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    Environmental impact of microplastics and potential health hazards
    (Critical Reviews in Biotechnology, 2024-06) Megha, KB; Anvitha, D; Parvathi, S; Neeraj, A; Sonia, J; Mohanan, PV
    Microscopic plastic (microplastic) pollutants threaten the earth’s biodiversity and ecosystems. As a result of the progressive fragmentation of oversized plastic containers and products or manufacturing in small sizes, microplastics (particles of a diameter of 5 mm with no lower limit) are used in medicines, personal care products, and industry. The incidence of microplastics is found everywhere in the air, marine waters, land, and even food that humans and animals consume. One of the greatest concerns is the permanent damage that is created by plastic waste to our fragile ecosystem. The impossibility of the complete removal of all microplastic contamination from the oceans is one of the principal tasks of our governing body, research scientists, and individuals. Implementing the necessary measures to reduce the levels of plastic consumption is the only way to protect our environment. Cutting off the plastic flow is the key remedy to reducing waste and pollution, and such an approach could show immense significance. This review offers a comprehensive exploration of the various aspects of microplastics, encompassing their composition, types, properties, origins, health risks, and environmental impacts. Furthermore, it delves into strategies for comprehending the dynamics of microplastics within oceanic ecosystems, with a focus on averting their integration into every tier of the food chain.
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    Nanoarchitectonics of fluorescent gold nanoclusters: A platform for image guided photodynamic therapy of hypoxic tumor
    (Applied Materials Today, 2024-06) Resmi, AN; Sivaselvam, S; Papasouli, E; Kunnumpurathu, J; Praveen, CS; Koukaras, EN; Rerat, M; Karamanis, P; Jayasree, RS
    Metal nanoclusters are atomically precise materials comprising metal core of few atoms exhibiting unique photoluminescence properties, unlike their bigger counterparts. Some metal nanocluster with ligand-to-metal charge transfer, long-lived excited state and excited triplet state contribute to inherent photosensitizing (PS) property. However, the therapeutic efficacy of PDT is hindered by the insufficient oxygen supply (O2) in tumor microenvironment. In the present work, cysteine-capped gold nanocluster (AuC) are studied for their unique molecular architecture for PS efficiency. The co-existence of monodispersed and self-assembled structures contribute to the photoluminescence from the quantum confinement of electronic states and aggregation-induced emission (AIE) based PS property, respectively. In-silico model was performed to study the interaction of cysteine to gold cluster, its ground and excited-state properties and the charge transfer mechanism. The AuC as PS generates cytotoxic radicals in both Type I and Type II photodynamic pathways and the dominant radical species involved were elucidated by EPR spectroscopy. In vitro analysis in HeLa cells showed excellent biocompatibility and bioimaging properties. The intracellular ROS production and Live/Dead assay confirmed the generation of ROS in HeLa cells upon laser irradiation. The image-guided photodynamic property with synergistic Type I and Type II PDT reactions of AuC promises its potential application in cancer therapy in both hypoxic and normoxic conditions
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    Insights into cellular initeractions of characterised Mg-Al Layered Double Hydroxide on L929 cells
    (Materials Chemistry and Physics, 2024-09) Megha, KB; Aneeta, S; .Joseph, X; Abey, J; Baiju. GN; Mohanan, PV
    Layered double hydroxides are members of an anionic clay family, characterised by unique two-dimensional layered structures and lend versatility in various applications. These biocompatible compounds have the potential to get intercalated with biological compounds and physico-chemically adsorbed onto organic molecules. Thus, making them important candidates for pharmaceutical and biomedical purposes. This study aims to synthesise, characterise and investigate the cellular toxicity interactions of Mg–Al LDH towards the mouse fibroblast L929 cell line. The Mg–Al LDH was synthesized by a meticulous process of co-precipitation followed by the hydrothermal method to ensure a well-defined and stable structure for suitable biological application. Characterisation techniques like Dynamic Light Scattering, Zeta potential, Scanning Electron Microscopy, Fourier transform infrared, and X-ray diffraction analysis were employed to provide deeper insights into the physiochemical properties and structural integrity of the synthesized Mg–Al LDH. The investigation of cellular interactions with the L929 fibroblast cell line served to assess the biocompatibility and potential cytotoxic effects of Mg–Al LDH. This was observed by assessing the morphological changes and evaluating the cytotoxic effects of Mg–Al LDH by utilising various techniques like phase contrast microscopy, fluorescent staining, and Giemsa staining. The cellular metabolic activity was assessed by MTT assay, and the subcellular lysosomal alteration was examined using the fluorescent staining method by the acridine orange staining. The dose-dependent response observed in the cellular interaction underscores the importance of dosage considerations for potential biomedical applications. By elucidating the dose-response relationship, this study contributes valuable information for the safe and effective usage of LDH in biomedical contexts.
