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An increase in anthropogenic activities results in metal contamination in the ecosystem which has proven to be a major health risk in humans, as they make entry into cellular organelles via agricultural products. Copper (Cu) is one such metal that acts as an essential cofactor for the activity of several enzymes, one being the cytochrome c oxidase. The increasing number of evidence suggests a substantial correlation of Cu overload with neurodegenerative disorders, including Parkinson's disease (PD). We aim to explore quercetin, a well-known polyphenol, as an alternative for combating Cu-induced toxicity in human neuroblastoma SH-SY5Y secondary cell lines. We observed that Cu increased intracellular reactive oxygen species (ROS) levels, triggered morphological deformities and condensation of nuclei, caused an imbalance in the mitochondrial membrane potential (MMP), and finally induced apoptotic cell deaths. We further investigated the effects of Cu in modulating the pro- and anti-apoptotic proteins, such as Bax, Bcl-2, etc. However, quercetin reversed these changes owing to its antioxidant and anti-apoptotic properties, resulting in autophagy induction as an outcome of upregulation of autophagosome-bound microtubules-associated protein light chain-3 (LC3II). Besides, we investigated the role of Cu in stimulating ER stress proteins, viz. PERK, CHOP, and the concomitant responses of quercetin in restoring the ER homeostasis in cellular organelles like mitochondria and ER, against Cu-induced toxic insults by modulating autophagic pathways. Overall, this research work proposes a remedial approach for Cu-mediated neurotoxicity through understanding the diverse molecular signaling inside a cell with an aim to develop effective therapeutics. [ABSTRACT FROM AUTHOR]

Single-Walled Carbon Nanotubes (SWCNTs) are widely used as potential carriers in drug delivery systems. The objective of this work was to observe the effects of pristine, and single-stranded DNA oligonucleotide functionalized SWCNT over the locomotion pattern in the nematode model, Caenorhabditis elegans. The implication of ssDNA in the as-modified SWCNT has been understood in terms of lowering the toxic effects of the pristine SWCNT and thereby normalizing the altered navigation pattern of the worms. Chemotaxis assay displayed an increased migration of the worms towards pristine and ssDNA functionalized SWCNT in comparison to ultrapure water as control. Additionally, paralytic movement was observed with SWCNT exposure in contrast to ssDNA-functionalized SWCNT-exposed animals. High doses of pristine SWCNT further displayed an increased expression of specific proteins obtained from the total protein extracts of the animals. Thus, the alteration in the navigation pattern of the worms, treated with pristine SWCNT, might be ascribed as a result of differentially expressed muscle proteins. Moreover, it is interesting to note that the modified SWCNT was effective in alleviating the atypical form of the inherent movements of the worm. Future investigation will further reveal the protein targets responsible for the altered navigation pattern of the worms. [ABSTRACT FROM AUTHOR]

Functionalized carbon nanotubes are recommended as potential drug-delivery tools due to their reduced toxicity and increased solubility or wettability. However, their applications are still restricted because of their dose- and time-dependent toxicity. The conflicting reports regarding toxicity assays of pristine and functionalized multiwalled carbon nanotubes (MWCNTs) in different in vivo and in vitro models inspired us to design a safe drug-releasing device and investigate its applicability in a widely used human-analogous in vivo model. We thereby propose a biocompatible drug-delivery vector that is nontoxic even at higher doses in the Caenorhabditis elegans nematode model. We further carried out a comparative analysis of the various biocompatibility assays of MWCNTs functionalized with inorganic and organic molecules. Synthetic single-stranded DNA (ssDNA) oligonucleotide (5′-GGG-GGG-GGG-G-3′)-functionalized MWCNTs were found to be the most biocompatible and nontoxic even at higher doses (320 µg/mL) of MWCNTs. In contrast, pristine and NH2-functionalized MWCNT were proven to be toxic at lower doses (20–160 µg/mL) of MWCNTs based on survival, locomotion, reproductive potential, and oxidative-stress-related endpoints. Thus, the order of cytotoxicity in animals was observed to be as follows: pristine MWCNTs > NH2-functionalized MWCNTs > ssDNA-functionalized MWCNT. [ABSTRACT FROM AUTHOR]

In this study, electronic properties of Manganese atom doped Graphene are studied using Atomistix Tool Kit-Virtual NanoLab (ATK-VNL), QuantumWise simulation package. All the calculations are done using density functional theory. The doping of Manganese atom creates a small band gap and this gap increases with increasing doping concentrations. Chemical potential measurements exhibit a rise in the values for pristine Graphene is − 10.48 to − 9.91 eV for single doped atom to − 9.87 eV for double doped Manganese atom to − 9.57 eV for triple atom doped Manganese. Total energy calculated for pristine, one, two and three Manganese atom doped Graphenes are as − 4506.6, − 4599.5, − 4691.97 and − 4789.31 eV, respectively. Optical spectrum plots also support the aforementioned characteristics deviation in the pristine Graphene. Transmission spectrum is also varied for pristine Graphene in comparison to one, two and three Manganese atom doped nanosheets. Density of states calculations also illustrates the rise in the values for the number of states occupied by electrons for pristine Graphene, one to three Manganese atom doped nanosheet, respectively. The flow of current reduces with increasing number of impure atoms. Understanding the effect of Manganese as dopant at different lattice sites of 2D-Graphene helps in designing conductivity tunable Graphene based electro-mechanical devices and sensors for myriad nanoelectronic applications. [ABSTRACT FROM AUTHOR]

