Targeted therapies for HPV-associated cervical cancer: Harnessing the potential of exosome-based chipsets in combating leukemia and HPV-mediated cervical cancer.

Exosomes play a crucial role in intercellular communication and have emerged as significant vehicles for transporting disease-specific biomarkers. This feature provides profound insights into the progression of diseases and the responses of patients to treatments. For example, in leukemia, exosomes convey critical information through the carriage of specific proteins and nucleic acids. In the case of human papillomavirus (HPV)-mediated cervical cancer, exosomes are particularly useful for noninvasive detection as they transport high-risk HPV DNA and specific biomolecules, which can be indicators of the disease. Despite their vast potential, there are several challenges associated with the use of exosomes in medical diagnostics. These include their inherent heterogeneity, the need for enhanced sensitivity in detection methods, the establishment of standardization protocols, and the requirement for cost-effective scalability in their application. Addressing these challenges is crucial for the effective implementation of exosome-based diagnostics. Future research and development are geared towards overcoming these obstacles. Efforts are concentrated on refining the processes of biomarker discovery, establishing comprehensive regulatory frameworks, developing convenient point-of-care devices, exploring methods for multimodal detection, and conducting extensive clinical trials. The ultimate goal of these efforts is to inaugurate a new era of precision diagnostics within healthcare. This would significantly improve patient outcomes and reduce the burden of diseases such as leukemia and HPV-mediated cervical cancer. The integration of exosomes with cutting-edge technology holds the promise of significantly reinforcing the foundations of healthcare, leading to enhanced diagnostic accuracy, better disease monitoring, and more personalized therapeutic approaches.

Targeted inhibition of colorectal cancer proliferation: The dual-modulatory role of 2,4-DTBP on anti-apoptotic Bcl-2 and Survivin proteins.

The anti-apoptotic proteins, Bcl-2 and Survivin, are consistently overexpressed in numerous human malignancies, notably in colorectal cancer. 2,4-Di-tert-butylphenol (2,4-DTBP) is a naturally occurring phenolic compound known for its diverse biological activities, including anti-cancer properties. The mechanism behind 2,4-DTBP-induced inhibition of cell proliferation and apoptosis in human colorectal cancer cells, specifically regarding Bcl-2 and Survivin, remains to be elucidated. In this study, we employed both in silico and in vitro methodologies to underpin this interaction at the molecular level. Molecular docking demonstrated a substantial binding affinity of 2,4-DTBP towards Bcl-2 (ΔG = -9.8 kcal/mol) and Survivin (ΔG = -5.6 kcal/mol), suggesting a potential inhibitory effect. Further, molecular dynamic simulations complemented by MM-GBSA calculations confirmed the significant binding of 2,4-DTBP with Bcl-2 (dGbind = -54.85 ± 6.79 kcal/mol) and Survivin (dGbind = -32.36 ± 1.29 kcal/mol). In vitro assays using HCT116 colorectal cancer cells revealed that 2,4-DTBP inhibited proliferation and promoted apoptosis in both a dose- and time-dependent manner. Fluorescence imaging and scanning electron microscopy illustrated the classical features associated with apoptosis upon 2,4-DTBP exposure. Cell cycle analysis through flow cytometry highlighted a G1 phase arrest and apoptosis assay demonstrated increased apoptotic cell population. Notably, western blotting results indicated a decreased expression of Bcl-2 and Survivin post-treatment. Considering the cytoprotective roles of Bcl-2 and Survivin through the inhibition of mitochondrial dysfunction, our findings of disrupted mitochondrial bioenergetics, characterized by reduced ATP production and oxygen consumption, further accentuate the functional impairment of these proteins. Overall, the integration of in silico and in vitro data suggests that 2,4-DTBP holds promise as a therapeutic agent targeting Bcl-2 and Survivin in colorectal cancer.

Investigation of Antioxidant Activity, Myco-Chemical Content, and GC-MS Based Molecular Docking Analysis of Bioactive Chemicals from Amanita konajensis (Agaricomycetes), a Tribal Myco-Food from India.

