Drug repurposing for Chagas disease: In vitro assessment of nimesulide against Trypanosoma cruzi and insights on its mechanisms of action.

Chagas disease is a neglected illness caused by Trypanosoma cruzi and its treatment is done only with two drugs, nifurtimox and benznidazole. However, both drugs are ineffective in the chronic phase, in addition to causing serious side effects. This context of therapeutic limitation justifies the continuous research for alternative drugs. Here, we study the in vitro trypanocidal effects of the non-steroidal anti-inflammatory drug nimesulide, a molecule that has in its chemical structure a toxicophoric nitroaromatic group (NO2). The set of results obtained in this work highlights the potential for repurposing nimesulide in the treatment of this disease that affects millions of people around the world.

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

In vitro biochemical characterization and genotoxicity assessment of Sapindus saponaria seed extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Sapindus saponaria, also popularly known as soapberry, has been used in folk medicinal values because of its therapeutic properties and several compounds in its composition, which represent a target in potential for drug discovery. However, few data about its potential toxicity has been reported. AIM OF THE STUDY: Plant proteins can perform essential roles in survival, acting as defense mechanism, as well functioning as important molecular reserves for its natural metabolism. The aim of the current study was to investigate the in vitro toxicity profile of protein extract of S. saponaria and detect protein potentially involved in biological effects such as collagen hydrolysis and inhibition of viral proteases. MATERIALS AND METHODS: Protein extract of soapberry seeds was investigated for its cytotoxic and genotoxic action using the Ames test. The protein extract was also subjected to a partial purification process of a protease and a protease inhibitor by gel chromatography filtration techniques and the partially isolated proteins were characterized biochemically. RESULTS: Seed proteins extract of S. saponaria was evaluated until 100 µg/mL concentration, presenting cytotoxicity and mutagenicity in bacterial model mostly when exposed to exogenous metabolic system and causing cytotoxic and genotoxic effects in HepG2 cells. The purification and partial characterization of a serine protease (43 kDa) and a cysteine protease inhibitor (32.8 kDa) from protein extract of S. Saponaria, corroborate the idea of ​​the biological use of the plant as an insecticide and larvicide. Although it shows cytotoxic, mutagenic and genotoxic effects. CONCLUSION: The overall results of the present study provide supportive data on the potential use of proteins produced in S. saponaria seeds as pharmacological and biotechnological agents that can be further explored for the development of new drugs.

Correction: The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT).

Correction for 'The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT)' by Pengyuan Qi et al., Biomater. Sci., 2020, 8, 2778-2785, DOI: .

Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation.

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2-3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

In Vitro Assessment of Cytoprotective Effects of CANOVA against Cell Death Induced by the Anti-malarial Artesunate - A Preliminary Experiment.

BACKGROUND: Artesunate (ATS) is a semi-synthetic compound derived from artemisinin, which is widely accepted in the treatment of malaria. However, there is evidence that ATS, under certain in vitro conditions, induces several impairments to normal cell functions. Canova (CA) is a Brazilian homeopathic formulation indicated for patients with depressed immune system. CA shows both in vitro and in vivo protective effects against mutagenic/carcinogenic compounds. Therefore, we aimed to assess in vitro the cytoprotective effects of CA against the cytotoxicity of ATS in Vero cells. METHODS: Viability of Vero cells exposed to ATS was assessed by MTT assay, whereas the anti-cytotoxic effect of CA was evaluated by apoptosis and necrosis quantification with fluorescent dyes. RESULTS: After 24 hours of ATS treatment, a reduction in cell viability was observed at 32 and 64 µg/mL, the latter being statistically significant (p < 0.05) in relation to the negative control. The concentration of 64 µg/mL was chosen for the subsequent experiments. ATS significantly induced both apoptosis and necrosis in Vero cells in relation to controls (p < 0.01). We also observed a statistically significant decrease in the number of apoptotic cells observed in the CA 16% + ATS co-treatment compared with ATS treatment (p < 0.01). Treatment with CA alone also had no influence on either type of cell death. CONCLUSION: Our results demonstrated that ATS is cytotoxic in the assessed conditions. However, such cytotoxicity was attenuated when the cells were treated simultaneously with ATS and CA.

