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Synthesis and photophysical properties of a fluorescent probe HBD is described. Probe upon interaction with metal ions, anions and nucleoside pyrophosphates (NPPs) showed fluorescence quenching with Cu2+ due to chelation enhanced quenching effect (CHEQ). Moreover, interaction of ensemble HBD.Cu2+ with anions and NPPs showed fluorescence "turn-On" response with ATP selectively. "On-Off-On" responses observed with Cu2+ and ATP is attributed to an interplay between ESIPT and TICT processes. Cyclic voltammogram of probe exhibited quasi-reversible redox behaviour with three oxidation and two reduction potentials and the change in band gaps of probe suggested the interaction with Cu2+ and ATP. The 2 : 1 and 1 : 1 binding stoichiometry for an interaction between probe and Cu2+ (LOD, 62â nM) and ensemble, HBD.Cu2+ with ATP (LOD, 0.4â µM) respectively are realised by Job's plot and HRMS data. Cell imaging studies carried out to detect Cu2+ and ATP in HeLa cells. Also, the output emission observed with Cu2+ and ATP is utilized to construct an implication (IMP) logic gate. Test paper strips showed naked-eye visible color responses to detect Cu2+ and ATP. In real water samples probe successfully detected copper (0.03â µM) between 5-6.5 ppb level (ICP-MS method).
Assuntos
Trifosfato de Adenosina , Cobre , Corantes Fluorescentes , Cobre/química , Humanos , Células HeLa , Trifosfato de Adenosina/análise , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Espectrometria de Fluorescência , Boro/química , Fluorescência , Estrutura MolecularRESUMO
Plastics are ubiquitous in today's lifestyle, and their indiscriminate use has led to the accumulation of plastic waste in landfills and oceans. The waste accumulates and breaks into micro-particles that enter the food chain, causing severe threats to human health, wildlife, and the ecosystem. Environment-friendly and bio-based degradable materials offer a sustainable alternative to the vastly used synthetic materials. Here, a polylactic acid and carbon nanofiber-based membrane and a paper-based colorimetric sensor have been developed. The membrane had a surface area of 3.02 m2 g-1 and a pore size of 18.77 nm. The pores were evenly distributed with a pore volume of 0.0137 cm3 g-1. The membrane was evaluated in accordance with OECD guidelines and was found to be safe for tested aquatic and terrestrial models. The activated PLA-CNF membrane was further used as a bio-based electrode for the electrochemical detection of nitrates (NO3-) in water samples with a detection limit of 0.046 ppm and sensitivity of 1.69 × 10-4 A ppm-1 mm-2, whereas the developed paper-based colorimetric sensor had a detection limit of 156 ppm for NO3-. This study presents an environment-friendly, low-carbon footprint disposable material for sensing applications as a sustainable alternative to plastics.
Assuntos
Carbono , Colorimetria , Nanofibras , Nitratos , Papel , Poliésteres , Nanofibras/química , Colorimetria/métodos , Colorimetria/instrumentação , Nitratos/análise , Nitratos/química , Poliésteres/química , Carbono/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Limite de Detecção , Poluentes Químicos da Água/análise , Condutividade Elétrica , Membranas ArtificiaisRESUMO
Microplastic (MP) pollution is becoming an emerging environmental concern across aquatic and terrestrial ecosystems. Plastic mulching and the use of pesticides in agriculture can lead to microplastics and agrochemicals in soil, which can result in unintended exposure to non-target organisms. The combined toxicity of multiple stressors represents a significant paradigm shift within the field of ecotoxicology, and its exploration within terrestrial ecosystems involving microplastics is still relatively limited. The present study investigated the combined effects of polyethylene MP (PE-MP) and the agrochemical carbendazim (CBZ) on the earthworm Eisenia fetida at different biological levels of organization. While E. fetida survival and reproduction did not exhibit significant effects following PE-MP treatment, there was a reduction in cocoon and hatchling numbers. Notably, prolonged exposure revealed delayed toxicity, leading to substantial growth impairment. Exposure to CBZ led to significant alterations in the endpoints mentioned above. While there was a decrease in cocoon and hatchling numbers, the combined treatment did not yield significant effects on earthworm reproduction except at higher concentrations. However, lower concentrations of PE-MP alongside CBZ induced a noteworthy decline in biomass content, signifying a form of potentiation interaction. In addition, concurrent exposure led to synergistic effects, from oxidative stress to modifications in vital organs such as the body wall, intestines, and reproductive structures (spermathecae, seminal vesicles, and ovarian follicles). The comparison of multiple endpoints revealed that seminal vesicles and ovarian follicles were the primary targets during the combined exposure. The research findings suggest that there are variable and complex responses to microplastic toxicity in terrestrial ecosystems, especially when combined with other chemical stressors like agrochemicals. Despite these difficulties, the study implies that microplastics can alter earthworms' responses to agrochemical exposure, posing potential ecotoxicological risks to soil fauna.