In humans, a wide range of health disorders have been induced due to an imbalanced metabolism and an excess generation of reactive oxygen species (ROS). Different biological properties found in mushrooms seem to be the reason for their customary use as a favourite delicacy. Therefore, exploration of wild edible mushrooms as a source of various biological compounds is gaining much importance today. Amanita konajensis, one of the underutilized macrofungi popularly consumed in Eastern India, demands a systematic study of its medicinal values. The study aims to explore the myco-chemical contents of A. konajensis ethanolic extract (EtAK1) and screen their antioxidant potency through various in vitro assays. GC-MS analysis identified the chemical components of EtAK1. Further, structure-based virtual screening of the identified compounds was analysed for drug-like properties and molecular docking with the human p38 MAPK protein, a potent targeting pathway for human lung cancer. The morpho-molecular features proved the authenticity of the collected mushroom. The screening assays showed that EtAK1 was abundant in flavonoids, followed by phenolics, ß-carotene, and lycopene, and had strong antioxidant activity with EC50 values of 640-710 µg/mL. The GC-MS analyses of EtAK1 identified the occurrence of 19 bioactive compounds in the mushroom. In silico analysis revealed that anthraergostatetraenol p-chlorobenzoate, one of the compounds identified, displayed high binding affinity (ΔG = -10.6 kcal/mol) with human p38 MAPK. The outcome of this study will pave the way for the invention of myco-medicine using A. konajensis, which may lead to a novel drug for human lung cancer.

In-silico molecular docking and molecular dynamic simulation of γ-elemene and caryophyllene identified from the essential oil of Kaempferia galanga L. against biofilm forming proteins, CrtM and SarA of Staphylococcus aureus.

Medicinal plants play an important role as antimicrobials by inhibiting various key targets of diverse microorganisms. A major antimicrobial component of plants is its essential oil, which are increasingly being studied for their antimicrobial properties as well as for their potential role in the inhibition of biofilm formation. In the present study, essential oil from Kaempferia galanga L was isolated resulting in the identification of eleven compounds. Of these, two of the compounds, γ-elemene and caryophyllene were found to dock with the target proteins, CrtM and SarA of Staphylococcus aureus, which are essential for the formation of biofilm. γ-elemene demonstrated the best binding affinity with CrtM with binding energy of -8.1 kcal/mol whereas caryophyllene and its derivative isocaryophyllene showed the best binding with SarA with binding energy -6.1 kcal/mol. ADMET study of the compounds also revealed that the compounds are non-toxic and can be used as probable compounds for inhibition of biofilms. Molecular dynamic simulation studies revealed high affinity of binding and stability of the molecules with their targets. PCA analysis helped in identifying the principal motions occurring within a trajectory that are essential in inducing conformational changes.Communicated by Ramaswamy H. Sarma.

Synthesis and computational insights of flavone derivatives as potential estrogen receptor alpha (ER-α) antagonist.

Hormone-related breast cancer is mostly caused by interactions with estrogen receptor alpha (ER-α), which functions as a transcription factor to control the transcription of numerous genes. Flavones are considered a good substrate for the estrogen receptor. Substitution of the N-heterocyclic ring on the flavon structure may potentiate its anticancer effect. A series of flavon derivatives with an N-heteroaryl ring at the 4' position of the B ring of flavon were designed, prepared and evaluated for in vitro breast cancer activity. Binding interactions of the PzFL, PzF, PiFL, PiF and IFL compounds with ER-α were studied by molecular docking. Molecular dynamics simulation studies were carried out in order to determine the stability and convergence of protein-ligand complexes. The compounds were produced by cyclizing chalcones and chalcones were produced by Claisen-Schmidt condensation of substituted aldehydes and 2-hydroxy acetophenone. Breast cancer activity was evaluated by the MTT assay on MCF-7 cell lines. Also, compounds were studied for their estrogen receptor binding potential on the same cell lines. Molecular docking of compounds showed a good docking score. The molecular dynamics of these compounds expressed stable root mean square deviation, stable radius of gyration and low binding energy, suggesting that ligand bound to protein is quite stable in the complex. MTT assay on MCF-7 cell lines reported PzF and IFL were the most active compounds with lower IC50 values. ER-α binding assay of these compounds revealed the presence of binding interactions with receptors. This study offers a viable reference point for the design of flavon-incorporated N-heterocyclic ring derivatives as breast cancer compounds.Communicated by Ramaswamy H. Sarma.

Rhamnetin, a nutraceutical flavonoid arrests cell cycle progression of human ovarian cancer (SKOV3) cells by inhibiting the histone deacetylase 2 protein.

