Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.     

Structure-based prediction of protein–protein interactions between GhWlim5 Domain1 and GhACTIN-1 proteins: a practical evidence with improved fibre strength

Cotton fibre quality is a multigenic trait. Genetic modification of different genes to achieve high quality fibre is difficult without knowing the mechanism lying behind genes interaction. Based on background knowledge an attempt to explore the potential structural interactions between Gossypium hirsutum Wlim5 domain1 and Gossypium hirsutum ACTIN-1 proteins was done in current study. Sequence features of the LIM domain1 of GhWlim5 protein were identified through multiple sequence alignment analysis, and a phylogenetic tree was built to identify evolutionary relationships between sequences. Conservation indicated the evolutionary importance of side chain residues and the presence of several aliphatic and/or bulky residues, which stabilize the protein core and facilitate packing of zinc fingers. The structures of GhWlim5 domain1 and GhACTIN-1 proteins were modelled and validated through computational methods. Validation of GhACTIN-1 and GhWlim5 domain1 structures indicated good structural quality with 99.7% and 100% of the favoured number of residues in allowed regions and Z-score, within the ranges of − 9.87 and − 4.17, respectively. Docking analysis indicated various possible modes of interaction between these two proteins with favourable binding affinities. Based on our strong binding interaction results between GhWlim5 domain1 and GhACTIN-1 proteins, we further investigated the role of over-expression of GhWlim5 by transformation in cotton plants under fibre specific promoter and transgenic plants displayed significant increases in fibre strength.

     

In-vitro and In-vivo management of Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler in cotton using organic’s

Root-knot nematodes Meloidogyne incognita (Kofoid and White) Chitwood and Rhizoctonia bataticola (Taub.) Butler, fungus, are very dangerous root damaging pathogens. Present study was planned to establish a chemical control of these root deteriorating pathogens under lab conditions as well as in field. Maximum death rate of nematode juveniles and minimum numbers of nematode eggs hatched were recorded in plates treated with Cadusafos (Rugby® 100G) @12 g/100 ml and Cartap® (4% G) @9g/100 ml. Chemical treatment of Rhizoctonia bataticola with Trifloxystrobin + Tebuconazole (Nativo®) @0.2 g/100 ml and Mancozeb + Matalaxyl (Axiom) @0.25 g/100 ml significantly controlled the mycelial growth in plates. The best treatments tested in laboratory were applied in field as protective and curative treatments. Results proved that chemical control of root-knot nematode and root rot fungi by tested chemicals at recommended time and dose is a significant management technique under field conditions.     

Correction for Irrelevant Absorption in Multicomponent Spectrophotometric Assay of Riboflavin, Formylmethylflavin, and Degradation Products: Kinetic Applications

In the spectrophotometric assay of multicomponent systems involved in drug degradation studies, some minor or unknown degradation products may be present. These products may interfere in the assay and thus invalidate the results due to their absorption in the range of analytical wavelengths. This interference may be eliminated by the application of an appropriate correction procedure to obtain reliable data for kinetic treatment. The present study is based on the application of linear and non-linear irrelevant absorption corrections in the multicomponent spectrophotometric assay of riboflavin and formylmethylflavin during the photolysis and hydrolysis studies. The correction procedures take into account the interference caused by minor or unknown products and have shown considerable improvement in the assay data in terms of the molar balance. The treatment of the corrected data has led to more accurate kinetic results in degradation studies.     

Interaction between Meloidogyne incognita and Pochonia chlamydosporia and their effects on the growth of Phaseolus vulgaris

An experiment was conducted to test the effect of different doses of 2, 4 and 8?g/2?kg of soil of Pochonia chlamydosporia against the root-knot nematode (Meloidogyne incognita) on Phaseolus vulgaris. It was observed that inoculation of plant with the nematode alone, and 15?days prior to fungal inoculation, reduced the plant growth when compared with the plant with fungal application followed by the nematode. Plant length, fresh and dry weight, chlorophyll, carotenoid, protein contents and nitrate reductase activity decreased in nematode-infested plants. Application of higher dose of 8?g/2?kg of soil of P. chlamydosporia increased all the plant growth parameters as well as biochemical parameters. Highest number of galls per root system was recorded on the plants infested with nematode but not treated with the fungus. However, application of fungus prior to nematode inoculation improved the plant growth and reduced the number of galls and the number of egg masses per root system.     

