MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

  Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski's rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile

Euler-Poincare' Characteristic and Phase Transition in the Potts Model

Recent results concerning the topological properties of random geometrical sets have been successfully applied to the study of the morphology of clusters in percolation theory. This approach provides an alternative way of inspecting the critical behaviour of random systems in statistical mechanics. For the 2d q-states Potts model with q <= 6, intensive and accurate numerics indicates that the average of the Euler characteristic (taken with respect to the Fortuin-Kasteleyn random cluster measure) is an order parameter of the phase transition.Comment: 17 pages, 8 figures, 1 tabl

A Novel Synthetic Smoothened Antagonist Transiently Inhibits Pancreatic Adenocarcinoma Xenografts in a Mouse Model

Hedgehog (Hh) signaling is over-activated in several solid tumors where it plays a central role in cell growth, stroma recruitment and tumor progression. In the Hh signaling pathway, the Smoothened (SMO) receptor comprises a primary drug target with experimental small molecule SMO antagonists currently being evaluated in clinical trials.Using Shh-Light II (Shh-L2) and alkaline phosphatase (AP) based screening formats on a "focused diversity" library we identified a novel small molecule inhibitor of the Hh pathway, MS-0022 (2-bromo-N-(4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl)benzamide). MS-0022 showed effective Hh signaling pathway inhibition at the level of SMO in the low nM range, and Hh pathway inhibition downstream of Suppressor of fused (SUFU) in the low µM range. MS-0022 reduced growth in the tumor cell lines PANC-1, SUIT-2, PC-3 and FEMX in vitro. MS-0022 treatment led to a transient delay of tumor growth that correlated with a reduction of stromal Gli1 levels in SUIT-2 xenografts in vivo.We document the in vitro and in vivo efficacy and bioavailability of a novel small molecule SMO antagonist, MS-0022. Although MS-0022 primarily interferes with Hh signaling at the level of SMO, it also has a downstream inhibitory effect and leads to a stronger reduction of growth in several tumor cell lines when compared to related SMO antagonists

Physics at the Light-Front

The light-front representation of quantum chromodynamics provides a frame-independent, quantum-mechanical representation of hadrons at the amplitude level, capable of encoding their multi-quark, hidden-color and gluon momentum, helicity, and flavor correlations in the form of universal process-independent hadron wavefunctions. The universality and frame-independence of the LCWF's thus allow a profound connection between diffractive dissociation, hard scattering exclusive processes such as elastic form factors, two-photon reactions, and heavy hadron decays. In this concluding talk of the ECT* International Conference On Light-Cone Physics: Particles And Strings (Trento 2001), I review recent calculations and new applications of light-front wavefunctions in QCD and other theories. I also review the distinction between the structure functions measured in deep inelastic lepton scattering and the quark distributions determined from light-front wavefunctions.Comment: Invited talk presented at the International Light-Cone Workshop "Light-cone Physics: Particles and Strings" at ECT* in Trento, Italy, September 3-11, 200

Epidemiology of Theileria bicornis among black and white rhinoceros metapopulation in Kenya

[Background] A huge effort in rhinoceros conservation has focused on poaching and habitat loss as factors leading to the dramatic declines in the endangered eastern black rhinoceros (Diceros bicornis michaeli) and the southern white rhinoceros (Ceratotherium simum simum). Nevertheless, the role disease and parasite infections play in the mortality of protected populations has largely received limited attention. Infections with piroplasmosis caused by Babesia bicornis and Theileria bicornis has been shown to be fatal especially in small and isolated populations in Tanzania and South Africa. However, the occurrence and epidemiology of these parasites in Kenyan rhinoceros is not known.[Results] Utilizing 18S rRNA gene as genetic marker to detect rhinoceros infection with Babesia and Theileria, we examined blood samples collected from seven rhinoceros populations consisting of 114 individuals of black and white rhinoceros. The goal was to determine the prevalence in Kenyan populations, and to assess the association of Babesia and Theileria infection with host species, age, sex, location, season and population mix (only black rhinoceros comparing to black and white rhinoceros populations). We did not detect any infection with Babesia in the sequenced samples, while the prevalence of T. bicornis in the Kenyan rhinoceros population was 49.12% (56/114). White rhinoceros had significantly higher prevalence of infection (66%) compared to black rhinoceros (43%). The infection of rhinoceros with Theileria was not associated with animal age, sex or location. The risk of infection with Theileria was not higher in mixed species populations compared to populations of pure black rhinoceros.[Conclusion] In the rhinoceros studied, we did not detect the presence of Babesia bicornis, while Theileria bicornis was found to have a 49.12% prevalence with white rhinoceros showing a higher prevalence (66%) comparing with black rhinoceros (43%). Other factors such as age, sex, location, and population mix were not found to play a significant role.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer reviewe

Changes in Midline Tremor and Gait Following Deep Brain Stimulation for Essential Tremor

Background: Essential tremor (ET) is a common movement disorder characterized by kinetic and postural tremor in the upper extremities and frequently in the midline. Persons with ET often also exhibit gait ataxia. Previous studies have observed associations between midline tremor severity and gait ataxia in persons with ET, suggesting a common pathophysiology distinct from that of upper extremity tremor. However, a causal link between midline tremor and gait impairment has not been established. Methods: We investigated tremor and gait in 24 persons with ET before and after implantation of unilateral deep brain stimulation into the ventralis intermedius nucleus of the thalamus. Results: Stimulation significantly improved tremor in the targeted upper extremity and midline. However, gait was unaffected at the cohort level. Furthermore, improvement in midline tremor was not significantly associated with gait improvement. Discussion: These findings revealed that midline tremor and gait impairment may be dissociable in persons with ET