Overexpression of HDAC 2 promotes cell proliferation in ovarian cancer. HDAC 2 is involved in chromatin remodeling, transcriptional repression, and the formation of condensed chromatin structures. Targeting HDAC 2 presents a promising therapeutic approach for correcting cancer-associated epigenetic abnormalities. Consequently, HDAC 2 inhibitors have evolved as an attractive class of anti-cancer agents. This work intended to investigate the anti-cancer abilities and underlying molecular mechanisms of Rhamnetin in human epithelial ovarian carcinoma cells (SKOV3), which remain largely unexplored. We employed various in vitro methods, including MTT, apoptosis study, cell cycle analysis, fluorescence microscopy imaging, and in vitro enzymatic HDAC 2 protein inhibition, to examine the chemotherapeutic sensitivity of Rhamnetin in SKOV3 cells. Additionally, we conducted in silico studies using molecular docking, MD simulation, MM-GBSA, DFT, and pharmacokinetic analysis to investigate the binding interaction mechanism within Rhamnetin and HDAC 2, alongside the compound's prospective as a lead candidate. The in vitro assay confirmed the cytotoxic effects of Rhamnetin on SKOV3 cells, through its inhibition of HDAC 2 activity. Rhamnetin, a nutraceutical flavonoid, halted at the G1 phase of the cell cycle and triggered apoptosis in SKOV3 cells. Furthermore, computational studies provided additional evidence of its stable binding to the HDAC 2 protein's binding site cavity. Based on our findings, we conclude that Rhamnetin effectively promotes apoptosis and mitigates the proliferation of SKOV3 cells through HDAC 2 inhibition. These results highlight Rhamnetin as a potential lead compound, opening a new therapeutic strategy for human epithelial ovarian cancer.Communicated by Ramaswamy H. Sarma.

Revolutionizing Human papillomavirus (HPV)-related cancer therapies: Unveiling the promise of Proteolysis Targeting Chimeras (PROTACs) and Proteolysis Targeting Antibodies (PROTABs) in cancer nano-vaccines.

Personalized cancer immunotherapies, combined with nanotechnology (nano-vaccines), are revolutionizing cancer treatment strategies, explicitly targeting Human papilloma virus (HPV)-related cancers. Despite the availability of preventive vaccines, HPV-related cancers remain a global concern. Personalized cancer nano-vaccines, tailored to an individual's tumor genetic mutations, offer a unique and promising solution. Nanotechnology plays a critical role in these vaccines by efficiently delivering tumor-specific antigens, enhancing immune responses, and paving the way for precise and targeted therapies. Recent advancements in preclinical models have demonstrated the potential of polymeric nanoparticles and high-density lipoprotein-mimicking nano-discs in augmenting the efficacy of personalized cancer vaccines. However, challenges related to optimizing the nano-carrier system and ensuring safety in human trials persist. Excitingly, the integration of nanotechnology with Proteolysis-Targeting Chimeras (PROTACs) provides an additional avenue to enhance the effectiveness of personalized cancer treatment. PROTACs selectively degrade disease-causing proteins, amplifying the impact of nanotechnology-based therapies. Overcoming these challenges and leveraging the synergistic potential of nanotechnology, PROTACs, and Proteolysis-Targeting Antibodies hold great promise in pursuing novel and effective therapeutic solutions for individuals affected by HPV-related cancers.

Screening of Phytocompounds for Identification of Prospective Histone Deacetylase 1 (HDAC1) Inhibitor: An In Silico Molecular Docking, Molecular Dynamics Simulation, and MM-GBSA Approach.

The upregulation of HDAC1 facilitate the induction of epigenetic repression of genes responsible for suppressing tumourigenesis, thereby triggering the development of cancer. HDAC1 inhibitors have thus emerged as possible therapeutic approaches against a variety of human malignancies, as they can inhibit the activity of certain HDACs, repair the overexpression of tumour suppressor genes, and induce cell differentiation, cell cycle arrest, and apoptosis. In this study, among 810 virtually screened compounds, Pinocembrin (PHUB000396) had a significant binding affinity (-7.99 kcal/mol). In molecular dynamics simulation (MD) studies for 200 ns time scale, the compound Pinocembrin effectively undergoes conformational optimization, thereby enabling its accommodation within the active site of the receptor. This outcome serves as a rational for the observed binding affinity. The optimal binding free energy calculations using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) (-35.86 ± 7.52 kcal/mol) showed the significant role of van der Waals forces and Coulomb interactions in the stability of the respective complex. The pharmacokinetic study showed its potential as a lead compound. The in-silico cytotoxicity prediction also confirmed its potential as an active anticancer phytocompound in lung and brain cancer. Therefore, it can be predicted that Pinocembrin could be a useful bioactive compound as an HDAC1 inhibitor and could be used in developing epigenetic therapy in cancer such as brain cancer and lung cancer to regulate gene expression.