Targeted nitric oxide delivery preferentially induces glioma cell chemosensitivity via altered p53 and O6‐Methylguanine‐DNA Methyltransferase activity

Glioblastoma multiforme is the most common malignant central nervous system tumor, and also among the most difficult to treat due to a lack of response to chemotherapeutics. New methods of countering the mechanisms that confer chemoresistance to malignant gliomas could lead to significant advances in the quest to identify novel drug combinations or targeted drug delivery systems for cancer therapy. In this study, we investigate the use of a targeted nitric oxide (NO) donor as a pretreatment to sensitize glioma cells to chemotherapy. The protein chlorotoxin (CTX) has been shown to preferentially target glioma cells, and we have developed CTX–NO, a glioma‐specific, NO‐donating CTX derivative. Pretreatment of cells with CTX–NO followed by 48‐h exposure to either carmustine (BCNU) or temozolomide (TMZ), both common chemotherapeutics used in glioma treatment, resulted in increased efficacy of both therapeutics. After CTX–NO exposure, both T98G and U‐87MG human malignant glioma cells show increased sensitivity to BCNU and TMZ. Further investigation revealed that the consequences of this combination therapy was a reduction in active levels of the cytoprotective enzyme MGMT and altered p53 activity, both of which are essential in DNA repair and tumor cell resistance to chemotherapy. The combination of CTX–NO and chemotherapeutics also led to decreased cell invasion. These studies indicate that this targeted NO donor could be an invaluable tool in the development of novel approaches to treat cancer. Biotechnol. Bioeng. 2013; 110: 1211–1220. © 2012 Wiley Periodicals, Inc.     

Supplementation with α-Lipoic Acid,CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice

Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10) on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group) and divided into trained (8 wks treadmill running) (n = 12/group) and untrained groups (n = 24/group). Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05). Furthermore, antioxidant-supplemented females (untrained) showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris) (p ≤ 0.05), reduced oxidative damage to muscle proteins (p ≤ 0.05), and increased expression of mitochondrial proteins (p ≤ 0.05) compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α) (p ≤ 0.05) via activation of AMP-activated protein kinase (AMPK) (p ≤ 0.05) by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations.     

Cell-cell interactions in regulating lung function

Tight junction barrier formation and gap junctional communication are two functions directly attributable to cell-cell contact sites. Epithelial and endothelial tight junctions are critical elements of the permeability barrier required to maintain discrete compartments in the lung. On the other hand, gap junctions enable a tissue to act as a cohesive unit by permitting metabolic coupling and enabling the direct transmission of small cytosolic signaling molecules from one cell to another. These components do not act in isolation since other junctional elements, such as adherens junctions, help regulate barrier function and gap junctional communication. Some fundamental elements related to regulation of pulmonary barrier function and gap junctional communication were presented in a Featured Topic session at the 2004 Experimental Biology Conference in Washington, DC, and are reviewed in this summary.     

Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity

While statins, hydroxymethylglutaryl-coenzyme A reductase (HMGCR) inhibitors, are clinically proven to reduce plasma cholesterol levels, a wide variation in inter-individual response to statin therapy has been observed. Pharmacogenetic studies have identified multiple loci that potentially contribute towards the statin response, including the HMGCR gene. To examine, if a statin-resistant, catalytically-active isoform of the human HMGCR could be generated, we have rationally altered the protein to include additional residues in the flap domain, which has a role in statin binding. Comparative enzyme assays with purified wild-type and mutant isoforms reveal the alteration imposes a slight (38%) decrease in the K(app)(M) for the substrate, a near 2-fold increase in turnover number, and a 480% increase in the Ki for lovastatin. Thus, alterations in HMGCR could contribute towards the synergistic effects of multiple loci in the statin response.