An automated and high-throughput-screening compatible pluripotent stem cell-based test platform for developmental and reproductive toxicity assessment of small molecule compounds.

The embryonic stem cell test (EST) represents the only validated and accepted in vitro system for the detection and classification of compounds according to their developmental and reproductive teratogenic potency. The widespread implementation of the EST, however, in particular for routine application in pharmaceutical development, has not been achieved so far. Several drawbacks still limit the high-throughput screening of potential drug candidates in this format: The long assay period, the use of non-homogeneous viability assays, the low throughput analysis of marker protein expression and the compatibility of the assay procedures to automation. We have therefore introduced several advancements into the EST workflow: A reduction of the assay period, an introduction of homogeneous viability assays, and a straightforward analysis of marker proteins by flow cytometry and high content imaging to assess the impact of small molecules on differentiation capacity. Most importantly, essential parts of the assay procedure have been adapted to lab automation in 96-well format, thus enabling the interrogation of several compounds in parallel. In addition, extensive investigations were performed to explore the predictive capacity of this next-generation EST, by testing a set of well-known embryotoxicants that encompasses the full range of chemical-inherent embryotoxic potencies possible. Due to these significant improvements, the augmented workflow provides a basis for a sensitive, more rapid, and reproducible high throughput screening compatible platform to predict in vivo developmental toxicity from in vitro data which paves the road towards application in an industrial setting. Graphical abstract •The embryonic stem cell test to predict teratogenicity was made automation-compatible. •Several key improvements to the assay procedure have been introduced to increase performance. •The workflow was adapted to human iPS cells and isogenic fibroblast donor cells.

Comparative assessment of toxic responses in 3D embryoid body differentiation model and mouse early embryos treated with 5-hydroxytryptophan.

Pluripotent stem cells recapitulate in vitro the early developmental stages and are considered promising cell models for predictive developmental toxicity studies. To investigate the consistency between adverse drug effects on early development and the early stages of embryonic stem cell differentiation in three-dimensional (3D) in vitro culture, the toxic responses to 5-hydroxytryptophan (5-HTP; 0.5-2 mM) were evaluated in early mouse embryos and the embryoid body (EB) differentiation model. 3D architectures, developmental and differentiation dynamics and the cell death rates were analyzed in early mouse embryos (E2.5-E5.5) and EBs at 1 and 6 days of differentiation using a combination of confocal immunofluorescence microscopy with high content imaging analysis and quantitative gene expression analysis. Comparative analysis of toxic responses in early embryos and EBs revealed a similar dose- and stage-dependent decrease in the 5-HTP toxic effects during development and differentiation. The integral toxic responses in the early embryos and EBs were significantly dependent on their 3D architecture and cellular composition. Treatment with 5-HTP (1 mM and above) induced developmental arrest, growth inhibition, and increased cell death in the early embryos without the trophoblasts (E2.5) and those with impaired trophoblasts and in early EBs, whereas later embryos and EBs were more resistant due to the protection of the extraembryonic tissues. This study demonstrates that the EB differentiation model is a relevant 3D-model of early mammalian development and can be useful for the predictive evaluation of toxic and teratogenic effects in embryos at the preimplantation and early post-implantation developmental stages.

Assessment of Collagen-Based Nanostructured Biomimetic Systems with a Co-Culture of Human Bone-Derived Cells.

Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and other factors, is considered a potential alternative to conventional treatments. Innovative scaffolds need to be tested in in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs), the two main players of bone remodeling, is required to mimic their crosstalk and molecular cooperation. To this aim, two composite materials were developed, based on type I collagen, and containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. The developed nanostructured systems underwent genipin chemical crosslinking and were then tested with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors, for 2-3 weeks. The favorable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of cells, encouraging a further investigation of the developed bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE.

18F-AraG PET for CD8 Profiling of Tumors and Assessment of Immunomodulation by Chemotherapy.

