
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 2
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Journal of Cutaneous Pathology, EarlyView.
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Journal of Cutaneous Pathology, EarlyView.
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Journal of Cutaneous Pathology, EarlyView.
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Clinical Endocrinology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Australasian Journal of Dermatology, EarlyView.
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Dermatologic Therapy, EarlyView.
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Dermatologic Therapy, EarlyView.
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Journal of Cosmetic Dermatology, EarlyView.
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Journal of Cosmetic Dermatology, EarlyView.
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Skin Research and Technology, EarlyView.
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Skin Research and Technology, EarlyView.
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Skin Research and Technology, EarlyView.
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British Journal of Dermatology, EarlyView.
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British Journal of Dermatology, EarlyView.
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British Journal of Dermatology, EarlyView.
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British Journal of Dermatology, EarlyView.
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British Journal of Dermatology, EarlyView.
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British Journal of Dermatology, EarlyView.
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Thank you for your concern and comment on our paper entitled " Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review".
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International Journal of Cosmetic Science, EarlyView.
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International Journal of Cosmetic Science, Volume 40, Issue 2, Page 199-206, April 2018.
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International Journal of Cosmetic Science, Volume 40, Issue 2, Page i-iv, April 2018.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, EarlyView.
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Clinical and Experimental Dermatology, Volume 43, Issue 4, Page i-373-374, June 2018.
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Clinical and Experimental Dermatology, EarlyView.
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AbstractBackground
Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.
ObjectivesThis prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity.
MethodsThe authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction.
ResultsPrimary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057).
ConclusionsIn this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450)
Abstract
Epicardial adipose tissue has unique properties that distinguish it from other depots of visceral fat. Rather than having distinct boundaries, the epicardium shares an unobstructed microcirculation with the underlying myocardium, and in healthy conditions, produces cytokines that nourish the heart. However, in chronic inflammatory disorders (especially those leading to heart failure with preserved ejection fraction), the epicardium becomes a site of deranged adipogenesis, leading to the secretion of proinflammatory adipokines that can cause atrial and ventricular fibrosis. Accordingly, in patients at risk of heart failure with preserved ejection fraction, drugs that promote the accumulation or inflammation of epicardial adipocytes may lead to heart failure, whereas treatments that ameliorate the proinflammatory characteristics of epicardial fat may reduce the risk of heart failure. These observations suggest that epicardial adipose tissue is a transducer of the adverse effects of systemic inflammation and metabolic disorders on the heart, and thus, represents an important target for therapeutic interventions.
AbstractBackground
Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol.
ObjectivesThis study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.
MethodsThe authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.
ResultsVariants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 x10–5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: –2.3% to –15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.
ConclusionsTTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.
AbstractBackground
Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates.
ObjectivesThis study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography.
MethodsPatients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction–defined major bleeding during 2 years of follow-up.
ResultsFrom September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction–defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1).
ConclusionsPFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)
AbstractBackground
Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who experience MALE.
ObjectivesAmong participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months.
MethodsWe analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation.
ResultsA total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was 3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio [HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43% (p = 0.01), total vascular amputations by 58% (p = 0.01), peripheral vascular interventions by 24% (p = 0.03), and all peripheral vascular outcomes by 24% (p = 0.02).
ConclusionsAmong individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]; NCT01776424)
Abstract
This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes.
AbstractBackground
Right ventricular pacing (RVP) is associated with heart failure and increased mortality. His bundle pacing (HBP) is a physiological alternative to RVP.
ObjectivesThis study sought to evaluate clinical outcomes of HBP compared to RVP.
MethodsAll patients requiring initial pacemaker implantation between October 1, 2013, and December 31, 2016, were included in the study. Permanent HBP was attempted in consecutive patients at 1 hospital and RVP at a sister hospital. Implant characteristics, all-cause mortality, heart failure hospitalization (HFH), and upgrades to biventricular pacing (BiVP) were tracked. Primary outcome was the combined endpoint of death, HFH, or upgrade to BiVP. Secondary endpoints were mortality and HFH.
ResultsHBP was successful in 304 of 332 consecutive patients (92%), whereas 433 patients underwent RVP. The primary endpoint of death, HFH, or upgrade to BiVP was significantly reduced in the HBP group (83 of 332 patients [25%]) compared to RVP (137 of 433 patients [32%]; hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.534 to 0.944; p = 0.02). This difference was observed primarily in patients with ventricular pacing >20% (25% in HBP vs. 36% in RVP; HR: 0.65; 95% CI: 0.456 to 0.927; p = 0.02). The incidence of HFH was significantly reduced in HBP (12.4% vs. 17.6%; HR: 0.63; 95% CI: 0.430 to 0.931; p = 0.02). There was a trend toward reduced mortality in HBP (17.2% vs. 21.4%, respectively; p = 0.06).
ConclusionsPermanent HBP was feasible and safe in a large real-world population requiring permanent pacemakers. His bundle pacing was associated with reduction in the combined endpoint of death, HFH, or upgrade to BiVP compared to RVP in patients requiring permanent pacemakers.
