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Abstract: The direct delivery of therapeutic molecules is generally inefficient and has several problems. Hence, nanomedicines with targeted and controlled delivery applications have been an exciting field of research for the past decade. In this regard, the adjustable properties of inorganic nanoparticles like particle size distribution, ability to change the targeting ligand to have a higher affinity towards the pathologic cell, and controlled delivery properties have made them indispensable for targeted drug delivery applications. Changing the ligand on the surface of the inorganic nanoparticle can direct different therapeutic molecules to different organs like the liver, spleen, kidney, bone, and even brain. However, while the other targeted nanomedicines are well-reported, the targeting of therapeutics to bone marrow cells is sparse in the literature. Hence, the administration of therapeutics for bone-related disorders, like bone metastases, leads to several problems, such as severe systemic toxicity and suboptimal efficacy. In this direction, we have shown our successful effort to functionalise a model inorganic nanoparticle (Fe2O3) by glutamate ligand which is reported to have a high affinity towards the NMDA receptors of the bone cells. We have performed spectroscopic studies to characterize the nano-hybrid. We have shown that the cargo or the Fe2O3 nanoparticle possesses the ability to generate photo-induced reactive oxygen species (ROS), thereby leading to a therapeutic opportunity for bone metastases. In addition, the nanoparticle also possesses the ability to generate enhanced ROS on X-ray irradiation, which may provide a new strategy for bone metastases and cancer therapy. Also, this paper reviews the advancement in the drug delivery applications of inorganic nanoparticles and highlights the crosstalk between the inorganic nanoparticles with the conjugated targeting ligand for efficient delivery applications. more...

Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-MnSevere neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine (PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated.Single oral dose (0.25 mg kgThis study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings.None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn more...

Oral delivery of rifampicin through chitosan nanoparticles.

With a facile halide and phase modulating approach, deep-blue emissive quasi-2D perovskite films involving fewer intervening 2D phases are realized, for efficient delivery of excitons to light-emitting phases via streamlined energy transfer. more...

The potentiality of Förster resonance energy transfer (FRET) for studying molecular interactions inside biological tissues with improved spatial (Angström) and temporal (picosecond) resolution is well established. On the other hand, the efficacy of diffuse reflectance spectroscopy (DRS) that uses optical radiation in order to determine physiological parameters including haemoglobin, and oxygen saturation is well known. Here we have made an attempt to combine diffuse reflectance spectroscopy (DRS) with picosecond-resolved FRET in order to show improvement in the exploration of molecular contacts in biological tissue models. We define the technique as ultrafast time-resolved diffuse reflectance spectroscopy (UTRDRS). The illuminated photon of the fluorophore from the surface of the tissue-mimicking layers carries the hidden information of the molecular contact. In order to investigate the validation of the Kubelka-Munk (KM) formulism for the developed UTRDRS technique in tissue phantoms, we have studied the propagation of incandescent and picosecond-laser light through several layers of cellulose membranes. While picosecond-resolved FRET in the diffuse reflected light confirms the hidden nano-contact (4.6 nm) of two different dye layers (8-anilino-1-naphthalenesulfonic acid and Nile blue), high-resolution optical microscopy on the cross-section of the layers reveals the proximity and contacts of the layers with limited spatial resolution (∼300 nm). We have also investigated two biologically relevant molecules, namely carboxyfluorescein and haemoglobin, in tissue phantom layers in order to show the efficacy of the UTRDRS technique. Overall, our studies based on UTRDRS in tissue mimicking layers may have potential applications in non-invasive biomedical diagnosis for patients suffering from skin diseases. more...

Cobalt (Co) although, an essential element playing a key role in several physiological and biological processes, can transform into a potential toxin when present in higher amounts or in certain chemical forms. The increasing usage of transition metals in industries, agriculture, medicines and technology has led to an alarming rise in cobalt poisoning cases. Exposure to cobalt can cause several health hazards including neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, etc. Cobalt may interact with several proteins in the cellular milieu, generating reactive oxygen species (ROS) and thereby triggering apoptosis of the neural cells via DNA damage. The most common method of removal of such metals from the body is by the use of metal chelators. In this study, we report a facile strategy for the clearance of Co (II) from the physiological milieu using citrate functionalized Mn3O4 NPs (C-Mn3O4 NPs). The chelation ability of C-Mn3O4 NPs has been evaluated using steady state and pico-second resolved optical spectroscopy. Our studies reveal that C-Mn3O4 NPs form a stable complex with cobalt ions, thereby reducing the ability of Co2+ to produce reactive oxygen species (ROS) via Fenton like reaction and hence function as a novel nanotherapeutic for the detoxification of cobalt in the human system. more...

