Phase II control charts for monitoring the depth-ratio of ball-bearings involving three normal variables.

This paper investigates the problem of monitoring the ratio involving three variables, jointly distributed as trivariate normal. The Shewhart-type and two exponentially weighted moving average (EWMA) type schemes for monitoring depth ratio are proposed. The ratio of a normal variable to the average of two other normal variables has wide applications in natural science, production, and engineering. It is defined with slightly different terminology in various contexts, such as depth or aspect ratios. In modern bearing manufacturing, the aspect ratio of width to the average of inner and outer diameters can be an essential indicator of product quality and process stability. While there are many helpful existing charts for monitoring the three components separately or jointly when these characteristics follow a normal distribution, the ratio aspect is often ignored. The Shewhart-type schemes' exact and approximated control limits are considered and analyzed. Numerical results based on Monte-Carlo are conducted using the average run length as a metric with different values of in-control ratio and correlation between the three variables. An application based on the parts manufacturing data illustrates the implementation design of the two control charts. The real-life data analysis shows the efficacy of the proposed monitoring schemes in practice.

Diclofenac enhances Boron nitride nanoparticle toxicity in freshwater green microalgae, Scenedesmus obliquus: Elucidating the role of oxidative stress.

Boron nanoparticles have numerous medical, industrial, and environmental applications as potential nanomaterials. Given the inevitable release of these particles in aquatic environments, they can combine with other pollutants like pharmaceuticals. Therefore, it is necessary to investigate their combined detrimental effects on freshwater biota. This study examined the joint impacts of Boron nitride nanoparticles (BNNPs) and Diclofenac (DCF) on freshwater microalgae Scenedesmus obliquus. Three different concentrations of BNNPs (0.1, 1, and 10 mg L-1) were mixed with 1 mg L-1 of DCF and were treated with algal cells, and biochemical analyses were performed. A concentration-dependent decrease in algal cell viability was observed after a 72-h interaction period with BNNPs and their binary combinations. The maximum toxic effects were observed for the highest combination of BNNPs + DCF, i.e., 10 mg L-1 BNNPs + 1 mg L-1 DCF. Similarly, an increase in the oxidative stress parameters and antioxidant enzyme activity was observed, which correlated directly to the decline in cell viability. The algal cells also showed reduced photosynthetic efficiency and electron transfer rate upon interaction with BNNPs. The results of this research emphasize the importance of considering the negative consequences of emerging pollutants and their combinations with other pollutants, BNNPs, and DCF as part of a thorough evaluation of ecotoxicity in freshwater algal species.

Tailored-Biomaterials Based Potential Strategies for Cardiovascular Disease.

Cardiovascular disease is a significant health concern worldwide, and varied effective treatment and prevention methods have been developed. Among these, tailored biomaterials-based strategies such as stents, scaffolds, patches, and drug delivery systems have emerged as a promising avenue. These devices are designed to match the mechanical and biological mechanisms of the cardiovascular system, ensuring optimal performance and compatibility. By effectively treating or preventing cardiovascular diseases, these devices have the potential to improve patient health outcomes significantly. They can restore blood flow by addressing blocked arteries and regenerate damaged cardiac tissue by delivering bioactive agents or cells directly to the affected area in a targeted, sustained, and controllable manner. Therefore, the objective of this article is to summarize the available evidence on these tailored biomaterial-based tunable cardiovascular devices. This knowledge can help to transform cardiovascular medicine for the treatment or prevention of cardiovascular disease and restore cardiac function to improve patients' quality of life.

Evaluating the role of soil EPS in modifying the toxicity potential of the mixture of polystyrene nanoplastics and xenoestrogen, Bisphenol A (BPA) in Allium cepa L.

