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and an increase in WNT5 signaling. In addition, it was possible to observe a higher magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the Phototherapy group. In the present investigation, it was demonstrated that exercise training associated with LLLT promotes an improvement in body composition and inflammatory processes as previously demonstrated. The Phototherapy group especially presented positive modifications of WNT5 signaling, FGF-21, and ANP, possible biomarkers associated with browning adiposity processes. This suggests that this kind of intervention promotes results applicable in clinical practice to control obesity and related comorbidities.

http://ift.tt/2sJGjnI

A comprehensive review on nano-molybdenum disulfide/DNA interfaces as emerging biosensing platforms

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Manil Kukkar, Girish C. Mohanta, Satish K. Tuteja, Parveen Kumar, Akhshay Singh Bhadwal, Pallabi Samaddar, Ki-Hyun Kim, Akash Deep
The development of nucleic acid-based portable platforms for the real-time analysis of diseases has attracted considerable scientific and commercial interest. Recently, 2D layered molybdenum sulfide (2D MoS2 from here on) nanosheets have shown great potential for the development of next-generation platforms for efficient signal transduction. Through combination with DNA as a biorecognition medium, MoS2 nanostructures have opened new opportunities to design and construct highly sensitive, specific, and commercially viable sensing devices. The use of specific short ssDNA sequences like aptamers has been proven to bind well with the unique transduction properties of 2D MoS2 nanosheets to realize aptasensing devices. Such sensors can be operated on the principles of fluorescence, electro-cheumuluminescence, and electrochemistry with many advantageous features (e.g., robust biointerfacing through various conjugation chemistries, facile sensor assembly, high stability with regard to temperature/pH, and high affinity to target). This review encompasses the state of the art information on various design tactics and working principles of MoS2/DNA sensor technology which is emerging as one of the most sought-after and valuable fields with the advent of nucleic acid inspired devices. To help achieve a new milestone in biosensing applications, great potential of this emerging technique is described further with regard to sensitivity, specificity, operational convenience, and versatility.



http://ift.tt/2BOpgUi

An optofluidic metasurface for lateral flow-through detection of breast cancer biomarker

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Yifei Wang, Md. Azahar Ali, Edmond K.C. Chow, Liang Dong, Meng Lu
The rapid growth of point-of-care tests demands for biosensors with high sensitivity and small size. This paper demonstrates an optofluidic metasurface that combines silicon-on-insulator (SOI) nanophotonics and nanofluidics to realize a high-performance, lateral flow-through biosensor. The metasurface is made of a periodic array of silicon nanoposts on an SOI substrate, and functionalized with specific receptor molecules. Bonding of a polydimethylsiloxane slab directly onto the surface results in an ultracompact biosensor, where analyte solutions are restricted to flow only in the space between the nanoposts. No flow exists above the nanoposts. This sensor design overcomes the issue with diffusion-limited detection of many other biosensors. The lateral flow-through feature, in conjunction with high-Q resonance modes associated with optical bound states of the metasurface, offers an improved sensitivity to subtle molecule-bonding induced changes in refractive index. The device exhibits a resonance mode around 1550 nm wavelength and provides an index sensitivity of 720 nm/RIU. Biosensing is conducted to detect the epidermal growth factor receptor 2 (ErbB2), a protein biomarker for early-stage breast cancer screening, by monitoring resonance wavelength shifts in response to specific analyte-ligand binding events at the metasurface. The limit of detection of the device is 0.7 ng mL⁻¹ for ErbB2.



http://ift.tt/2olehKO

Silver-dendrimer nanocomposites as oligonucleotide labels for electrochemical stripping detection of DNA hybridization

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Xin Jin, Ling Zhou, Bo Zhu, Xue Jiang, Ningning Zhu
Silver-dendrimer nanocomposites were synthesized and used as oligonucleotide labels for electrochemical stripping detection of DNA hybridization. The synthesized silver-dendrimer nanocomposites were characterized by UV–vis spectrophotometry, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Ratios of silver/dendrimer were optimized in order to obtain stable nanocomposites with maximal silver loading in the interior of a polymeric shell. The silver-dendrimer nanocomposites were attached to sequence-known DNA probes specific to colitoxin, and used to detect probe hybridization by dissolution of the silver nanoparticles in the interior of dendrimer in a diluted nitric acid, followed by measurement of Ag⁺ ions by anodic stripping voltammetry (ASV). Use of differential pulse voltammetry for the stripping step, along with optimization of the ASV conditions, enabled a detection limit of 0.78 pM. The present strategy, in combination with dendrimer-encapsulated copper labeled oligonucleotides probe reported previously, could potentially be used to detect single or multiple DNA targets in one sample.



