Simulated microgravity increases heavy ion radiation-induced apoptosis in human B lymphoblasts

Aims

Microgravity and radiation, common in space, are the main factors influencing astronauts' health in space flight, but their combined effects on immune cells are extremely limited. Therefore, the effect of simulated microgravity on heavy ion radiation-induced apoptosis, and reactive oxygen species (ROS)-sensitive apoptosis signaling were investigated in human B lymphoblast HMy2.CIR cells.

Main methods

Simulated microgravity was achieved using a Rotating Wall Vessel Bioreactor at 37 °C for 30 min. Heavy carbon-ion irradiation was carried out at 300 MeV/u, with a linear energy transfer (LET) value of 30 keV/μm and a dose rate of 1 Gy/min. Cell survival was evaluated using the Trypan blue exclusion assay. Apoptosis was indicated by Annexin V/propidium iodide staining. ROS production was assessed by cytometry with a fluorescent probe dichlorofluorescein. Malondialdehyde was detected using a kit. Extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase phosphatase-1 (MKP-1) and caspase-3 activation were measured by immunoblotting.

Key findings

Simulated microgravity decreased heavy ion radiation-induced cell survival and increased apoptosis in HMy2.CIR cells. It also amplified heavy ion radiation-elicited intracellular ROS generation, which induced ROS-sensitive ERK/MKP-1/caspase-3 activation in HMy2.CIR cells. The above phenomena could be reversed by the antioxidants N-acetyl cysteine (NAC) and quercetin.

Significance

These results illustrated that simulated microgravity increased heavy ion radiation-induced cell apoptosis, mediated by a ROS-sensitive signal pathway in human B lymphoblasts. Further, the antioxidants NAC and quercetin, especially NAC, might be good candidate drugs for protecting astronauts' and space travelers' health and safety.     

A possible theranostic approach of chitosan-coated iron oxide nanoparticles against human colorectal carcinoma (HCT-116) cell line

Iron oxides have become increasingly popular for their use as a diagnostic and therapeutic tool in oncology. This study aimed to improve pharmacological valuable of Fe₃O₄, which may be use to diagnosis colorectal cancers (CRC). Here, we have developed chitosan (CS) coated Fe₃O₄ through a cost-effective procedure. First, we determined the characterization of OA-C-Fe₃O₄ by FTIR, UV–Vis spectra, and TEM. Then, we evaluated the photodynamic therapeutic (PDT) activity of OA-C-Fe₃O₄ in human colorectal carcinoma cell lines (HCT 116). Current results revealed that the light-induced enhanced reactive oxygen species (ROS) activity of the nanoparticles (NPs) and caused cell death via the activity of caspase 9/3. The in vitro magnetic resonance imaging (MRI) experiments in (HCT 116) and human embryonic kidney cells (HEK 293) illustrated that nanohybrid is an effective MRI contrasting agents for the diagnosis of colorectal cancer.     

Significance of phenols in cadmium and nickel uptake

The effects of 2-aminoindane-2-phosphonic acid (AIP), a potent phenylalanine ammonia-lyase (PAL) inhibitor, on the accumulation of cadmium and nickel in chamomile (Matricaria chamomilla) were examined in this study. In vitro assay of AIP effect showed a 90% reduction in PAL activity. In plants cultured for 7 days in Cd or Ni solutions with AIP, PAL activity was higher in both shoots and roots (in comparison with metals without AIP), and was correlated with changes in free phenylalanine content. Individual amino acids were both positively and negatively affected by AIP, with the accumulation of tyrosine and proline showing increases in some variants. Contents of soluble phenols and flavonoids were not considerably affected, while amounts of coumarin-related compounds, cell wall-bound phenols and phenolic acids were substantially reduced in AIP-treated variants. Lignin accumulation decreased in controls and increased in Cd variants in response to AIP. Shoot Cd content was depleted, but shoot Ni was elevated by AIP. Total root content of Cd and Ni decreased in +AIP variants. AIP also caused more expressive changes in hydrogen peroxide and superoxide content in Cd than in Ni variants. Our results indicate that phenols have important roles in the uptake of Cd and Ni. The present findings are discussed in the context of available data regarding AIP's effect on phenols.     

Cu,Zn-superoxide dismutase is differently regulated by cadmium and lead in roots of soybean seedlings

The cadmium (Cd²⁺) and lead (Pb²⁺)-induced changes in Cu,Zn-SOD gene expression on the level of mRNA accumulation and enzyme activity were analyzed in roots of soybean (Glycine max) seedlings. The Cd²⁺ caused the induction of copper–zinc superoxide dismutase (Cu,Zn-SOD) mRNA accumulation, at each analyzed metal concentration (5–25 mg/l), whereas in Pb²⁺-treated roots this effect was observed only at the medium metal concentrations (50–100 mg/l of Pb²⁺). The analysis of Cu,Zn-SOD activity proved an increase in enzyme activity during Cd²⁺/Pb²⁺ stresses, however in Pb²⁺-treated plants the activity of enzyme was not correlated with respective mRNAs level. Presented data suggest that different metals may act on various level of Cu,Zn-SOD expression in plants exposed to heavy metals stress.     

A modeling and simulation perspective on the mechanism and function of respiratory complex I

Respiratory complex I is a giant redox-driven proton pump, and central to energy production in mitochondria and bacteria. It catalyses the reduction of quinone to quinol, and converts the free energy released into the endergonic proton translocation across the membrane. The proton pumping sets up the proton electrochemical gradient, which propels the synthesis of ATP. Despite the availability of extensive biochemical, biophysical and structural data on complex I, the mechanism of coupling between the electron and proton transfer reactions remain uncertain. In this work, we discuss current state-of-the-art in the field with particular emphasis on the molecular mechanism of respiratory complex I, as deduced from computational modeling and simulation approaches, but in strong alliance with the experimental data. This leads to novel synthesis of mechanistic ideas on a highly complex enzyme of the electron transport chain that has been associated with a number of mitochondrial and neurodegenerative disorders.     

Green synthesis of ZnO nanoparticles for antimicrobial and vegetative growth applications: A novel approach for advancing efficient high quality health care to human wellbeing

The present work aims to synthesize zinc oxide (ZnO) nanoparticles via green approaches using leaf extract of Parthenium hysterophorus. UV–vis and FT-IR tests confirmed the existence of biomolecules, active materials, and metal oxides. The X-ray diffraction structural study exposes the ZnO nanoparticles formation with hexagonal phase structures. SEM and TEM analysis reveal surface morphologies of ZnO nanoparticles and most of them are spherical with a size range of 10 nm. ZnO nanoparticles were revealed strong antimicrobial activity against both bacterial and fungal strains. The germination of seeds and vegetative growth of Sesamum indicum has been greatly improved.     

Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles

Abstract

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more 5-ALA or 5-ALA-Me (for MCF-7) and 7 µg/mL of 15 nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of the levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence or absence of AuNPs. Cytotoxicity was observed irrespective of the presence of serum and medium. Production of ROS in cell free samples containing 5-ALA-Me was monitored by EPR as the DMPO-OH spin adduct and also showed a catalytic effect of AuNPs. Both SOD and CAT inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy.     

The role of nitrite ion in phagocyte function—perspectives and puzzles

Macrophages and neutrophils are essential elements of host cellular defense systems that function, at least in part, by generating respiration-driven oxidative toxins in response to external stimuli. In both cells, encapsulation by phagocytosis provides a mechanism to direct the toxins against the microbes. The toxic chemicals formed by these two phagocytic cells differ markedly, as do the enzymatic catalysts that generate them. Nitrite ion is microbicidal under certain conditions, is generated by activated macrophages, and is present at elevated concentration levels at infection sites. In this review, we consider potential roles that nitrite might play in cellular disinfection by these phagocytes within the context of available experimental information. Although the suggested roles are plausible, based upon the chemical and biochemical reactivity of , studies to date provide little support for their implementation within phagosomes.     

CD95 activation in the liver: ion fluxes and oxidative signaling

Apoptosis is characterized by typical features as cell shrinkage, nuclear condensation, DNA fragmentation, and apoptotic body formation. Whereas some signs of apoptosis are cell type-and death signal-dependent, apoptotic cell volume decrease is an early and ubiquitous event and little is known about the signalling events, which are localized upstream of the plasma membrane transport steps leading to apoptotic cell volume decrease and the proapoptotic events, which are induced by osmolyte loss and cell shrinkage. Ion fluxes and oxidative signaling were recently shown to play an important role in signal transduction with respect to apoptotic cell death within the liver, as a ceramide-dependent activation of the NADPH oxidase was identified as the source of reactive oxygen species generation in rat hepatocytes upon treatment with CD95 ligand, hydrophobic bile salts or hyperosmolarity. The NADPH oxidase-derived ROS signal then allows via Yes, JNK, and EGFR activation for CD95 tyrosine phosphorylation as a prerequisite for CD95 targeting to the plasma membrane and formation of the death inducing signalling complex. Other covalent modifications such as CD95-tyrosine-nitration or CD95-serine/threonine-phosphorylation can interfere with the CD95 activation process. The findings not only provide a mechanistic explanation for the high susceptibility of dehydrated cells for apoptosis, but also give insight into the role of ion fluxes and oxidative signaling with respect to apoptotic cell death within the liver.     

Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.     

Inactivation of <Emphasis Type="Italic">Escherichia coli</Emphasis> and coliform bacteria in traditional brass and earthernware water storage vessels

The detection and enumeration of indicator bacteria such as Escherichia coli is used to assess the extent of faecal contamination of drinking water. On the basis of this approach, the effectiveness of storing water contaminated with faecal indicator bacteria in brass or earthern vessels (mutkas) of the type used in rural India have been investigated. Suspensions of bacteria in sterile distilled water were maintained for up to 48 h in each vessel and enumerated by surface plate counts on nutrient agar (non-selective) and several selective coliform media at 37 °C either under standard aerobic conditions, or under conditions designed to neutralise reactive oxygen species (ROS), e.g. using an anaerobic cabinet to prepare plates of pre-reduced growth medium or by inclusion of sodium pyruvate in the growth medium, with incubation of aerobically-prepared plates in an anaerobic jar. The counts obtained for E. coli decreased on short-term storage in a brass mutka; counts for selective media were lower than for equivalent counts for non-selective medium, with ROS-neutralised conditions giving consistently higher counts than aerobic incubation. However, after 48 h, no bacteria were cultivable under any conditions. Similar results were obtained using water from environmental sources in the Panjab, and from rural households where brass and earthern mutkas are used for storage of drinking water, with enumeration on selective coliform media (presumptive total coliforms). In all cases results indicated that, while storage of water in a brass mutka can inactivate E. coli and coliforms over a 48 h period, standard aerobic plate counting using selective media may not be fully effective in enumerating sub-lethally damaged bacteria.     

A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus

Glabridin a polyphenolic flavonoid from Glycyrrhiza glabra is known to possess several therapeutic properties. In the present study, we report for the first time the in vitro antibacterial activity (MIC values ranging from 3.12 to 25 μg/mL) of glabridin against multidrug-resistant clinical isolates of S. aureus by inducing oxidative stress. Increased levels of H₂O₂ and NO were observed in a dose-dependent manner after treatment of glabridin that further affected macromolecules such as DNA, lipids, and proteins. Surprisingly, glabridin was found to possess antioxidant properties when used at lower concentrations using three different methods including DPPH, FRAP, and SOD assays. These observations were further validated through the expression analysis of oxidative stress-responsive genes using qRT-PCR wherein glabridin was observed to up- and down-regulate these genes at lower and higher concentrations, respectively. In in vitro combination experiments, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the MIC of glabridin itself was found to be reduced by up to 8-fold in the presence of antibiotics. A synergistic interaction was observed between norfloxacin and glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy.     

PEGylated ceria nanoparticles used for radioprotection on human liver cells under γ-ray irradiation

Ceria nanoparticles (CNPs) have recently been shown to protect cells and animals from radiation-induced damage. However, most of the CNPs used in previous studies were either naked or weakly protected by surfactants, which inevitably encounter many obstacles in biological applications. Here, alendronate was used as an ideal anchor to graft polyethylene glycol (PEG) onto CNPs, leading to enhanced stability, reduced cytotoxicity, and improved biological properties. Further investigation assessed the protective ability of the nanoparticles against radiation-induced effects for human normal liver cells (L-02), indicating that the PEGylated CNPs (CNPs–AL–PEG) were more efficient than naked CNPs. We determined that enhanced Ce³⁺/Ce⁴⁺ ratios improved intracellular dispersion and that the ameliorated intracellular distribution of CNPs–AL–PEG contributes to the elevated expression of SOD2, which leads to increased protection of normal cells against ROS and reduces the oxidatively generated DNA damage. These studies hold tremendous promise for radioprotection and biological applications.     

Skeletal muscle reactive oxygen species: A target of good cop/bad cop for exercise and disease

Abstract

Metabolic stresses associated with disease, ageing, and exercise increase the levels of reactive oxygen species (ROS) in skeletal muscle. These ROS have been linked mechanistically to adaptations in skeletal muscle that can be favourable (i.e. in response to exercise) or detrimental (i.e. in response to disease). The magnitude, duration (acute versus chronic), and cellular origin of the ROS are important underlying factors in determining the metabolic perturbations associated with the ROS produced in skeletal muscle. In particular, insulin resistance has been linked to excess ROS production in skeletal muscle mitochondria. A chronic excess of mitochondrial ROS can impair normal insulin signalling pathways and glucose disposal in skeletal muscle. In contrast, ROS produced in skeletal muscle in response to exercise has been linked to beneficial metabolic adaptations including mitochondrial biogenesis and muscle hypertrophy. Moreover, unlike insulin resistance, exercise-induced ROS appears to be primarily of non-mitochondrial origin. The present review summarizes the diverse ROS-targeted metabolic outcomes associated with insulin resistance versus exercise in skeletal muscle, thus, presenting two contrasting perspectives of pathologically harmful versus physiologically beneficial ROS. Here, we discuss the key sites of ROS production during exercise and the effect of ROS in skeletal muscle of people with type 2 diabetes.     

Toxicity of gold nanoparticles (AuNPs): A review

Gold nanoparticles are a kind of nanomaterials that have received great interest in field of biomedicine due to their electrical, mechanical, thermal, chemical and optical properties. With these great potentials came the consequence of their interaction with biological tissues and molecules which presents the possibility of toxicity. This paper aims to consolidate and bring forward the studies performed that evaluate the toxicological aspect of AuNPs which were categorized into in vivo and in vitro studies. Both indicate to some extent oxidative damage to tissues and cell lines used in vivo and in vitro respectively with the liver, spleen and kidney most affected. The outcome of these review showed small controversy but however, the primary toxicity and its extent is collectively determined by the characteristics, preparations and physicochemical properties of the NPs. Some studies have shown that AuNPs are not toxic, though many other studies contradict this statement. In order to have a holistic inference, more studies are required that will focus on characterization of NPs and changes of physical properties before and after treatment with biological media. So also, they should incorporate controlled experiment which includes supernatant control Since most studies dwell on citrate or CTAB-capped AuNPs, there is the need to evaluate the toxicity and pharmacokinetics of functionalized AuNPs with their surface composition which in turn affects their toxicity. Functionalizing the NPs surface with more peculiar ligands would however help regulate and detoxify the uptake of these NPs.     

Proteome of plant peroxisomes: new perspectives on the role of these organelles in cell biology

Peroxisomes are cell organelles bounded by a single membrane with a basically oxidative metabolism. Peroxisomes house catalase and H₂O₂‐producing flavin‐oxidases as the main protein constituents. However, since their discovery in early fifties, a number of new enzymes and metabolic pathways have been reported to be also confined to these organelles. Thus, the presence of exo‐ and endo‐peptidases, superoxide dismutases, the enzymes of the plant ascorbate‐glutathione cycle plus ascorbate and glutathione, several NADP‐dehydrogenases, and also L‐arginine‐dependent nitric oxide synthase activity has evidenced the relevant role of these organelles in cell physiology. In recent years, the study of new functions of peroxisomes has become a field of intensive research in cell biology, and these organelles have been proposed to be a source of important signal molecules for different transduction pathways. In plants, peroxisomes participate in seed germination, leaf senescence, fruit maturation, response to abiotic and biotic stress, photomorphogenesis, biosynthesis of the plant hormones jasmonic acid and auxin, and in cell signaling by reactive oxygen and nitrogen species (ROS and RNS, respectively). In order to decipher the nature and specific role of the peroxisomal proteins in these processes, several approaches including in vivo and in vitro import assays and generation of mutants have been used. In the last decade, the development of genomics and the report of the first plant genomes provided plant biologists a powerful tool to assign to peroxisomes those proteins which harbored any of the two peroxisomal targeting signals (PTS, either PTS1 or PTS2) described so far. Unfortunately, those molecular approaches could not give any response to those proteins previously localized in plant peroxisomes by classical biochemical and cell biology methods that did not contain any PTS. However, more recently, proteomic studies of highly purified organelles have provided evidence of the presence in peroxisomes of new proteins not previously reported. Thus, the contribution of proteomic approaches to the biology of peroxisomes is essential, not only for elucidation of the mechanisms involved in the import of the PTS1‐ and PTS2‐independent proteins, but also to the understanding of the role of these organelles in the cell physiology of plant growth and development.     

Neuroprotective potential of combination of resveratrol and 4-amino 1,8 naphthalimide in experimental diabetic neuropathy: Focus on functional,sensorimotor and biochemical changes

The present study investigated whether combination of resveratrol and 4-amino 1,8 naphthalimide (4-ANI) is effective in the development of diabetic neuropathy (DN). After 6 weeks of diabetes induction, rats were treated for 2 weeks with resveratrol and 4-amino 1,8 naphthalimide (4-ANI) either alone or in combination. Experimental end points included functional, behavioural and biochemical parameters along with PAR immunohistochemistry and were performed at the end of treatment. Combination of resveratrol (10 mg/kg) and 4-ANI (3 mg/kg) attenuated conduction and nerve blood flow deficits and resulted in amelioration of diabetic neuropathic pain. Significant reversal of biochemical alterations (peroxynitrite, MDA and NAD levels) were also observed, as well as PAR accumulation in the sciatic nerve. This study suggests the beneficial effect of combining resveratrol and 4-ANI in experimental diabetic neuropathy.