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Under alkaline treatment, zirconyl chloride (ZrOCl 2 .8H 2 O) became a zirconia gel and formed a stable complex with beta-cyclodextrin (βCD). This complex was highly active in reactive oxygen species (ROS) formation via H 2 O 2 decomposition. Its surface with numerous hydroxyl groups acts as an ionic sponge to capture the charged reaction intermediates, including superoxide (O 2 -• ) and the hydroxyl radical ( • OH). ROS, especially • OH radicals, are harmful to living microorganisms because of their kinetic instability, high oxidation potential, and chemical nonselectivity. Therefore, • OH radicals can engage in fast reactions with virtually any adjacent biomolecule. With H 2 O 2 , the complex with cationic and hydrophobic moieties interacted with the anionic bacterial membrane of two Gram-positive ( Staphylococcus aureus and S. epidermidis ) and two Gram-negative ( Escherichia coli and Klebsiella pneumoniae ) strains. The Zr-βCD-H 2 O 2 also eradicated more than 99% of the biofilm of these four pathogens. Considering the difficult acquisition of resistance to the oxidation of • OH, the results suggested that this βCD-based nanomaterial might be a promising agent to target both drug-resistant pathogens with no cytotoxicity and exceptional antimicrobial activity.

Abstract Cell cycle dysregulation is typical in human cancers, and CDK4/6 inhibitors targeting cell cycle have potential antiapoptosis effect. The aim of this work is to identify the regulatory effect of Palbociclib on apoptosis of H9c2 cells induced by high glucose (HG) and to elucidate the fundamental mechanisms. It was observed that Palbociclib decreased intracellular ROS production, augmented mitochondrial membrane potential and hindered apoptosis of H9c2 cells. Palbociclib increased the Bcl-2/Bax ratio, diminished the expressions of Bax and cleaved-caspase-3, and affected the RB phosphorylation and p53 expression. Altogether, the anti-apoptotic efficacy of Palbociclib could be attributed in part to the modulation of the mitochondria apoptotic pathway. Highlights • CDK4/6 inhibitor Palbociclib protects high glucose-induced apoptosis in H9c2 cells. • Palbociclib decreased intracellular ROS production, augmented mitochondrial membrane potential of H9c2 cells. • RB phosphorylation and p53 are involved the protection effect of Palbociclib. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We designed and synthesized 26 compounds containing a Michael acceptor. • The structural conditions required to obtain stronger cytotoxicity against cancer cells were derived based on the relationships between the cell growth inhibitory concentration of the compounds and their physicochemical properties. • The title compound triggered apoptosis through ROS generation, which then led to stimulation of the caspase pathway. Abstract A moderate elevation in reactive oxygen species (ROS) levels can generally be controlled in normal cells, but may lead to death of cancer cells as the ROS level in cancer cells is already elevated. Therefore, a ROS-generating compound can act as a selective chemotherapeutic agent for cancer cells that does not affect normal cells. In our previous study, a compound containing a Michael acceptor was selectively cytotoxic to cancer cells without affecting normal cells; therefore, we designed and synthesized 26 compounds containing a Michael acceptor. Their cytotoxicities against HCT116 human colon cancer cell lines were measured by using a clonogenic long-term survival assay. To derive the structural conditions required to obtain stronger cytotoxicity against cancer cells, the relationships between the half-maximal cell growth inhibitory concentration values of the synthesized compounds and their physicochemical properties were evaluated by Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis. It was confirmed that the compound with the best half-maximal cell growth inhibitory concentration triggered apoptosis through ROS generation, which then led to stimulation of the caspase pathway. [ABSTRACT FROM AUTHOR]

Abstract Bismuth oxide nanoparticles (Bi 2 O 3 NPs) have shown great potential for several applications including cosmetics and biomedicine. However, there is paucity of research on toxicity of Bi 2 O 3 NPs. In this study, we first examined dose-dependent cytotoxicity and apoptosis response of Bi 2 O 3 NPs in human breast cancer (MCF-7) cells. We further explored the potential mechanisms of cytotoxicity of Bi 2 O 3 NPs through oxidative stress. Physicochemical study demonstrated that Bi 2 O 3 NPs have crystalline structure and spherical shape with mean size of 97 nm. Toxicity studies have shown that Bi 2 O 3 NPs reduce cell viability and induce membrane damage dose-dependently in the concentration range of 50–300 μg/ml. Bi 2 O 3 NPs also disturbed cell cycle of MCF-7 cells. Oxidative stress response of Bi 2 O 3 NPs was evident by generation of reactive oxygen species (ROS), higher lipid peroxidation, reduction of glutathione (GSH) and low superoxide dismutase (SOD) enzyme activity. Interestingly, supplementation of external antioxidant N-acetyl-cysteine almost negated the effect of Bi 2 O 3 NPs induced oxidative stress and cell death. We also found that exposure of Bi 2 O 3 NPs induced apoptotic response in MCF-7 cells suggested by impaired regulation of Bcl-2, Bax and caspase-3 genes. Altogether, we found that Bi 2 O 3 NPs induced cytotoxicity in MCF-7 cells through modulating the redox homeostasis via Bax/Bcl-2 pathway. This study warranted further research to delineate the underlying mechanism of Bi 2 O 3 NPs induced toxicity at in vivo level. Graphical abstract Image 1 Highlights • Dose-dependent cytotoxicity was observed in Bi 2 O 3 NPs treated MCF-7 cells. • Bi 2 O 3 NPs induced ROS generation, lipid peroxidation and GSH depletion. • Cytotoxicity of Bi 2 O 3 NPs was found to be mediated through oxidative stress. • Bi 2 O 3 NPs exposure impaired the regulation of genes associated with apoptosis. [ABSTRACT FROM AUTHOR]

Abstract Although sweetpotato is an important crop worldwide, there has been almost no research on the occurrence of internal browning (IB) to date. In this study, we clarified the mechanism of occurrence of the disorder by using two types of cultivars with different IB susceptibility. In cells around the secondary vascular tissue, large size of starch grains accumulated in IB-susceptible cultivar compared with resistant one. Histochemical observation performed on cells around the secondary vascular tissues showed the presence of high levels of polyphenol oxidase activity, chlorogenic acid, and hydrogen peroxide in cells from the IB-affected regions in IB-susceptible cultivar. Likewise, high levels of starch content, hydrogen peroxide concentration, and polyphenol content were detected in the affected regions of IB-susceptible cultivar. In IB-susceptible cultivar, both the transcript levels of gens related starch and polyphenol biosynthesis were higher at an early stage of root maturation, while the levels in resistant cultivar were low at this stage and thereafter increased relatively more moderately. These observations suggest that the occurrence of IB disorder in sweetpotato largely depends on the morphology and timing of accumulated starch grain in cells around the secondary vascular tissues. Highlights • Intervarietal differences with respect to the severity of internal browning in sweetpotato were examined. • Active ROS generation and polyphenol biosynthesis were observed in cells from affected regions in susceptible cultivar compared with resistant one. • In susceptible cultivar, both the transcript levels of gens related starch and polyphenol biosynthesis were higher at an early stage of root maturation compared with resistant one. [ABSTRACT FROM AUTHOR]

Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18–65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC50: 41 µM), and induced a general dose-dependent depletion of polyunsaturated lipids (10–20 µM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tri- tert -butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects. [ABSTRACT FROM AUTHOR]

In recent years, nanoparticles are being used extensively in personal healthcare products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal oxide nanoparticles are gaining competence as key industrial constituents, progressing toward a remarkable rise in their applications. Zinc oxide and titanium oxide nanoparticles are the most commonly employed metal oxide nanoparticles in sunscreens, ointments, foot care, and over the counter topical products. Dermal exposure to these metal oxides predominantly occurs through explicit use of cosmetic products and airway exposure to nanoparticle dusts is primarily mediated via occupational exposure. There is a compelling need to understand the toxicity effects of nanoparticles which can easily enter the cells and induce oxidative stress. Consequently, these products have become a direct source of pollution in the environment and thereby greatly impact our ecosystem. A complete understanding of the toxicity mechanism of nano-ZnO is intended to resolve whether and to what extent such nanoparticles may pose a threat to the environment and to human beings. In this review article, we have discussed the characteristics of metal oxide nanoparticles and its applications in the cosmetic industry. We have also highlighted about their toxicity effects and their impact on human health. [ABSTRACT FROM AUTHOR]

Abstract Oral squamous cell carcinoma (OSCC) is known as one of the most common cancer influencing the head and neck region. However, the molecular mechanisms revealing OSCC progression is largely unclear. Aurora kinase A (AURKA) is a serine-threonine kinase that functions in mitotic spindle formation and chromosome segregation, and is associated with the progression of human cancers. But its role in regulating OSCC development has not yet been investigated. In the study, we found that AURKA expression was up-regulated in OSCC cell lines and tumor specimens from patients. OSCC patients with high expression of AURKA exhibited a significant decreased overall survival rate. In vitro, AURKA knockdown markedly reduced the proliferation, migration and invasion of OSCC cells using cell counting kit-8 (CCK-8), EdU, colony formation and transwell analysis. EMT was suppressed by AURKA silence, as evidenced by the up-regulated expression of E-cadherin and down-regulated Vimentin in OSCC cells. In addition, apoptosis was markedly induced by AURKA inhibition through promoting the expression of cleaved Caspase-3 and poly (ADP)-ribose polymerase (PARP). Reactive oxygen species (ROS) production was also markedly enhanced in AURKA-knockdown OSCC cells. Importantly, we found that repressing ROS generation using its scavenger of n-acetylcysteine (NAC) significantly abolished AURKA silence-induced apoptosis, accompanied with restored proliferation and EMT. In vivo, AURKA knockdown notably inhibited tumor growth. Therefore, knockdown of AURKA suppressed cell proliferation, migration and invasion, and also induced apoptosis and ROS generation in OSCC possibly via the production of ROS, demonstrating that AURKA inhibition might represent a novel therapeutic target for the prevention of OSCC. Highlights • AURKA knockdown inhibited the proliferation and ETM in OSCC cell lines. • Silencing AURKA induced apoptosis and ROS in OSCC cell lines. • AURKA knockdown inhibited tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Nano- and microplastics have been shown to cause negative effects on marine organisms. However, the toxicities of nano- and microplastics toward marine bacteria are poorly understood. In this study, we investigated the toxic effects of polystyrene nano- and microplastics on the marine bacterium Halomonas alkaliphila by determining growth inhibition, chemical composition, inorganic nitrogen conversion efficiencies and reactive oxygen species (ROS) generation. The results showed that both nano- and microplastics inhibited the growth of H. alkaliphila in high concentrations, while nanoplastics rather than microplastics influenced the growth inhibition, chemical composition and ammonia conversion efficiencies of H. alkaliphila at concentration of 80 mg/L. The ROS generation indicated oxidative stress induced by nano- but not microplastics, and the oxidative stress induced by nanoplastics may provide a significant effect on bacteria. Furthermore, the positively charged nanoplastics (amine-modified 50 nm) induced higher oxidative stress toward bacteria than that induced by negatively charged nanoplastics (non-modified 55 nm). The increased extracellular polymeric substances as evidenced by transmission electron microscope (TEM) observation suggested the possible bacterial protective mechanisms. The present study illustrates for the first time the impact of plastics debris on the inorganic nitrogen conversion efficiencies of marine bacteria. Our findings highlight the effects of microplastics on the ecological function of marine organisms. [ABSTRACT FROM AUTHOR]

Abstract Since their advent a few decades ago, engineered nanoparticles (ENPs) have been extensively used in consumer products and industrial applications and their use is expected to continue at the rate of thousands of tons per year in the next decade. The widespread use of ENPs poses a potential risk of large scale environmental proliferation of ENPs which can impact and endanger environmental health and safety. Recent studies have shown that microbial biofilms can serve as an important biotic component for partitioning and perhaps storage of ENPs released into aqueous systems. Considering that biofilms can be one of the major sinks for ENPs in the environment, and that the field of biofilms itself is only three to four decades old, there is a recent and growing body of literature investigating the ENP-biofilm interactions. While looking at biofilms, it is imperative to consider the interactions of ENPs with the planktonic microbial cells inhabiting the bulk systems in the vicinity of surface-attached biofilms. In this review article, we attempt to establish the state of current knowledge regarding the interactions of ENPs with bacterial cells and biofilms, identifying key governing factors and interaction mechanisms, as well as prominent knowledge gaps. Since the context of ENP-biofilm interactions can be multifarious—ranging from ecological systems to water and wastewater treatment to dental/medically relevant biofilms— and includes devising novel strategies for biofilm control, we believe this review will serve an interdisciplinary audience. Finally, the article also touches upon the future directions that the research in the ENP-microbial cells/biofilm interactions could take. Continued research in this area is important to not only enhance our scientific knowledge and arsenal for biofilm control, but to also support environmental health while reaping the benefits of the ‘nanomaterial revolution’. Highlights • Hydrophobicity and aggregation of engineered nanoparticles (ENPs) affect toxicity. • ENP-biofilm interactions are less studied than ENP-bacterial interactions. • ENPs may significantly partition to natural biofilms in aquatic systems. • Disintegration of extracellular polymeric substance (EPS) could remove biofilms. • ENPs may inhibit biofilms by interfering with quorum sensing. [ABSTRACT FROM AUTHOR]

