Environmental impact of microplastics and potential health hazards.

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.

A novel benzothiophene incorporated Schiff base acting as a "turn-on" sensor for the selective detection of Serine in organic medium.

A novel fluorogenic sensor N-benzo[b]thiophen-2-yl-methylene-4,5-dimethyl-benzene-1,2-diamine (BTMPD) was synthesized and characterized by using spectroscopic methods including UV-visible, FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The designed fluorescent probe, owing to its remarkable properties, behaves as an efficient turn-on sensor for the sensing of amino acid Serine (Ser). Also, the strength of the probe enhances upon the addition of Ser via charge transfer, and the renowned properties of the fluorophore were duly found. The sensor BTMPD shows incredible execution potential with respect to key performance indicators such as high selectivity, sensitivity, and low detection limit. The concentration change was linear ranging from 5 × 10-8 M to 3 × 10-7 M, which is an indication of the low detection limit of 1.74 ± 0.02 nM under optimal reaction conditions. Interestingly, the Ser addition leads to an increased intensity of the probe at λ = 393 nm which other co-existing species did not. The information about the arrangement and the features of the system and the HOMO-LUMO energy levels was found out theoretically using DFT calculations which is fairly in good agreement with the experimental cyclic voltammetry results. The fluorescence sensing using the synthesized compound BTMPD reveals the practical applicability and its application in real sample analysis.

Pharmacological safety of dimethoxy curcumin-human serum albumin conjugate for potential therapeutic purpose.

Medicinal properties of curcumin are widely published. Previously, researchers used curcuminoid mixture comprising three chemical forms, out of which, the highest quantity is the most active molecule-dimethoxy curcumin (DMC). Reduced bioavailability, poor aqueous solubility, and quick hydrolytic degradation of DMC have projected challenges limiting its therapeutic value. However, selective conjugation of DMC with human serum albumin (HSA) enhances drug stability and solubility by several folds. Studies using animal models demonstrated potential anti-cancer/anti-inflammatory effects of DMCHSA; both studies showed results of local administration in peritoneal cavity and rabbit knee joint. DMC has prospects as intravenous therapeutic agent because carrier is HSA. However, before in vivo testing, important preclinical data required are toxicological safety and bioavailability of soluble forms of DMC. This study evaluated absorption, distribution, metabolism, and excretion of DMCHSA. Imaging technology and molecular analysis proved bio-distribution. The study also assessed the pharmacological safety of DMCHSA in mice in terms of its acute and sub-acute toxicity, complying with regulatory toxicology. Overall, the study demonstrated the safety pharmacology of DMCHSA upon intravenous infusion. This is a novel study establishing the safety of highly soluble and stable formulation of DMCHSA, qualifying it for intravenous administration and further efficacy evaluation in suitable disease models.

Intracellular inflammatory signalling cascades in human monocytic cells on challenge with phytohemagglutinin and 2,4,6-trinitrophenol.

Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.

Crystal structure, DFT studies, Hirshfeld surface and energy framework analysis of 4-(5-nitro-thiophen-2-yl)-pyrrolo [1, 2-a] quinoxaline: A potential SARS-CoV-2 main protease inhibitor.

The title compound 4-(5-nitro-thiophen-2-yl)-pyrrolo[1,2-a] quinoxaline (5NO2TAAPP) was obtained by a straightforward catalyst-free reaction of 5-nitro-2- thiophene carboxaldehyde and 1-(2-aminophenyl) pyrrole in methanol and was structurally characterized by FT IR, UV-Vis, NMR spectroscopic techniques and elemental analysis. The structure of the compound has been confirmed by the single-crystal X-ray diffraction technique. The compound crystallizes in a monoclinic crystal system with space group P21/c. Unit cell dimensions: a = 12.2009(17) A0, b = 8.3544(9) A0, c = 13.9179(17) A0 and ß = 104.980(5) A0. Hirshfeld surface analysis was carried out to understand the different intermolecular interactions. The two-dimensional fingerprint plot revealed the most prominent interactions in the compound. Theoretical calculations were executed using Density functional theory (DFT) by Gaussian09 software to develop optimized geometry and frontier molecular orbital analysis. Molecular docking studies revealed that the title compound is a potent inhibitor of Main protease 3CLpro with PDB ID: 6LU7, the viral protease which is responsible for the new Corona Virus Disease (COVID-19).

Organ distribution and biological compatibility of surface-functionalized reduced graphene oxide.