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    Low Reynolds number pressure-flow analysis across a valve: Comparison between three-point and multipoint gap functions with CFD results
    (NAFEMS International Journal of CFD Case Studies, 2023-11) Gopinathan, A; Vipin Dev, V; Jithu Raj, R; Subhash Kumar, MS; Sukanya, LJ; Muraleedharan, CV
    The pressure-flow characteristics of a valve that are used in major medical and industrial applications depend on the structural properties of the valve components, properties of the fluid flowing across the valve as well as the profile of the bounding region ensured by the valve-plug (moving part of the valve) and valve-seating (fixed inlet port of valve). The pressure-flow behaviour is an important aspect as far as the design of the valve is considered. The pressure difference between the inlet and outlet of the valve at a particular flow rate could either be estimated through the method of Computational Fluid Dynamics (CFD) or mathematical analytical methods. An analytical model is being developed derived from the Navier Stokes equation in which the boundary profile equations contributed by valve-plug and valve-seating along with fluid properties were being used along with the fluid parameters. As part of the exercise, the gap function which is variation in distance between the plug and seating profile along the flow direction is derived. Two different methods which are a three-point method of circular arc extraction and multipoint method of polynomial curve extraction have been discussed in this paper for obtaining the gap function.
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    Cadmium selenium quantum dot based nanosensor with femto molar level sensitivity for the detection of the pesticide endosulfan
    (Journal of Polymer Science and Engineering., 2024-01) Nair, LV; Nair. RV; Jayasree, RS
    Endosulfan (6,7,8,9,10,10-Hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine-3-oxide) is an off-patent insecticide used in agricultural farms. Its usage as a pesticide has become highly controversial during the last decades. This is due to its reported hazardous nature to the health and side effects like growth retardation, hydrocephalus, and undesired changes in the male and female hormones leading to complications in sexual maturity. Endosulfan is the main culprit among all pesticide poisoning incidents around the world. Though the usage of this dreaded pesticide is banned by most countries, the high stability of this molecule to withstand degradation for a long period poses a threat to mankind even today. So, it has become highly essential to detect the presence of this poisonous pesticide in the drinking water and milk around these places. It is also advisable to check the presence of this toxic material in the blood of the population living in and around these places so that an early and appropriate management strategy can be adopted. With this aim, we have developed a sensor for endosulfan that displayed high selectivity and sensitivity among all other common analytes in water and biological samples, with a wide linear concentration range (2 fM to 2 mM), a low detection limit (2 fM), and rapid response. A citrate functionalized cadmium selenium quantum dot was used for this purpose, which showed a concentration-dependent fluorescence enhancement, enabling easy and sensitive sensing. This sensor was utilized to detect endosulfan in different sources of water, human blood serum and milk samples with good recoveries. It is also noted that the quantum dot forms a stable complex with endosulfan and is easy to separate it from the contaminated source, paving a solution for purifying the contaminated water. More detailed tests and validation of the sensor is needed to confirm these observations.
