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Aim This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells. Materials and Methods Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye. Alteration of 6-OHDA-caused mitochondrial membrane potential and nuclear condensation was investigated with the help of rhodamine-123 and hoechest stain. Immunoblotting was performed to detect the expression level of 6-OHDA-caused alpha-synuclein (á-syn), Bcl-2 associated protein X (BAX), caspase 3, cleaved Poly ADP – ribose polymerase (PARP) and Bcell lymphoma 2 proteins (Bcl-2). Result Through MTT assay, quercetin was selected over myricetin and kaempferol to counter 6-OHDA-caused cell death. The research delves into unraveling the intricate mechanisms underlying 6-OHDA-induced neurotoxicity, encompassing alterations in cellular morphology, escalation of oxidative stress, perturbation in mitochondrial membrane potential, and nuclear condensation. Exposure to 6-OHDA is implicated in the upregulation of á-syn protein, contributing to the aggravation of neurotoxicity. Concurrently, 6-OHDA orchestrates the apoptotic pathway by upregulating the expression of proapoptotic proteins such as BAX, caspase 3, and PARP, while down regulating the expression of the Bcl-2, affirming its role in apoptosis induction. Quercetin demonstrated ability to attenuate the expression of á-syn in the presence of 6-OHDA-caused injury in SH-SY5Y cells. Conclusion Taken together, these findings collectively underscore the therapeutic potential of quercetin as a promising agent against neurotoxicity caused by 6-OHDA. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) cause cell dysfunction with a gradual loss of neurons in the central nervous system and aberrant accumulation of aggregated proteins such as synuclein, tau, and amyloid. Alzheimer's disease and Parkinson's disease are the two frequently occurring neurodegenerative disorders. Nanobiotechnology being an emerging field used in applied biotechnology holds great potential for the advancement of treatments. This review aims to give a brief but comprehensive idea about the possibilities of utilizing the advanced nanotechnological aspect to treat the Alzheimer's and Parkinson's NDs that can be explored through proper investigations. In the present study, various kinds of literature were surveyed and reviewed to appreciate the neurodegenerative disease manifestation. It is becoming challenging to treat and discuss the potentiality of effective nano-mediated treatment strategies for Alzheimer's and Parkinson's diseases. The capability of current drugs to cross the blood-brain barrier (BBB) makes NDs' treatment even more challenging. Recent therapies for such kinds of diseases are focused on symptomatic relief. Nanoparticulate drug delivery systems address all the challenges from all aspects and offer novel therapeutics for NDs. With targeted drug delivery of the required drug or protein to the site of interest, this approach is expected to turn out to be an exact and advanced therapeutic approach. [ABSTRACT FROM AUTHOR]

In this paper, ultra-low level selective detection of bovine serum albumin (BSA) has been demonstrated, based on chemically derived graphene i.e., reduced graphene oxide (RGO) nanosheets. The working principle of the sensor is based upon change in conductance of the RGO nanosheets with different concentration of BSA. The change in conductance is based on the charge transfer between BSA and functional groups of RGO. The morphological and structural characterizations of RGO nanosheets were carried out by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Raman spectroscopy is performed to further validate the interaction between RGO sensing layer and BSA molecules. Electrical impedance spectroscopy is performed to observe the impedance variation when BSA interacts with RGO. The sensor device exhibits sensitivity of 10 nA/pM. The lower limit of detection (LOD) of the sensor is found to be 1 pM and response time around 35 s, confirming very high sensitivity for BSA. All electrical (current-voltage) measurements were carried out at 2 V bias for low power operation. The sensor exhibits highest sensitivity at 30 °C and for RGO thickness ~4 nm. The RGO based sensor device is selective towards BSA when compared to proteins like L-Histidine, HSA, BHB and Biotin. Our results suggest that RGO based devices are promising for low-cost, portable and real time detection of BSA at room temperature. [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]

