ExoDS: a versatile exosome-based drug delivery platform to target cancer cells and cancer stem cells.

Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer. Although they are toxic, they are still widely used to treat cancer. Delivering chemotherapy drugs directly to cancer cells to reduce side effects remains a challenge. Moreover, modern research gave rise to cancer stem cell theory, which implicated cancer stem cells in tumor initiation, progression, and relapse. This makes it imperative to target cancer stem cells to achieve complete remission. Our work highlights the development of an exosome-based targeted drug delivery vehicle. These exosomes were isolated from mature dendritic cells (mDCs) and encapsulated with doxorubicin (ExoDS). Our results showed that ExoDS specifically targeted breast cancer cells and breast cancer stem cells. Further analysis revealed that ExoDS did not induce any significant apoptosis in healthy mammary cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and breast cancer patients. ExoDS was also found to target circulating tumor cells (CTCs) isolated from patient blood. ExoDS also showed equal efficiency compared to free doxorubicin in vivo. We also observed that ExoDS reduced the expression of cancer stem cell markers in murine tumor tissues. Altogether, this work provides novel insights into how mDC-derived exosomes can be used to specifically target cancer cells and cancer stem cells.

Molecular insights to in vitro biocompatibility of endodontic Pulpotec with macrophages determined by oxidative stress and apoptosis.

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.

Nanoparticle-mediated metronomic chemotherapy in cancer: A paradigm of precision and persistence.

Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.

Perilous paradigm of graphene oxide and its derivatives in biomedical applications: Insight to immunocompatibility.

With advancements in nanotechnology and innovative materials, Graphene Oxide nanoparticles (GONP) have attracted lots of attention among the diverse types of nanomaterials owing to their distinctive physicochemical characteristics. However, the usage at scientific and industrial level has also raised concern to their toxicological interaction with biological system. Understanding these interactions is crucial for developing guidelines and recommendations for applications of GONP in various sectors, like biomedicine and environmental technologies. This review offers crucial insights and an in-depth analysis to the biological processes associated with GONP immunotoxicity with multiple cell lines including human whole blood cultures, dendritic cells, macrophages, and multiple cancer cell lines. The complicated interactions between graphene oxide nanoparticles and the immune system, are highlighted in this work, which reveals a range of immunotoxic consequences like inflammation, immunosuppression, immunostimulation, hypersensitivity, autoimmunity, and cellular malfunction. Moreover, the immunotoxic effects are also highlighted with respect to in vivo models like mice and zebrafish, insighting GO Nanoparticles' cytotoxicity. The study provides invaluable review for researchers, policymakers, and industrialist to understand and exploit the beneficial applications of GONP with a controlled measure to human health and the environment.

Circadian Rhythms in Cardiovascular Metabolism.

Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of the day, to ensure temporal needs for ATP, building blocks, and metabolism-based signaling molecules are met. What has become increasingly clear is that in addition to classic signal-response coupling (termed reactionary mechanisms), cardiovascular-relevant cells use autonomous circadian clocks to temporally orchestrate metabolic pathways in preparation for predicted stimuli/stresses (termed anticipatory mechanisms). Here, we review current knowledge regarding circadian regulation of metabolism, how metabolic rhythms are synchronized with cardiovascular function, and whether circadian misalignment/disruption of metabolic processes contribute toward the pathogenesis of cardiovascular disease.

The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling.

