Mechanistic Insights into Cellular and Molecular Basis of Protein-Nanoplastic Interactions.

Plastic waste is ubiquitously present across the world, and its nano/sub-micron analogues (plastic nanoparticles, PNPs), raise severe environmental concerns affecting organisms' health. Considering the direct and indirect toxic implications of PNPs, their biological impacts are actively being studied; lately, with special emphasis on cellular and molecular mechanistic intricacies. Combinatorial OMICS studies identified proteins as major regulators of PNP mediated cellular toxicity via activation of oxidative enzymes and generation of ROS. Alteration of protein function by PNPs results in DNA damage, organellar dysfunction, and autophagy, thus resulting in inflammation/cell death. The molecular mechanistic basis of these cellular toxic endeavors is fine-tuned at the level of structural alterations in proteins of physiological relevance. Detailed biophysical studies on such protein-PNP interactions evidenced prominent modifications in their structural architecture and conformational energy landscape. Another essential aspect of the protein-PNP interactions includes bioenzymatic plastic degradation perspective, as the interactive units of plastics are essentially nano-sized. Combining all these attributes of protein-PNP interactions, the current review comprehensively documented the contemporary understanding of the concerned interactions in the light of cellular, molecular, kinetic/thermodynamic details. Additionally, the applicatory, economical facet of these interactions, PNP biogeochemical cycle and enzymatic advances pertaining to plastic degradation has also been discussed.

Tyrosol-gold nanoparticle functionalized acacia gum-PVA nanofibers for mitigation of Candida biofilm.

Increasing incidences of fungal infections and prevailing antifungal resistance in healthcare settings has given rise to an antifungal crisis on a global scale. The members of the genus Candida, owing to their ability to acquire sessile growth, are primarily associated with superficial to invasive fungal infections, including the implant-associated infections. The present study introduces a novel approach to combat the sessile/biofilm growth of Candida by fabricating nanofibers using a nanoencapsulation approach. This technique involves the synthesis of tyrosol (TYS) functionalized chitosan gold nanocomposite, which is then encapsulated into PVA/AG polymeric matrix using electrospinning. The FESEM, FTIR analysis of prepared TYS-AuNP@PVA/AG NF suggested the successful encapsulation of TYS into the nanofibers. Further, the sustained and long-term stability of TYS in the medium was confirmed by drug release and storage stability studies. The prepared nanomats can absorb the fluid, as evidenced by the swelling index of the nanofibers. The growth and biofilm inhibition, as well as the disintegration studies against Candida, showed 60-70 % biofilm disintegration when 10 mg of TYS-AuNP@PVA/AG NF was used, hence confirming its biological effectiveness. Subsequently, the nanofibers considerably reduced the hydrophobicity index and ergosterol content of the treated cells. Considering the challenges associated with the inhibition/disruption of fungal biofilm, the fabricated nanofibers prove their effectiveness against Candida biofilm. Therefore, nanocomposite-loaded nanofibers have emerged as potential materials that can control fungal colonization and could also promote healing.

LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases.

Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Few quality control (QC) E3 ubiquitin ligases interplay an important role to specifically recognize misfolded proteins for their intracellular degradation. Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) is a really interesting new gene (RING) class protein that possesses E3 ubiquitin ligase activity with promising applications in PQC. LRSAM1 is also known as RING finger leucine repeat rich (RIFLE) or TSG 101-associated ligase (TAL). LRSAM1 has various cellular functions as it modulates the protein aggregation, endosomal sorting machinery and virus egress from the cells. Thus, this makes LRSAM1 interesting to study not only in protein conformational disorders such as neurodegeneration but also in immunological and other cancerous disorders. Furthermore, LRSAM1 interacts with both cellular protein degradation machineries and hence it can participate in maintenance of overall cellular proteostasis. Still, more research work on the quality control molecular functions of LRSAM1 is needed to comprehend its roles in various protein aggregatory diseases. Earlier findings suggest that in a mouse model of Charcot-Marie-Tooth (CMT) disease, lack of LRSAM1 functions sensitizes peripheral axons to degeneration. It has been observed that in CMT the patients retain dominant and recessive mutations of LRSAM1 gene, which encodes most likely a defective protein. However, still the comprehensive molecular pathomechanism of LRSAM1 in neuronal functions and neurodegenerative diseases is not known. The current article systematically represents the molecular functions, nature and detailed characterization of LRSAM1 E3 ubiquitin ligase. Here, we review emerging molecular mechanisms of LRSAM1 linked with neurobiological functions, with a clear focus on the mechanism of neurodegeneration and also on other diseases. Better understanding of LRSAM1 neurobiological and intracellular functions may contribute to develop promising novel therapeutic approaches, which can also propose new lines of molecular beneficial targets for various neurodegenerative diseases.

A review on multifaceted biomedical applications of heparin nanocomposites: Progress and prospects.