Silica based nanoparticles have emerged as a promising vaccine delivery system for cancer immunotherapy, but their bio-degradability, adjuvanticity and the resultant antitumor activity remain to be largely improved. In this study, we report biodegradable glutathione-depletion dendritic mesoporous organosilica nanoparticles (GDMON) with a tetrasulfide-incorporated framework as a novel co-delivery platform in cancer immunotherapy. Functionalized GDMON are capable of co-delivering an antigen protein (ovalbumin) and a toll-like receptor 9 (TLR9) agonist into antigen presenting cells (APCs) and inducing endosome escape. Moreover, decreasing the intracellular glutathione (GSH) level through the -S-S-/GSH redox chemistry increases the ROS generation level both in vitro and in vivo , facilitating cytotoxic T lymphocyte (CTL) proliferation and reducing tumour growth in an aggressive B16-OVA melanoma tumour model. Our results have shown the potential of GDMON as a novel self-adjuvant and co-delivery nanocarrier for cancer vaccine. [ABSTRACT FROM AUTHOR]

This research was conducted to evaluate effects of biochar (50 and 100 g kg −1 soil) and lignite (50 and 100 g kg −1 soil) treatments on H + -ATPase and H + -PPase activity of root tonoplast, nutrient content, and performance of mung bean under salt stress. High saline conditions increased H + -ATPase and H + -PPase activities in root tonoplast, sodium (Na) content, reactive oxygen species (H 2 O 2 and O 2 − ) generation, relative electrolyte leakage (REL) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) activity in root and leaf, but decreased relative water content (RWC), chlorophyll content index, leaf area, potassium (K), calcium (Ca), magnesium (Mg), zinc (Zn) and iron (Fe) content of plant tissues, root and shoot dry weight of mung bean. Lignite and biochar treatments decreased the H + -ATPase and H + -PPase activities of root tonoplast under salt stress. Moreover, these treatments increased the cation exchange capacity of soil and nutrient values in plant tissues. Biochar and lignite diminished the generation of reactive oxygen species and DPPH activity in root and leaf cells, and these superior effects improved chlorophyll content index, leaf area and growth of mung bean under both conditions. In general, the results of this study demonstrated that biochar and lignite decreased the entry of Na ion into the cells, enriched plant cells with nutrients, and consequently improved mung bean performance under salt toxicity. [ABSTRACT FROM AUTHOR]

Dioscorea villosa, commonly known as “Wild Yam” and native to North America, is well documented for its pharmacological properties due to the presence of steroidal glycosides. However, the hepatoprotective potential of these compounds has not been studied so far. The present investigation was aimed to study the hepatoprotective effect of the steroidal glycosides from D. villosa against H2O2, a known hepatotoxin, in human liver cell line (HepG2). Cytotoxicity assessment was carried out in cells exposed to various concentrations (10–50 μM) of compounds for 24 h using MTT assay and morphological changes. All tested compounds were known and among them, spirostans (zingiberensis saponin I, dioscin, deltonin and progenin III) were found to be cytotoxic whereas, furostans (huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin) were non-cytotoxic. Further, HepG2 cells were pretreated with biologically safe concentrations (10, 30, and 50 μM) of non-cytotoxic compounds and then cytotoxic (0.25 mM) concentration of H2O2. After 24 h, cell viability was assessed by MTT and NRU assays, while morphological changes were observed under the microscope. The results showed that treatment of HepG2 cells with compounds prior to H2O2 exposure effectively increased cell viability in a concentration-dependent manner. Furthermore, huangjiangsu A, pseudoprotodioscin, methyl protobioside, protodioscin, and protodeltonin at 50 μM increased GSH level and decreased intracellular ROS generation against H2O2-induced damages. The results from this study revealed that compounds isolated from D. villosa have hepatoprotective potential against H2O2-induced cytotoxicity and ROS generation and could be promising as potential therapeutic agents for liver diseases. [ABSTRACT FROM AUTHOR]

We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H - benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC. [ABSTRACT FROM AUTHOR]

A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus (MIC = 4 µg/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c –DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity. [ABSTRACT FROM AUTHOR]

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P-450-induced 20-HETE synthesis which in turn results in vascular dysfunction. However, the effect of testosterone plus estrogen in the cardiovascular system is still very poorly studied. The aim of the present study is to evaluate the role of cytochrome P-450 pathway in a postmenopausal hypertensive female treated with testosterone plus estrogen. For that, hypertensive ovariectomized rats (OVX-SHR) were used as a model of postmenopausal hypertension and four groups were created: SHAM-operated (SHAM), ovariectomized SHR (OVX), OVX treated for 15 days with conjugated equine estrogens [(CEE) 9.6 µg/Kg/day/po] or CEE associated to testosterone [(CEECT) 2.85 mg/kg/weekly/im]. Phenylephrine-induced contraction and generation of reactive oxygen species (ROS) were markedly increased in aortic rings from OVX-SHR compared to SHAM rats which were restored by CEE treatment. On the other hand, CEECT abolished vascular effects by CEE and augmented both systolic and diastolic blood pressure of SHR. Treatment of aortic rings with the CYP/20-HETE synthesis inhibitor HET0016 (1 µM) reduced phenylephrine hyperreactivity and the augmented ROS generation in the CEECT group. These results are paralleled by the increased CYP4F3 protein expression and activity in aortas of CEECT. In conclusion, we showed that association of testosterone to estrogen therapy produces detrimental effects in cardiovascular system of ovariectomized hypertensive females via CYP4F3/20-HETE pathway. Therefore, our findings support the standpoint that the CYP/20-HETE pathway is an important therapeutic target for the prevention of cardiovascular disease in menopausal women in the presence of high levels of testosterone. [ABSTRACT FROM AUTHOR]

We describe the synthesis of three new manganese (II) complexes containing the bidentate ligands 2-(1-methyl-3-pyrazolyl)pyridine (pypz-Me) and ethyl 2-(3-(pyridine-2-yl)-1H–pyrazol-1-yl)acetate (pypz-CH 2 COOEt), with formula [MnX 2 (pypz-Me) 2 ] (X = Cl − 1 , CF 3 SO 3 − 2 ) and [Mn(CF 3 SO 3 ) 2 (pypz-CH 2 COOEt) 2 ] 3 . Complexes 1 – 3 have been characterized through analytical, spectroscopic and electrochemical techniques, as well as by monocrystal X-ray diffraction analysis. The complexes show a six-coordinated Mn(II) ion though different stereoisomers have been isolated for the three compounds. Complexes 1 – 3 , together with the previously described compounds [MnCl 2 (pypz-H) 2 ] 4 , [Mn(CF 3 SO 3 ) 2 (pypz-H) 2 ] 5 , [Mn(NO 3 ) 2 (pypz-H) 2 ] 6 , [MnCl 2 (H 2 O) 2 (pypz-H) 2 ] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and ([Mn(CF 3 SO 3 ) 2 ((−)-L) 2 ] 8 , ((−)-L = (−)-pinene[5,6]bipyridine), were tested in vitro for cytotoxic activity against NCI-H460 and OVCAR-8 cancer cell lines. The geometry of a specific compound does not seem to influence its activity in a significant extent. However, among the tested compounds those that display hydrophobic substituents on the pyrazole ring and triflate ions as labile ligands show the best antiproliferative properties. Specifically, compound 8 containing the pinene-bipyridine ligand presents an antiproliferative activity similar to that of cisplatin and higher than that of carboplatin, and displays selectivity for tumour cells. Its antiproliferative effect is due to the generation of ROS species that allow the compound to interact with DNA. [ABSTRACT FROM AUTHOR]

