A COMPARATIVE STUDY OF ANTI-ANGIOGENIC ACTIVITIES OF MEDICINAL PLANTS AND ITS THERAPEUTIC POTENTIAL IN ANGIOGENESIS-DEPENDENT DISORDERS

AbstractIntroductionAngiogenesis, the process of new vessel growth from pre-existing capillaries is involved in physiological and pathological process such as embryonic development, wound healing, diabetic retinopathy ,chronic inflammation, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) induced angiogenesis plays an important role in the pathogenesis of diabetic retinopathy and cancer and anti VEGF factor agents are found to be effective . VEGF inhibitors from plant sources show promising result recently. So this study is designed to evaluate and compare the VEGF inhibitory effect of the herbs Osimum Sanctum, Andrographis paniculata, Syzygium cumini and Ginkgo biloba by using in vivo models.Methods: Both Corneal neovascularization assay and Chick Chorioallantoic membrane assays were used for evaluation. The induced neovascularization was compared with control and extract treated groups.Results: The acute and repeated dose toxicity tests showed that the extracts are safe on oral administration. And also the results showed significant antiangiogenic effect of individual extract and their combination in both in vivo models. However the combination of the extract showed excellent result (p <0.001) by reducing neovascularization in both modelsConclusion: The above results suggested that combination of the above extracts have promising future in the management of angiogenesis dependent disorders.Key words: Osimum Sanctum, Andrographis paniculata, Syzygium cumini, Ginkgo biloba,   Angiogenesis, chorioallantoic membrane, angiogenesis dependent disorders

Zika Virus- Emergence, Evolution, Pathology, Diagnosis, and Control: Current Global Scenario and Future Perspectives- A Comprehensive Review

This review converses the Zika virus which has attained global concern due to its rapid pandemic potential and impact on humans. Though Zika virus was first isolated in 1947, till the recent large-scale outbreak which occurred in Micronesia, in 2007, the virus was placed into the innocuous pathogen category. The World Health Organization on 1 February 2016 declared it as a Public Health Emergency of International Concern.\u27 Of the note, American as well as Pacific Island strains/isolates is relatively closer to Asian lineage strains. The African and American strains share more than 87.5% and 95% homologies with Asian strains/isolates, respectively. Asian strains form independent clusters, except those isolated from China, suggesting relatively more diversity than African strains. Prevention and control are mainly aimed at the vector population (mosquitoes) with Aedes aegypti being the main species. Surveys in Africa and Asia indicated seropositivity in various animal species. However, so far its natural reservoir is unknown. There is an urgent need to understand why Zika virus has shifted from being a virus that caused mild illness to unforeseen birth defects as well as autoimmune-neurological problems. Unfortunately, an effective vaccine is not available yet. Availability of cryo-electron microscopy based on 3.8 angstrom resolution revealing mature Zika virus structure and the probable virus attachment site to host cell would provide critical insights into the development of antiviral treatments and vaccines

Brzo i vidljivo petljom posredovano izotermno umnažanje za dokazivanje Brucella spp. i njegova primjena u epidemiologiji bruceloze goveda.