Assuntos
Benzimidazóis , Carbamatos , Oligoquetos , Praguicidas , Poluentes do Solo , Animais , Feminino , Masculino , Microplásticos/toxicidade , Plásticos/toxicidade , Polietileno/toxicidade , Ecotoxicologia , Ecossistema , Poluentes do Solo/análise , Solo/química , Praguicidas/farmacologiaRESUMO
Demyelination is the loss of myelin in CNS, resulting in damaged myelin sheath. Oxidative stress and neuroinflammation play a key role in inducing demyelinating diseases like MS; hence, controlling oxidative stress and neuroinflammation is important. Cuprizone (CPZ), a copper chelator, generates oxidative stress and neuroinflammation, thereby inducing demyelination. Therefore, the CPZ-induced demyelinating mouse model (CPZ model) is widely used in research. The present study was intended to unravel a mechanism of inhibition of demyelination by arsenic in a CPZ model, which is otherwise known for its toxicity. We investigated an alternative mechanism of inhibition of demyelination by arsenic through the reversal of SOD1 activity employing in silico analysis, analytical chemistry techniques, and in vitro and in vivo experiments. In vivo experiments showed protection of body weight, survivability, and myelination of the corpus callosum in CPZ and arsenic-co-exposed animals, where neuroinflammation was apparently not involved. In vitro experiments revealed that arsenic-mediated reversal of impaired SOD1 activity leads to reduced cellular ROS levels and better viability of primary oligodendrocytes. Reversal of SOD1 activity was also observed in the corpus callosum tissue isolated from experimental animals. In silico and analytical chemistry studies revealed that similar to copper, arsenic can potentially bind to CPZ and thereby make the copper freely available for SOD1 activity. Suitable neurobehavior tests further validated the protective effect of arsenic. Taken together, the present study revealed that arsenic protects oligodendrocytes and demyelination of corpus callosum by reversing CPZ-induced impaired SOD1 activity.
Assuntos
Arsênio , Corpo Caloso , Cuprizona , Doenças Desmielinizantes , Modelos Animais de Doenças , Microglia , Animais , Cuprizona/toxicidade , Corpo Caloso/patologia , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Microglia/efeitos dos fármacos , Microglia/patologia , Microglia/metabolismo , Arsênio/toxicidade , Camundongos Endogâmicos C57BL , Camundongos , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Masculino , Superóxido Dismutase-1/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Rapeseed, the second-most-important vegetable oil source, is cultivated in various areas of India where both groundwater and soil are contaminated with fluoride (F-). Furthermore, the frequent use of F- contaminated groundwater for irrigation leads to accumulation of F- in surface and sub-surface soil. The study aims to compare the morphological and biochemical changes in Brassica juncea L., the variations in its fatty acids (FAs) composition and oil yield, under two regimes of F- contaminated soils: (i) pre-contaminated soil (Tr) and (ii) irrigation with F- contaminated water (Ir). The level of F- (µg g-1) in the plant tissues (root, leaf, and grain) was significantly higher in Ir_10 (18.3, 14.7, and 2.8, respectively) than in Tr_10 (4.3, 2.6, and 0.77, respectively), while the oil yield was significantly lower with Ir_10 (19.5%) than with Tr_10 (44.9%). The phytoremediation potential of F- by Brassica juncea L. is greater in Tr regime than in the Ir regime. The erucic acid content (%), which is detrimental to cardiac health, increased to 67.37% (Ir_10) and 58.3% (Tr_10) from 57.73% (control). Thus, the present study shows that irrigation with F- contaminated water results in greater toxicity and accumulation in plants and is not safe for human health.
Irrigation with F contaminated water results in a greater accumulation of F in mustard than cultivated on pre-contaminated soil. The level of erucic acid in mustard oil enhances against F exposure.
