Size Dependent Dual Functionality of CeO2 Quantum Dots: A Correlation among Parameters for Hydrogen Gas Sensor and Pollutant Remediation.

The metal oxide-based nanostructures of variable size and shape are found effective in optimizing the gas sensing ability and pollutant degradation. The size induced lattice strain and large band gap in 3 nm CeO2 quantum dots evolved the ability towards hydrogen gas sensing and dye degradation compared to nanopebbles and nanoparticles of sizes 15 ± 3, and 30 ± 12 nm. The smaller CeO2 quantum dots than Debye length was found underlying reason for nearly four times sensor response and selectivity towards reducing hydrogen gases than the oxidizing gases at 1 to 10 ppm level. The lattice strain calculated by Rietveld refinement and W-H analysis was found in-line with the size of CeO2 nanostructures. The enhancement in lattice strain and optical band gap (2.66, 2.78, and 2.89 eV) with decrease in size are found critical for determining the overall efficiency of CeO2 nanostructures for photocatalytic activity, attributed to the strong quantum confinement effect. The higher catalytic activity of 98 % was achieved CeO2 quantum dots in comparison to the 95 % and 94 % obtained for CeO2 nanopebbles and nanoparticles. The impact of change in degradation efficacy and gas sensing ability of different CeO2 nanomaterials is discussed in detail. This work offers a novel and simplistic method to produce CeO2 quantum dots as an efficient sensor for selective detection of H2 gas and photocatalyst. The correlation between size, Debye length, band gap, and lattice strain gives an insight for understanding the underlying detection mechanism for selective detection of reducing gas molecules and efficient pollutant remediation.

Aberrant glycosylation of secretory mucin from the oral cavity in tobacco consumers: a pilot study.

Mucins are a family of high-molecular-weight O-linked glycoproteins which are the primary structural components of mucus and maintain homeostasis in the oral cavity. The present study was conducted as the first step towards establishing a correlation of aberrant mucin glycosylation with tobacco-associated clinical conditions. Tobacco habituates for the study were identified on the basis of type, duration, amount, and frequency of using tobacco products. The secretory mucin and its saccharides were determined from the saliva collected from smokers, smokeless tobacco habituates, and healthy, nonsmoking individuals. On the one hand, the salivary mucin content was markedly reduced in smokeless tobacco habituates with respect to smokers. On the other hand, the amount of sialic acid and fucose moieties of salivary mucin was increased in both smokers and smokeless tobacco habituates compared to the healthy cohort. Furthermore, the duration of tobacco exposure have been identified as the main factor influencing the extent of damage to the oral mucosa in terms of mucin secretion. The reduced secretory mucin content with aberrant glycosylation in the oral cavity may have a significant role in the further development or progression of oral diseases.

Effectiveness of a school-based behavioural change intervention in reducing chronic disease risk factors in Chandigarh, India: a cluster-randomised controlled trial.

Background: Early behavioural risk factors such as unbalanced diets, physical inactivity and tobacco and alcohol consumption lead to chronic diseases in later life. We conducted a cluster-randomised controlled trial to measure the effect of a school-based health-promotion intervention in reducing the behavioural risk factors of chronic diseases. Methods: Twelve public schools in the Chandigarh, India were randomised to the intervention and control arm. Adolescents studying in eighth grade (n = 453), their parents (n = 395) and teachers (n = 94) were recruited for the current study. The Precede-Proceed Model was followed for intervention development. Intervention in each cluster comprised of one classroom session, four physical activity (PA) sessions every week for adolescents and four separate sessions for parents and teachers. Primary outcomes were eight binary or continuous measures of behavioural risk factors among adolescents (n = 359). Physical Activity Questionnaire-Adolescents (PAQ-A) scores were used to estimate physical activity. The ANCOVA based on cluster proportions or means was used to estimate the intervention effect accounting for baseline data. Findings: Among adolescents, the intervention reduced salt intake by 0.5 g/d (95% CI: -0.9, -0.1), proportion of current alcohol users by 5% (95% CI: -9, -0.007), and increased fruit consumption by 18 g/d (95% CI: 5, 30) and PA by 0.2 PAQ-A score (95% CI: 0.07, 0.3). However, the intervention had no effect on the sugar and vegetable intake and on smokers and tobacco chewers. Exploratory analysis revealed that among parents, PA increased by 205 metabolic equivalents task (MET) units (95% CI: 74.5, 336), fruits intake by 20 g/d (95% CI: 6, 34), and vegetable intake by 117 g/d (95% CI: 50.5, 183). Whereas salt consumption decreased by 0.5 g/d (95% CI: 0.15, 0.9) and the proportion of current alcohol users declined by 5% (95% CI: 9, -1) among parents. Vegetable consumption increased by 149 g/d (95% CI: 12, 286) among teachers. Interpretation: The intervention package implemented among adolescents by involving parents and teachers is an effective model for school-based behaviour-change interventions. Funding: MK received partial funding from the George Institute for Global Health, Hyderabad, India for the salt-reduction component of the study.