The detection of a specific biothiol in a mixture of biothiols is a challenging task because of their similarity in structure and reactivity. To discriminate between glutathione (GSH) and cysteine (Cys)/homocysteine (Hcy) at physiological pH, the fluorometric “off–on” displacement approach was adopted, utilizing a Cu(ii)-complex of a Schiff-base ligand (L1) containing a phenolic aldimine group attached to a triazole moiety along with a dangling benzylic alcohol branch. The weakly fluorescent L1 (quantum yield (ΦF) ∼ 0.006) formed a non-fluorescent 1 : 1 Cu(ii)/L1 stoichiometric complex (1) and remained as a dimeric [Cu–L1]22+ species in an aqueous medium. The Cu(ii)-centre in 1 is highly susceptible to interactions with the –SH moiety of biothiol to participate in demetallation reactions. Unlike other solvents, the GSH-induced decomplexation of 1 generates strong fluorescence intensity in an aqueous medium, indicating the liberation of the modified L1 (L1′). Experimental evidence suggests that the benzylic alcohol moiety of L1 is itself oxidized to the formyl group during the course of the GSH interaction with 1. However, Cys/Hcy liberates L1 by the partial decomplexation of 1 (∼40%) in the usual displacement pathway to exhibit an intensity increase of less than 5% in comparison to GSH under similar experimental conditions. Unlike L1, there was an acidity increase by about 2.5 pH units for the phenolic-OH of L1′ (pKa∼ 7.0) with ∼65% phenol to fluorophoric phenolate conversion at pH 7.3, attributed to a large GSH-induced increase in the fluorescence intensity (ΦF = 0.18). It is proposed that GSH induced a comparatively rapid attack at the Cu(ii) center in 1, favouring the possibility for radical generation resulting in ligand modification of L1′ along with decomplexation. This is the first report of a biothiol-selective ligand modification exhibiting an “off–on” fluorescence response in the displacement strategy. For biogenic GSH detection and its effect on different biothiol quenchers, in vivo fluorescence imaging was carried out in the multicellular domain on Caenorhabditis elegans (C. elegans), as well as in living human neuroblastoma SH-SY5Y cells. GSH depletion in the presence of a pain killer drug, acetaminophen, was also monitored for C. elegans. [ABSTRACT FROM AUTHOR]

Two different morphological forms of graphene nanosheets: improved reduced graphene oxide (IRGO) and modified reduced GO (rGO) (MRGO) have been synthesised by improved and modified methods, respectively. Physical characterisations of these graphene nanosheets were carried out using X‐ray diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy. Colloidal stability of these nanosheets toward a selected bacterium (e.g. Staphylococcus aureus) was ascertained by zeta potential. In the present study, the authors for the first time made an attempt to study and compare the potentialities of these two different forms of graphene nanosheets as efficient bactericidal agents. Field‐emission scanning electron microscopy and TEM with energy dispersive X‐ray spectroscopy (EDAX) studies of IRGO and MRGO have been carried out to explore their underlying mechanism of antibacterial responses through physical as well as chemical interactions with the selected bacterial species. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurological disorder where many pathogenic signaling cascades are simultaneously activated. Moreover, their inter-relations and molecular reasons for activations are not completely understood, which impedes the development of therapeutics for AD. Multi-target drug discovery has recently come into prominence, particularly in the case of AD, due to the ability of the potential hits to simultaneously inhibit many pathways causing the disease. The present study reports the application of an FDA approved sweetener, neohesperidin dihydrochalcone (NHD), as a multi-target inhibitor for AD therapeutics. NHD shows a high BACE1 and amyloid aggregation inhibition ability as well as strong anti-oxidant activity. NHD binds to the active site of BACE1 and thus induces a conformational transition to a closed complex, which excludes substrate recognition, evident from steady-state and time-resolved fluorescence spectroscopy. 500 nM NHD completely inhibits the activity of BACE1. 8-Anilino-1-naphthalenesulfonic acid (ANS), Thioflavin-T fluorescence assay and Atomic Force Microscopy (AFM) studies confirm that co-incubation of equimolar NHD with Aβ25–35 almost completely inhibits Aβ25–35 fibril formation. Co-incubation of NHD with Aβ25–35 entirely alleviates the neurotoxic effects of equimolar Aβ25–35. NHD dose-dependently inhibits Aβ25–35 induced cellular ROS generation. In vitro bio-assays confirm that NHD is itself a strong anti-oxidant and shows scavenging activity against a wide variety of radicals. Our results clearly indicate that NHD changes the aggregation pathways of Aβ in such a way that the formations of toxic oligomeric/fibrillar forms are reduced significantly. The present study demonstrates the multi-target inhibitory potency of NHD in AD therapeutics identified via drug repurposing screening. [ABSTRACT FROM AUTHOR]