Graphene is an sp2 hybridized allotrope of carbon with a honeycomb lattice structure that has many applications in biomedicine owing to its unique physico-chemical properties. Graphene has attracted much interest from scientists for its biomedical potential, including in drug/gene delivery, fluorescent labeling of target analytes, tissue engineering, regenerative medicine and MRI contrast enhancement. However, there are very limited data available concerning the toxicity of graphene, and efforts have been made to study the bio-nano interactions of Pluronic functionalized reduced graphene oxide (rGO-P) in animal models. The present study aimed to evaluate the systemic toxicity of rGO-P and its ability to cross the blood-brain barrier in Swiss Albino mice subject to acute exposure to 10 mg kg-1 body weight of rGO-P. Prolonged exposure was evaluated in female Wistar rats by analyzing feto-placental transmission and any associated developmental neurotoxicity after intravenous administration of 5 mg kg-1 and 10 mg kg-1 body weight of rGO-P. Biodistribution analysis using confocal Raman mapping indicated that tiny amounts of rGO-P accumulated in major organs of both dams and pups, with no evident toxic response. The accumulation of rGO-P in various tissues of rat pups born to treated dams is ample evidence of feto-placental transmission. The present study clearly suggests that rGO-P is not toxic under any of the experimental conditions. These findings can therefore be carried forward for application of rGO-P in drug/gene delivery, early diagnosis and treatment of various diseases in neonates and adults. The results of the study show that rGO-P is an auspicious and promising material for future healthcare applications.

Dextran stabilized fullerene soot induced toxicity on alveolar epithelial cells (A549 cells).

Fullerene comprises the major allotrope of carbon holding several fruitful potentials to be applied in various industrial and biomedical scenarios. Scientists have acquired large number of data on fullerene research using its derivatives like C60, C70 etc. Nevertheless, a precise focus on fullerene soot nanopaticles and its toxic impacts in living tissue is still behind mainstay even if it represents the crude parent form of all other derivatives. Present study addresses an acute toxicity profiling of fullerene soot nanoparticles in alveolar epithelial cells (A549) as a paradigm of pulmonary exposure. Surface functionalization was given for fullerene soot nanoparticles using dextran polymer as a mean to establish a stable homogenous dispersion (denoted as dFSNPs hereafter). Following functionalization, dFSNPs were characterized for various parameters including size, surface charge, morphology and functional groups using DLS, Zeta potential analysis, TEM and FT-IR measurements respectively. Effective dextran functionalization was evident from the characteristic peaks in FTIR spectra. Cell viability assessed using MTT and NRU assays; both of which showed a dose dependent cytotoxic response. Thymidine incorporation also confirmed similar trend in viability rate. In accordance with literatures, DCFHDA assay confirmed free radical scavenging activity of fullerene nanoparticles. An altered cellular morphology was observed under fluorescent microscope. Sub-cellular functionalities including lysosomal integrity and mitochondrial stability were found to be compromised at highest tested concentration of dFSNPs (160 µg/ml) without any genotoxic impacts within nuclear premises. FACS analysis following Annexin-PI staining confirmed apoptotic cell death. Hence the overall study substantiated dose dependent toxicity of dFSNPs which is likely to occur during pulmonary exposure.

Bio-interactions and risks of engineered nanoparticles.

Nano technological research offered uncountable opportunities for engineered nanoparticles (ENPs) in the field of biomedical, pharmaceutical, agricultural, cosmetics, textiles, automobiles and electronic industry. Large scale commercial production and use of nanoparticles with smaller size and characteristic physico-chemical properties enhance the possibility of amenable toxicity to the environment. Primary important species of the ecosystem like bacteria, algae, fishes and plants are at high risk with nanoparticle (NP) toxicity. ENP distributed in air, water and soil can directly affect the livelihood or even the existence of smaller organisms. In day-today life, human beings are getting exposed to thousands of NPs via dermal contact, inhalation or ingestion. Topical application of sunscreens and cosmetics containing ENPs has the potential to induce photo toxicity under ultra violet irradiation. ENP intentionally or non-intentionally enter into the body will affect the entire organ system and execute their toxicity even in reproduction and fetal developmental stages. Unfortunately the existing researches to evaluate the in vivo and in vitro toxic effects of ENPs are inefficient to give the exact nature and depth of toxicity. Hence an effort was made to discuss on the characteristics, classification, synthesis, applications and toxic potentials of various classes of commercially relevant ENPs along with a detailed review on currently available literatures.

In vitro interaction and biocompatibility of titanate nanotubes with microglial cells.

Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis.

Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis.

Background & objectives: Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Methods: Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Results: Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Interpretation & conclusions: Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.

The making of indigenous vascular prosthesis.

