Short term biodistribution and in vivo toxicity assessment of intravenously injected pristine graphene oxide nanoflakes in SD rats.

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.

Isolation of Amyloid-like Protein Aggregates (APA) from white bread and their characterisation.

High temperature, acidic pH, and physical agitation are commonly observed during cooking or industrial food processing, which are often considered as favorable conditions, at least for some proteins, to misfold and form amyloid-like protein aggregates (APA). The proteins in various bakery products generally experience high temperatures that might lead to the formation of APA. To test this hypothesis, the presence of APA in white bread was examined in this study. The APA isolated from white bread displayed typical characteristics of amyloids, like bathochromic shift in Congo red (CR) absorbance maxima, increased fluorescence of Thioflavin T (ThT) & 8-anilino-1-naphthalene sulfonic acid (ANS), fibrillar morphology of >200 nm long with average diameter of 10-12 nm and negative minima at 223 nm in Circular Dichroism (CD) spectrum. The SDS- and native PAGE revealed the presence of gliadin and glutenin as the constituent proteins in the isolated protein aggregates. Although, the presence of amyloid-like structures in white bread is evident, further studies would be essential to establish their functional role and health implications.

Mitigating neuroinflammation in Parkinson's disease: Exploring the role of proinflammatory cytokines and the potential of phytochemicals as natural therapeutics.

Parkinson's disease (PD) is one of the most prevalent neuroinflammatory illnesses, characterized by the progressive loss of neurons in the brain. Proinflammatory cytokines play a key role in initiating and perpetuating neuroinflammation, which can lead to the activation of glial cells and the deregulation of inflammatory pathways, ultimately leading to permanent brain damage. Currently, available drugs for PD mostly alleviate symptoms but do not target underlying inflammatory processes. There is a growing interest in exploring the potential of phytochemicals to mitigate neuroinflammation. Phytochemicals such as resveratrol, apigenin, catechin, anthocyanins, amentoflavone, quercetin, berberine, and genistein have been studied for their ability to scavenge free radicals and reduce proinflammatory cytokine levels in the brain. These plant-derived compounds offer a natural and potentially safe alternative to conventional drugs for managing neuroinflammation in PD and other neurodegenerative diseases. However, further research is necessary to elucidate their underlying mechanisms of action and clinical effectiveness. So, this review delves into the pathophysiology of PD and its intricate relationship with proinflammatory cytokines, and explores how their insidious contributions fuel the disease's initiation and progression via cytokine-dependent signaling pathways. Additionally, we tried to give an account of PD management using existing drugs along with their limitations. Furthermore, our aim is to provide a thorough overview of the diverse groups of phytochemicals, their plentiful sources, and the current understanding of their anti-neuroinflammatory properties. Through this exploration, we posit the innovative idea that consuming nutrient-rich phytochemicals could be an effective approach to preventing and treating PD.

In-vitro toxicity assessment of a textile dye Eriochrome Black T and its nano-photocatalytic degradation through an innovative approach using Mf-NGr-CNTs-SnO2 heterostructures.

The present study aimed to assess the in-vitro toxicity of a popular azodye, Eriochrome Black T (EBT) which may be an environmental hazard causing water pollution if released by textile industries as waste effluents to nearby water ponds. We explored the toxic potential of EBT at 200, 400 and 800 µg/ml concentrations, which were selected based on quantification of EBT present in the pond water near carpet industries. We investigated the permeability of EBT across the organ barriers and found it to be 6.48 ± 0.44% at the highest concentration. EBT also showed up to 26.46 ± 0.533% hemolytic potential on human RBCs. MTT assay revealed toxicity of up to 64.9 ± 10.12%. A dose-dependent increase in intracellular ROS levels and Caspase 3/7 activity was observed and confocal microscopy also demonstrated a similar trend of cellular apoptosis indicating ROS mediated induction of apoptosis as a mechanism of EBT induced cytotoxicity. After establishing the toxicity of EBT, an innovative nano-photocatalytic approach for dye remediation was applied by using as synthesized Mf-NGr-CNTs-SnO2 heterostructures. This catalyst showed dye degradation potential of up to 82% in 2 h in the presence of sun light. The degraded dye products were tested to have up to 30% reduced cellular toxicity as compared to the parent compound. This work successfully establishes the toxicity of EBT along with devising an innovative approach towards dye degradation where the catalyst is adhered on melamine foam and not being mixed in the effluents directly, thereby, reducing the possibility of catalyst being leached out into the river water.