The coexistence of emerging pollutants like nanoplastics and xenoestrogen chemicals such as Bisphenol A (BPA) raises significant environmental concerns. While the individual impacts of BPA and polystyrene nanoplastics (PSNPs) on plants have been studied, their combined effects are not well understood. This study examines the interactions between eco-corona formation, physicochemical properties, and cyto-genotoxic effects of PSNPs and BPA on onion (Allium cepa) root tip cells. Eco-corona formation was induced by exposing BPA-PSNP mixtures to soil extracellular polymeric substances (EPS), and changes were analyzed using 3D-EEM, TEM, FTIR, hydrodynamic diameter, and contact angle measurements. Onion roots were treated with BPA (2.5, 5, and 10 mgL-1) combined with plain, aminated, and carboxylated PSNPs (100 mgL-1), with and without EPS interaction. Toxicity was assessed via cell viability, oxidative stress markers (superoxide radical, total ROS, hydroxyl radical), lipid peroxidation, SOD and catalase activity, mitotic index, and chromosomal abnormalities. BPA alone increased cytotoxic and genotoxic parameters in a dose-dependent manner. BPA with aminated PSNPs exhibited the highest toxicity among the pristine mixtures, revealing increased chromosomal abnormalities, oxidative stress, and cell mortality with rising BPA concentrations. In-silico experiments demonstrated the relationship between superoxide dismutase (SOD), catalase enzymes, PSNPs, BPA, and their mixtures. EPS adsorption notably reduced cyto-genotoxic effects, lipid peroxidation, and ROS levels, mitigating the toxicity of BPA-PSNP mixtures.

Release kinetic study of microplastics from N95 face masks and consequent effects on freshwater alga Scenedesmus obliquus.

The uncontrolled disposal of N95 face masks, widely used during the recent COVID-19 pandemic can release significant amounts of microplastics and other additives into aquatic bodies. This study aimed to: (i) to quantify and analyze the released microplastics and heavy metals from N95 face masks weathered for various time periods (24, 48, 72, 96, 120, and 144 h) and (ii) to assess the cytotoxicity potential of the leachates on a model organism, freshwater alga Scenedesmus obliquus. The mask leachates contained microplastics, polypropylene in different shapes and sizes, and heavy metals like Cu, Cd, and Zn. The leachates significantly reduced cell viability and increased reactive oxygen species (ROS) generation, antioxidant enzyme activity, and membrane damage. The effects were also accompanied by a significant drop in the photosynthetic yield. All of the examined parameters indicated a dose-response relationship, with longer leaching periods resulting in higher microplastic concentrations. Mask leachates severely damaged the structural integrity of the algal cells, as seen in scanning electron microscopy images. The findings of our study confirm that the releases from disposable N95 face masks pose a severe threat to freshwater microalgae, and the cascading effects would harm the aquatic ecosystems.

Influence of algal-extracellular polymeric substances (EPS) on the pristine and combined toxicity of TiO2 NPs and PSNPs in Artemia salina: Eco-corona enhances the toxic effects.

The study on the influence of Natural Organic Matter (NOM) over the individual and combined effects of different nanomaterials on marine species is pertinent. The current study explores the role of Extracellular Polymeric Substances (EPS) in influencing the individual and combined toxic effects of polystyrene nanoplastics (PSNPs) viz. aminated (NH2-PSNPs), carboxylated (COOH-PSNPs), and plain PSNPs and TiO2 NPs in the marine crustacean, Artemia salina. A. salina was interacted with pristine PSNPs, pristine TiO2 NPs, EPS incubated PSNPs, EPS incubated TiO2 NPs, binary mixture of PSNPs and TiO2 NPs, and EPS adsorbed binary mixture of PSNPs and TiO2 NPs for 48 h. The present study proves that, when compared to the pristine toxicity of PSNPs and TiO2 NPs, the coexposure of TiO2 NPs with PSNPs resulted in increased toxicity. The adsorption of algal EPS on the NMs (both in their pristine and combined forms) significantly increased the toxic nature of the NMs against A. salina. It was observed that with an increase in the hydrodynamic diameter of the particles, the mortality, oxidative stress, and ingestion of the NMs by A. salina increased. The uptake of Ti by A. salina from 8 mg/L TiO2 NPs, EPS adsorbed 8 mg/L TiO2 NPs, 8 mg/L TiO2 NPs + NH2-PSNPs and the EPS adsorbed mixture of 8 mg/L TiO2 NPs, 8 mg/L TiO2 NPs + NH2-PSNPs was observed to be 0.043, 0.047, 0.186, and 0.307 mg/g of A. salina. The adsorption of algal EPS on the NMs (both in their pristine and combined forms) significantly increased the toxic nature of the NMs against A. salina. The major outcomes from the current study highlight the role of EPS in exacerbating the toxicity of NMs in marine crustaceans.

