Publication date: Available online 5 January 2017
Source:Medical Journal Armed Forces India
Author(s): Ravi Bhushan, Arijit Sen
BackgroundVery few Indian studies exist on evaluation of pre-analytical variables affecting "Prothrombin Time" the commonest coagulation assay performed. The study was performed in an Indian tertiary care setting with an aim to assess quantitatively the prevalence of pre-analytical variables and their effects on the results (patient safety), for Prothrombin time test. The study also evaluated their effects on the result and whether intervention, did correct the results.MethodsThe firstly evaluated the prevalence for various pre-analytical variables detected in samples sent for Prothrombin Time testing. These samples with the detected variables wherever possible were tested and result noted. The samples from the same patients were repeated and retested ensuring that no pre-analytical variable is present. The results were again noted to check for difference the intervention produced.ResultsThe study evaluated 9989 samples received for PT/INR over a period of 18 months. The prevalence of different pre-analytical variables was found to be 862 (8.63%). The proportion of various pre-analytical variables detected were haemolysed samples 515 (5.16%), over filled vacutainers 62 (0.62%), under filled vacutainers 39 (0.39%), low values 205 (2.05%), clotted samples 11 (0.11%), wrong labeling 4 (0.04%), wrong vacutainer use 2 (0.02%), chylous samples 7 (0.07%) and samples with more than one variable 17 (0.17%). The comparison of percentage of samples showing errors were noted for the first variables since they could be tested with and without the variable in place. The reduction in error percentage was 91.5%, 69.2%, 81.5% and 95.4% post intervention for haemolysed, overfilled, under filled and samples collected with excess pressure at phlebotomy respectively.ConclusionCorrecting the variables did reduce the error percentage to a great extent in these four variables and hence the variables are found to affect "Prothrombin Time" testing and can hamper patient safety.
http://ift.tt/2iYXGbt
Παρασκευή 6 Ιανουαρίου 2017
Quantitative assessment of prevalence of pre-analytical variables and their effect on coagulation assay. Can intervention improve patient safety?
Knowledge of breastfeeding practices in doctors and nurses: A questionnaire-based survey
Publication date: Available online 5 January 2017
Source:Medical Journal Armed Forces India
Author(s): Subhash Chandra Shaw, Amit Devgan
BackgroundAs the primary physicians and nurses in hospitals are the first contact with the mothers, we carried out a questionnaire-based survey to assess the knowledge of the MBBS nonspecialist doctors and general duty nurses regarding breastfeeding of normal newborns.MethodsThirty-four MBBS, nonspecialist doctors and ninety-seven general duty nurses were enrolled in the study between August 2016 and September 2016 in a tertiary care teaching hospital, and a questionnaire comprising of 10 questions on breastfeeding was provided to each.ResultsAll doctors (100%) and nurses (100%) agreed that breastfeeding must be started within 1h of birth and all nurses (100%) agreed that breastfeeding alone is sufficient for a newborn baby during the first 2–3 days of life. However, 58.8% of the doctors and 25.7% of the nurses believed that after 6 months of life, the mother must give her infant cow's milk or formula for better growth. Only 52.9% of doctors and 40.2% of nurses agreed that breastfeeding should be advised to be continued for 2 years and beyond. Among doctors only 67.6% believed that breastfeeding for a normal newborn should be on demand only and not by clock.ConclusionThere is scope of improvement regarding knowledge of breastfeeding in both doctors and nurses. All healthcare providers must provide correct information to mothers to help them in successful breastfeeding.
http://ift.tt/2i0WnKF
Intracranial hypotension: An uncommon entity with common presentation
Publication date: Available online 6 January 2017
Source:Medical Journal Armed Forces India
Author(s): Vinay K. Maurya, R. Ravikumar, Mukul Bhatia, Y.S. Sirohi
Headache disorders are among the most common presenting complaints in any neurology outpatient department. International Headache Society classifies headaches as "primary" or "secondary". The causes of secondary headaches are varied and intracranial hypotension is one of them. It typically presents clinically with postural headaches but most of the times, its diagnosis is delayed, as it is an uncommon cause and there is poor awareness among the medical fraternity about this condition. Imaging, especially magnetic resonance imaging (MRI), plays a crucial role in the diagnosis of intracranial hypotension by not only confirming the diagnosis but also detecting the cause in some cases. This case series tries to highlight the MRI findings of intracranial hypotension in three cases with different etiologies.
http://ift.tt/2iYOpA5
Genetic analysis of CHCHD2 and CHCHD10 in Italian patients with Parkinson’s disease
Publication date: Available online 5 January 2017
Source:Neurobiology of Aging
Author(s): Elisa Rubino, Livia Brusa, Ming Zhang, Silvia Boschi, Flora Govone, Alessandro Vacca, Annalisa Gai, Lorenzo Pinessi, Leonardo Lopiano, Ekaterina Rogaeva, Innocenzo Rainero
In recent years, CHCHD2 and CHCHD10 mutations were reported to be associated with a broad spectrum of neurodegenerative diseases, including Parkinson's disease (PD), although with conflicting results in different populations. The present study aimed to evaluate CHCHD2 and CHCHD10 coding variants in Italian patients with PD. All the coding regions and flanking intronic splice sites of CHCHD2 and CHCHD10 were sequenced. None of our 119 PD cases carried CHCHD2 mutations, while one sporadic PD patient showed the Pro34Ser substitution in CHCHD10. Our data suggest that CHCHD2 and CHCDH10 mutations are not a relevant cause of PD in Italian population.
http://ift.tt/2jc6nhQ
CO2: Editorial Board/Subscription info.
Source:Progress in Neurobiology, Volume 148
http://ift.tt/2hY5FbW
Role of D2 dopamine receptors of the ventral pallidum in inhibitory avoidance learning
Source:Behavioural Brain Research, Volume 321
Author(s): László Lénárd, Tamás Ollmann, Kristóf László, Anita Kovács, Rita Gálosi, Veronika Kállai, Tóth Attila, Erika Kertes, Olga Zagoracz, Zoltán Karádi, László Péczely
In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm.Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals.In the experiment with the D2 DA receptor agonist, only the 0.1μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments.Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm.
http://ift.tt/2i0IPP2
Mutations de DOCK8 et le dermatologue
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Dereure
http://ift.tt/2i0FTC6
Value of pH regulators in the diagnosis, prognosis and treatment of cancer
Source:Seminars in Cancer Biology
Author(s): Sara Granja, Diana Tavares-Valente, Odília Queirós, Fátima Baltazar
Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets.
http://ift.tt/2iQdVKn
Nutrition Across the Lifespan for Healthy Aging: Proceedings of a Workshop—in Brief.
On September 13-14, 2016, the National Academies of Sciences, Engineering, and Medicine's Food Forum convened a workshop in Washington, DC, to (1) examine trends and patterns in aging and factors related to healthy aging in the United States with a focus on nutrition; (2) examine how nutrition can sustain and promote healthy aging, not only in late adulthood, but beginning in pregnancy and early childhood and extending throughout the lifespan; (3) highlight the role of nutrition in the aging process at various stages in life; (4) discuss changes in organ systems over the lifespan, including the skeletal, muscular, and cardiovascular systems, and changes that occur with age related to cognitive, brain, and mental health; diet-related sensory preferences; oral health; and the microbiome; and (5) explore opportunities to move forward in promoting healthy aging in the United States.
http://ift.tt/2i0kEAg
Using Health Care Claims Data to Assess the Prevalence of Hodgkin Lymphoma and Relapsed or Refractory Hodgkin Lymphoma in the United States
Source:Clinical Therapeutics
Author(s): Jay Lin, Lisa R. Siegartel, Melissa Lingohr-Smith, Brandy Menges, Dinara Makenbaeva
PurposeAlthough most patients with Hodgkin lymphoma (HL) respond to primary therapy, some patients experience relapses or are refractory to treatment (RR-HL). The objectives of this study were to investigate the prevalence of HL and RR-HL in the United States by using a large health care claims database.MethodsPatients with ≥1 diagnosis for HL between January 1, 2013, and September 30, 2014 (prevalence assessment period), in the MarketScan Commercial and Medicare databases were identified. RR-HL patients were identified as any HL patient with any record for either an autologous stem cell transplantation (ASCT) or brentuximab vedotin (BV) treatment between January 1, 2010, and September 30, 2014 (entire study period). Prevalence rates of HL and RR-HL were calculated as the number of patients with HL or RR-HL divided by the total number of persons with insurance enrollment during the prevalence assessment period (January 1, 2013–September 30, 2014) in the MarketScan databases. Age- and sex-specific prevalence rates for HL and RR-HL were estimated. The estimated prevalence rates based on the claims database analysis were applied to the US national population estimates from the US Census Bureau to project the national prevalence of HL and RR-HL in the United States.FindingsOf persons with any insurance enrollment in the MarketScan databases during the prevalence assessment period (N = 58,968,235), 24,812 (0.04%) were identified as having HL (mean age, 48.6 years) between January 1, 2013, and September 30, 2014. Of this HL population, 712 (2.87%) were identified as RR-HL patients, with 432 (1.74%) having received ASCT, 199 (0.80%) having received BV, and 81 (0.33%) having received both ASCT and BV treatments during the study period. According to the national projection according to the US Census population estimate, the overall number of persons with HL in the United States was estimated at 149,615 (469.2 per 1 million) in 2014, with 2.72% (N = 4077; 12.8 per 1 million) having RR-HL.ImplicationsAmong patients in the United States with HL, the proportion of RR-HL patients during the study period was estimated at <3% of the HL population.