Emerging approaches of neural regeneration using physical stimulations solely or coupled with smart piezoelectric nano-biomaterials.

Neural regeneration is a challenging venture as it is limited by various intrinsic physiological parameters such as the presence of biomolecules like Nogo-A, Ephrin-B3 and Neurocan, that inhibit Central nervous system (CNS) regeneration, and the absence of conducive factors such as ATF3, Sox2 and GAP-43, that promote the neuronal differentiation and regeneration. The design of an effective strategy for neuronal repair or regeneration is a daunting task as neural cells are responsive to a very narrow window of the conductive cellular microenvironment. It requires specific inductive signals and chemical cues from neighbouring cells that can trigger the process of regeneration or repair. It is this complexity that adds to the plight in the scenarios of patients confronted with trauma resulting in spinal cord injury (SCI) or traumatic brain injury (TBI). SCI or TBI may cause temporary or permanent locomotory disorders in patients, affecting the quality of their lives. The regenerative potential of neural cells in the CNS is comparatively lesser than that of peripheral nervous system (PNS). Also, the activation and migration of astrocytes to the injury site causes glial scar, thus hindering further repair process, especially in CNS injuries. Therefore, an effective strategy for stimulating neuritic branching and growth can be a solution to the problem. This review discusses the various facets of strategies that have been adopted to understand and improve the progress of neural tissue engineering for treating the conditions like SCI and TBI. This review also provides an insight regarding the influence of various nano-topographical cues on neuronal cell behavior, the importance of inherent piezoelectric properties in biological systems, various forms of physical stimulation methods that can drive the process of neuritic outgrowth, and finally concludes with the elucidations of advances in development of various biomaterials that have been found effective in achieving enhancement in neuronal physiological properties. It also shares some opinions as perspectives that may help in the further advancement of this field.

Isolation and characterisation of milk-derived amyloid-like protein aggregates (MAPA) from cottage cheese.

Cottage cheese, extensively consumed worldwide, contains coagulated milk protein (casein), produced through boiling and acidification of milk. Casein forms amyloid or amyloid-like structures at high temperatures and low pH. Due to the similarities in the preparation of casein amyloids and cottage cheese, we hypothesized the presence of amyloid or amyloid-like protein aggregates in cottage cheese. To examine this hypothesis, cottage cheese was prepared from cow (Bos indicus) milk and isolated amyloids through a water extraction method. The isolated protein aggregates displayed typical characteristics of amyloids, such as a bathochromic shift in the wavelength of maximum absorption (λmax) of Congo red (CR), high thioflavin T (ThT) binding, increased surface hydrophobicity, and high ß-sheet structure. However, they did not show antibacterial activity and toxic properties against erythrocytes. Our study revealed that the heat-treatment and subsequent acidification during cottage cheese preparation lead to the formation of non-toxic amyloid-like aggregates.

Heat treatment of soluble proteins isolated from human cataract lens leads to the formation of non-fibrillar amyloid-like protein aggregates.

The loss of crystallins solubility with aging and the formation of amyloid-like aggregates is considered the hallmark characteristic of cataract pathology. The present study was carried out to assess the effect of temperature on the soluble lens protein and the formation of protein aggregates with typical amyloid characteristics. The soluble fraction of lens proteins was subjected for heat treatment in the range of 40-60 °C, and the nature of protein aggregates was assessed by using Congo red (CR), thioflavin T (ThT), and 8-anilinonaphthalene-1-sulfonic acid (ANS) binding assays, circular dichroism (CD), Fourier-transform infrared (FT-IR) spectroscopy, and transmission electron microscopy (TEM). The heat-treated protein samples displayed a substantial bathochromic shift (≈15 nm) in the CR's absorption maximum (λmax) and increased ThT and ANS binding. The heat treatment of lens soluble proteins results in the formation of nontoxic, ß-sheet rich, non-fibrillar, protein aggregates similar to the structures evident in the insoluble fraction of proteins isolated from the cataractous lens. The data obtained from the present study suggest that the exposure of soluble lens proteins to elevated temperature leads to the formation of non-fibrillar aggregates, establishing the role of amyloid in the heat-induced augmentation of cataracts pathology.

Exposure of calcium carbide induces apoptosis in mammalian fibroblast L929 cells.