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The review focused on the role that media reporting plays in the level of public awareness about osteoporosis and its influence on osteoporosis treatment decisions.
We reviewed the literature on the role of media on three main aspects influencing patient adherence to osteoporosis treatment: the awareness of osteoporosis as a major health problem, the perception of the effectiveness of osteoporosis medications, and the fear of adverse effects with osteoporosis medications.
A review of the literature confirmed what is routinely observed in clinical practice—that media report can strongly influence the level of awareness of osteoporosis and fracture risk. Inadequate and/or incorrect information on osteoporosis in the media are associated with a low level of awareness of the disease. High-risk patients may have a poor understanding of the need for treatment. Alarming information in the media over the last 2 decades regarding effectiveness and safety of long-term osteoporosis treatment is associated with reduction in the use of osteoporosis medications.
There is a gap between the application of clinical recommendations and patient perceptions of osteoporosis and its treatment. There is a need for better education of patients and practitioners aimed at recognizing the serious consequences of fractures and understanding the expected benefits and potential risks of treatment. Media reports that disseminate evidence-based information on the balance of benefits and risks could help to reduce the osteoporosis treatment gap and mitigate the crisis in osteoporosis care.
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High-fat (HF) diets promote an increased uptake and storage of free fatty acids (FFAs) and triglycerides (TGs) in hepatocytes, which initiates steatosis and induces lipotoxicity, inflammation and insulin resistance. Activation and signaling of Toll-like receptor 4 (TLR4) by FFAs induces inflammation evident in NAFLD and insulin resistance. Currently, there are no effective treatments to specifically target inflammation associated with this disease. We have established the efficacy of phenylmethimazole (C10) to prevent lipopolysaccharide and palmitate-induced TLR4 signaling. Because TLR4 is a key mediator in pro-inflammatory responses, it is a potential therapeutic target for NAFLD. Here, we show that treatment with C10 inhibits HF diet-induced inflammation in both liver and mesenteric adipose tissue measured by a decrease in mRNA levels of pro-inflammatory cytokines. Additionally, C10 treatment improves glucose tolerance and hepatic steatosis despite the development of obesity due to HF diet feeding. Administration of C10 after 16 weeks of HF diet feeding reversed glucose intolerance, hepatic inflammation, and improved hepatic steatosis. Thus, our findings establish C10 as a potential therapeutic for the treatment of NAFLD.
Estrogen induces proliferation of breast epithelial cells and is responsible for breast development at puberty. This tightly regulated control is lost in estrogen-receptor-positive (ER+) breast cancers, which comprise over 70% of all breast cancers. Currently, breast cancer diagnosis and treatment considers only the α isoform of ER; however, there is a second ER, ERβ. Whilst ERα mediates estrogen-driven proliferation of the normal breast in puberty and breast cancers, ERβ has been shown to exert an anti-proliferative effect on the normal breast. It is not known how the expression of each ER (alone or in combination) correlates with the ability of estrogen to induce proliferation in the breast. We assessed the levels of each ER in normal mouse mammary glands subdivided into proliferative and non-proliferative regions. ERα was most abundant in the proliferative regions of younger mice, with ERβ expressed most abundantly in old mice. We correlated this expression profile with function by showing that the ability of estrogen to induce proliferation was reduced in older mice. To show that the ER profile associated with breast cancer risk, we assessed ER expression in parous mice which are known to have a reduced risk of developing ERα breast cancer. ERα expression was significantly decreased yet co-localization analysis revealed ERβ expression increased with parity. Parous mice had less unopposed nuclear ERα expression and increased levels of ERβ. These changes suggest that the nuclear expression of ERs dictates the proliferative nature of the breast and may explain the decreased breast cancer risk with parity.

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Due to the absence of randomized trials, the optimal management for squamous cell cancer of unknown primary in the head and neck region (SCCHN CUP) remains controversial. Current strategies are based on retrospective studies, clinical experience, and institutional policies.
An anonymous questionnaire with a total of 24 questions was created and distributed by the use of an online version (Google Forms®, Google, Mountain View, CA, USA) as well as a printout version as equivalent option. An email with a link to the survey and the questionnaire as attachment was sent to 361 DEGRO(German Society of Radiation Oncology)-associated departments. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of practice. Representativity of the sample size for the DEGRO was also evaluated.
66 responses were received including answers from 20 (30%) university departments, 16 (24%) non-university institutions, and 30 (46%) radiation oncology practices. 95% of the participants routinely present these cases in an interdisciplinary tumor board and use intensity modulated radiotherapy (IMRT) techniques for SCCHN CUP treatment. Surgery includes neck dissection in 83% and tonsillectomy in 73% of the cases. Human papilloma virus (HPV) status is routinely determined in 82% of the departments. Statistically significant differences between universities and institutions and clinics and practices could be found with respect to positron emission tomography-computed tomography (PET-CT) utilization, indications for chemotherapy, radiotherapy volumes, and cumulative doses.
Diagnostics and treatment for SCCHN CUP within the DEGRO remain heterogeneous. A prospective register trial with standard operation procedures is warranted to homogenize and possibly improve management.
