Publication date: November 2017
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): T. Xu, F.C. Cardoso, A. Pineda, E. Trevisi, X. Shen, F. Rosa, J.S. Osorio, J.J. Loor
Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR. Among the 28 biomarkers analyzed in blood 12 h after grain challenge on d 5, the concentrations of fatty acids and bilirubin increased in HIG Holstein but not Jersey cows. In Holsteins, feeding HIG also increased total protein and albumin while decreasing ceruloplasmin, myeloperoxidase, and alkaline phosphatase concentrations. At the molecular level, hepatic genes associated with inflammation (IL1B, IL6, TNF, TLR4, MYD88, and NFKB1) were upregulated in Holstein cows fed HIG versus CON. Despite such response, expression of the acute-phase proteins SAA and HP in Holsteins fed HIG compared with CON was markedly downregulated. In Holsteins fed HIG versus CON, the marked downregulation of SCD, ELOVL6, and MTTP along with upregulated CPT1A, ACOX1, and APOA5 indicated alterations in fatty acid and lipoprotein metabolism during grain challenge. Genes related to ketogenesis (HMGCS2 and ACAT1) were upregulated in Jerseys, and gluconeogenic genes (PDK4 and PCK1) were upregulated in Holstein cows fed HIG, suggesting alterations in ketone body and glucose production. Expression of phosphorylated p70S6K1, RPS6, and 4EBP1 proteins, as well as total mechanistic target of rapamycin (mTOR) protein, decreased in Holsteins fed HIG, whereas phosphorylated mTOR and 4EBP1 proteins increased in Jerseys fed HIG. From a metabolic and inflammatory biomarker standpoint, data indicate that Jersey cows better tolerated the acute grain challenge. Alterations in mTOR signaling proteins in both Jerseys and Holsteins fed HIG suggest a potential role for exogenous AA in the hepatic adaptations to grain challenge. It remains to be determined if these acute responses to a grain challenge can elicit long-term liver dysfunction, which could negatively affect welfare of the cow.
http://ift.tt/2ygsUEC
Τετάρτη 11 Οκτωβρίου 2017
Grain challenge affects systemic and hepatic molecular biomarkers of inflammation, stress, and metabolic responses to a greater extent in Holstein than Jersey cows
Short communication: Sensitive detection of norbixin in dried dairy ingredients at concentrations of less than 1 part per billion
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): B.G. Carter, C.W. Park, M.A. Drake
Norbixin is the water-soluble carotenoid in annatto extracts used in the cheese industry to color Cheddar cheese. The purpose of norbixin is to provide cheese color, but norbixin is also present in the whey stream and contaminates dried dairy ingredients. Regulatory restrictions dictate that norbixin cannot be present in dairy ingredients destined for infant formula or ingredients entering different international markets. Thus, there is a need for the detection and quantification of norbixin at very low levels in dried dairy ingredients to confirm its absence. A rapid method for norbixin evaluation exists, but it does not have the sensitivity required to confirm norbixin absence at very low levels in compliance with existing regulations. The current method has a limit of detection of 2.7 μg/kg and a limit of quantification of 3.5 μg/kg. The purpose of this study was to develop a method to extract and concentrate norbixin for quantification in dried dairy ingredients below 1 μg/kg (1 ppb). A reverse-phase solid-phase extraction column step was applied in the new method to concentrate and quantify norbixin from liquid and dried WPC80 (whey protein concentrate with 80% protein), WPC34 (WPC, 34% protein), permeate, and lactose. Samples were evaluated by both methods for comparison. The established method was able to quantify norbixin in whey proteins and permeates (9.39 μg/kg to 2.35 mg/kg) but was unable to detect norbixin in suspect powdered lactose samples. The newly developed method had similar performance to the established method for whey proteins and permeates but was also able to detect norbixin in powdered lactose samples. The proposed method had a >90% recovery in lactose samples and a limit of detection of 28 ppt (ng/kg) and a limit of quantification of 94 ppt (ng/kg). The developed method provides detection and quantification of norbixin for dairy ingredients that have a concentration of <1 ppb.
http://ift.tt/2xySK2Z
The global regulator CodY responds to oxidative stress by the regulation of glutathione biosynthesis in Streptococcus thermophilus
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): Y. Wang, H.Y. He, H.H. Li, W.W. Lu, T.T. Guo, J. Kong
CodYst is a global transcriptional regulator that modulates the metabolic network in Streptococcus thermophilus ST2017. In this study, experimental data showed that the cell survival of the codYst defective mutant obviously declined at the presence of 10 mM H2O2, suggesting CodYst was involved in response to the oxidative stress. To investigate this phenomenon, transcriptome analysis and real time-quantitative PCR were performed and the results indicated that the transcriptional level of a bifunctional glutathione synthetase gene (gshF) was downregulated by about 3-fold in the codYst defective mutant, along with a decrease by 20% of the glutathione yield compared with the wild-type in minimal chemical defined medium, whereas half of the viable cells remained after H2O2 challenge. In vitro gel shift assays showed that the purified CodYst could bind to the promoter region of gshF, with a conserved CodYst box, confirming the regulation of CodYst on the gshF gene. To our knowledge, this is first report of CodYst in response to oxidative stress mediated by the regulation of gshF in S. thermophilus.
http://ift.tt/2yg7RBO
Differential enumeration of subpopulations in concentrated frozen and lyophilized cultures of Lactobacillus delbrueckii ssp. bulgaricus
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): Yuyu Shao, Zhaoxia Wang, Qiuhua Bao, Heping Zhang
Differential enumeration of subpopulations in concentrated frozen and lyophilized cultures of Lactobacillus delbrueckii ssp. bulgaricus ND02 derived from 2 propagation procedures was determined. The subpopulations consisted of 3 categories (physiological states): viable cells capable of forming colonies on agar plates (VC+), viable cells incapable of forming colonies on agar plates (VC−), widely referred to as viable but nonculturable (VBNC) cells, and nonviable or dead cells (NVC). Counts of VC+ were recorded using a conventional plate count procedure. A fluorescent vital staining procedure that discriminates between viable (VC+ and VC−) and NVC cells was used to determine the number of viable and nonviable cells. Both propagation procedures had 2 variables: in procedure (P)1, the propagation medium was rich in yeast extract (4.0%) and the pH was maintained at 5.7; in P2, the medium was devoid of yeast extract and the pH was maintained at 5.1. The results showed that post-propagation operations—concentration of cells by centrifugation and subsequent freezing or lyophilization of cell concentrate—induced different degrees of transience from VC+ to VC− states in cells derived from P1 and P2. Compared with cells derived from P2, cells from P1 were more labile to stress associated with centrifugation, freezing, and lyophilization, as revealed by differential counting.
http://ift.tt/2xzcTWx
Longitudinal assessment of dairy farm management practices associated with the presence of psychrotolerant Bacillales spores in bulk tank milk on 10 New York State dairy farms
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): S.N. Masiello, D. Kent, N.H. Martin, Y.H. Schukken, M. Wiedmann, K.J. Boor
The ability of certain spore-forming bacteria in the order Bacillales (e.g., Bacillus spp., Paenibacillus spp.) to survive pasteurization in spore form and grow at refrigeration temperatures results in product spoilage and limits the shelf life of high temperature, short time (HTST)-pasteurized fluid milk. To facilitate development of strategies to minimize contamination of raw milk with psychrotolerant Bacillales spores, we conducted a longitudinal study of 10 New York State dairy farms, which included yearlong monthly assessments of the frequency and levels of bulk tank raw milk psychrotolerant spore contamination, along with administration of questionnaires to identify farm management practices associated with psychrotolerant spore presence over time. Milk samples were first spore pasteurized (80°C for 12 min) and then analyzed for sporeformer counts on the initial day of spore pasteurization (SP), and after refrigerated storage (6°C) for 7, 14, and 21 d after SP. Overall, 41% of samples showed sporeformer counts of >20,000 cfu/mL at d 21, with Bacillus and Paenibacillus spp. being predominant causes of high sporeformer counts. Statistical analyses identified 3 management factors (more frequent cleaning of the bulk tank area, the use of a skid steer to scrape the housing area, and segregating problem cows during milking) that were all associated with lower probabilities of d-21 Bacillales spore detection in SP-treated bulk tank raw milk. Our data emphasize that appropriate on-farm measures to improve overall cleanliness and cow hygiene will reduce the probability of psychrotolerant Bacillales spore contamination of bulk tank raw milk, allowing for consistent production of raw milk with reduced psychrotolerant spore counts, which will facilitate production of HTST-pasteurized milk with extended refrigerated shelf life.
http://ift.tt/2ygsKNw
Prevalence, antimicrobial susceptibility, and molecular characterization of Staphylococcus aureus isolated from dairy herds in northern China
Publication date: November 2017
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): Huimin Liu, Songli Li, Lu Meng, Lei Dong, Shengguo Zhao, Xinyi Lan, Jiaqi Wang, Nan Zheng
Staphylococcus aureus is one of the main pathogens involved in dairy cow mastitis. Monitoring of antibiotic use would prove useful to assess the risk of Staph. aureus in raw milk. The objective of this work was to investigate the prevalence of Staph. aureus strais isolated from raw milk in northern China, and to characterize antimicrobial susceptibility of these strains and their key virulence genes. In total, 195 raw milk samples were collected from 195 dairy farms located in 4 cities of northern China from May to September 2015. Out of 195 samples, 54 (27.7%) were positive for Staph. aureus. Among these 54 samples, 54 strains of Staph. aureus were isolated, and 16 strains were identified as methicillin-resistant Staph. aureus. The strains exhibited high percentages of resistance to penicillin G (85.2%), ampicillin (79.6%), and erythromycin (46.3%). Moreover, 72% of the strains showed resistance to more than one antimicrobial agent. Overall, 63% of penicillin-resistant strains possessed the blaZ gene, and 60% of the erythromycin-resistant strains possessed erm(A), erm(B), erm(C), msr(A), or msr(B) genes with 8 different gene patterns. All isolates resistant to gentamicin, kanamycin, and oxacillin carried the aac6'-aph2", ant(4')-Ia, and mecA genes, respectively. Two tet(M)-positive isolates carried specific genes of the Tn916-Tn1545 transposon. The most predominant virulence genes were sec, sea, and pvl, which encode staphylococcal enterotoxins (sec and sea) and Panton-Valentine leukocidin, respectively. Thirty-two isolates (59.2%) harbored one or more virulence genes. The majority of Staph. aureus strains were multidrug resistant and carried multiple virulence genes, which may pose a risk to public health. Our data indicated that antimicrobial resistance of Staph. aureus was prevalent in dairy herds in northern China, and that antibiotics, especially penicillin G and ampicillin, to treat mastitis caused by Staph. aureus should be used with caution in northern China.