Zinc oxide nanomaterials (ZnO NM) have been used in a large number of applications due to their interesting physicochemical properties. However, the increasing use of ZnO NM has led to concerns regarding their environmental impacts. In this study, the acute and chronic toxicity of ZnO nanorods (NR) bare (ZnONR) and amine-functionalized (ZnONR@AF) toward the freshwater microcrustacean Daphnia magna was evaluated. The ZnO NR were characterized by transmission electron microscopy (TEM), X–Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and the zeta potential and hydrodynamic diameter (HD). The acute EC50 (48h) values for D. magna revealed that the ZnONR@AF were more toxic than the ZnONR. The generation of reactive oxygen species (ROS) was observed in both NM. Regarding the chronic toxicity, the ZnONR@AF were again found to be more toxic than the ZnONR toward D. magna . An effect on longevity was observed for ZnONR, while ZnONR@AF affected the reproduction, growth and longevity. In the multigenerational recovery test, we observed that maternal exposure can affect the offspring even when these organisms are not directly exposed to the ZnO NR. [ABSTRACT FROM AUTHOR]

Abstract: This study investigates the exposure of lead‐induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK‐2 cells). Following treatment of HK‐2 cells with an increasing concentration of lead nitrate (0–50 μM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose‐dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK‐2 cells. Lead exposure also induced apoptosis through caspase‐3 activation at 30 μg/mL. Pretreatment with N‐acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead‐induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase‐3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead‐induced DNA damage and apoptosis in an exposed person. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first report demonstrating the effects of different types of fermentation on the in vitro bioaccessibility of açai anthocyanins. • Spontaneous fermentation of açai increases the bioaccessibility in vitro of cyanidin-3-glucoside. • Alcoholic fermentation of açai reduces reactive oxygen species generated by H 2 O 2 in the HCT8 cell line. • Alcoholic fermentation of açai reduces chromosomal aberrations in A549 cells. This work describes the kinetic study of different types (spontaneous, lactic and alcoholic) of açai fermentation in terms of total phenolics and total anthocyanins, as well as antioxidant capacity, before and after simulated digestion (SD). Cytotoxicity (A549, HCT8 and IMR90 cells) and formation of reactive oxygen species (A549 cells) were also evaluated. The results revealed that spontaneous fermentation (SF) for 24 h, followed by SD, generated a product with greater bioaccessibility of phenolics (52.68%) and cyanidin-3-glucoside (27.01%) than unfermented açai. Likewise, lactic fermentation (LF) for 72 h improved the bioavailability of phenolics (64.49%) and cyanidin-3-rutinoside (20.00%). On the other hand, alcoholic fermentation (AF) decreased the bioaccessibility of phenolic compounds and anthocyanins after SD. The SF 24 h (10.16 ± 1.25 μmol Trolox /g) and LF 72 h (15.90 ± 0.51 μmol Trolox /g) significantly increased the antioxidant capacity after SD, when compared to unfermented açai (SF 0 h, 4.00 ± 0.09 μmol Trolox /g; LF 0 h, 10.57 ± 0.91 μmol Trolox /g). It was concluded that the samples did not show cytotoxicity in the cell lines tested and, in addition, AF 24 h showed antioxidant and antimutagenic effects in vitro , reducing about 40% of chromosomal aberrations. The results obtained provide important information that can be used to produce foods with greater bioaccessibility of bioactive compounds. [ABSTRACT FROM AUTHOR]

Binary Co(II) complexes having anthraquinoe-based ligands show ct -DNA and human serum albumin binding afiinity and highly significant in vitro photo-enhanced cytotoxicty in HeLa and A549 cancer cells with low dark toxicity via generation of ROS. [Display omitted] • Anthraquinone-based binary Co(II) complexes display excellent light-activated cytotoxicity in cancer cells. • They generate cytotoxic reactive oxygen species on excitation with visible light. • They show significant binding affinity to DNA and human serum albumin. Co(II) is a bioessential ion and its complexes are less prone to reduction by cellular thiols thereby reducing the probability of dark toxicity. Based on the above analogy, we have designed and synthesized five anthraquinone-based binary cobalt(II) complexes viz. [Co(HL1) 2 ] (1), [Co(HL2) 2 ] (2), [Co(HL3) 2 ] (3), [Co(HL4) 2 ] (4) and [Co(HL5) 2 ] (5), where H 2 L1 = 2-(2-hydroxyphenyl)-1 H -anthra[1,2- d ]imidazole-6,11-dione; H 2 L2 = 2-(4-(diethylamino)-2-hydroxyphenyl)-1 H -anthra[1,2- d ]imidazole-6,11-dione; H 2 L3 = (2-(2-hydroxy-3-methoxyphenyl)-1 H -anthra[1,2- d ]imidazole-6,11-dione; H 2 L4 = 2-(3-hydroxy-6-(hydroxymethyl)-2-methylpyridin-4-yl)-1 H anthra[1,2- d ]imidazole-6,11 dione and H 2 L5 = 2-(3-hydroxynaphthalen-2-yl)-1 H -anthra[1,2- d ]imidazole-6,11-dione. The complexes were thoroughly characterized by spectroscopic and analytical methods and their potential application in photoactivated chemotherapy have been evaluated. The complexes 1 – 5 showed an irreversible voltammetric response at 0.43 V to 0.88 V corresponding to Co(II)/Co(III) couple. Three other responses were observed at ∼ -0.92 V, ∼ -1.16 V and ∼ -1.48 V for the ligands present in the binary Co(II) complexes due to quinone (Q)/ semiquinone (SQ -) and semiquinone (SQ -)/ catecholate (Cat2-) redox couples. The complexes display significant binding affinity to human serum albumin (HSA) displaying binding constants in the range 6.70 (±0.10) × 104 to 3.13 (±0.05) × 105 M−1. They also bind to calf-thymus (ct) DNA showing K b values in the order ∼ 105-106 M−1. In vitro light-activated cytotoxicity studies showed significant photocytotoxicity against human cervical carcinoma, HeLa (IC 50 ∼ 1.6–4.2 µM) and human lung carcinoma, A549 (IC 50 ∼ 2.1–6.1 µM) cells with minimal dark toxicity (IC 50 > 70 µM). Flow cytometric experiments reveal that complex 5 is able to produce reactive oxygen species (ROS) on exposure to visible light which responsible for photoactivated cytotoxicity. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) generation and utilization were the foundation for the photocatalytic degradation of pollutants or anti-bactericidal effect. Especially for solid-phase film photocatalysis, a simple and firm immobilization method that ensured exposure of active sites and effective production of ROS was the key. Presently, a P25 network films was achieved using water-based polyurethane acrylate (WPUA) as adhesive through a simple and convenient direct spraying method. The physical and chemical properties of the P25 network films were characterized and the results showed that P25 was firmly adhered on the metal wire mesh and fully exposed the active sites of P25. Dynamic generation of ROS on 304SS@P25 films interface was systematically investigated. The concentration of hydroxyl radicals (•OH), superoxide radicals (O 2 •−) and hydrogen peroxide (H 2 O 2) on 10 cm × 3 cm 304SS@P25 after 2 h of UV irradiation were 9.4 ± 0.3 × 10−9 M, 7.6 ± 0.3 × 10−9 M, and 11.7 ± 0.9 × 10−6 M, respectively, which was similar with ROS generation of P25 nanoparticle suspensions. In addition, the ROS-mediated antibacterial effect of 304SS@P25 films was investigated, and a linear correlation was found between the concentration of ROS generated and the E. coli sterilization rate. Furthermore, 304SS@P25 films could be successfully applied in the air sterilizer to exhibit a good bactericidal effect. This ROS-oriented photocatalyst immobilization method opened up a new pathway for water and air purification and provided a new strategy in the field of photocatalytic antibacterial technology. • WPUA was used to achieve a firm immobilization of P25 on the metal mesh. • P25 network films maintained a high catalytic activity and were easy to recycle. • P25 films ensured the exposure of active sites and efficient ROS generation. • The ROS production was linearly related to the anti-bactericidal effect of P25 films. [ABSTRACT FROM AUTHOR]