Publication date: 1 September 2018
Source:Talanta, Volume 187
Author(s): Qunfang Xu, Kaixin Liang, Ren-Yu Liu, Liu Deng, Min Zhang, Liangfang Shen, You-Nian Liu
The accurate quantification of p53 protein expression level is of great importance for cancer diagnosis. Here, a highly sensitive fluorescent sensor based on DNA functionalized magnetic nanoparticles was developed for the detection of p53 protein expression. Instead of a monoclonal antibody, a consensus DNA was employed to capture p53 protein. Meanwhile the fluorescent dye tethered DNA was used as the signal output instead of enzyme tagged nanoparticle or antibody. Consequently, our developed method is cost-effective for both the p53 capture and detection by compared with the conventional immunoassay. The biosensor developed by the above strategy was used to quantitatively detect p53, which yields a detection limit of 8 p.M. with the linear range of 50 p.M. to 2 nM. The sensitive for specific p53 detection was achieved due to the facile magnetic separation from the complex condition, and the reduced non-specific absorption effect by dextran. Moreover, the method is able to measure p53 from real cell lysate without extensive sample pretreatment/separation. The developed p53 biosensor has high sensitivity, good selectivity and reliable accuracy. It demonstrates great potential in clinical cancer diagnosis and early detection of cancer.
Publication date: 1 September 2018
Source:Talanta, Volume 187
Author(s): Mustafa Bener, Furkan Burak Şen, Reşat Apak
Sensing of total antioxidant capacity (TAC) as an integrated parameter showing the collective action of various antioxidants is an important challenge in food, biochemical and drug analysis. A novel heparin-stabilized gold nanoparticles (AuNPs)-based 'cupric reducing antioxidant capacity' (CUPRAC) colorimetric sensor was designed for TAC measurement. Heparin, a sulfated polysaccharide, was both the reducing and stabilizing agent for distinct negatively-charged AuNPs synthesis. The stabilized AuNPs were added to the copper(I)-neocuproine (Cu(I)-Nc) solution formed from the reaction of Cu(II)-Nc with antioxidants, and the absorbance of the resulting Cu(I)-Nc-AuNPs (Cu(I)-Nc cationic chelate electrostatically adsorbed on gold nanoparticles) was measured at 455 nm. As opposed to other similar AuNPs-based sensors, the proposed nano-sensor exhibited excellent (1000-fold) tolerance toward inert electrolytes without aggregation. The linear range was wider than that of conventional CUPRAC, with lower LOD (0.2 µM for trolox) and higher molar absorptivity (8.36 × 104 M−1 cm−1 for quercetin). The 'trolox equivalent antioxidant capacity' (TEAC) values and activity order for a number of antioxidants were in accordance with those of the reference CUPRAC assay. Antioxidant additions to black tea extract gave recoveries of 93–97% and RSD 2–6%. This green sensor significantly reduced reagent consumption, and operated in complex food samples with a simple, reliable and robust methodology.
Publication date: 1 September 2018
Source:Talanta, Volume 187
Author(s): Abdullah A. Abdullah, Yavuz Yardım, Zühre Şentürk
In the present paper, an electroanalytical methodology was developed for the determination of an important catechol-containing flavonoid derivative, quercetin using adsorptive stripping voltammetry at a cathodically pretreated boron-doped diamond electrode. In cyclic voltammetry, the compound showed a couple of oxidation/reduction peak at low positive potentials, and additional two oxidation peaks at more positive potentials. The sensitivity of the stripping voltammetric measurements was significantly improved when the cationic surfactant, cetyltrimethylammonium bromide (CTAB) was present in the electrolyte solution. Using square-wave stripping mode, a highly linear analytical curve was obtained for quercetin determination in 0.1 M acetate buffer solution (pH 4.7) containing 3 × 10−4 M CTAB at + 0.37 V (vs. Ag/AgCl) (after 30 s accumulation at open-circuit condition) in the range of 0.5–200 ng mL−1 (1.7 × 10−9–3.3 × 10−7 M), with a detection limit of 0.132 ng mL−1 (4.4 × 10−10 M). As an example, the practical applicability of proposed method was successfully tested with the measurement of quercetin concentration in commercial apple juice samples.
Hexabromocyclododecanes (HBCDs) are a class of widely used brominated flame retardants (BFRs) that exhibit strong hydrophobicity. The ubiquity and persistence of HBCDs in sediment have attracted significant attention because of public health concerns. The environmental fate and ecological risks of HBCDs closely depend on their phase distribution in sediments. However, little information is available regarding the freely dissolved concentrations (Cfree ) of HBCDs in sediment porewater. In this study, we developed a method to measure Cfree of HBCDs in sediment porewater using triolein-embedded cellulose acetate membranes (TECAM). The TECAM-to-water partitioning coefficient (log KTECAM ) was 4.69, 4.77, and 4.63 for α-HBCD, β-HBCD, and γ-HBCD, respectively. In sediments, HBCDs sorbed to the sediment solid phase accounted for more than 99% of the total chemical mass. The dissolved organic carbon (DOC)-water partition coefficient (KDOC ) values were derived from TECAM measurements, and the log KDOC values ranged from 5.77 to 6.23 for the three HBCD diastereomers, suggesting a strong tendency for HBCDs to sorb to DOC. The high sorption of HBDCs for DOC implies a potential for DOC-facilitated transport which may enhance the environmental mobility of HBCDs.