Bio-synthesis of silver nanoparticles (AgNPs) was made by using the aqueous leaf extract of Ardisia solanacea. Rapid formation of AgNPs was observed from silver nitrate upon treatment with the aqueous extract of A. solanacea leaf. The formation and stability of the AgNPs in the colloidal solution were monitored by UV-visible spectrophotometer. The mean particle diameter of AgNPs was calculated from the DLS with an average size ~4 nm and ~65 nm. ATR-FTIR spectroscopy confirmed the presence of alcohols, aldehydes, flavonoids, phenols and nitro compounds in the leaf which act as the stabilizing agent. Antimicrobial activity of the synthesized AgNPs was performed using agar well diffusion and broth dilution method against the Gram-positive and Gram-negative bacteria. Further, robust anti-oxidative potential was evaluated by DPPH assay. The highest antimicrobial activity of synthesized AgNPs was found against Pseudomonas aeruginosa (28.2 ± 0.52 mm) whereas moderate activity was found against Bacillus subtilis (16.1 ± 0.76), Candida kruseii (13.0 ± 1.0), and Trichophyton mentagrophytes (12.6 ± 1.52). Moreover, the potential wound healing activity was observed against the BJ-5Ta normal fibroblast cell line. Current research revealed that A. solanacea was found to be a suitable source for the green synthesis of silver nanoparticles. [ABSTRACT FROM AUTHOR]

Bio‐ synthesis of silver nanoparticles (AgNPs) was made by using the aqueous leaf extract of Ardisia solanacea. Rapid formation of AgNPs was observed from silver nitrate upon treatment with the aqueous extract of A. solanacea leaf. The formation and stability of the AgNPs in the colloidal solution were monitored by UV–visible spectrophotometer. The mean particle diameter of AgNPs was calculated from the DLS with an average size ∼4 nm and ∼65 nm. ATR‐FTIR spectroscopy confirmed the presence of alcohols, aldehydes, flavonoids, phenols and nitro compounds in the leaf which act as the stabilizing agent. Antimicrobial activity of the synthesized AgNPs was performed using agar well diffusion and broth dilution method against the Gram‐positive and Gram‐negative bacteria. Further, robust anti‐oxidative potential was evaluated by DPPH assay. The highest antimicrobial activity of synthesized AgNPs was found against Pseudomonas aeruginosa (28.2 ± 0.52 mm) whereas moderate activity was found against Bacillus subtilis (16.1 ± 0.76), Candida kruseii (13.0 ± 1.0), and Trichophyton mentagrophytes (12.6 ± 1.52). Moreover, the potential wound healing activity was observed against the BJ‐5Ta normal fibroblast cell line. Current research revealed that A. solanacea was found to be a suitable source for the green synthesis of silver nanoparticles. [ABSTRACT FROM AUTHOR]