[Display omitted] • Six new Pd(II) complexes was synthesized and characterized. • The Pd(II) complexes binds with DNA via non-intercalation mode. • Photophysical study of binding mechanism of Pd(II) complexes with BSA. • DNA and BSA binding effect have also been approved using molecular docking studies. • In vitro assay confirmed the dose dependent and cell selective cytotoxic potential of the Pd(II) complexes. A series of Pd(II) complexes Pd-1 to Pd-6 ; out of these [Pd(PIEAM)(LC)]+; Pd-3 , [Pd(PIEAM)(NALC)]; Pd-4 , [Pd(PIEAM)(GSH)]; Pd-5 and [Pd(PIEAM)(DL-meth)]2+; Pd-6 have been synthesized from water soluble stable diaqua complex [Pd(PIEAM)(OH 2) 2 ](NO 3) 2 ; Pd-2. The Pd-2 complex was obtained from hydrolysis of [Pd(PIEAM)Cl 2 ]; Pd-1 (where, PIEAM = 1,2-Aminoethyl piperidine, a bidentate carrier ligand and with ancillary groups like; LC = L-cysteine, NALC = N-acetyl-L-cysteine, GSH = Glutathione, DL-meth = DL-methionine). All these Pd-1-Pd-6 complexes were characterized by different spectroscopic studies, like; UV–Vis, FT-IR, 1H NMR, and ESI Mass analyses. The bioactivity and drug-likeness properties of the complexes were assessed by PASS and ADME prediction software. The bioactivity of the complexes was experimentally investigated on DNA binding properties by gel electrophoresis, electronic, fluorescence, and viscometric methods. The binding constant values of Pd-3 complex with CT DNA bining in both absorption (K b = 7.50 × 104M−1)and fluorosence titration (K SV = 35.10 × 103 M−1) was found greater than other Pd-1 , Pd-2 , Pd-4 - Pd-6 complexes (K b = (4.25–0.64) × 104 M−1; K SV = (13.57–1.11) × 103 M−1). The comparison in BSA bining of Pd(II) complexes also suggested the higher binding constant of Pd-3 complex in both spectroscopic method (K b = 32 × 103M−1; K SV = 2.32 × 104 M−1) than other Pd(II) complexes (K b = 16–2.4 × 103M−1; K SV = 1.99–1.53 × 104 M−1). A theoretical investigation of the structural property and TD-DFT of the complexes was executed by DFT calculations. The detailed BSA binding activity of the complexes was performed by fluorescence quenching, synchronous, and 3D-fluorescence spectroscopic methods. Molecular docking of the complexes with DNA and BSA was under study for their binding mode and different weak forces. Their cytotoxic behaviors, like; anticancer activity by MTT assay and ROS (Reactive Oxygen Species) generation by NBT (Nitro Blue Tetrazolium) assay, were investigated. The cytotoxicity of the complexes was under investigation on human lung adenocarcinoma cell A549, colorectal carcinoma cell HCT 116, and normal human embryonic kidney cell HEK 293. [ABSTRACT FROM AUTHOR]

Fluorene was previously reported to have anticancer activity against human cancer cells. In this study, we examined the in vitro function of 9-methanesulfonylmethylene-2, 3-dimethoxy-9 H -fluorene (MSDF), a novel fluorene derivative, its anticancer potential in human hepatocellular carcinoma (HCC) cells and its underlying molecular mechanism. The disruption of cellular homeostasis caused by MSDF was found to promote reactive oxygen species (ROS) generation, leading to the activation of cellular apoptosis. As a survival strategy, cells undergo autophagy during oxidative stress. MSDF-induced apoptosis occurred through both receptor-mediated extrinsic and mitochondrial-mediated intrinsic routes. The development of acidic vesicular organelles and the accumulation of LC3-II protein suggest an increase in the autophagic process. Apoptosis was detected by double staining. The MAPK/ERK and PI3K/Akt signaling pathways were indeed suppressed during treatment. Along with elevated ROS generation and apoptosis, MSDF also caused anoikis and cell death by causing cells to lose contact with their extracellular matrix. ROS production was induced by MSDF and sustained by an NAC scavenger. MSDF-induced apoptosis led to increased autophagy, as shown by the suppression of apoptosis by Z -VAD-FMK. However, inhibition of autophagy by inhibitor 3-MA increased MSDF-induced apoptosis. More evidence shows that MSDF downregulated the expression of immune checkpoint proteins, suggesting that MSDF could be used in the future as an adjuvant to improve the effectiveness of HCC immunotherapy. Altogether, our results highlight the potential of MSDF as a multitarget drug for the treatment of HCC. A fluorene derivative inhibits human hepatocellular carcinoma cells by ROS-mediated apoptosis, anoikis, and autophagy. Graphic abstract: MSDF, a fluorene derivative, induces ROS generation and caspase-dependent death in HCC cells. Cell death and ERK/PI3K pathway inhibition result. Anoikis caused by cell-matrix interactions also eliminates HCC cells. HCC treatment may also benefit from MSDF-induced immune checkpoint reduction. Therefore, MSDF increases ROS generation, apoptosis, anoikis, and immunosuppression to sensitize HCC cells to cell death. [Display omitted] [ABSTRACT FROM AUTHOR]

