Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment

Cancer is a complex disease orchestrated by various extrinsic and intrinsic pathways. In recent years, there has been a keen interest towards the development of natural extracts-based cancer therapeutics with minimum adverse effects. In pursuit of effective strategy, a wide variety of natural products-derived compounds have been addressed for their anticancer effects. Apigenin is a naturally-occurring flavonoid present abundantly in various fruits and vegetables. Decades of research have delineated the pharmacological and biological properties of apigenin. Specifically, the apigenin-mediated anticancer activities have been documented in various types of cancer, but the generalized scientific evidence encompassing various molecular interactions and processes, such as regulation of the apoptotic machinery, aberrant cell signaling and oncogenic protein network have not been comprehensively covered. In this sense, in this review we have attempted to focus on the apigenin-mediated regulation of oncogenic pathways in various cancers. We have also addressed the cutting-edge research which has unveiled the remarkable abilities of apigenin to interact with microRNAs to modulate key cellular processes, with special emphasis on the nano-formulations of apigenin that can help their targeted delivery and can be a therapeutic solution for the treatment of various cancers.N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Nanotechnology-Based Strategies for Berberine Delivery System in Cancer Treatment: Pulling Strings to Keep Berberine in Power

Cancer is a multifactorial disease characterized by complex molecular landscape and altered cell pathways that results in an abnormal cell growth. Natural compounds are target-specific and pose a limited cytotoxicity; therefore, can aid in the development of new therapeutic interventions for the treatment of this versatile disease. Berberine is a member of the protoberberine alkaloids family, mainly present in the root, stem, and bark of various trees, and has a reputed anticancer activity. Nonetheless, the limited bioavailability and low absorption rate are the two major hindrances following berberine administration as only 0.5% of ingested berberine absorbed in small intestine while this percentage is further decreased to 0.35%, when enter in systemic circulation. Nano-based formulation is believed to be an ideal candidate to increase absorption percentage as at nano scale level, compounds can absorb rapidly in gut. Nanotechnology-based therapeutic approaches have been implemented to overcome such problems, ultimately promoting a higher efficacy in the treatment of a plethora of diseases. This review present and critically discusses the anti-proliferative role of berberine and the nanotechnology-based therapeutic strategies used for the nano-scale delivery of berberine. Finally, the current approaches and promising perspectives of latest delivery of this alkaloid are also critically analyzed and discussed.NC-M acknowledges the Portuguese Foundation for Science and Technology under Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

CryoEM and stability analysis of virus-like particles of potyvirus and ipomovirus infecting a common host

Sweet potato feathery mottle virus (SPFMV) and Sweet potato mild mottle virus (SPMMV) are members of the genera Potyvirus and Ipomovirus, family Potyviridae, sharing Ipomoea batatas as common host, but transmitted, respectively, by aphids and whiteflies. Virions of family members consist of flexuous rods with multiple copies of a single coat protein (CP) surrounding the RNA genome. Here we report the generation of virus-like particles (VLPs) by transient expression of the CPs of SPFMV and SPMMV in the presence of a replicating RNA in Nicotiana benthamiana. Analysis of the purified VLPs by cryo-electron microscopy, gave structures with resolutions of 2.6 and 3.0 Å, respectively, showing a similar left-handed helical arrangement of 8.8 CP subunits per turn with the C-terminus at the inner surface and a binding pocket for the encapsidated ssRNA. Despite their similar architecture, thermal stability studies reveal that SPMMV VLPs are more stable than those of SPFMV

Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender

<p>Abstract</p> <p>Background</p> <p>The association between periodontal conditions, oral yeast colonisation and salivary proteins in subjects with type 2 diabetes (T2D) is not yet documented. The present study aimed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender.</p> <p>Methods</p> <p>Fifty-eight type 2 diabetic subjects (23 males and 35 females) with random blood glucose level ≥ 11.1 mmol/L were investigated. Periodontal conditions (plaque index [PI], bleeding on probing [BOP], probing pocket depth [PD] (4 to 6 mm and ≥ 6 mm), oral yeasts, salivary immunoglobulin (Ig) A, IgG and total protein concentrations, and number of present teeth were determined.</p> <p>Results</p> <p>Periodontal conditions (PI [<it>p </it>< 0.00001], BOP [<it>p </it>< 0.01] and PD of 4 to 6 mm [<it>p </it>< 0.001], salivary IgG (μg)/mg protein (<it>p </it>< 0.001) and salivary total protein concentrations (<it>p </it>< 0.05) were higher in type 2 diabetic females with <it>Candida albicans </it>(<it>C. albicans</it>) colonisation compared to males in the same group. Type 2 diabetic females with <it>C. albicans </it>colonisation had more teeth compared to males in the same group (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>Clinical and salivary parameters of periodontal inflammation (BOP and IgG (μg)/mg protein) were higher in type 2 diabetic females with oral <it>C. albicans </it>colonisation compared to males in the same group. Further studies are warranted to evaluate the association of gender with these variables in subjects with T2D.</p

Role of rapid urease test and histopathology in the diagnosis of Helicobacter pylori infection in a developing country

BACKGROUND: The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection. METHODS: One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard test for the diagnosis of H. pylori infection was histopathology. RESULTS: Sixty-one percent (66/109) patients were males with mean age of 43 ± 14.1 years and age range 17–80 years. Fifty-two percent (57/109) were not on any medications while 48% (52/109) used PPI before presentation to the outpatients. Pronto Dry was positive in 40% (44/109) and negative in 60% (65/109). Histopathology was positive for H. pylori in 57% (62/109) and negative in 43% (47/109). The sensitivity, specificity, PPV, NPV and like-hood ratio of a positive and negative Pronto Dry test with and without PPI were 43.3%, 86.4%, 81.3%, 3.18, 0.656 and 52.8% vs 71.9%, 80%, 82.1%, 69%, 3.59 and 0.35. CONCLUSION: This study shows that the sensitivity, specificity, NPV and PPV of rapid urease test was reduced in patients who are on PPI. The exclusive use of the rapid urease test for the diagnosis of Helicobacter pylori cannot be recommended in patients with prior PPI use

Awareness and attitudes amongst basic surgical trainees regarding radiation in orthopaedic trauma surgery

This study investigated the awareness and attitudes of basic surgical trainees. Trainees were asked to answer questions from a pre-set questionnaire. Fifty basic surgical trainees from England and Wales were involved in the study. The areas covered were basic knowledge of radiation hazards, use of protective wear, pregnancy test in female trauma victims of reproductive age, and principles of safe radiation. All the questions were asked in the context of orthopaedic trauma surgery. All questions were evidence based

Influence of Stefan blowing on nanofluid flow submerged in microorganisms with leading edge accretion or ablation

The unsteady forced convective boundary layer flow of viscous incompressible fluid containing both nanoparticles and gyrotactic microorganisms, from a flat surface with leading edge accretion (or ablation), is investigated theoretically. Utilizing appropriate similarity transformations for the velocity, temperature, nanoparticle volume fraction and motile microorganism density, the governing conservation equations are rendered into a system of coupled, nonlinear, similarity ordinary differential equations. These equations, subjected to imposed boundary conditions, are solved numerically using the Runge-Kutta-Fehlberg fourth-fifth order numerical method in the MAPLE symbolic software. Good agreement between our computations and previous solutions is achieved. The effect of selected parameters on flow velocity, temperature, nano-particle volume fraction (concentration) and motile microorganism density function is investigated. Furthermore, tabular solutions are included for skin friction, wall heat transfer rate, nano-particle mass transfer rate and microorganism transfer rate. Applications of the study arise in advanced micro-flow devices to assess nanoparticle toxicity

Lysosomotropic agents as HCV entry inhibitors

HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH4Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV

Age-dependent alteration of TGF-β signalling in osteoarthritis

Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling might trigger the differentiation of articular chondrocytes with an autolytic phenotype

Numerical study of chemical reaction effects in magnetohydrodynamic Oldroyd B oblique stagnation flow with a non-Fourier heat flux model

Reactive magnetohydrodynamic (MHD) flows arise in many areas of nuclear reactor transport. Working fluids in such systems may be either Newtonian or non-Newtonian. Motivated by these applications, in the current study, a mathematical model is developed for electrically-conducting viscoelastic oblique flow impinging on stretching wall under transverse magnetic field. A non-Fourier Cattaneo-Christov model is employed to simulate thermal relaxation effects which cannot be simulated with the classical Fourier heat conduction approach. The Oldroyd-B non-Newtonian model is employed which allows relaxation and retardation effects to be included. A convective boundary condition is imposed at the wall invoking Biot number effects. The fluid is assumed to be chemically reactive and both homogeneous-heterogeneous reactions are studied. The conservation equations for mass, momentum, energy and species (concentration) are altered with applicable similarity variables and the emerging strongly coupled, nonlinear non-dimensional boundary value problem is solved with robust well-tested Runge-Kutta-Fehlberg numerical quadrature and a shooting technique with tolerance level of 10−4. Validation with the Adomian decomposition method (ADM) is included. The influence of selected thermal (Biot number, Prandtl number), viscoelastic hydrodynamic (Deborah relaxation number), Schmidt number, magnetic parameter and chemical reaction parameters, on velocity, temperature and concentration distributions are plotted for fixed values of geometric (stretching rate, obliqueness) and thermal relaxation parameter. Wall heat transfer rate (local heat flux) and wall species transfer rate (local mass flux) are also computed and it is observed that local mass flux increases with strength of heterogeneous reactions whereas it decreases with strength of homogeneous reactions. The results provide interesting insights into certain nuclear reactor transport phenomena and furthermore a benchmark for more general CFD simulations