http://ift.tt/2BMMvhx

Signal-on electrochemiluminescence biosensor for microRNA-319a detection based on two-stage isothermal strand-displacement polymerase reaction

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Minghui Wang, Yunlei Zhou, Huanshun Yin, Wenjing Jiang, Haiyan Wang, Shiyun Ai
MicroRNAs play crucial role in regulating gene expression in organism, thus it is very necessary to exploit an efficient method for the sensitive and specific detection of microRNA. Herein, a signal-on electrochemiluminescence biosensor was fabricated for microRNA-319a detection based on two-stage isothermal strand-displacement polymerase reaction (ISDPR). In the presence of target microRNA, amounts of trigger DNA could be generated by the first ISDPR. Then, the trigger DNA and the primer hybridized simultaneously with the hairpin probe to open the stem of the probe, and then the ECL signal will be emitted. In the presence of phi29 DNA polymerase and dNTPs, the trigger DNA could be displaced to initiate a new cycle which was the second ISDPR. Due to the two-stage amplification, this method presented excellent detection sensitivity with a low detection limit of 0.14 fM. Moreover, the applicability of the developed method was demonstrated by detecting the change of microRNA-319a content in the leaves of rice seedlings after the rice seeds were incubated with chemical mutagen of ethyl methanesulfonate.

Graphical abstract

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A nonenzymatic DNA nanomachine for biomolecular detection by target recycling of hairpin DNA cascade amplification

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Jiao Zheng, Ningxing Li, Chunrong Li, Xinxin Wang, Yucheng Liu, Guobin Mao, Xinghu Ji, Zhike He
Synthetic enzyme-free DNA nanomachine performs quasi-mechanical movements in response to external intervention, suggesting the promise of constructing sensitive and specific biosensors. Herein, a smart DNA nanomachine biosensor for biomolecule (such as nucleic acid, thrombin and adenosine) detection is developed by target-assisted enzyme-free hairpin DNA cascade amplifier. The whole DNA nanomachine system is constructed on gold nanoparticle which decorated with hundreds of locked hairpin substrate strands serving as DNA tracks, and the DNA nanomachine could be activated by target molecule toehold-mediated exchange on gold nanoparticle surface, resulted in the fluorescence recovery of fluorophore. The process is repeated so that each copy of the target can open multiplex fluorophore-labeled hairpin substrate strands, resulted in amplification of the fluorescence signal. Compared with the conventional biosensors of catalytic hairpin assembly (CHA) without substrate in solution, the DNA nanomachine could generate 2–3 orders of magnitude higher fluorescence signal. Furthermore, the DNA nanomachine could be used for nucleic acid, thrombin and adenosine highly sensitive specific detection based on isothermal, and homogeneous hairpin DNA cascade signal amplification in both buffer and a complicated biomatrix, and this kind of DNA nanomachine could be efficiently applied in the field of biomedical analysis.



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A highly specific and ultrasensitive near-infrared fluorescent probe for imaging basal hypochlorite in the mitochondria of living cells

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Baocun Zhu, Liu Wu, Meng Zhang, Yawei Wang, Caiyun Liu, Zuokai Wang, Qingxia Duan, Pan Jia
The development of highly specific and ultrasensitive fluorescent probes for tracking basal mitochondrial hypochlorite is very important to unravel its diverse cellular functions in the mitochondria of living cells. In this paper, we have developed a water-soluble, mitochondria-targeted near-infrared fluorescent probe NB-OCl for selectively measuring OCl^- in the presence of higher concentration (500 μM) other biologically important substances. Surprisingly, the obtained results demonstrated that probe NB-OCl could sensitively determine OCl^- in the range of 0–200 pM with the detection limit of 10.8 pM. To the best of our knowledge, NB-OCl is the first fluorescent probe for the specific determination of OCl^- at the picomolar level. Moreover, probe NB-OCl exhibits a fast response for OCl^- (< 5 s), which would be in favor of tracking the highly reactive and short-lived OCl^- in the living systems. The preeminent recognition properties of probe NB-OCl enable its applications in the monitoring of basal OCl^- and the fluctuations of endogenous/exogenous OCl^- levels in the mitochondria of living cells.