Hydrothermal assisted Zinc Oxide (ZnO)-polyphenol nanohybrid (NHs) have been synthesized using natural products. The formation of nanohybrid was confirmed by UV VIS spectroscopy, fluorescence spectroscopy, and time resolved fluorescence spectroscopy. The crystalline morphology and size distribution was studied by TEM analysis. The synthesized zinc oxide (ZnO) nanohybrid exhibited antioxidant property by exerting excellent DPPH free radical scavenging activity. Whereas, no ROS generation was observed against DCFH. No inherent cytotoxicity of the synthesized nanohybrid was observed on 3T3L1 adipocyte cells. The study further demonstrated a cytoprotective activity of the nanohybrid on H2O2 induced oxidative stress on 3T3L1 cells indicating the potential therapeutic activity of the synthesized ZnO-Polyphenol nanohybrid. more...

Water molecules in the immediate vicinity of biomacromolecules and biomimetic organized assemblies often exhibit a markedly distinct behavior from that of their bulk counterparts. The overall sluggish behavior of biological water substantially affects the stability and integrity of biomolecules, as well as the successful execution of various crucial water-mediated biochemical phenomena. In this Minireview, insights are provided into the features of truncated hydrogen-bond networks that grant biological water its unique characteristics. In particular, experimental results and theoretical investigations, based on chemical kinetics, are presented that have shed light on the dynamics and energetics governing such characteristics. It is emphasized how such details help us to understand the energetics of biological water, an aspect relatively less explored than its dynamics. For instance, when biological water at hydrophilic or charged protein surfaces was explored, the free energy of H-bond breakage was found to be of the order of 0.4 kcal mol-1 higher than that of bulk water. more...

X-ray crystallography was used to elucidate the effect of a single-site mutation on the activity of a native metalloenzyme. The subtle structural modifications around the active site of the enzyme were correlated with the retarded catalytic efficiency in terms of the mechanistic steps and their kinetics., Enzymes are catalysts of biological processes. Significant insight into their catalytic mechanisms has been obtained by relating site-directed mutagenesis studies to kinetic activity assays. However, revealing the detailed relationship between structural modifications and functional changes remains challenging owing to the lack of information on reaction intermediates and of a systematic way of connecting them to the measured kinetic parameters. Here, a systematic approach to investigate the effect of an active-site-residue mutation on a model enzyme, human carbonic anhydrase II (CA II), is described. Firstly, structural analysis is performed on the crystallographic intermediate states of native CA II and its V143I variant. The structural comparison shows that the binding affinities and configurations of the substrate (CO2) and product (HCO3 −) are altered in the V143I variant and the water network in the water-replenishment pathway is restructured, while the proton-transfer pathway remains mostly unaffected. This structural information is then used to estimate the modifications of the reaction rate constants and the corresponding free-energy profiles of CA II catalysis. Finally, the obtained results are used to reveal the effect of the V143I mutation on the measured kinetic parameters (k cat and k cat/K m) at the atomic level. It is believed that the systematic approach outlined in this study may be used as a template to unravel the structure–function relationships of many other biologically important enzymes. more...

The study was aimed to evaluate the performance of a newly developed non-invasive and non-contact bilirubin measurement device (AJO-Neo) as an alternative to the conventional invasive biochemical method of total serum bilirubin (TSB) estimation in preterm and term neonates suffering from hyperbilirubinemia associated with risk factors, and/or undergoing phototherapy. The safety and efficacy of the device were assessed in 1968 neonates with gestational ages ranging from 28 to 41 weeks and suffering from incidences of hyperbilirubinemia. Linear regression analysis showed a good correlation between AJO-Neo and the conventional method of TSB (Pearson’s coefficient, r = 0.79). The small bias (0.27 mg/dL) and limits of agreements (− 3.44 to 3.99 mg/dL) were within the range of clinical acceptance. The device was also precise in the measurement of bilirubin levels in all subgroups of the study. The receiver operator curve (ROC), that takes account of both sensitivity and specificity of a device showed high efficacy of the device (area under the curve, AUC = 0.83) in the detection of bilirubin. While monitoring the bilirubin level during phototherapy, the device indicated promising results showing good agreement with TSB. Specificities and sensitivities of the device indicated a much higher accuracy in neonates with associated risk factors for hyperbilirubinemia. Hence, the newly developed device (AJO-Neo) is reliable in measuring bilirubin level in preterm, and term neonates irrespective of gestational or postnatal age, sex, risk factors, feeding behavior or skin color. more...

Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k more...

The excited-state proton transfer (ESPT) of a cationic superphotoacid

Attachment of microbial bodies including the corona virus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a triboelectroceutical fabric (TECF) consisting of commonly available materials, namely, nylon and silicone rubber (SR), for the fabrication of protective gloves on the nitrile platform as model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and nylon on nitrile can generate more than 20 V transient or 41 μW output power, which is capable of charging a capacitor up to 65 V in only ∼50 s. The importance of the present work relies on the TECF-led antimicrobial activity through the generation of an electric current in saline water. The fabrication of TECF-based functional prototype gloves can generate hypochlorite ions through the formation of electrolyzed water upon rubbing them with saline water. Further, computational modelling has been employed to reveal the optimum structure and mechanistic pathway of antimicrobial hypochlorite generation. Detailed antimicrobial assays have been performed to establish effectiveness of such TECF-based gloves to reduce the risk from life-threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other materials with comparable properties, as a material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19. © 2021 American Chemical Society. more...

Iron ion, an essential element for environmental as well as biological systems, has to be present in a controlled manner. Presence of excess iron and also the deficiency of iron ions in environmental (groundwater) and biological systems (blood serum and parts of the plant) is an enduring concern. Here we have developed a nano-sensor (FeNSOR) using a neutral micelle (TX-100) duly sensitized by porphyrin. We have also fabricated an instrument called “FeNSOR Device” (Iron sensor) based on the developed nano-sensor using a digital Pi-camera with associated hardware and software. The device works on the principle of fluorescence spectrophotometry. The efficacy of the nano-sensor and the device for the detection and estimation of iron ions in groundwater as well as in human blood serum is found to be in sub-molar range, having minimum interference with other ions. The limit of detection and the standard deviation of the mean were found to be $0.07~\mu \text{M}$ and $0.016~\mu \text{M}$ , respectively. The developed device is easy to handle, and has a higher sensitivity and repeatability than the commercially available ones. more...

Enzymes are dynamical macromolecules and their conformation can be altered via local fluctuations of side chains, large scale loop and even domain motions which are intimately linked to their function. Herein, we have addressed the role of dynamic flexibility in the catalytic activity of a thermostable enzyme almond beta-glucosidase (BGL). Optical spectroscopy and classical molecular dynamics (MD) simulation were employed to study the thermal stability, catalytic activity and dynamical flexibility of the enzyme. An enzyme assay reveals high thermal stability and optimum catalytic activity at 333 K. Polarization-gated fluorescence anisotropy measurements employing 8-anilino-1-napthelenesulfonic acid (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. A study of the atomic 3D structure of the enzyme shows the presence of four loop regions (LRs) strategically placed over the catalytic barrel as a lid. MD simulations have indicated that the flexibility of BGL increases concurrently with temperature through different fluctuating characteristics of the enzyme's LRs. Principal Component Analysis (PCA) and the Steered Molecular Dynamics (SMD) simulation manifest the gatekeeper role of the four LRs through their dynamic fluctuations surrounding the active site which controls the catalytic activity of BGL. more...

Nanomedicine, the offspring born from the marriage of nanotechnology and medicine, has already brought momentous advances in the fight against a plethora of unmet diseases from cardiovascular and neurodegenerative to diabetes and cancer. Here, we review a conceptual framework that will provide a basic understanding about the molecular mechanism of action of a therapeutic nanomaterial inside biological milieu. In this review, we highlight how the catalytic nature of a transition metal oxide nanomaterial influences the cellular redox homeostasis, supports the cellular antioxidant defence system and reactivates the reactive oxygen species (ROS) mediated signalling to perform normal cell functions like cell cycle, differentiation, apoptosis, inflammation, toxicity, and protein interactions. With numerous examples, we describe the redox modulatory nature of d-block metal oxide nanomaterials and their biomimetic nanozyme activities to protect the mitochondria, the cellular redox mediator which prevents an organism from various diseases. This knowledge will be useful to design new nanomaterials capable of intracellular redox modulation, which in turn can be effective therapeutic agents for treatment of various unmet diseases that are beyond the ability of modern synthetic medicine. more...