Explainable deep-neural-network supported scheme for tuberculosis detection from chest radiographs.

Chest radiographs are examined in typical clinical settings by competent physicians for tuberculosis diagnosis. However, this procedure is time consuming and subjective. Due to the growing usage of machine learning techniques in applied sciences, researchers have begun applying comparable concepts to medical diagnostics, such as tuberculosis screening. In the period of extremely deep neural nets which comprised of hundreds of convolution layers for feature extraction, we create a shallow-CNN for screening of TB condition from Chest X-rays so that the model is able to offer appropriate interpretation for right diagnosis. The suggested model consists of four convolution-maxpooling layers with various hyperparameters that were optimized for optimal performance using a Bayesian optimization technique. The model was reported with a peak classification accuracy, F1-score, sensitivity and specificity of 0.95. In addition, the receiver operating characteristic (ROC) curve for the proposed shallow-CNN showed a peak area under the curve value of 0.976. Moreover, we have employed class activation maps (CAM) and Local Interpretable Model-agnostic Explanations (LIME), explainer systems for assessing the transparency and explainability of the model in comparison to a state-of-the-art pre-trained neural net such as the DenseNet.

In Vitro Modulation of Genotoxicity and Oxidative Stress by Polyphenol-Rich Fraction of Chinese Ladder Brake (Pteris vittata L.).

Pteris vittata L. is a terrestrial genus growing in moist, shady forests and on hillsides. The plant has considerable ethnomedicinal importance. Investigations have been carried out on chemical profiling and antioxidant compounds from some genera of pteridophytes but studies on the biological properties of P. vittata are lacking. Therefore, the present study investigates antioxidant, antigenotoxic, and antiproliferative potential of the aqueous fraction of P. vittata (PWE). A battery of assays were carried out to assess the antioxidant potential of the PWE. SOS chromotest and DNA nicking assay were used to evaluate the antigenotoxicity of the fraction. The cytotoxic effect of PWE was analyzed using MTT and Neutral Single Cell Gel Electrophoresis comet assay. EC50 of 90.188 µg/ml, 80.13 µg/ml, 142.836 µg/ml, and 12.274 µg/ml was obtained in DPPH, superoxide anion scavenging, reducing power and lipid peroxidation assays, respectively. PWE was potent in inhibiting Fenton's reagent-induced nicking of pBR322 plasmid. The fraction significantly inhibited hydrogen peroxide (H2O2) and 4-nitroquinoline-N-oxide (4NQO) induced mutagenicity and a reduction in induction factor was found with increased PWE concentration. GI50 of 147.16 µg/ml was obtained in MTT assay in human MCF-7 breast cancer cell line. PWE induced apoptosis as confirmed from confocal microscopy studies. The protective effects can be attributed to the presence of the phytochemicals in PWE. These results will be helpful in the development of functional food characteristics, as well as unravel the benefits of pteridophytes as promoters of health.

Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight.

Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance.

Targeting Akt/NF-κB/p53 Pathway and Apoptosis Inducing Potential of 1,2-Benzenedicarboxylic Acid, Bis (2-Methyl Propyl) Ester Isolated from Onosma bracteata Wall. against Human Osteosarcoma (MG-63) Cells.

Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. This plant is commonly used in the preparation of traditional Ayurvedic drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the present study aimed to investigate the antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata, ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide radical scavenging assay and lipid peroxidation assay with an EC50 value of 95.12 and 80.67 µg/mL, respectively. Silica gel column chromatography of ethyl acetate (Obea) fraction of O. bracteata yielded a pure compound, which was characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was evaluated for the antiproliferative potential against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay and exhibited GI50 values of 37.53 µM, 56.05 µM, and 47.12 µM, respectively. In MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously decreased the mitochondria membrane potential (MMP) potential by arresting cells at the G0/G1 phase, suggesting the initiation of apoptosis. Western blotting analysis revealed the upregulation of p53, caspase3, and caspase9 while the expressions of p-NF-κB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also showed upregulation in the expression of p53 and caspase3 and downregulation in the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis displayed the interaction between BDCe fraction with p53 (-151.13 kcal/mol) and CDK1 (-133.96 kcal/mol). The results of the present work suggest that the BDCe fraction has chemopreventive properties against osteosarcoma (MG-63) cells through the induction of cell cycle arrest and apoptosis via Akt/NF-κB/p53 pathways. This study contributes to the understanding of the utilization of BDCe fraction in osteosarcoma treatment.