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Hierarchical CuInS2-based heterostructure: Application for photocathodic bioanalysis of sarcosine

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Xin-Yuan Jiang, Ling Zhang, Yi-Li Liu, Xiao-Dong Yu, Yan-Yu Liang, Peng Qu, Wei-Wei Zhao, Jing-Juan Xu, Hong-Yuan Chen
In this study, on the basis of hierarchical CuInS2-based heterostructure, a novel cathodic photoelectrochemical (PEC) enzymatic bioanalysis of the sarcosine detection was reported. Specifically, heterostructured CuInS2/NiO/ITO photocathode was prepared and sarcosine oxidases (SOx) were integrated for the construction of the enzymatic biosensor. In the bioanalysis, the O2-dependent suppression of the cathodic photocurrent can be observed due to the competition between the as-fabricated O2-sensitive photocathode and the SOx-catalytic event toward O2 reduction. Based on the sarcosine-controlled O2 concentration, a novel photocathodic enzymatic biosensor could be realized for the sensitive and specific sarcosine detection. This work manifested the great potential of CuInS2-based heterostructure as a novel platform for future PEC bioanalytical development and also a PEC method for sarcosine detection, which could be easily extended to numerous other enzymatic systems and to our knowledge has not been reported. This work is expected to stimulate more interest in the design and implementation of numerous CuInS2-based heterostructured photocathodic enzymatic sensing.



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Risk stratification of heart failure from one drop of blood using hand-held biosensor for BNP detection

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Indu Sarangadharan, Shin-Li Wang, Tse-Yu Tai, Anil Kumar Pulikkathodi, Chen-Pin Hsu, Hui-Hua Kenny Chiang, Lawrence Yu-Min Liu, Yu-Lin Wang
Continued risk assessment by evaluating cardiac biomarkers in healthy and unhealthy individuals can lower the mortality rate of cardiovascular diseases (CVDs). In this research, we have developed a hand-held biosensor system to rapidly screen for brain natriuretic peptide (BNP) from a single drop of whole blood. The sensor methodology is based on extended gate design of electrical double layer (EDL) field effect transistor (FET), that can directly detect BNP in whole blood, without extensive sample pre-treatments, thereby eliminating the limitations of charge screening in high ionic strength solutions. A simple sensor array chip is fabricated to integrate with the MOSFET sensor system. Sensing characteristics are elucidated using purified BNP samples in 1 × PBS (with 4% BSA), spiked BNP samples in whole blood and clinical whole blood samples. The blood cells can be gravitationally separated without the use of any external actuation. The sensor exhibits very high sensitivity over wide dynamic range of detection. The sensing characteristics are not adversely affected by the presence of background proteins or blood cells, even without gravitational blood cell separation. Thus, the biosensor system can allow users to perform rapid whole blood diagnostics with minimal user protocols, in 5 min. The features of high sensitivity, cost-effectiveness and convenience of usage empower this technology to revolutionize the mobile diagnostics and healthcare industry.



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Gold-copper bimetallic nanoparticles supported on nano P zeolite modified carbon paste electrode as an efficient electrocatalyst and sensitive sensor for determination of hydrazine