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human and other biotic members. In last few decades, understanding of toxicity of these materials has been given the centre stage of research using many in vitro and in vivo models. Zebrafish (Danio rerio), a freshwater fish and a member of the minnow family has garnered much attention due to its distinct features, which make it an important and frequently used animal model in various fields of embryology and toxicological studies. Given that fertilization and development of zebrafish eggs take place externally, they serve as an excellent model organism for studying early developmental stages. Moreover, zebrafish possess a comparable genetic composition to humans and share almost 70% of their genes with mammals. This particular model organism has become increasingly popular, especially for developmental research. Moreover, it serves as a link between in vitro studies and in vivo analysis in mammals. It is an appealing choice for vertebrate research, when employing high-throughput methods, due to their small size, swift development, and relatively affordable laboratory setup. This small vertebrate has enhanced comprehension of pathobiology and drug toxicity. This review emphasizes on the recent developments in toxicity screening and assays, and the new insights gained about the toxicity of drugs through these assays. Specifically, the cardio, neural, and, hepatic toxicology studies inferred by applications of nanoparticles have been highlighted.

Proximal discrepancies in intrinsic atomic interaction determines comparative in vivo biotoxicity of Chlorpyrifos and 3,5,6-trichloro-2-pyridinol in embryonic zebrafish.

Bioaccumulation of Chlorpyrifos (CP) as pesticides due to their aggrandized use in agriculture has raised serious concern on the health of ecosystem and human beings. Moreover, their degraded products like 3,5,6-trichloro-2-pyridinol (TCP) has enhanced the distress due to their unpredictable biotoxicity. This study evaluates and deduce the comparative in vivo mechanistic biotoxicity of CP and TCP with zebrafish embryos through experimental and computational approach. Experimental cellular and molecular analysis showed higher induction of morphological abnormalities, oxidative stress and apoptosis in TCP exposed embryos compared to CP exposure due to upregulation of metabolic enzymes like Zhe1a, Sod1 and p53. Computational analysis excavated the differential discrepancies in intrinsic atomic interaction as a reason of disparity in biotoxicity of CP and TCP. The mechanistic differences were deduced due to the differential accumulation and internalisation leading to variable interaction with metabolic enzymes for oxidative stress and apoptosis causing physiological and morphological abnormalities. The study unravelled the information of in vivo toxicity at cellular and molecular level to advocate the attention of taking measures for management of CP as well as TCP for environmental and human health.

Boosting Copper Biocidal Activity by Silver Decoration and Few-Layer Graphene in Coatings on Textile Fibers.

The outbreak of the Coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of developing antiviral surface coatings that are capable of repelling pathogens and neutralizing them through self-sanitizing properties. In this study, a novel coating design based on few-layer graphene (FLG) is proposed and silver-decorated micro copper flakes (CuMF) that exhibit both antibacterial and antiviral properties. The role of sacrificial anode surfaces and intrinsic graphene defects in enhancing the release of metal ions from CuMF embedded in water-based binders is investigated. In silico analysis is conducted to better understand the molecular interactions of pathogen-repelling species with bacterial or bacteriophage proteins. The results show that the optimal amount of CuMF/FLG in the coating leads to a significant reduction in bacterial growth, with reductions of 3.17 and 9.81 log for Staphylococcus aureus and Escherichia coli, respectively. The same coating also showed high antiviral efficacy, reducing bacteriophage phi6 by 5.53 log. The antiviral efficiency of the coating is find to be doubled compared to either micro copper flakes or few-layer graphene alone. This novel coating design is versatile and can be applied to various substrates, such as personal protective clothing and face masks, to provide biocidal activity against both bacterial and viral pathogens.

Intrinsic insights to antimicrobial effects of Nitrofurantoin to multi drug resistant Salmonella enterica serovar Typhimurium ms202.