The Schiff base ligand (L1) showing large fluorescence intensity in an aqueous medium owing to a ground state intramolecular proton transfer (GSIPT) reaction was utilized in a complexation process to generate a highly stable non-fluorescent Cu(ii)/L1 (1) in its “turn-off” mode. The 3:2 Cu(ii)/L1 stoichiometric complex (1), isolated in the solid form, exhibited a cysteine (Cys)-induced “turn-on” fluorescence response with a unique time-dependent intensity variation. Unlike other biothiols, the partially deprotonated –SH moiety in Cys is highly susceptible for participating in an ionic interaction with Cu(ii)-centres in 1 at a physiological pH of ∼7.4, followed by reduction to Cu(i), and then a subsequent demetallation, resulting in a large increment of the fluorescence intensity for free fluorophoric L1, which persists for about 4 –13 min owing to an unexpected stability of the Cu(i) ions. After Cys consumption, Cu(i) ions in aqueous solution rapidly oxidize to participate further in complexation with the existing free L1. The resulting complex may again be susceptible to Cys-induced abovementioned decomplexation followed by complexation for at least four different external Cys additions in four successive cyclic pathways. This multiple Cys sensing behaviour has been exploited to recognize the existence of Cys in multicellular Caenorhabditis elegans (C. elegans). [ABSTRACT FROM AUTHOR]

The present study reports on biogenic-synthesised silver nanoparticles (AgNPs) derived by treating Ag ions with an extract of Cassia fistula leaf, a popular Indian medicinal plant found in natural habitation. The progress of biogenic synthesis wasmonitored time to time using a ultraviolet-visible spectroscopy. The effect of phytochemicals present in C. fistula including flavonoids, tannins, phenolic compounds and alkaloids on the homogeneous growth of AgNPs was investigated by Fouriertransform infrared spectroscopy. The dynamic light scattering studies have revealed an average size and surface Zeta potential of the NPs as, -39.5 nm and -21.6 mV, respectively. The potential antibacterial and antifungal activities of the AgNPs were evaluated against Bacillus subtilis, Staphylococcus aureus, Candida kruseii and Trichophyton mentagrophytes. Moreover, their strong antioxidant capability was determined by radical scavenging methods (1,1-diphenyl-2-picryl-hydrazil assay). Furthermore, the AgNPs displayed an effective cytotoxicity against A-431 skin cancer cell line by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, with the inhibitory concentration (IC50) predicted as, 92.2 ± 1.2 µg/ml. The biogenically derived AgNPs could find immense scope as antimicrobial, antioxidant and anticancer agents apart from their potential use in chemical sensors and translational medicine. [ABSTRACT FROM AUTHOR]

The Caenorhabditis elegans peroxidasins, PXN-1 and PXN-2, are extracellular peroxidases; pxn-2 is involved in muscleepidermal attachment during embryonic morphogenesis and in specific axon guidance. Here we investigate potential roles of the other homologue of peroxidasin, pxn-1, in C. elegans. A pxn-1 deletion mutant showed high lethality under heat-stress conditions. Using a transcriptional GFP reporter, pxn-1 expression was observed in various tissues including neurons, muscles, and hypodermis. A translational fusion showed that PXN-1::GFP was secreted and localized in extracellular matrix, particularly along body wall muscles and pharyngeal muscles. Various neuronal developmental defects were observed in pxn-1 mutants and in pxn-1 over-expressing animals, including handedness, branching, breakage, tangling, and defasciculation. These results suggest that pxn-1, like other peroxidasins, plays an important role throughout development. [ABSTRACT FROM AUTHOR]

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway. [ABSTRACT FROM AUTHOR]

Abstract: Nramp1 (natural resistance-associated macrophage protein-1) is a functionally conserved iron–manganese transporter in macrophages. Manganese (Mn), a superoxide scavenger, is required in trace amounts and functions as a cofactor for most antioxidants. Three Nramp homologs, smf-1, smf-2, and smf-3, have been identified thus far in the nematode Caenorhabditis elegans. A GFP promoter assay revealed largely intestinal expression of the smf genes from early embryonic through adult stages. In addition, smf deletion mutants showed increased sensitivity to excess Mn and mild sensitivity to EDTA. Interestingly, these smf deletion mutants demonstrated hypersensitivity to the pathogen Staphylococcus aureus, an effect that was rescued by Mn feeding or knockdown of the Golgi calcium/manganese ATPase, pmr-1, indicating that Mn uptake is essential for the innate immune system. This reversal of pathogen sensitivity by Mn feeding suggests a protective and therapeutic role of Mn in pathogen evasion systems. We propose that the C. elegans intestinal lumen may mimic the mammalian macrophage phagosome and thus could be a simple model for studying Mn-mediated innate immunity. [Copyright &y& Elsevier]

Calcineurin is a calcium/calmodulin-dependent serine/threonine protein phosphatase. It is a heterodimeric protein consisting of a catalytic subunit calcineurin A, and a regulatory calcium-binding subunit, calcineurin B. The primary sequence of both subunits and heterodimeric structure is highly conserved from yeast to mammals. Calcineurin has long been implicated in various signaling pathways. Calcineurin genes (cna- 1/tax-6 and cnb-1) have been identified in the nematode Caenorhabditis elegans, which share high homology with their Drosophila and mammalian counterparts. C. elegans calcineurin binds calcium and functions as a heterodimeric protein phosphatase establishing its biochemical conservation. Calcineurin expresses in diverse tissues implicating its important role in various physiological processes. This review will focus in brief on the expression pattern and regulation of calcineurin including its effect on growth and development, locomotion, egg-laying, and sensory responses. [ABSTRACT FROM AUTHOR]

Presents information on a study which discussed the pulse propagation effects on lossy thin film planes. Film plane architecture; Description of the wide band frequency domain model; Measurement to modeling correlation.

The polygenic nature of Alzheimer's disease (AD) and cross-talk between several signaling cascades make it harder to decode the disease pathogenesis. β-secretase (BACE1) works upstream in the amyloidogenic processing of amyloid precursor protein (APP) to generate Aβ that rapidly aggregates to form fibrils, the most abundant component of plaques observed in AD brains. Here, we report dual inhibition of BACE1 and Aβ aggregation by neohesperidin, a flavonoid glycoconjugate, using multi-spectroscopic approaches, force microscopy, molecular modeling, and validated the potency in SH-SY5Y neuroblastoma cell lines. Steady-state and time-resolved fluorescence reveal that neohesperidin binds close to the catalytic aspartate dyad. This binding conformationally restricts the protein in closed form which possibly precludes APP recognition and thereby inhibits BACE1 activity. Neohesperidin also dose-dependently inhibits the amyloid fibril formation, as evident from ANS, ThT assay, and AFM. Neohesperidin ameliorates aggregated Aβ 25 – 35 induced ROS generation and mitochondrial dysfunction in the SH-SY5Y cell line. As a result, the amyloid induced apoptosis is significantly prohibited and normal neuronal morphology is rescued. These findings suggest neohesperidin as an inhibitor of the pathogenic conversion of Aβ to fibrillar amyloid assembly. Neohesperidin thus emerges as a non-toxic multi-potent scaffold for the development of AD therapeutics. • Neohesperidin inhibits both BACE1, Aβ aggregation. • Neohesperidin binding conformationally restricts BACE1. • Neohesperidin inhibits amyloid induced ROS generation and mitochondrial dysfunction. • Amyloid induced apoptosis is significantly prohibited by neohesperidin. • Neohesperidin inhibits pathogenic conversion of Aβ into fibrillar amyloid assembly. [ABSTRACT FROM AUTHOR]

Two novel non-toxic Schiff-base-Cu 2+ complexes, acting as fluorescent probes, synthesized in solid (1) and generated in situ (2), exhibit unprecedented selectivity and rapid sensitivity for sensing cysteine (Cys) and gluthathione (GSH), respectively, in 100% aqueous medium in off – on mode, exploiting the “displacement approach”. Reason behind remarkable swing from Cys to GSH for switchover from 1 to 2 is well established by experimental as well as theoretical evidences. The solid complex (probe 1 ), reluctant to interact with bulky tri-peptide GSH owing to large steric congestion around Cu(II) centers, selectively detects small amino acid Cys by exploiting prompt decomplexation followed by Schiff-base ligand (L 1 ) hydrolysis and subsequent fluorogenic 4-methyl-2,6-diformyl phenol (DFC) generation. On the contrary, for sterically less congested in situ complex (probe 2 ), the generation of the formyl moiety by means of partial hydrolysis of L 1 during complexation, fails to sense Cys owing to formation of stable non-fluorescent cyclic thiazolidine derivative, but reacts with GSH to produce DFC with almost same selectivity and sensitivity similar to probe 1 . Ratiometric responses at physiological detection level and bio-imaging studies to monitor Cys and GSH individually are analytically tuned for the first time in multi-cellular domain using the nematode, Caenorhabditis elegans . [ABSTRACT FROM AUTHOR]

Ca2+/calmodulin-dependent calcineurin has been shown to have important roles in various Ca2+ signaling pathways. We have previously reported that cnb-1(jh103) mutants, null mutants of a regulatory B subunit, displayed pleiotropic defects including uncoordinated movement and delayed egg laying in Caenorhabditis elegans. Interestingly, gain-of-function mutants of a catalytic A subunit showed exactly opposite phenotypes to those of cnb-1(null) mutants providing an excellent genetic model to define calcium-mediated signaling pathway at the organism level. Furthermore, calcineurin is also important for normal cuticle formation, which is required for maintenance of normal body size in C.elegans. Genetic interactions between tax-6 and several mutants including egl-30 and egl-10, which are known to be involved in G-protein signaling pathways suggest that calcineurin indeed regulates locomotion and serotonin-mediated egg laying through goa-1(Goα) and egl-30(Gqα). Our results indicate that, along with CaMKII, calcineurin regulates G-protein-coupled phosphorylation signaling pathways in C.elegans. [Copyright &y& Elsevier]

A conserved family of calcineurin-regulating proteins whose members have been implicated in several disease models such as Down syndrome, Alzheimer''s disease, and cardiac hypertrophy has been identified in several organisms including yeast, mice, and humans. We have characterized Caenorhabditis elegans rcn-1, which belongs to this family of calcineurin regulators, and shows approximately 40% identity with the human homologue DSCR-1. rcn-1 is expressed in hypodermal cells, nerve cords and various neurons, vulva epithelial and muscle cells, marginal cells of the pharynx, and structures of the male tail. rcn-1 expression is upregulated by calcineurin activity. RCN-1 binds to calcineurin A from C. elegans lysate in a calcium-dependent manner, and inhibits bovine calcineurin phosphatase activity dose-dependently. In addition, overexpression of RCN-1 results in calcineurin-deficient phenotypes such as small body size, cuticle defects, fertility defects, slow growth, and serotonin-resistant egg-laying defects. Moreover, phenotypes observed in gain-of-function calcineurin mutant animals were restored to normal by RCN-1 overexpression. These results demostrate an effective and specific inhibition of calcineurin in vitro as well as in vivo by RCN-1. [Copyright &y& Elsevier]

