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Background The conventional Papanicolaou-stained cervical smear is the most common screening test for cervical cancer. The sensitivity of the test in detecting abnormal cells is 67–75% in various studies. Owing to the volume of smears at cancer screening centres, significant man-hours are expended in the test. We have developed a software program for identification of foci of abnormal cells from conventional smears. We have chosen the convolutional neural network (CNN) model for its efficacy in image classification. Methods A total of 1838 microphotographs from cervical smears, containing 1301 ‘normal’ foci and 537 ‘abnormal’ foci were included in the study. The data set was split into training, testing and validation sets. A CNN was developed in the Python programming language. The CNN was trained with the training and testing set. At the end of training, 94.64% accuracy was achieved in the testing set. The CNN was then run on the validation set (441 images). Results The CNN showed 94.28% sensitivity, 96.01% specificity, 91.66% positive predictive value and 97.30% negative predictive value. The CNN could recognise normal squamous cells, overlapping cells, neutrophils and debris and classify the focus appropriately. False positives were reported when the CNN failed to recognise overlapping cells (2.7% microphotographs). It could correctly label cell clusters with high nuclear cytoplasmic ratio and hyperchromasia. In 1.8% of microphotographs, a false negative was reported. Conclusion The CNN showed 95.46% diagnostic accuracy, suggesting potential use in screening.

Tobacco smoking is considered as one of the major risk factors for development of oral cancer. In vitro studies indicate that cigarette smoke initiates transformation of epithelial cells toward development of oral cancer through altering mitochondrial metabolic pathways. However the present in vitro models need to be improved to correlate these molecular changes with epithelial transformations. In present study, we investigated the association of mitochondrial metabolic events with oral cancer progression under cigarette smoke extract (CSE). In this regard, an in vitro model of oral keratinocyte cell line (MOE1A) was developed by exposing them with different concentrations of CSE. Alterations in cellular phenomena were confirmed by Fourier-transform infrared spectroscopy (FTIR) study, which indicated changes in important functional groups of CSE-induced oral cells. Enhanced reactive oxygen species (ROS) of exposed cells altered the mitochondrial metabolic activities in terms of increased mitochondrial mass and DNA content. Further, mitochondrial heme-metabolism was investigated and real-time PCR study showed altered expression of important genes like ALAS1, ABCB6, CPOX, FECH, HO-1. Both transcriptomic and proteomic studies showed up- and down-regulation of important biomarkers related to cellular cancer progression. Overall data suggest that CSE alters mitochondrial heme metabolic pathway and initiates cancer progression through modifying cellar biomarkers in oral epithelial cells.

Background The wives of serving soldiers constitute a special demographic cohort, as they spend variable amount of time in co-habitation with their husbands. The present study aims to find if any independent association, adjusted for age, exists between the time spent living together with the husband and findings on cervical smear. Methods Over a period of one year, cervical smears were taken from subjects at two different hospitals. The approximate length of co-habitation with husbands in the last 10 years was elicited through a questionnaire. Results Among 262 subjects, majority of smears showed normal findings (82.06%). 17.93% of the smears displayed abnormality, the maximum proportion of cases with abnormal findings were seen in the group who have spent 61–90 months, in the last ten years. Age adjusted chi square statistics failed to show statistically significant association between period of co-habitation and abnormal Pap smear. Odds’ ratio (OR) for each age stratum varied from each other and was also different from the overall (crude) OR, suggesting that age is an effect modifier. Variation in epithelial cytology did not appear to be an effect of duration of cohabitation but was because of the increasing age. Conclusions Cervical cytology does not show association with length of cohabitation with husbands in this study. However, age is seen to be an effect modifier.