http://ift.tt/2xyA0At
Rapid and simultaneous quantification of viable Escherichia coli O157:H7 and Salmonella spp. in milk through multiplex real-time PCR
Source:Journal of Dairy Science, Volume 100, Issue 11
Author(s): Baoqing Zhou, Taobo Liang, Zhongxu Zhan, Rui Liu, Fan Li, Hengyi Xu
Escherichia coli O157:H7 and Salmonella spp. in milk are 2 common pathogens that cause foodborne diseases. An accurate, rapid, specific method has been developed for the simultaneous detection of viable E. coli O157:H7 and Salmonella spp. in milk. Two specific genes, namely, fliC from E. coli O157:H7 and invA from Salmonella spp., were selected to design primers and probes. A combined treatment containing sodium deoxycholate (SDO) and propidium monoazide (PMA) was applied to detect viable E. coli O157:H7 and Salmonella spp. only. Traditional culture methods and SDO-PMA-multiplex real-time (mRT) PCR assay were applied to determine the number of viable E. coli O157:H7 and Salmonella spp. in cell suspensions with different proportions of dead cells. These methods revealed consistent findings regarding the detected viable cells. The detection limit of the SDO-PMA-mRT-PCR assay reached 102 cfu/mL for Salmonella spp. and 102 cfu/mL for E. coli O157:H7 in milk. The detection limit of SDO-PMA-mRT-PCR for E. coli O157:H7 and Salmonella spp. in milk was significantly similar even in the presence of 106 cfu/mL of 2 nontarget bacteria. The proposed SDO-PMA-mRT-PCR assay is a potential approach for the accurate and sensitive detection of viable E. coli O157:H7 and Salmonella spp. in milk.
http://ift.tt/2yfSbP0
Scholar : Acta Odontologica Scandinavica, Volume 75, Issue 8, November 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online
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Director Field Analysis (DFA): Exploring Local White Matter Geometric Structure in Diffusion MRI
Publication date: Available online 11 October 2017
Source:Medical Image Analysis
Author(s): Jian Cheng, Peter J. Basser
In Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging (HARDI), a tensor field or a spherical function field (e.g., an orientation distribution function field), can be estimated from measured diffusion weighted images. In this paper, inspired by the microscopic theoretical treatment of phases in liquid crystals, we introduce a novel mathematical framework, called Director Field Analysis (DFA), to study local geometric structural information of white matter based on the reconstructed tensor field or spherical function field: 1) We propose a set of mathematical tools to process general director data, which consists of dyadic tensors that have orientations but no direction. 2) We propose Orientational Order (OO) and Orientational Dispersion (OD) indices to describe the degree of alignment and dispersion of a spherical function in a single voxel or in a region, respectively; 3) We also show how to construct a local orthogonal coordinate frame in each voxel exhibiting anisotropic diffusion; 4) Finally, we define three indices to describe three types of orientational distortion (splay, bend, and twist) in a local spatial neighborhood, and a total distortion index to describe distortions of all three types. To our knowledge, this is the first work to quantitatively describe orientational distortion (splay, bend, and twist) in general spherical function fields from DTI or HARDI data. The proposed DFA and its related mathematical tools can be used to process not only diffusion MRI data but also general director field data, and the proposed scalar indices are useful for detecting local geometric changes of white matter for voxel-based or tract-based analysis in both DTI and HARDI acquisitions. The related codes and a tutorial for DFA will be released in DMRITool.
Graphical abstract
http://ift.tt/2hAoVJb
Scholar : These new articles for Amyloid are available online
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Innate Lymphoid Cell Regulation: Meeting the Long-Lost Cousin
Publication date: Available online 10 October 2017
Source:Trends in Immunology
Author(s): Matthew R. Hepworth
Innate lymphoid cells (ILCs) play critical roles in immune homeostasis and immunity to pathogens. Increasing evidence implicates dysregulated ILC responses as drivers of disease pathogenesis in multiple inflammatory disorders. A recent study reveals how inflammatory ILC responses can be suppressed by a newly defined subset of ILCs with regulatory function.
http://ift.tt/2fZsXuu
Diagnosis and treatment of TSH-secreting adenomas: review of a longtime experience in a reference center
Abstract
Purpose
TSH-secreting pituitary adenomas are among the less prevalent pituitary tumors, corresponding to 0.9–1.5% of all pituitary adenomas in surgical series.
Methods
A series of 11 patients with TSH-secreting and cosecreting adenomas diagnosed and treated in the last 25 years in a single center is described.
Results
The mean age at diagnosis was 37 years (range 18–80 years; median 23 years); the ratio of male-to-female patients was similar (6M:5F). Only three patients was the correct diagnosis established shortly after the initial medical evaluation. Other four patients were initially diagnosed with other pituitary adenomas (prolactinoma, acromegaly, and non-secreting pituitary tumor) and another four diagnosed with primary hyperthyroidism. There was a mean diagnostic delay of 6.0 years (range 0.5–25 years; median 2 years). Nine patients had macroadenomas and two patients had microadenomas. Seven patients underwent pituitary surgery which controlled the disease in only two (one micro- and one noninvasive macroadenoma). The other treatments were directed to the thyroid gland (surgery or 131I radiotherapy), pituitary radiotherapy, and somatostatin analog.