Glioblastoma Multiforme (GBM), an aggressive brain tumor (grade-IV astrocytoma), poses treatment challenges. Poor prognosis results from the rapid growth, highlighting the role of EIF4A3 in regulating non-coding RNAs. EIF4A3 promotes the expression of several non-coding RNAs, viz, Circ matrix metallopeptidase 9 (MMP9), a prominent oncogene, by interacting with the upstream region of the circMMP9 mRNA transcript and acts on cell proliferation, migration, and invasion of GBM. However, research shows that EIF4A3 knockdown inhibits glioblastoma progression and increases apoptosis. In this study, we explored the efficiency of the phytochemicals from plants like Withania somnifera and Castanea sativa with potential anti-glioblastoma effects as obtained from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Consequently, we have performed a virtual screening of the compounds against the protein EIF4A3. We further investigated the efficiency of the shortlisted compounds based on docking scores evaluated using GOLD, AutoDock4.2, LeDock, and binding free energy analyses using Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). Among the phytochemicals studied so far, several Withania -specific compounds from Withania somnifera and a single dietary compound, viz., Thiamine from Castanea sativa , have exhibited comparatively good blood-brain barrier permeability, significant binding affinity towards the EIF4A3, and good ADMET properties. Furthermore, we have verified the interaction stability of the lead molecules with EIF4A3 using MD simulations. Thus, the present study offers an opportunity to develop drug candidates targeting glioblastoma caused by EIF4A3 over-expression, integrating phytotherapy into precision oncology to create tailored and precise natural treatment strategies for cancer.Communicated by Ramaswamy H. Sarma.

Background: Glioblastoma multiforme, commonly known as GBM or glioblastoma is a grade IV astrocytoma. Brain tumors are difficult to treat and lead to poor prognosis and survival in patients. Gliomas are categorized into four different grades among which GBM is the worst grade primary brain tumor with a survival of less than a year. The genomic heterogeneity of the brain tumor results in different profiles for patients diagnosed with glioblastoma. Precision medicine focuses on this specific tumor type and suggests specialized treatment for better prognosis and overall survival (OS)., Purpose: With the recent advancements in Genome-Wide Studies (GWS) and various characterizations of brain tumors based on genetic, transcriptomic, proteomic, epigenetic, and metabolomics, this review discusses the advancements and opportunities of precision medicine therapeutics, drugs, and diagnosis methods based on the different profiles of glioblastoma., Methods: This review has exhaustively surveyed several pieces of works from various literature databases., Conclusion: It is evident that most primary brain tumors including glioblastoma require specific and precision therapeutics for better prognosis and OS. In present and future, molecular understanding and discovering specific therapies are essential for treatment in the field of neurooncology., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (© the Author(s).)

The Caenorhabditis elegans peroxidasins, PXN-1 and PXN-2, are extracellular peroxidases; pxn-2 is involved in muscle-epidermal attachment during embryonic morphogenesis and in specific axon guidance. Here we investigate potential roles of the other homologue of peroxidasin, pxn-1, in C. elegans. A pxn-1 deletion mutant showed high lethality under heat-stress conditions. Using a transcriptional GFP reporter, pxn-1 expression was observed in various tissues including neurons, muscles, and hypodermis. A translational fusion showed that PXN-1::GFP was secreted and localized in extracellular matrix, particularly along body wall muscles and pharyngeal muscles. Various neuronal developmental defects were observed in pxn-1 mutants and in pxn-1 over-expressing animals, including handedness, branching, breakage, tangling, and defasciculation. These results suggest that pxn-1, like other peroxidasins, plays an important role throughout development.

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

Calcineurin is a Ca(2+)-calmodulin-dependent serine/threonine protein phosphatase that has been implicated in various signaling pathways. Here we report the identification and characterization of calcineurin genes in Caenorhabditis elegans (cna-1 and cnb-1), which share high homology with Drosophila and mammalian calcineurin genes. C. elegans calcineurin binds calcium and functions as a heterodimeric protein phosphatase establishing its biochemical conservation in the nematode. Calcineurin is expressed in hypodermal seam cells, body-wall muscle, vulva muscle, neuronal cells, and in sperm and the spermatheca. cnb-1 mutants showed pleiotropic defects including lethargic movement and delayed egg-laying. Interestingly, these characteristic defects resembled phenotypes observed in gain-of-function mutants of unc-43/Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and goa-1/G(o)-protein alpha-subunit. Double mutants of cnb-1 and unc-43(gf) displayed an apparent synergistic severity of movement and egg-laying defects, suggesting that calcineurin may have an antagonistic role in CaMKII-regulated phosphorylation signaling pathways in C. elegans.