• Quinoline and isoquinoline alkaloids evaluated against Trypanosoma evansi. • Concentration dependent anti-trypanosomal activity and cytotoxicity observed. • Quinine, berbamine and emetine showed higher apoptotic effects among six. • Dose-dependent and time dependent ROS generation observed in treated parasites. Trypanosoma evansi , a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC 50 /24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC 50 to IC 50. Among the selected alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in reactive oxygen species (ROS) production. Therefore, increased apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi -infected mice model. [Display omitted] [ABSTRACT FROM AUTHOR]

The green synthesis of nanoparticles and their specific role in the field of medicine are getting humongous attention worldwide. Their eco friendly and non toxic behaviour gives them such immense priority in the field of medicines. In our study, we explored the antiurolithiatic potential of green synthesized Ag nanorods (AgNRs) from the root extract of Pleurolobus gangeticus (L.) J. St.- Hil. Ex H. Ohashi & K. Ohashi.(PG) on oxalate-induced injury to renal tubular epithelial cells. The extract obtained from P. gangeticus were successfully reduced to silver ions and silver nanorods were synthesized further. The PG derived AgNRs were characterized using UV–Visible Spectroscopy (UV–Vis), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction analysis (XRD), Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The results revealed that the synthesized silver nanoparticles are rod shaped nano clusters with an average diameter of 100–200 nm and an average length of 3–4 μm with a poly dispersive index value of 0.214. The AgNRs at a concentration of 500 μg/mL showed promising inhibitory potential on the CaOx crystals in a dose dependent manner with a maximum absorption of 0.178 ± 0.08. The AgNRs also showed potent cytoprotective effects on oxalate-induced Madin-Darby Canine Kidney (MDCK) renal epithelial cells in a dose dependent manner via reducing the reactive oxygen species (ROS) generation in the cells. Overall, our findings suggest the role of PG derived AgNRs as a potent source of antiurolithiatic agents and open a wide range of possibilities in the use of silver nanosystems for the treatment of urolithiasis. • Pleurolobus gangeticus (L.) J. St.- Hil. Ex H. Ohashi & K. Ohashi is an important medicinal plant which exhibits versatile medicinal applications. • This is the first report of the antiurolithiatic potential of AgNRs from this plant species. • Green synthesized AgNRs from Pleurolobus gangeticus showed good antiurolithiatic potential against renal cellular injury in MDCK cells. • The findings opens a wide range of possibilities in the use of silver nanosystems for the treatment of urolithiasis. [ABSTRACT FROM AUTHOR]

Acrylamide (AA) toxicity remains an interesting subject in toxicological research. The aim of the research performed in this paper was to determine mechanisms of cyto- and genotoxic effects of AA on the human colon adenocarcinoma cell line Caco-2, to estimate the inhibitory concentration (IC)50 values in cell viability assays, to measure the basal and oxidative DNA damage as well as the oxidative stress leading to apoptosis, and to assess the morphological changes in cells using microscopic methods. It has been proven that AA induces cytotoxic and genotoxic effects on Caco-2 cells. Higher cytotoxic activity was gained in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay compared with the PrestoBlue assay, with IC50 values of 5.9 and 8.9 mM after 24 h exposure, respectively. In the single-cell gel electrophoresis assay, the greatest DNA damage was caused by the highest concentration of acrylamide equal to 12.5 mM (89.1% ± 0.9%). AA also induced oxidative DNA damage and generated reactive oxygen species (ROS), which was concentration dependent and correlated with the depletion of mitochondrial membrane potential and apoptosis induction. In the microscopic staining of cells, AA in the dosage close to the IC50 induced morphological changes typical for apoptosis. Taken together, these results demonstrate that AA has a pro-oxidative effect on Caco-2 cells, leading to apoptotic cell death.

2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

Two complexes of bis(aminobenzoato)zirconium(IV) phthalocyanine and their graphite oxide-based composites were synthesized and characterized in respect of their photochemical properties. Structures of phthalocyanines were confirmed by Mass and infrared spectroscopies. The absorption and photoluminescence spectra were investigated to show various behavior of the complexes in different media (dimethyl sulfoxide and saline). Optical technique (monitoring variation of absorption spectra of diphenylisobenzofuran used as an indicator) was used to prove the generation of reactive oxygen species (ROS) by under light irradiation in the range of the first biological window. The photoactivity of the materials was compared and discussed in terms of their potential ability to be used in biomedical applications, for example, as photosensitizers in photodynamic therapy.

In search of an effective antibacterial agent that is useful in photodynamic therapy, new derivatives of zirconium(IV) phthalocyanine (ZrPc) complexes were obtained and linked to graphite oxide flakes. In the syntheses of ZrPc derivatives, two bis-axially substituted ligands with terminal amino group and different lengths of linear carbon chain (C4 in 4-aminobutyric acid or C11 in 11-aminoundecanoic acid) were used. The optical properties (absorption and photoluminescence spectra) of ZrPcs and the composites were examined. Broadband red−near-infrared lamp was tested as an external stimulus to activate ZrPcs and the composites. Optical techniques were used to show generation of singlet oxygen during irradiation. Considering the application of graphite oxide-based materials as bacteriostatic photosensitive additives for endodontic treatment of periapical tissue inflammation, the antibacterial activity was determined on one Escherichia coli strain isolated directly from an infected root canal of a human tooth and one strain with silver and antibiotic resistance. Looking at the obtained results, modified levels of activity toward different bacterial strains are discussed.

Rhizoma paridis is a popularly-used Chinese medicine in clinics, based on the pharmacodynamic properties of its saponin components. The four main saponins in Rhizoma paridis are designated saponins I, II, VI, and VII. At present, much attention is focused on the anticancer effect of Rhizoma paridis which is manifested in its cytotoxicity to various cancer cells. The purpose of this study was to investigate the hepatocellular toxicities of the four saponins in Rhizoma paridis and the relative intensities of their cytotoxic effects. It was found that the four saponins were cytotoxic to two types of hepatocytes-HL-7702 and HepaRG cells. The cytotoxicities of the four saponins to the two cell models were compared. One of the most cytotoxic saponins was Rhizoma paridis saponin I (PSI). This was used to determine the mechanism of hepatocellular toxicity. Results from MTT assays demonstrated that the four saponins induced apoptosis of the two hepatocyte models in a dose-dependent and time-dependent manner. In addition, fluorescent 4′,6-diamidino-2-phenylindole (DAPI) staining was used to observe the morphological changes of HepaRG cells after saponin administration. Further, as the concentration increased, PSI-induced lactate dehydrogenase (LDH) release from HepaRG cells increased gradually. In addition, PSI enhanced the levels of reactive oxygen species (ROS) and blocked the S and G2 phases of the cell cycle in HepaRG cells. A western blot indicated that PSI upregulated the protein expression levels of p53, p21, and Fas. Furthermore, the PSI-induced changes in the p53 protein increased the Bax/bcl-2 ratio, resulting in enhancement of the release of mitochondrial cytochrome c, activation of caspases-3, -8, and -9, poly-ADP ribose polymerase (PARP), and ultimately apoptosis. Increased Fas protein activated caspase-8, which led to the activation of caspase-3 and its downstream PARP protein, resulting in cell apoptosis. These results indicate that PSI induced apoptosis in HepaRG cells through activation of ROS and death receptor pathways. The results obtained in this study suggest that the hepatocellular toxicity of saponins in Rhizoma paridis should be considered during the clinical application of this drug. In addition, they provide a reference for future anti-cancer studies on Rhizoma paridis.

