Ameliorative Effect of Ocimum forskolei Benth on Diabetic,Apoptotic, and Adipogenic Biomarkers of Diabetic Rats and 3T3-L1 Fibroblasts Assisted by In Silico Approach

Diabetes mellitus (DM) is a complicated condition that is accompanied by a plethora of metabolic symptoms, including disturbed serum glucose and lipid profiles. Several herbs are reputed as traditional medicine to improve DM. The current study was designed to explore the chemical composition and possible ameliorative effects of Ocimum forskolei on blood glucose and lipid profile in high-fat diet/streptozotocin-induced diabetic rats and in 3T3-L1 cell lines as a first report of its bioactivity. Histopathological study of pancreatic and adipose tissues was performed in control and treatment groups, along with quantification of glucose and lipid profiles and the assessment of NF-κB, cleaved caspase-3, BAX, and BCL2 markers in rat pancreatic tissue. Glucose uptake, adipogenic markers, DGAT1, CEBP/α, and PPARγ levels were evaluated in the 3T3-L1 cell line. Hesperidin was isolated from total methanol extract (TME). TME and hesperidin significantly controlled the glucose and lipid profile in DM rats. Glibenclamide was used as a positive control. Histopathological assessment showed that TME and hesperidin averted necrosis and infiltration in pancreatic tissues, and led to a substantial improvement in the cellular structure of adipose tissue. TME and hesperidin distinctly diminished the mRNA and protein expression of NF-κB, cleaved caspase-3, and BAX, and increased BCL2 expression (reflecting its protective and antiapoptotic actions). Interestingly, TME and hesperidin reduced glucose uptake and oxidative lipid accumulation in the 3T3-L1 cell line. TME and hesperidin reduced DGAT1, CEBP/α, and PPARγ mRNA and protein expression in 3T3-L1 cells. Moreover, docking studies supported the results via deep interaction of hesperidin with the tested biomarkers. Taken together, the current study demonstrates Ocimum forskolei and hesperidin as possible candidates for treating diabetes mellitus.     

Antitumor Activity of Some Novel 1,2,5-Thiadiazole Derivatives

Some novel thiourea,1,2,4-triazole, quinazoline, thieno[2,3-d]pyrimi-dine, and thiazolidine derivatives were synthesized to evaluate their antitumor activity. Compound (3f) is nearly as active as reference drug, (Doxorubicin) as positive control.     

The effects of relativistic and nonlocal nonlinearities on modulational instabilities in inhomogeneous plasma

A general detailed analysis of the nonlinear generation of localized fields due to the existence of a strong pump field inside an inhomogeneous plasma has been performed taking into account the effects of relativistic and nonlocal nonlinearities on the structure of the plasma resonance region. The nonlinear Schrödinger equation describing the localized fields is investigated. A generalized dispersion relation is obtained to study the modulational instabilities in different cases.     

Structures of oxaliplatin‐oligonucleotide adducts from DNA

Oxaliplatin, [(1R,2R)‐cyclohexane‐1,2‐diamine](ethanedioato‐O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA–protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin‐DNA intrastrand and interstrand adducts at the oligomer level using high‐performance liquid chromatography/electrospray ionization‐tandem mass spectrometry (HPLC/ESI‐MS/MS) and HPLC/inductively coupled plasma‐MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI‐ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level. Copyright © 2012 John Wiley & Sons, Ltd.     

Amberlite IR-120 catalyzed,microwave-assisted rapid synthesis of 2-aryl-benzimidazoles

An expeditious synthesis of 2-aryl-benzimidazoles by the condensation of o-phenylenediamine with various araldehydes is described. This greener protocol is catalyzed by Amberlite IR-120, and proceeds efficiently in the absence of any organic solvent under microwave irradiation within 3–5 min.     

