Исследование методом сетевой фармакологии и молекулярного докинга для выявления потенциальной противораковой активности морских цитотоксинов — осциллатоксинов D, E, и F

Oscillatoxins (OTXs) are cytotoxins produced by some marine cyanobacteria. Their unique structures show a great potency as an anticancer agent. The limited availability of OTX derivatives in nature provides little information about their biological activity. Some of OTX activities have been tested in the in vitro or in vivo studies toward cancer cell lines, but their exact mechanism of action on the target is unclear. In this study, we used the network pharmacology analysis method to predict the target and mechanism of action of oscillatoxin D (OTX-D), 30 methyl oscillatoxin D (30-methyl-OTX-D), oscillatoxin E (OTX-E), and oscillatoxin F (OTX-F). There are 20 possible targets of the four compounds toward cancer, and the main targets of them are PIK3CA, CDK1, and MTOR. This was also followed by the molecular docking study to understand the interaction between the four compounds and their targets. Molecular docking showed that the four compounds interacted well with the key targets. In this study, four derivatives of OTXs and their three key targets for the anticancer action were revealed suggesting multiple signaling pathways, including PD-L1 expression and PD‑1 checkpoint pathway in cancer, proteoglycans in cancer, and pathways in cancer, establishing a theoretical framework for the further experimental study.Осциллатоксины (OTXs) —  это цитотоксины, продуцируемые некоторыми морскими цианобактериями. Их уникальные структуры показывают высокую эффективность в качестве противораковых средств. Ограниченная доступность производных OTXs в природе дает мало информации об их биологической активности. Было тестировано несколько активностей OTXs в исследованиях in vitro или in vivo в отношении линий раковых клеток, но их точный механизм действия на мишень не ясен. В данном исследовании мы использовали метод сетевой фармакологии для прогнозирования мишеней и механизмов действия осциллатоксина D (OTX-D), 30 метил-осциллатоксина D (30-метил-OTX-D), осциллатоксина E (OTX-E), и осциллатоксина F (OTX-F). Существуют 20 возможных мишеней четырех соединений против рака и их основными мишенями являются PIK3CA, CDK1 и MTOR. Затем было проведено исследование методом молекулярного докинга для понимания взаимодействия между 4 соединениями и их мишенями. Молекулярный докинг показал, что 4 соединения хорошо взаимодействовали с ключевыми мишенями. В данной работе было выявлено 4 производных OTXs и 3 ключевых мишени для противоракового действия, указывая на множественные сигнальные пути, включая путь экспрессии PD-L1 и контрольной точки PD-1 при раке, протеогликаны при раке и пути при раке, устанавливая теоретические рамки для дальнейшего экспериментального исследования

NIGER GRAIN FLY DIOZINA-SORORCULA A SERIOUS PEST OF NIGER GUIZOTIA-ABYSSINICA IN CENTRAL INDIA

Volume: 80Start Page: 439End Page: 44

Expect the unexpected: Endometriosis mimicking a rectal carcinoma in a post-menopausal lady

Altered bowels habits along with rectal mass in an elderly would point toward a rectal cancer. We report an unusual case of a post-menopausal lady who presented with these complaints. We had difficulties in establishing a pre-operative diagnosis. With a tentative diagnosis of a rectal cancer/gastrointestinal stromal tumor, she underwent a laparoscopic anterior resection. On histopathology, this turned out to be endometriosis. Bowel endometriosis is an uncommon occurrence. That it occurred in a post-menopausal lady was a very unusual finding. We discuss the case, its management, and the relevant literature

Remazol brilliant blue reactive dye decolouration and mustard straw utilization by white rot fungi

144-148The remazol brilliant blue reactive (RBBR) dye decolouration and mustard (Brassica campestris) straw (MuS) nutrient utilization by various white rot fungi, viz. Phanerochaete chrysosporium, Ganoderma applanatum, G. lucidum, Pleurotus ostreatus, P. sajorcaju, Polyporus arcularius, P. versicolor, P. adustus, P. sanguineus-970, P. sanguineus-154, Trametes hirsuta, Parva mentocela and Longyites strata, were studied. The visual detection of decolouration was found complementary to its quantitative estimation. P. sanguineus-970 showed the highest RBBR dye decolouration in agar as well as in broth medium (74%). The dry matter utilization of MuS was low (20-27%) by all the white rot fungi. However, they preferentially degraded lignin (18-42%) in comparison to cellulose (0-12%). The highest lignin utilization was shown by P. chrysosporium. Whereas, P. sanguineus-154 showed both higher RBBR dye decolouration (66.5%) and lignin degradation (33%) and could be used for modification of MuS as animal feed