Time dependent release of microplastics from disposable face masks poses cyto-genotoxic risks in Allium cepa.

The use of disposable face masks (DFMs) increased during the COVID-19 pandemic and has become a threat to the environment due to the release of microplastics (MPs). Although many reports have characterized and explored the release of MPs from DFMs and their effects in aquatic ecosystems, there is a lack of investigation into the effects in terrestrial plants. This report aims to fill this research gap by characterizing whole mask leachates (WMLs) collected at different time points and examining their toxicity on Allium cepa, a terrestrial model plant. Various analytical techniques including FE-SEM, FT-IR, and Raman spectroscopy were used to identify MPs in WMLs. The MPs are composed of polypropylene mostly and the concentration of smaller-sized MPs increased with leachate release time. The WMLs showed a MP concentration-dependent cytogenotoxic effect (72 %, 50 %, and 31 %, on 1, 5, and 11-day WMLs, respectively) on A. cepa root cells due to elevated oxidative stress (19 %, 45 %, and 70 %, on 1, 5, and 11-day WMLs, respectively). Heavy metal content of the WMLs was negligible and, thus, not a significant contributor to toxicity in the plant. Overall, this report highlights the fate of DFMs in the environment and their biological impacts in a model plant.

The impact of nTiO2 and GO (graphene oxide), and their combinations, on freshwater Chlorella sp.: a comparative study in lake water and BG-11 media.

Titanium dioxide nanoparticles (nTiO2) and graphene oxide (GO) are extensively used nanomaterials in various products and applications. Freshwater ecosystems are a crucial sink for these pollutants, posing severe threats to aquatic organisms. Although multiple studies have investigated the pristine toxicity of nTiO2 and GO in freshwater organisms, the combined toxicity of these materials remains unexplored. Interaction media is a crucial factor in evaluating toxicity nanomaterial toxicity towards algae. In this study, we have investigated the comparative effect of sterilized and filtered freshwater and BG-11 medium on the pristine and combined toxicity of nTiO2 and GO on freshwater algae Chlorella sp. Results indicated that the combination of nTiO2 and GO showed more toxicity when compared to their respective pristine forms. This could be due to the additive effect exhibited by nTiO2 and GO on Chlorella sp. The enhanced growth inhibition for the combined toxicity was in the order of 1 mg L-1 nTiO2 + 1 mg L-1 GO > 1 mg L-1 nTiO2 + 0.1 mg L-1 GO > 0.1 mg L-1 nTiO2 + 1 mg L-1 GO > 0.1 mg L-1 nTiO2 + 0.1 mg L-1 GO. All test groups that interacted in BG-11 media exhibited less toxicity when compared to corresponding groups in the lake water medium. This could be attributed to the cushioning effect of BG-11 medium, providing supplementary nutrition to the algal cells. This signifies that the environmentally relevant conditions could be more detrimental than the laboratory conditions. This study elucidates valuable insights into the potential detrimental effects associated with the combination of nTiO2 and GO on freshwater algae. Furthermore, we have evaluated the growth inhibition, oxidative stress, and photosynthetic activity of Chlorella sp. in both environmentally relevant interaction medium and well-defined culture medium.

Assessing the role of the graphene family nanomaterials (GFNs: Graphene, GO, rGO) in modifying the toxicity potential and environmental risk of flame retardant, tetrabromobisphenol-A (TBBPA) in the marine microalgae Chlorella sp.

