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Item 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, RSEndosulfan (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.Item 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, GNSkin, 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.Item 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, PVBone 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.Item 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, PVMelatonin, 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.Item 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, LVNanoarchitectonics, 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.Item Infrared Spectroscopy for Rapid Triage of Cancer Using Blood Derivatives: A Reality Check(Anal Chem., 2024-01) Nazeer, SS; Venkataraman, RK; Jayasree, RS; Bayry, JInfrared (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.Item 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, PBone 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.Item 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, PVLDHs, 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.Item Prosthetics and orthotics for persons with movement disabilities in India in the postpandemic milieu(Prosthet Orthot Int, 2023-11) Prajapati, AK; Komath, M; Subhash, NNThe 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.Item 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, PVThe 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.Item Nanoarchitectonics of photothermal materials to enhance the sensitivity of lateral flow assays(Beilstein Journal of Nanotechnology, 2023-10) Sarathkumar, S; Anjana, RS; Jayasree, RSLateral 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.Item A review of immune modulators and immunotherapy in infectious diseases(Mol Cell Biochem., 2023-09) Sangeetha Vijayan, P; Xavier, J; Mohanan, PVThe 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.Item 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, SJThe 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.Item 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, RSProlonged 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.Item Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells(J Biochem Mol Toxicol, 2023-07) Megha, KB; Mohanan, PVKetamine 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.Item Novel Bone Void Filling Cement Compositions Based on Shell Nacre and Siloxane Methacrylate Resin: Development and Characterization(Bioengineering (Basel), 2023-06) Wilson, BJ; Lizymol, PPShell 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.Item Antineoplastic effects of cassava-cyanide extract on human glioblastoma (LN229) cells(Toxicon, 2023-07) Sreejith, S; Joseph, T; Sangeetha, VP; Vandana, U; Joseph, X; Jayaprakas, CA; Mohanan, PVSeveral natural compounds reduce tumour cell growth and metastasis by inducing programmed cell death. Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides such as, linamarin and lotaustralin, can be enzymatically cleaved by linamarase to release hydrogen cyanide (HCN), which can have therapeutic benefits against hypertension, asthma, and cancer. We have developed a technology for isolating bio-active principles from cassava leaves.The present study is designed to analyze the cytotoxic effect of cassava cyanide extract (CCE) against human glioblastoma cells (LN229). The treatment of CCE demonstrated a dose dependent toxicity on glioblastoma cells. At higher concentration tested, the CCE (400 μg/mL) was found to be cytotoxic, reducing the cell viability to 14.07 ± 2.15% by negatively influencing the mitochondrial activity, and lysosomal and cytoskeletal integrity. Coomassie's brilliant blue staining confirmed cells' morphological aberration after 24 h of treatment with CCE. Moreover, DCFH-DA assay and Griess reagent showed an increase in ROS but a decrease in RNS production at a concentration of CCE. Flow cytometry analysis revealed that CCE interfered with G0/G1, S, and G2/M stages of the cell cycle of glioblastoma, and Annexin/PI staining indicated a dose-dependent increase in cell death, confirming the toxic nature of CCE on LN229 cells. These findings suggest that cassava cyanide extract has potential as an antineoplastic agent against glioblastoma cells, which is an aggressive and difficult-to-treat type of brain cancer. However, it is important to note that the study was conducted in vitro, and further research is necessary to assess the safety and efficacy of CCE in vivo. Additionally, it is essential to establish the optimal dose and potential side effects before considering its use as a therapeutic agent.Item Bifunctional cysteine gold nanocluster for β-amyloid fibril inhibition and fluorescence imaging: A distinctive approach to manage Alzheimer's disease(Journal of Materials Chemistry B, 2023-04) Resmi, AN; Rekha, CR; Dhushyandhun, ME; Sarathkumar, E; Shenoy, SJ; Gulia, KK; Jayasree, RSAlzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to β-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD.Item Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review(International Journal of Biological Macromolecules, 2023-04) Amir, S; Arathi, A; Reshma, S; Mohanan, PVMicrofluidics is a revolutionary technology that has promising applications in the biomedical field.Integrating microfluidic technology with the traditional assays unravels the innumerable possibilities for translational biomedical research. Microfluidics has the potential to build up a novel platform for diagnosis and therapy through precise manipulation of fluids and enhanced throughput functions. The developments in microfluidics-based devices for diagnostics have evolved in the last decade and have been established for their rapid, effective, accurate and economic advantages. The efficiency and sensitivity of such devices to detect disease-specific macromolecules like proteins and nucleic acids have made crucial impacts in disease diagnosis. The disease modelling using microfluidic systems provides a more prominent replication of the in vivo microenvironment and can be a better alternative for the existing disease models. These models can replicate critical microphysiology like the dynamic microenvironment, cellular interactions, and biophysical and biochemical cues. Microfluidics also provides a promising system for high throughput drug screening and delivery applications. However, microfluidics-based diagnostics still encounter related challenges in the reliability, real-time monitoring and reproducibility that circumvents this technology from being impacted in the healthcare industry. This review highlights the recent microfluidics developments for modelling and diagnosing common diseases, including cancer, neurological, cardiovascular, respiratory and autoimmune disorders, and its applications in drug development.Item Contact Guidance Mediated by Hybrid Thread Topography Enhances Osseointegration of As-machined Ti6Al4V Dental Implant.(Regenerative Engineering and Translational Medicine, 2023-03) Mishra, D; Neethu, RS; Shetty, V; Shenoy, SJ; Komath, M; Varma, HK; Sabareeswaran, A; Basu, BPurpose The main objective of this study is to investigate the key role of as-machined implant design features on the osseointegration. The bone regeneration ability of the newly developed Ti6Al4V hybrid threaded tapered implant without any surface modification has been validated and benchmarked against Straumann® implant (control) in the rabbit model for 12 weeks. Material and Methods The test and control implants were implanted in the femur medial condyle of twelve adult New Zealand white rabbits on the contralateral limbs; each femoral medial condyle received a test or control implant randomly. The bone formation and osseointegration around the implants were assessed qualitatively and quantitatively using histology, micro-computed tomography (Micro-CT), molecular gene studies, and histomorphometric analysis after 12 weeks of implantation. Results The overall assessment suggests homogenous and continuous neobone formation and osseointegration around the hybrid threads of the test implants. Superior bone-to-implant contact percentage (BIC) was observed in the case of hybrid threaded test implants with an average value of 80.8%, compared to 67.1% for the control implant. Upregulated expression of osteogenic (COL1A1, RUNX2, SPARC, and SPP1) and angiogenic (VEGF) genes in the case of test implant indicates better coupled osseointegrationa and angiogenesis. Conclusion It can be concluded that the extent of neobone formation and expression of the osteogenic/angiogenic genes is positively correlated with optimal design features of the implant, which leads to the contact guidance of the osteoblasts on the implant surface. The study also advocates that the novel tapered multithreaded implant design concept alone, without any surface modification, can facilitate osseointegration in a manner better than clinically used surface-modified implants. Lay Summary Dental implants are artificial tooth roots and are used to treat complete or partial toothlessness. The new implant design concept reported here is expected to support both soft tissue and hard tissue attachment and to improve primary stability. This study unraveled the effect of the novel external hybrid thread design on the implant integration with the surrounding bone. This aspect was validated in the rabbit model and benchmarked against the commercially available Straumann® implant. This study has unambiguously demonstrated the ability of as-machined Ti implants to facilitate better new bone and new blood vessels formation than the commercial implant.