Conclusion
In spite of its relatively straightforward diagnosis, which includes clinical/subclinical hyperthyroidism with or without goiter, increased free thyroxine and nonsuppressed TSH levels, and pituitary mass, the diagnosis of TSH-secreting and cosecreting adenomas was frequently unrecognized and thus much delayed. Serum alpha-subunit levels were high in nearly all patients with TSH-secreting adenomas and useful in excluding other conditions in the differential diagnosis. Proper indication and interpretation of simple laboratory tests should be emphasized in medical education to improve diagnostic accuracy.
http://ift.tt/2yeKU2p
Chemoradiotherapy Versus Esophagectomy After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinoma
Interventions: Procedure: Esophagectomy; Drug: 5-fluorouracil; Drug: Cisplatin; Radiation: Radiation therapy
Sponsors: Samsung Medical Center; Ministry of Health & Welfare, Korea
Not yet recruiting
http://ift.tt/2ygnR6M
Small molecules convey big messages: Boosting non-viral nucleic acid delivery with low molecular weight drugs
Publication date: Available online 10 October 2017
Source:Nano Today
Author(s): Freya Joris, Stefaan C. De Smedt, Koen Raemdonck
There is no doubt regarding the therapeutic potential of nucleic acids (NA). However, to be functional NA require delivery into the cytoplasm or nucleus of the target cell. To overcome the extra-and intracellular barriers, NA are generally packaged into nanoparticles (i.e. nanomedicines). Unfortunately, current nanomedicines largely fail to deliver their NA cargo to its intracellular site of action. Interestingly, increasing evidence exists that major delivery hurdles can in part be overcome through helpful biological functions of low molecular weight compounds. This review summarizes how various (classes of) compounds can intervene at distinct stages of the NA delivery pathway. Small molecules are reported to influence processes including nanomedicine internalization, endosomal escape, intracellular trafficking and transgene expression. Of note, a number of compounds exert their effect by simultaneously affecting several of these steps. Interestingly, the low molecular weight adjuvants can be incorporated into the nanocarrier, conjugated to the nucleic acid or added before, during or after nanocarrier administration, indicating the versatility of this approach.
Graphical abstract
http://ift.tt/2ybnysh
Scholar : Philosophical Magazine, Volume 97, Issue 31, November 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Aphasiology are available online
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Muscle-derived extracellular superoxide dismutase inhibits endothelial activation and protects against multiple organ dysfunction syndrome in mice
Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Jarrod A. Call, Jean Donet, Kyle S. Martin, Ashish K. Sharma, Xiaobin Chen, Jiuzhi Zhang, Jie Cai, Carolina A. Galarreta, Mitsuharu Okutsu, Zhongmin Du, Vitor A. Lira, Mei Zhang, Borna Mehrad, Brian H. Annex, Alexander L. Klibanov, Russell P. Bowler, Victor E. Laubach, Shayn M. Peirce, Zhen Yan
Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other peripheral organs through the circulation and enriches at the endothelium of the vasculatures. TG mice are resistant to endotoxemia (induced by lipopolysaccharide [LPS] injection) in developing MODS with significantly reduced mortality and organ damages compared with the wild type littermates (WT). Heterogenic parabiosis between TG and WT mice conferred a significant protection to WT mice, whereas mice with R213G knock-in mutation, a human single nucleotide polymorphism leading to reduced binding EcSOD in peripheral organs, exacerbated the organ damages. Mechanistically, EcSOD inhibits vascular cell adhesion molecule 1 expression and inflammatory leukocyte adhesion to the vascular wall of vital organs, blocking an early step of the pathology in organ damage under endotoxemia. Therefore, enhanced expression of EcSOD in skeletal muscle profoundly protects against MODS by inhibiting endothelial activation and inflammatory cell adhesion, which could be a promising therapy for MODS.
Graphical abstract
http://ift.tt/2i33Nzg
Occurrence of selected elements (Ti, Sr, Ba, V, Ga, Sn, Tl, and Sb) in deposited dust and human hair samples: implications for human health in Pakistan
Abstract
The current study determined, for the first time, the levels of titanium (Ti), strontium (Sr), barium (Ba), vanadium (V), gallium (Ga), tin (Sn), thallium (Tl), and antinomy (Sb), in deposited dust, and human hair collected from general population of different geographical areas of Pakistan. All the samples were prepared by microwave digestion and measured by ICP-MS. The results showed that on deposited dust samples, the detected elements followed the descending trend as: Ti > Sr > Ba > V > Ga > Sn > Tl > Sb similar to the upper continental crust. The deposited dust samples from low elevation areas exhibited highest levels of all studied elements (except antimony which was higher in soil samples from mountainous areas), followed by rive plains, mountainous areas, and highland valleys. In contrast, on human hair samples, the elements followed the descending trend as: Sr > Ba > Ti > Ga > V > Sn > Sb > Tl respectively. Ba, Ga, and V concentrations were higher in soil samples from lower elevation Indus plain, and Sr, Tl, Sb, and Ti were higher in samples from mountainous areas. The bioaccumulation trend of all studied elements was in descending order as follows: Sb, Ga, Sn, Ba, Sr, Ti, V, Tl, respectively. Principal component analysis (PCA) and correlation matrix evidenced both geological influences and anthropogenic activities as potential sources of these studied elements. On the other hand, the risk estimation (HI > 1) concluded that population were at higher health risk (non-carcinogenic) for Ga and Ti. All other studied rare elements were within safe limit for humans from all zones.
http://ift.tt/2fZhScA
Scholar : AIDS Care, Volume 29, Issue 12, December 2017 is now available online on Taylor & Francis Online
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Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats
Publication date: December 2017
Source:Biomedicine & Pharmacotherapy, Volume 96
Author(s): Seyed Reza Fatemi Tabatabaei, Shahab Ghaderi, Mohammad Bahrami-Tapehebur, Yaghoob Farbood, Masome Rashno
Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals.