In recent years, a growing concern has emerged regarding the environmental implications of flame retardants (FRs) like tetrabromobisphenol-A (TBBPA) and graphene family nanomaterials (GFNs), such as graphene, graphene oxide (GO), and reduced graphene oxide (rGO), on marine biota. Despite these substances' well-established individual toxicity profiles, there is a notable gap in understanding the physicochemical interactions within the binary mixtures and consequent changes in the toxicity potential. Therefore, our research focuses on elucidating the individual and combined toxicological impacts of TBBPA and GFNs on the marine alga Chlorella sp. Employing a suite of experimental methodologies, including Raman spectroscopy, contact angle measurements, electron microscopy, and chromatography, we examined the physicochemical interplay between the GFNs and TBBPA. The toxicity potentials of individual constituents and their binary combinations were assessed through growth inhibition assays, quantifying reactive oxygen species (ROS) generation and malondialdehyde (MDA) production, photosynthetic activity analyses, and various biochemical assays. The toxicity of TBBPA and graphene-based nanomaterials (GFNs) was examined individually and in combinations. Both pristine TBBPA and GFNs showed dose-dependent toxicity. While lower TBBPA concentrations exacerbated toxicity in binary mixtures, higher TBBPA levels reduced the toxic effects compared to pristine TBBPA treatments. The principal mechanism underlying toxicity was ROS generation, resulting in membrane damage and perturbation of photosynthetic parameters. Cluster heatmap and Pearson correlation were employed to assess correlations between the biological parameters. Finally, ecological risk assessment was undertaken to evaluate environmental impacts of the individual components and the mixture in the algae.

Adsorptive removal of norfloxacin from aqueous solutions by Fe/Cu CNS-embedded alginate-carboxymethyl cellulose-chitosan beads.

The pervasive application of pharmaceuticals in aquatic environments has acquired much focus owing to their nonbiodegradability and eco-toxicity, which might readily destroy the ecological balance. Developed chitosan-coated Fe-Cu CNS alginate-CMC beads (NBs) were utilized in this study to adsorb the quinolone antibiotic norfloxacin (NOR) from water for the first time. Under ideal conditions (CNOR: 20 mg L-1; sorbent conc.: 2000 mg L-1; sorbent dosage: 0.15 g; interaction time: 300 min; solution pH: 6.0), about 86% NOR removal was achieved through batch mode. The removal performance for NOR was examined concerning pH, ionic strength, and coexisting micropollutants. The greatest NOR removal was attained on NBs with the greatest Langmuir adsorption capacity of 355 mg g-1 due to numerous mechanisms such as sorbent pore filling, electrostatic attraction, π-π attraction and hydrogen bonding. Studies using environmentally significant algae, such as Scenedesmus sp., to analyze the residual toxicity of treated NOR solution revealed a significant reduction in their toxic effects. Current research has demonstrated that nanocomposite beads are an excellent wastewater treatment material with promising industrial applications due to their ease of synthesis, exceptional surface adsorption properties, stability, and environmentally friendly reaction.

Genetically Engineered Probiotic Limosilactobacillus reuteri Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer.

Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of Limosilactobacillus reuteri in releasing IL-22 (LR-IL-22) as an effective radiation mitigator, and we have now assessed its effect in an ovarian cancer mouse model. We hypothesized that an LR-IL-22 gavage would enable intestinal radioprotection by modifying the tumor microenvironment and, subsequently, improving overall survival in female C57BL/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer. Herein, we report that the LR-IL-22 gavage not only improved overall survival in mice when combined with a PD-L1 inhibitor by inducing differential gene expression in irradiated stem cells but also induced PD-L1 protein expression in ovarian cancer cells and mobilized CD8+ T cells in whole abdomen irradiated mice. The addition of LR-IL-22 to a combined treatment modality with fractionated whole abdomen radiation (WAI) and systemic chemotherapy and immunotherapy regimens can facilitate a safe and effective protocol to reduce tumor burden, increase survival, and improve the quality of life of a locally advanced ovarian cancer patient.

Naturally weathered polypropylene microplastic from environment and its toxic behaviour in Artemia salina.

The increasing use of polypropylene (PP) in consumer products leads to the microplastic (PP MPs) contamination of the aquatic ecosystems. Comprehensive toxicological studies of weathered/aged and new PP MPs with Artemia salina are a need of the hour. Our study explores the toxicological differences between naturally weathered (aged) and prepared new PP MPs on Artemia salina. Both the weathered and new PP MPs were prepared using controlled grinding and sieving at ≤ 125 µm. Artemia salina was treated with different concentrations (0.25, 0.5, and 1 mg/mL) of PP MP particles for up to 48 h. The uptake of weathered PP MP particles by Artemia salina was higher than the new PP MPs. The accumulation of PP MP particles was found in the intestine. There was increased oxidative stress recorded in the animal treated with the weathered PP MPs than the new PP MPs. Artemia salina treated with weathered PP MPs showed higher ROS generation and increased, activity of oxidative enzymes like LPO, SOD, and CAT. Collectively, our findings underscore the detrimental effects of weathered and prepared new PP MPs on Artemia salina, which is an ecologically significant species of zooplankton. There is an urgent need and effective measures required to address plastic disposal strategies in an environmentally safe manner.

Polystyrene nanoplastics alter the ecotoxicological effects of diclofenac on freshwater microalgae Scenedesmus obliquus.

Due to the escalating risk of plastic pollution, nanoplastics have attracted considerable attention in the recent past. They can co-exist and interact with other contaminants like pharmaceuticals in the aquatic environment. Therefore, it is pertinent to understand how these pollutants interact with one another in the ecosystem. The current study examined the individual and combined effects of fluorescent polystyrene nanoplastics (FNPs) and diclofenac (DCF) on Scenedesmus obliquus using a full factorial design. The toxicity of S. obliquus significantly increased in a dose-dependent manner upon exposure to pristine forms of DCF and FNPs. The major cause of individual toxicity of DCF and FNPs in S. obliquus was oxidative stress. In the combined toxicity tests when FNPs (0.01, 0.1, and 1 mg L-1) and DCF (1 mg L-1) were mixed, a synergistic effect was noted compared to the respective pristine FNPs. However, when the DCF concentration in the mixture was decreased to 0.25 mg L-1, the combined toxicity with FNPs (0.01, 0.1, and 1 mg L-1) reduced indicating an antagonistic effect. The independent action model also showed an antagonistic effect for low-dose combinations of DCF and a synergistic effect for high-dose combinations. The estimation of oxidative stress parameters, antioxidant enzyme activity, and photosynthetic pigment content in the algae further validated the cytotoxicity data. The mean hydrodynamic diameter and surface charge analyses further indicated that the colloidal stability of the FNPs in the medium was affected when they were combined with DCF. The key reason for differences in the cytotoxicity of combinations could be observed variations in the aggregation of FNPs and differential adsorption patterns of DCF on the FNPs. These factors efficiently altered cell-particle interactions in the mixture demonstrating a hormesis effect. Thus, this current study highlighted the hazardous nature of the nanoplastics and their co-exposure risks with pharmaceuticals on microalgae in freshwater environments.

EPS-corona formation on graphene family nanomaterials (GO, rGO and graphene) and its role in mitigating their toxic effects in the marine alga Chlorella sp.

GFNs have widespread applications but can harm marine systems due to excessive use and improper disposal. Algae-secreted EPS can mitigate nanomaterial harm, but their impact on GFN toxicity is understudied. Hence, in the present study, we investigated the toxicity of three GFNs, graphene oxide (GO), reduced graphene oxide (rGO), and graphene, in pristine and EPS-adsorbed forms in the marine alga Chlorella sp. At an environmentally relevant concentration of 1 mgL-1, all three GFNs induced considerable oxidative stress and impeded growth and photosynthetic activity of the algae. The order of the toxic potential followed GO > rGO > graphene. The various facets of adsorption of EPS (1:1 mixture of loosely bound, and tightly bound EPS) on GFNs were investigated through microscopy, surface chemical analyses, fluorescence quenching studies, and isotherm and kinetics studies. Amongst the pristine GFNs treated with algal cells, GO was found to exert the maximum negative effects on algal growth. Upon adsorption of EPS over the GFNs, a significant decline in growth inhibition was observed compared to the respective pristine forms which strongly correlated with reduced oxidative stress and enhanced photosynthetic parameters in the cells. The formation of a layer of eco-corona after interaction of GFNs with EPS possibly caused a barrier effect which in turn diminished their toxic potential. The findings from the present investigation offer valuable insights into the environmental toxicity of GFNs and show that the eco-corona formation may lessen the risk posed by these materials in the marine environment.