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    3D printed arrowroot starch-gellan scaffolds for wound healing applications
    (International Journal of Biological Macromolecules, 2024-03) Abey, J; Fathah, M; Athira, SV; Joseph, X; Megha, KB; Akash, K; Nigina, G; Mohanan, PV; Baiju, GN
    Skin, the largest organ in the body, blocks the entry of environmental pollutants into the system. Any injury to this organ allows infections and other harmful substances into the body. 3D bioprinting, a state-of-the-art technique, is suitable for fabricating cell culture scaffolds to heal chronic wounds rapidly. This study uses starch extracted from Maranta arundinacea (Arrowroot plant) (AS) and gellan gum (GG) to develop a bioink for 3D printing a scaffold capable of hosting animal cells. Field emission scanning electron microscopy (FE-SEM) and X-ray diffraction analysis (XRD) prove that the isolated AS is analogous to commercial starch. The cell culture scaffolds developed are superior to the existing monolayer culture. Infrared microscopy shows the AS-GG interaction and elucidates the mechanism of hydrogel formation. The physicochemical properties of the 3D-printed scaffold are analyzed to check the cell adhesion and growth; SEM images have confirmed that the AS-GG printed scaffold can support cell growth and proliferation, and the MTT assay shows good cell viability. Cell behavioral and migration studies reveal that cells are healthy. Since the scaffold is biocompatible, it can be 3D printed to any shape and structure and will biodegrade in the requisite time.
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    Development of a 3D multifunctional collagen scaffold impregnated with peptide LL-37 for vascularised bone tissue regeneration
    (Int J Pharm., 2024-01) Megha, KB; Syama, S; Sangeetha, VP; Vandana, U; Oyane, A; Mohanan, PV
    Bone is a highly dynamic connective tissue that provides structural support, locomotion and acts as a shield for many vital organs from damage. Bone inherits the ability to heal after non-severe injury. In case of severe bone abnormalities due to trauma, infections, genetic disorders and tumors, there is a demand for a scaffold that can enhance bone formation and regenerate the lost bone tissue. In this study, a 3D collagen scaffold (CS) was functionalized and assessed under in vitro and in vivo conditions. For this, a collagen scaffold coated with hydroxyapatite (Ap-CS) was developed and loaded with a peptide LL-37. The physico-chemical characterisation confirmed the hydroxyapatite coating on the outer and inner surfaces of Ap-CS. In vitro studies confirmed that LL-37 loaded Ap-CS promotes osteogenic differentiation of human osteosarcoma cells without showing significant cytotoxicity. The efficacy of the LL-37 loaded Ap-CS for bone regeneration was evaluated at 4 and 12 weeks post-implantation by histopathological and micro-CT analysis in rabbit femur defect model. The implanted LL-37 loaded Ap-CS facilitated the new bone formation at 4 weeks compared with Ap-CS without LL-37. The LL-37 loaded Ap-CS incorporating apatite and peptide LL-37 would be useful as a multifunctional scaffold for bone tissue engineering.
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    Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management
    (Mol Neurobiol., 2024-01) Megha, KB; Arathi, A; Shikha, S; Alka, R; Ramya, P; Mohanan, PV
    Melatonin, the ‘hormone of darkness’ is a neuronal hormone secreted by the pineal gland and other extra pineal sites. Responsible for the circadian rhythm and seasonal behaviour of vertebrates and mammals, melatonin is responsible for regulating various physiological conditions and the maintenance of sleep, body weight and the neuronal activities of the ocular sites. With its unique amphiphilic structure, melatonin can cross the cellular barriers and elucidate its activities in the subcellular components, including mitochondria. Melatonin is a potential scavenger of oxygen and nitrogen-reactive species and can directly obliterate the ROS and RNS by a receptor-independent mechanism. It can also regulate the pro- and anti-inflammatory cytokines in various pathological conditions and exhibit therapeutic activities against neurodegenerative, psychiatric disorders and cancer. Melatonin is also found to show its effects on major organs, particularly the brain, liver and heart, and also imparts a role in the modulation of the immune system. Thus, melatonin is a multifaceted candidate with immense therapeutic potential and is still considered an effective supplement on various therapies. This is primarily due to rectification of aberrant circadian rhythm by improvement of sleep quality associated with risk development of neurodegenerative, cognitive, cardiovascular and other metabolic disorders, thereby enhancing the quality of life.
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    Porphyrin and doxorubicin mediated nanoarchitectonics of copper clusters: a bimodal theranostics for cancer diagnosis and treatment in vitro
    (J Mater Chem B., 2024-01) Joseph, M; Rahman Pathiripparambath, MS; Thomas, V; Tharayil, H; Jayasree, RS; Nair, LV
    Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.
