Inhibition of TNF-α, and NF-κB and JNK pathways accounts for the prophylactic action of the natural phenolic,allylpyrocatechol against indomethacin gastropathy

Background

The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically.

Methods

Mice were pre-treated with APC for 1 h followed by IND (18 mg kg^− 1) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration.

Results

IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5 mg kg^− 1), trolox (50 mg kg^− 1) and NAC (250 mg kg^− 1) showed similar protection that was better than that by misoprostol (5 μg kg^− 1) and omeprazole (3 mg kg^− 1).

Conclusions

The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis.

General significance

Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent.     

Identification of a Region in the Stalk Domain of the Nipah Virus Receptor Binding Protein That Is Critical for Fusion Activation

Paramyxoviruses, including the emerging lethal human Nipah virus (NiV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral and target cell membranes. For paramyxoviruses, membrane fusion is the result of the concerted action of two viral envelope glycoproteins: a receptor binding protein and a fusion protein (F). The NiV receptor binding protein (G) attaches to ephrin B2 or B3 on host cells, whereas the corresponding hemagglutinin-neuraminidase (HN) attachment protein of NDV interacts with sialic acid moieties on target cells through two regions of its globular domain. Receptor-bound G or HN via its stalk domain triggers F to undergo the conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We show that chimeric proteins containing the NDV HN receptor binding regions and the NiV G stalk domain require a specific sequence at the connection between the head and the stalk to activate NiV F for fusion. Our findings are consistent with a general mechanism of paramyxovirus fusion activation in which the stalk domain of the receptor binding protein is responsible for F activation and a specific connecting region between the receptor binding globular head and the fusion-activating stalk domain is required for transmitting the fusion signal.     

In vitro screening of some plant extracts against fungal pathogens of mulberry ( Morus spp.)

Twenty one plant species were screened in vitro for their fungitoxic properties against four fungal pathogens viz., Phyllactinia corylea (Powdery mildew), Peridiopsora mori (Brown rust) and Pseudocercospora mori (Black leaf spot) by slide germination method and Myrothecium roridum (Brown leaf spot) by poisoned food technique. Conidial germination of P. corylea was significantly reduced in 5% (w/v) ethanolic extracts all tested plant. Extract of Cassia tora and Cassia sophera completely inhibited conidial germination of P. corylea. Other effective plant extracts inhibited >?90% germination were Allium sativum (99.56%), Ocimum sanctum (97.80%), Moringa oleifera (97.32%). Conidial germination of Pseudocercospora mori was completely inhibited in extract of A. sativum and D. metel. More than 90% inhibition was observed with extract of Holarrhena antidysentrica (93.10%), Adhatoda Zeylanica (91.40%) and Calotropis gigentia (90.40%). Urediniospore germination of Peridiopsora mori was significantly reduced in 19 plant extracts. Extract of A. sativum and D. metel completely inhibited urediniospore germination P. mori. Other effective plant extracts, which inhibited >?90% germination were Calotropis gigentia (99.40%), Targets patula (98.96%), Azadirachta indica (98.85%), Mirabilis jalapa (95.50%) and Chromoleana odorata (90.51%). Maximum inhibition (33.33%) of colony growth of M. roridum was observed with amendment of 5% solvent extracts of D. metel followed by A. sativum (25%), Chromoleana odorata (20%) and Eucalyptus citriodora (16.66%).     

A Simple One Pot Purification of Bacterial Amylase From Fermented Broth Based on Affinity Toward Starch-Functionalized Magnetic Nanoparticle

Surface-functionalized adsorbant particles in combination with magnetic separation techniques have received considerable attention in recent years. Selective manipulation on such magnetic nanoparticles permits separation with high affinity in the presence of other suspended solids. Amylase is used extensively in food and allied industries. Purification of amylase from bacterial sources is a matter of concern because most of the industrial need for amylase is met by microbial sources. Here we report a simple, cost-effective, one-pot purification technique for bacterial amylase directly from fermented broth of Bacillus megaterium utilizing starch-coated superparamagnetic iron oxide nanoparticles (SPION). SPION was prepared by co-precipitation method and then functionalized by starch coating. The synthesized nanoparticles were characterized by transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID, zeta potential, and ultraviolet–visible (UV-vis) and Fourier-transform infrared (FTIR) spectroscopy. The starch-coated nanoparticles efficiently purified amylase from bacterial fermented broth with 93.22% recovery and 12.57-fold purification. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the molecular mass of the purified amylase was 67 kD, and native gel showed the retention of amylase activity even after purification. Optimum pH and temperature of the purified amylase were 7 and 50°C, respectively, and it was stable over a range of 20°C to 50°C. Hence, an improved one-pot bacterial amylase purification method was developed using starch-coated SPION.     

Bioethics and Its Gatekeepers: Does Institutional Racism Exist in Leading Bioethics Journals?

Who are the gatekeepers in bioethics? Does editorial bias or institutional racism exist in leading bioethics journals? We analyzed the composition of the editorial boards of 14 leading bioethics journals by country. Categorizing these countries according to their Human Development Index (HDI), we discovered that approximately 95 percent of editorial board members are based in (very) high-HDI countries, less than 4 percent are from medium-HDI countries, and fewer than 1.5 percent are from low-HDI countries. Eight out of 14 leading bioethics journals have no editorial board members from a medium- or low-HDI country. Eleven bioethics journals have no board members from low-HDI countries. This severe underrepresentation of bioethics scholars from developing countries on editorial boards suggests that bioethics may be affected by institutional racism, raising significant questions about the ethics of bioethics in a global context.     

Synthesis and anticancer activity of certain mononuclear Ru (II) Complexes

Bis(1,10-phenanthroline/2,2′-bipyridine) ruthenium(II)complexes containing TCP, TTZ OPBI, and BTSC ligands (where, TCP = 1-thiocarbamoyl-3,5-diphenyl-2-pyrazoline,TTZ = 2-(3,5-diphenyl-4,5-dihydropyrazol-1-yl)-4-phenylthiazole, OPBI = 2-hydroxyphenyl benzimidazole and BTSC = benzoin thiosemicarbazone) have been prepared and characterized. The spectral data suggested that the ligands were coordinated with the metal through nitrogen, sulfur and oxygen atoms. The target complexes were tested in vivo for anticancer activity against transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC). All these complexes increased the life span of the EAC-bearing mice, decreased their tumor volume and viable ascitic cell count as well as improved Hb, RBC and WBC counts. These results suggest that the Ru(II) complexes exhibit significant antitumor activity in EAC-bearing mice. It was also observed that the ruthenium complexes protected red blood cells from 2,2′-azo-bis(2-methylpropionamidine) dihydrochloride (AAPH)- induced hemolysis. The inhibitory effect was dose-dependent at a concentration of 20–120 μg/ml.