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Mostardeira , Poluentes do Solo , Humanos , Mostardeira/química , Ácidos Graxos , Fluoretos , Biodegradação Ambiental , Solo/química , ÁguaRESUMO
Combining antiangiogenic and chemotherapeutic agents has shown promising clinical benefits in cancer cures when the therapeutic intervention takes into account the tissue and molecular targets. Moreover, the risk of induced drug resistance is minimized when multiple pathways are involved in the treatment regimen, yielding a better therapeutic outcome. Nanodrug delivery systems have proven to be a prudent approach to treating complex disease pathologies. As such, combining antiangiogenic and chemotherapeutic drugs within multimodal nanocarriers synergistically augments the clinical efficiency of the drugs. This study reports the combinatorial efficacy of heparin (Hep), selenium NPs (SeNPs), and doxorubicin (Dox) to inhibit tumor growth and progression. Both Se@Hep-NPs and Se@Hep-Dox-NPs with excellent water dispersity having a size and charge in the range of 250 ± 5 and 253 ± 5 nm and -53 ± 0.4 and -48.4 ± 6.4 mV, respectively, showed strong anticancer potential assessed through in vitro assays like cell viability, specificity, colony formation, and wound scratch in MCF7 cells. Strong synergistic interactions among SeNPs, Hep, and Dox in Se@Hep-Dox-NPs render it to be an antiangiogenic and proapoptotic cancer cell death inducers. In vivo imaging highlights the dual-mode attributes of Se@Hep-NPs with desirable passive tumor targeting and biomedical imaging ability when tagged with Cy7.5, while Se@Hep-Dox-NPs significantly reduce the tumor burden and prolong the longevity of subcutaneous EAC-bearing mice. Histopathology studies reveal no signs of toxicity in major organs. Collectively, these results qualify Se@Hep-Dox-NPs as a plausible clinical therapeutic candidate.
Assuntos
Antineoplásicos , Nanopartículas , Selênio , Animais , Camundongos , Selênio/farmacologia , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Apoptose , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/farmacologia , Heparina/farmacologia , Nanopartículas/uso terapêutico , Linhagem Celular TumoralRESUMO
Bioelectrodes with low carbon footprint can provide an innovative solution to the surmounting levels of e-waste. Biodegradable polymers offer green and sustainable alternatives to synthetic materials. Here, a chitosan-carbon nanofiber (CNF) based membrane has been developed and functionalized for electrochemical sensing application. The surface characterization of the membrane revealed crystalline structure with uniform particle distribution, and surface area of 25.52 m2/g and pore volume of 0.0233 cm3/g. The membrane was functionalized to develop a bioelectrode for the detection of exogenous oxytocin in milk. Electrochemical impedance spectroscopy was employed to determine oxytocin in a linear concentration range of 10 to 105 ng/mL. The developed bioelectrode showed an LOD of 24.98 ± 11.37 pg/mL and sensitivity of 2.77 × 10-10 Ω / log ng mL-1/mm2 for oxytocin in milk samples with 90.85-113.34 percent recovery. The chitosan-CNF membrane is ecologically safe and opens new avenues for environment-friendly disposable materials for sensing applications.
Assuntos
Técnicas Biossensoriais , Quitosana , Nanofibras , Carbono/química , Quitosana/química , Ocitocina/química , Eletrodos , Técnicas Biossensoriais/métodosRESUMO
The rapidly growing electronic and plastic waste has become a global environmental concern. Developing advanced and environmentally safe agro-based materials is an emerging field with an enormous potential for applications in sensors and devices. Here, an agro-based material as membrane has been developed by incorporating tapioca starch and banana peel powder in polylactic acid, with uniform dispersibility and amorphous nature. The material was used for the development of electrochemical sensor for S-gene of SARS-CoV-2. Further, the membrane was used for the development of a non-invasive, colorimetric skin patch for the detection of glucose and a sensor for the assessment of fruit juice quality. Using OECD-recommended model systems, the developed membrane was found to be non-toxic towards aquatic and terrestrial non-target organisms. The developed conductive material opens new avenues in various electrochemical, analytical, and biological applications.
