Nitric Oxide Water-driven Immunogenic Cell Death: Unfolding Mitochondrial Dysfunction's Role in Sensitizing Lung Adenocarcinoma to Ferroptosis and Autophagic Cell Death.

Non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), significantly influences cancer-related mortality and is frequently considered by poor therapeutic responses due to genetic alterations. Cancer cells possess an inclination to develop resistance to individual treatment modalities, thus it is necessary to investigate several pathways simultaneously to obtain insights that will aid in the establishment of improved therapeutic approaches. Exploring regulated cell death (RCD) mechanisms offers promising avenues to augment immunotherapy by reshaping the tumor microenvironment (TME). Here, we investigated the prospective of microwave plasma-infused Nitric oxide water (NOW) to initiate immunogenic cell death (ICD) while concurrently modulating autophagy and ferroptosis signaling in LUAD-associated A549 cells. Plasma-treatment results in stable NO species nitrite/nitrate (NO2-/NO3-) in the water, altering its physiochemical properties. Analysis of ICD markers reveals increased expression of damage-associated molecular patterns (DAMPs) at both protein and mRNA levels post-NOW exposure. Intracellular reactive oxygen and nitrogen species (RONS) accumulation suggests NO-mediated mitochondrial dysfunction, triggering autophagy induction. Flow cytometry and western blotting confirm alterations in autophagy regulators Beclin-1 and SQSTM1. Furthermore, NOW treatment induces lipid peroxidation and upregulates ferroptosis-associated genes, as determined by qRT-PCR. Transmission electron microscopy (TEM) imaging reveals autophagosome formation and loss of cristae structures, corroborating the occurrence of autophagy and ferroptosis. Our findings propose that NOW may considered as as inducer of ICD and the stimulation of other RCD related protiend may enhance the anti-tumor immunogenicity.

Biocompatible plasma-treated liquids: A sustainable approach for decontaminating gastrointestinal-infection causing pathogens.

Nosocomial infections are a serious threat and difficult to cure due to rising antibiotic resistance in pathogens and biofilms. Direct exposure to cold atmospheric plasma (CAP) has been widely employed in numerous biological research endeavors. Nonetheless, plasma-treated liquids (PTLs) formulated with physiological solutions may offer additional benefits such as enhanced portability, and biocompatibility. Additionally, CAP-infused long-lived reactive oxygen and nitrogen species (RONS) such as nitrite (NO2-), nitrate (NO3-), and hydrogen peroxide (H2O2) can synergistically induce their antibacterial activity. Herein, we investigated those argon-plasma jet-treated liquids, including Ringer's lactate (RL), phosphate-buffered saline (PBS), and physiological saline, have significant antibacterial activity against nosocomial/gastrointestinal-causing pathogens, which might be due to ROS-mediated lipid peroxidation. Combining the conventional culture-based method with propidium iodide monoazide quantitative PCR (PMAxx™-qPCR) indicated that PTLs induce a minimal viable but non-culturable (VBNC) state and moderately affect culturable counts. Specifically, the PTL exposure resulted in pathogenicity dysfunction via controlling T3SS-related effector genes of S. enterica. Overall, this study provides insights into the effectiveness of PTLs for inducing ROS-mediated damage, controlling the virulence of diarrheagenic bacteria, and modulating homeostatic genes.

Surface air gas discharge plasma: An ecofriendly virus inactivation approach to enhance CPRRs mediated antiviral genes expression against airborne bio-contaminant (human Coronavirus-229E).