1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).

Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone- and guanidine-containing molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1–4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bis-guanylhydrazones were between 2 and 15.6 μg/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitro DNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent. [ABSTRACT FROM AUTHOR]

Nanoparticles have emerged as a boon for the public health applications such as drug delivery, diagnostic, and imaging. Biodegradable and non-bio degradable nanoparticles have been used at a large scale level to increase the efficiency of the biomedical process at the cellular, animal and human level. Exponential use of nanoparticles reinforces the adverse immunological changes at the human health level. Physical and chemical properties of nanoparticles often lead to a variety of immunotoxic effects such as activation of stress-related genes, membrane disruption, and release of pro-inflammatory cytokines. Delivered nanoparticles in animal or human interact with various components of the immune system such as lymphocytes, macrophages, neutrophils etc. Nanoparticles delivered above the threshold level damages the cellular physiology by the generation of reactive oxygen and nitrogen species. This review article represents the potential of nanoparticles in the field of nanomedicine and provides the critical evidence which leads to develop immunotoxicity in living cells and organisms by altering immunological responses. [ABSTRACT FROM AUTHOR]

The present investigation was aimed to discover the activity of raw (RCNTs) and functionalized multi-walled carbon nanotubes (FCNTs) for their cytotoxic potential in human breast cancer (MCF-7) cells. The RCNTs were functionalized with the acid treatment method and were characterized by SEM and TEM. The morphology of RCNTs and FCNTs were found to be variable with a size range of ∼10–15 nm diameter were as the length goes up to 2–4 μm. For, cytotoxicity assessments, MCF-7 cells were exposed to RCNTs and FCNTs at 5–400 μg/ml concentrations for 24 h. The cytotoxicity was measured by MTT and NRU assays, and cellular morphology using phase contrast microscope. Further, intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were also studied. The results of MTT and NRU assays exhibited a concentration-dependent decrease in cell viability of MCF-7 cells. The RCNTs and FCNTs exposed cells were also found to alter the normal morphology of MCF-7 cells. Furthermore, the cells showed significant induction in ROS generation and reduction in MMP level. The results of this study, demonstrated that RCNTs and FCNTs has the potential to induce cytotoxicity in MCF-7 cells which could be mediated through the reactive oxygen species (ROS) generation. [ABSTRACT FROM AUTHOR]

Salt toxicity of agricultural land is a natural phenomenon which is due to agricultural irrigation. This toxicity is harmful to crop productivity via increasing oxidative stress products. In a factorial controlled trial, four levels of lignite-enriched soil (soil lignite content: none, 50, 75 and 100 g kg −1 ) were exposed to three levels of soil salinity (0, 5 and 10 dS m −1 NaCl). Then reactive oxygen species (ROS) generation (hydrogen peroxide and superoxide radical), lipid peroxidation, antioxidant enzymes activities (peroxidase, catalase and super oxide dismutase), proline, glycine betaine, soluble sugars and soluble protein contents of soybean plants were compared across different lignite concentration and saline toxicity. Under the 5 and 10 dS m −1 NaCl, sodium entry to the leaf and root cells, hydrogen peroxide concentration, superoxide radical generation, lipid peroxidation and osmoprotectants creation increased and consequently plant growth reduced (12–49%). Lignite applications by improving the cation exchange capacity of soil (8–16%), enriched the leaf and root cells with potassium (5–26%), calcium (40–56%), magnesium (30–42%) and inhibited the sodium entry to the cells, and consequently increased potassium/sodium ratio and reduced oxidative stress, antioxidant activities and synthesis of osmoprotectants in soybean leading to increased plant biomass (18–37%). Lignite usage in 75 and 100 g kg −1 soil showed a better effect than 50 g kg −1 soil on reducing harmful effects of salt toxicity. Soil enrichment with lignite improves plant tolerance to salt toxicity via decreased oxidative stress. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is reported as a promising anti-cancer therapeutic agent. Nevertheless, a variety of cancer cells, including human malignant glioma cells, are resistant to TRAIL treatment, indicating that it is necessary to find effective strategies to overcome the TRAIL resistance. Linarin (LIN), a natural flavonoid compound in Flos Chrysanthemi Indici (FCI) , has been exhibited to exert various pharmacological activities, including anti-cancer. Here in our study, we found that non-cytotoxic doses of LIN (5 μM) dramatically potentiated TRAIL (80 ng/ml)-induced cytotoxicity (52.36 ± 1.58%) and apoptosis (68.50 ± 1.23%) using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry assays, respectively, in human glioma cells of U87MG. Apoptosis was evidenced by enhanced cleavage of Caspase-8/-9/-3 and poly (ADP-ribose) polymerase (PARP), and reduced anti-apoptotic proteins, including B-cell leukemia/lymphoma 2 (Bcl-2), mantle cell lymphoma (Mcl)-1, and Survivin. Moreover, both intrinsic and extrinsic apoptosis pathways were included in apoptosis induced by LIN and TRAIL co-treatment, along with high release of Cyto-c into cytoplasm and enhancement of fas-associated protein with death domain (FADD), death-inducing signaling complex (DISC), death receptor 4 (DR) 4 and DR5, respectively. Reactive oxygen species (ROS) generation, up to 39.86 ± 2.32%, was also highly triggered by TRAIL and LIN combinational treatment, which was accompanied with high phosphorylation of c-Jun-N-terminal kinase (JNK). In vivo, TRAIL and LIN double treatment significantly reduced the tumor growth using xenograft tumor model through inducing apoptosis. We demonstrated that combining LIN with TRAIL treatments might be effective against TRAIL-resistant glioma cells through inducing apoptosis regulated by ROS generation. [ABSTRACT FROM AUTHOR]

Isoquercetin exerts multiple pharmacological effects against various diseases. The present research sought to further investigate the role of isoquercetin in hypoxia/reoxygenation (H/R)-treated cardiomyocytes and its potential mechanism involved. The H/R model in H9C2 cells was established to mimic myocardial I/R injury in vitro . Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. We found that isoquercetin protected H9C2 cells from H/R-induced injury as the evidences that isoquercetin administration attenuated the effects of H/R treatment on H9C2 cell viability, cell apoptosis and ROS generation after H/R treatment. More importantly, isoquercetin protects mitochondrial function and prevents cytochrome c release in H9C2 cells after I/R injury. In conclusion, these results revealed the potential cardiovascular protective effects of isoquercetin in the treatment of I/R-related myocardial injury. [ABSTRACT FROM AUTHOR]