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Fatemeh Amiripour, Seyed Naser Azizi, Shahram Ghasemi
In this report, a facile, efficient and low cost electrochemical sensor based on bimetallic Au-Cu nanoparticles supported on P nanozeolite modified carbon paste electrode (Au-Cu/NPZ/CPE) was constructed and its efficiency for determination of hydrazine in trace level was studied. For this purpose, agro waste material, stem sweep ash (SSA) was employed as the starting material (silica source) for the synthesis of nano P zeolite (NPZ). After characterization of the synthesized NPZ by analytical instruments (scanning electronic microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy), construction of Au-Cu/NPZ/CPE was performed by three steps procedure involving preparation of nano P zeolite modified carbon paste electrode (NPZ/CPE), introducing Cu⁺² ions into nano zeolite structure by ion exchange and electrochemical reduction of Cu⁺² ions upon applying constant potential. This procedure is followed by partial replacement of Cu by Au due to galvanic replacement reaction (GRR). The electrochemical properties of hydrazine at the surface of Au-Cu/NPZ/CPE was evaluated using cyclic voltammetry (CV), amperometry, and chronoamperometry methods in 0.1 M phosphate buffer solution (PBS). It was found that the prepared sensor has higher electrocatalytic activity at a relatively lower potential compared to other modified electrodes including Au/NPZ/CPE, Cu/NPZ/CPE, Au-Cu/CPE and etc. Moreover, the proposed electrochemical sensor presented the favorable analytical properties for determination of hydrazine such as low detection limit (0.04 µM), rapid response time (3 s), wide linear range (0.01–150 mM), and high sensitivity (99.53 µA mM⁻¹) that are related to the synergic effect of bimetallic of Au-Cu, porous structure and enough surface area of NPZ. In addition, capability of Au-Cu/NPZ/CPE sensor was successfully tested in real samples with good accuracy and precision.

Graphical abstract

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Portable and quantitative point-of-care monitoring of Escherichia coli O157:H7 using a personal glucose meter based on immunochromatographic assay

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Haoran Huang, Guangying Zhao, Wenchao Dou
Here we innovate a portable and quantitative immunochromatographic assay (ICA) with a personal glucose meter (PGM) as readout for the detection of Escherichia coli O157:H7 (E. coli O157:H7). The carboxyl group coated Fe3O4 nanoparticles (MNPs) were synthesized by a one pot method and used as carriers of invertase and monoclonal antibody against E. coli O157:H7. Initially, the invertase and antibody double functionalized MNPs (Invertase-MNPs-IgG) conjugates were prepared and used as label probe in this assay system. Before laminating onto the baking card, the absorbent pad was soaked in sucrose solution and desiccated. MNPs produced brown band at the detection zone of the ICA when acting as direct labels. As they were also coupled with invertase, the invertase catalyzed the hydrolysis of sucrose on the absorbent pad into glucose, which was detected by the PGM. To increase the sensitivity, antibody functionalized MNPs were used to enrich E. coli O157:H7 from sample solution. The innovative aspect of this approach lies in the visualization and quantification of E. coli O157:H7 through Invertase-MNPs-IgG and the detection of glucose concentration using PGM. Although the feasibility is demonstrated using E. coli O157:H7 as a model analyte, this approach can be easily developed to be a universal analysis system and applied to detection of a wide variety of foodborne pathogens and protein biomarkers. This study proposed a qualitative and quantitative analysis device for the clinic diagnostics and food safety analysis.



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Electrochemical detection of influenza virus H9N2 based on both immunomagnetic extraction and gold catalysis using an immobilization-free screen printed carbon microelectrode

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Maher Sayhi, Oussama Ouerghi, Kamel Belgacem, Marwa Arbi, Yudum Tepeli, Abdeljalil Ghram, Ülkü Anik, Lars Österlund, Dhafer Laouini, Mohamed Fethi Diouani
Influenza is a viral infectious disease considered as a source of many health problems and enormous socioeconomic disruptions. Conventional methods are inadequate for in-field detection of the virus and generally suffer from being laborious and time-consuming. Thus, studies aiming to develop effective alternatives to conventional methods are urgently needed. In this work, we developed an approach for the isolation and detection of influenza A virus subtype H9N2. For this aim, two specific influenza receptors were used. The first, anti-matrix protein 2 (M2) antibody, was attached to iron magnetic nanoparticles (MNPs) and used for the isolation of the virus from allantoic fluid. The second biomolecule, Fetuin A, was attached to an electrochemical detectable label, gold nanoparticles (AuNPs), and used to detect the virus tacking advantage from fetuin-hemagglutinin interaction. The MNP-Influenza virus-AuNP formed complex was isolated and treated by an acid solution then the collected gold nanoparticles were deposited onto a screen printed carbon electrode. AuNPs catalyzes the hydrogen ions reduction in acidic medium while applying an appropriate potential, and the generated current signal was proportional to the virus titer. This approach allows the rapid detection of influenza virus A/H9N2 at a less than 16 HAU titer.