Edible mushrooms are natural sources for numerous bioactive properties which can protect human body from oxidative damages, hypertension, abnormal cell growth etc., The present study disclosed that, bioactive properties of mushroom proteins are significantly enhanced by adopting enzymatic hydrolysis. This study established the mushroom protein hydrolysates (MPHs), produced from freshly cultivated edible mushroom, Pleurotus ostreatus, could be the supreme source of both bioactive and nutraceutical compounds. Here, both unhydrolysed mushroom extract (UME) and proteinase K treated MPHs of different degrees of hydrolysis DH% (55%, 60%, 65%, 70% and 80%) under optimized condition were evaluated for antioxidative, angiotensin rennin converting enzyme (ACE) inhibitory and antiproliferative activities at different concentrations (2.5, 5 and 10 mg/ml). Among these, 65% DH at 10 mg/ml exhibited profound antioxidative (DPPH, ABTS, hydroxyl radical scavenging, metal chelating, linoleic acid auto-oxidation, FRAP, and reducing power) and ACE inhibitory activities. Maximum amount of total phenolic and flavonoid content was also obtained in this case. MTT assay confirmed the remarkable antiproliferative properties of MPHs against human cervical carcinoma cell line (HeLa). Presence of a wide range of phenolic (i.e., gallic, trans-cinnamic, caffeic, ferulic, aspartic and vanillic acid) and flavonoid (quercetin) compounds in both UME and MPHs were identified through HPLC.

This article reviews the current status and contemporary challenges involved in 3D inkjet powder printing of metallic biomaterials. The process physics, comprising of drop-on-demand methodology and binder-powder interaction are briefly discussed. For the later, various dimensionless numbers (Re, Oh and We) are emphasized as they govern the morphology and travel of the binder droplet. The post-impact interaction with powder particles are described into three sequential stages as, impact driven, capillary driven and equilibrium attainment. A review of several binder formulations to 3D print metallic biomaterials is presented along with the guidelines. Non-destructive 3D structural analysis, using advanced X Ray micro-computed tomography (XCT) technique is emphasized for porous architecture assessment (pore volume fraction, pore shape and size distribution, % interconnectivity) and dimensional tolerance. Finally, the processing and post-processing related challenges in terms of the suitable models for real time powder-binder interaction study, limitations in depowdering, heat treatment strategy, surface roughness are emphasized.

Habitual smokers are known to be at higher risk for developing oral cancer, which is increasing at an alarming rate globally. Conventionally, oral cancer is associated with high mortality rates, although recent reports show the improved survival outcomes by early diagnosis of disease. An effective prediction system which will enable to identify the probability of cancer development amongst the habitual smokers, is thus expected to benefit sizable number of populations. Present work describes a non-invasive, integrated method for early detection of cellular abnormalities based on analysis of different cyto-morphological features of exfoliative oral epithelial cells. Differential interference contrast (DIC) microscopy provides a potential optical tool as this mode provides a pseudo three dimensional (3-D) image with detailed morphological and textural features obtained from noninvasive, label free epithelial cells. For segmentation of DIC images, gradient vector flow snake model active contour process has been adopted. To evaluate cellular abnormalities amongst habitual smokers, the selected morphological and textural features of epithelial cells are compared with the non-smoker (-ve control group) group and clinically diagnosed pre-cancer patients (+ve control group) using support vector machine (SVM) classifier. Accuracy of the developed SVM based classification has been found to be 86% with 80% sensitivity and 89% specificity in classifying the features from the volunteers having smoking habit.

The present study investigates the efficiency of electrospun montmorillonite-impregnated cellulose acetate nanofiber membranes (MMT-CA-NFM) for adsorptive removal of ciprofloxacin (CIP). Surface morphology, nanofiber characteristics and pHzpc of NFM were analysed by FE-SEM, EDS and pH drift method, respectively. The surface morphology of NFM showed random arrangements of nanofiber. Experiments were performed in batch mode to examine the effect of contact time, adsorbent dose, initial CIP concentration, pH, electrolyte, temperature and agitation speed. It was observed that 60 min contact was sufficient to reach reaction equilibrium and corresponding percentage removal was 76 % when CIP concentration, MMT-CA-NFM dose and solution pH were 10 mg/L, 4 g/L and 6.0 respectively. Equilibrium of the adsorption was described well by both Langmuir and Freundlich isotherm models. The sorption capacity was determined to be 13.8 mg/g. The sorption most closely followed Elovich kinetics model among the models tested. The pH range 6–7.5, where the zwitter ionic nature of CIP was dominant, was found to be most favourable for adsorption. Decrease of ΔG with increase in temperature demonstrated that CIP removal was favourable at higher temperature and positive values of ΔH confirmed endothermic nature of reaction. In continuous mode of operation using fixed bed column, the height of mass transfer zone was found to be 14.96 cm and adsorption rate and capacity constant in continuous mode were also calculated. The regeneration experiments indicated that 10 mM NaOH solution can desorb CIP from exhausted NFM and adsorbent demonstrated good reusability for removal of the antibiotic studied.

Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future.

In the last two decades, additive manufacturing (AM) has made significant progress towards the fabrication of biomaterials and tissue engineering constructs. One direction of research is focused on the development of mechanically stable implants with patient-specific size/shape and another direction has been to fabricate tissue-engineered scaffolds with designed porous architecture to facilitate vascularization. Among AM techniques, three dimensional powder printing (3DPP) is suitable for fabrication of bone related prosthetic devices, while three dimensional plotting (3DPL) is based on extrusion of biopolymers to create artificial tissues. In the present review, we aim to develop a better understanding of the science and engineering aspects of these low temperature AM techniques (3DPP and 3DPL) in the context of the bone-tissue engineering applications. While recognizing multiple property requirements of a 3D scaffold, the central theme is to discuss the critical roles played by the binder and powder properties together with the interplay among processing parameters in the context of the physics of binder-material interaction for the fabrication of implants with predefined architecture having structural complexity. An effort also has been exerted to discuss the existing challenges to translate the design concepts and material/binder formulations to develop implantable scaffolds with a more emphasis on bioceramics and biopolymers. Summarizing, this review highlights the need to adopt intelligent processing approaches and targeted application-specific biocompatibility characterization, while fabricating mechanically stable and biologically functionalized 3D tissue equivalents. (C) 2016 Elsevier B.V. All rights reserved.

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu(III)(OH)3], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosphorylation using the specific MEK inhibitor U0126 partially abrogates the autophagy as well as the clearance of mutant huntingtin protein aggregates mediated by EHNs suggesting that nanorods stimulate the activation of MEK/ERK1/2 signaling pathway during autophagy process. In contrast, another mTOR-independent autophagy inducer trehalose has been found to induce autophagy without activating ERK1/2 signaling pathway. Interestingly, the combined treatment of EHNs and trehalose leads to more degradation of mutant huntingtin protein aggregates than that obtained with single treatment of either nanorods or trehalose. Our results demonstrate the rational that further enhanced clearance of intracellular protein aggregates, needed for diverse neurodegenerative diseases, may be achieved through the combined treatment of two or more autophagy inducers, which stimulate autophagy through different signaling pathways.

In the present paper, we synthesized and characterized four N-donor polypyridyl copper(II) complexes (C1-C4); [Cu(mono-CN-PIP)2]2+ (C1), [Cu(tri-OMe-PIP)2]2+ (C2), [Cu(di-CF3-PIP)2]2+ (C3) and [Cu(DPPZ)2]2+ (C4). The (Calf-Thymus) CT-DNA binding studies depicted that the complexes could interact with DNA via intercalative mode. All the complexes, particularly C3 and C4 attenuated the proliferation as well as migration of various cancer cells, indicating their anti-cancer and anti-metastatic activity. Additionally, chick embryo angiogenesis (CEA) assay exhibited the inhibition of vascular sprouting in presence of C3 and C4, suggesting their potential in inhibiting the blood vessel growth. Mechanistic studies revealed that the complexes induced the excessive production of cellular reactive oxygen species (ROS) leading to apoptosis through up regulation of p53 and downregulation of Bcl-xL, which might be the plausible mechanisms underlying their anti-cancer properties. To understand the feasibility of practical application of anti-cancer copper complexes C3 and C4, in vivo sub-chronic toxicity study (4 weeks) was performed in C57BL6 mice and the results exhibited almost non-toxic effects induced by these complexes in terms of haematology and serum biochemical analyses, suggesting their biocompatible nature. The current study provides the basis for future advancement of other novel biocompatible metal complexes that could be employed for the therapy of different cancers.