The comparative effects of visible light and UV-A radiation on the combined toxicity of P25 TiO2 nanoparticles and polystyrene microplastics on Chlorella sp.

The ubiquitous presence of TiO2 nanoparticles (nTiO2) and microplastics (MPs) in marine ecosystems has raised serious concerns about their combined impact on marine biota. This study investigated the combined toxic effect of nTiO2 (1 mg/L) and NH2 and COOH surface functionalized polystyrene MPs (PSMPs) (2.5 and 10 mg/L) on Chlorella sp. All the experiments were carried out under both visible light and UV-A radiation conditions to elucidate the impact of light on the combined toxicity of these pollutants. Growth inhibition results indicated that pristine nTiO2 exhibited a more toxic effect (38%) under UV-A radiation when compared to visible light conditions (27%). However, no significant change in the growth inhibitory effects of pristine PSMPs was observed between visible light and UVA radiation conditions. The combined pollutants (nTiO2 + 10 mg/L PSMPs) under UV-A radiation exhibited more growth inhibition (nTiO2 + NH2 PSMPs 66%; nTiO2 + COOH PSMPs 50%) than under visible light conditions (nTiO2 + NH2 PSMPs 55%; TiO2 + COOH PSMPs 44%). Independent action modeling indicated that the mixture of nTiO2 with PSMPs (10 mg/L) exhibited an additive effect on the algal growth inhibition under both the light conditions. The photoactive nTiO2 promoted increased production of reactive oxygen species under UV-A exposure, resulting in cellular damage, lipid peroxidation, and impaired photosynthesis. The effects were more pronounced in case of the mixtures where PSMPs added to the oxidative stress. The toxic effects of the binary mixtures of nTiO2 and PSMPs were further confirmed through the field emission electron microscopy, revealing specific morphological abnormalities. This study provides valuable insights into the potential risks associated with the combination of nTiO2 and MPs in marine environments, considering the influence of environmentally relevant light conditions and the test medium.

Investigating the transport and colloidal behavior of Fe3O4 nanoparticles in aqueous and porous media under varying solution chemistry parameters.

The possible adverse effects of engineered iron oxide nanoparticles, especially magnetite (Fe3O4 NP), on human health and the environment, have raised concerns about their transport and behavior in soil and water systems. Accumulating these NPs in the environment can substantially affect soil and water quality and the well-being of aquatic and terrestrial organisms. Therefore, it is essential to examine the factors that affect Fe3O4 NP transportation and behavior in soil and water systems to determine their possible environmental fate. In this work, experiments were conducted in aqueous and porous media using an environmentally relevant range of pH (5, 7, 9), ionic strength (IS) (10, 50, 100 mM), and humic acid (HA) (0.1, 1, 10 mg L-1) concentrations. Fe3O4 NPs exhibited severe colloidal instability at pH 7 (⁓ = pHPZC) and showed an improvement in apparent colloidal stability at pH 5 and 9 in aquatic and terrestrial environments. HA in the background solutions promoted the overall transport of Fe3O4 NPs by enhancing the colloidal stability. The increased ionic strength in aqueous media hindered the transport by electron double-layer compression and electrostatic repulsion; however, in porous media, the transport was hindered by ionic compression. Furthermore, the transport behavior of Fe3O4 NPs was investigated in different natural waters such as rivers, lakes, taps, and groundwater. The interaction energy pattern in aquatic systems was estimated using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. This study showed the effects of various physical-chemical conditions on Fe3O4 NP transport in aqueous and porous (sand) media.

Eco-corona formation diminishes the cytogenotoxicity of graphene oxide on Allium cepa: Role of soil extracted-extracellular polymeric substances in combating oxidative stress.

Graphene oxide (GO) is widely acknowledged for its exceptional biological and industrial applications. However, its discharge into the environment negatively impacts the ecosystem. This study aimed to investigate the toxicity of GO in Allium cepa root tip cells and the role of extracellular polymeric substances (EPS) in modulating its toxic effects. To evaluate toxicity, various endpoints like cell viability using Evans blue dye, cytotoxicity (mitotic index), genotoxicity (chromosomal aberrations), and oxidative stress assessments (total ROS, superoxide, hydroxyl radical production, and lipid peroxidation) were considered. The results suggest that pristine GO caused a dose-dependent increase in various toxicity parameters, especially the genotoxic effects. Oxidative stress generation by GO is proposed to be the principal mode of action. The EPS-corona formed on GO could potentially counteract the toxic effects, substantially reducing the oxidative stress within the cells.