Consumption of excess fluorides through drinking water and its adverse effects on human health is of global concern. Given that people from at least 25 countries are suffering from fluorosis, globa... more...

Conformational dynamics of macromolecules including enzymes are essential for their function. The present work reports the role of essential dynamics in alpha-chymotrypsin (CHT) which correlates with its catalytic activity. Detailed optical spectroscopy and classical molecular dynamics (MD) simulation were used to study thermal stability, catalytic activity and dynamical flexibility of the enzyme. The study of the enzyme kinetics reveals an optimum catalytic efficiency at 308K. Polarization gated fluorescence anisotropy with 8-anilino-1-napthelene sulfonate (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. Examination of the structure of CHT reveal the presence of five loop regions (LRs) around the catalytic S1 pocket. MD simulations have indicated that flexibility increases concurrently with temperature which decreases beyond optimum temperature. Principal component analysis (PCA) of the eigenvectors manifests essential dynamics and gatekeeping role of the five LRs surrounding the catalytic pocket which controls the enzyme activity. more...

Enzyme conformations can be altered via modification of its amino acid residues, side chains and large-scale domain modifications, which are closely linked to its function. Herein, we have addressed the role of residue modification in catalytic activity and molecular recognition of an enzyme alpha-chymotrypsin (CHT) in presence of covalent cross-linker formalin. Optical spectroscopy studies exhibit reduced catalytic activity of the enzyme with increased formalin concentration. Polarization gated anisotropy studies of a fluorophore 8-anilino-1-napthelenesulfonic acid (ANS) in CHT show a dip rise pattern in presence of formalin which is consistent with the generation of multiple ANS binding sites in the enzyme owing to modifications of its local amino acid residues. Molecular docking study on minimal local residue modifications in CHT reveals formation of a stable enzyme-substrate complex even with the serine-histidine cross-linked enzyme which prohibits product formation giving rise to reduced catalytic activity. Keywords: amino acid modification; chymotrypsin; formalin; cross-linking; spectroscopy; molecular docking more...

Precise control of intracellular redox status, i.e., maintenance of physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress) is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, or depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in animal model in order to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use. more...

Centers for Disease Control and Prevention (CDC) warns the use of one-way valves or vents in free masks for potential threat of spreading COVID-19 through expelled respiratory droplets. Here, we have developed a nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanomaterial for potential use as membrane filter in the one way valve for the ease of breathing without the threat of COVID-19 spreading. A detailed computational study revealed that zinc oxide nanoflowers (ZnO NF) with almost two-dimensional petals trap SARS-CoV-2 spike proteins, responsible to attach to ACE-2 receptors in human lung epithelial cells. The study also confirm significant denaturation of the spike proteins on the ZnO surface, revealing removal of virus upon efficient trapping. Following the computational study, we have synthesized ZnO NF on cotton matrix using hydrothermal assisted strategy. Electron microscopic, steady-state and picosecond resolved spectroscopic studies confirm attachment of ZnO NF to the cotton (i.e., cellulose) matrix at atomic level to develop the nanoceutical fabric. A detailed antimicrobial assay using Pseudomonas aeruginosa bacteria (model SARS-CoV-2 mimic) reveals excellent anti-microbial efficiency of the developed nanoceutical fabric. To our understanding the novel nanoceutical fabric used in one-way valve of a face mask would be the choice to assure breathing comfort along with source control of COVID-19 infection. The developed nanosensitized cloth can also be used as antibacterial/anti CoV-2 washable dress material in general.GRAPHICAL ABSTRACTA novel nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanoflower can potentially be used as membrane filter in the one way valve of face mask to assure breathing comfort along with source control of COVID-19 infection. The nanoceutical fabric denatures the SARS-CoV-2 spike protein and makes the microorganism ineffective. more...