http://ift.tt/2hYlLx4
Three consecutive days of application of LED therapy is necessary to inhibit experimentally induced root resorption in rats: a microtomographic study
Abstract
Previous studies have suggested that phototherapy may modulate orthodontic tooth movement and the incidence of root resorption. We aimed to identify a minimal dose-response relationship to LED therapy with regard to orthodontic tooth movement (OTM) and root resorption in rats. Forty-eight male Wistar rats were divided into six groups with equal and random distribution: control (C) no intervention; three daily LED irradiation (CLED); submitted only to OTM (RR); OTM and LED irradiation on the first day (LED1); OTM and two LED irradiation on the first and second days (LED2); and OTM and three LED irradiation on the first, second, and third days (LED3). Orthodontic appliance was installed in groups RR, LED1, LED2, and LED3 to promote OTM. Animals from groups CLED, LED1, LED2, and LED3 received LED therapy (940 nm, 4 J, 4 J/cm2) according to each group of treatment. After 7 days, all the animals were sacrificed. The jaws were fixed and scanned with microtomography (micro-CT). The micro-CT images were reconstructed on 2D and 3D models. These models were used to identify and measure root resorption number and dimensions (diameter, depth, and volume). The distance between the first and second molars was used to verify tooth displacement. The results showed that LED3 group had significantly lower number of root resorption. The root resorption dimensions (diameter and depth) had no significant differences among the experimental groups. LED3 group had significant tooth displacement in relation to C and CLED groups. In conclusion, three daily LED therapy doses are required to inhibit root resorption after appliance of orthodontic forces.
http://ift.tt/2hXLHxU
Nocturnal enuresis in children between laser acupuncture and medical treatment: a comparative study
Abstract
Nocturnal enuresis (NE) is intermittent involuntary voiding during sleep in a child aged 5 years or more. The study was conducted to compare the effect of using laser acupuncture and medication for the treatment of children with nocturnal enuresis (NE) and evaluation of urodynamic parameter after treatment. A randomized study included 45 children ranged from 5 to 15 years presenting with NE. They were randomized into three equal groups—group A, managed with desmopressin acetate; group B, managed with laser acupuncture; and group C, managed with a combination of laser acupuncture and desmopressin—all groups received behavioral therapy. The children were evaluated before and after 3 months of the study to record the efficacy of therapy, side effects and bladder capacity, and 3 months of follow-up after cessation of treatment by bladder diary. A statistically significant higher cure rate was reported in group B patients (73.3 %), while in groups A and C, improvement was reported in 20.0 and 13.3 %, respectively (p value = 0.002). Laser acupuncture is noninvasive, painless tool, with no side effects and lower recurrence rate which can be considered as an alternative therapy for patients with NE.
http://ift.tt/2jbwG7E
One-year follow-up results of intradiscal diode laser, radiofrequency, and pulsed radiofrequency therapies: a retrospective study
Abstract
This study aims to investigate the efficacy of three different percutaneous intradiscal therapies in patients with chronic low back pain (CLBP) due to lumbar disc herniation (LDH). Medical files of a total of 120 patients who received percutaneous intradiscal therapy were retrospectively analyzed. All patients were divided into three groups: group L: diode laser (n = 40), group R: radiofrequency (RF) (n = 40), and group P: pulsed radiofrequency (PRF) (n = 40). The visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores were calculated at 1, 3, 6, and 12 months for all patients. One-year follow-up results were as follows: group L: pre-treatment (PreT) VAS 5.6 ± −1, ODI 37.6 ± −4.7, post-treatment 12th month (PT12) VAS 2.8 ± −1.4, ODI 14.1 ± −7.1; group P: PreT VAS 6.0 ± 1, ODI 37.5 ± 5.9, PT12 VAS 3.1 ± 1.3, ODI 20.3 ± 17.0; and group R: PreT VAS 5.6 ± 1.0, ODI 37.9 ± 4.7, PT12 VAS 3.3 ± 1.4, ODI 27.2 ± 14.1. In each of the three groups, there was a statistically significant reduction in the VAS and ODI scores at 1, 3, 6, and 12 months, compared to the baseline values (p < 0.05). The highest reduction in the VAS and ODI scores was observed in group L, whereas the lowest reduction was in group R. We consider that in groups with patient selection criteria at our study; diode laser, RF, and PRF, which are administered using the percutaneous intradiscal route for CLBP patients diagnosed with LDH, may be used as an alternative treatment option.
http://ift.tt/2hXC56o
Influence of dentin thickness on intrapulpal temperature under simulated pulpal pressure during Nd:YAG laser irradiation
Abstract
The aim of this study was to evaluate the effects of dentin thickness and pulpal pressure simulation (PPS) on the variation of intrapulpal temperature (∆T) when submitted to an adhesive technique using laser irradiation. Sixty sound human molars were sectioned and randomly divided into two groups (n = 30): group 1—1 mm of dentin thickness; group 2—2 mm of dentin thickness. Each group was divided into two subgroups (n = 15): subgroup A—absence of PPS; subgroup P—presence of PPS (15 cm H2O), sequentially treated with the following: 37 % phosphoric acid, adhesive system (Adper Single Bond), irradiation with Nd:YAG laser (1064 nm, 10 Hz, 60 s) using 60, 80, and 100 mJ/pulse energy parameters and light-curing (10 s). The ∆T was evaluated during the laser irradiation with a digital thermometer. Data were analyzed by three-way ANOVA and Tukey tests (p < 0.05). Three-way ANOVA revealed no significant differences for dentin thickness (p = 0.6512) on ∆T. PPS significantly reduced ∆T (p = 0.0001). The laser energy parameters (p = 0.0027) indicated that 100 mJ presented with significantly greater ∆T when compared to the groups irradiated with 80 and 60 mJ. Dentin thickness did not affect ∆T. The presence of PPS reduced the mean temperature values. The Nd:YAG laser energy parameters had a negative influence on the variation of temperature in the absence of PPS. In the presence of PPS, there was no risk to the pulp, since this study obtained temperature increases below 5.5 °C for all energy parameters, showing the technical viability for in vivo conditions.
http://ift.tt/2jbICWS
Synergistic effect of high-intensity focused ultrasound and low-fluence Q-switched Nd:YAG laser in the treatment of the aging neck and décolletage
Abstract
High-intensity focused ultrasound (HIFU) is regarded as an effective skin-lifting device; however, literature regarding treatment of the aging neck and décolletage with HIFU is scarce. Our study aimed to evaluate the efficacy of combination with HIFU and low-fluence Q-switched Nd:YAG (LQSNY) laser on the aging neck and décolletage. Nineteen women were assessed. HIFU at two visits and LQSNY laser at six visits were used to irradiate the neck and chest. At week 16, improvements were rated using the Dedo classification, Fabi/Bolton Chest Wrinkle Scale (FBCWS), and Global Aesthetic Improvement Scales (GAIS). Erythema and melanin indices (EMIs) and cervicomental angle were measured. Subject GAIS and satisfaction were evaluated at follow-up visits. At week 16, neck sagging and chest rhytides were improved on Dedo classification and FBCWS, respectively. Pigmentation and rhytides of the neck and chest were rated as improved in 30 % or more of the subjects by physician GAIS and in approximately 80 % of the subjects by subject GAIS. The above differences seemed to be attributable to the initial expectation level and mild severity pertaining to dress custom in Korea. Eighty-four percent of subjects were satisfied with treatment outcomes. EMIs were decreased on the chest. The combination of HIFU and LQSNY is an effective treatment option to mitigate rhytides and pigmentation of the neck and décolletage.
http://ift.tt/2hXyuoF
Wiring visual systems: common and divergent mechanisms and principles
Source:Current Opinion in Neurobiology, Volume 42
Author(s): Alex L Kolodkin, P Robin Hiesinger
The study of visual systems has a rich history, leading to the discovery and understanding of basic principles underlying the elaboration of neuronal connectivity. Recent work in model organisms such as fly, fish and mouse has yielded a wealth of new insights into visual system wiring. Here, we consider how axonal and dendritic patterning in columns and laminae influence synaptic partner selection in these model organisms. We highlight similarities and differences among disparate visual systems with the goal of identifying common and divergent principles for visual system wiring.
http://ift.tt/2hXJv9m
Molecular docking, discovery, synthesis, and pharmacological properties of new 6-substituted-2-(3-phenoxyphenyl)-4-phenyl quinoline derivatives; an approach to developing potent DNA gyrase inhibitors/antibacterial agents
Publication date: Available online 6 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Manikandan Alagumuthu, Sivakumar Arumugam
Synthesis and molecular validation of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives (4a-h) as antibacterial/DNA gyrase inhibitors reported. Primarily, 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives were docked into the active sites of DNA gyrase A&B, to ensure the binding mode of the compounds, and the results were superior on DNA gyrase A over DNA gyrase B. Based on this, S.aureus DNA gyrase A assay was proposed and executed. Most prominent DNA gyrase inhibition showed by 6-fluoro-2-(3-phenoxyphenyl)-4-phenylquinoline (4c), IC50 0.389 μg/mL; 2-(3-phenoxyphenyl)-4-phenylquinolin-6-ol (4e), IC50 0.328 μg/mL; and 5,7-dichloro-2-(3-phenoxyphenyl)-4-phenylquinolin-6-ol (4h), IC50 0.214 μg/mL which were substituted with fluorine (-4F), nitrile (-4CN), hydroxyl group (-4OH) and dichloro- hydroxyl (-3,5Cl, -4OH) groups in the quinoline scaffold. Antimicrobial activity on Gram-ve bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), and Gram+ve bacteria Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) was evaluated. Excellent antibacterial activity showed by S.aureus and S.pyogenes which indicates the activity dominance of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives on Gram+ve bacteria rather than Gram-ve. Subsequently, the cytotoxicity of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives was evaluated. Cytotoxicity results of MCF-7 (human breast cancer) and G361 (skin melanoma cancer) cell lines reveals that the 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives are highly toxic to cancer cells. Predicted SAR, Lipinski's filter, Pharmacokinetic, and ADMET properties were also ensured the druggability probabilities of most favorable compounds among 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives.