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach.

The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.

In-silico studies to recognize repurposing therapeutics toward arginase-I inhibitors as a potential onco-immunomodulators.

Rudolf Virchow was the first person to point out the important link between immune function and cancer. He did this by noticing that leukocytes were often found in tumors. Overexpression of arginase 1 (ARG1) and inducible nitric oxide synthase (iNOS) in myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) depletes both intracellular and extracellular arginine. TCR signalling is slowed as a result, and the same types of cells produce reactive oxygen and nitrogen species (ROS and RNS), which aggravates the situation. Human arginase I is a double-stranded manganese metalloenzyme that helps L-arginine break down into L-ornithine and urea. Thus, a quantitative structure-activity relationship (QSAR) analysis was performed to unearth the unrecognised structural aspects crucial for arginase-I inhibition. In this work, a balanced QSAR model with good prediction performance and clear mechanistic interpretation was developed using a dataset of 149 molecules encompassing a broad range of structural scaffolds and compositions. The model was made to meet OECD standards, and all of its validation parameters have values that are higher than the minimum requirements (R2 tr = 0.89, Q2 LMO = 0.86, and R2 ex = 0.85). The present QSAR study linked structural factors to arginase-I inhibitory action, including the proximity of lipophilic atoms to the molecule's centre of mass (within 3A), the position of the donor to the ring nitrogen (exactly 3 bonds away), and the surface area ratio. As OAT-1746 and two others are the only arginase-I inhibitors in development at the time, we have performed a QSAR-based virtual screening with 1650 FDA compounds taken from the zinc database. In this screening, 112 potential hit compounds were found to have a PIC50 value of less than 10 nm against the arginase-I receptor. The created QSAR model's application domain was evaluated in relation to the most active hit molecules identified using QSAR-based virtual screening, utilising a training set of 149 compounds and a prediction set of 112 hit molecules. As shown in the Williams plot, the top hit molecule, ZINC000252286875, has a low leverage value of HAT i/i h* = 0.140, placing it towards the boundary of the usable range. Furthermore, one of 112 hit molecules with a docking score of -10.891 kcal/mol (PIC50 = 10.023 M) was isolated from a study of arginase-I using molecular docking. Protonated ZINC000252286875-linked arginase-1 showed 2.9 RMSD, whereas non-protonated had 1.8. RMSD plots illustrate protein stability in protonated and non-protonated ZINC000252286875-bound states. Protonated-ZINC000252286875-bound proteins contain 25 Rg. The non-protonated protein-ligand combination exhibits a 25.2-Rg, indicating compactness. Protonated and non-protonated ZINC000252286875 stabilised protein targets in binding cavities posthumously. Significant root mean square fluctuations (RMSF) were seen in the arginase-1 protein at a small number of residues for a time function of 500 ns in both the protonated and unprotonated states. Protonated and non-protonated ligands interacted with proteins throughout the simulation. ZINC000252286875 bound Lys64, Asp124, Ala171, Arg222, Asp232, and Gly250. Aspartic acid residue 232 exhibited 200% ionic contact. 500-ns simulations-maintained ions. Salt bridges for ZINC000252286875 aided docking. ZINC000252286875 created six ionic bonds with Lys68, Asp117, His126, Ala171, Lys224, and Asp232 residues. Asp117, His126, and Lys224 showed 200% ionic interactions. In protonated and deprotonated states, GbindvdW, GbindLipo, and GbindCoulomb energies played crucial role. Moreover, ZINC000252286875 meets all of the ADMET standards to serve as a drug. As a result, the current analyses were successful in locating a novel and potent hit molecule that inhibits arginase-I effectively at nanomolar concentrations. The results of this investigation can be used to develop brand-new arginase I inhibitors as an alternative immune-modulating cancer therapy.

Bioactive plantaricins as potent anti-cancer drug candidates: double docking, molecular dynamics simulation and in vitro cytotoxicity analysis.