In this work, we have developed a low-cost and green strategy for nanoscale zero-valent iron (ZVI) in situ encapsulated in lignin-derived hydrochar (Fe@HC) by a facile one-pot synthesis route. The as-synthesized Fe@HC was characterized for physicochemical properties by X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), transmission electron microscope (TEM), thermal gravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FT-IR). Further catalytic experiment revealed that phenol could be completely degraded by Fe@HC-800 within 20 min with peroxymonosulfate (PMS) at mild temperatures. Fe@HC-800 catalyst also exhibited stable performance after three runs of regeneration. The XPS and XRD results proved the key role of Fe0 in the degradation of phenol. This approach is of great potential to the development of green materials biomass-derived carbon materials for wastewater treatment applications.
The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer's disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermates, APP-deficient mice were resistant to diet-induced obesity, which was linked to higher energy expenditure and lipid oxidation throughout the dark phase and was associated with increased spontaneous physical activity. Consistent with this lean phenotype, APP-deficient mice fed a high-fat diet (HFD) had normal insulin tolerance. However, despite normal insulin action, these mice were glucose intolerant, similar to WT mice fed a HFD. This was associated with reduced plasma insulin in the early phase of the glucose tolerance test. Analysis of the pancreas showed that APP was required to maintain normal islet and β-cell mass under high fat feeding conditions. These studies show that, in addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.
Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to preeclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH) plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal liver gene expression, resulting from CSH deficiency. We sought to examine the impact of CSH deficiency on fetal and placental size earlier in gestation (50 dGA), and to examine placental gene expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a 41% reduction (P ≤ 0.05) in uterine vein concentrations of CSH, and significant (P ≤ 0.05) reductions (21%) in both fetal body and liver weights. Placentae harvested at 50 and 135 dGA exhibited reductions in IGF1 and IGF2 mRNA concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast, mRNA concentrations for various members of the System A, System L and System y+ amino acid transporter families were not significantly impacted. The IUGR observed at the end of the first-third of gestation indicates that the near-term IUGR reported previously, began early in gestation, and may have in part resulted from deficits in the paracrine action of CSH within the placenta. These results provide further compelling evidence for the importance of CSH in the progression and outcome of pregnancy.
The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (kl/kl) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D in kl/kl mice. The same effects were seen in rodent bone models in vitro, in which we also detected formation of a sKL complex with FGF23-FGFR and decreased Phex (gene responsible for X-linked hypophosphatemic rickets (XLH)/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralization in vitro was rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.
Publication date: 30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Celio Ferreira, Paul Hagen, Melanie Stern, Janine Hussner, Uwe Zimmermann, Markus Grube, Henriette E. Meyer zu Schwabedissen
The protein family of Organic Anion Transporting Polypeptides (OATPs) summarizes various transporters known to facilitate cellular uptake of xenobiotics. One member of this family is OATP2B1. This transporter is ubiquitously expressed and possesses a PDZ-binding motif at the C-terminus. PDZK1 (PDZ domain-containing 1) is a scaffold protein that influences function of different membrane proteins by sorting/stabilization of their membrane localization. It was aim of the herein reported study to investigate whether there is an interaction between OATP2B1 and PDZK1, and to further characterize its impact on transport function. At first expression of both OATP2B1 and PDZK1 was evaluated in liver, kidney and intestine. Based on the existence of a C-terminal PDZ-class I binding motif in OATP2B1 and the co-expression in all tested tissues an interaction was likely. Testing the influence of PDZK1 on OATP2B1 transport function revealed enhanced transport capacity for estrone 3-sulfate, thereby suggesting a change in OATP2B1 amount in the membrane. This assumption was validated by Western blot analysis. Finally, deletion of the C-terminal PDZ-binding motif in OATP2B1 lowered the impact of PDZK1 on transport function. Taken together, we report an interaction of PDZK1 with OATP2B1, which influences localization and function of the transporter. Changes in PDZK1 expression may therefore be one factor contributing to interindividual differences in OATP2B1 mediated pharmacokinetic processes.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Yan Qin, Qianqian Zhai, Yan Li, Meng Cao, Yun Xu, Kelei Zhao, Tao Wang