Emerging bio-contaminants (airborne viruses) exploits and manipulate host (human) metabolism to produce new viral particles, evading the host's immune defences and leading to infections. Non-thermal plasma, operating at atmospheric pressure and ambient temperature, is explored for virus inactivation, generating RONS that interact and denatures viral proteins. However, various factors affecting virus survival influence the efficacy of non-thermal plasma. Glucose analogue 2-DG, a metabolic modifier used in this study, disrupts the glycolysis pathway viruses rely on, creating an unfavourable environment for replication. Here, airborne HCoV-229E bio-contaminant was treated with plasma for inactivation, and the presence of RONS was analysed. Metabolically altered lung cells were subsequently exposed to the treated airborne viruses. Cytopathic effect, spike protein, and cell death were evaluated via flow cytometry and confocal microscopy, and CPRRs mediated antiviral gene expression was evaluated using PCR. Gas plasma-treated viruses led to reduced virus proliferation in unaltered lung cells, although few virus particles survived the exposure, as confirmed by biological assessment (cytopathic effects and live/dead staining). A combination approach of gas plasma-treated viruses and altered lung cells displayed drastic virus reduction compared to the control group, established through confocal microscopy and flow cytometry. Furthermore, altered lung cell enhances gene transcription responsible for innate immunity when exposed to the gas plasma-treated virus, thereby impeding airborne virus propagation. This study demonstrates the significance of a surface air gas plasma and metabolic alteration approach in enhancing genes targeted towards antiviral innate immunity and tackling outbreaks of emerging bio-contaminants of concerns (airborne viruses).

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.

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.

Glycolytic stress deteriorates 229E virulence to improve host defense response.

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.

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.

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 translational paradigm of nanobiomaterials: Biological chemistry to modern applications.

Recently nanotechnology has evolved as one of the most revolutionary technologies in the world. It has now become a multi-trillion-dollar business that covers the production of physical, chemical, and biological systems at scales ranging from atomic and molecular levels to a wide range of industrial applications, such as electronics, medicine, and cosmetics. Nanobiomaterials synthesis are promising approaches produced from various biological elements be it plants, bacteria, peptides, nucleic acids, etc. Owing to the better biocompatibility and biological approach of synthesis, they have gained immense attention in the biomedical field. Moreover, due to their scaled-down sized property, nanobiomaterials exhibit remarkable features which make them the potential candidate for different domains of tissue engineering, materials science, pharmacology, biosensors, etc. Miscellaneous characterization techniques have been utilized for the characterization of nanobiomaterials. Currently, the commercial transition of nanotechnology from the research level to the industrial level in the form of nano-scaffolds, implants, and biosensors is stimulating the whole biomedical field starting from bio-mimetic nacres to 3D printing, multiple nanofibers like silk fibers functionalizing as drug delivery systems and in cancer therapy. The contribution of single quantum dot nanoparticles in biological tagging typically in the discipline of genomics and proteomics is noteworthy. This review focuses on the diverse emerging applications of Nanobiomaterials and their mechanistic advancements owing to their physiochemical properties leading to the growth of industries on different biomedical measures. Alongside the implementation of such nanobiomaterials in several drug and gene delivery approaches, optical coding, photodynamic cancer therapy, and vapor sensing have been elaborately discussed in this review. Different parameters based on current challenges and future perspectives are also discussed here.

Proximal discrepancy in intrinsic atomic interaction arrests G2/M phase by inhibiting Cyclin B1/CDK1 to infer molecular and cellular biocompatibility of D-limonene.

The quest for different natural compounds for different biomedical applications especially in the treatment of cancer is at a high pace with increasing incidence of severity. D-limonene has been portrayed as one of the effective potential candidate centered to the context of breast cancer. The anticipation of its count as an effective biomedical agent required a detailed understanding of their molecular mechanism of biocompatibility. This study elucidates the mechanistic action of D-limonene channelized by the induction of apoptosis for controlling proliferation in breast cancer cells. The possible mechanism was explored through an experimental and computational approach to estimate cell proliferation inhibition, cell cycle phase distribution, apoptosis analysis using a flow cytometry, western blotting and molecular docking. The results showed reduced dose and time-dependent viability of MCF7 cells. The study suggested the arrest of the cell cycle at G2/M phase leading to apoptosis and other discrepancies of molecular activity mediated via significant alteration in protein expression pattern of anti-apoptotic proteins like Cyclin B1 and CDK1. Computational analysis showed firm interaction of D-limonene with Cyclin B1 and CDK1 proteins influencing their structural and functional integrity indicating the mediation of mechanism. This study concluded that D-limonene suppresses the proliferation of breast cancer cells by inducing G2/M phase arrest via deregulation of Cyclin B1/CDK1.

Phage-tail-like bacteriocins as a biomedical platform to counter anti-microbial resistant pathogens.