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Sensitive, selective, disposable electrochemical dopamine sensor based on PEDOT-modified laser scribed graphene

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Guangyuan Xu, Zahraa A. Jarjes, Valentin Desprez, Paul A. Kilmartin, Jadranka Travas-Sejdic
The fabrication of a novel, and highly selective electrochemical sensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT) modified laser scribed graphene (LSG), and detection of dopamine (DA) in the presence of ascorbic acid (AA) and uric acid (UA) is described. LSG electrodes were produced with a 3-dimensional macro-porous network and large electrochemically-active surface area via direct laser writing on polyimide sheets. PEDOT was electrodeposited on the LSG electrode, and the physical properties of the obtained films were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray diffraction microanalysis (EDAX). The modified electrodes were applied for the determination of DA in the presence of AA and UA using cyclic voltammetry (CV), and differential pulse voltammetry (DPV) techniques. The linear range for dopamine detection was found to be 1–150 µM with a sensitivity of 0.220 ± 0.011 µA μM⁻¹ and a detection limit of 0.33 µM; superior values to those obtained without PEDOT. For the first time, PEDOT-modified LSG have been fabricated and assessed for high-performance dopamine sensing using cost-effective, disposable electrodes, with potential for development in further sensing applications.



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Stretchable wireless system for sweat pH monitoring

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Wenting Dang, Libu Manjakkal, William Taube Navaraj, Leandro Lorenzelli, Vincenzo Vinciguerra, Ravinder Dahiya
Sensor-laden wearable systems that are capable of providing continuous measurement of key physiological parameters coupled with data storage, drug delivery and feedback therapy have attracted huge interest. Here we report a stretchable wireless system for sweat pH monitoring, which is able to withstand up to 53% uniaxial strain and more than 500 cycles to 30% strain. The stretchability of the pH sensor patch is provided by a pair of serpentine-shaped stretchable interconnects. The pH sensing electrode is made of graphite-polyurethane composite, which is suitable for biosensor application. The sensing patch validated through in-depth electrochemical studies, exhibits a pH sensitivity of 11.13 ± 5.8 mV/pH with a maximum response time of 8 s. Interference study of ions and analyte (Na⁺, K⁺ and glucose) in test solutions shows negligible influence on the pH sensor performance. The pH data can be wirelessly and continuously transmitted to smartphone through a stretchable radio-frequency-identification antenna, of which the radiating performance is stable under 20% strain, as proved by vector network analyzer measurement. To evaluate the full system, the pH value of a human sweat equivalent solution has been measured and wirelessly transmitted to a custom-developed smart phone App.



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Theoretical and experimental study for the biomimetic recognition of levothyroxine hormone on magnetic molecularly imprinted polymer

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Silio Lima Moura, Laura Martinez Fajardo, Leonardo dos Anjos Cunha, Maria Del Pilar Taboada Sotomayor, Francisco Bolivar Correto Machado, Luiz Fernando Araújo Ferrão, Maria Isabel Pividori
This study addresses the rational design of a magnetic molecularly imprinted polymer (magnetic-MIP) for the selective recognition of the hormone levothyroxine. The theoretical study was carried out by the density functional theory (DFT) computations considering dispersion interaction energies, and using the D2 Grimme's correction. The B97-D/def2-SV(P)/PCM method is used not only for studying the structure of the template the and monomer-monomer interactions, but also to assess the stoichiometry, noncovalent binding energies, solvation effects and thermodynamics properties such as binding energy. Among the 13 monomers studied in silico, itaconic acid is the most suitable according to the thermodynamic values. In order to assess the efficiency of the computational study, three different magnetic-MIPs based on itaconic acid, acrylic acid and acrylamide were synthesized and experimentally compared. The theoretical results are in agreement with experimental binding studies based on laser confocal microscopy, magneto-actuated immunoassay and electrochemical sensing. Furthermore, and for the first time, the direct electrochemical sensing of L-thyroxine preconcentrated on magnetic-MIP was successfully performed on magneto-actuated electrodes within 30 min with a limit of detection of as low as 0.0356 ng mL⁻¹ which cover the clinical range of total L-thyroxine. Finally, the main analytical features were compared with the gold standard method based on commercial competitive immunoassays. This work provides a thoughtful strategy for magnetic molecularly imprinted polymer design, synthesis and application, opening new perspectives in the integration of these materials in magneto-actuated approaches for replacing specific antibodies in biosensors and microfluidic devices.