The exponential increase in the use of digital technology in day-to-day life has generated an excessive aggregation of electronic waste (e-waste), which is one of the major sources of environmental contamination in the twenty-first century. Amongst them, lithium (Li) is the most pronounced one due to the extensive use of Li-ion batteries in nearly every electronic device. Disposal of lithium-ion batteries in soil and water leads to various adverse effects not only on human health but also on plants and aquatic creatures. Toxic effects on cardiovascular, gastrointestinal, and endocrine systems are a few to mention. Therefore, the determination and quantification of the lithium level in the soil and water are extremely crucial. Here, we have developed a device and technique that can instantly quantify the lithium concentration in water and soil samples, at the site of sampling. The device is based on the principles of optical emission spectroscopy. To obtain the optical signals and to compute the electrolyte concentration a user-friendly software is developed. As proof of concept, we measured time-dependent Li-ion leaching in water and soil using the developed device and obtained promising results. The device is also IoT enabled for easy transfer of data from a remote place. Compared to the conventional techniques, our device is cost-effective, easily portable, requires less expertise and sample preparation, and also requires less time. As per our understanding, the current work will be pertinent in combating the adverse effects of e-waste in the environment using a non-invasive approach. more...

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine for the therapeutic benefit as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that an indigenously developed nanomedicine comprising of Mn3O4nanoparticles duly functionalized by biocompatible ligand citrate (C-Mn3O4NPs) can maintain cellular redox balance in an animal model. We developed a cisplatin-induced CKD model in C57BL/6j mice where severe mitochondrial dysfunction resulting in oxidative distress lead to the pathogenesis. Four weeks of treatment with C-Mn3O4NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis in CKD mice. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, the subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis. more...

Attachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 µW output power, which is capable of charging a capacitor up to 65 V in only ∼50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19. more...

Regular monitoring of electrolyte balance is essential for patients suffering from chronic kidney disease (CKD), particularly those undergoing dialysis. In the context of the recent COVID-19 pandemic, more severe forms of infection are observed in elderly individuals and patients having co-morbidities like CKD. The repeated blood tests for the monitoring of electrolyte balance predispose them not only to COVID-19 but also other to hospital-acquired infections (HAI). Therefore, a non-invasive method for easy detection of essential electrolyte (K+ and Na+) levels is urgently needed. In this study, we developed an optical emission spectroscopy-based non-invasive device for simultaneous monitoring of salivary Na+ and K+ levels in a fast and reliable way. The device consisted of a closed spark chamber, micro-spectrometer, high voltage spark generator, electronic circuits, optical fiber, and an indigenously developed software based on the LabVIEW platform. The optical emission originating from the biological sample (i.e., saliva) due to recombination of ions energized by impingement of electrons returning from high voltage spark provides necessary information about the concentration of electrolytes. A small-scale clinical trial on 30 healthy human subjects shows the potential of the indigenously developed device in determining salivary Na + and K+ concentration. The low-cost, portable, point-of-care device requires only 2 mL of sample, and can simultaneously measure 1.0–190.0 mM Na+, and 1.0–270.9 mM K+ . To our understanding, the present work will find its relevance in combating COVID-19 morbidities, along with regular CKD patient-care. more...

BackgroundTargeted degradation of bilirubinin vivomay enable safer and more effective approach to manage incipient bilirubin encephalopathy consequent to severe neonatal hyperbilirubinemia (SNH). This report builds on the use of a spinel structured mixed-valence transition metal oxide (trimanganese tetroxide) nanoparticle duly functionalized with biocompatible ligand citrate (C-Mn3O4NP) having the ability to degrade bilirubin without photo-activation.MethodThe efficiency of C-Mn3O4NP inin vivodegradation of serum bilirubin and amelioration of severe bilirubin encephalopathy and associated neurobehavioral changes was evaluated in C57BL/6j animal model of SNH.ResultsOral single dose (0.25 mg kg-1body weight) of the NPs efficiently reduced serum bilirubin levels (both conjugated and unconjugated) in study mice. It prevents bilirubin-induced neurotoxicity with reduction of SNH as observed by neurobehavioral and movement studies of SNH-mice. Pharmacokinetic data suggests intestinal reabsorption of the NPs and explain sustainable action. Biodistribution, pharmacokinetics, and biocompatibility of the NPs were tested during sub-chronic exposure.ConclusionThus, we report preliminary studies that explore an affordable chemoprevention mechanism to acutely prevent or minimize bilirubin neurotoxicity in newborn infants.IMPACT STATEMENTDespite several attempts, no pharmaco-therapeutics are available for the treatment of severe neonatal hyperbilirubinemia (SNH) and associated neurotoxicity.Our newly developed nanodrug, citrate functionalized Mn3O4nanoparticles (C-Mn3O4NPs), can efficiently ameliorate SNH and associated neurotoxicity as investigated in preclinical rodent model.Chemoprevention effect of the nanodrug is found to be safe and sustainable.If successfully translated into clinical trials, C-Mn3O4NPs could become the first drug to treat SNH. more...