Advances in polymer-based nanocomposites have revolutionized biomedical applications over the last two decades. Heparin (HP), being a highly bioactive polymer of biological origin, provides strong biotic competence to the nanocomposites, broadening the horizon of their applicability. The efficiency, biocompatibility, and biodegradability properties of nanomaterials significantly improve upon the incorporation of heparin. Further, inclusion of structural/chemical derivatives, fractionates, and mimetics of heparin enable fabrication of versatile nanocomposites. Modern nanotechnological interventions have exploited the inherent biofunctionalities of heparin by formulating various nanomaterials, including inorganic/polymeric nanoparticles, nanofibers, quantum dots, micelles, liposomes, and nanogels ensuing novel functionalities targeting diverse clinical applications involving drug delivery, wound healing, tissue engineering, biocompatible coatings, nanosensors and so on. On this note, the present review explicitly summarises the recent HP-oriented nanotechnological developments, with a special emphasis on the reported successful engagement of HP and its derivatives/mimetics in nanocomposites for extensive applications in the laboratory and health-care facility. Further, the advantages and limitations/challenges specifically associated with HP in nanocomposites, undertaken in this current review are quintessential for future innovations/discoveries pertaining to HP-based nanocomposites.

Baicalin functionalized PEI-heparin carbon dots as cancer theranostic agent.

The worldwide prevalence of cancer and its significantly rising risks with age have garnered the attention of nanotechnology for prompt detection and effective therapy with minimal or no adverse effects. In the current study, heparin (HP) polymer derived heteroatom (N, S-) co-doped CDs were synthesized using hydrothermal synthesis method to efficiently deliver natural anticancer compound baicalin (BA). Heparin carbon dots (HCDs) were passivated with polyethylenimine (PEI) to improve its fluorescence quantum yield. The surface passivation of CDs by polycationic PEI polymer not only facilitated loading of BA, but also played a crucial role in the pH-responsive drug delivery. The sustained release of BA (up to 80 %) in mildly acidic pH (5.5 and 6.5) conditions endorsed its drug delivery potential for cancer-specific microenvironments. BA-loaded PHCDs exhibited enhanced anticancer activity as compared to BA/PHCDs indicating the effectiveness of the nanoformulation, Furthermore, the flow cytometry analysis confirmed that BA-PHCDs treated cells were arrested in the G2/M phase of cell cycle and had a higher potential for apoptosis. Bioimaging study demonstrated the excellent cell penetration efficiency of PHCDs with complete cytoplasmic localization. All this evidence comprehensively demonstrates the potency of BA-loaded PHCDs as a nanotheranostic agent for cancer.

Eugenol-acacia gum-based bifunctional nanofibers as a potent antifungal transdermal substitute.

Aim: Fungal biofilms interfere with the wound healing processes. Henceforth, the study aims to fabricate a biomaterial-based nano-scaffold with the dual functionalities of wound healing and antibiofilm activity. Methods: Nanofibers comprising acacia gum, polyvinyl alcohol and inclusion complex of eugenol in ß-cyclodextrin (EG-NF) were synthesized using electrospinning. Antibiofilm studies were performed on Candida species, and the wound-healing activity was evaluated through an in vivo excision wound rat model. Results: The EG-NF potentially eradicated the mature biofilm of Candida species and their clinical isolates. Further, EG-NF also enhanced the re-epithelization and speed of wound healing in in vivo rat experiments. Conclusion: The study established the bifunctional applications of eugenol nanofibers as a transdermal substitute with antifungal potency.

Eucalyptol/ ß-cyclodextrin inclusion complex loaded gellan/PVA nanofibers as antifungal drug delivery system.

Fungal infections pose a serious threat to humankind due to the toxicity of conventional antifungal therapy and continuous emerging incidence of multidrug resistance. Essential oils fascinated researchers because of their broad antimicrobial activity and minimal cytotoxicity. However, hydrophobic, volatile and low water solubility of essential oils hinder their applications in pharmaceutical industries. Therefore, in this study we have loaded eucalyptol/ ß-cyclodextrin inclusion complex to gellan/polyvinyl alcohol nanofibers (EPNF) to eradicate Candida albicans and Candida glabrata biofilms. The electrospun nanofibers characterized by various physicochemical techniques and it was observed that EPNF possess highly hydrophilic surface property that facilitate rapid drug release. EPNF inhibited approximately 70% biofilm of C. albicans and C. glabrata. Time kill results depicted that eucalyptol (EPTL) encapsulation in the nanofibers prolonged its antifungal activity than the pure EPTL. Electron microscopy studies revealed that EPNF disrupted the cell surface of Candida. Collectively the current study suggested nanofiber encapsulation enhanced antibiofilm activity of eucalyptol and these nanoscale systems can serve as an alternative therapeutic strategy to treat fungal infections. Further, the developed nanofibrous materials can be applied as cost effective coating agent for biomedical implants.

Glycosaminoglycan-based resorbable polymer composites in tissue refurbishment.

Regeneration of tissue structure with the aid of bioactive polymer matrices/composites and scaffolds for respective applications is one of the emerging areas of biomedical engineering. Recent advances in conjugated glycosaminoglycan (GAG) hybrids using natural and synthetic polymers have opened new avenues for producing a wide variety of resorbable polymer matrices. These hybrid scaffolds are low-immunogenic, highly biocompatible and biodegradable with incredible mechanical and tensile properties. GAG-based resorbable polymeric matrices are being exploited in migration of stem cells, cartilage and bone replacement/regeneration and production of scaffolds for various tissue engineering applications. In the current review, we will discuss the role of GAG-based resorbable polymer matrices in the field of regenerative medicine.