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    Infrared Spectroscopy for Rapid Triage of Cancer Using Blood Derivatives: A Reality Check
    (Anal Chem., 2024-01) Nazeer, SS; Venkataraman, RK; Jayasree, RS; Bayry, J
    Infrared (IR) spectroscopy of serum/plasma represents an alluring molecular diagnostic tool, especially for cancer, as it can provide a molecular fingerprint of clinical samples based on vibrational modes of chemical bonds. However, despite the superior performance, the routine adoption of this technique for clinical settings has remained elusive. This is due to the potential confounding factors that are often overlooked and pose a significant barrier to clinical translation. In this Perspective, we summarize the concerns associated with various confounding factors, such as fluid sampling, optical effects, hemolysis, abnormal cardiovascular and/or hepatic functions, infections, alcoholism, diet style, age, and gender of a patient or normal control cohort, and improper selection of numerical methods that ultimately would lead to improper spectral diagnosis. We also propose some precautionary measures to overcome the challenges associated with these confounding factors.
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    In Vitro Osteogenesis Study of Shell Nacre Cement with Older and Young Donor Bone Marrow Mesenchymal Stem/Stromal Cells
    (Bioengineering (Basel)., 2024-02) Wilson, BJ; Owston, HE; Iqbal, N; Giannoudis, PV; McGonagle, D; Pandit, H; Philipose Pampady kandathil, L; Jones, E; Ganguly, P
    Bone void-filling cements are one of the preferred materials for managing irregular bone voids, particularly in the geriatric population who undergo many orthopedic surgeries. However, bone marrow mesenchymal stem/stromal cells (BM-MSCs) of older-age donors often exhibit reduced osteogenic capacity. Hence, it is crucial to evaluate candidate bone substitute materials with BM-MSCs from the geriatric population to determine the true osteogenic potential, thus simulating the clinical situation. With this concept, we investigated the osteogenic potential of shell nacre cement (SNC), a bone void-filling cement based on shell nacre powder and ladder-structured siloxane methacrylate, using older donor BM-MSCs (age > 55 years) and young donor BM-MSCs (age < 30 years). Direct and indirect cytotoxicity studies conducted with human BM-MSCs confirmed the non-cytotoxic nature of SNC. The standard colony-forming unit-fibroblast (CFU-F) assay and population doubling (PD) time assays revealed a significant reduction in the proliferation potential (p < 0.0001, p < 0.05) in older donor BM-MSCs compared to young donor BM-MSCs. Correspondingly, older donor BM-MSCs contained higher proportions of senescent, β-galactosidase (SA-β gal)-positive cells (nearly 2-fold, p < 0.001). In contrast, the proliferation capacity of older donor BM-MSCs, measured as the area density of CellTrackerTM green positive cells, was similar to that of young donor BM-MSCs following a 7-day culture on SNC. Furthermore, after 14 days of osteoinduction on SNC, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) showed that the amount of calcium and phosphorus deposited by young and older donor BM-MSCs on SNC was comparable. A similar trend was observed in the expression of the osteogenesis-related genes BMP2, RUNX2, ALP, COL1A1, OMD and SPARC. Overall, the results of this study indicated that SNC would be a promising candidate for managing bone voids in all age groups.
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    Co-precipitation-hydrothermal mediated synthesis, characterization and toxicity evaluation of 2D Zn–Al LDHs in human osteoblast cells
    (J Mater Sc, 2023-11) Ashtami, J; Mohanan, PV
    LDHs, 2D (two-dimensional) clay material with memory effect clutches noteworthy properties like high surface area, ion-exchange capacity, tunable properties and possibility for wide elemental as well as anion combinations. A variety of LDHs are being explored for profuse applications including catalysis, absorbent material, flame retardants, drug delivery, polymer additives and bone regeneration. Recent research updates reveal the promising potential of LDHs in bone tissue engineering and are expected to grab a major hold in futuristic medicare. There have been tremendous efforts concentrated on fine-tuning the LDHs properties by controlling the growth parameters to improve its multi-functionality. In this study, an effort has been made to synthesize and characterize Zn–Al LDHs via the co-precipitation method with control over the nucleation and hydrothermal growth steps. The interactions of the fabricated Zn–Al LDHs with human osteoblast (HOS) cells were explored in the context of bone regeneration applications. The effect of Zn–Al LDHs on the mitochondrial function of HOS cells was examined. The study also evaluated the potential of LDHs to trigger apoptosis by using DNA fragmentation as the marker. The potential impact of positively charged LDHs on negatively charged DNA was also probed using the DNA laddering assay, as an audit on genotoxic potential.