Emerging multidrug resistant (MDR) serovar of Salmonella has raised the concern of their impactful effect on pathogenic infection and mortality in human lead by the enteric diseases. In order to combat the battle against these MDR Salmonella pathogen, new drug molecules need to be evaluated for their potent antibacterial application. This study evaluates the mechanistic antimicrobial effect of nitrofurantoin against a MDR strain of Salmonella named S. enterica Typhimurium ms202. The antimicrobial effect of nitrofurantoin was studied through experimental and computational approach using standard microbiological and molecular techniques like growth curve analysis, live-dead analysis, oxidative stress evaluation using high throughput techniques like flow cytometry and fluorescent microscopy. The result showed a potent dose dependent antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202 with a MIC value of 64 µg/ml. Moreover, the mechanistic excavation of the phenomenon described the mechanism as an effect of molecular interaction of nitrofurantoin molecule with membrane receptor proteins OmpC of S. enterica Typhimurium ms202 leading to internalization of the nitrofurantoin heading towards the occurrence of cellular physiological disturbances through oxidative stress impeded by nitrofurantoin-Sod1 C protein interaction. The results indicated towards a synergistic effect of membrane damage, oxidative stress and genotoxicity for the antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202. The study described the potent dose-dependent application of nitrofurantoin molecule against MDR strains of Salmonella and guided towards their use in further discovered MDR strains.

Posterity of nanoscience as lipid nanosystems for Alzheimer's disease regression.

Alzheimer's disease (AD) is a type of dementia that affects a vast number of people around the world, causing a great deal of misery and death. Evidence reveals a relationship between the presence of soluble Aß peptide aggregates and the severity of dementia in Alzheimer's patients. The BBB (Blood Brain Barrier) is a key problem in Alzheimer's disease because it prevents therapeutics from reaching the desired places. To address the issue, lipid nanosystems have been employed to deliver therapeutic chemicals for anti-AD therapy in a precise and targeted manner. The applicability and clinical significance of lipid nanosystems to deliver therapeutic chemicals (Galantamine, Nicotinamide, Quercetin, Resveratrol, Curcumin, HUPA, Rapamycin, and Ibuprofen) for anti-AD therapy will be discussed in this review. Furthermore, the clinical implications of the aforementioned therapeutic compounds for anti-AD treatment have been examined. Thus, this review will pave the way for researchers to fashion therodiagnostics approaches based on nanomedicine to overcome the problems of delivering therapeutic molecules across the blood brain barrier (BBB).

Biofilm modifiers: The disparity in paradigm of oral biofilm ecosystem.

A biofilm is a population of sessile microorganisms that has a distinct organized structure and characteristics like channels and projections. Good oral hygiene and reduction in the prevalence of periodontal diseases arise from minimal biofilm accumulation in the mouth, however, studies focusing on modifying the ecology of oral biofilms have not yet been consistently effective. The self-produced matrix of extracellular polymeric substances and greater antibiotic resistance make it difficult to target and eliminate biofilm infections, which lead to serious clinical consequences that are often lethal. Therefore, a better understanding is required to target and modify the ecology of biofilms in order to eradicate the infection, not only in instances of oral disorders but also in terms of nosocomial infections. The review focuses on several biofilm ecology modifiers to prevent biofilm infections, as well as the involvement of biofilm in antibiotic resistance, implants or in-dwelling device contamination, dental caries, and other periodontal disorders. It also discusses recent advances in nanotechnology that may lead to novel strategies for preventing and treating infections caused by biofilms as well as a novel outlook to infection control.

Synergistic degradation of Chlorpyrifos by modified solar Photo-Fenton process with bacterial metabolism reduces in vivo biotoxicity in zebrafish (Danio rerio).

The extensive use of Chlorpyrifos (CP) as insecticide has raised concern to their hazardous impact on human health and ecosystems. Bioremediation has been proved as one of the key eco-compatible method for reducing these environmental toxicants. This study explores and evaluate the effectiveness of a combined process including solar Photo-Fenton process followed by bacterial degradation using Ochrobactrum sp. CPD-03 for effective CP degradation in wastewater. Moreover, the in vivo molecular biotoxicity of CP and degraded CP has been evaluated with embryonic zebrafish. The solar Photo-Fenton treatment showed CP degradation efficiency of ∼42 % in 4 h and ∼92 % in 96 h with combined bacterial degradation process. In vivo biotoxicity analysis showed increased survivability of embryonic zebrafish exposed to CP with CPD-03 in water with lesser morphological abnormalities. The mechanistic molecular analysis showed decreased acetylcholinesterase inhibition and GST activity in embryos exposed to CP with CPD-03 for a lesser apoptosis due to influential intrinsic interaction with metabolic proteins. The study advocated to the use of solar Photo-Fenton process followed by bacterial degradation for an efficient ecological degradation of CP for effective reduction of in vivo biotoxicity.

