Effect of β-Caryophyllene on insulin resistance in skeletal muscle of high fat diet and fructose-induced type-2 diabetic rats

High fat diet feeding results in hyperglycemia and insulin resistance, which is a major pathological feature of type-2 diabetes mellitus. The use of oral hypoglycaemic drugs is limited due to its deleterious side effects and there is a need to find more efficacious agents for diabetes management. Hence, it is of interest to show the mechanism of action of β-Caryophyllene on insulin signalling molecules in gastrocnemius muscle of high fat diet - induced type-2 diabetic rats. An oral effective dose of with β-Caryophyllene (200 mg/kg b.wt) was given for 30 days to high fat diet (comprising 2% cholesterol, 1% cholic acid, 30% coconut oil, 67% conventional rat feed) and fructose fed type-2 diabetic rats to find out whether β-Caryophyllene regulates IRS-1/Akt pathway of insulin signalling. The data shows that, β-Caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) in diabetic rats whereas there is no significant difference in mRNA expression of insulin receptor-substrate-1 (IRS-1) was observed among groups. The Akt mRNAand GLUT-4mRNA and protein level were also improved in gastrocnemius muscle of type-2 diabetic rats. Thus, we concluded that β-Caryophyllene could be used as potential phyto medicine for type-2 diabetes management.     

A CENH3 mutation promotes meiotic exit and restores fertility in SMG7-deficient Arabidopsis

Meiosis in angiosperm plants is followed by mitotic divisions to form multicellular haploid gametophytes. Termination of meiosis and transition to gametophytic development is, in Arabidopsis, governed by a dedicated mechanism that involves SMG7 and TDM1 proteins. Mutants carrying the smg7-6 allele are semi-fertile due to reduced pollen production. We found that instead of forming tetrads, smg7-6 pollen mother cells undergo multiple rounds of chromosome condensation and spindle assembly at the end of meiosis, resembling aberrant attempts to undergo additional meiotic divisions. A suppressor screen uncovered a mutation in centromeric histone H3 (CENH3) that increased fertility and promoted meiotic exit in smg7-6 plants. The mutation led to inefficient splicing of the CENH3 mRNA and a substantial decrease of CENH3, resulting in smaller centromeres. The reduced level of CENH3 delayed formation of the mitotic spindle but did not have an apparent effect on plant growth and development. We suggest that impaired spindle re-assembly at the end of meiosis limits aberrant divisions in smg7-6 plants and promotes formation of tetrads and viable pollen. Furthermore, the mutant with reduced level of CENH3 was very inefficient haploid inducer indicating that differences in centromere size is not the key determinant of centromere-mediated genome elimination.     

A novel acid-producing fungus isolated from bauxite residue: the potential to reduce the alkalinity

Abstract

Globally, bauxite residue is creating extensive environmental problems. Nevertheless, there are numerous functional microorganisms that exist in this extreme environment, and fungus has an essential role in the pedogenesis of bauxite residue. This study describes a microbial method to reduce the alkalinity of bauxite residue through the actions of a functional fungus to produce acidic substances. Bauxite residue samples were screened for fungal activity, and fungal tolerance was assessed using saline and alkaline media of varying concentrations, using aniline blue-PDA medium to evaluate acid production. A tolerant fungus with the ability to produce acidic substances was selected and named EEEL01 (Environmental Ecological Engineering Laboratory No. 01). Further morphological and molecular characterization identified this fungus as Penicillium oxalicum. Factors including pH, NaCl concentration, carbon and nitrogen sources were used to test the efficiency of acid production by the fungus. Based on optimal growth conditions, bauxite residue inoculated with EEEL01 reduced pH from 10.26 to 6.48 over 11?days. These results suggest that EEEL01 could effectively grow and release organic acids under extreme alkaline and saline conditions, which provide the potential for remediation.     

Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer

The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.     

Structural studies on the enzyme complex isopropylmalate isomerase (LeuCD) from Mycobacterium tuberculosis

The absence of the leucine biosynthesis pathway in humans makes the enzymes of this pathway in pathogenic bacteria such as Mycobacterium tuberculosis potential candidates for developing novel antibacterial drugs. One of these enzymes is isopropylmalate isomerase (IPMI). IPMI exists as a complex of two subunits: the large (LeuC) and the small (LeuD) subunit. The functional LeuCD complex catalyzes the stereospecific conversion reaction of α‐isopropylmalate to β‐isopropylmalate. Three C‐terminally truncated variants of LeuD have been analyzed by X‐ray crystallography to resolutions of 2.0 Å (LeuD_1–156), 1.2 Å (LeuD_1–168), and 2.5 Å (LeuD_1–186), respectively. The two most flexible parts of the structure are the regions of residues 30–37, the substrate discriminating loop, and of residues 70–74, the substrate binding loop. The three determined structures were also compared with the structures of other bacterial LeuDs. This comparison suggests the presence of two LeuD subfamilies. A model for the structure of the inactive enzyme complex has been obtained from solution X‐ray scattering experiments. The crystal structure of LeuD was shown to be compatible with the solution X‐ray scattering data from the small subunit. In contrast, the solution scattering results suggest that the large subunit LeuC and the LeuCD complex have overall shapes, which are radically different from the ones observed in the crystals of the functional homolog mitochondrial aconitase. Proteins 2010. © 2010 Wiley‐Liss, Inc.