Diabetic nephropathy (DN) is a common complication of diabetes and the major cause of chronic kidney disease. Cyanidin 3-glucoside (C3G) is the most widespread anthocyanin in nature. In the present study, we aimed to investigate the possible effects of C3G on DN in db/db mice. We found that body weights and high levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure in diabetic mice were significantly reduced by C3G. C3G also reduced the ratio of kidney to body weight and the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological changes of kidneys, reduced the surface area of Bowman's capsule, glomerular tuft, Bowman's space, and decreased renal expression of collagen IV, fibronectin, transforming growth factor β 1 (TGFβ1), matrix metalloprotein 9 (MMP9) and α-smooth muscle actin (α-SMA) in db/db mice. The Lee's index, perirenal white adipose tissue weight, and high levels of blood and renal triglyceride and cholesterol were decreased by C3G. Moreover, C3G reduced systemic levels and renal expression of tumor necrosis factor ɑ (TNFɑ), IL-1ɑ, and monocyte chemotactic protein-1 (MCP-1), indicating the inhibition of inflammation. Furthermore, C3G increased glutathione (GSH) level and decreased GSSG level in kidneys of diabetic mice. The renal mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) was increased by C3G in diabetic mice. Buthionine sulphoximine (BSO), an inhibitor of GSH synthesis, inhibited the effects of C3G on glucose metabolic dysfunction and DN. The data demonstrates that enhancement of GSH pool is involved in the renal-protective effects of C3G. Overall, C3G could be a promising therapeutic option for attenuation of diabetes and DN.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Dou Yu, Yu Qin, Lei Jun-qiang, Guo Shun-lin
Platinum-based chemotherapeutic drugs, especial cisplatin, are the most common and effective anticancer drugs to treat the non-small cell lung cancer (NSCLC), but the major obstacle of this treatment is the resistance to chemotherapeutic drugs due to the anti-apoptosis of cancer cells. In our study, we found that Canopy homolog 2 (CNPY2) is increased in NSCLC tissues compared to the normal lung tissues, and the upregulation of CNPY2 is correlated with poor survival. Next, colony formation, annexin V-binding and TUNEL assays revealed that overexpression of CNPY2 inhibits the apoptosis of NSCLC cells induced by cisplatin. Further assays demonstrated that the anti-apoptosis may be aroused by the hyperactivation of NF-κB signaling pathway, and blocking the NF-κB pathway promotes the apoptosis of CNPY2-upregulating cells. The above results suggest that CNPY2 can serves as a therapeutic target to promote the effect of chemotherapy in NSCLC.
https://ift.tt/2Gf95Ov
Publication date: August 2018
Source:Biomedicine & Pharmacotherapy, Volume 104
Author(s): Ebrahim Nabaee, Mahnaz Kesmati, Ali Shahriari, Lotfollah Khajehpour, Mozhgan Torabi
Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation.Male Wistar rats (weighing 200 ± 20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain.72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups.Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems.
https://ift.tt/2KY3Oys
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Feng Han, Xin-xin Xia, Meng dou, Yu-xiang Wang, Wu-Jun Xue, Xiao-Ming Ding, Jin Zheng, Chen-guang Ding, Pu-Xun Tian
Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9 mg/kg/d) via oral gavage for 7 consecutive days prior to I/R. Notably, ATG aggravated kidney I/R injury with the concentration increases. Multiple biochemical assays and histological examination showed ATG significantly alleviated the inflammatory response as reflected by a decreased expression of proinflammatory cytokine, TLR4/MyD88, and NF-κB, along with the infiltration of CD68+ macrophage and CD11b+Gr1+ neutrophil in the kidneys. Meanwhile, ATG alleviated I/R-induced oxidative stress proved by increasing kidney manganese superoxide dismutase and glutathione peroxidase activity but reducing levels of malonaldehyde and inducible nitric oxide synthase. On the contrary, apoptosis was significantly increased in kidneys of ATG-treated mice compared with vehicle-treated controls, especially in tubular cells. There were increased numbers of TUNEL positive cells and increased Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 expression. The current study demonstrates that pretreatment of ATG aggravates I/R induced acute kidney injury by increasing apoptosis of tubular cells despite reducing infiltrating inflammatory cells and proinflammatory cytokine.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Jin Soo Kim, Seul Gi Lee, Kyoungjin Min, Taeg Kyu Kwon, Ha-Jeong Kim, Ju-Ock Nam
Eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) is a flavonoid compound from Artemisia species that possesses beneficial biological activities such as anti-cancer, anti-oxidation, and anti-inflammatory activities. However, an anti-adipogenic effect has not yet been reported. In this study, we found that eupatilin significantly inhibited the adipogenesis of 3T3-L1 adipocytes. Eupatilin decreased intracellular lipid accumulation and suppressed the expression level of key adipogenic regulators in 3T3-L1 adipocytes, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT-enhancer-binding protein alpha (C/EBPα), in a concentration-dependent manner. These results show that eupatilin significantly inhibits 3T3-L1 cell differentiation and suggest that it has potential as a novel anti-obesity therapy.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Quadri K. Alabi, Rufus O. Akomolafe, Joseph G. Omole, Modinat A. Adefisayo, Olaofe L. Ogundipe, Ayodeji Aturamu, Joseph O. Sanya