Health promotion intervention to prevent risk factors of chronic diseases: Protocol for a cluster randomized controlled trial among adolescents in school settings of Chandigarh (India).

BACKGROUND: Chronic diseases like diabetes, cardiovascular diseases and cancers are on the rise. Most of the risk factors of these diseases commence in Adolescence. Therefore, a cluster randomised controlled trial is designed to evaluate the effect of school-based health promotion intervention on the risk factors of chronic diseases. METHODOLOGY: Considering school as a cluster, twelve schools will be randomly selected from the public schools of Chandigarh, a city in India. After baseline assessment, six schools will be randomly allocated to intervention and six to the control arm. Study participants will be students of 8th grade (age 10-16 years), their parents and teachers. A sample of 360 students (12 clusters x 30 students) has been estimated to provide statistically valid inference. The PRECEDE PROCEED Model will be used to develop health promotion interventions to prevent the use of an unbalanced diet, physical inactivity, alcohol, and tobacco. Interventions will be implemented for six-months in the school setting. For students, the intervention will comprise interactive learning sessions of 30 minutes duration per week and physical activity sessions of 30 minutes duration four times every week. Educational sessions will be conducted for parents and teachers for 30 minutes, four times during the intervention period. Primary outcomes will be changes in the prevalence of behavioural risk factors from pre- to post-intervention. Changes in anthropometric, physiological, and biochemical measures will be the secondary outcomes. The difference-in-difference (DID) method will be used to measure the net change in the outcomes. DISCUSSION: It is essential to understand whether health promotion interventions implemented in the school setting simultaneously targeting adolescents, teachers, and parents are effective. Using the PRECEDE-PROCEED model for planning, implementing, and evaluating the intervention as part of a cluster Randomized Controlled Trial design with DID analysis, could objectively assess the impact.

Predicting clinical outcomes of cancer patients with a p53 deficiency gene signature.

The tumor suppressor p53, encoded by the TP53 gene, is mutated or nullified in nearly 50% of human cancers. It has long been debated whether TP53 mutations can be utilized as a biomarker to predict clinical outcomes of cancer patients. In this study, we applied computational methods to calculate p53 deficiency scores (PDSs) that reflect the inactivation of the p53 pathway, instead of TP53 mutation status. Compared to TP53 mutation status, the p53 deficiency gene signature is a powerful predictor of overall survival and drug sensitivity in a variety of cancer types and treatments. Interestingly, the PDSs predicted clinical outcomes more accurately than drug sensitivity in cell lines, suggesting that tumor heterogeneity and/or tumor microenvironment may play an important role in predicting clinical outcomes using p53 deficiency gene signatures.

Precise control over the silica shell thickness and finding the optimal thickness for the peak heat diffusion property of AuNR@SiO2.

Silica-coated gold nanorods (AuNRs) exhibit significantly enhanced photothermal effects and photoacoustic (PA) signal intensities, which is beneficial for various nanophotonic applications in materials science. However, the silica shell thickness for optimum enhancement is not fully understood and is even controversial depending on the physical state of the silica shell. This is because of the lack of systematic investigations of the nanoscale silica shell thickness and the photothermal effect. This study provides a robust synthetic method to control the silica shell thickness at the nanoscale and the physical state-dependent heat diffusion property. The selected base and solvent system enabled the production of silica-coated AuNRs (AuNR@SiO2) with silica shell thicknesses of 5, 10, 15, 20, 25, 30, 35, and 40 nm. AuNRs with a 20 nm silica shell showed the highest photothermal effect with a 1.45-times higher photothermal efficiency than that of AuNRs without a silica shell. The low density of the silica shell on the AuNRs showed a low photothermal effect and photostability. It was found that the disruption of cetyltrimethyl ammonium bromide (CTAB) layers on the AuNRs was responsible for the low photostability of the AuNRs. The simulation study for the heat diffusion property showed facilitated heat diffusion in the presence of a 20 nm silica shell. In a cell-based study, AuNRs with a 20 nm silica shell showed the most sensitive photothermal effect for cell death. The results of this robust study can provide conclusive conditions for the optimal silica shell thickness to obtain the highest photothermal effect, which will be useful for the future design of nanomaterials in various fields of application.

SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1.

PTOV1 is an oncogenic protein, initially identified in prostate cancer, that promotes proliferation, cell motility, and invasiveness. However, the mechanisms that regulate PTOV1 remain unclear. Here, we identify 14-3-3 as a PTOV1 interactor and show that high levels of 14-3-3 expression, like PTOV1, correlate with prostate cancer progression. We discover an SGK2-mediated phosphorylation of PTOV1 at S36, which is required for 14-3-3 binding. Disruption of the PTOV1-14-3-3 interaction results in an accumulation of PTOV1 in the nucleus and a proteasome-dependent reduction in PTOV1 protein levels. We find that loss of 14-3-3 binding leads to an increase in PTOV1 binding to the E3 ubiquitin ligase HUWE1, which promotes proteasomal degradation of PTOV1. Conversely, our data suggest that 14-3-3 stabilizes PTOV1 protein by sequestering PTOV1 in the cytosol and inhibiting its interaction with HUWE1. Finally, our data suggest that stabilization of the 14-3-3-bound form of PTOV1 promotes PTOV1-mediated expression of cJun, which drives cell-cycle progression in cancer. Together, these data provide a mechanism to understand the regulation of the oncoprotein PTOV1. IMPLICATIONS: These findings identify a potentially targetable mechanism that regulates the oncoprotein PTOV1.

Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers.

With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations.In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body.With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.

Antiproliferative and Oxidative Damage Protection Activities of Endophytic Fungi Aspergillus fumigatus and Chaetomium globosum from Moringa oleifera Lam.

The current study was conducted to evaluate the antiproliferative and oxidative damage protection potential of endophytic fungi Aspergillus fumigatus and Chaetomium globosum isolated from Moringa oleifera. The chloroformic extract (CE) of both the fungi showed dose dependent antiproliferative activity against human prostate adenocarcinoma (PC-3) cell line with (IC50) value of 0.055 mg/ml and 0.008 mg/ml, respectively. Further, CE of both the fungi was studied for their ability to induce apoptosis in PC-3 cell line. Various deformities in the cancerous cells treated with CE of both the fungi have been observed by confocal microscopy which indicates the cell death by apoptosis. Further apoptosis inducing ability of CE of both the fungi was observed using various flow cytometric studies. The chloroformic extract of both the fungi showed slight increase in the level of reactive oxygen species to induce apoptosis. It also showed arrest of cancerous cells at G0/G1 phase of cell cycle to induce apoptosis. The externalization of phosphatidylserine (PS) to induce apoptosis was also observed when analysed using Annexin V-FITC/PI double staining assay where the CE of A. fumigatus and C. globosum showed the total apoptosis of 94.2% and 90.3%, respectively, at the highest tested concentration of GI70. The CE of both the fungi further showed the protective behaviour for plasmid DNA pBR322, when tested for their effect against the oxidative stress caused by the Fenton's reagent. Thus, the studies demonstrated a good antiproliferative and oxidative damage protection potential of the endophytic fungi.

Dietary patterns, food groups and nutrients in Crohn's disease: associations with gut and systemic inflammation.

This study examined associations between dietary intake and gut and systemic inflammation assessed by fecal calprotectin ≤ or > 100 µg/mg (FCP), C-reactive protein ≤ or > 5 mg/L (CRP) and serum cytokine profiles in Crohn's disease (CD) patients in clinical remission. A 3-month observational study was conducted at the University of Calgary in Calgary, Alberta, Canada between 2016 and 2018 in 66 outpatients with CD in clinical remission. FCP was obtained from stool samples at baseline and 3-months and serum CRP and serum cytokines were assessed at 3-months only (n = 41). Dietary intakes were collected using 3-day food records at baseline and 3-months and categorized as: PREDIMED Mediterranean diet scores (pMDS) total and individual components, the dietary inflammatory index (DII), food groups, and common micro- and macro-nutrients. Statistical models were developed to identify relationships between dietary factors and FCP, CRP and cytokine levels. Daily intake of leafy green vegetables was associated with FCP ≤ 100 µg/mg (p < 0.05). Increasing omega 6:3 ratio was associated with CRP ≤ 5 mg/L (p = 0.02). Different cytokines were significantly associated with various dietary variables. Future studies in patients with greater disease activity should be undertaken to explore these relationships.