Brucellosis is a devastating disease, once an abortion storm starts in a herd, and hence early diagnosis is important. Loop mediated isothermal amplification (LAMP) has enlightened the darker part of the diagnostic world by its simplicity and swiftness, and has the advantage of working in isothermal conditions so that it can be applied to the field. LAMP for Brucella spp., that already exists has not been exploited for visual detection and the time needed for completion of the reaction has not been reduced. In the present study, an attempt was made to seal these cracks by developing a fast and visually detectable LAMP for Brucella spp., which needs only 30 min detection time, and SYBR green aided easier result visualization. The LAMP test targeting the omp25 gene was found to be highly sensitive and specific for detecting Brucella spp. Comparison of the LAMP test with the available PCR assay revealed that the LAMP test was more sensitive than PCR, following testing of 438 field samples of cattle origin, and it showed prevalence of Brucella of 14.7 % in different parts of India. Being highly sensitive, specific and speedy, the standardized visual LAMP test can be widely used for epidemiological surveys of this economically important and zoonotic pathogen.Bruceloza je razorna bolest kad se u stadu pojavi u obliku pobačaja što iziskuje brzo postavljanje dijagnoze. Upotreba metode nazvane „petljom posredovano izotermno umnažanje“ (engl. loop mediated isothermal amplification, LAMP)“ omogućila je poboljšanje dijagnostike svojom jednostavnošću i brzinom, a prednost joj je da se može izvesti na postojanoj temperaturi pa se može primijeniti u terenskim uvjetima. U dosada razvijenim postupcima LAMP-a nije bio rabljen vizualni dokaz i nije se uspjelo skratiti vrijeme reakcije. U ovom istraživanju pokušalo se ukloniti te nedostatke razvitkom brzog postupka za vizualni dokaz Brucella spp., za što je potrebno samo 30 minuta i SYBR zeleno. LAMP test za dokaz gena omp25 pokazao se visoko osjetljivim i specifičnim za dokaz Brucella spp. Pretraga 438 terenskih uzoraka podrijetlom od goveda pokazala je da je LAMP osjetljiviji od raspoloživih testova PCR-a. Tim je testom dokazana prevalencija bruceloze od 14,7 % u različitim dijelovima Indije. Kao vrlo osjetljiv, specifičan i brz, LAMP test se može naširoko upotrijebiti u epidemiološkim istraživanjima bruceloze

Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV

Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1)

Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described

A Comprehensive Review on Equine Influenza Virus:Etiology, Epidemiology, Pathobiology, Advances in Developing Diagnostics, Vaccines, and Control Strategies

Among all the emerging and re-emerging animal diseases, influenza group is the prototype member associated with severe respiratory infections in wide host species. Wherein, Equine influenza (EI) is the main cause of respiratory illness in equines across globe and is caused by equine influenza A virus (EIV-A) which has impacted the equine industry internationally due to high morbidity and marginal morality. The virus transmits easily by direct contact and inhalation making its spread global and leaving only limited areas untouched. Hitherto reports confirm that this virus crosses the species barriers and found to affect canines and few other animal species (cat and camel). EIV is continuously evolving with changes at the amino acid level wreaking the control program a tedious task. Until now, no natural EI origin infections have been reported explicitly in humans. Recent advances in the diagnostics have led to efficient surveillance and rapid detection of EIV infections at the onset of outbreaks. Incessant surveillance programs will aid in opting a better control strategy for this virus by updating the circulating vaccine strains. Recurrent vaccination failures against this virus due to antigenic drift and shift have been disappointing, however better understanding of the virus pathogenesis would make it easier to design effective vaccines predominantly targeting the conserved epitopes (HA glycoprotein). Additionally, the cold adapted and canarypox vectored vaccines are proving effective in ceasing the severity of disease. Furthermore, better understanding of its genetics and molecular biology will help in estimating the rate of evolution and occurrence of pandemics in future. Here, we highlight the advances occurred in understanding the etiology, epidemiology and pathobiology of EIV and a special focus is on designing and developing effective diagnostics, vaccines and control strategies for mitigating the emerging menace by EIV

A facile one-pot conversion of acetates of the Baylis-Hillman adducts to [E]-α-methylcinnamic acids

A simple and convenient stereoselective synthesis of [E]-α-methylcinnamic acids via the nucleophilic addition of hydride ion from sodium borohydride to methyl 3-acetoxy-3-aryl-2-methylenepropanoates followed by hydrolysis and crystallization is described. Efficacy of this methodology in the synthesis of [E]-p-(myristyloxy)-α-methylcinnamic acid, an active hypolipidemic agent, and [E]-p-(carbomethoxy)-α -methylcinnamic acid, a valuable synthon for an orally active serine protease inhibitor, is also demonstrated

Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand

We describe the design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors containing bicyclic isoxazoline carboxamides as the P3 ligand in combination with methyl cysteine, methylsulfonylalanine and Boc-amino alanine as P2 ligands. Inhibitor 3a displayed a BACE1 Kivalue of 10.9 nM and EC50of 343 nM. The X-ray structure of 3a bound to the active site of BACE1 was determined at 2.85 Å resolution. The structure revealed that the major molecular interactions between BACE1 and the bicyclic tetrahydrofuranyl isoxazoline heterocycle are van der Waals in nature