Chemical Carcinogen (Dimethyl-benzanthracene) Induced Transplantable Cancer in Fanconi Anemia (Fanca-/-) Mice.

BACKGROUND/AIM: Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations. MATERIALS AND METHODS: Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA). RESULTS: A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells. CONCLUSION: This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer.

Comparative toxicity assessment of individual, binary and ternary mixtures of SiO2, Fe3O4, and ZnO nanoparticles in freshwater microalgae, Scenedesmus obliquus: Exploring the role of dissolved ions.

Metal oxide nanoparticles (NPs) are considered among the most prevalent engineered nanomaterials. To have a deeper understanding of the mode of action of multiple metal oxide nanoparticles in mixtures, we have used a unicellular freshwater microalga Scenedesmus obliquus as a model organism. The toxicity of silicon dioxide (SiO2), iron oxide (Fe3O4), and zinc oxide (ZnO) NPs was studied individually as well as in their binary (SiO2 + Fe3O4, Fe3O4 + ZnO, and ZnO + SiO2) and ternary (SiO2 + Fe3O4 + ZnO) combinations. The effects of metal ions from ZnO and Fe3O4 were investigated as well. The results observed from the study, showed that a significant amount of toxicity was contributed by the dissolved ions in the mixtures of the nanoparticles. Decreases in the cell viability, ROS generation, lipid peroxidation, antioxidant enzyme activity, and photosynthetic efficiency were analyzed. Among all the individual particles, ZnO NPs showed the maximum effects and increased the toxicities of the binary mixtures. The binary and ternary mixtures of the NPs clearly showed increased toxic effects in comparison with the individual entities. However, the ternary combination had lesser toxic effects than the binary combination of Fe3O4 + ZnO. The decline in cell viability and photosynthetic efficiency were strongly correlated with various oxidative stress biomarkers emphasizing the crucial role of reactive oxygen species in inducing the toxic effects. The findings from this study highlight the importance of evaluating the combinatorial effects of various metal oxide NPs as part of a comprehensive ecotoxicity assessment in freshwater microalgae.

Formulation and characterization of cisplatin-loaded hydroxyl functionalized single-walled carbon nanotubes for targeting gastric cancer stem cells.

Chemotherapy is the most commonly used therapeutic method for treating many malignancies including gastric cancer. Due to their non-specific and non-targeted drug delivery, it causes resistance leading to cancer progression, relapse, and metastasis of cancer. To overcome this problem we carried out a study aimed to develop a new cisplatin (Cisp) loaded hydroxyl functionalized single-walled carbon nanotube (OH-SWCNT) nanocarrier system to selectively eliminate gastric cancer stem cells. To our understanding, this is the first study of the non-covalent interaction of cisplatin loaded on the surface of hydroxyl-functionalized single-walled carbon nanotubes by ultrasonication. The physical and morphological characterization was carried out by UV-Vis, FTIR spectroscopy, and TEM. A sustained and controlled release of cisp from OH-SWCNT at all three pHs 3.5, 5.5, and 7.4 was observed. Gastric cancer stem cells were isolated from primary cells and were identified by using CD133+ and CD44+ specific markers. Cisplatin-loaded OH-SWCNT nanocarrier was capable of limiting the self-renewal capacity of both CD133+ and CD44+ populations and also decreasing the number of tumorspheres in gastric CSCs. The cell viability percent of AGS cells was 20% at 250 µg/ml concentration. The IC50 value was less than 50% mol/L at both 200 µg/ml and 250 µg/ml of cisplatin-loaded OH-SWCNT. Our findings suggest that cisplatin-loaded OH-SWCNT nanocarrier complexes could target gastric CSCs and also could provide a potential strategy for selectively targeting and efficiently eliminating gastric CSCs. This could be a promising approach to prevent gastric cancer recurrence and metastasis and also improve gastric cancer therapy.