Atmospheric microplastic and nanoplastic: The toxicological paradigm on the cellular system.

The increasing demand for plastic in our daily lives has led to global plastic pollution. The improper disposal of plastic has resulted in a massive amount of atmospheric microplastics (MPs), which has further resulted in the production of atmospheric nanoplastics (NPs). Because of its intimate relationship with the environment and human health, microplastic and nanoplastic contamination is becoming a problem. Because microplastics and nanoplastics are microscopic and light, they may penetrate deep into the human lungs. Despite several studies demonstrating the abundance of microplastics and nanoplastics in the air, the potential risks of atmospheric microplastics and nanoplastics remain unknown. Because of its small size, atmospheric nanoplastic characterization has presented significant challenges. This paper describes sampling and characterization procedures for atmospheric microplastics and nanoplastics. This study also examines the numerous harmful effects of plastic particles on human health and other species. There is a significant void in research on the toxicity of airborne microplastics and nanoplastics upon inhalation, which has significant toxicological potential in the future. Further study is needed to determine the influence of microplastic and nanoplastic on pulmonary diseases.

Amelioration of lipopeptide biosurfactants for enhanced antibacterial and biocompatibility through molecular antioxidant property by methoxy and carboxyl moieties.

Biosurfactants having surface-active biomolecules have been the cynosure in environment research due to their vast application. However, the lack of information about their low-cost production and detailed mechanistic biocompatibility limits the applicability. The study explores techniques for the production and design of low-cost, biodegradable, and non-toxic biosurfactants from Brevibacterium casei strain LS14 and excavates the mechanistic details of their biomedical properties like antibacterial effects and biocompatibility. Taguchi's design of experiment was used to optimize for enhancing biosurfactant production by optimal factor combinations like Waste glycerol (1%v/v), peptone (1%w/v), NaCl 0.4% (w/v), and pH 6. Under optimal conditions, the purified biosurfactant reduced the surface tension to 35 mN/m from 72.8 mN/m (MSM) and a critical micelle concentration of 25 mg/ml was achieved. Spectroscopic analyses of the purified biosurfactant using Nuclear Magnetic Resonance suggested it as a lipopeptide biosurfactant. The evaluation of mechanistic antibacterial, antiradical, antiproliferative, and cellular effects indicated the efficient antibacterial activity (against Pseudomonas aeruginosa) of biosurfactants due to free radical scavenging activity and oxidative stress. Moreover, the cellular cytotoxicity was estimated by MTT and other cellular assays revealing the phenomenon as the dose-dependent induction of apoptosis due to free radical scavenging with an LC50 of 55.6 ± 2.3 mg/ml.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.

Emerging bio-contaminants such as viruses have affected health and environment settings of every country. Viruses are the minuscule entities resulting in severe contagious diseases like SARS, MERS, Ebola, and avian influenza. Recent epidemic like the SARS-CoV-2, the virus has undergone mutations strengthen them and allowing to escape from the remedies. Comprehensive knowledge of viruses is essential for the development of targeted therapeutic and vaccination treatments. Animal models mimicking human biology like non-human primates, rats, mice, and rabbits offer competitive advantage to assess risk of viral infections, chemical toxins, nanoparticles, and microbes. However, their economic maintenance has always been an issue. Furthermore, the redundancy of experimental results due to aforementioned aspects is also in examine. Hence, exploration for the alternative animal models is crucial for risk assessments. The current review examines zebrafish traits and explores the possibilities to monitor emerging bio-contaminants. Additionally, a comprehensive picture of the bio contaminant and virus particle invasion and abatement mechanisms in zebrafish and human cells is presented. Moreover, a zebrafish model to investigate the emerging viruses such as coronaviridae and poxviridae has been suggested.