The medical community is desperate for a reliable source of medications to alleviate the severity of conventional cancer treatments and prevent secondary microbial infections in oncological patients. In this regard, plantaricins from lactic acid bacteria were explored as prospective drug candidates against known anti-cancer drug targets. Three plantaricins, JLA-9, GZ1-27 and BN, have a binding affinity of -8.8, -8.6 and -7.2 kcal/mol, respectively, with squalene synthase (SQS), a key molecule in lung cancer metastasis. All three plantaricins displayed analogous binding patterns as SQS inhibitors and generated hydrogen and hydrophobic interactions with ARG 47, ARG 188, PHE24, LEU183 and PRO292. Structural stability of docked complexes was validated using molecular dynamics simulation derived parameters such as RMSD, RMSF and radius of gyration. Based on MD simulation results, conformational changes and stabilities of docked SQS/plantaricin complexes with respect to the time frame were evaluated using machine learning (logistic regression algorithm). Double docking with SQS/matrix metalloproteinase MMP1 and PCA analysis revealed the potential of plantaricin JLA-9 as a multi-substrate inhibitor. Further, plantaricin JLA-9 induced a significant cytotoxic response against the lung carcinoma cell line (A549) in a dose and time dependent manner with inhibition concentration (IC50) of 0.082 µg/ml after 48 h. However, plantaricin JLA-9 did not induce cytotoxicity in normal lung cells (L-132), as the IC50 value was not obtained even at a higher dose of 0.8 µg/ml. In silico pharmacokinetic (ADMET) profile implies that plantaricin JLA-9 could be developed as new age anti-cancer therapeutic with a preference for parenteral administration.Communicated by Ramaswamy H. Sarma.

Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review.

Centella asiatica is an ethnomedicinal herbaceous species that grows abundantly in tropical and sub-tropical regions of China, India, South-Eastern Asia and Africa. It is a popular nutraceutical that is employed in various forms of clinical and cosmetic treatments. C. asiatica extracts are reported widely in Ayurvedic and Chinese traditional medicine to boost memory, prevent cognitive deficits and improve brain functions. The major bioactive constituents of C. asiatica are the pentacyclic triterpenoid glycosides, asiaticoside and madecassoside, and their corresponding aglycones, asiatic acid and madecassic acid. Asiaticoside and madecassoside have been identified as the marker compounds of C. asiatica in the Chinese Pharmacopoeia and these triterpene compounds offer a wide range of pharmacological properties, including neuroprotective, cardioprotective, hepatoprotective, wound healing, anti-inflammatory, anti-oxidant, anti-allergic, anti-depressant, anxiolytic, antifibrotic, antibacterial, anti-arthritic, anti-tumour and immunomodulatory activities. Asiaticoside and madecassoside are also used extensively in treating skin abnormalities, burn injuries, ischaemia, ulcers, asthma, lupus, psoriasis and scleroderma. Besides medicinal applications, these phytocompounds are considered cosmetically beneficial for their role in anti-ageing, skin hydration, collagen synthesis, UV protection and curing scars. Existing reports and experimental studies on these compounds between 2005 and 2022 have been selectively reviewed in this article to provide a comprehensive overview of the numerous therapeutic advantages of asiaticoside and madecassoside and their potential roles in the medical future.

Enhancing plant-derived smart nano inhibitor in targeting mammalian target of rapamycin (mTOR) in breast cancer using Curcuma longa-derived compound curcumin.

Breast cancer is a diverse female malignancy; its classification is based on clinical evidence and pathological elucidation. Large public drug screening data databases combined with transcriptome measures have helped develop predictive computational models. Breast cancer is frequent among women worldwide. Several genes increase breast cancer risk. The Mammalian Target of Rapamycin (popularly known as mTOR) is a risk factor mutated in numerous breast carcinoma types. This has caught the scientific community's focus, which is attempting to generate creative, potent, and bio-available ligands for future anti-cancer treatments to establish a practical therapeutic approach. mTOR is a protein kinase involved in cell proliferation, survival, metabolism, and immune response. Activating mTOR promotes cancer growth and spread. To generate a bioavailable and effective mTOR inhibitor, we used computer-aided drug design to study chromones and flavonoids, two naturally occurring chemicals with many biological activities. We used Curcuma longaderived tiny nano-molecules, which can be coated using liposomes to target mTOR to prevent breast cancer growth. The significant interactions of Curcumin were anticipated using molecular docking. It had the highest binding affinity at -12.26 kcal/mol. 100 nanoseconds of molecular dynamic modelling confirmed Curcumin and mTOR receptor interaction. Liposomes are a form of medicine carrier. To improve healthcare, more liposome-like nanostructures are being made. Nanostructures' interactions with living creatures are being studied. Half-life, tissue accumulation, and toxicity have been studied. Future medication distribution may use nanocarriers having a liposome-like form, enabling targeted nano-delivery. Curcumin's interaction with the active site increased the complex's structural stability during its expansion. Our results may help future investigations of Curcumin's efficacy as a possible lead treatment targeting mTOR receptors in breast cancer. Using Curcumin as a potential anti-cancer drug with lipid-coated nano-particles allows for tailored administration.