Phage Tail Like bacteriocins (PTLBs) has been an area of interest in the last couple of years owing to their varied application against multi-drug resistant (MDR), anti-microbial resistant (AMR) pathogens and their evolutionary link with the dsDNA virus and bacteriophages. PTLBs are defective phages derived from Myoviridae and Siphoviridae phages, PTLBs are distinguished into R-type (Rigid type) characterized by a non-flexible contractile nanotube resembling Myoviridae phage contractile tails, and F-type (Flexible type) with a flexible non-contractile rod-like structure similar to Siphoviridae phages. In this review, we have discussed the structural association, mechanism, and characterization of PTLBs. Moreover, we have elucidated the symbiotic biological function and application of PTLBs against MDR and XDR pathogens and highlighted the evolutionary role of PTLBs. The difficulties that must be overcome to implement PTLBs clinically are also discussed. It is imperative that these issues be addressed by academics in future studies before being implemented in clinical settings. This article is novel in its way as it will not only provide us with a gateway that acts as a novel strategy for scholars to mitigate and control the uprising issue of AMR pathogens but also promote the development of clinical studies for PTLBs.

Emerging trends in the nanomedicine applications of functionalized magnetic nanoparticles as novel therapies for acute and chronic diseases.

High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry.

Theragnostic application of nanoparticle and CRISPR against food-borne multi-drug resistant pathogens.

Foodborne infection is one of the leading sources of infections spreading across the world. Foodborne pathogens are recognized as multidrug-resistant (MDR) pathogens posing a significant problem in the food industry and healthy consumers resulting in enhanced economic burden, and nosocomial infections. The continued search for enhanced microbial detection tools has piqued the interest of the CRISPR-Cas system and Nanoparticles. CRISPR-Cas system is present in the bacterial genome of some prokaryotes and is repurposed as a theragnostic tool against MDR pathogens. Nanoparticles and composites have also emerged as an efficient tool in theragnostic applications against MDR pathogens. The diagnostic limitations of the CRISPR-Cas system are believed to be overcome by a synergistic combination of the nanoparticles system and CRISPR-Cas using nanoparticles as vehicles. In this review, we have discussed the diagnostic application of CRISPR-Cas technologies along with their potential usage in applications like phage resistance, phage vaccination, strain typing, genome editing, and antimicrobial. we have also elucidated the antimicrobial and detection role of nanoparticles against foodborne MDR pathogens. Moreover, the novel combinatorial approach of CRISPR-Cas and nanoparticles for their synergistic effects in pathogen clearance and drug delivery vehicles has also been discussed.

In vivo intrinsic atomic interaction infer molecular eco-toxicity of industrial TiO2 nanoparticles via oxidative stress channelized steatosis and apoptosis in Paramecium caudatum.

The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.

Hydoxylated ß- and δ-Hexacholorocyclohexane metabolites infer influential intrinsic atomic pathways interaction to elicit oxidative stress-induced apoptosis for bio-toxicity.

Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to ß-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment.

Aurora Borealis in dentistry: The applications of cold plasma in biomedicine.

Plasma is regularly alluded to as the fourth form of matter. Its bounty presence in nature along with its potential antibacterial properties has made it a widely utilized disinfectant in clinical sciences. Thermal plasma and non-thermal (or cold atmospheric) plasma (NTP) are two types of plasma. Atoms and heavy particles are both available at the same temperature in thermal plasma. Cold atmospheric plasma (CAP) is intended to be non-thermal since its electrons are hotter than the heavier particles at ambient temperature. Direct barrier discharge (DBD), atmospheric plasma pressure jet (APPJ), etc. methods can be used to produce plasma, however, all follow a basic concept in their generation. This review focuses on the anticipated uses of cold atmospheric plasma in dentistry, such as its effectiveness in sterilizing dental instruments by eradicating bacteria, its advantage in dental cavity decontamination over conventional methods, root canal disinfection, its effects on tooth whitening, the benefits of plasma treatment on the success of dental implant placement, and so forth. Moreover, the limitations and probable solutions has also been anticipated. These conceivable outcomes thus have proclaimed the improvement of more up-to-date gadgets, for example, the plasma needle and plasma pen, which are efficient in treating the small areas like root canal bleaching, biofilm disruption, requiring treatment in dentistry.

The Hha-TomB toxin-antitoxin module in Salmonella enterica serovar Typhimurium limits its intracellular survival profile and regulates host immune response.

