Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the Scene

Both diabetes and cancer are prevalent diseases whose incidence rates are increasing worldwide, especially in countries that are undergoing rapid industrialization changes. Apparently, lifestyle risk factors including diet, physical inactivity and obesity play pivotal, yet preventable, roles in the etiology of both diseases. Epidemiological studies provide strong evidence that subjects with diabetes are at significantly higher risk of developing many forms of cancer and especially solid tumors. In addition to pancreatic and breast cancer, the incidence of colorectal cancer and prostate cancer is increased in type 2 diabetes. While diabetes (type 2) and cancer share many risk factors, the biological links between the two diseases are poorly characterized. In this review, we highlight the mechanistic pathways that link diabetes to colorectal and prostate cancer and the use of Metformin, a diabetes drug, to prevent and/or treat colorectal and prostate cancer. We review the role of AMPK activation in autophagy, oxidative stress, inflammation, apoptosis, and cell cycle progression.This publication was made possible by grant #NPRP 5-409-3-112 from the Qatar National Research Fund (a member of Qatar Foundation)

Two Legendre-Dual-Petrov-Galerkin Algorithms for Solving the Integrated Forms of High Odd-Order Boundary Value Problems

Two numerical algorithms based on dual-Petrov-Galerkin method are developed for solving the integrated forms of high odd-order boundary value problems (BVPs) governed by homogeneous and nonhomogeneous boundary conditions. Two different choices of trial functions and test functions which satisfy the underlying boundary conditions of the differential equations and the dual boundary conditions are used for this purpose. These choices lead to linear systems with specially structured matrices that can be efficiently inverted, hence greatly reducing the cost. The various matrix systems resulting from these discretizations are carefully investigated, especially their complexities and their condition numbers. Numerical results are given to illustrate the efficiency of the proposed algorithms, and some comparisons with some other methods are made

Anti-hypertensive Herbs and their Mechanisms of Action: Part I

The use of herbal therapies for treatment and management of cardiovascular diseases (CVDs) is increasing. Plants contain a bounty of phytochemicals that have proven to be protective by reducing the risk of various ailments and diseases. Indeed, accumulating literature provides the scientific evidence and hence reason d'etre for the application of herbal therapy in relation to CVDs. Slowly, but absolutely, herbal remedies are being entrenched into evidence-based medical practice. This is partly due to the supporting clinical trials and epidemiological studies. The rationale for this expanding interest and use of plant based treatments being that a significant proportion of hypertensive patients do not respond to Modern therapeutic medication. Other elements to this equation are the cost of medication, side-effects, accessibility, and availability of drugs. Therefore, we believe it is pertinent to review the literature on the beneficial effects of herbs and their isolated compounds as medication for treatment of hypertension, a prevalent risk factor for CVDs. Our search utilized the PubMed and ScienceDirect databases, and the criterion for inclusion was based on the following keywords and phrases: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine (CAM), nitric oxide, vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B, oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with herb in question, and where possible with its constituent molecule(s). In this first of a two-part review, we provide a brief introduction of hypertension, followed by a discussion of the molecular and cellular mechanisms. We then present and discuss the plants that are most commonly used in the treatment and management of hypertension.NPRP# 4-571-3-171 from the Qatar National Research Fund (a member of Qatar Foundation)

The Molecular Hydrogen Deficit in Gamma-Ray Burst Afterglows

Recent analysis of five gamma-ray burst (GRB) afterglow spectra reveal the absence of molecular hydrogen absorption lines, a surprising result in light of their large neutral hydrogen column densities and the detection of H$_2$ in similar, more local star-forming regions like 30 Doradus in the Large Magellanic Cloud (LMC). Observational evidence further indicates that the bulk of the neutral hydrogen column in these sight lines lies 100 pc beyond the progenitor and that H$_2$ was absent prior to the burst, suggesting that direct flux from the star, FUV background fields, or both suppressed its formation. We present one-dimensional radiation hydrodynamical models of GRB host galaxy environments, including self-consistent radiative transfer of both ionizing and Lyman-Werner photons, nine-species primordial chemistry with dust formation of H$_2$, and dust extinction of UV photons. We find that a single GRB progenitor is sufficient to ionize neutral hydrogen to distances of 50 - 100 pc but that a galactic Lyman-Werner background is required to dissociate the molecular hydrogen in the ambient ISM. Intensities of 0.1 - 100 times the Galactic mean are necessary to destroy H$_2$ in the cloud, depending on its density and metallicity. The minimum radii at which neutral hydrogen will be found in afterglow spectra is insensitive to the mass of the progenitor or the initial mass function (IMF) of its cluster, if present.Comment: 12 pages, 7 figures, accepted for Ap

Triple-negative breast cancer: Current perspective on the evolving therapeutic landscape

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy

Jacobi rational-Gauss collocation method for Lane-Emden equations of astrophysical significance

In this paper, a new spectral collocation method is applied to solve Lane-Emden equations on a semi-infinite domain. The method allows us to overcome difficulty in both the nonlinearity and the singularity inherent in such problems. This Jacobi rational-Gauss method, based on Jacobi rational functions and Gauss quadrature integration, is implemented for the nonlinear Lane-Emden equation. Once we have developed the method, numerical results are provided to demonstrate the method. Physically interesting examples include Lane-Emden equations of both first and second kind. In the examples given, by selecting relatively few Jacobi rational-Gauss collocation points, we are able to get very accurate approximations, and we are thus able to demonstrate the utility of our approach over other analytical or numerical methods. In this way, the numerical examples provided demonstrate the accuracy, efficiency, and versatility of the method

Quality Evaluation of Feed Resources at the Newly Reclaimed Area in Egypt

The objective of this study was to examine the productivity of Egyptian clover (Trifolium alexandrinum L.) interseeded with ryegrass (Lolium multiflorum) and alfalfa (Medicaga sativa L.). These species were planted in newly reclaimed land in Ismailia, Egypt under two fertilization systems; organic (OF) or chemical (CF) during winter season of (1994-1995) using a split plot design. Feeding quality of forages was evaluated by conducting digestibility trials with rams and feeding trials with growing lambs where forage was offered ad. libitum with 1% of LBW concentrate. Productivity data indicated that organic fertilization yielded significantly more DM. Chemical analysis showed that DM content with (CF) was higher than with (OF) and it was found that alfalfa had higher CP content than that of E. Clover mixture. Digestibility of nutrients was higher with (CF) than with (OF) and it was found that CP was more digested in alfalfa than the Egyptian clover mixture. TDN values for both forages were determined by proximate analysis. Group of lambs fed chemically fertilized alfalfa attained significantly better weight gain which was attributed to high forage DM intake

7-O-methylpunctatin, a novel homoisoflavonoid, inhibits phenotypic switch of human arteriolar smooth muscle cells

Remodeling of arterioles is a pivotal event in the manifestation of many inflammation-based cardio-vasculopathologies, such as hypertension. During these remodeling events, vascular smooth muscle cells (VSMCs) switch from a contractile to a synthetic phenotype. The latter is characterized by increased proliferation, migration, and invasion. Compounds with anti-inflammatory actions have been successful in attenuating this phenotypic switch. While the vast majority of studies investigating phenotypic modulation were undertaken in VSMCs isolated from large vessels, little is known about the effect of such compounds on phenotypic switch in VSMCs of microvessels (microVSMCs). We have recently characterized a novel homoisoflavonoid that we called 7-O-methylpunctatin (MP). In this study, we show that MP decreased FBS-induced cell proliferation, migration, invasion, and adhesion. MP also attenuated adhesion of THP-1 monocytes to microVSMCs, abolished FBS-induced expression of MMP-2, MMP-9, and NF-?B, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22?, SM-?) and mid-term (calponin and caldesmon) differentiation markers and a decrease in osteopontin, a protein highly expressed in synthetic VSMCs. MP also reduced transcription of cyclin D1, CDK4 but increased protein levels of p21 and p27. Taken together, these results corroborate an anti-inflammatory action of MP on human microVSMCs. Therefore, by inhibiting the synthetic phenotype of microVSMCs, MP may be a promising modulator for inflammation-induced arteriolar pathophysiology. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the American University of Beirut (Grant # MPP 320133 to A.E.), University of Petra (Grant #: 5/4/2019) to A.B., E.B., and A.E., and the National Council for Scientific Research (CNRS) to M.F.Scopu

Fracture resistance and failure pattern of endodontically treated teeth restored with computer-aided design/ computer-aided manufacturing post and cores: A pilot study

Aim: To evaluate the fracture resistance and failure pattern of custom made computer-aided design & computer-aided manufacturing (CAD/CAM) post and cores using a fiber reinforced composite material (FRC) and a high-density-polymer. Materials and methods: Thirty extracted mandibular second premolars were selected, endodontically treated and prepared to receive the posts. The specimens were randomly divided into three groups (n = 10) according to each material: group 1 (RXP): fiber posts (Rely X, 3M-ESPE) with composite core build-up (Filtek Bulk Fill Posterior, 3M-ESPE) as a control group; group 2 (BLC): one-piece milled post and core from fiber reinforced composite blocks (Trilor, Bioloren); and group 3 (AMC): one-piece milled post and core from hybrid ceramic disks (Ambarino, Creamed). All the posts were cemented using a self-adhesive resin cement (Rely X U200, 3M ESPE). Fracture resistance was tested using a universal testing machine, failure patterns were then observed visually and radiographically then evaluated under SEM. Data was analyzed using One-way analysis of variance (ANOVA) followed by Tamhane post-hoc test in order to determine significant differences among groups (α = 0.05). Results: The mean fracture resistance values were: 426.08 ± 128.26 N for group 1 (R X P), 367.06 ± 72.34N for group 2 (BLC), and 620.02 ± 5 4.29N f or g roup 3 ( AMC). S tatistical analysis revealed that group 3 (AMC) had the highest mean load to fracture in comparison to the other groups (p = 0.000). failures were cohesive in group 2 and 3 and mixed in group 1 with no catastrophic failures reported in all groups. Conclusion: All systems evaluated presented sufficient mean load-to-failure values for endodontically treated teeth restorations. CAD/CAM post and cores made from high-densitypolymer showed a better performance than prefabricated fiber posts