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AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Mohammad Rizwan, Syazwani Elma, Syazana Abdullah Lim, Minhaz Uddin Ahmed
In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA-immunosensors was studied using cyclic voltammetry (CV) and square wave voltammetry (SWV). By combining the advantages of large surface area and electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS, AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200% increase in effective surface area and electronic conductivity. The calibration plot gave a negative linear relationship between log[concentration] of CEA and electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor demonstrated a wide linear detection range of 100 fg mL⁻¹ to 400 ng mL⁻¹ with a low detection limit of 100 fg mL⁻¹. In addition to high sensitivity, reproducibility and large stability, CEA-immunosensor provided an excellent selectivity and resistant-to-interference in the presence of other antigens in serum and hence a potential to be used with real samples.



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Nursing and Politics.

Author: Brodbeck, Jessica MSN, RN, AOCNS

Page: 10

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Nursing and Politics.

Author: Newcomb, Patricia PhD, RN, CPNP

Page: 10

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Ethical Issues.

Author: Marylyn, via ajnoffthecharts.com

Page: 10

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AMA Resolution Opposes Independent Practice by APRNs.

Author: Sofer, Dalia

Page: 12

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ED Visits for Self-Harm by Girls Are on the Rise.

Author: Stockwell, Serena

Page: 13

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Seniors Need Hip Fracture Surgery Within 24 Hours.

Author: Potera, Carol

Page: 14

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CMS Delays Fines for Nursing Home Infractions.

Author: Mechcatie, Elizabeth BSN

Page: 15

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NewsCAP: The WHO reports global circulation of fraudulent medical products.

Author:

Page: 15

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The CDC's HI-5 Initiative.

Author: Nelson, Roxanne

Page: 18-19

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AJN On the Cover.

Author: Szulecki, Diane Editor

Page: 20

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AJN On the Web.

Author:

Page: 20

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FDA Warns Against Unregulated Products.

Author: Aschenbrenner, Diane S. MS, RN

Page: 22-23

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Risk of Heart-Related Death From Gout Medication.

Author: Aschenbrenner, Diane S. MS, RN

Page: 23

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Conversation.

Author: Carini, Simona MA

Page: 33

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Luminal A Breast Cancer and Molecular Assays: A Review

AbstractPurpose.Chemotherapy has been the historical mainstay of treatment for patients with breast cancer, with immunohistochemical markers and tumor characteristics driving treatment decisions. The discovery of different intrinsic subtypes of breast cancer has advanced the understanding of breast cancer, with gene‐based assays shedding further light on tumor behavior and response to treatment.Design.This review focuses on the landscape of the luminal A subtype, its definition based on immunohistochemistry (IHC) and gene assays, the prognostic and predictive value of these assays, guideline recommendations, and treatment implications.Results.Clinical studies of the prognostic value of gene‐based and IHC‐based assays in patients with luminal A‐subtype breast cancers suggest a better prognosis for these patients compared with those with breast cancers of other subtypes.Conclusion.In today's era of precision medicine, the best treatment regimen for patients with luminal A‐subtype tumors is still undetermined, but available data raise the question whether chemotherapy can be omitted and endocrine therapy alone is sufficient for this patient population.Implications for Practice.Immunohistochemical markers have traditionally guided treatment decisions in breast cancer. However, advances in gene‐expression profiling and availability of gene‐based assays have launched these newer tests into everyday clinical practice. Luminal A‐subtype tumors are a unique subset that may have favorable tumor biology. Properly defining this tumor subtype is important and may identify a subset of patients for whom endocrine therapy alone is sufficient.

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Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG)

AbstractLessons Learned. Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study.Background.The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70.Materials and Methods.Patients aged ≥70 years with a KPS <70 and biopsy‐proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130–150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks.Results.The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19–27.6), and the median progression‐free survival (PFS) was 15.3 weeks (95% CI, 12.9–19.3). Twenty‐two (33%) patients became transiently capable of self‐care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%).Conclusion.This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.