Assuntos
Técnicas Biossensoriais , COVID-19 , Manihot , Musa , Musa/química , Colorimetria , COVID-19/diagnóstico , SARS-CoV-2 , Amido/químicaRESUMO
Microplastic (MP) pollution has pressing concerns regarding environmental health and the availability of safe food for humans. Information on the occurrence of MP in freshwater biota in the Indian scenario is currently lacking. The present study examined MP contamination in edible and non-edible tissues of widely consumed freshwater fishes. All the fish species (n = 35/species) analyzed had microplastic contamination with the highest MP abundance of 7.86 ± 2.0 items/individual in Channa punctatus followed by Labeo rohita (4.17 ± 0.6 items/individual) and Labeo bata (3.03 ± 0.4 items/individual); whereas MP abundance in small indigenous fishes (SIF) such as Salmostoma bacaila and Puntius amphibius accounts for 0.83 ± 0.13 and 0.77 ± 0.2 items/individual respectively. The principal component analysis results showed a 77.434% variance from two components identified for MP distribution. Fibre type MP was the most dominant type besides fragments and pellets that opined the type of MP required for ecotoxicity assessment, the need of the hour. Raman spectroscopy analysis confirms high-density and low-density polyethylene-type polymers. Evidence of MP in edible tissue indicates the translocation phenomenon resulting in human exposure through the consumption of biota contaminated with MP. Risk assessment revealed a low risk of MP based on its abundance while polymer type indicates a high risk for the fish species investigated. A thorough investigation of the level of adsorbed organic contaminants in the MP is warranted to address the interactive effects on biota. To the best of our knowledge, this is the first detailed report on MP contamination and its risk assessment in Indian freshwater fishes.
Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Humanos , Plásticos/análise , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Peixes , Água Doce , Índia , Medição de RiscoRESUMO
Delayed wound healing in patients having type-II diabetes mellitus (T2DM) often results in a high rate of amputation. We report an innovative Guar Gum-based macroporous hydrogel (HG) infused with an antibacterial agent (Ag NPs), and antioxidant, epigallocatechin gallate (EGCG) to address rapid wound healing and interestingly could inhibit the associated pathophysical bone infection in a high-fat-diet-induced T2DM C57BL/6 mice model. The HG-Ag-EGCG elicits scar-free wound healing in subcutaneous wounds and histopathological evidence confirmed HG-Ag-EGCG hydrogel patch elicits better wound healing through enhanced cell proliferation, mature connecting tissue fiber formation, minimum void spaces formation, and better re-epithelialization when compared with a market available hydrogel patch material (Luofucon®). Supportive of the in vivo outcomes, in vitro experiments delineated better-wound closure due to improved management of ROS by the HG-Ag-EGCG. Additionally, a favorable non-toxicity outcome assessed through both in vitro and in vivo conditions confirmed its potential applicability in clinical wound care management.
Assuntos
Diabetes Mellitus Tipo 2 , Prata , Animais , Catequina/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidrogéis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/farmacologia , Prata/farmacologia , CicatrizaçãoRESUMO
Arsenic is infamous for its adverse health effects worldwide. It is known to induce cognitive impairment in experimental model animals and children in the arsenic-affected area. Although the effect of arsenic on neuronal health is well studied, but the involvement of the brain immune component, microglia, has not been well explored. The present study is focused on examining the role of microglia in arsenic-induced cognitive impairment. We have used balb/c mice for the study. Pregnant dams were gavaged with sodium arsenite (0.38 mg/kg body weight) from gestational day 5 (GD5) till postnatal day 22 (PND22). Mice were sacrificed on PND 7, 14, 22 and isolated brains were used for various assays. The study reveals that perinatal arsenic exposure keeps the microglia activated and skews them towards the M1 phenotype. Increased microglial proliferation, ROS, NO, higher levels of proinflammatory cytokines and chemokines were observed in the arsenic exposed group. Enhanced phagocytosis and phagocytic receptor TREM2, along with decreased expression of SNAP25 and PSD95, were correlated for enhanced neuronal pruning leading to impaired learning and memory response. Taken together, the study reveals an association between arsenic exposure and altered cognitive response where enhanced neuronal pruning by arsenic-activated microglia plays an important role in developing mice.