Graphical abstract
http://ift.tt/2i0gbNT
A conceptually novel construction of the 6a-hydroxypterocarpan skeleton – synthesis of (±)-variabilin
Publication date: Available online 5 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Philipp Ciesielski, Peter Metz
A new access to the 6a-hydroxypterocarpan variabilin was established. Key step of this concise total synthesis is a challenging cyclization of a haloketone via halogen–metal exchange and subsequent intramolecular addition to the carbonyl function.
Graphical abstract
http://ift.tt/2i0gBUR
Synthesis of Ofornine mimics from natural product l-Vasicine as anti-hypertensive agents
Publication date: Available online 6 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mushtaq A. Aga, Sheikh Rayees, Abdul Rouf, Brijesh Kumar, Anjna Sharma, P.V.V.S. Nagaraju, Gurdarshan Singh, Subhash C. Taneja
We report the chemical synthesis of Ofornine mimics from l-vasicine, structure-activity relationship studies and their in vivo screening for anti-hypertensive action in Wistar rats. It was observed that most of the analogs possessed anti-hypertensive effect; however, the duration of the effect was variable and mostly transient. The results demonstrated that the analogs 12, 13, 14, 15, and 16 showed a sharp and significant decrease in systolic and diastolic blood pressure for 30-60 min after intravenous administration. Analog (S)-(3-hydroxypyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone (8) showed a significant decrease in blood pressure in a dose dependent manner whose maximal response lowered to 79.29±4.26 mmHg of SBP and 62.55±2.9 of DBP at 10 mg/kg intravenous dose. Further, the significant anti-hypertensive effect of 8 lasted for about 2.5 h at 10 mg/kg dose. We also evaluated the acute toxicity of the analog 8 as per the OECD guidelines and the compound was found to be safe upto the dose of 2000 mg/kg body weight. These preclinical findings suggest that the analog 8 could be considered as a promising lead and a durable anti-hypertensive drug candidate and deserves further investigation. The SAR studies clearly showed that the amide, hydroxyl and pyridine ring plays important role in showing the activity.
Graphical abstract
http://ift.tt/2iJpbb1
Activation of Anti-oxidant Nrf2 Signaling by Substituted trans Stilbenes
Publication date: Available online 6 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Lorraine M. Deck, Lisa J. Whalen, Lucy A. Hunsaker, Robert E. Royer, David L. Vander Jagt
Nrf2, which is a member of the cap'n'collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation of anti-oxidant Nrf2 signaling may have therapeutic potential. A number of Nrf2 activators have entered into clinical trials. Nrf2 exists in the cytosol in complex with its binding partner Keap1, which is a thiol-rich redox-sensing protein. In response to oxidative and electrophilic stress, select cysteine residues of Keap1 are modified, which locks Keap1 in the Nrf2-Keap1 complex and allows newly synthesized Nrf2 to enter the nucleus. Numerous Nrf2-activating chemicals, including a number of natural products, are electrophiles that modify Keap1, often by Michael addition, leading to activation of Nrf2. One concern with the design of Nrf2 activators that are electrophilic covalent modifiers of Keap1 is the issue of selectivity. In the present study, substituted trans stilbenes were identified as activators of Nrf2. These activators of Nrf2 are not highly electrophilic and therefore are unlikely to activate Nrf2 through covalent modification of Keap1. Dose-response studies demonstrated that a range of substituents on either ring of the trans stilbenes, especially fluorine and methoxy substituents, influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2. The stilbene backbone appears to be a privileged scaffold for development of a new class of Nrf2 activators.
Graphical abstract
http://ift.tt/2iJ7IQ9
Cystatin C peptidomimetic derivative with antimicrobial properties as a potential compound against wound infections
Publication date: Available online 5 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Michał Pikuła, Maria Smużyńska, Adam Krzystyniak, Maciej Zieliński, Paulina Langa, Milena Deptuła, Adriana Schumacher, Jakub Łata, Mirosława Cichorek, Anders Grubb, Piotr Trzonkowski, Franciszek Kasprzykowski, Sylwia Rodziewicz-Motowidło
A peptidomimetic called A20 (Cystapep 1) structurally based upon the N–terminal fragment of human cystatin C is known to have strong antibacterial properties. A20 is characterized by high activity against several bacterial strains often isolated from infected wounds, including methicillin-resistant S. aureus (MRSA). In this work we wanted to explore the therapeutic potential of A20 in the treatment of wound infections. We examined, cytotoxicity, allergenicity and impact of A20 on the proliferation and viability of human keratinocytes. Furthermore, the previously described antimicrobial action of A20 has been confirmed here with reference strains of bacteria and extended by several other species. The A20 was highly active against Gram-positive bacteria with minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) between 8 and 128 ug/ml. A20 did not affect proliferation of primary human keratinocytes in concentrations up to 50 μg/mL. At the same time, it did not activate Peripheral Blood Mononuclear Cells (PBMCs), including basophils or neutrophils in vitro. Interestingly A20 was found to display immunomodulatory functions as it influences the production of Th2 cytokines (IL-4 and IL-13) by activated PBMCs. It was also resistant to degradation for at least 48h in human plasma. The results indicate that A20 is effective against the multiantibiotic-resistant bacteria and has a high safety profile, which makes it a promising antimicrobial drug candidate.
Graphical abstract
http://ift.tt/2iJfNnU
Recent developments in the isolation, biological function, biosynthesis, and synthesis of phenazine natural products
Publication date: Available online 5 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nikolaus Guttenberger, Wulf Blankenfeldt, Rolf Breinbauer
Phenazines are natural products which are produced by bacteria or by archaeal Methanosarcina species. The tricyclic ring system enables redox processes, which producing organisms use for oxidation of NADH or for the generation of reactive oxygen species (ROS), giving them advantages over other microorganisms. In this review we summarize the progress in the field since 2005 regarding the isolation of new phenazine natural products, new insights in their biological function, and particularly the now almost completely understood biosynthesis. The review is complemented by a description of new synthetic methods and total syntheses of phenazines.
Graphical abstract
http://ift.tt/2iJfv06
Prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies
Abstract
Purpose
To determine prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies
Methods
We performed retrospective analysis of patients who were hospitalized on any of the four hematology services or bone marrow transplant service and who received systemic steroids during a 2-month period. Mean glucoses for days 1–4 and maximum glucose were calculated and the total daily steroid dose was converted to equivalent dose of dexamethasone. Hyperglycemia was defined as any glucose >9.917 mmol/l during days 1–4. We examined associations between variables using Spearman's correlations and multivariable linear regression
Results
168 patients were included in the analysis. Mean age was 57.1 ± 14.4 years with 59% males and 90% Caucasians. The prevalence of hyperglycemia was 39%. Eight patients received intravenous insulin. In patients without diabetes, steroid dose equivalent to >12 mg dexamethasone and longer acting steroids caused greater degree of hyperglycemia compared to a dose <12 mg. Maximum glucose was a predictor of hospital length of stay among patients without diabetes (but not those with diabetes), and with acute leukemia or stem cell transplant (but not other hematologic malignancies). There were no significant differences in in mortality or other outcomes between the groups with and without hyperglycemia
Conclusions
Hyperglycemia is common in patients with hematologic malignancies, which require frequent corticosteroids. Higher steroid dose and long-acting steroids caused a greater degree of hyperglycemia. Maximum glucose was a predictor of length of stay but this was only significant for patients without diabetes, those with acute hematologic malignancy or stem cell transplant.
http://ift.tt/2hXCW72
A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer
Intervention: Biological: CAR-T cell immunotherapy
Sponsor: First Affiliated Hospital of Chengdu Medical College
Recruiting - verified January 2017
http://ift.tt/2jbCJsX
Secured Access to Pembrolizumab for Adult Patients With Selected Rare Cancer Types
Intervention: Drug: Pembrolizumab
Sponsors: UNICANCER; National Cancer Institute, France; Ligue contre le cancer, France; Merck Sharp & Dohme Corp.
Not yet recruiting - verified January 2017
http://ift.tt/2i0fQes
Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types
Intervention: Drug: Nivolumab
Sponsors: UNICANCER; National Cancer Institute, France; Ligue contre le cancer, France; Bristol-Myers Squibb
Not yet recruiting - verified January 2017
http://ift.tt/2jbsQeH
Pain Perception: Lidocaine Rate/Temp/Buffer
Interventions: Procedure: Slow, Room Temperature Injection; Procedure: Rapid, Room Temperature Injection; Procedure: Slow, Warm Temperature Injection; Procedure: Rapid, Warm Temperature Injection; Procedure: Buffered Injection; Procedure: Non-Buffered Injection; Drug: Lidocaine; Drug: Buffer
Sponsor: Northwestern University
Recruiting - verified January 2017
http://ift.tt/2i03HGj
Patient Comfort During Dermatologic Procedures
Interventions: Procedure: Hand-holding; Procedure: Stress Ball
Sponsor: Northwestern University
Not yet recruiting - verified January 2017
http://ift.tt/2jbBr18
Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution
Publication date: Available online 5 January 2017
Source:Immunity
Author(s): Jesmond Dalli, Romain A. Colas, Hildur Arnardottir, Charles N. Serhan
Uncovering mechanisms that control immune responses in the resolution of bacterial infections is critical for the development of new therapeutic strategies that resolve infectious inflammation without unwanted side effects. We found that disruption of the vagal system in mice delayed resolution of Escherichia coli infection. Dissection of the right vagus decreased peritoneal group 3 innate lymphoid cell (ILC3) numbers and altered peritoneal macrophage responses. Vagotomy resulted in an inflammatory peritoneal lipid mediator profile characterized by reduced concentrations of pro-resolving mediators, including the protective immunoresolvent PCTR1, along with elevated inflammation-initiating eicosanoids. We found that acetylcholine upregulated the PCTR biosynthetic pathway in ILC3s. Administration of PCTR1 or ILC3s to vagotomized mice restored tissue resolution tone and host responses to E. coli infections. Together these findings elucidate a host protective mechanism mediated by ILC3-derived pro-resolving circuit, including PCTR1, that is controlled by local neuronal output to regulate tissue resolution tone and myeloid cell responses.