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    Prosthetics and orthotics for persons with movement disabilities in India in the postpandemic milieu
    (Prosthet Orthot Int, 2023-11) Prajapati, AK; Komath, M; Subhash, NN
    The SARS-CoV-2 disease had a severe impact on global socioeconomic growth, and its harmful effects continue with virus mutation. Over the past 3 years, the pandemic has caused isolation, mental trauma, stress, financial losses, and various health complications in individuals. Recent reports have stressed the sufferings of the physically abled population. However, we should not neglect the challenges faced by the disabled population, which were more severe in many ways due to their dependency on others at various levels. The strategies implemented to contain the virus have further aggravated their sufferings and made it even worse because health care priorities were skewed toward public-centered care. As a result, it is difficult to determine the extent of care the disabled population received during the pandemic. Moreover, a single-centered study reports that amputations in India increased by 54.1% compared with those during the prepandemic era. This indicates the need for special attention to the physically disabled community, especially persons with movement disabilities. These individuals are partially dependent and have the potential to make significant contributions to the gross domestic product if included in the human resources pool. The Indian government had launched various initiatives to improve their living status. But delays in policy implementation, reduction in budget allocation, and the ongoing pandemic have derailed the efforts. For these reasons, this article emphasizes several challenges in movement disability care. In addition, it makes recommendations for improving the quality of life of persons with movement disabilities. These include collaboration, creating start-up businesses, applying state-of-the-art logistics, establishing a technological ecosystem, raising public awareness, accessing high-quality care, and using contemporary medical devices.
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    Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2
    (Mol Neurobiol, 2023-10) Megha, KB; Reshma, S; Amir, S; Ajai Krishnan, MJ; Shimona, A; Alka, R; Mohanan, PV
    The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.
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    Nanoarchitectonics of photothermal materials to enhance the sensitivity of lateral flow assays
    (Beilstein Journal of Nanotechnology, 2023-10) Sarathkumar, S; Anjana, RS; Jayasree, RS
    Lateral flow assays (LFAs) are currently the most widely used point-of-care testing technique with remarkable advantages such as simple operation, rapid analysis, portability, and low cost. Traditionally, gold nanoparticles are employed as tracer element in LFAs due to their strong localised surface plasmon resonance. However, this conventional LFA technique based on colorimetric analysis is neither useful to determine critical analytes with desired sensitivity, nor can it quantify the analytes. Various signal amplification strategies have been proposed to improve the sensitivity and the quantitative determination of analytes using LFAs. One of the promising strategies is to enhance the photothermal properties of nanomaterials to generate heat after light irradiation, followed by a temperature measurement to detect and quantify the analyte concentration. Recently, it has been observed that the nanoscale architecture of materials, including size, shape, and nanoscale composition, plays a significant role in enhancing the photothermal properties of nanomaterials. In this review, we discuss the nanoarchitectonics of nanomaterials regarding enhanced photothermal properties and their application in LFAs. Initially, we discuss various important photothermal materials and their classification along with their working principle. Then, we highlight important aspects of the nanoscale architecture (i.e., size, shape, and composition) to enable maximum light-to-heat conversion efficiency. Finally, we discuss some of the recent advances in photothermal LFAs and their application in detecting analytes.
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    A review of immune modulators and immunotherapy in infectious diseases
    (Mol Cell Biochem., 2023-09) Sangeetha Vijayan, P; Xavier, J; Mohanan, PV
    The human immune system responds to harmful foreign invaders frequently encountered by the body and employs defense mechanisms to counteract such assaults. Various exogenous and endogenous factors play a prominent role in maintaining the balanced functioning of the immune system, which can result in immune suppression or immune stimulation. With the advent of different immune-modulatory agents, immune responses can be modulated or regulated to control infections and other health effects. Literature provides evidence on various immunomodulators from different sources and their role in modulating immune responses. Due to the limited efficacy of current drugs and the rise in drug resistance, there is a growing need for new therapies for infectious diseases. In this review, we aim to provide a comprehensive overview of different immune-modulating agents and immune therapies specifically focused on viral infectious diseases.