Colitis is a chronic inflammation and ulcer on the inner lining of the large intestine. For many centuries Ocimum gratissimum (OG) leaves have been used in folk medicine in Nigeria to treat inflammatory bowel diseases, however, to date, the anti-colitis effects of OG have not been scientifically proven. In this study we investigated the effects of polyphenol rich extract of Ocimum gratissimum (PREOG) leaf on colonic mucosa injury in colitis, its mechanisms, initial administration time and dosage. Dextran sodium sulfate (DSS)-induced rat colitis models was used. PREOG administration was initiated at 3 and 7 d after the model was established at doses of 200, 400 and 800 mg/kg for 7 d. 5-aminosalicylic acid (5-ASA) was used as a reference drug. The disease activity index (DAI), vascular permeability, markers of oxidative stress, granulocyte infiltration, inflammation and histopathological alteration were evaluated. Obvious colonic inflammation and mucosa injuries were observed in DSS-induced colitis groups. PREOG administration promoted repair of colonic mucosa injuries, attenuated inflammation, and decreased DAI scores in rats with colitis. PREOG also decreased the plasma concentrations of Interleukin-(IL)-6 and tumor necrosis factor (TNF)-α, and concentrations of myeloperoxidase, nitric oxide, cyclooxygenase-2 and malondialdehyde in the colon, and increased the plasma concentrations of IL-4 and IL-10 as well as the concentration of superoxide dismutase, catalase and reduced glutathione in the colon. The efficacy of PREOG was dosage dependent. In conclusion, OG repairs colonic mucosa injury in experimental colitis through its ant-inflammatory and ant-oxidant. Its efficacy related to initial administration time and dose.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Qiuling Sang, Daju Sun, Zonghan Chen, Weijia Zhao
ObjectiveIt has been reported that sciatic nerve injury (SNI) leads to degeneration, damage, and apoptosis of motor neurons. Nerve growth factor (NGF) plays a pivotal role in regeneration and reestablishment of neuronal function via activating PI3K/Akt survival signaling pathways. Curcumin owns neuroprotective effect following brain injury. In the present study, we attempt to investigate underlying mechanism of neuroprotective effect of curcumin through elucidating its correlation with NGF and PI3K/Akt signaling pathways in vitro and in vivo.MethodsPC-12 cells were exposed H2O2 in order to induce neuron cell injury and cells were then treated with curcumin. Caspase-3, NGF level and Akt phosphorylation were determined using flow cytometry and western blotting. Then, cells were treated with NGF specific siRNA followed by measurement of apoptosis, NGF and Akt phosphorylation levels. In animal model, rats were subjected to SNI and then randomly designated into four different groups: curcumin, curcumin + LY294002, curcumin + NGF shRNA, and negative controls and 12 rats in each group (n = 12). After four weeks of continuous treatment, tissue samples were obtained and subjected to TUNEL, NeuN double staining and western blotting.ResultsCurcumin significantly reduced the number of apoptotic cells induced by H2O2 and this effect was associated with upregulation of TrkA, Akt and downregulation of p17. ProNGF level was significantly decreased while mature NGF level was increased with curcumin treatment. When NGF was suppressed, anti-apoptotic effect of curcumin was attenuated. In addition, inhibition of PI3K/Akt results in increased apoptotic rate compared to vehicles following curcumin treatment which was reflected by decreased p17, Ki67, and cyclin D1. Suppression of NGF and inhibition of PI3K led to increased neuron cell death through increasing proNGF and decreasing mNGF, Akt, TrkA, p75NTR, and p17.ConclusionOur findings revealed that curcumin exerts its protective effect against injured neurons through stimulating NGF release which further activates TrkA and PI3K/Akt cell survival signaling.
https://ift.tt/2jVcF7V
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Linqi Guo, Yu Zhou, Ying Chen, Huawei Sun, Yue Wang, Yikun Qu
Over the past decades, lncRNAs have attracted more and more attentions of researchers. It has been verified that lncRNAs can modulate multiple biological behaviors in various human cancers. LncRNA ASAP1-IT1 has been certified to be a tumor facilitator in several malignant tumors. This study aims to investigate the effects of dysregulated ASAP1-IT1 on biological processes of Cholangiocarcinoma. The high expression level of ASAP1-IT1 was tested in Cholangiocarcinoma tissues and cells with qRT-PCR. Upregulation of ASAP1-IT predicted the unfavorable prognosis for Cholangiocarcinoma patients. Next, ASAP1-IT1 was knocked down in cancerous cells for loss-of function assay. MTT, colony formation and transwell and western bot assays were performed to demonstrate the specific impacts of ASAP1-IT1 on proliferation, migration and EMT progression of Cholangiocarcinoma. Cells. As a results, the Cholangiocarcinoma progression was inhibited. Hedgehog signaling pathway has been discovered to be a treatment target in Cholangiocarcinoma. In this study, the interaction between ASAP1-IT1 and hedgehog pathway was specifically investigated. Smo and Gli1, two hedgehog-related proteins were examined in Cholangiocarcinoma cells. The results of qRT-PCR and western blot assay suggested that ASAP1-IT1 could positively modulate Smo and Gli1 in Cholangiocarcinoma. Finally, rescue assays were carried out to prove that ASAP1-IT1 could improve Cholangiocarcinoma progression and development via hedgehog signaling pathway.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Qi Li, Jiade Li, Yanli Liu, Mingyu Zhang, Chang Chen
Dipeptidyl peptidase IV (DPP-IV) inhibitors are novel oral anti-hyperglycemic agents. Here, the anti-apoptotic effect of Anagliptin in human umbilical vein endothelial cells (HUVECs) was evaluated. Cultured HUVECs were pre-incubated with Anagliptin, and then treated hydrongen peroxide (H2O2) to induce apoptosis. The apoptosis of HUVECs were detected by viability, LIVE/DEAD staining assay and flow cytometry assays. HUVECs were transfected with plasmid harboring human NADPH oxidases (NOX) 4 or an empty vector. The formation of reactive oxygen species (ROS) was measured by immunofluorescence. Apoptotic and anti-apoptotic factor were detected by Western Blot. Pre-incubation with Anagliptin protected HUVECs from H2O2 induced apoptosis. The transfection assay also indicated that pre-incubation with Anagliptin inhibited the apoptosis of HUVECs induced by NADPH oxidase 4 (NOX-4) overexpression. Immunofluorescence demonstrated that pre-incubation with Anagliptin suppressed the formation of ROS in apoptotic HUVECs. Pre-incubation with Anagliptin inhibited NOX-4 mediated the Bax, caspase-3, cleave caspase-3 and Cyto C overexpression, but up-regulated the protein level of Bcl-2 in HUVECs. The data help us to better understand the effect of Anagliptin on apoptosis, and will be valuable in identifying new targets to prevent the endothelial cell apoptosis after injury.
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Guangling Yang, Ruipeng Song, Limin Wang, Xuejian Wu
Long non-coding RNA P73 antisense RNA 1 T (lncRNA TP73-AS1) has been shown to involve in the progression of numerous tumors. Nevertheless, the expression as well as the functional mechanisms of TP73-AS1 in osteosarcoma (OS) are still largely unknown. This study aimed to explore the roles and underlying mechanism of TP73-AS1 in OS progression. In thye present study, TP73-AS1 expression was significantly increased in OS tissues and cell lines. High TP73-AS1 expression was associated with poor overall survival of OS patients. TP73-AS1 knockdown suppressed OS cells proliferation and invasion in vitro as well as tumor growth in vivo. Furthermore, we identified that miR-142 could act as a direct target for TP73-AS1 and miR-142 inhibition reversed the suppression of OS cells proliferation and invasion induced by TP73-AS1 knockdown. In addition, we showed that TP73-AS1 could function as a sponge of miR-142 to positively regulate Rac1 in OS cells. Thus, our data suggested that TP73-AS1 served as an oncogenic lncRNA in OS progression, and could be regarded as an efficient therapeutic target in the treatment of OS.
https://ift.tt/2GeI2ms
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Muhammad Abbas, Alessia Faggian, Dahiru Nasiru Sintali, Ghulam Jilany Khan, Shagufta Naeem, Meiqi Shi, Chen Dingding
Gastric cancer is the fourth most common worldwide cause of cancer-related death. Early gastric cancer has no associated symptoms, for this reason, patients come to the attention of the clinicians only in advanced stages. This paper aims to give a global view on the biomarkers for gastric cancer and the therapy in use. We discuss VEGF family, HER family, E-cadherin, PD-L1, and PD-L2, FGFR, mTOR. Finally, we considered emerging biomarkers as MET, microsatellite instability, and microRNA variations. Furthermore, we have analyzed in depth the chemotherapeutic and adjuvant therapies used in the clinic nowadays, comparing the overall and progression-free survival between them. Identifying and validating diagnostic, prognostic, predictive, and pharmacodynamic biomarkers will be mandatory to the huge impact on patients' outcomes and for improving the efficiency of the drug development process.
https://ift.tt/2jTsNGM
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Hongtao Wang, Hongli Liu, Shengping Min, Yuanbing Shen, Wei Li, Yuqing Chen, Xiaojing Wang
Cyclin-dependent kinase 16 (CDK16, PCTAIRE1) expression is upregulated in a wide variety of human malignancies. However, the function(s) of CDK16 in non-small cell lung cancer (NSCLC) remain unknown. Therefore, here we investigated the role of CDK16 in NSCLC. From 43 NSCLC tumors and matching healthy control lung tissues, immunohistochemistry revealed significantly greater CDK16 and phospho-p27Ser10 staining levels in NSCLC samples relative to healthy controls. The NSCLC cell line EKVX was transfected with a control siRNA, a CDK16-siRNA, or CDK16-siRNA + p27-siRNA. We found significantly decreased proliferation levels and significantly increased apoptosis levels in CDK16-silenced NSCLC cells. However, these effects were abrogated in cells treated with both the CDK16-siRNA and the p27-siRNA. In CDK16-silenced NSCLC cells, we found upregulated p27 and downregulated phospho-p27Ser10 protein expression but downregulated ubiquitinated p27 and ubiquitinated phospho-p27Ser10 protein expression. Cycloheximide-treated CDK16-silenced NSCLC cells displayed a much milder reduction in p27 protein expression over time relative to untreated CDK16-silenced NSCLC cells. In summary, CDK16 is significantly upregulated in human NSCLC tumor tissue and plays an oncogenic role in NSCLC cells via promoting cell proliferation and inhibiting apoptosis in a p27-dependent manner. Moreover, CDK16 negatively regulates expression of the p27 via ubiquination and protein degradation.
https://ift.tt/2GdBfJL
Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Ariadna Lafourcade Prada, Jesús Rafael Rodríguez Amado, Hady Keita, Edgar Puente Zapata, Helison Carvalho, Emersom Silva Lima, Tatiane Pereira de Sousa, José Carlos Tavares Carvalho
IntroductionCassia grandis Lf fruits are ethnobotanically used for digestive disorders, anemia, and for reducing blood glucose. However, there are no studies about the antidiabetic activity nor the oral toxicity of the plant fruit-extracts. This paper aims to evaluate the hypoglycemic effect of C. grandis fruits extract in vivo, and assess the acute oral toxicity, and sub-acute oral toxicity. The antioxidant activity and the α-glycosidase inhibitor effect were also evaluated.MethodsThe extract was obtained by maceration of the fruit pulp with 70% hydroalcoholic solution (1:2, m:v). The extractive solution was concentrated in a vacuum rotary evaporator, up to a drug: solvent ratio of 2:1 (g/ml). Soluble solids, relative density, refractive index, pH, total phenolics, and flavonoids were determined. A preliminary phytochemical screening was made, followed by the quantitation of volatiles by GC/MS. The acute and sub-acute oral toxicity was evaluated in Sprague Dawley rats, by using biochemical and hematological parameters. The radical scavenging activity (DPPH, ABTS) and α-glycosidase inhibitory effect were tested. The hypoglycemic effect was assessed in alloxan-induced diabetic rats.ResultsThe extract of C. grandis contains alkaloids, coumarins, flavonoids, free amino acids, amines, phenols, tannins, reduced sugars, resins, saponins, steroids, and triterpenes, plus 38 volatile compounds, being linalool the most abundant (1,66%). The extract exhibited an LD50 > 2000 mg/kg, and after a continuous administration (1000 mg/kg, 28-days), the hematological and biochemical parameters were normal. The extract showed hypoglycemic effect, being the dose 200 mg/kg no statistically different from glibenclamide at 25 mg/kg. Good antioxidant activity and a potent α-glycosidase inhibitory effect were also observed.ConclusionC. grandis extract is an excellent hypoglycemic and non-toxic plant product. The hypoglycemic mechanism could be associated with the antioxidant effect and with the α-glycosidase inhibition. Up to the best of our knowledge, this is the first report on the hypoglycemic effect in vivo of C. grandis fruits extract.
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Publication date: 10 August 2018
Source:Journal of Ethnopharmacology, Volume 222
Author(s): Igor Rafael Praxedes De Sales, Rodrigo De Oliveira Formiga, Flávia Danniele Frota Machado, Raphaela Francelino Nascimento, Matheus Marley Bezerra Pessoa, Monique Emanuela Frutuoso Xavier Barros, Giciane Carvalho Vieira, Francisco Allysson Assis Ferreira Gadelha, Alexsandro Fernandes Marinho, José Maria Barbosa Filho, Raimundo Fernandes De Araújo Júnior, Aurigena Araújo Antunes, Leônia Maria Batista
Ethnopharmacological relevanceThe leaves and roots of Cissampelos sympodialis (Menispermaceae) are used by indian tribes and in folk medicine to treat genitourinary infections, inflammation, asthma and gastrointestinal disorders.Material and methodsThe standardized ethanolic extract (Cs-EtOHE) and alkaloids total fraction (Cs-TAF) obtained from aerial parts of C. sympodialis were evaluated in several models of acute gastric ulcers. The antisecretory and/or neutralizing mechanisms of the gastric acid secretion, cytoprotective, antioxidant and immunoregulatory mechanisms were also evaluated.ResultsCs-EtOHE and Cs-TAF presented a reduction in gastric mucosa lesions against ethanol, NSAIDs, hypothermic restraint-stress and gastric juice containment induced ulcer models. This activity is related to alkaloids present in the extract, and involves the participation of sulfhydryl compounds, nitric oxide, KATP channels, prostaglandins, decreased levels of IL-1β and TNF-α and increased levels of GSH and IL-10.ConclusionThe data indicate gastroprotective activity, due to the participation of the cytoprotective, antioxidant and immunoregulatory mechanisms.

Publication date: Available online 12 May 2018
Source:Acta Biomaterialia
Author(s): Xiang-long Tang, Jun Wu, Ben-lan Lin, Sheng Cui, Hong-mei Liu, Ru-tong Yu, Xiao-dong Shen, Ting-wei Wang, Wei Xia
Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg–Gly–Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T1-weighted magnetic resonance imaging (T1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T1-weighted MRI diagnosis and PDT of glioma for antitumor therapy.Statement of SignificanceA near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (R/G) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated red-emitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T1-weighted magnetic resonance imaging agent for tumor diagnosis.