The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin-antitoxin (TA) system is known to play a vital role in response to stress adaptation, drug resistance, biofilm formation, intracellular survival, persistence as well as pathogenesis. In the present study, we investigated the role of Hha-TomB TA system in regulating virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in a host model system, where we showed that deletion of hha and tomB genes displayed impaired cell adhesion, invasion, and uptake. The isogenic hha and tomB mutant strain was also found to be deficient in intracellular replication in vitro, with a highly repressed Salmonella Pathogenicity Island-2 (SPI-2) genes and downregulation of Salmonella Pathogenicity Island-1 (SPI-1) genes. In addition, the Δhha and ΔtomB did not show acute colitis in C57BL/6 mice and displayed less dissemination to systemic organs followed by their cecal pathology. The TA mutants also showed reduction in serum cytokine and nitric oxide levels both in vitro and in vivo. However, the inflammation phenotype was restored on complementing strain of TA gene to its mutant strain. In silico studies depicted firm interaction of Hha-TomB complex and the regulatory proteins, namely, SsrA, SsrB, PhoP, and PhoQ. Overall, we demonstrate that this study of Hha-TomB TA system is one of the prime regulating networks essential for S. Typhimurium pathogenesis. 1. Role of Hha-TomB toxin-antitoxin (TA) system in Salmonella pathogenesis was examined. 2. The TA mutants resulted in impaired invasion and intracellular replication in vitro. 3. The TA mutants displayed alteration in SPI-1 and SPI-2 regulatory genes inside host cells. 4. Mutation in TA genes also limited systemic colonization and inflammatory response in vivo.

Molecular toxicity of Benzo(a)pyrene mediated by elicited oxidative stress infer skeletal deformities and apoptosis in embryonic zebrafish.

Benzo(a)pyrene (BaP) has become an integral component of disposed of plastic waste, organic pollutants, and remnants of combustible materials in the aquatic environment due to their persistent nature. The accumulation and integration of these polycyclic aromatic hydrocarbons (PAHs) have raised concern to human health and ecological safety. This study assessed the BaP-induced in vivo molecular toxicity with embryonic zebrafish inferred by oxidative stress and apoptosis. BaP was found to induce morphological and physiological abnormalities like delayed hatching (p < 0.05). Computational analysis demonstrated the high-affinity interaction of BaP with the zebrafish hatching enzyme (ZHE1) with Arg, Cys, Ala, Tyr, and Phe located at the active site revealing the influence of BaP on delayed hatching due to alteration of the enzyme structure. RT-PCR analysis revealed significant down-regulation of the skeletal genes Sox9a, SPP1/OPN, and Col1a1 (p < 0.05) genes. The cellular investigations unraveled that the toxicity of BaP extends to the skeletal regions of zebrafish (head, backbone, and tail) because of the elicited oxidative stress leading to apoptosis. The study extended the horizon of understanding of BaP toxicity at the molecular level which will enhance the indulgent and designing of techniques for better ecological sustainability.

Parkinson's Disease and Impairment in Mitochondrial Metabolism: A Pathognomic Signature.

Mitochondrial bioenergetics is vital for the proper functioning of cellular compartments. Impairments in mitochondrial DNA encoding the respiratory chain complexes and other assisting proteins, accumulation of intracellular reactive oxygen species, an imbalance in cellular calcium transport, or the presence of organic pollutants, high fat-ketogenic diets or toxins, and advancing age can result in complex disorders, including cancer, metabolic disease, and neurodegenerative disorders. Such manifestations are distinctly exhibited in several age-related neurodegenerative diseases, such as in Parkinson's disease (PD). Defects in complex I along with perturbed signaling pathways is a common manifestation of PD. Impaired oxidative phosphorylation could increase the susceptibility to PD. Therefore, unraveling the mechanisms of mitochondrial complexes in clinical scenarios will assist in developing potential early biomarkers and standard tests for energy failure diagnosis and assist to pave a new path for targeted therapeutics against PD.

Intrinsic atomic interaction at molecular proximal vicinity infer cellular biocompatibility of antibacterial nanopepper.

Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 µM and 2.1 µM in HCT116 colon cells. Components of pepper, piperine and ß-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction. Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 µM and 2.1 µM in HCT116 colon cells. Components of pepper, piperine and ß-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction.