Vulpinic acid as a natural compound inhibits the proliferation of metastatic prostate cancer cells by inducing apoptosis

Molecular Biology Reports - Lichen secondary metabolites have drawn considerable attention in recent years due to the limitations of current treatment options. Vulpinic acid (VA) obtained from...     

Effect of peripherally-injected glucagon-like peptide-1 on gastric mucosal blood flow

The aim of this study was to investigate the mechanisms involved in the effect of glucagon-like peptide-1 (GLP-1) on the decrease in gastric mucosal blood flow (GMBF) induced by intragastric ethanol.After preparation of the stomach for GMBF recording, a probe was placed to the gastric mucosa and basal GMBF recordings were obtained by a laser Doppler flowmeter after a 30-minute stabilization period. Following GLP-1 (1000 ng/kg; i.p.) injection, 1 ml of absolute ethanol was applied to the gastric chamber and GMBF was recorded continuously during a 30-minute period. GLP-1 (1000 ng/kg; i.p.) prevented the decrease in GMBF induced by ethanol. Nitric oxide (NO) synthase inhibitor L-NAME, (30 mg/kg; s.c.), calcitonine gene-related peptide (CGRP) receptor antagonist CGRP-(8–37) (10μg/kg; i.p.), and cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.) all inhibited the GMBF-improving effect of GLP-1.We concluded that, NO, CGRP and prostaglandins may be involved in the effect of peripherally-injected GLP-1 on GMBF reduction induced by intraluminal ethanol.     

Particle simulation on the Cell BE architecture

This paper presents two parallel formulations for the Barnes-Hut algorithm on the Cell architecture, which differ in tree distribution and construction phases of the algorithm. In the initial parallelization, the domains are dynamically partitioned and assigned to the synergistic processing elements (SPEs), and SPEs construct local trees of the sub-domains in parallel. The enhanced parallelization scheme provides better clustering of the particles by sequentially constructing the global tree of the entire work space in the power processing element (PPE) and by partitioning the tree into sub-trees that can fit in the Local Store. SPEs operate on the sub-tree data and construct local trees in parallel. Our experimental evaluation indicates that this application performs much faster on the Cell BE compared to the Intel Xeon based system. Specifically, our first and second methods on the Cell BE outperform Intel Xeon by a factor of 5.8 and 7.1 for 8192 particles, respectively.     

Induction of liver fibrosis by CCl4 mediates pathological alterations in the spleen and lymph nodes: The potential therapeutic role of propolis

In an animal models, carbon tetrachloride (CCl₄) is a carcinogenic agent that causes liver fibrosis. The current study aims to investigate whether induction in liver-fibrosis by CCl₄ in the mouse model could promote the initiation of fibrosis in lymph node and spleen due to sustained increase of inflammatory signals and also aimed to clarify the protective therapeutic effects of propolis. The male mice (BALB/c) were categorized into three experimental sets and each group involved 15 mice. Control group falls into first group; group-II and group-III were injected with CCl₄ to induce liver-fibrosis and oral supplementation with propolis was provided in group-III for 4-weeks. A major improvement with hepatic collagen and α-smooth muscle actin (α-SMA) production was aligned with the activation of liver fibrosis from CCl₄. Mice treated with CCl₄ exhibited collagen deposition towards liver sections, pathological alterations in spleen and lymph node architectures, and a significantly increase the circulation of both T&B cells in secondary lymphoid organs. Mechanically, the secondary lymphoid organs treated with CCl₄ in mice exposed a positive growth in α-SMA and collagen expression, increased in proinflammatory cytokine levels and a significant increase in TGF-β, NO and ROS levels. A manifest intensification in the expression of Nrf2, COX-2, and eNOS and upregulation of ASK1 and P38 phosphorylation. Interestingly, addition of propolis-treated CCl₄ mice, substantially suppressed deposition of liver collagen, repealed inflammatory signals and resorted CCl₄-mediated alterations in signaling cascades, thereby repairing the architectures of the secondary lymphoid organs. Our findings revealed benefits of propolis against fibrotic complications and enhancing secondary lymphoid organ architecture.     

Synthesis of Imidazole-2,3-dihydrothiazole Compounds as VEGFR-2 Inhibitors and Their Support with in Silico Studies

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1′-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole ( 4h ) was chosen as the most active derivative in the series. According to the MTT results, compounds 4h and 4k showed activity with IC₅₀=4.566±0.246 μM and IC₅₀=4.537±0.463 μM, respectively. Unlike other derivatives, compound 4h carries a phenyl ring in the 4th position of the phenyl ring. This bulky group allowed the compound to settle in the enzyme active site. Dynamic studies show that the stability of the compound does not change over 40 ns. RMSD, RMSF and Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding of the enzyme active site with the important amino acids Cys919, Glu885 and Asp1046 proves the inhibitory potential of compound 4h on the VEGFR-2 enzyme. It is thought that more active compounds will be reached with the derivatives to be synthesized starting from compound 4h .     

Changes in zinc levels and superoxide dismutase activities in the skin of acute, ultraviolet-B-irradiated mice after treatment with ginkgo biloba extract

Acute ultraviolet-B (UV-B) irradiation is known to act as an initiator in the formation of reactive oxygen species. These oxygen products are highly reactive and they are able to cause irreversible damage to cellular components. Oxygen free radicals are normally neutralized by very efficient systems in the body. These include antioxidant enzymes like superoxide dismutase (SOD). In a healthy subject, there is a balance between free radicals and the levels of antioxidants. In some pathological conditions such as oxidative stress, the level of antioxidants is significantly reduced. The skin contains relatively high levels of zinc (Zn), an essential element known to be a cofactor in some metabolic pathways. Zinc has also been reported to have antioxidant properties. In the present study, we investigated the effect of ginkgo biloba extract (Gbe), a potent free-radical scavenger, on UV-B-irradiated skin by measuring SOD activity and Zn levels in the skin, before and after treatment. The SOD activity was decreased after UV-B exposure, in comparison with the control group (p<0.05). After Gbe treatment, the SOD activity increased (p<0.05) as compared with the untreated UV-B irradiated group. The Zn levels changed in the same pattern as the SOD activity values.     

The structure of Get4 reveals an α-solenoid fold adapted for multiple interactions in tail-anchored protein biogenesis

Tail-anchored proteins play important roles in protein translocation, membrane fusion and apoptosis. They are targeted to the endoplasmic reticulum membrane via the guided-entry of tail-anchored proteins (Get) pathway. We present the 2 Å crystal structure of Get4 which participates in early steps of the Get pathway. The structure shows an α-solenoid fold with particular deviations from the regular pairwise arrangement of α-helices. A conserved hydrophobic groove accommodates the flexible C-terminal region in trans. The structural organization of the Get4 helical hairpin motifs provides a scaffold for protein-protein interactions in the Get pathway.     

Histopathology Characteristics of two Different Benign Tumours in Capoeta capoeta

The aim of the present study was to determine the morphologic and histopathologic characteristics of tumors observed in samples from moribund Capoeta capoeta. For this purpose, ten fish, captured from the Fırat River located in southeastern Anatolia of Turkey, were examined for gross malformations and histopathological morphology. Externally, two different morphological types of tumours were detected in the anus region and on the ventral part of the operculum of one of the examined fish. In this study, tumours in a moribund fish were identified as benign because they were well differentiated, non-infiltrative and non-metastatic. In the histological examination, the external growth located in the ventral region of the operculum was characteristic of a papilloma showing exophytic inverted development. This is our first report on both melanomacrophage and green fibrils in the papilloma. The other observed pathological growth, covered with hemorrhagic skin and located near the anus, was characteristic of a benign tumour (subcutaneous lipoma) which constituted typical adipocytes. Thus, our study detected two different types of benign tumours in Capoeta capoeta, and it is the first time being reported in a cyprinid species