Most clinical trials exploring various combinations of chemo- and immunotherapy rely on serial biopsy to provide information on immune response. The aim of this study was to assess the value of 18F-arabinosyl guanine (18F-AraG) as a noninvasive tool that profiles tumors on the basis of the key player in adaptive antitumor response, CD8+ cells, and evaluates the immunomodulatory effects of chemotherapy. Methods: To evaluate the ability of 18F-AraG to report on the presence of CD8+ cells within the tumor microenvironment, we imaged a panel of syngeneic tumor models (MC38, CT26, LLC, A9F1, 4T1, and B16F10) and correlated the signal intensity with the number of lymphocytes found in the tumors. The capacity of 18F-AraG to detect immunomodulatory effects of chemotherapy was determined by longitudinal imaging of tumor-bearing mice (MC38 and A9F1) undergoing 2 types of chemotherapy: oxaliplatin/cyclophosphamide, shown to induce immunogenic cell death, and paclitaxel/carboplatin, reported to cause immunogenically silent tumor cell death. Results: In the tumor panel, 18F-AraG revealed strikingly different uptake patterns resembling cancer-immune phenotypes observed in the clinic. A statistically significant correlation was found between the 18F-AraG signal and the number of PD-1-positive CD8+ cells isolated from the tumors (r2 = 0.528, P < 0.0001). In the MC38 model, paclitaxel/carboplatin did not result in an appreciable change in signal after therapy (1.69 ± 0.25 vs. 1.50 ± 0.33 percentage injected dose per gram), but oxaliplatin/cyclophosphamide treatment led to close to a 2.4-fold higher 18F-AraG signal (1.20 ± 0.31 vs. 2.84 ± 0.93 percentage injected dose per gram). The statistically significant increase in signal after oxaliplatin/cyclophosphamide was also observed in the A9F1 model (0.95 ± 0.36 vs. 1.99 ± 0.54 percentage injected dose per gram). Conclusion: The ability of 18F-AraG PET to assess the location and function of CD8+ cells, as well immune activity within tumors after immune priming therapy, warrants further investigation into its utility for patient selection, evaluation of optimal time to deliver immunotherapies, and assessment of combinatorial therapies.

Shortened derivatives from native antimicrobial peptide LyeTx I: In vitro and in vivo biological activity assessment.

In the continuing search for novel antibiotics, antimicrobial peptides are promising molecules, due to different mechanisms of action compared to classic antibiotics and to their selectivity for interaction with microorganism cells rather than with mammalian cells. Previously, our research group has isolated the antimicrobial peptide LyeTx I from the venom of the spider Lycosa erythrognatha. Here, we proposed to synthesize three novel shortened derivatives from LyeTx I (LyeTx I mn; LyeTx I mnΔK; LyeTx I mnΔKAc) and to evaluate their toxicity and biological activity as potential antimicrobial agents. Peptides were synthetized by Fmoc strategy and circular dichroism analysis was performed, showing that the three novel shortened derivatives may present membranolytic activity, like the original LyeTx I, once they folded as an alpha helix in 2.2.2-trifluorethanol and sodium dodecyl sulfate. In vitro assays revealed that the shortened derivative LyeTx I mnΔK presents the best score between antimicrobial (↓ MIC) and hemolytic (↑ EC50) activities among the synthetized shortened derivatives, and LUHMES cell-based NeuriTox test showed that it is less neurotoxic than the original LyeTx I (EC50 [LyeTx I mnΔK] ⋙ EC50 [LyeTx I]). In vivo data, obtained in a mouse model of septic arthritis induced by Staphylococcus aureus, showed that LyeTx I mnΔK is able to reduce infection, as demonstrated by bacterial recovery assay (∼10-fold reduction) and scintigraphic imaging (less technetium-99m labeled-Ceftizoxime uptake by infectious site). Infection reduction led to inflammatory process and pain decreases, as shown by immune cells recruitment reduction and threshold nociception increment, when compared to positive control group. Therefore, among the three shortened peptide derivatives, LyeTx I mnΔK is the best candidate as antimicrobial agent, due to its smaller amino acid sequence and toxicity, and its greater biological activity.

Erythrocytes as model cells for biocompatibility assessment, cytotoxicity screening of xenobiotics and drug delivery.