http://ift.tt/2g0D6XD
Use of 5-alpha-reductase inhibitors as alternatives to luteinizing-hormone releasing hormone (LHRH) analogues or anti-androgens for prostate downsizing prior to brachytherapy
Source:Practical Radiation Oncology
Author(s): Hee Joon Bae, Omar Mian, Dhananjay Vaidya, Theodore L. DeWeese, Daniel Y. Song
IntroductionProstate hypertrophy, median lobe hypertrophy (MLH) and pubic arch interference (PAI) are relative contraindications to brachytherapy due to potential morbidity and technical considerations. GnRH analogues or non-steroidal anti-androgens are currently utilized to achieve prostatic downsizing prior to brachytherapy. However, such agents have been associated with effects on body habitus, metabolism, and quality of life. In contrast, 5-alpha reductase inhibitors (5-ARI) are far less frequently associated with these morbidities.Materials and MethodsPatients with large gland size, MLH or PAI were offered 5-ARI therapy. Repeat TRUS was performed at 3–4months, followed by brachytherapy if resolution achieved. If downsizing was inadequate, then patients were offered continuation of 5-ARI for additional 3months, or GnRH agonist or antiandrogen therapy, or other curative treatment.ResultsOf 59 patients with follow-up available, 42 (71%) were deemed to have adequate downsizing; 37 (63%) after 3–4months of 5-ARI, and 5 (8%) after 7–8months. Seventeen patients (29%) received other treatments due to inadequate effect. Median volume reduction was 20%.Of 41 patients undergoing brachytherapy, 4 (9.7%) required temporary catheterization due to obstruction. Median follow-up after implantation was 25months (1–64months). Median time for return to IPSS ≤5 of baseline score was 7months (IQR 6–13months). All but 1 patient who received brachytherapy remain biochemically controlled.Discussion5-ARI monotherapy is an alternative for downsizing in patients with hypertrophy or PAI, with over 70% achieving adequate downsizing without use of GnRH analogues or antiandrogens. Patients who received brachytherapy experienced typical rates of post-implant urinary morbidity.SummaryAndrogen suppression in the form of luteinizing-hormone releasing hormone analogues or anti-androgens are currently utilized prior to brachytherapy for patients who have prostate hypertrophy or pubic arch interference. However, these agents have undesirable side effect profiles and have been associated with increased risk of cardiac mortality. We describe our experience with utilizing 5-alpha-reductase inhibitors alone as an alternative for this indication.
http://ift.tt/2wNM3dH
Spinal segmental myoclonus resembling “belly dance” in a pregnant woman
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Arens Taga, Irene Florindo, Ariane Kiener, Tiziana Frusca, Giovanni Pavesi
http://ift.tt/2gbdRpp
Fasciculations in nerve and muscle disorders – A prospective study of muscle ultrasound compared to electromyography
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): M.T. Johansson, H.R. Ellegaard, H. Tankisi, A. Fuglsang-Frederiksen, E. Qerama
ObjectivesWe examined the clinical utility of muscle ultrasound (MUS) in detecting fasciculations in patients with nerve and muscle disorders (NMD) and investigated the impact on diagnostic sensitivity when combining electromyography (EMG) and MUS.MethodsWe included 58 consecutive patients suspected to have NMD and 38 healthy subjects (HS). Patients and HS underwent MUS in 14 skeletal and two bulbar muscles and the video recordings of the MUS were anonymised. Only patients underwent EMG.ResultsThe follow-up diagnoses were: 15 Amyotrophic lateral sclerosis (ALS), 15 polyneuropathy, 14 patients had other diagnoses (disease-control group) and 14 patients had no pathological findings.MUS detected more muscles with fasciculations among ALS patients compared to all other groups. In ALS patients, the dominating pattern of fasciculations was continuous (45%). More proximal muscles showed fasciculations among ALS patients compared to all other patient groups. MUS was more sensitive than EMG in detecting fasciculations (58% vs. 48%). When combining the two methods, the sensitivity in detecting fasciculations increased to 65%. Fasciculations in nine muscles could predict the ALS diagnosis with high sensitivity and specificity.ConclusionsMUS is a sensitive tool in detecting fasciculations in patients with NMD and performs well compared to EMG in diagnosing ALS.SignificanceMUS may add valuable information in the clinic, especially in diagnosing ALS.
http://ift.tt/2yeFOmG
Comparison of injection site reactions between the etanercept biosimilar SB4 and the reference etanercept in patients with rheumatoid arthritis from a Phase III study
Abstract
Injection site reactions (ISRs) are common adverse reactions to biologic drugs, consisting of itching, erythema, and induration at the injection site1. ISRs usually appear within 24-48 hours after injection and subside within a few days. They typically occur in the first two months of treatment and subsequently decrease in frequency; incidence varies by drug. While ISRs seldom result in discontinuation of treatment, ISRs remain a safety concern when using biologic drugs.
This article is protected by copyright. All rights reserved.
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ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from ‘binge-like’ ethanol exposure in rats
Source:Behavioural Brain Research
Author(s): Marta Marszalek-Grabska, Ewa Gibula-Bruzda, Anna Bodzon-Kulakowska, Piotr Suder, Kinga Gawel, Sylwia Talarek, Joanna Listos, Ewa Kędzierska, Wojciech Danysz, Jolanta H. Kotlinska
Repeated exposure to and withdrawal from ethanol induces deficits in spatial reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors are implicated in synaptic plasticity and learning and memory. These receptors functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation of one type results in the activation of the other. We examined whether (S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX-47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates deficits in reversal learning induced by withdrawal (11-13days) from 'binge-like' ethanol input (5.0g/kg, i.g. for 5days) in the Barnes maze (a spatial learning) task in rats. We additionally examined the effects of ADX-47273 on the expression of the NMDA receptors subunit, GluN2B, in the hippocampus and prefrontal cortex, on the 13th day of ethanol withdrawal. Herein, withdrawal from repeated ethanol administration impaired reversal learning, but not the probe trial. Moreover, ADX-47273 (30mg/kg, i.p.) given prior to the first reversal learning trial for 3days in the Barnes maze, significantly enhanced performance in the ethanol-treated group. The 13th day of ethanol abstinence decreased the expression of the GluN2B subunit in the selected brain regions, but ADX-47273 administration increased it. In conclusion, positive allosteric modulation of mGlu5 receptors recovered spatial reversal learning impairment induced by withdrawal from 'binge-like' ethanol exposure. Such effect seems to be correlated with the mGlu5 receptors mediated potentiation of GluN2B-NMDA receptor mediated responses in the hippocampus and prefrontal cortex. Thus, our results emphasize the role of mGlu5 receptor PAM in the adaptive learning impaired by ethanol exposure.
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(+)-Borneol improves the efficacy of edaravone against DSS-induced colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway
Publication date: December 2017
Source:International Immunopharmacology, Volume 53
Author(s): Xiong Zhang, Fang Xu, Li Liu, Lili Feng, Xuefeng Wu, Yan Shen, Yang Sun, Xudong Wu, Qiang Xu
Compound edaravone injection (C.EDA), a compound preparation composed of edaravone (EDA) and (+)-Borneol with the mass ratio of 4: 1, displays a better anti-inflammatory activity than EDA. However, its precise mechanism remains to be further studied. In this work, we investigated whether (+)-Borneol could improve the efficacy of EDA against DSS-induced colitis. We found that C.EDA at 7.5 and 15mg/kg could significantly relieve the disease activity index (DAI) and reduce the loss of body weight and colon length in a dose-dependent manner, while EDA or (+)-Borneol alone only had moderate effects even at the highest dose. Additionally, ELISA revealed that C.EDA could more dramatically decrease the protein levels of inflammatory cytokines and increase the levels of anti-inflammatory cytokine than EDA or (+)-Borneol alone both in colon tissues and serum. H&E staining and IHC assay also indicated that C.EDA exhibited more prominent effects on increasing the population of M2 macrophages, decreasing M1 macrophages infiltration and protecting intestinal barrier integrity. Furthermore, in vitro studied demonstrated that C.EDA, EDA or (+)-Borneol failed in inhibiting M1 macrophages activation but could specifically induce the activation of M2 macrophages in a STAT3-dependent manner. Knockdown the expression of STAT3 successfully abolished the effect of C.EDA and EDA on promoting M2 macrophages activation. Consistent with in vivo study, C.EDA exhibited a more efficient ability of inducing M2 macrophages polarization and STAT3 activation than EDA or (+)-Borneol alone in vitro. In conclusion, we confirmed that (+)-Borneol improved the efficacy of EDA against DSS-induced colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway.
Graphical abstract
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Τρίτη 10 Οκτωβρίου 2017
Comparative evaluation of electrospraying and lyophilization techniques on solid state properties of Erlotinib nanocrystals: Assessment of In-vitro cytotoxicity
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Shreya Thakkar, Dilip Sharma, Manju Misra
IntroductionErlotinib is a well known FDA approved drug from category of tyrosine kinase inhibitors; used for the treatment of lung cancer. However its use is limited because of its poor water solubility.ObjectiveThe aim of present work was to improve solubility by developing a stable nanocrystal based drug delivery system of ERL with the aid of sodium lauryl sulfate as potential stabilizer and to carry out comparative evaluation of electrospraying and lyophilization as solidification techniques on its solid state properties.ExperimentalNanocrystal formulation was developed with antisolvent precipitation method having particle size, polydispersity index and zetapotential of 232.4±4.3nm, 0.162 and −9.82mV respectively. Further comparative evaluation of lyophilization and electrospraying was commenced as potential solidification techniques and solid powder matrix obtained from both the solidification techniques were compared in terms of size after re-dispersion (260±4.8 and 329±5.2nm respectively), particle morphology, surface area (0.984±0.11 and 0.341±0.05m2/g respectively), pore volume (0.0014 and 0.0009cc/g respectively), solid state of drug present and % drug release (~100% and ~78% respectively in 600min). In vitro cytotoxicity studies shared that obtained formulation was having reduced IC50 values in comparison to drug. Further intracellular reactive oxygen species production was found to be higher for formulation treated cells when compared to free drug. Overall developed formulation was found to be potential drug delivery system for lung cancer therapy.
Graphical abstract
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Statistical investigation of the full concentration range of fasted and fed simulated intestinal fluid on the equilibrium solubility of oral drugs
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Jeremy Perrier, Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G. Wilson, Gavin Halbert
Upon oral administration the solubility of a drug in intestinal fluid is a key property influencing bioavailability. It is also recognised that simple aqueous solubility does not reflect intestinal solubility and to optimise in vitro investigations simulated intestinal media systems have been developed. Simulated intestinal media which can mimic either the fasted or fed state consists of multiple components each of which either singly or in combination may influence drug solubility, a property that can be investigated by a statistical design of experiment technique. In this study a design of experiment covering the full range from the lower limit of fasted to the upper limit of fed parameters and using a small number of experiments has been performed. The measured equilibrium solubility values are comparable with literature values for simulated fasted and fed intestinal fluids as well as human fasted and fed intestinal fluids. The equilibrium solubility data range is statistically equivalent to a combination of published fasted and fed design of experiment data in six (indomethacin, phenytoin, zafirlukast, carvedilol, fenofibrate and probucol) drugs with three (aprepitant, tadalafil and felodipine) drugs not equivalent. In addition the measured equilibrium solubility data sets were not normally distributed. Further studies will be required to determine the reasons for these results however it implies that a single solubility measurement without knowledge of the solubility distribution will be of limited value. The statistically significant media factors which promote equilibrium solubility (pH, sodium oleate and bile salt) were in agreement with published results but the number of determined significant factors and factor interactions was fewer in this study, lecithin for example did not influence solubility. This may be due to the reduction in statistical sensitivity from the lower number of experimental data points or the fact that using the full range will examine media parameters ratios that are not biorelevant. Overall the approach will provide an estimate of the solubility range and the most important media factors but will not be equivalent to larger scale focussed studies. Further investigations will be required to determine why some drugs do not produce equivalent DoE solubility distributions, for example combined fasted and fed DoE, but this simply may be due to the complexity and individuality of the interactions between a drug and the media components.