BACKGROUND & OBJECTIVES: Vascular illnesses are on the rise in India, due to increase in lifestyle diseases and demographic transition, requiring intervention to save life, organ or limbs using vascular prosthesis. The aim of this study was to develop indigenous large diameter vascular graft for treatment of patients with vascular pathologies. METHODS: The South India Textile Research Association, at Coimbatore, Tamil Nadu, India, developed seamless woven polyester (Polyethylene terephthalate) graft at its research wing. Further characterization and testing followed by clinical trials were conducted at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fifteen in vivo experiments were carried out in 1992-1994 in pigs as animal model. Controlled (phase I) clinical trial in ten patients was performed along with control graft. Thereafter, phase II trial involved 22 patients who underwent multi-centre clinical trial in four centres across India. RESULTS: Laboratory testing showed that polyester graft was non-toxic, non-leeching and non-haemolytic with preserved long-term quality, further confirming in pigs by implanting in thoracic aorta, comparable to control Dacron grafts. Perigraft incorporation and smooth neointima formation which are prime features of excellent healing characteristics, were noted at explantation at planned intervals. Subsequently in the phase I and II clinical trials, all patients had excellent recovery without mortality or device-related adverse events. Patients receiving the test graft were followed up for 10 and 5 years, respectively. Serial clinical, duplex scans and CT angiograms performed periodically confirmed excellent graft performance. INTERPRETATION & CONCLUSIONS: Indigenously developed Chitra vascular graft was comparable to commercially available Dacron graft, ready for clinical use at affordable cost to patients as against costly imported grafts.

Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells.

Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO(2) and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6-8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn(+) ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.

Bio distribution and acute toxicity profiling of Pluronic F127 coated Titanium dioxide nanotubes in adult Wistar rats.

Metal and metal oxide nanoparticles are gaining immense attention among researchers owing to their admirable application potentials in various therapeutic events. Titanium dioxide (TiO2) has been recognized as one of the leading candidates in this category and holds wide interest within the scientific community. Among the various morphological nanoforms of TiO2, nanotube is grabbing remarkable attention as they have succeeded as an active vehicle in various medical procedures like intravascular stenting, drug delivery, as biosensors etc. This ultimately demands toxicity profiling of nanotubes in various aspects. Present study elaborates a concept through which acute toxicity profiling of TiO2 nanotubes in adult Wistar rats is presented. TNTs were synthesized via solvo-thermal approach and surface coated with a biocompatible polymer; Pluronic-F127 (P-F127). This step assists in ameliorating the troubles associated with the nanomaterial dispersion stability. The experimental rats were intraperitoneally administered with TNT-P (10 mg/kg) and sacrificed on different time periods (3rd, 7th and 14th days). Biodistribution of the material was tracked in major tissues including brain, liver, spleen and kidneys. A set of acute toxicity studies was performed which comprises hematology evaluation, biochemical studies, antioxidant detection, analysis of urine parameters, immune modulation study and histopathology evaluation. Many of the experiments revealed an unaltered physiological response in rats; except for some biochemical and hematology parameters. Overall study suggests that, TNT-P do not result into a negative response in Wistar rats over 14 days.

Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management.

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.

Analysis of mitochondrial DNA damage using 8-hydroxy 2'deoxyguanosine on in vitro and in vivo exposure of biomaterials.

The present study was carried out to evaluate the effect of HAP-EVA, fibrin glue, HA-BG, Latex and Dental material on oxidative stress related mtDNA damage by in vitro and in vivo methods. In vivo studies of these biomaterials were carried out by implanting biomaterials (five materials) on animals for period of 1, 4, 12, 26 and 52 weeks. At the end of observations, animals were anesthetized, sacrificed and tissues surrounding the implanted materials were collected. Brain, bone and muscles were used for the extraction of mtDNA. Similarly mtDNA was extracted from the homogenate of fresh brain, bone and muscles on exposure to the physiological saline extract of all the above five biomaterials (In vitro). The extracted mtDNA were subjected to analyse the presence of 8-OHdG. The results of study indicated that there was no significant increase in the level of 8-OHdG and thereby does not influence on the GC-TA transversions.

Effect of fibrin glue on antioxidant defense mechanism, oxidative DNA damage and chromosomal aberrations.

Oxidative stress is involved in diverse biological phenomenon, and is caused by the imbalance between reactive oxygen species (ROS) and antioxidant defense system. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is the most critical biomarker in the estimation of ROS-induced DNA damage. This investigation focuses on the effect of fibrin glue on lipid peroxidation (LPO), antioxidant enzymes and oxidative DNA damage (both in vitro and in vivo). The blood biochemical parameters of the implanted animals and in vitro chromosomal aberrations were also studied. Fibrin glue was applied on the calvarial defect made on the anesthetized rats for an observation period of 4, 12, 26 and 52 weeks. At the end of the observation period, animals were anesthetized; blood was collected for serum analysis and was sacrificed. Brain was collected for the detection of 8-OHdG using competitive ELISA and liver was collected for analyzing the antioxidant enzymes and LPO. The results of this study suggest that the effect of fibrin glue on rat brain (in vivo and in vitro) and mice liver (in vitro) did not make any significant influence on LPO and antioxidant defense system. Similarly, there was no change observed in the expression of 8-OHdG. Serum constituents of implanted rats were observed to be within the normal range. The normal karyotype obtained indicates that the physiological saline extract of fibrin glue does not induce any chromosomal anomalies. Hence, it was concluded that the fibrin glue material does not have any potential to produce oxidative stress, alterations in the C-8 position of guanine and chromosomal anomalies.

Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review.

Microfluidics 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.

Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.

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.