Erythrocytes (RBCs) represent the main cell component in circulation and recently have become a topic of intensive scientific interest. The relevance of erythrocytes as a model for cytotoxicity screening of xenobiotics is under the spotlight of this review. Erythrocytes constitute a fundamental cellular model to study potential interactions with blood components of manifold novel polymer or biomaterials. Morphological changes, subsequent disruption of RBC membrane integrity, and hemolysis could be used to determine the cytotoxicity of various compounds. Erythrocytes undergo a programmed death (eryptosis) which could serve as a good model for evaluating certain mechanisms which correspond to apoptosis taking place in nucleated cells. Importantly, erythrocytes can be successfully used as a valuable cellular model in examination of oxidative stress generated by certain diseases or multiple xenobiotics since red cells are subjected to permanent oxidative stress. Additionally, the antioxidant capacity of erythrocytes, and the activity of anti-oxidative enzymes could reflect reactive oxygen species (ROS) generating properties of various substances and allow to determine their effects on tissues. The last part of this review presents the latest findings on the possible application of RBCs as drug delivery systems (DDS). In conclusion, all these findings make erythrocytes highly valuable cells for in vitro biocompatibility assessment, cytotoxicity screening of a wide variety of substances as well as drug delivery.

Therapeutic Potential Assessment of Green Synthesized Zinc Oxide Nanoparticles Derived from Fennel Seeds Extract.

PURPOSE: To study the cytotoxic evaluation, antimicrobial and confocal analysis of zinc oxide nanoparticles (ZnO NPs) obtained from a novel plant product fennel (Foeniculum vulgare Mill.) seed extract (FSE). METHODS: ZnO NPs were analyzed using UV-Vis spectroscopy, XRD, FTIR, TEM and EDX techniques. The MTT cell cytotoxicity assay measured the proliferation and survival of MCF-7 cells treated at different concentrations of FSE-derived ZnO NPs. The antimicrobial activity towards pathogenic bacteria and yeast strains was investigated. RESULTS: The UV-Vis spectra showed two peaks at 438 nm and 446 nm, confirming nanoparticle formation. The SEM morphology results showed porous ranging from 23-51 nm. The antitumor activity value (IC50) was at 50 µg/mL and 100 µg/mL. Besides, morphological changes of MCF-7, cells treated at different concentrations of FSE of ZnO NPs were observed in cell cultures transfected with a transient pCMV6-XL4-GFP-expressing vector containing C-terminal domain GFP-tagged proteins, which resulted in an apoptotic effect. Antimicrobial IZ ranged up No Inhibition to 18.00 ± 0.4. The IZ revealed at the highest concentration was E. faecium VRE and yeast Cryptococcus sp. (18.00 ± 0.4. mm), followed by S. aureus (17.00 ± 0.2 mm) and P. aeruginosa and the yeast C. parapsilosis (16 ± 0.4 mm). The IZ was equal to that caused by the nystatin to Cryptococcus sp., which was significantly highest than ampicillin treatments of S. aureus, P. aeruginosa, C. albicans, and C. parapsilosis. The MIC value of the FSE-derived ZnO NPs tested against E.faecium and C.albicans was 6.00 µg/mL (E. faecium and C. albicans). It was 32.00 µg/mL (S. aureus, S. typhimurium and Cryptococcus sp.), 64.00 µg/mL (P. aeruginosa), and 128 µg/mL (C. parapsilosis). CONCLUSION: As far as it is to our knowledge, this study established, for the first time, the biological activities of biosynthesized ZnO NPs from FSE and their synergistic therapeutic potential.

Toxicological assessment of 3-monochloropropane-1,2-diol (3-MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway.