Assuntos
Arsênio , Disfunção Cognitiva , Animais , Arsênio/metabolismo , Arsênio/toxicidade , Cognição , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Feminino , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Microglia , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/metabolismoRESUMO
Ability of the cells to adhere to an extracellular material is central to successful tissue genesis. Arg-Gly-Asp (RGD) sequences found in extracellular matrix proteins are well known for cell adhesion, however, enzymatic degradation and lack of specificity have limited their widespread use. Besides, a multifunctional material with inherent antimicrobial ability would help in invigorating the practical tissue engineering applications. Here, we report novel modified RGD (MR) and RGD mimic [R(K)] peptides (MOH and MNH2) which were synthesized post-in-silico screening, based on their interactions with integrin protein αVß3 using HEX 8.0 docking server. These mimics, containing hydrophobic Phe-Phe (FF) moiety which has been specifically introduced to initiate the self-assembling process of ß-sheet structures, were characterized thoroughly using various physicochemical and spectroscopic techniques. Under physiological conditions, these mimetics displayed thixotropic behavior rendering them highly suitable as injectable hydrogels having an added advantage of site-specific targeting abilities. Electron microscopy further revealed the formation of nanofibers upon self-assembly of these peptides. Besides, enhanced cell adhesiveness by these peptides compared to the commercial Poly l-lysine coated surfaces as well as the inherent antimicrobial potential against both sensitive and antibiotic-resistant pathogens (Methicillin-resistant Staphylococcus aureus and multi-drug resistant Salmonella enteritidis) substantiated the applicability of these unique injectable hydrogels wherein the porous fibrous framework offered a favorable environment for drug entrapment and 3D cell culture. Altogether, these properties render these novel RGD mimic peptides as promising multifunctional candidates for various tissue regenerative applications.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Peptidomiméticos , Materiais Biocompatíveis , Hidrogéis/química , Oligopeptídeos/farmacologia , Peptídeos/química , Peptidomiméticos/farmacologia , Conformação Proteica em Folha betaRESUMO
Arsenic activates microglia and exerts bystander effects on neuron. The present study is focused to test whether minocycline, a second generation antibiotic, can reverse the effect of developmental arsenic exposure on microglial activation and function. Pregnant Balb/c dams were gavaged with sodium arsenite (0.38 mg/kg bd wt) from gestational day 5 (GD5) till post natal day 21 (PND21) and then one group of pups continued till PND59 with arsenic gavage. Minocycline (33 mg/kg bd wt) was administered intraperitoneally two weeks till sacrifice, every alternate day. Mice were sacrificed on PND22 and PND60 and used for various assays. Primary microglial were isolated (ex vivo microglia) from experimental animals and used to measure reactive oxygen species (ROS), nitric oxide (NO), cytokine production and phagocytosis. The whole brain lysate was used for western blot analysis of microglial marker CD68 and synaptic marker, post synaptic density protein 95 (PSD95). For real-time PCR analysis of triggering receptor expressed on myeloid cells 2 (TREM2) and PSD95, RNA isolated from whole brain was used. The study reveals that minocycline administration reversed arsenic-induced increased expression of CD68, ROS, NO, cytokine production, phagocytosis and TREM2 expression. Arsenic-induced reduced expression of PSD95 protein was reversed by minocycline, although the mRNA of PSD95 was unaltered among different groups. Finally, we have checked the learning and memory response of the experimental animals using Y-maze test to correlate the arsenic-induced altered level of synaptic protein. Taken together, the present study finds minocycline to reduce arsenic-induced microglial activation and function which in turn reverses the arsenic-induced impaired learning and memory response.