Mangiferin: the miraculous xanthone with diverse pharmacological properties.

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one) is a bioactive component derived primarily from the mango tree. Belonging to the Xanthone family, its structure allows it to engage with a variety of pharmacological targets. The symmetric linked core of xanthones has a heterogeneous biogenetic background. The carbon atoms are designated in a biochemical order, which reveals the reason of ring A (C1-C4) being referred to as acetate originated, and ring B (C5-C8) is referred to as shikimate originated. The antibacterial, hypocholesterolemic, antiallergic, cardiotonic, antidiabetic, anti-neoplastic, neuroprotective, antioxidant and immunomodulatory properties have all been demonstrated for the secondary metabolite. This study assessed and explained the important medical properties of mangiferin available in published literature, as well as its natural source, biosynthesis, absorption and bioavailability; multiple administration routes; metabolism; nanotechnology for enhanced efficacy of mangiferin and its toxicity, to aid the anticipated on-going potential of mangiferin as a novel diagnostic treatment.

Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.

Exosomes are the phospholipid-membrane-bound subpopulation of extracellular vesicles derived from the plasma membrane. The main activity of exosomes is cellular communication. In cancer, exosomes play an important rolefrom two distinct perspectives, one related to carcinogenesis and the other as theragnostic and drug delivery tools. The outer phospholipid membrane of Exosome improves drug targeting efficiency. . Some of the vital features of exosomes such as biocompatibility, low toxicity, and low immunogenicity make it a more exciting drug delivery system. Exosome-based drug delivery is a new innovative approach to cancer treatment. Exosome-associated biomarker analysis heralded a new era of cancer diagnostics in a more specific way. This Review focuses on exosome biogenesis, sources, isolation, interrelationship with cancer and exosome-related cancer biomarkers, drug loading methods, exosome-based biomolecule delivery, advances and limitations of exosome-based drug delivery, and exosome-based drug delivery in clinical settings studies. The exosome-based understanding of cancer will change the diagnostic and therapeutic approach in the future.

Microbial strategies for degradation of microplastics generated from COVID-19 healthcare waste.

COVID-19 pandemic has led to the generation of massive plastic wastes, comprising of onetime useable gloves, masks, tissues, and other personal protective equipment (PPE). Recommendations for the employ of single-use disposable masks made up of various polymeric materials like polyethylene, polyurethane, polyacrylonitrile, and polypropylene, polystyrene, can have significant aftermath on environmental, human as well as animal health. Improper disposal and handling of healthcare wastes and lack of proper management practices are creating serious health hazards and an extra challenge for the local authorities designated for management of solid waste. Most of the COVID-19 medical wastes generated are now being treated by incineration which generates microplastic particles (MPs), dioxin, furans, and various toxic metals, such as cadmium and lead. Moreover, natural degradation and mechanical abrasion of these wastes can lead to the generation of MPs which cause a serious health risk to living beings. It is a major threat to aquatic lives and gets into foods subsequently jeopardizing global food safety. Moreover, the presence of plastic is also considered a threat owing to the increased carbon emission and poses a profound danger to the global food chain. Degradation of MPs by axenic and mixed culture microorganisms, such as bacteria, fungi, microalgae etc. can be considered an eco-sustainable technique for the mitigation of the microplastic menace. This review primarily deals with the increase in microplastic pollution due to increased use of PPE along with different disinfection methods using chemicals, steam, microwave, autoclave, and incineration which are presently being employed for the treatment of COVID-19 pandemic-related wastes. The biological treatment of the MPs by diverse groups of fungi and bacteria can be an alternative option for the mitigation of microplastic wastes generated from COVID-19 healthcare waste.