Teaser
Resolution of the inflammatory response to infections is important to prevent damage to the host. Dalli et al. find that the vagus nerve promotes bacterial clearance by regulating tissue ILC3 numbers and upregulating the protective mediator PCTR1, which conditions peritoneal macrophage responses and promotes resolution of infection.http://ift.tt/2hXHOc7
Cosmetics, Vol. 4, Pages 3: Relative Free Radicals Scavenging and Enzymatic Activities of Hippophae rhamnoides and Cassia fistula Extracts: Importance for Cosmetic, Food and Medicinal Applications
Hippophae rhamnoides L. and Cassia fistula L. extracts have great potential as food, medicinal, or cosmetic ingredients. The aim of our study was to assess their relative antioxidant activities and key enzymatic activities. Thereby, H. rhamnoides' fruit and C. fistula's pod extracts were evaluated by spectrophotometry, based on their respective total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) ferric-reducing power, capacity in nitric oxide, hydroxyl and superoxide radicals scavenging, as well as on their β-glucuronidase, α-glucosidase and α-tyrosinase inhibition activities. H. rhamnoides and C. fistula extracts exhibited similarly high TPC levels, hydroxyl ion [OH•] quenching activity, and α-glucosidase and α-tyrosinase IC50 values (p > 0.05). However, their respective DPPH radical, nitric oxide radical [NO•], and superoxide anion [O2−•] scavenging activities, as well as their IC50 values for β-glucuronidase, significantly differed (p ≤ 0.05), with results showcasing the highest values in C. fistula extracts. In sum, our in vitro data explicitly suggest that the pod extracts of C. fistula exert better antioxidant and enzymatic properties than those exhibited by the fruit extract of H. rhamnoides. They also implicitly encourage performing multiple in vitro assays in order to thoroughly select a plant extract destined to a given medicinal, dietetic, or esthetic application.
http://ift.tt/2iLlmQO
Sclareol ameliorate lipopolysaccharide-induced acute lung injury through inhibition of MAPK and induction of HO-1 signaling
Publication date: March 2017
Source:International Immunopharmacology, Volume 44
Author(s): Yung-Hung Hsieh, Jeng-Shyan Deng, Hsin-Pao Pan, Jung-Chun Liao, Shyh-Shyun Huang, Guan-Jhong Huang
Sclareol is a natural fragrance compound that is used widely in the cosmetic and food industries. This study examined the effect of sclareol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Mice were treated with sclareol 1h before an intratracheal (I.T.) LPS challenge to induce an ALI model. The effects on lung tissue and lung injury were evaluated 6h after LPS induction. Pretreatment with sclareol noticeably improved the LPS-induced histological alterations and edema in lung tissue. Sclareol also inhibited the release of pro-inflammatory mediators. Differences in nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and IL-10 were found in the bronchoalveolar lavage fluid (BALF) 6h after LPS-induced lung injury. This study also found a reduced number of total cells and reduced protein concentrations in the BALF. There were also changes in the pulmonary wet/dry (W/D) weight ratio, antioxidant enzyme activity, and myeloperoxidase activity in lung tissues. Sclareol effectively blocked the phosphorylation of mitogen-activated protein kinases (MAPKs) and impeded the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The compound boosted the expression of heme oxygenase-1 (HO-1) and inhibited the breakdown of nuclear factor-kappa B (NF-κB) and inhibitor of kappa B (IκBα). To the best of the authors' knowledge, this study is the first to demonstrate that sclareol effectively inhibits acute lung edema, and the results suggest that sclareol may be a potential agent for the treatment of ALI. The potential therapeutic benefits may include the attenuation of LPS-induced pulmonary inflammation due to sclareol's effects on several pathways, including NF-κB, MAPKs and HO-1, as well as the regulation of antioxidant enzyme activity.
Graphical abstract
http://ift.tt/2hZSgOQ
Erratum to “Immunomodulatory effects of natural polysaccharides assessed in human whole blood culture and THP-1 cells show greater sensitivity of whole blood culture” [Int. Immunopharmacol. (2016) 315–323]
Publication date: Available online 5 January 2017
Source:International Immunopharmacology
Author(s): Satbir Kaur Gill, Nahidul Islam, Iain Shaw, Andreia Ribeiro, Benjamin Bradley, Timothy O'Brien, Michelle Kilcoyne, Rhodri Ceredig, Lokesh Joshi
http://ift.tt/2hZT1HI
Group-focused morality is associated with limited conflict detection and resolution capacity: Neuroanatomical evidence
Source:Biological Psychology
Author(s): Kyle Nash, Thomas Baumgartner, Daria Knoch
Group-focused moral foundations (GMFs) − moral values that help protect the group's welfare − sharply divide conservatives from liberals and religiously devout from non-believers. However, there is little evidence about what drives this divide. Moral foundations theory and the model of motivated social cognition both associate group-focused moral foundations with differences in conflict detection and resolution capacity, but in opposing directions. Individual differences in conflict detection and resolution implicate specific neuroanatomical differences. Examining neuroanatomy thus affords an objective and non-biased opportunity to contrast these influential theories. Here, we report that increased adherence to group-focused moral foundations was strongly associated (whole-brain corrected) with reduced gray matter volume in key regions of the conflict detection and resolution system (anterior cingulate cortex and lateral prefrontal cortex). Because reduced gray matter is reliably associated with reduced neural and cognitive capacity, these findings support the idea outlined in the model of motivated social cognition that belief in group-focused moral values is associated with reduced conflict detection and resolution capacity.
http://ift.tt/2iXSbcI
Inhibition of collagen production by ICG-001, a small molecule inhibitor for Wnt/β-catenin signaling, in skin fibroblasts
Publication date: Available online 6 January 2017
Source:Journal of Dermatological Science
Author(s): Kyung-Il Kim, Do-Sun Jeong, Tae-Jin Yoon, Eui Chang Jung, Jeung-Hoon Lee, Chang Deok Kim
http://ift.tt/2iPAvTE
Association between –1082 A/G polymorphism in IL-10 and oral lichen planus: A meta-analysis
Publication date: Available online 6 January 2017
Source:Journal of Dermatological Science
Author(s): Min Qiu, Jiayi Wang, Pengfei He, Hao Xv, Jiao Wei, Wang Gong, Lu Jiang, Qianming Chen
http://ift.tt/2iLvJDY
Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction
Publication date: Available online 5 January 2017
Source:Journal of Dermatological Science
Author(s): Wen-Yen Huang, Yi-Ching Huang, Kai-Shin Huang, Chih-Chieh Chan, Hsien-Yi Chiu, Ren-Yeu Tsai, Jung-Yi Chan, Sung-Jan Lin
BackgroundHair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood.ObjectiveThis work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging.MethodsDermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo.ResultDermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo.ConclusionStress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.
http://ift.tt/2iPLqwn
Altered Balance of Epidermis-Related Chemokines in Epidermolysis Bullosa
Publication date: Available online 5 January 2017
Source:Journal of Dermatological Science
Author(s): Inkin Ujiie, Yasuyuki Fujita, Chihiro Nakayama, Wakana Matsumura, Shotaro Suzuki, Satoru Shinkuma, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu
BackgroundEpidermolysis bullosa (EB) is a congenital, refractory skin disease and there are no fundamental treatments. Recently, allogenic cell therapies are beginning to be applied as potential treatments, that are based on the concept that the allogenic cells can migrate into the skin and reconstitute the skin components. Although the mechanisms of cell migration into skin are not fully understood, chemokines are regarded as key factors in recruiting bone marrow-derived cells.ObjectivesOur study aims to elucidate the expression of chemokines in the EB patients.MethodsWe determined the expression of wound-healing related chemokines in the sera, keratinocytes, and skin tissues of EB patients and compared them to those of healthy volunteers by enzyme-linked immunosorbent assays, quantitative reverse transcription PCR, and immunofluorescence staining.ResultsThe serum levels of CXCL12 and HMGB1 were found to be significantly elevated in the EB patients. Conversely, the serum levels of CCL21 were found to be lower in the EB patients than in healthy controls. In addition, the serum levels of CXCL12 tended to increase and the serum levels of CCL27 tended to decrease with an increase in the affected body surface areas. To detect the origin of the circulating chemokines, we performed immunofluorescence staining. CCL21, CCL27, HMGB1 and CXCL12 were stained more broadly in the EB patient tissues than those in the control tissues.ConclusionsThese results suggest that fluctuations in chemokine levels may contribute in a coordinated way to the wound-healing process and lend clues toward efficient cell therapies for EB.
