Exposure to Secondhand Smoke Extract Increases Cisplatin Resistance in Head and Neck Cancer Cells.

Chemotherapy and radiotherapy resistance are major obstacles in the long-term efficacy of head and neck squamous cell carcinoma (HNSCC) treatment. Secondhand smoke (SHS) exposure is common and has been proposed as an independent predictor of HNSCC recurrence and disease-free survival. However, the underlying mechanisms responsible for these negative patient outcomes are unknown. To assess the effects of SHS exposure on cisplatin efficacy in cancer cells, three distinct HNSCC cell lines were exposed to sidestream (SS) smoke, the main component of SHS, at concentrations mimicking the nicotine level seen in passive smokers' saliva and treated with cisplatin (0.01-100 µM) for 48 h. Compared to cisplatin treatment alone, cancer cells exposed to both cisplatin and SS smoke extract showed significantly lower cisplatin-induced cell death and higher cell viability, IC50, and indefinite survival capacity. However, SS smoke extract exposure alone did not change cancer cell viability, cell death, or cell proliferation compared to unexposed control cancer cells. Mechanistically, exposure to SS smoke extract significantly reduced the expression of cisplatin influx transporter CTR1, and increased the expression of multidrug-resistant proteins ABCG2 and ATP7A. Our study is the first to document that exposure to SHS can increase cisplatin resistance by altering the expression of several proteins involved in multidrug resistance, thus increasing the cells' capability to evade cisplatin-induced cell death. These findings emphasize the urgent need for clinicians to consider the potential role of SHS on treatment outcomes and to advise cancer patients and caregivers on the potential benefits of avoiding SHS exposure.

The Effect of Flow Rate on a Third-Generation Sub-Ohm Tank Electronic Nicotine Delivery System-Comparison of CORESTA Flow Rates to More Realistic Flow Rates.

Many types of electronic cigarettes (ECs) are currently in use, but the default flow rate used to simulate puffing is centered on tobacco cigarette flow rates. CORESTA offers several methods and technical guides for evaluation of ECs but there are few puffing topography studies focusing on sub-ohm ECs; differences between real-world usage and that found in the literature appear large. This study focuses on how power and flow rate affect the nicotine yield of a sub-ohm EC. A puffing system (Puff3rd) has been designed and used to produce and collect EC aerosol. Nicotine yield was measured by GC-MS at three power levels and four flow rates. Data analysis was conducted in SAS using the MIXED procedure. Power, flow rate, and their interaction were all significant predictors of nicotine yield. Nicotine yield increased with both the vaping power and the puff flow rate with significant interaction of the two. Findings indicate that using the current CORESTA flow rate (1100 mL/min) to evaluate third-generation ECs underestimates nicotine yield and likely overestimates pyrolysis products. Real users are expected to have 2-3× the nicotine dose measured at 1100 mL/min, which could confound epidemiological studies seeking to link nicotine delivery to product satisfaction and acceptability.

Electronic cigarette aerosols alter the expression of cisplatin transporters and increase drug resistance in oral cancer cells.

Tobacco smoking is the leading preventable cause of cancer. Moreover, continued smoking during cancer therapy reduces overall survival. Aware of the negative consequences of tobacco smoking and the challenges of smoking cessation, cancer patients are inquiring whether they should switch to electronic cigarettes (e-cigarettes). To obtain evidence-based data to inform this decision, we examined the effects of e-cigarette aerosol exposure on cisplatin resistance in head and neck cancer cells. Our results show that cancer cells exposed to e-cigarette aerosol extracts and treated with cisplatin have a significant decrease in cell death, increase in viability, and increase in clonogenic survival when compared to non-exposed cells. Moreover, exposure to e-cigarette aerosol extracts increased the concentration of cisplatin needed to induce a 50% reduction in cell growth (IC50) in a nicotine-independent manner. Tobacco smoke extracts induced similar increases in cisplatin resistance. Changes in the expression of drug influx and efflux transporters, rather than activation of cell growth-promoting pathways or DNA damage repair, contribute to e-cigarette induced cisplatin resistance. These results suggest that like combustible tobacco, e-cigarette use might increase chemotherapy resistance, and emphasize the urgent need for rigorous evaluation of e-cigarettes health effects to ensure evidence-based public health policies.

Scale-up of non-toxic poly(butylene adipate-co-terephthalate)-Chitin based nanocomposite articles by injection moulding and 3D printing.