Inclusion complex of N-nitroso,N-(2-chloroethyl), N′, N′-dibenzylsulfamid with β-Cyclodextrin: Fluorescence and molecular modeling

The inclusion complex of N-nitroso, N-(2-chloroethyl), N′, N′-dibenzylsulfamid with β-Cyclodextrin have been investigated using the spectrofluorescence technique ¹H NMR spectroscopy. The stoichiometric ratio of the complex was found to be 1:1 and the stability constant was evaluated using the Benesi-Hildebrand equation. In order to find the most favorable structure, molecular mechanics calculations were employed to study the inclusion of CENS-Dibenz in β-CD in vacuum and in the presence of water as a solvent. The driving forces for complexation are dominated by non-bonded van der Waals host-guest interactions with very little electrostatic contribution in both environments. After this stage of calculation, both the most stable complexes obtained by MM+ were re-optimized using semi-empirical and quantum mechanical calculations. It was found that the PM3 and the hybrid method ONIOM2 calculations predict the same mode of inclusion of the drug molecule in the host cavity. In the most stable conformation (i.e. Complex A), one of the two aromatic cycles is dipped within the relatively less polar cavity of β-cyclodextrin, while the other aromatic cycle as well as the active groupings (alkylating agent and nitroso group) are directed towards the exterior through the narrow rim of β-CD. This orientation is preferred because it is the most energetically favorable structure. Moreover, statistical thermodynamic calculations demonstrate that the formation of the inclusion complex is an enthalpy-driven process. A comparison between the experimental and theoretical values of ΔG⁰ proves that simulation of the complexes without an explicit treatment of the solvent leads to dubious results.     

An improved max-flow-based lower bound for minimizing maximum lateness on identical parallel machines

In this paper, we introduce a new concept of semi-preemptive scheduling and we show how it can be used to derive a maximum-flow-based lower bound for the P|r_j|L_max which dominates the well-known preemptive lower bound. We show that, in some cases, the proposed bound strictly dominates the preemptive one while having the same complexity.     

Some remarks on the Jensen-Hadamard inequalities and applications

We provide some inequalities and integral inequalities connected to the Jensen-Hadamard inequalities for convex functions. In particular, we give some refinements to these inequalities. Some natural applications and further extensions are given.

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Sunto Forniamo alcune diseguaglianze e diseguaglianze integrali connesse alle dise-gueglianze di Jensen-Hadamard per funzioni convesse. In particolare, diamo qualche miglioramento di queste diseguaglianze. Alcune applicazioni naturali ed ulteriori estensioni sono date.

     

LINEAR SEARCH FOR A BROWNIAN TARGET MOTION

A target is assumed to move according to a Brownian motion on the real line. The searcher starts from the origin and moves in the two directions from the starting point.The object is to detect the target. The purpose of this paper is to find the conditions under which the expected value of the first meeting time of the searcher and the target is finite,and to show the existence of a search plan which made this expected value minimum.     

Extending the Balas-Yu bounds on the number of maximal independent sets in graphs to hypergraphs and lattices

A result of Balas and Yu (1989) states that the number of maximal independent sets of a graph G is at most ^p+1, where is the number of pairs of vertices in G at distance 2, and p is the cardinality of a maximum induced matching in G. In this paper, we give an analogue of this result for hypergraphs and, more generally, for subsets of vectors in the product of n lattices =₁××_n, where the notion of an induced matching in G is replaced by a certain binary tree each internal node of which is mapped into . We show that our bounds may be nearly sharp for arbitrarily large hypergraphs and lattices. As an application, we prove that the number of maximal infeasible vectors x=₁××_n for a system of polymatroid inequalities does not exceed max{Q,^logt/c(2Q,)}, where is the number of minimal feasible vectors for the system, , , and c(,) is the unique positive root of the equation 2^c(^c/log–1)=1. This bound is nearly sharp for the Boolean case ={0,1}ⁿ, and it allows for the efficient generation of all minimal feasible sets to a given system of polymatroid inequalities with quasi-polynomially bounded right-hand sides . This research was supported by the National Science Foundation (Grant IIS-0118635), and by the Office of Naval Research (Grant N00014-92-J-1375). The second and third authors are also grateful for the partial support by DIMACS, the National Science Foundation's Center for Discrete Mathematics and Theoretical Computer Science.Mathematics Subject Classification (2000):20E28, 20G40, 20C20