trans-Anethole Abrogates Cell Proliferation and Induces Apoptosis through the Mitochondrial-Mediated Pathway in Human Osteosarcoma Cells.

trans-Anethole, the major bioactive component of Illicium verum Hook. commonly known as star anise exhibits various pharmacological activities including anti-inflammatory, antimicrobial, insecticidal, and antitumor. Osteosarcoma is an extremely aggressive malignant bone tumor that affects children and young adults and accounts for around 60% of all sarcomas. The study was planned to evaluate the potential of trans-Anethole against Human osteosarcoma cell line MG-63. The antiproliferative activity of trans-Anethole was assessed by MTT assay. trans-Anethole exhibited apoptotic cell death as monitored by confocal/electron microscopy and flow cytometry studies. Modulation of gene expression was studied by Western blot and RT-PCR analysis. The present study revealed that trans-Anethole inhibited osteosarcoma proliferation in a dose-dependent manner with a GI50 value of 60.25 µM and showed pro-apoptotic activity as analyzed by Annexin V-FITC/PI assay. Flow cytometric analysis revealed that trans-Anethole induced cell cycle arrest at the G0/G1 phase with the generation of reactive oxygen species and reduction in mitochondrial membrane potential (ΔΨm). Immunoblotting results showed the increased expression of caspase-9/-3, p53, and decreased expression of Bcl-xL suggesting the involvement of the p53 and mitochondrial intrinsic pathway. This work provides a rationale that trans-Anethole might be considered as a promising chemotherapeutic/nutraceutical agent for the management of osteosarcoma.Highlightstrans-Anethole inhibited cell growth and caused G0/G1 arrest in Human osteosarcoma MG-63 cell line.trans-Anethole led to the loss of mitochondrial membrane permeability along with ROS generation.trans-Anethole upregulates the expression of p53, Caspase-9/-3, and downregulate Bcl-xL expression.

Novel Vitamin E TPGS based docetaxel nanovesicle formulation for its safe and effective parenteral delivery: Toxicological, pharmacokinetic and pharmacodynamic evaluation.

Docetaxel (DTX) is a highly lipophilic, BCS class IV drug with poor aqueous solubility (12.7 µg/mL). Presently, only injectable formulation is available in the market which uses a large amount of surfactant (Tween 80) and dehydrated alcohol as a solubilizer. High concentrations of Tween 80 in injectable formulations are associated with severe consequences i.e. nephrotoxicity, fluid retention, and hypersensitivity reactions. The present study aims to eliminate Tween 80, thus novel biocompatible surfactant Vitamin E TPGS based nanovesicle formulation of DTX (20 mg/mL) was developed and evaluated for different quality control parameters. Optimized nanovesicular formulation (NV-TPGS-3) showed nanometric size (102.9 ± 2.9 nm), spherical vesicular shape, high drug encapsulation efficiency (95.2 ± 0.5%), sustained-release profile and high dilution integrity with normal saline. In vitro cytotoxicity assay, showed threefold elevation in the IC50 value of the optimized formulation in comparison to the commercial formulation. Further, no mortality and toxicity were observed during 28 days repeated dose sub-acute toxicity studies in Swiss albino mice up to the dose of 138 mg/kg, whereas, commercial formulation showed toxicity at 40 mg/kg. In addition, in vivo anticancer activity on Ehrlich Ascites Carcinoma induced mice showed a significant tumour growth inhibition of 76.3 ± 5.3% with the NV-TPGS-3 treatment when compared to Ehrlich Ascites Carcinoma control. Results demonstrated that the developed Vitamin E TPGS based nanovesicular formulation of DTX could be a better alternative to increase its clinical uses with improved therapeutic efficacy, reduced toxicity and dosing frequency, and sustained drug release behaviour.

Onosma bracteata Wall. induces G0/G1 arrest and apoptosis in MG-63 human osteosarcoma cells via ROS generation and AKT/GSK3ß/cyclin E pathway.