Graphical abstract
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Studying of drug solubility in water and alcohols using drug-ammonium ionic liquid-compounds
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Mohammad Halayqa, Aneta Pobudkowska, Urszula Domańska, Maciej Zawadzki
Synthesis of three mefenamic acid (MEF) derivatives - ionic liquid compounds composed of MEF in an anionic form and ammonium cation (choline, MEF1), or {di(2-hydroxyethyl)dimethyl ammonium (MEF2)}, or {tri(2-hydroxyethyl)methyl ammonium compound (MEF3)} is presented. The basic thermal properties of pure compounds i.e. fusion temperatures, and the enthalpy of fusion of these compounds have been measured with differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The solubilities of MEF1, MEF2 and MEF3 using the dynamic method were measured at constant pH in a range of temperature from (290 to 370) K in three solvents: water, ethanol and 1-octanol. The experimental solubility data have been correlated by means of three commonly known GE equations: the Wilson, NRTL and UNIQUAC with the assumption that the systems studied here present simple eutectic behaviour. The activity coefficients of pharmaceuticals at saturated solutions in each binary mixture were calculated from the experimental data. The formation of MEF-ionic liquid compounds greatly increases the solubility in water in comparison with pure MEF or complexes with 2-hydroxypropyl-β-cyclodextrin. The development of these compounds formulations will assist in medication taking into account oral solid or gel medicines.
Graphical abstract
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Binding affinity toward human prion protein of some anti-prion compounds — Assessment based on QSAR modeling, molecular docking and non-parametric ranking
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Strahinja Kovačević, Milica Karadžić, Sanja Podunavac-Kuzmanović, Lidija Jevrić
The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein (huPrPC) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome.
Graphical abstract
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Insight into lipophilicity of deoxyribonucleoside‑boron cluster conjugates
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Aneta Dąbrowska, Michał Matuszewski, Krzysztof Zwoliński, Anna Ignaczak, Agnieszka B. Olejniczak
Lipophilicity was investigated for 20 2′-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D7.4) for ionic compounds were determined as a lipophilicity descriptor using a shake-flask method. All modified nucleosides had P/D7.4 values higher than those of an appropriate unmodified 2′-closo-dodecaborane and metallacarborane was found to be three orders of magnitude higher than that of its unmodified counterpart. The lowest impact on the P/D7.4 values of the conjugates was observed for the 7,8-dicarba-nido-undecaborate anion. A preliminary molecular modeling study of a thymidine-carborane conjugate with β-cyclodextrin confirmed the ability of the components to form an inclusion complex.
Graphical abstract
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Tuning the rheological properties of an ammonium methacrylate copolymer for the design of adhesives suitable for transdermal patches
Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Gaia M.G. Quaroni, Chiara G.M. Gennari, Francesco Cilurzo, Guylaine Ducouret, Costantino Creton, Paola Minghetti
Eudragit® RL (EuRL) matrices have been proposed to release a drug to the skin. However, no information is available on both viscoelastic and adhesive properties of such compositions. This work focuses on the evaluation of both rheological and texture properties of EuRL differently plasticized with tributyl citrate (TBC) or triacetin (TRI) in order to design a pressure sensitive adhesive suitable for transdermal patch preparation. The patch adhesive properties (i.e. tack, peel adhesion and shear adhesion) as well as its in vitro biopharmaceutical performances were determined after loading ibuprofen, ketoprofen or flurbiprofen. The addition of 40–60% w/w TBC or 40–50% w/w TRI to EuRL permitted to obtain matrices with the desired adhesive properties. Moreover, the increase of plasticizer content and loading of the drug reduced the relaxation time (τR). Consequently, the shear adhesion values decreased and the in vitro drug release constants (k) increased. Indeed, the k values from patches containing TBC were lower than the corresponding with TRI because of the lower fluidity of such matrices. In conclusion, the 60/40 EuRL/TBC binary blend is suitable for the design of transdermal patches since the in vitro permeability of the three selected drugs appeared comparable to those described in literature for marketed products.
Graphical abstract
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Effect of a high-cholesterol diet on lipoprotein metabolism and xanthoma formation in rabbits
Summary
Background
Xanthelasma is the most common type of cutaneous xanthoma and often occurs on the eyelids. Xanthoma has been reported to be highly correlated with abnormal lipoprotein metabolism.
Aims
In this study, we wanted to investigate the effects of a high-cholesterol diet on xanthoma formation and lipoprotein metabolism in rabbits.
Methods
In animals fed with high-cholesterol diet, deteced plasma lipid [ie, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (L-DLC)] levels and pathology of xanthoma.