Effect of sodium hydroxide and alkaline hydrogen peroxide treatment on physical and chemical characteristics and IVOMD of mustard straw

Abstract Mustard straw (MS) was soaked for 6 h in the solutions containing 0% (S 0 ), 1% (S 1 ) or 2% (S 2 ) sodium hydroxide (NaOH) and 0% (H 0 ) or 1.5% (H 1 ) hydrogen peroxide (H 2 O 2 ) following a 3Â2 factorial design. The pH of the untreated MS (near neutral) was increased to more than 10 after treatment with NaOH (S 1 H 0 and S 2 H 0 ) or alkaline hydrogen peroxide (AHP; S 1 H 1 and S 2 H 1 ). The treatment effect on tenacity was not signi®cant. The NDF and ADF contents of MS increased signi®cantly (p<0.01) in the treatment S 0 H 1 , whereas these decreased signi®cantly (p<0.01) in the treatments S 2 H 0 and S 2 H 1 . However, the change in NDF and ADF was not signi®cant in S 0 H 0 , S 1 H 0 and S 1 H 1 treatments. The content of both NDF and ADF decreased linearly (p<0.01) with increasing level of NaOH in the soaking medium. The effect of various treatments on cellulose content was almost similar to that of NDF and ADF. The acid detergent lignin content of MS increased signi®cantly (p<0.01) in case of S 1 H 0 , S 0 H 1 and S 1 H 1 but the differences were not signi®cant among UMS, S 0 H 0 , S 2 H 0 and S 2 H 1 . The IVOMD content of untreated MS was 162 g kg À1 DM and it increased signi®cantly (p<0.01) when straw was soaked in S 1 H 0 , S 2 H 0 , S 1 H 1 and S 2 H 1 , whereas it reduced slightly due to either water (S 0 H 0 ) or H 2 O 2 (S 0 H 1 ) treatment. With the increasing level of NaOH, the IVOMD improved signi®cantly (p<0.01). It is concluded that the cell wall constituents and IVOMD of MS were modi®ed by NaOH with or without H 2 O 2 in a way that in vitro organic matter digestibility (IVOMD) of treated MS was 82±112% units higher than untreated MS. # 2000 Elsevier Science B.V. All rights reserved

Sustainable synthesis and theoretical studies of polyhedral gold nanoparticles displaying high SERS activity, NIR absorption, and cellular uptake

The preparation of gold nanoparticles with multimodal properties such as near-infrared absorption, high surface-enhanced Raman scattering, cell internalization and low cytotoxicity is a challenging task. In this study, we developed a sustainable protocol to develop gold nanoparticles, using trisodium citrate as reducing, stabilizing, and shape-modulating agent at ambient conditions (25 °C). Reduction of gold salt at room temperature at a peculiar ratio R(Ccitrate/CHAuCl4) and concentration of reactants resulted in the formation of non-spherical, homogenous mixture of gold nanoparticles with polyhedral shapes. The protocol is extremely simple and does not even require stirring or mechanical shaking. The as-synthesized gold nanoparticles, even though multi-shaped, displayed a single monomodal peak in dynamic light scattering with polydispersity index of 0.098, representative of a fairly good monodisperse system. We investigated the optical properties of the nanoparticles both experimentally and by two-dimensional Finite-Difference-Time-Domain modeling. Due to the presence of shapes such as nanorods, nanotriangles, and prismatic, these nanoparticles exhibited a high surface-enhanced Raman scattering activity and a wide absorption range extending up to the near-infrared region, which makes them useful candidate for photothermal therapy too. We characterized the nanoparticles by electron microscopy, UV–vis–NIR spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. We have also developed an enhanced numerical diffusion limited aggregation model to simulate the growth of the particles, including the particle interfacial energy as a parameter of the system. Numerical results matched with the experimental data, and the model revealed being effective in reproducing size, shape, and morphological characteristics of non-spherical nanoparticles obtained under real experimental conditions. Finally, in vitro studies and nanoparticles cellular uptake were performed on a model cell line of mouse brain endothelium (bEnd.3) to assess biocompatibility. The main advantage of the proposed method lies in its simplicity with no other requirement like refluxing at elevated temperature, mechanical stirring, electromagnetic radiations, ultrasound, toxic chemicals, or seed mediation