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Cancer Diagnosis: A Trauma for Patients and Doctors Alike

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The emerging use of bioluminescence in medical research

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Sana Sharifian, Ahmad Homaei, Roohullah Hemmati, Rodney B. Luwor, Khosro Khajeh
Bioluminescence is the light produced by a living organism and is commonly emitted by sea life with Ca²⁺-regulated photoproteins being the most responsible for bioluminescence emission. Marine coelenterates provide important functions involved in essential purposes such as defense, feeding, and breeding. In this review, the main characteristics of marine photoproteins including aequorin, clytin, obelin, berovin, pholasin and symplectin from different marine organisms will be discussed. We will focused on the recent use of recombinant photoproteins in different biomedical research fields including the measurement of Ca²⁺ in different intracellular compartments of animal cells, as labels in the design and development of binding assays. This review will also outline how bioluminescent photoproteins have been used in a plethora of analytical methods including ultra-sensitive assays and in vivo imaging of cellular processes. Due to their unique properties including elective intracellular distribution, wide dynamic range, high signal-to-noise ratio and low Ca²⁺-buffering effect, recombinant photoproteins represent a promising future analytical tool in several in vitro and in vivo experiments.



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The clinical significance and biological function of tropomyosin 4 in colon cancer

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Rui Yang, Gang Zheng, Defa Ren, Chunzhou Chen, Cheng Zeng, Wei Lu, Hua Li
Tropomyosin 4 (TPM4) has been found to be dys-regulated, and function as oncogene or anti-oncogene in human cancers. However, there was no report on the clinical significance and biological function of TPM4 in colon cancer. This study was designed to investigate the clinical value and biological function of TPM4 in colon cancer. Thus, we detected the TPM4 expression in colon cancer clinical samples, and conducted the gain-of-function in colon cancer cell lines. In our results, TPM4 mRNA and protein expressions were reduced in colon cancer tissues and cell lines compared with normal colon tissues and colon epithelial cell line, respectively. TPM4 protein low-expression was obviously associated with clinical stage, T classification (invasion depth), N classification (lymph node metastasis), distant metastasis and differentiation. Survival analysis showed low-expression of TPM4 was an unfavorable independent prognostic factor for colon cancer patients. Moreover, the experiments in vitro suggested up-regulated TPM4 expression suppressed colon cancer cell migration, invasion and metastasis-associated gene expression including MMP-2, MMP-9 and MT1-MMP, but had no effect on cell proliferation. In conclusion, TPM4 is associated with clinical progression in colon cancer patient and acts as a tumor suppressor in colon cancer cell.

Graphical abstract

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Kockdown of OIP5-AS1 expression inhibits proliferation, metastasis and EMT progress in hepatoblastoma cells through up-regulating miR-186a-5p and down-regulating ZEB1

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Ze Zhang, Feng Liu, Fan Yang, Yahui Liu
Long non-coding RNA OIP5-AS1 has been studied in human diseases, including several kinds of cancers. It was not studied or reported in hepatoblastoma, so we chose it to do our research in hepatoblastoma. We thought OIP5-AS1 was oncogenic in hepatoblastoma for the high expression of it in hepatoblastoma tissues and cells. OIP5-AS1 knockdown was carried out in cancer cells. Unsurprisingly, this action was verified to be able to inhibit cell proliferation, metastasis and EMT progress in hepatoblastoma. We then measured the low expression level of miR-186a-5p and the high expression level of ZEB1 in hepatoblastoma tissues and cells. The relevance among them was analyzed by using correlation analysis. In order to prove the ceRNA pattern in this study, nuclear separation experiment, RIP assay and dual luciferase assays were all put into use. We discovered OIP5-AS1 is located in nucleus of cancerous cells. It could target to miR-186a-5p and up-regulate the target gene of miR-186a-5p (ZEB1). Finally, rescue assay was utilized and proved the effect of OIP5-AS1-miR-186a-5p-ZEB1 axis on hepatoblastoma cell activities. Based on all above findings, we came into a conclusion that OIP5-AS1 is a ceRNA in Hepatoblastoma cells through modulating miR-186a-5p/ZEB1.



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