http://ift.tt/2iLzvgV
Synthesis, antioxidant and antimelanogenic activities of PEGylated α-tocopheryl lipoate conjugates
Publication date: Available online 5 January 2017
Source:Journal of Dermatological Science
Author(s): Jianmei Ma, Hao Wang, Chenglin Wang, Huanxiang Yuan, Dongsheng Bai, Kyu Yun Chai, Chichong Lu
http://ift.tt/2iPAeQt
Real-time imaging of human epidermal calcium dynamics in response to point laser stimulation
Publication date: Available online 6 January 2017
Source:Journal of Dermatological Science
Author(s): Junichi Kumamoto, Makiko Goto, Masaharu Nagayama, Mitsuhiro Denda
BACKGROUNDChanges of epidermal calcium ion concentration are involved in regulation of barrier homeostasis and keratinocyte differentiation. Moreover, intracellular calcium dynamics might play a role in skin sensation. But, although calcium dynamics of cultured keratinocytes in response to mechanical stresses has been well studied, calcium propagation in stimulated human epidermis is still poorly understood.OBJECTIVEThe aim of this study was to demonstrate a novel method for real-time measurement of calcium dynamics in response to point stimulation of human epidermis at the single-cell level.METHODSWe examined calcium propagation in cross-sectional samples of living human epidermis ex vivo, as well as in cultured human keratinocytes, by means of two-photon microscopy after stimulating cells in stratum granulosum with the emission laser of a two-photon microscope.RESULTSCells in different epidermal layers showed different responses, and those in stratum basale showed the greatest elevation of intracellular calcium. Calcium propagation in epidermis was inhibited in the presence of apyrase (which degrades adenosine triphosphate; ATP) or gap-junction blockers. In cultured keratinocytes, on the other hand, calcium propagated in a simple concentric wave-like manner from the stimulation site, and propagation was strongly suppressed by apyrase.CONCLUSIONOur results suggested that ATP and gap junctions play important roles in calcium propagation induced by point laser stimulation of the uppermost layer of epidermis. Our method should be broadly useful to study calcium dynamics, epidermal physiological mechanisms, and mechanisms of skin sensation at the single-cell level.
http://ift.tt/2iLu4ys
Cutaneous blastomycosis and dermatophytic pseudomycetoma in a Persian cat from Bangkok, Thailand
Publication date: Available online 6 January 2017
Source:Medical Mycology Case Reports
Author(s): Lerpen Duangkaew, Lawan Larsuprom, Chaiyan Kasondorkbua, Charles Chen, Ariya Chindamporn
This is a case report of concurrent of blastomycosis and pseudomycetoma in a 3 year-old Persian cat from Bangkok, Thailand. Histopathology from antemortem and postmortem samples revealed blastomycosis and dermatophyte pseudomycetoma. The PCR analysis of the formalin-embedded tissue of antemoretem sample confirmed that blastomycosis was caused by Blastomyces dermatitidis. Dermatophyte infection was caused by Microsporum canis. According to the author's knowledge, this is the first case of Blastomyces dermatitidis and dermatophyte pseudomycetoma in South-East Asia.
http://ift.tt/2ij3kUT
The unifying concept of Histiocytosis with raisinoid nuclei: a new evidence that intravascular/intralymphatic histiocytosis and MICE belong in the same spectrum of lesions.
Publication date: Available online 5 January 2017
Source:Pathology - Research and Practice
Author(s): Michael Michal, Michal Michal
http://ift.tt/2iPwVsJ
Encapsulated follicular variant of papillary thyroid carcinoma/Noninvasive follicular thyroid neoplasm with papillary-like nuclear features with Spindle Cell Metaplasia: case report and review of literature
Publication date: Available online 5 January 2017
Source:Pathology - Research and Practice
Author(s): Mohamed Rizwan Haroon Al Rasheed, Andres Acosta, Gabor Tarjan
Spindle cell lesions of the thyroid are rare overall, and span a wide clinical spectrum that ranges from spindle cell metaplasia (SCM11 SCM- Spindle cell metaplasia) to anaplastic carcinoma. Their differentiation is only seldom straightforward, and usually requires the integration of the clinical, histological and immunohistochemical data. Only a handful of publications have described cases of SCM in the thyroid and we add to that literature by reporting a unique case of encapsulated follicular variant of papillary thyroid carcinoma/noninvasive follicular thyroid neoplasm with papillary-like nuclear features with SCM. In addition, we review the literature on the relationship between SCM and different thyroid lesions, summarizing the morphological and immunohistochemical features that aid in its differentiation from more aggressive spindle cell proliferations.
http://ift.tt/2iLr4Ss
Ethnomedicine based evaluation of osteoprotective properties of Tinospora cordifolia on in vitro and in vivo model systems
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): G. Abiramasundari, C.M. Mohan Gowda, G. Pampapathi, Sheela Praveen, S. Shivamurugan, M. Vijaykumar, A. Devi, M. Sreepriya
Indian ethnomedicine acclaims the use of Tinospora cordifolia (TC) in the treatment of bone fractures and vat rakta (gout). The objective of the study is to investigate the effects of alcoholic extract of Tinospora cordifolia on bone remodeling (involving osteoblastic and osteoclastic actions) in vitro and protect against ovariectomy-induced bone loss in vivo. Human osteoblast-like cells MG-63 and primary osteoblast cells isolated from rat femur were used as osteoblast models and RAW macrophage cell line 264.7 induced to take up osteoclastic lineage using RANK ligand were used as osteoclast models in the current study. Sirius red staining, quantification of osteocalcin, cytopathological analysis by Hematoxylin/eosin staining and semiquantitative reverse transcription PCR (RT-PCR) was carried out to ascertain the effects of T. cordifolia extract on osteoblast cells. MTT assay was perfomed to understand the influence of T. cordifolia extract on osteoclast cells. Adult female Sprague-Dawley rats were used as in vivo models to study the effect of T. cordifolia on ovariectomy induced bone loss. Radiological (DEXA analysis), Biochemical (markers of bone formation and resorption), histopathological (Hematoxylin/eosin staining) and histomorphometric analysis of the bone was carried out. Treatment with T. cordifolia extract resulted in enhanced collagen deposition, increased levels of osteocalcin, increased expression of osteogenic genes all indicative of favourable osteoblastogenesis. Treatment with T. cordifolia extract did not exert any significant influence on the proliferation of osteoclasts. Pretreatment with T. cordifolia extract at a dose of 50mg/kg body wt/day orally for 21days followed by treatment for 12 weeks post ovariectomy was able to prevent ovariectomy-induced bone loss in vivo. Results of the study support the use of T. cordifolia in Indian ethnomedicine for the treatment of bone diseases and fractures.
Graphical abstract
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Dermal/transdermal delivery of small interfering RNA and antisense oligonucleotides- advances and hurdles
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Kevin Ita
A diverse array of nucleic acids has been studied by several researchers for the management of several diseases. Among these compounds, small interfering RNA and antisense oligonucleotides have attracted considerable attention. Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA while siRNAs, on the other hand, are double-stranded RNA molecules which can hybridize with a specific mRNA sequence and block the translation of numerous genes. One of the main obstacles in the dermal or transdermal delivery of these compounds is their low skin permeability. In this review, various techniques used to enhance the delivery of these molecules into or across the skin are described and in some cases, the correlation between enhanced dermal/transdermal delivery and therapeutic efficacy is highlighted.
http://ift.tt/2jb2GZw
A brief review on the application of nanoparticle enclosed herbal medicine for the treatment of infective endocarditis
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Mehrdad Namdari, Ali Eatemadi, Maryam Soleimaninejad, Aiyelabegan T. Hammed
Herbal medicines have been routinely employed all over the world dated back from the ancient time and have been identified by patients and physicians for their excellent therapeutic value as they have lower adverse effects when compared with the modern medicines. Phytotherapeutics requires a scientific technique to deliver the active herbal extract in a controlled manner to avoid repeated administration and increase patient compliance. This can be reached by fabricating a novel drug delivery systems (NDDS) for herbal components. NDDSs does not only decrease the repeated dose to overcome ineffectiveness, but also help to increase potency by decreasing toxicity and elevating drug bioavailability. Nano-sized DDS of herbal drugs have a potential application for improving the activity and countering the problems related to herbal medicines. Hence, application of nanocarriers as an NDDS in the traditional herbal medicine system is important to treat more chronic diseases like infectious endocarditis.
http://ift.tt/2hXnIyI
Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Dong-Xue Zhang, Li-Min Zhang, Xiao-Chun Zhao, Wenbo Sun
ObjectiveErythropoietin (EPO)-induced activation of the EPO receptor (EPOR) against sevoflurane-induced neuronal apoptosis is an effective intervention, but the underlying mechanism is poorly understood. Previous studies have shown that alteration of the nuclear factor erythroid 2-related factor (Nrf2)/BTB-to-CNC homology 1 (Bach1) ratio by extracellular signal-related kinases (Erk) 1/2 ameliorates the oxidative stress which occurs in human macrophages. In this study, we determined whether or not EPO attenuates sevoflurane-induced neuronal apoptosis via the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.MethodsPrimary rat cortical neurons were exposed to 4% sevoflurane for 6h. Neuronal viability, injury, apoptosis, and oxidative stress were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), propidium iodide uptake (PI), malondialdehyde (MDA), and superoxide dismutase (SOD) assays. A real-time PCR assay was used to measure EPOR expression. Western blotting was used to assess Nrf2, Bach1, and heme oxygenase-1 (HO-1) expression.ResultsSevoflurane exposure increased cell apoptosis, injury, and MDA (P<0.05), but decreased cell viability and the Nrf2:Bach1 ratio (P<0.05), and down-regulated superoxide dismutase (SOD; P<0.05), while EPO partially rescued the neurotoxicity induced by sevoflurane (P<0.05). Inhibition of EPOR via EPO-specific monoclonal antibody or Erk1/2 phosphorylation via PD98059 reversed the protective effect of EPO (P<0.05).ConclusionThe neuroprotective effects of EPO against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involves the EPOR-Erk1/2-Nrf2/Bach1 signal pathway.