The subject Area of the Conference was interdisciplinary. Therefore, Contributors enquired and looked at the broad question of Sustainable Development (Theme of our Conference) from the point of view of Natural sciences, Social Sciences, and Literature, Culture, and Language. The latest insights have been shared on the said themes as the contributors are from diverse background area. more...

Why metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 Å) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties., Metalloenzymes often show different catalytic activities in the presence of non-native metal ions. Here, the authors report structures of carbonic anhydrase bound to zinc and several other metal ions and demonstrate that metal ion coordination geometries directly impact catalytic activity of the enzyme. more...

Treatment of cancer using nanoparticles made of inorganic and metallic compounds has been increasingly used, owing to their novel intrinsic physical properties and their potential to interact with specific cellular sites, thereby significantly reducing severe secondary effects. In this study, we report a facile strategy for synthesis of folate capped Mn3O4 nanoparticles (FA-Mn3O4 NPs) with high colloidal stability in aqueous media using a hydrothermal method for potential application in photodynamic therapy (PDT) of cancer. The capping of FA to Mn3O4 NPs was confirmed using various spectroscopic techniques. In adenocarcinomic human alveolar basal epithelial cells (A549), the nanohybrid synthesised with a combination of FA and Mn3O4 shows remarkable PDT activity via intracellular ROS generation (singlet oxygen). As established by a DNA fragmentation assay and fluorescence studies, the nanohybrid can cause significant nuclear DNA damage by light induced enhanced ROS generation. In the assessment of Bax, Bcl2 provides strong evidence of apoptotic cellular death. Cumulatively, the outcomes of this study suggest that these newly synthesized FA-Mn3O4 NPs can specifically destroy cells with overexpressed folate receptors, thereby providing a solution in the journey of cancer eradication. more...

Electrolytes like sodium, potassium, magnesium, calcium etc. are essential for maintaining the fluid balance and homeostasis in the human body. They are also useful biomarkers in understanding the pathophysiology of a host of diseases. The major aim of this study is to develop a strategy for fast, reliable and simultaneous assessment of sodium (Na+), lithium (Li+) and potassium (K+) in human samples. The device is developed utilizing the basic principle of optical emission spectroscopy (OES). The atomic emission spectra of the ions during their transition are acquired and analysed for the simultaneous detection of the specific electrolytes. Our self-developed software is used to acquire the optical signals and to calculate the electrolyte concentration. The device shows a satisfactory adjusted R2 value for the three electrolytes (0.954, 0.932 and 0.984 for Na+, Li+ and K+, respectively) with respect to the standard ISE method. The device utilizes a very small amount (∼100 μL) of serum and provides a good correlation with commercially available costly devices like blood gas analysers and ion selective electrodes for blood electrolyte analysis. Our self-developed low-cost device has the ability to offer a simultaneous assessment of the essential electrolytes. To our understanding, this device would be ideal for the point of care management of constantly recurring physiological disorders including Chronic Kidney Diseases (CKD) and bipolar disorder in economically challenged countries. more...

We developed an integrated device composed of a single-probe Electroencephalogram (EEG) and Charge Coupled Device (CCD) based motion sensors for objective measurement of Attention-deficit Hyperactivity Disorder (ADHD). While the measurement of attention-deficit hyperactivity disorder (MAHD) relies on the EEG signal for the assessment of attention during a given structured task, the CCD sensor depicts the movement pattern of the subjects engaged in a continuous performance task. A statistical analysis of attention and movement patterns was performed, and the accuracy of completed tasks was analyzed using indigenously developed software. The device with the embedded software is intended to improve certainty with criterion E. We used the EEG signal from a single-channel dry sensor placed on the frontal lobe of the head of the subjects (3–5 year old pre-schoolers). During the performance of the task power for delta and beta, EEG waves from the subjects are found to be correlated with relaxation and attention/cognitive load conditions. While the relaxation condition of the subject hints at hyperactivity, a more direct CCD-based motion sensor is used to track the physical movement of the subject engaged in a continuous performance task. We used our indigenously developed software for statistical analysis to derive a scale for the objective assessment of ADHD. We also compared our scale with clinical ADHD evaluations and found a significant correlation between the objective assessment of the ADHD subjects and the clinician’s conventional evaluation. MAHD, the integrated device, is supposed to be an auxiliary tool to improve the accuracy of ADHD diagnosis by supporting greater criterion E certainty. more...