Results
Plasma lipid levels were dramatically elevated within 8 weeks. In addition, high dietary cholesterol promoted xanthoma formation on the napex. Microscopic examination showed that foam cells laden with cholesterol deposits accumulated around the dermal capillaries and cutaneous appendages within the skin of the napex.
Conclusion
These findings indicate a critical role for a high-cholesterol diet in the dysregulation of lipoprotein metabolism and the development of xanthoma in rabbits. The results suggest that abnormal lipid metabolism may increase the occurrence of xanthoma.
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Reconsidering the H&E stain as the gold standard in assessing the depth of burn wounds
While histological examination is considered by most as the gold standard for burn depth assessment, it has no practical use in the clinical setting. It has, however, been used in the research setting, as a mean for evaluating emerging techniques of depth measurement. Due to the limitations of the H&E stain, other stains have also been explored, such as lactate dehydrogenase (LDH), as presented in this issue, in "Improving the Histologic Characterization of Burn Depth." As the determination of burn depth is not a typical subject in dermatopathology, a summary of selected techniques and the possible role for the LDH stain in future research, is described herein.
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Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP and PFC
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Missing ozone-induced potential aerosol formation in a suburban deciduous forest
Publication date: Available online 10 October 2017
Source:Atmospheric Environment
Author(s): T. Nakayama, Y. Kuruma, Y. Matsumi, Y. Morino, K. Sato, H. Tsurumaru, S. Ramasamy, Y. Sakamoto, S. Kato, Y. Miyazaki, T. Mochizuki, K. Kawamura, Y. Sadanaga, Y. Nakashima, K. Matsuda, Y. Kajii
As a new approach to investigating formation processes of secondary organic aerosol (SOA) in the atmosphere, ozone-induced potential aerosol formation was measured in summer at a suburban forest site surrounded by deciduous trees, near Tokyo, Japan. After passage through a reactor containing high concentrations of ozone, increases in total particle volume (average of 1.4 × 109 nm3/cm3, which corresponds to 17% that of pre-existing particles) were observed, especially during daytime. The observed aerosol formations were compared with the results of box model simulations using simultaneously measured concentrations of gaseous and particulate species. According to the model, the relative contributions of isoprene, monoterpene, and aromatic hydrocarbon oxidation to SOA formation in the reactor were 24, 21, and 55%, respectively. However, the model could explain, on average, only ∼40% of the observed particle formation, and large discrepancies between the observations and model were found, especially around noon and in the afternoon when the concentrations of isoprene and oxygenated volatile organic compounds were high. The results suggest a significant contribution of missing (unaccounted-for) SOA formation processes from identified and/or unidentified volatile organic compounds, especially those emitted during daytime. Further efforts should be made to explore and parameterize this missing SOA formation to assist in the improvement of atmospheric chemistry and climate models.
Graphical abstract
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MTA promotes chemotaxis and chemokinesis of immune cells through distinct calcium-sensing receptor signaling pathways
Source:Biomaterials, Volume 150
Author(s): Fengjiao Chang, Jin Man Kim, Youngnim Choi, Kyungpyo Park
Mineral trioxide aggregate (MTA) has been introduced as a choice material for regenerative dentistry. To date, the diverse biological activities of MTA, including its anti-inflammatory effects, have been extensively discussed. However, there is limited insight into the link between MTA and immune cell migration. In this study, we report the role of MTA in enhancing both chemotactic and chemokinetic immune cell migration through distinct signaling pathways. By using versatile live imaging techniques, we demonstrated that MTA-mediated CaSR activation induced diverse downstream pathways to govern cell migratory capacity. In this context, Cdc42 generates cytoskeleton-driven cellular protrusions to steer directional cell migration (chemotaxis) whereas Ca2+-calmodulin dependent myosin light chain kinase induces cell contractility that plays an important role in speeding up the average migration speed (chemokinesis). Our findings illuminate an unrecognized role for MTA and the related CaSR signaling network in immune cell migration, providing evidence that can drive development of novel approaches to immunological therapy.
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Enhanced antitumor efficacy of arginine modified amphiphilic nanoparticles co-delivering doxorubicin and iSur-pDNA via the multiple synergistic effect
Source:Biomaterials, Volume 150
Author(s): Yudong Song, Cui Tang, Chunhua Yin
Arginine and α-tocopherol succinate (α-TOS) double grafted N-trimethyl chitosan chloride (TMC) nanoparticles (TAS NPs) were designed and developed for effective co-delivery of doxorubicin (DOX) and Survivin shRNA-expressing pDNA (iSur-pDNA). With DOX loading into the hydrophobic core and iSur-pDNA combining to the hydrophilic shell, TAS/DOX/pDNA NPs demonstrated favorable structural stability and sustained release properties in vitro. With the special non-clathrin-dependent endocytosis, TAS/DOX/pDNA NPs presented higher cellular uptake and mainly distributed in ER and Golgi rather than lysosomes following internalization. The in vitro nuclear localization, gene silencing efficiency, cell apoptosis, and growth inhibition of tumor cells were significantly promoted by arginine modification. In the tumor-bearing mice model, TAS/DOX/pDNA NPs possessed the maximum antitumor efficiency as compared with single delivery of DOX or iSur-pDNA. Particularly, blank TAS NPs were selectively be toxic to tumor cells as evidenced by their capabilities to inhibit proliferation and induce apoptosis of tumor cells. The promising tumor treatment of TAS/DOX/pDNA NPs via a multiple synergistic manner arising from DOX and pDNA as well as the vectors would provide a potential strategy for a dual-delivery system to improve their therapeutic efficacies.
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Editorial board
Source:Biomaterials, Volume 148
http://ift.tt/2ze0J7A
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