http://ift.tt/2hXlKys
Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone
Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Nelli Giribabu, Pamanji Sreenivasula Reddy
Di-n-butyl phthalate (DBP) widely spread industrial chemical that made drastic alteration in male reproductive system. The present study elucidates the protective role of testosterone on reproductive toxicity in prenatal DBP exposed adult male rats. Pregnant rats were injected with corn oil or 100 and 500mg/kg body weight of DBP on gestation day (GD) 1, 7 and 14. F1 male rats were weaned, injected with either testosterone or vehicle. On postnatal day (PND) 100 F1 adult male rats were cohabited with untreated female rats. Then rats were sacrificed and analyzed for other reproductive end points. Prenatal DBP exposed male rat testes, seminal vesicle weight, sperm count, motility, viability and HOS tail coiled sperm were significantly decreased with increased sperm morphological abnormalities. The levels of testicular 3β, 17βHSD, serum testosterone were significantly decreased with increased FSH, LH levels in experimental rats. The fertility studies revealed that increased pre, post-implantation losses and resorptions in normal females cohabited with experimental rats. Higher testicular LPO with lower SOD, CAT and GPx activity levels in experimental rats. Administration of testosterone to prenatal DBP treated male rats showed significant protection in above all parameters. In conclusions, testosterone deteriorates prenatal DBP induced reproductive and fertility toxicity by decreased oxidative stress and increased testicular antioxidant enzymes.
http://ift.tt/2jb9czp
Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor
Publication date: Available online 5 January 2017
Source:Cell Metabolism
Author(s): Masaji Sakaguchi, Shiho Fujisaka, Weikang Cai, Jonathon N. Winnay, Masahiro Konishi, Brian T. O'Neill, Mengyao Li, Rubén García-Martín, Hirokazu Takahashi, Jiang Hu, Rohit N. Kulkarni, C. Ronald Kahn
Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance. This phenotype, however, resolves over 10–30 days due to a proliferation of preadipocytes and rapid regeneration of both brown and white adipocytes as identified by mTmG lineage tracing. This cycle can be repeated with a second round of receptor inactivation. Leptin administration prior to tamoxifen treatment blocks development of the metabolic syndrome without affecting adipocyte loss or regeneration. Thus, IR is critical in adipocyte maintenance, and this loss of adipose tissue stimulates regeneration of brown/white fat and reversal of metabolic syndrome associated with fat loss.
Graphical abstract
Teaser
Sakaguchi et al. show that insulin signaling is necessary for maintenance of white and brown adipocytes mice in adult mice. Adipose tissue loss is reversed by a marked increase in both white and brown preadipocyte proliferation, indicating the presence of an adipostatic sensor. Adipocyte regeneration is leptin independent.http://ift.tt/2iP4bQQ
Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats
Publication date: Available online 5 January 2017
Source:Cell Metabolism
Author(s): Mohammed K. Hankir, Florian Seyfried, Constantin A. Hintschich, Thi-Ai Diep, Karen Kleberg, Mathias Kranz, Winnie Deuther-Conrad, Luis A. Tellez, Michael Rullmann, Marianne Patt, Jens Teichert, Swen Hesse, Osama Sabri, Peter Brust, Harald S. Hansen, Ivan E. de Araujo, Ute Krügel, Wiebke K. Fenske
Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.
Graphical abstract
Teaser
Roux-en-Y gastric bypass (RYGB) surgery causes marked reductions in fat appetite. Hankir et al. show in a rat model of RYGB that this is due to enhanced gut-lipid sensing through PPARα, which in turn is transmitted to the CNS by sensory vagal afferents, culminating in increased dorsal striatal D1R signaling.http://ift.tt/2iP9jVa
Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication
Publication date: Available online 5 January 2017
Source:Cell Metabolism
Author(s): Yoshiko Nakamura, Yuchio Yanagawa, Shaun F. Morrison, Kazuhiro Nakamura
Hypothalamic neuropeptide Y (NPY) elicits hunger responses to increase the chances of surviving starvation: an inhibition of metabolism and an increase in feeding. Here we elucidate a key central circuit mechanism through which hypothalamic NPY signals drive these hunger responses. GABAergic neurons in the intermediate and parvicellular reticular nuclei (IRt/PCRt) of the medulla oblongata, which are activated by NPY-triggered neural signaling from the hypothalamus, potentially through the nucleus tractus solitarius, mediate the NPY-induced inhibition of metabolic thermogenesis in brown adipose tissue (BAT) via their innervation of BAT sympathetic premotor neurons. Intriguingly, the GABAergic IRt/PCRt neurons innervating the BAT sympathetic premotor region also innervate the masticatory motor region, and stimulation of the IRt/PCRt elicits mastication and increases feeding as well as inhibits BAT thermogenesis. These results indicate that GABAergic IRt/PCRt neurons mediate hypothalamus-derived hunger signaling by coordinating both autonomic and feeding motor systems to reduce energy expenditure and to promote feeding.
Graphical abstract
Teaser
Hypothalamic neuropeptide Y (NPY) plays a key role in eliciting hunger responses to reduce energy expenditure and increase food intake. Nakamura et al. reveal how GABAergic medullary reticular neurons coordinate both autonomic and feeding motor systems in response to hypothalamic NPY-driven signaling to inhibit brown adipose tissue thermogenesis and stimulate mastication and feeding.http://ift.tt/2iPeVid
A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice
Source:Vaccine
Author(s): Pablo F. Céspedes, Emma Rey-Jurado, Janyra A. Espinoza, Claudia A. Rivera, Gisela Canedo-Marroquín, Susan M. Bueno, Alexis M. Kalergis
Human respiratory syncytial virus (hRSV) is a major health burden worldwide, causing the majority of hospitalizations in children under two years old due to bronchiolitis and pneumonia. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that take place throughout the patient life. Although significant efforts have been invested worldwide, currently there are no licensed vaccines to prevent hRSV infection. Here, we describe that a recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV) confers protective immunity to the virus in mice. Our results show that a single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×107 plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8. Compared to unimmunized infected controls, vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages, parameters that are characteristic of hRSV infection in mice. Also, ex vivo re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-γ and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8+ and CD4+ T cell response capable of both restraining viral spread and preventing damage of the lungs. All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population.
http://ift.tt/2ji04NF
Could the RTS,S/AS01 meningitis safety signal really be a protective effect of rabies vaccine?
Source:Vaccine
Author(s): Bradford D. Gessner, Darryn L. Knobel, Anne Conan, Adam Finn
The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5–17month but not the 6–12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5–17month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates. No single hypothesis postulating an adverse effect from RTS,S/AS01 unites these observations. Unlike the 6–12week group, the control population in the 5–17month old age group received rabies vaccine. This raises the possibility that non-specific rabies vaccine effects had a protective effect against central nervous system infection, a hypothesis consistent with the epidemiologic data. The lack of a confirmed biologic mechanism for such an effect emphasizes the need for additional studies.
http://ift.tt/2iiuvPF
Back to the future: Immunization with M-001 prior to trivalent influenza vaccine in 2011/12 enhanced protective immune responses against 2014/15 epidemic strain
Source:Vaccine
Author(s): George H. Lowell, Sagit Ziv, Svetlana Bruzil, Ron Babecoff, Tamar Ben-Yedidia
We previously reported a 2011/12 study in elderly showing that immunization with the universal influenza vaccine candidate, M-001, three weeks before administering trivalent influenza vaccine (TIV) enhanced seroconversion of Hemagglutination Inhibition (HAI) antibodies against known influenza vaccine strains circulating at that time. We now report that those subjects primed with M-001 prior to TIV in 2011 also showed, in their 2011 sera, significantly more HAI antibodies with improved seroprotection and seroconversion against strain A/Switzerland/9715293/2013(H3N2-like) that caused the 2014/15 influenza epidemic and that wasn't known to circulate in 2011/12. These data indicate that M-001 can provide broadened enhanced immunity extending even to influenza strains destined to circulate in future years. The fact that M-001 stimulates T cell activation and is devoid of HA hypervariable epitopes indicates that such broadened HAI responses effected by M-001 priming is due to extensive T cell priming.
http://ift.tt/2iinezk
Quantitative analysis of the yield of avian H7 influenza virus haemagglutinin protein produced in silkworm pupae with the use of the codon-optimized DNA: A possible oral vaccine
Source:Vaccine
Author(s): Kuniaki Nerome, Sayaka Matsuda, Kenichi Maegawa, Shigeo Sugita, Kazumichi Kuroda, Kazunori Kawasaki, Reiko Nerome
In this study, we aimed to quantitatively compare the increased production of three H7 influenza virus-like particle (VLP) haemagglutinin (HA) with the use of a codon-optimized single HA gene in silkworm pupae. Recombinant baculovirus (Korea H7-BmNPV) could produce 0.40 million HA units per pupa, corresponding to 1832μg protein. The yield of the HA produced in larva was estimated to be approximately 0.31 million HA units per larva, and there were no significant differences between the three HA proteins. We could establish efficient recovery system of HA production in larvae and pupae with the use of three cycles sonication methods. Next, we compared yields of HA proteins from three different H7 and two H5 recombinant baculoviruses based on the amount of mRNA synthesized in BmN cells, suggesting that mRNA synthesis may be also a useful indicator for the production of HA. Based on HA titres from four recombinants, the yield of HA had a great influence on the codon-optimized effect and the characteristics of the viral HA gene. The recombinant containing codon optimized HA DNA of A/tufted duck/Fukushima/16/2011 (H5N1) did produce more than one million HA units, although another recombinant including of the wild H5N1 strain failed to show HA activity. Electron microscopy revealed the presence of large VLP and small HA particle in the heavy and light fractions. The purified VLPs reacted with the authentic anti-H7 antibodies and the antibodies prepared after immunization with the VLP H7 antigen. Also H5 and H7VLPs could produce HI antibody in chickens and mice with oral immunization. The antibodies elicited with oral immunization were confirmed in fluorescent antibody analysis and western blotting in Korea H5-BmNPV and H7HA-BmNPV recombinant infected BmN cells. Taken together, these findings provided important insights into future oral vaccine development.