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    The impact of e-cigarette exposure on different organ systems: A review of recent evidence and future perspectives
    (J Hazard Mater, 2023-09) Ali, N; Xavier, J; Engur, M; Mohanan, PV; Bernardino, SJ
    The use of electronic cigarettes (e-cigs) is rapidly increasing worldwide and is promoted as a smoking cessation tool. The impact of traditional cigs on human health has been well-defined in both animal and human studies. In contrast, little is known about the adverse effects of e-cigs exposure on human health. This review summarizes the impact of e-cigs exposure on different organ systems based on the rapidly expanding recent evidence from experimental and human studies. A number of growing studies have shown the adverse effects of e-cigs exposure on various organ systems. The summarized data in this review indicate that while e-cigs use causes less adverse effects on different organs compared to traditional cigs, its long-term exposure may lead to serious health effects. Data on short-term organ effects are limited and there is no sufficient evidence on long-term organ effects. Moreover, the adverse effects of secondhand and third hand e-cigs vapour exposure have not been thoroughly investigated in previous studies. Although some studies demonstrated e-cigs used as a smoking cessation tool, there is a lack of strong evidence to support it. While some researchers suggested e-cigs as a safer alternative to tobacco smoking, their long-term exposure health effects remain largely unknown. Therefore, more epidemiological and prospective studies including mechanistic studies are needed to address the potential adverse health effects of e-cigs to draw a firm conclusion about their safe use. A wide variation in e-cigs products and the lack of standardized testing methods are the major barriers to evaluating the existing data. Specific regulatory guidelines for both e-cigs components and the manufacturing process may be effective to protect consumer health.
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    Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis
    (Scientific Reports, 2023-08) Nazeer, SS; Saraswathy, A; Nimi, N; Santhakumar, H; Radhakrishnapillai Suma, P; Shenoy, SJ; Jayasree, RS
    Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM−1 s−1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.
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    Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells
    (J Biochem Mol Toxicol, 2023-07) Megha, KB; Mohanan, PV
    Ketamine is generally a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long-term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long-term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN-229 cells in a dose-dependent manner. According to the cell viability assays, there is a dose-dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro-inflammatory cytokine (interleukin [IL]-β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long-term exposure rather than a single exposure as an anesthetic agent.
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    Novel Bone Void Filling Cement Compositions Based on Shell Nacre and Siloxane Methacrylate Resin: Development and Characterization
    (Bioengineering (Basel), 2023-06) Wilson, BJ; Lizymol, PP
    Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research regarding using shell nacre powder as a cement with improved biological and physicochemical properties. To address this, bone void filling cement was formulated by incorporating shell nacre powder and an organically modified ceramic resin (ormocer). The shell nacre powder was specifically processed from the shells of Pinctada fucata and analysed using thermogravimetric analysis (TGA), X-ray diffraction spectroscopy, Fourier transform infrared (FTIR), and Raman spectroscopy, confirming the presence of organic constituents and inorganic aragonite. Trace element analysis confirmed the eligibility of shell nacre powder for biomedical applications. Next, the ormocer SNLSM2 was synthesized through a modified sol–gel method. FTIR, Raman, TGA, and transmission electron microscopy studies revealed the presence of a ladder-structured siloxane backbone and methacrylate side chain. To develop chemical curable composite shell nacre cement (SNC), different amounts of shell nacre (24%, 48%, and 72%) were added to the SNLSM2 resin, and the impact on the physicochemical properties of the cement was studied. Among the compositions, SNC 72 exhibited significantly lower linear polymerization shrinkage (0.4%) and higher compressive (>100 MPa) and flexural strength (>35 MPa). SNC 72 was radiopaque, and the exotherm generated during the cement curing was minimal. Cytotoxicity studies with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the findings of this study prove that the shell nacre cement is a promising candidate for managing bone voids.