3-Monochloropropane-1,2-diol (3-MCPD) as a main source of food contamination has always been known as a carcinogenic agent. Kidney, liver, testis, and heart seem to be the main target organs for 3-MCPD. Because oxidative stress and mitochondrial dysfunction have been realized to be involved in 3-MCPD-induced cytotoxicity, the present study aimed to investigate the probable toxicity mechanisms of 3-MCPD in isolated mitochondria, HEK-293 cell line, and cell isolated from the rats' liver and kidney through measuring multiparametric oxidative stress assay. Based on the data indicating no significant difference between 3-MCPD-treated groups and control group, metabolites of 3-MCPD have a key role in organ toxicity caused by them. To further investigating the suggested hypothesis, the effect of 3-MCPD toxicity on HEK-293 cell line was examined. Although the proliferation declined after exposure to a low dose of 3-MCPD (10 to 200 µM), controversial responses in higher concentration (2 to 10 mM) have led to studies on the effect of oxidative stress and cell death signaling on isolated kidney and liver cells. Treatment of the isolated kidney and liver cells with 3-MCPD resulted in an increase in the level of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential (MMP), and activation of cell death signaling without creating any significant difference in the amount of reduced glutathione. In fact, 3-MCPD can disrupt the mitochondrial electron transfer in isolated cells, which is correlated with the impairment of mitochondrial oxidative phosphorylation system, the rise of ROS level, and the failure of MMP, leading to the release of cytochrome c from mitochondria to cytosol and finally the activation of cell death signaling.

Combined effects of cisplatin and photon or proton irradiation in cultured cells: radiosensitization, patterns of cell death and cell cycle distribution.

The purpose of the current study was to investigate the biological effects of protons and photons in combination with cisplatin in cultured cells and elucidate the mechanisms responsible for their combined effects. To evaluate the sensitizing effects of cisplatin against X-rays and proton beams in HSG, EMT6 and V79 cells, the combination index, a simple measure for quantifying synergism, was estimated from cell survival curves using software capable of performing the Monte Carlo calculation. Cell death and apoptosis were assessed using live cell fluorescence imaging. HeLa and HSG cells expressing the fluorescent ubiquitination-based cell cycle indicator system (Fucci) were irradiated with X-rays and protons with cisplatin. Red and green fluorescence in the G1 and S/G2/M phases, respectively, were evaluated and changes in the cell cycle were assessed. The sensitizing effects of ≥1.5 µM cisplatin were observed for both X-ray and proton irradiation (P < 0.05). In the three cell lines, the average combination index was 0.82-1.00 for X-rays and 0.73-0.89 for protons, indicating stronger effects for protons. In time-lapse imaging, apoptosis markedly increased in the groups receiving ≥1.5 µM cisplatin + protons. The percentage of green S/G2/M phase cells at that time was higher when cisplatin was combined with proton beams than with X-rays (P < 0.05), suggesting more significant G2 arrest. Proton therapy plus ≥1.5 µM cisplatin is considered to be very effective. When combined with cisplatin, proton therapy appeared to induce greater apoptotic cell death and G2 arrest, which may partly account for the difference observed in the combined effects.

Selenium Nanoparticles Synthesized Using Pseudomonas stutzeri (MH191156) Show Antiproliferative and Anti-angiogenic Activity Against Cervical Cancer Cells.

PURPOSE: Selenium nanoparticles (SeNP) have several applications in the field of biotechnology, including their use as anti-cancer drugs. The purpose of the present study is to analyze the efficacy of green synthesis on the preparation of SeNP and its effect on their anti-cancer properties. METHODS: A bacterial strain isolated from a freshwater source was shown to efficiently synthesize SeNP with potential therapeutic properties. The quality and stability of the NP were studied by scanning electron microscopy, X-ray diffraction, zeta-potential and FTIR analysis. A cost-effective medium formulation from biowaste having 6% banana peel extract enriched with 0.25 mM tryptophan was used to synthesize the NP. The NP after optimization was used to analyze their anti-tumor and anti-angiogenic activity. For this purpose, first, the cytotoxicity of the NP against cancer cells was analyzed by MTT assay and then chorioallantoic membrane assay was performed to assess anti-angiogenic activity. Further, cell migration assay and clonogenic inhibition assay were performed to test the anti-tumor properties of SeNP. To assess the cytotoxicity of SeNP on healthy RBC, hemolysis assay was performed. RESULTS: The strain identified as Pseudomonas stutzeri (MH191156) produced phenazine carboxylic acid, which aids the conversion of Se oxyanions to reduced NP state, resulting in particles in the size range of 75 nm to 200 nm with improved stability and quality of SeNP, as observed by zeta (ξ) potential of the particles which was found to be -46.2 mV. Cytotoxicity of the SeNP was observed even at low concentrations such as 5 µg/mL against cervical cancer cell line, ie, HeLa cells. Further, neovascularization was inhibited by upto 30 % in CAMs of eggs coinoculated with SeNp when compared with untreated controls, indicating significant anti-angiogenic activity of SeNP. The NP also inhibited the invasiveness of HeLa cells as observed by decreased cell migration and clonogenic proliferation. These observations indicate significant anti-tumor and anti-angiogenic activity of the SeNP in cervical cancer cells. CONCLUSION: P. stutzeri (MH191156) is an efficient source of Se NP production with potential anti-angiogenic and anti-tumor properties, particularly against cervical cancer cells.