http://ift.tt/2ji1EyY
Functional Dissection of the m6A RNA Modification
Publication date: Available online 4 January 2017
Source:Trends in Biochemical Sciences
Author(s): Brooke Huisman, Gabriel Manske, Stephen Carney, Sundeep Kalantry
http://ift.tt/2jaJ1ce
Characterization of water in hydrated Bombyx mori silk fibroin fiber and films by 2H NMR relaxation and 13C solid state NMR
Publication date: Available online 5 January 2017
Source:Acta Biomaterialia
Author(s): Tetsuo Asakura, Kotaro Isobe, Shunsuke Kametani, Obehi T. Ukpebor, Moshe C. Silverstein, Gregory S. Boutis
The mechanical properties of Bombyx mori silk fibroin (SF), such as elasticity and tensile strength, change remarkably upon hydration. However, the microscopic interaction with water is not currently well understood on a molecular level. In this work, the dynamics of water molecules interacting with SF was studied by 2H solution NMR relaxation and exchange measurements. Additionally, the conformations of hydrated [3-13C]Ala-, [3-13C]Ser- and [3-13C]Tyr-SF fibers and films were investigated by 13C DD/MAS NMR. Using an inverse Laplace transform algorithm, we were able to identify four distinct components in the relaxation times for water in SF fiber. Namely, A: bulk water outside the fiber, B: water molecules trapped weakly on the surface of the fiber, C: bound water molecules located in the inner surface of the fiber and D: bound water molecules located in the inner part of the fiber were distinguishable. In addition, four components were also observed for water in the SF film immersed in methanol for 30 seconds, while only two components for the film immersed in methanol for 24 hours. The effects of hydration on the conformation of Ser and Tyr residues in the site-specific crystalline and non-crystalline domains of 13C selectively labeled SF, respectively, could be determined independently. Our measurements provide new insight relating the characteristics of water and the hydration structure of silk, which are relevant in light of current interest in the design of novel silk-based biomaterials.Statements of SignificanceThe mechanical properties of Bombyx mori silk fibroin (SF) change remarkably upon hydration. However, the microscopic interaction between SF and water is not currently well understood on a molecular level. We were able to identify four distinct components in the relaxation times for water in SF fiber by 2H solution NMR relaxation and exchange measurements. In addition, the effects of hydration on the conformation of Ser and Tyr residues in the site-specific crystalline and non-crystalline domains of 13C selectively labeled SF, respectively, could be determined independently. Thus, our measurements provide new insight relating the characteristics of water and the hydration structure of silk, which are relevant in light of current interest in the design of novel silk-based biomaterials.
Graphical abstract
http://ift.tt/2hX8k5A
Susan Lee Lindquist (1949–2016)
Publication date: Available online 5 January 2017
Source:Trends in Biochemical Sciences
Author(s): James Shorter
Lindquist was a visionary and pioneer who transformed our understanding of how protein folding sculpts biology, evolution, and disease. She revealed several unanticipated mechanisms by which protein folding can buffer, release, and potentiate genetic variation in response to environmental stress, thereby enabling the rapid evolution of beneficial new traits. Her discoveries provide a rich framework for innovative therapeutic interventions in several fatal diseases, including Alzheimer's disease, Parkinson's disease, and cancer.
http://ift.tt/2hWZbdn
Targeted glioma chemotherapy by cyclic RGD peptide-functionalized reversibly core-crosslinked multifunctional poly(ethylene glycol)-b-poly(ε-caprolactone) micelles
Publication date: Available online 5 January 2017
Source:Acta Biomaterialia
Author(s): Ya Fang, Yu Jiang, Yan Zou, Fenghua Meng, Jian Zhang, Chao Deng, Huanli Sun, Zhiyuan Zhong
Cyclic RGD peptide-functionalized reversibly core-crosslinked biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) micelles (cRGD-RCCMs) were designed and developed for highly potent and targeted glioma chemotherapy. To achieve crosslinkable core, dithiolane-functionalized trimethylene carbonate (DTC) was incorporated into PCL block. Interestingly, cRGD-RCCMs displayed a high doxorubicin (DOX) loading content of ∼18 wt.%, small hydrodynamic size of ∼50 nm, and excellent colloidal stability with minimum drug leakage under physiological conditions whilst fast DOX release under cytoplasmic-mimicking reductive environments. MTT, confocal microscopy and flow cytometry measurement results pointed out that cRGD-RCCMs with 30% cRGD surface density (cRGD30-RCCMs) showed an evident selectivity, efficient cytoplasmic drug release, and superior antitumor activity to clinically used pegylated liposomal doxorubicin (DOX-LPs) in αvβ3 integrin overexpressing U87MG glioblastoma cells. Strikingly, DOX-loaded cRGD30-RCCMs demonstrated a prolonged circulation time showing an elimination half-life of ∼ 4.7 h, three times exceeding that of the non-crosslinked counterparts, and a remarkably enhanced tumor accumulation of 7.7%ID/g. Furthermore, in vivo therapeutic studies revealed that DOX-loaded cRGD30-RCCMs effectively suppressed tumor growth, significantly prolonged survival time, and lessened side effects in subcutaneous U87MG glioblastoma-bearing nude mice. These reversibly core-crosslinked multifunctional biodegradable micelles might be developed into advanced and clinically viable targeted anticancer nanomedicines.Statement of SignificanceNanomedicines based on biodegradable micelles and nanoparticles offer a most promising treatment for malignant tumors. The therapeutic outcomes of current nanomedicines are, however, trimmed by their instability, low tumor retention, inefficient tumor cell uptake, and inferior drug release control. We report herein that cRGD-functionalized, rapidly glutathione-responsive, and reversibly core-crosslinked biodegradable micellar doxorubicin based on PEG-PCL block copolymer mediates potent and targeted glioma chemotherapy, affording significantly better treatment efficacy and lower systemic toxicity than the non-crosslinked micellar doxorubicin and clinically used pegylated liposomal doxorubicin controls. These reversibly core-crosslinked multifunctional biodegradable micelles have emerged as a robust, simple, versatile, and safe nanoplatform that might elegantly bridge the gap between the scientific and translational anticancer nanomedicine research.
Graphical abstract
http://ift.tt/2iiujzX
Linking metabolic reprogramming to therapy resistance in cancer
Publication date: Available online 5 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Andrea Morandi, Stefano Indraccolo
Metabolic rearrangements are essential to satisfy the different requirements of cancer cells during tumorigenesis and recent studies have highlighted a role for such metabolic reprogramming in response and adaptation to therapies. However, therapy-resistant experimental models have been described to be either glycolysis-dependent or OXPHOS-addicted. Here we discuss the recent literature on metabolic reprogramming of cancer in therapy resistance with a plausible explanation of the observed differences which collectively indicate that dis-regulated metabolic pathways could be considered a potential therapeutic target in tumors resistant to conventional therapy.
http://ift.tt/2iOQa5q
Surveillance for Secure Differentiation
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): William B. Hamilton, Joshua M. Brickman
The precise place and time where embryonic differentiation begins is regulated by regionalized signaling. In this issue of Cell Stem Cell, Wang et al. (2017) investigate how converging Wnt and Nodal signals promote mesendoderm through a p53, Wnt3 feed-forward loop, pointing to a mechanism by which cells gauge time and fitness during differentiation.
Teaser
The precise place and time where embryonic differentiation begins is regulated by regionalized signaling. In this issue of Cell Stem Cell, Wang et al. (2017) investigate how converging Wnt and Nodal signals promote mesendoderm through a p53, Wnt3 feed-forward loop, pointing to a mechanism by which cells gauge time and fitness during differentiation.http://ift.tt/2iXk3xU
Created of Warm Blood and Nerves: Restoring an Enteric Nervous System in Organoids
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Christopher R. Schlieve, Tracy C. Grikscheit
The enteric nervous system (ENS) regulates numerous gastrointestinal functions, including epithelial barrier permeability and motility. In a recent Nature Medicine study, Workman et al. (2016) propose a method for introducing human pluripotent stem cell-derived enteric neural crest cells into developing human intestinal organoids, thereby restoring ENS cell types and contractile function.
Teaser
The enteric nervous system (ENS) regulates numerous gastrointestinal functions, including epithelial barrier permeability and motility. In a recent Nature Medicine study, Workman et al. (2016) propose a method for introducing human pluripotent stem cell-derived enteric neural crest cells into developing human intestinal organoids, thereby restoring ENS cell types and contractile function.http://ift.tt/2iOOZmu
Dominating the Negative: How DNMT3A Mutations Contribute to AML Pathogenesis
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Grant A. Challen
Somatic mutations in DNMT3A are one of the most prevalent genetic abnormalities found in acute myeloid leukemia (AML) patients. A new study by Guryanova et al. sheds mechanistic insight into how the most common DNMT3A variant protein contributes to AML using a combination of mouse genetics and primary patient samples.