Onosma bracteata Wall. (Boraginaceae), commonly known as "gaozaban" is a highly valuable medicinal herb, useful in the treatment of body swellings, abdominal pain, eye-related problems, fever, and urinary calculi. The present study was performed to investigate the antioxidant properties of extract/fractions, viz. ethanol (Obeth) extract, hexane (Obhex) fraction, chloroform (Obcl) fraction, ethyl acetate (Obea) fraction, butanol (Obbu) fraction, and aqueous (Obaq) fraction isolated from O. bracteata. Obea fraction showed stronger free radical quenching ability in various antioxidant assays, as compared to the other fractions. Obea fraction with effective free radical-scavenging properties was further evaluated for the antiproliferative activity against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay. Obea fraction showed strong cytotoxicity with GI50 value of 88.56, 101.61, and 112.7 µg/ml towards MG-63, IMR-32, and A549 cells respectively. Mechanistic studies revealed that Obea fraction in osteosarcoma MG-63 cells increased reactive oxygen species (ROS) level and reduced mitochondrial membrane potential. In the presence of Obea, the cells were found to be arrested in the G0/G1 phase in a dose-dependent manner which is also confirmed by the enhancement in the early apoptotic cell population in flow cytometer analysis. Western blotting demonstrated the decrease in expression of p-NFκB, COX-2, p-Akt, and Bcl-xL, whereas upregulation was observed in the expression of GSK-3ß, p53, caspase-3, and caspase-9 proteins. RT-qPCR studies revealed downregulation of Bcl-2, cyclin E, CDK2, and mortalin gene expression and upregulation in the expression of p53 genes. The antioxidant and cytotoxic potential of Obea was attributed to the presence of catechin, kaempferol, onosmin A, and epicatechin, as revealed by HPLC analysis. This is the first report regarding the antiproliferative potential of O. bracteata against osteosarcoma.

Modulation of mutagenicity in Salmonella typhimurium and antioxidant properties and antiproliferative effects of fractions from Cassia fistula L. on human cervical HeLa and breast MCF-7 cancer cells.

The present study investigated the antimutagenic, antioxidant, and antiproliferative properties of extracts of Cassia fistula prepared by sequentially fractionation of 80% methanolic (CaLM extract) extract of C. fistula leaves, namely CaLH (hexane), CaLC (chloroform), CaLE (ethyl acetate), CaLB (n-butanol), and CaLA (aqueous) fractions. The antimutagenicity of the fractions was tested against mutagens viz. S9-independent, namely 4-nitro-o-phenylenediamine (TA98) and sodium azide (TA100) and S9-dependent, 2-AF (2-aminofluorene). Among the tested fractions, CaLE fraction showed a potent efficacy with an inhibition percentage of 85.57% (TA98) and 89.93% (TA100) against the mutagenicity induced by 2-aminofluorene. The CaLE fraction could significantly scavenge free radicals in various assays, namely DPPH, lipid peroxidation inhibition, and superoxide anion radical scavenging assays with an IC50 of 12.80, 144, and 257.3 µg/ml respectively. The antiproliferative potential of the effective CaLE fraction was assessed using MTT assay against HeLa and MCF-7 cancer cells with GI50 value of 243.4 and 324.6 µg/ml respectively. The fraction exhibited remarkable apoptosis-inducing effects through the externalization of phosphatidylserine in HeLa cells as analyzed by annexin V-FITC/PI double staining assay. The HPLC analysis of CaLE revealed the presence of catechin, epiafzelechin, and chlorogenic acid which are responsible for its antimutagenic and antiproliferative efficacy. Graphical abstract.

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness.

Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 106 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN®). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

Antiproliferative and apoptogenic effects of Cassia fistula L. n-hexane fraction against human cervical cancer (HeLa) cells.

The current study was performed to evaluate the antiproliferative and apoptosis-inducing potential of n-hexane fraction from Cassia fistula L. (Caesalpinioideae) fruits. The antiproliferative property of the fraction was determined by MTT assay against cancer cell lines including HeLa, MG-63, IMR-32, and PC-3 with GI50 value of 97.69, 155.2, 143, and 160.2 µg/ml respectively. The fraction was further explored for its apoptotic effect using confocal, SEM, and flow cytometry studies in HeLa cells. It was observed that the treatment of fraction revealed fragmentation of DNA, chromatin condensation, membrane blebbing, and formation of apoptotic bodies in a dose-dependent manner. The fraction also showed a remarkable increase in the level of ROS, mitochondrial depolarization and G0/G1 phase cell cycle arrest, and induction in the phosphatidylserine externalization analyzed using Annexin V-FITC/PI double staining assay in HeLa cells. Kaempferol, Ellagic acid, and Epicatechin are the major phytoconstituents present in the fraction as revealed by the HPLC. The treatment of n-hexane fraction showed downregulation in the gene expression of Bcl-2 and upregulation in the expression level of p53, Bad, and caspase-3 genes analyzed using semi-quantitative RT-PCR in HeLa cells. These results suggest that n-hexane fraction from C. fistula inhibited the proliferation of cervical cancer cells efficiently by the induction of apoptosis. Graphical abstract.