Background: The special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection. Methods: Cellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration. Results: Internalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period. Conclusion: Our data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health. [ABSTRACT FROM AUTHOR]

Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (Fe 3 O 4 ) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble Fe 3 O 4 nanoparticles (Fe 3 O 4 @DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy. The combination of photothermal therapy combined with chemotherapy results demonstrated that the synthesized Fe 3 O 4 @DMSA/DOX is an excellent candidate for pH- and NIR-light induced phothothermal agent for an effective delivery of anticancer drug (DOX) into the target sub-cellular level into the human breast cancer (MDA-MB-231) cells. Furthermore, the Fe 3 O 4 @DMSA/DOX nanoparticles induced an excellent temperature elevation upon NIR light irradiation and controlled DOX release in vitro. The Fe 3 O 4 @DMSA/DOX nanoparticles exhibited synergistic effect when combining chemotherapy with photothermal therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition, the combined chemo-photothermal therapy of Fe 3 O 4 @DMSA/DOX nanoparticles promoted an effective cell death by mitochondrial disruption mediated by ROS generation. Thus, the synthesized Fe 3 O 4 @DMSA/DOX nanoparticles could be utilized as potential anticancer agents for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex [Cu(ttpy)]Cl was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C-H···π inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin. Hoechst 33258, AO/EB and PI (flow cytometry) staining methods suggest that the complex can induce apoptosis in EAC cells. Cell cycle analyses also support the induced apoptosis. Cellular uptake studies revealed that the complex can go into the cytoplasm and accumulate in the cell nuclei. The complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway by activating caspase 3 and caspase 7 and regulates the Bcl-2 family proteins. In vivo study of the complex was validated against the animal tumor growth (EAC) cell in Swiss albino mice. Graphical abstract: The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway and significantly reduced the body weight and solid tumor volume in Swiss albino mice. [ABSTRACT FROM AUTHOR]

Cancer is one of the life-threatening diseases and a leading cause of death worldwide. Herbal medicine has a potential of treating many diseases. Nigella sativa L. is a widely used plant in traditional systems of medicine. The cytotoxic potential of Nigella sativa seed oil (NSO) was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), neutral red uptake (NRU) assays and morphological alterations in HepG2, MCF-7, A-549 and HEK293 cell lines. Further, the influence of cytotoxic concentrations (50–250 μg/ml) of NSO on oxidative stress markers (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) and mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9, Bax, Bcl-2) were studied. The results exhibited significant decrease in the percentage cell viability of HepG2, MCF-7 and A-549 cells in a concentration-dependent manner. However, NSO showed higher cytotoxic response in HepG2 cells and less in HEK293 cells. Therefore, HepG2 cells were selected to further investigate the underlying mechanism(s) responsible for the cytotoxic response. NSO was found to induce oxidative stress in a concentration-dependent manner, which was indicated by induction of ROS and LPO along with decrease in reduction in GSH and MMP. Quantitative real-time PCR data showed that following the exposure of HepG2 cells to NSO, the level of mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9 and bax) was up-regulated whereas, anti-apoptotic gene bcl-2 was down-regulated. The results demonstrated that NSO induced cytotoxicity and apoptosis in HepG2 cells via ROS generation, which is likely mediated through the p53 pathway. [ABSTRACT FROM AUTHOR]

The present study reports the chemical synthesis of gold nanoparticles (AuNPs) using sodium borohydride as a reducing and capping agent. The various temperatures and time intervals were investigated for controlled formation of AuNPs. The characterization of AuNPs was studied using UV-vis spectrophotometer, transmission electron microscope (TEM), selected area diffraction (SAED), energy-dispersive X-ray spectrophotometer (Edx), dynamic light scattering (DLS), zeta potential, and X-ray powder diffraction (XRD), and results indicated that AuNPs were spheroid in shape and cubic lattice and face centered in nature with 29 nm in size. AuNPs have potential antimicrobial activity against selected human clinical pathogens. IC concentration of AuNPs was determined as 20 μg/ml against non-small cell lung cancer (NSCLC) cell lines using MTT assay. The morphological and apoptosis effects of AuNPs on NSCLC were investigated using acridine orange/ethidium bromide (AO/EB), 2′,7′-dichlorofluorescein-diacetate (DCFH-DA), rhodamine 123, and 4′,6-diamidino-2-phenylindole (DAPI) staining method, and results indicated that AuNPs have potential anticancer activity against NSCLC cell lines. The anticancer activity of AuNPs is that it has less toxicity against human HBL100 normal cells. These anticancer potentials of AuNPs were compared with the standard drug cisplatin. Moreover, after 24 h exposure, AuNPs arrest the cell cycle at G2/M phase in A549 cells. These findings suggested that AuNPs could act as a potential anticancer agent against lung cancer. [ABSTRACT FROM AUTHOR]

The current study is to develop a natural drug carrier with seaweed derived polymers namely κ-Carrageenan (κ-Car) for drug delivery applications. κ-Car is a natural polysaccharide which derived from edible red seaweeds, they are easily available, non-toxic, cost effective, biodegradable and biocompatible nature. Curcumin (Cur) is a yellow-orange polyphenol existing in turmeric, which is predominantly used as spice and food coloring agent. The ultimate use of polymeric composites, especially those composed of natural polymers, has become a very interesting approach in recent drug delivery applications, due to their non-toxicity and biological origin. In this study the primary approach which depends on the loading of Curcumin into κ-Carrageenan was accomplished, and which (κ-Car-Cur) an active drug carrier was developed for drug delivery against selected lung cancer cells (A549). Thus, the κ-Car-Cur was synthesized by solvent evaporation method followed by freeze drying, and it was further characterized. From this study, it has been reported that the high encapsulation efficiency, good stability, and successful release of Cur from the carrier (κ-Car) was achieved. The drug release was more active at acidic pH 5.0 with the cumulative release of 78%, which is the favorable condition present in tumor microenvironments. The in vitro cellular applications studies of κ-Car-Cur demonstrated that, κ-Car-Cur composites induced higher cytotoxicity against selected cancer cells than free Cur and effectively involved to trigger cellular apoptosis in A549 cancer cells. Further, it was also possessed that inhibition of cell growth and changes in metabolic activity of cancer cells are the unique characteristic features of cellular apoptosis, through reactive oxygen species (ROS) generation. It also observed that there was a decrease in mitochondrial membrane potential ( ΔψmΔψm ) which leads to a cellular apoptosis during treatment with κ-Car-Cur. Hence, the study outcomes may provide the potential outline for the use of κ-Car-Cur as a promising tool to deliver drugs at intracellular level. [ABSTRACT FROM AUTHOR]