Teaser
Somatic mutations in DNMT3A are one of the most prevalent genetic abnormalities found in acute myeloid leukemia (AML) patients. A new study by Guryanova et al. sheds mechanistic insight into how the most common DNMT3A variant protein contributes to AML using a combination of mouse genetics and primary patient samples.http://ift.tt/2iXdETe
Hacking the Matrix
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Michael Czerwinski, Jason R. Spence
Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix.
Teaser
Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix.http://ift.tt/2iOVpC5
Seq-ing Markers of Midbrain Dopamine Neurons
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Teresia Osborn, Penelope J. Hallett
Transplantation of human pluripotent stem cell-derived dopaminergic neurons is a promising approach to treating Parkinson's disease. In this issue of Cell Stem Cell, Kee et al. (2017) and Kirkeby et al. (2017) identify specific markers of midbrain dopaminergic progenitors to improve their derivation and predict dopamine neuron content after engraftment.
Teaser
Transplantation of human pluripotent stem cell-derived dopaminergic neurons is a promising approach to treating Parkinson's disease. In this issue of Cell Stem Cell, Kee et al. (2017) and Kirkeby et al. (2017) identify specific markers of midbrain dopaminergic progenitors to improve their derivation and predict dopamine neuron content after engraftment.http://ift.tt/2iXeFe3
Exosomal Small Talk Carries Strong Messages from Muscle Stem Cells
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Janelle M. Spinazzola, Emanuela Gussoni
Exosome-dependent intercellular communication is an emerging signaling mechanism involved in tissue repair and regeneration. Now in this issue of Cell Stem Cell, Fry et al. (2016) show that muscle stem cells communicate with fibrogenic cells by exosomal trafficking of microRNA-206 to regulate extracellular matrix deposition and muscle tissue remodeling.
Teaser
Exosome-dependent intercellular communication is an emerging signaling mechanism involved in tissue repair and regeneration. Now in this issue of Cell Stem Cell, Fry et al. (2016) show that muscle stem cells communicate with fibrogenic cells by exosomal trafficking of microRNA-206 to regulate extracellular matrix deposition and muscle tissue remodeling.http://ift.tt/2iOZDtL
Achieving Efficient Manufacturing and Quality Assurance through Synthetic Cell Therapy Design
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Yonatan Y. Lipsitz, Patrick Bedford, Anthony H. Davies, Nicholas E. Timmins, Peter W. Zandstra
New methods to manipulate gene and cell state can be used to engineer cell functionality, simplify quality assessment, and enhance manufacturability. These strategies could help overcome unresolved cell therapy manufacturing challenges and complement frameworks to design quality into these complex cellular systems, ultimately increasing patient access to living therapeutics.
Teaser
New methods to manipulate gene and cell state can be used to engineer cell functionality, simplify quality assessment, and enhance manufacturability. These strategies could help overcome unresolved cell therapy manufacturing challenges and complement frameworks to design quality into these complex cellular systems, ultimately increasing patient access to living therapeutics.http://ift.tt/2iXjFPS
New Insights into Early Human Development: Lessons for Stem Cell Derivation and Differentiation
Publication date: 5 January 2017
Source:Cell Stem Cell, Volume 20, Issue 1
Author(s): Janet Rossant, Patrick P.L. Tam
Pathways underlying mouse embryonic development have always informed efforts to derive, maintain, and drive differentiation of human pluripotent stem cells. However, direct application of mouse embryology to the human system has not always been successful because of fundamental developmental differences between species. The naive pluripotent state of mouse embryonic stem cells (ESCs), in particular, has been difficult to capture in human ESCs, and appears to be transitory in the human embryo itself. Further studies of human and non-human primate embryo development are needed to untangle the complexities of pluripotency networks across mammalian species.
Teaser
Direct comparisons between events of pre- and peri-implantation development in the human, as well as in non-human primates, and the mouse have highlighted numerous similarities and differences. Rossant and Tam summarize those findings and discuss their relevance to derivation of human pluripotent stem cells and their differentiation in vitro.http://ift.tt/2iOZHtl
Πέμπτη 5 Ιανουαρίου 2017
Applications of Burow's Grafts in the Reconstruction of Mohs Micrographic Surgery Defects.
http://ift.tt/2iXb3si
Squamous Cell Carcinoma In Situ Upstaged to Invasive Squamous Cell Carcinoma: A 5-Year, Single Institution Retrospective Review.
http://ift.tt/2hZ49o0
Broader Practice Indications for Mohs Surgical Defect Healing by Secondary Intention: A Survey Study.
http://ift.tt/2hZd4FX
Targeting Epidermal Growth Factor Receptor in Triple Negative Breast Cancer: New Discoveries and Practical Insights for Drug Development
Source:Cancer Treatment Reviews
Author(s): Ricardo Costa, Ami N. Shah, Cesar A. Santa-Maria, Marcelo R. Cruz, Devalingam Mahalingam, Benedito A. Carneiro, Young Kwang Chae, Massimo Cristofanilli, William J. Gradishar, Francis J. Giles
Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor + and HER2 + breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epithelial Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC.
http://ift.tt/2iKKkQj
Efferent Vision Therapy.
http://ift.tt/2hWKmam
A Giant Tumefactive Virshow-Robin Space: A Rare Cause of a Homonymous Quadrantanopia.
http://ift.tt/2iKMTl6
Acral and digital angioleiomyomata: Fourteen year experience at the Cleveland Clinic and review of the literature
ABSTRACT
Background
Angioleiomyoma is a benign neoplasm thought to derive from the tunica media of small venous vessels. Angioleiomyomata most frequently occur in the lower extremities with less common occurrences on the trunk, head, and upper extremities. Few cases of acral and digital angioleiomyoma have been described in the literature.
Methods
We add a series of twenty-one patients with acral angioleiomyoma including six cases of digital angioleiomyoma to the body of clinical and histologic findings along with a review of the literature of digital angioleiomyomata.
Results
Digital angioleiomyoma are equally distributed between male and female patients and are more often painful than the angioleiomyoma of all body sites. Acral angioleiomyomata favor the feet over hands at a ratio of 2.5:1, while digital angioleiomyoma favor the fingers over toes at a ratio of 4.3:1.
Conclusions
We suggest that vascular leiomyoma be included in the differential diagnosis of smooth muscle tumors with particular regard to the digits of both the hands and feet. Digital angioleiomyomata differ from acral angioleiomyomata in their equal gender distribution, increased tendency to cause pain, and preponderance for the fingers over the toes.
http://ift.tt/2hX0MLd
Is Psoriasis an autoimmune disease: interpretations from an immunofluorescence based study
Abstract
Introduction
Psoriasis is a multisystem, immune-mediated inflammatory disease. Some authors have proposed an autoimmune basis for psoriasis; however, till date, it has not been definitely established. The present study was conducted to explore the autoimmune nature of psoriasis.
Materials and methods
This was a prospective study in which 43 psoriasis patients were assessed for detailed clinical, histopathological and immunopathological features to explore the diagnostic utility of subtypes, intensity, and number of immunoreactants in lesional and non-lesional skin in these patients. In addition, the sera of these patients were analyzed for the presence of various autoantibodies.
Results
The patients' age ranged from 14 to 75 years with a M:F ratio of 1.52:1. Nine patients(20.93%) were positive for anti-nuclear and 2(4.65%) for anti-smooth muscle antibodies. Direct immunofluorescence (DIF) was positive in 31(72%) biopsies from the lesional and 27(63%) biopsies from non-lesional skin. In all these DIF positive cases, granular deposits of C5b-9 were detected at the dermo-epidermal junction. No significant difference was observed on comparing the type and pattern of immunoreactant positivity, amongst lesional and non-lesional skin biopsies(p > 0.05).
Conclusion
No significant association between psoriasis and immunoreactant deposition as well as autoantibody seroprevalence was observed, thereby refuting a definite autoimmune basis for psoriasis.
http://ift.tt/2jhya4s
Influence of ultrasonic activation over final irrigants in the removal of photosensitizer from root canal walls after photodynamic therapy
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Matheus Albino Souza, Bianca Pazinatto, Karolina Frick Bischoff, Huriel Scartazzini Palhano, Doglas Cecchin, José Antônio Poli de Figueiredo
IntroductionThe aim of the present study was to evaluate the influence of ultrasonic activation (US) of the final irrigant in the removal of the photosensitizer from root canal walls after photodynamic therapy.MethodsThe root canals of 60 single-rooted bovine extracted teeth were filled with 0.01% methylene blue and submitted to photodynamic therapy for 90seconds. After that, the roots were divided into six groups (n=10) according to the final irrigation protocol: distilled water (DW), DW+US, 17% EDTA, QMix, EDTA+US, and QMix+US. Then, the samples were submitted to scanning electron microscopy where a scoring system was used to evaluate the images and effectiveness of proposed treatments in the cervical, middle and apical regions of the root canals. The data were statistically analyzed by the Kruskal-Wallis and Mann-Whitney U tests for intergroup comparisons as well as the Wilcoxon and Friedman tests for intragroup comparisons at 5% of significance.ResultsThe 17% EDTA+US and QMix+US treatments were most effective in the removal of the photosensitizer in all regions of the root canal; the difference was statistically significant when compared to all other groups (p<0.05). There were no significant differences in the intragroup analysis comparing the effectiveness in the different regions of the same group (p<0.05).ConclusionsUS can aid 17% EDTA and QMix in removing the photosensitizer after photodynamic therapy and contributes to cleaning root canal walls.
http://ift.tt/2ii0bVe
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Ειδοποίηση Μελετητή:[ ωτα ] [HTML] Gender, identity and material: Film screening C Brand - 2017 ftypM4V *M4V M4A mp42isom*a┌moovlmvhd...
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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...