The paradigm of prophylactic viral outbreaks measures by microbial biosurfactants.

The recent emergence and outbreak of the COVID-19 pandemic confirmed the incompetence of countries across the world to deal with a global public health emergency. Although the recent advent of vaccines is an important prophylactic measure, effective clinical therapy for SARS-Cov-2 is yet to be discovered. With the increasing mortality rate, research has been focused on understanding the pathogenic mechanism and clinical parameters to comprehend COVID-19 infection and propose new avenues for naturally occurring molecules with novel therapeutic properties to alleviate the current situation. In accordance with recent clinical studies and SARS-CoV-2 infection markers, cytokine storm and oxidative stress are entwined pathogenic processes in COVID-19 progression. Lately, Biosurfactants (BSs) have been studied as one of the most advanced biomolecules of microbial origin with anti-inflammatory, antioxidant, antiviral properties, antiadhesive, and antimicrobial properties. Therefore, this review inspects available literature and proposes biosurfactants with these properties to be encouraged for their extensive study in dealing with the current pandemic as new pharmaceutics in the prevention and control of viral spread, treating the symptoms developed after the incubation period through different therapeutic approaches and playing a potential drug delivery model.

The paradigm of miRNA and siRNA influence in Oral-biome.

Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches.

Emerging Trends in Advanced Translational Applications of Silver Nanoparticles: A Progressing Dawn of Nanotechnology.

Nanoscience has emerged as a fascinating field of science, with its implementation in multiple applications in the form of nanotechnology. Nanotechnology has recently been more impactful in diverse sectors such as the pharmaceutical industry, agriculture sector, and food market. The peculiar properties which make nanoparticles as an asset are their large surface area and their size, which ranges between 1 and 100 nanometers (nm). Various technologies, such as chemical and biological processes, are being used to synthesize nanoparticles. The green chemistry route has become extremely popular due to its use in the synthesis of nanoparticles. Nanomaterials are versatile and impactful in different day to day applications, resulting in their increased utilization and distribution in human cells, tissues, and organs. Owing to the deployment of nanoparticles at a high demand, the need to produce nanoparticles has raised concerns regarding environmentally friendly processes. These processes are meant to produce nanomaterials with improved physiochemical properties that can have significant uses in the fields of medicine, physics, and biochemistry. Among a plethora of nanomaterials, silver nanoparticles have emerged as the most investigated and used nanoparticle. Silver nanoparticles (AgNPs) have become vital entities of study due to their distinctive properties which the scientific society aims to investigate the uses of. The current review addresses the modern expansion of AgNP synthesis, characterization, and mechanism, as well as global applications of AgNPs and their limitations.

Challenges and future scope of exosomes in the treatment of cardiovascular diseases.

Exosomes are nanosized vesicles that carry biologically diverse molecules for intercellular communication. Researchers have been trying to engineer exosomes for therapeutic purposes by using different approaches to deliver biologically active molecules to the various target cells efficiently. Recent technological advances may allow the biodistribution and pharmacokinetics of exosomes to be modified to meet scientific needs with respect to specific diseases. However, it is essential to determine an exosome's optimal dosage and potential side effects before its clinical use. Significant breakthroughs have been made in recent decades concerning exosome labelling and imaging techniques. These tools provide in situ monitoring of exosome biodistribution and pharmacokinetics and pinpoint targetability. However, because exosomes are nanometres in size and vary significantly in contents, a deeper understanding is required to ensure accurate monitoring before they can be applied in clinical settings. Different research groups have established different approaches to elucidate the roles of exosomes and visualize their spatial properties. This review covers current and emerging strategies for in vivo and in vitro exosome imaging and tracking for potential studies.