Inspite of various health warnings from Government and health organizations, Calcium carbide (CaC2) is still the most commonly and widely used artificial fruit ripener, probably due to its easy availability, low cost and convenience of usage. Assessment of the hazardous effects of the CaC2 applications for fruit ripening has been a matter of interest since long. Several in vivo studies have reported the toxicological outcomes such as histopathological changes in lungs and kidneys, haematological and immunological responses, upon exposure with CaC2. However, a well-controlled study investigating the effects of CaC2 under in-vitro setup was lacking. Hence, this study has been conducted to explore the toxicity associated cellular events in L929 cells exposed with varying concentrations of CaC2 (0.00312-0.2 µg/µl) for 24 h exposure time. A 23.14% reduction in cell viability was observed at the highest dose of CaC2. A similar trend in cellular stress levels at 0.2 µg/µl dose was observed in terms of rounded cellular morphology and decreased adherence as compared to the control. Furthermore, Annexin V FITC/PI staining and subsequent confocal imaging revealed a similar trend of CaC2 induced apoptosis in a dose dependent manner. A gradual elevation of intracellular ROS has also been observed up to 0.025 µg/µl dose. Thus, the study concludes that short term CaC2 exposure may increase the cellular oxidative stress and disturb the redox balance of the cell which then undergoes apoptosis. The study concludes that the exposure of CaC2 can be associated with severe diseases and suggests to stop the uses of CaC2 as fruit ripening agent.

Emerging Roles of DHHC-mediated Protein S-palmitoylation in Physiological and Pathophysiological Context.

Protein S-palmitoylation refers to a post-translational modification (PTM) wherein palmitic acid, a 16-carbon long saturated fatty acid gets covalently attached to Cys sidechain of a protein. It has been known to the literature for almost 50 years and in general, this PTM is believed to facilitate membrane attachments of proteins for the obvious hydrophobicity of the palmitoyl group. But after the discovery of the protein palmitoyl acyltransferases (PATs, also known as DHHC-PATs), a major paradigm shift has been observed in the field of protein S-palmitoylation. A family of 23 mammalian DHHC-PATs has been identified and the majority of them are associated with many human diseases spanning from neuropsychiatric diseases to cancers. Novel unique and essential role of DHHC-mediated protein S-palmitoylation has been revealed apart from its membrane trafficking role. Biomedical importance of DHHCs has also been reiterated with small molecule inhibitors for DHHCs as well as in DHHC-knockout mice or mouse Xenograft models. In this review, we present recent advances in the field of protein S-palmitoylation and the involvement of individual DHHC isoforms in human diseases. In addition, the recent development of the analytical tools to study S-palmitoylation and their inhibitors are discussed in detail. We also highlight the issues that need to be addressed in detail to further develop our understanding on protein S-palmitoylation and strongly believe that pharmacological modulation of DHHC-mediated protein S-palmitoylation has a massive potential to emerge as a novel therapeutic strategy for human diseases. It will not be surprising if reversible protein S-palmitoylation prove to be an indispensable PTM that regulates a host of cellular processes, just like protein phosphorylation or ubiquitination.

Isolation and characterization of plant synergistic bacteria capable of degrading xenobiotics from oil spillage sites.

Oil spillage sites primarily contain various types of hydrocarbons, such as linear chain, polycyclic, and aromatic compounds, posing several detrimental effects on plants. Results from our previous study showed an alteration of various metabolomic parameters, indirectly resulting in an observable decline of growth in the mung seedlings upon incubation with phenol, toluene, xylene, and hexane. This study evaluates the role of these compounds upon plant growth and focusses to mitigate the effect of the same, using some isolated plant synergistic bacteria. We isolated Proteus sp., Streptococcus sp., and Enterococcus sp., and tested the synergism of them in mung seedlings (Vigna radiata) by hydroponics. Treatment with the above-mentioned compounds significantly reduced the root and shoot length of the seedlings when compared to the control. The bacterial treatment helped in reducing the adversity due to the xenobiotic insult, by improving the root shoot length of the treated seedlings. Proteus sp. was found to be the most promising among other isolates. In another experiment, plasmid profiling of the bacterial isolates was done, yielding a band of 4.5 kb common for all, serving as a clue to be the most probable plasmid responsible for the degradation of the compounds. Results from this study clearly indicate that Proteus sp. can be explored further for its plant synergism and xenobiotic degradative capability to exploit its potential in oil spillage land reclamation and establishing vegetation.