The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT).

The potential role of borophene as a radiosensitizer in PT and BNCT was investigated. Our study focused on two aspects: (1) the synthesis and characterization of borophene nanomaterials; and (2) biocompatibility and dose enhancement. To overcome the limitation of vapor-based technology, we successfully deployed the liquid-phase exfoliation (LPE) method to produce borophene targeting for biomedical applications. Bringing together spatial distribution and dose deposition, the in vitro microdosimetry study was carried out in the presence of borophene. A quantitative study of the dose enhancement ratio (DER) was performed with Monte-Carlo simulation. The synthesized borophene showed good biocompatibility with less than 10% cell death at a concentration of up to 0.2 mg ml-1. The uptake of borophene within individual cells penetrated through cell membranes but outside the nucleus. For proton PT, no significant change in the DER is found. For carbon PT, the DER increases by about 5% as the concentration of 10B reaches 1 mg g-1. For BNCT, a DER of more than 2 can be obtained for a concentration as low as 100 µg g-1. This study lays a foundation for utilizing novel borophene-based nanomaterials as radiosensitizers as well as imaging probes in cancer treatment.

A simple, low-cost and green method for controlling the cytotoxicity of MXenes.

MXene phases are a member of the intriguing 2D material family, beyond graphene. They are good candidates for many applications, however, their potential toxicity is of crucial importance for future development. Herein, we present a simple, low-cost and fully green approach for controlling the potential cytotoxicity of 2D MXenes after delamination by harnessing the interactions that occur between the surface of MXene phases and natural biomacromolecule - collagen. We also demonstrate that the step-by-step adsorption and desorption of collagen from the surface of 2D MXenes is easily controlled using in situ zeta potential measurements coupled with dynamic light scattering (DLS) method. The obtained results demonstrated that the electrostatically driven unprecedented susceptibility of the MXenes' surfaces to collagen. Surface-modification reduces toxicity of MXenes in vitro i.e. adjust cells' viabilities as well as reduce their oxidative stress. This indicates enhanced biocompatibility of 2D Ti3C2 and Ti2C MXenes surface-modified with collagen, which is involved in many bio-interactions as important building blocks in the human body. The presented study opens new avenues for designing MXenes with defined surface properties and paves the way for their future successful management in nano-medicinal applications.

Assessment of cytotoxic and antimicrobial activity of selected gingival haemostatic agents - in vitro study.

PURPOSE: The present research aimed to determine whether and how the aluminium chloride - based materials affect the cell line of the bacterial line and fungi. METHODS: Cytotoxicity of haemostatic astringents: Alustat (liquid), Alustat (gel), Alustat (foam), Alustin, Hemostat, Racestyptine and Traxodent containing AlCl3 was conducted on L929 cell line with the use of MTT and SRB assays. The antimicrobial activity (CFU and MIC) against C. albicans, S. mutans, L. rhamnosus was determined. RESULTS: In the MTT results, cell viability for all agents were very low. In SRB, the lowest cytotoxicity was demonstrated for Hemostat and Alustat (foam), Traxodent and Racestyptine. Total reduction of the CFU of S. mutans was observed. Alustat (gel) and Alustat (liquid) completely inhibited the growth of C. albicans, S. mutans and L. rhamnosus. CONCLUSIONS: The viability of L929 cells obtained in the SRB assay is more reliable than that obtained in the MTT assay, in the case of gingival haemostatic agents.