The detrimental impact on the food chain due to the overuse of rotenone is partly responsible for alpha-synuclein (α-syn) mediated neurotoxicity. It is hypothesized that rotenone overdose leads to cytosolic proteopathy resulting in modulation of apoptosis and autophagic pathways. The aim of our study is to explore the neuroprotective role of quercetin, a beneficial polyphenol against rotenone-induced neurotoxicity in dopaminergic human SH-SY5Y cell lines. In our study we demonstrated the correlation of rotenone-induced neurotoxicity through elevation of intracellular reactive oxygen species (ROS) and imbalance in the mitochondrial membrane potential (MMP). Moreover, the morphological distortion of cell, condensation of nuclei, externalization of the inner phosphatidylserine, cleavage of caspase 3, and Poly ADP Ribose Polymerase (PARP) confirmed apoptosis. However, all these lethal effects were ameliorated by treatment of quercetin to the cells. On the other hand rotenone has a strong effect on autophagy which is a regulated degrading and recycling cellular process to remove dysfunctional proteins. Indeed, rotenone-mediated autophagy resulted in the enhancement of autophagosome-bound microtubule-associated protein light chain-3 (LC3-II) expression. Furthermore, excess accumulation of acidic vesicles was detected in presence of rotenone. Lysosome associated membrane protein (LAMP-2A) is yet another crucial protein that recruits overexpressed or misfolded proteins into the lumen of lysosome to trigger autophagy. In all cases the impact of rotenone on the cells acquired significant protection through quercetin treatment. In the present work we therefore opine the prospects of quercetin as a therapeutic candidate against neurotoxicity. [ABSTRACT FROM AUTHOR]

DEHP (Di-ethyl hexyl phthalate), an ubiquitous chemical constituent of plasticizer, cosmetics etc. poses different abnormal neurological and behavioral responses in eukaryotic model organism C. elegans (Caenorhabditis elegans). Based upon such reports, we hypothesized that due to exposure of DEHP, the larval growth of C. elegans was altered and animals went into dauer at high concentrations of exposure at 8.26 ppm. Using chemosensory assay, the orientation of repulsion (− 0.1) of the nematodes were determined with exposure of DEHP at 4.78 ppm and 8.26 ppm. We show that N2 wild type worms display a preferential food choice and search for favorable food, and alter two modes of locomotion (forward and backward) that measures the maximum bending rate of an adult worm. Thermo sensation also plays a crucial role in determining the toxicity level in C. elegans at 15 °C, 20 °C, and 25 °C. Understanding the chemosensory pattern towards a specific chemical for C. elegans, the recent work could shed light in exploring the molecular mechanism involved in the tactile movement of the worms against a specific chemical, thereby making worms a potential biological sensing platform for external stimuli perception. [ABSTRACT FROM AUTHOR]

Iron accumulation plays a major role in neuronal cell death which has severe effects on mental health like neurodegenerative disorders. The present work aims to explore the involvement of molecular pathways involved in iron-mediated neuronal cell death using Ferric Ammonium Citrate (FAC) as a source of iron to treat neuroblastoma SH-SY5Y cells. In this study, it was found that cytotoxicity induced by iron treatment is highly correlated with enhanced intracellular reactive oxygen species (ROS) generation and loss of mitochondrial integrity. Appearance of early and late apoptotic cells with altered nuclear morphology and increased expression of effector proteins, i.e., cleaved Caspase 3 and cleaved PARP (Poly-ADP-ribose Polymerase), clearly confirmed iron-induced apoptotic cell deaths. Furthermore, excess accumulation of acidic vesicles and microtubule-associated protein 1 light chain 3 (LC3) puncta and LC3II/I expressions were observed. Simultaneously, ultrastructural studies of SH-SY5Y cells demonstrated the accumulation of a large number of autophagosomes, autophagic vacuolization, and swollen mitochondria which further confirmed the induction of autophagy concomitant with mitochondrial damage. Furthermore, increased incorporation of lysosome-specific dye, LysoTracker Deep Red, and the red fluorescence retention of LC3-GFP-RFP constructs indicates the incomplete autophagy or autophagy dysfunction due to altered lysosomal activity. Hence, the present work unveiled the interruption in autophagy progression caused by the plausible suppression of lysosomal activity due to iron treatment resulting in autophagic cell death in SH-SY5Y cell lines. In general, both apoptotic and autophagic pathways were prominent and each of the pathways played their prospective roles, in iron-mediated neuronal cell death. [ABSTRACT FROM AUTHOR]