Poly(butylene adipate-co-terephthalate) (PBAT), a compostable polymer, filled with different weight percentage of unbleached nano chitin (NC; 10%, 30% and 50%), a biodegradable filler from crustacean waste, were prepared from the extruded blends by injection moulding and 3D printing. The nanochitin required was prepared from chitin isolated from prawn shells (Fenneropenaeus indicus). The nanochitin crystals were observed to contain carboxylic acid surface functional groups as assessed by FT-IR, 13C solid state NMR (SS NMR) spectroscopy, zeta potential measurements and the extent of the same was estimated by potentiometric titration. The PBAT-NC nanocomposites were characterized SS NMR spectroscopy, FT-IR spectroscopy, wide angle X-ray diffraction, dynamic mechanical analysis, DSC and TGA. Thermal and mechanical properties of the nanocomposites were determined. The moulded nanocomposites changed more and more rigid with increasing weight percentage of NC without significant change in the tensile strength. The TGA indicated that the thermal stability of PBAT could be improved but not significantly by the addition of NC. Wound healing was enhanced in the presence of the nanocomposite while in vivo toxicity was significant at high concentration. The PBAT-NC nanocomposites could be moulded in to useful articles such as laptop charger cover, rat cover for washing machine, planters and key holders under conditions similar to that used in the processing of LDPE.

Biocompatible hydrogels of chitosan-alkali lignin for potential wound healing applications.

Biocompatible hydrogels were prepared by mixing aqueous-acidic solution of chitosan with alkali lignin, a major by-product of the paper producing industries, for the first time, by sustainable means. Electrostatic interactions between the phenoxide groups in lignin and the ammonium groups on the chitosan backbone were found to be responsible for the ionotropic cross-linking. These gels were non-toxic to Mesenchymal stem cells, in vitro, and to zebrafish up to 100 µg/ml, in vivo. In addition, these gels provided a conducive surface for cell attachment and proliferation, making it suitable for application as scaffolds in tissue engineering. In presence of the hydrogel, NIH 3T3 mouse fibroblast cells showed good cell migration characteristics suggesting that the gel might be suitable for wound healing application. The chitosan-alkali lignin gelation system was further capable of removing ferric ions from contaminated water by way of complexation and coagulation. Cross-linked films of chitosan and alkali lignin could also be prepared by simply immersing chitosan films into a solution of alkali lignin. Alkali lignin was observed to diffuse into the chitosan "crystal", forming electrostatic cross-links between the chitosan chains. The choice of lignin, in comparison to the other ionotropic cross-linkers for chitosan, makes the cross-linking system, inexpensive and sustainable.

Biocompatible Porous Scaffolds of Chitosan/Poly(EG-ran-PG) Blends with Tailored Pore Size and Nontoxic to Mesenchymal Stem Cells: Preparation by Controlled Evaporation from Aqueous Acetic Acid Solution.

The preparation of porous films (average size variation from 1 to 32 µm) of a 1:1 blend of chitosan with poly(EG-ran-PG) by the controlled evaporation of water from a 2 wt % aqueous acetic acid solution is reported. Interestingly, the blend exhibited porosity that could be tailored from 1 to 32 µm with the temperature of preparation of the blend film. The powder X-ray diffraction, Fourier transform infrared, and differential scanning calorimetry analyses of the films suggested the formation of partially miscible blends. Temperature-induced phase separation of the blend appears to be the mechanism of pore formation. The tensile strength, cytotoxicity, and biocompatibility of the blend films for the growth of mesenchymal stem cells were assessed vis-a-vis chitosan. The 1:1 blend film was observed to lack cytotoxicity and was also viable for the growth of mesenchymal stem cells. The tensile properties of the 1:1 blend were superior to those of the chitosan film. The simple preparation of porous, nontoxic, and biocompatible films could find use as a scaffold in the growth of tissue, and especially bone tissue, in wound dressing, and in filtration if a better control over pore size is achieved.

Chitosan-based nano-formulation enhances the anticancer efficacy of hesperetin.

Cancer is one of the major causes of increased morbidity and mortality in modern society. Colorectal cancer is the third leading cause for cancer related death worldwide. Current chemotherapeutics are not very effective and have severe side effects. Hesperetin is a bioflavonoid from citrus fruits and its clinical use is restricted because of the poor water solubility. Folate receptor is overexpressed in various cancer cells. Therefore, we synthesized the chitosan folate hesperetin nanoparticle (CFH) by covalently conjugating folic acid with chitosan molecules. The size of the CFH nanoparticles is around 450nm, which is advantageous for passively targeting the cancer cell specifically due to the leaky vasculature of the tumour. Particle surface and size were observed using SEM and TEM studies. The results show that hesperetin has an IC50 value of 190µM and it induces apoptosis in HCT15 cells, however, CFH is very potent in inhibiting the proliferation with the IC50 value of 28µM. In addition, CFH inhibited colony formation and induced apoptosis by regulating the expression of proapoptotic genes expression. Therefore, the chitosan - folic acid conjugation appears to be the suitable carrier for colorectal cancer cell-specific delivery of hesperetin.

Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage.

BACKGROUND: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. OBJECTIVE: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. METHODS: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. RESULTS: EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. CONCLUSIONS: Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.