NOVEL NANOCARRIERS FOR ETHNOPHARMACOLOGICAL FORMULATIONS

A numerous novel drug delivery system has been emerged by combining herbal medicine with nanotechnology to administer drugs encompassing the enhancement of compatibility and efficacy. The herbal phytoconstituents are compatible compared to the chemical active pharmaceutical ingredients (APIs). But the therapeutic consequence of the phytoconstituent is limited due to poor aqueous solubility. Therefore, the demand to develop a system which improves the solubility of the phytomedicine is mounting rapidly. Nanotechnology plays a vital role in increasing the solubility, enhancing the bioavailability and improving the drug specificity of bioactive constituents. Nanosystems such as liposomes, nanoparticles, phytosomes, ethosomes, nanoemulsions and solid lipid nanoparticles are used to deliver the bioactive constituent at an adequate dose to the site of action and during the entire treatment period. The current review discusses the various novel drug delivery systems which have been developed to attain better therapeutic response of the herbal drug

Dissection of Mobility Model Routing Protocols in MANET on QoS Criterion

Essential difficulties in Mobile Ad Hoc Networks (MANET) are routing selection and Quality of Service(QoS) support. Several different approaches have been described in the literature, and a number of performance simulations have been produced, in an attempt to tackle this challenging problem. In this study, we take a close look at the relative merits of several popular routing protocols. In this research, we looked into how changing QoS parameters in tandem with routing protocol choices affected network throughput. Typical measures for measuring network efficiency include average throughput, packet delivery ratio (PDR), average delay, and power usage. NS-3 is used to run the simulations

Triazole Inhibitors of Cryptosporidium parvum Inosine 5?-Monophosphate Dehydrogenase

Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. This protozoan parasite cannot salvage guanine or guanosine and therefore relies on inosine 5?-monophosphate dehydrogenase (IMPDH) for biosynthesis of guanine nucleotides and hence for survival. Because C. parvum IMPDH is highly divergent from the host counterpart, selective inhibitors could potentially be used to treat cryptosporidiosis with minimal effects on its mammalian host. A series of 1,2,3-triazole containing ether CpIMPDH inhibitors are described. A structure?activity relationship study revealed that a small alkyl group on the ?-position of the ether was required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring were best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retained inhibitory activity both in the presence and absence of bovine serum albumin. The 1,2,3-triazole CpIMPDH inhibitors provide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeutics for treating cryptosporidiosis

Ocular progenitor cells and current applications in regenerative medicines – Review

The recent emerging field of regenerative medicine is to present solutions for chronic diseases which cannot be sufficiently repaired by the body's own mechanisms. Stem cells are undifferentiated biological cells and have the potential to develop into many different cell types in the body during early life and growth. Self renewal and totipotency are the characteristic features of stem cells and it holds a promising result for treating various diseases like diabetic foot ulcer, heart diseases, lung diseases, Autism, Skin diseases, arthritis including eye disease. Failure of complete recovery of eye diseases and complications that follow conventional treatments have shifted search to a new form of regenerative medicine using Stem cells. The ocular progenitor cells are remarkable in stem cell biology and replenishing degenerated cells despite being present in low quantity and quiescence in our body has a high therapeutic value. In this paper we have review the applications on ocular progenitor stem cells in treatment of human eye diseases and address the strategies that have been exploited in an effort to regain visual function in the advance treatment of stem cells without any side effects and also present the significance in advance stem cell research

Fault Diagnosis of Cascaded Multilevel Inverter Using Multiscale Kernel Convolutional Neural Network

Over the last decade, multilevel inverter (MLI) has gained a global research paradigm in power electronics. The high-power application of multilevel inverters necessitates the safe and reliable operation of the inverter. Fault diagnosis of MLI is inevitable to enhance the reliability of the inverter. The real-time applications monitor the intricate switching process of the MLI using data from sensors like voltage, current, and temperature. Obtaining complementary fault features through conventional methods is difficult due to operating complexity and limited switch-fault samples. These methods heavily depend on prior knowledge. To deal with this problem, this paper proposes a new multiscale kernel convolution neural network (MKCNN) for fast fault diagnosis of cascaded MLI. Firstly, the proposed method necessitates using frequency domain samples instead of raw signals, which can leverage the power of a convolution neural network (CNN) to obtain hierarchical features from the images through a short-time Fourier transform (STFT). Secondly, the multiscale kernel convolution network model is constructed to capture and analyze low- to high-level fault features. This method improves the traditional CNN by extracting discriminative fault information through multiple convolution kernels of different scales with varying resolutions obtaining high diagnosis accuracy under single and multiple open circuit and short circuit faults. Finally, the softmax layer generates the output of the fault diagnosis results. Simulation results validate the effectiveness of the proposed model, demonstrating a high diagnosis accuracy rate of 98.3%. The model exhibits robustness in diagnosing single and multiple switch faults across different fault cases of an MLI. Comparison with other intelligent models further emphasizes the superiority of the proposed method

Facile one-pot synthesis of thio and selenourea derivatives: a new class of potent urease inhibitors

A facile, one-pot synthesis of thio and selenourea derivatives from amines using tetrathiomolybdate 1 and tetraselenotungstate 2 as sulfur and selenium transfer reagents, respectively, is reported. The compounds were tested for their activity as urease inhibitors and some of the compounds showed potent activity in the nanomolar range towards jack bean urease

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway

Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis

Inflammasome-activated caspase-1 cleaves gasdermin D to unmask its pore-forming activity, the predominant consequence of which is pyroptosis. Here, we report an additional biological role for gasdermin D in limiting cytosolic DNA surveillance. Cytosolic DNA is sensed by Aim2 and cyclic GMP-AMP synthase (cGAS) leading to inflammasome and type I interferon responses, respectively. We found that gasdermin D activated by the Aim2 inflammasome suppressed cGAS-driven type I interferon response to cytosolic DNA and Francisella novicida in macrophages. Similarly, interferon-beta (IFN-beta) response to F. novicida infection was elevated in gasdermin D-deficient mice. Gasdermin D-mediated negative regulation of IFN-beta occurred in a pyroptosis-, interleukin-1 (IL-1)-, and IL-18-independent manner. Mechanistically, gasdermin D depleted intracellular potassium (K(+)) via membrane pores, and this K(+) efflux was necessary and sufficient to inhibit cGAS-dependent IFN-beta response. Thus, our findings have uncovered an additional interferon regulatory module involving gasdermin D and K(+) efflux

The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses

Inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1beta (IL-1beta) and IL-18. AIM2 has been shown to bind DNA and engage the caspase-1-activating adaptor protein ASC to form a caspase-1-activating inflammasome. Using Aim2-deficient mice, we identify a central role for AIM2 in regulating caspase-1-dependent maturation of IL-1beta and IL-18, as well as pyroptosis, in response to synthetic double-stranded DNA. AIM2 was essential for inflammasome activation in response to Francisella tularensis, vaccinia virus and mouse cytomegalovirus and had a partial role in the sensing of Listeria monocytogenes. Moreover, production of IL-18 and natural killer cell-dependent production of interferon-gamma, events critical in the early control of virus replication, were dependent on AIM2 during mouse cytomegalovirus infection in vivo. Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity