Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles

In the present study, a novel poly-lactic glycolic acid (PLGA)-based microparticle formulation of perillyl alcohol (POH) was prepared and characterized. Further, its efficacy was evaluated against di-methyl benzo anthracene-induced skin papilloma in Swiss albino mice. The characterization studies showed that POH-bearing PLGA microparticles were of the size 768 ± 215 nm with a ζ-potential value of −7.56 ± 0.88 mV. The entrapment efficiency of the active drug in particles was 42.4% ± 3.5%. POH-bearing PLGA microparticles were stable and released entrapped drug gradually over an extended time period. The in vitro efficacy of POH-bearing PLGA microparticles was evaluated by examining their differential cytotoxicity and assessing their ability to inhibit epidermoid carcinoma cell line (A253). The POH-based microparticles when administered to tumor-bearing animals caused greater tumor regression and increased survival rate (∼80%) as compared with the group receiving free form of POH (survival rate 40%). The superiority of POH-PLGA microparticles over free form of POH was further evident from their ability to modulate apoptosis-regulating factors

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma

Nanoemulsion Adjuvant Augments Retinaldehyde Dehydrogenase Activity in Dendritic Cells via MyD88 Pathway

Mucosal surfaces are the primary point of entry for many infectious agents and mucosal immune responses serve as the primary defense to these pathogens. In order to mount an effective mucosal immune response, it is important to induce T cell homing to mucosal surfaces. Conventional vaccine adjuvants induce strong systemic immunity but often fail to produce mucosal immunity. We have developed an oil-in-water nanoemulsion (NE) adjuvant that provides mucosal immunity and efficient protection against mucosal pathogens when administered as part of an intranasal vaccine. In the present study, we demonstrate that intranasal immunization with NE indirectly activates the retinaldehyde dehydrogenase (RALDH) activity in dendritic cells through epithelial cell activity leading to SIgA as well as potent cellular responses and expression of α4β7 and CCR9 gut homing receptors on T cells. Confirming these findings, ex-vivo stimulation of splenocytes from NE nasally immunized animals showed increase in Th1/Th17 cytokines while suppressing Th2 responses. In examining mechanisms underlying this activation NE activated RALDH via MyD88 dependent pathways in DCs but did not activate the retinoic acid receptor directly. These results suggest that RALDH immune activities can be achieved by epithelial activation without direct RAR activation, which has significant implications for understanding mucosal immunity and the design of mucosal vaccines

Role of plants in anticancer drug discovery

Cancer is one of the major causes of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Worldwide the alarming rise in mortality rate due to cancer has fuelled the pursuit for effective anticancer agents to combat this disease. Finding novel and efficient compounds of natural origin has been a major point of concern for research in the pharmaceutical sciences. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for cancer treatment. Many successful anti-cancer drugs currently in use or their analogues are plant derived and many more are under clinical trials. This review aims to highlight the invaluable role that plants have played, and continue to play, in the discovery of anticancer agents.We acknowledge the University of Pretoria for Postdoctoral fellowship to J.K. and B.A.M.http://www.elsevier.com/locate/phytolhb2017ChemistryGenetic

Smart Prosthetic Hand Development using Deep Learning and Inertial Measurement Unit Data

The main contribution of this work is to exhibit an improved developed and evaluation of architectures with higher accuracy for prosthetic hand by deep learning with IMU using 9 degrees of freedom. Deep Learning has been gaining popularity due to its numerous implementations and continuous growing capabilities, including the prosthetics industry which has contributed by developing prosthetic minded by deep learning. Previously conducted research on prosthetic arm that utilizes deep learning with inertial measurement unit (IMU) produced promising results with only using single aspect of the device. This research expanded on that by utilizing accelerometer, gyroscope, and magnetometer. This research study was successfully developed various architectures that yielded promising results with improving on the previous work by achieving 99.2% accuracy

Deep Model Compression based on the Training History

Deep Convolutional Neural Networks (DCNNs) have shown promising results in several visual recognition problems which motivated the researchers to propose popular architectures such as LeNet, AlexNet, VGGNet, ResNet, and many more. These architectures come at a cost of high computational complexity and parameter storage. To get rid of storage and computational complexity, deep model compression methods have been evolved. We propose a novel History Based Filter Pruning (HBFP) method that utilizes network training history for filter pruning. Specifically, we prune the redundant filters by observing similar patterns in the L1-norms of filters (absolute sum of weights) over the training epochs. We iteratively prune the redundant filters of a CNN in three steps. First, we train the model and select the filter pairs with redundant filters in each pair. Next, we optimize the network to increase the similarity between the filters in a pair. It facilitates us to prune one filter from each pair based on its importance without much information loss. Finally, we retrain the network to regain the performance, which is dropped due to filter pruning. We test our approach on popular architectures such as LeNet-5 on MNIST dataset and VGG-16, ResNet-56, and ResNet-110 on CIFAR-10 dataset. The proposed pruning method outperforms the state-of-the-art in terms of FLOPs reduction (floating-point operations) by 97.98%, 83.42%, 78.43%, and 74.95% for LeNet-5, VGG-16, ResNet-56, and ResNet-110 models, respectively, while maintaining the less error rate

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

Mohammad Farazuddin,1 Bhavyata Dua,2 Qamar Zia,1 Aijaz Ahmad Khan,3 Beenu Joshi,2 Mohammad Owais1 1Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 2Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (NJIL), Agra, 3Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India Abstract: Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. Keywords: diferuloylmethane, carcinogenesis, microparticle, nanocells, cancer, Curcuma long

A Comparative Study on Caprini RAM Vs DOH Tool for Thromboprophylaxis in ICU Setting at Tertiary Care Hospital

The aim of the study was to assess DVT prophylaxis using two models (Caprini RAM & DOH tool) for the prevention of DVT in postoperative or critically ill patients and for better predictability of disease. In this prospective observational study, we compared the Caprini RAM and DOH tool in the ICU setting on 229 patients (140 men and 89 women). 205 patients were considered in the study, out of which 97 had Caprini RAM and 108 had DOH tool. A Prospective, observational comparative study was carried out in a tertiary care hospital for a period of 6 months. Patients were divided into two groups according to the RAM. The data were analyzed using SPSS software and the results were compared using the student t-test. Both GROUP A and GROUP B revealed that the majority of the patients (67.1% & 55.6%) were above 60 years and a large proportion of them required DVT prophylaxis. In GROUP A 93% of forms were complete with 79% accuracy. In GROUP B 83% were complete. The most appropriate prophylaxis received by patients was Enoxaparin sodium 40 mg OD for about 97 (30%) patients and Heparin 5000 IU BD for 108 (30%) based on their Caprini scores and NICE guidelines respectively. The majority of patients in Group A did not require dosage adjustments, but in 20% of cases, it was necessary. Statistical significance was achieved with a p-value less than 0.05. The study demonstrates DOH tool is better than Caprini RAM to be used in hospitals, for risk assessment of VTE in both medical and surgical patients for accuracy and predictability of the prophylaxis. Keywords: DVT, Risk assessment, Caprini RAM, DOH tool, pharmacological and mechanical Prophylaxis