Graphene has been conjugated with Silicene which is a 2D nanosheet of silicon crystal to analyze myriad physico-chemical properties. Upon intercalation of silicene between two graphene nanosheets, there has been a significant shift in the energy of electronic configuration at different isovalues from − 0.12 to + 0.12. Similarly, by analyzing the electronic energy states of silicene–graphene–silicene, a range of isovalues from − 0.08 to + 0.08 were observed. I–V curve exhibited a linear response for graphene–silicene–graphene sandwiched structure and a semiconducting like behavior for silicene–graphene–silicene structure. Band gap measurement in case of graphene–silicene–graphene system is reported to be ~ 0.18 eV, which is a narrow region. While in case of silicene–graphene–silicene, a band gap value of ~ 1.01 eV is calculated that appears to be a pretty broad region. Transmission spectrum also shows intensity in peaks for Gr–Si–Gr case as compared to Si–Gr–Si combinations. Silicon is widely perceived to exhibit outstanding semiconducting behavior and has already been used in devising various electronic devices. In this present work, we try to analyze the outcome of the silicene and graphene at the nanometer scale in various combinations in a bid to understand the potential interaction mechanism between the two nanosheets which would help in the fabrication of the silicene–graphene based optoelectronic devices. [ABSTRACT FROM AUTHOR]

Conversion of the metallic SWCNT to semiconducting SWCNT was achieved by band structure engineering of the nanotube by functionalization of the DNA nucleobase, guanine. The band structure analysis revealed that metallic SWCNT (6, 0), when surface engineered with guanine nucleobase with H-atom attachment as the functional group, is converted to a semiconductor one by opening a narrow bandgap with a value of 0.08 eV. This phenomenon was brought about by strong chemisorption due to hydrogenation by inducing partial sp3 hybridization in the nanotube structure. No bandgap openings were observed when guanine was adsorbed on the pristine nanotube surface by its nitrogen site and oxygen site respectively. Related zero-bias transmission spectra and IV-curve supported the result also. The entire study was done at room temperature using ATK-VNL simulation software. [ABSTRACT FROM AUTHOR]

Pristine metallic single-walled carbon nanotubes (6, 0), surface engineered with pyrimidine type DNA nucleobases, thymine and cytosine respectively, are transformed into semimetal forms by band structure engineering of the nanotubes. The hybrid systems are designed using ATK–VNL simulation software. Band structure and zero bias transmission spectra analysis witness a very small overlap between the conduction and valence bands around the Fermi level. IV-characteristic curves also support the semimetallic nature of SWCNT–DNA nucleobase coupling. The altered electronic structure of SWCNT is achieved due to strong chemisorption imparted by hydrogenation of DNA nucleobases which induce partial sp3 hybridization in the nanotube structure. Metal to semimetal conversion results in conductivity modulation in SWCNT and it has several applications in various fields like nano-electronics including NEMS design. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "In Vivo Biointeraction and Alleviation of Toxicity of MWCNTs upon Functionalization with ssDNA in a Caenorhabditis elegans Model" published in February 6, 2023 issue.

Calcineurin, a well-conserved protein phosphatase 2B (PP2B), is a Ca-calmodulin-dependent serine/threonine protein phosphatase that is known to be involved in a myriad of cellular processes and signal transduction pathways. The biological role of calcineurin has been extensively studied in diverse groups of organisms. Homologues of mammalian and Drosophila calcineurin subunits exist in the nematode, Caenorhabditis elegans. The C. elegans counterpart of the catalytic subunit, calcineurin A, cna-1/ tax-6, and the regulatory subunit, calcineurin B, cnb-1, are known to express ubiquitously in multiple tissues including neurons. The characterization of C. elegans calcineurin mutants facilitates identification of its physiological functions and signaling pathways. Genetic interactions between cna-1/ tax-6 and cnb-1 mutants with a number of mutants involved in several signaling pathways have exemplified the pivotal role of calcineurin in regulating nematode development, behaviour and lifespan (aging). The present review has been aimed to provide a succinct summary of the multiple functions of calcineurin in C. elegans relating to its development, fertility, proliferation, behaviour and lifespan. Analyses of cna-1/ tax-6 and cnb-1 interacting proteins and regulators of the phosphatase in this fascinating worm model have an immense scope to identify potential drug targets in various parasitic nematodes, which cause many diseases inflicting huge economic loss; and also for many human diseases, particularly neurodegenerative and myocardial diseases. [ABSTRACT FROM AUTHOR]

Specific binding of Hg to ouabain-sensitive Na-K-ATPase of rat liver plasma membrane was demonstrated with a K of 2.64¥10 and B of 1.6nmole mg protein. The binding of mercury to the enzyme also causes significant inhibition of the enzyme, which is greater than its ouabain sensitivity. In the cytosol Hg binding to reduced glutathione (GSH) is stimulated by GSH-S-transferase (GST), the activity of which was found to be significantly enhanced by 15mM Na and 10mM Hg. It is proposed that the transport of Hg2 inside the cell takes place by increased dissociation of Hg from the membrane due to greater avidity of Hg towards cytosolar GSH binding. The GSH-Hg complex enters the nucleus where it dissociates to bind the metal response element (MRE) of the metallothionein (MT) gene to induce MT transcription. [ABSTRACT FROM AUTHOR]