Assuntos
Arsênio , Minociclina , Animais , Arsênio/metabolismo , Arsênio/toxicidade , Citocinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Microglia , Minociclina/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/metabolismoRESUMO
Fluoride (F-) contamination in groundwater of Unnao district, Uttar Pradesh was reported for the first time in 1994, however comprehensive monitoring of F- in different environmental matrices remains to be undertaken. The presented study reports spatio-temporal monitoring of F- content in groundwater, crops and soil from F- affected district Unnao, in pre-monsoon (PRM), monsoon (MO) and post-monsoon (PMO), to establish F- groundwater-soil-plant continuum. More than 80% of groundwater samples were contaminated with F-> 1.0 mg L-1 with highest level (mg L-1), at Patiyara (3.6 ± 0.64), during PRM > Pathakpur (2.73 ± 0.57) during PMO > Sarukheda (2.40 ± 0.43) during PRM. High Cr in groundwater was observed in Jajmau (7.08 ± 1.42). The level of F- (mg Kg-1) in agricultural soils followed 3.4 ± 0.71 at Patiyara (MO) > 2.9 ± 0.14 at Badlikheda (PRM) 1.89 ± 0.28 at Jagatkhera (PRM). Among the different edible parts of crops in selected sites, highest F- content (mg Kg-1), F- level in grains of Oryza sativa ranged between 0.23 ± 0.02 to 2.01 ± 0.24. Whereas in the edible fruit of Trichosanthes diocia contained 1.47 ± 0.32 and Momordica charantia 1.47 ± 0.02. Leaf of spinach (1.03 ± 0.22) and seed of Brassica juncea (0.73 ± 0.08). Overall, comparing across all the three seasons, level of F- was highest in all the plants during MO, as compared to PRM and PMO. The regression analysis of physiochemical properties of groundwater show negative relationship between Na+ and F- whereas soil alkalinity exhibited strong influence in soil F-. The high F- content in soil and groundwater at Patiyara and Shekhpur also coincided with presence of several brick kilns, possibly contributing to the high F-.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Agricultura , Produtos Agrícolas , Monitoramento Ambiental , Fluoretos/análise , Água Subterrânea/química , Índia , Solo , Poluentes Químicos da Água/análiseRESUMO
Arsenic (As) exposure is progressively associated with chronic kidney disease (CKD), a leading public health concern present worldwide. The adverse effect of As exposure on the kidneys of people living in As endemic areas have not been extensively studied. Furthermore, the impact of only prenatal exposure to As on the progression of CKD also has not been fully characterized. In the present study, we examined the effect of prenatal exposure to low doses of As 0.04 and 0.4 mg/kg body weight (0.04 and 0.4 ppm, respectively) on the progression of CKD in male offspring using a Wistar rat model. Interestingly, only prenatal As exposure was sufficient to elevate the expression of profibrotic (TGF-ß1) and proinflammatory (IL-1α, MIP-2α, RANTES, and TNF-α) cytokines at 2-day, 12- and 38-week time points in the exposed progeny. Further, alteration in adipogenic factors (ghrelin, leptin, and glucagon) was also observed in 12- and 38-week old male offspring prenatally exposed to As. An altered level of these factors coincides with impaired glucose metabolism and homeostasis accompanied by progressive kidney damage. We observed a significant increase in the deposition of extracellular matrix components and glomerular and tubular damage in the kidneys of 38-week-old male offspring prenatally exposed to As. Furthermore, the overexpression of TGF-ß1 in kidneys corresponds with hypermethylation of the TGF-ß1 gene-body, indicating a possible involvement of prenatal As exposure-driven epigenetic modulations of TGF-ß1 expression. Our study provides evidence that prenatal As exposure to males can adversely affect the immunometabolism of offspring which can promote kidney damage later in life.
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CD200R1 is an inhibitory surface receptor expressed in microglia and blood macrophages. Microglial CD200R1 is known to control neuroinflammation by keeping the microglia in resting state, and therefore, tight regulation of its expression is important. CCAAT/enhancer-binding protein ß (CEBPß) is the known regulator of CD200R1 transcription. In the present study, our specific intention was to find a possible posttranscriptional regulatory mechanism of CD200R1 expression. Here we investigated a novel regulatory mechanism of CD200R1 expression following exposure to an environmental stressor, arsenic, combining in silico analysis, in vitro, and in vivo experiments, as well as validation in human samples. The in silico analysis and in vitro studies with primary neonatal microglia and BV2 microglia revealed that arsenic demethylates the promoter of a microRNA, miR-129-5p, thereby increasing its expression, which subsequently represses CD200R1 by binding to its 3'-untranslated region and shuttling the CD200R1 mRNA to the cytoplasmic-processing body in mouse microglia. The role of miR-129-5p was further validated in BALB/c mouse by stereotaxically injecting anti-miR-129. We found that anti-miR-129 reversed the expression of CD200R1, as well as levels of inflammatory molecules IL-6 and TNF-α. Experiments with a CD200R1 siRNA-induced loss-of-function mouse model confirmed an miR-129-5pâCD200R1âIL-6/TNF-α signaling axis. These main findings were replicated in a human cell line and validated in human samples. Taken together, our study revealed miR-129-5p as a novel posttranscriptional regulator of CD200R1 expression with potential implications in neuroinflammation and related complications.
Assuntos
Arsênio , MicroRNAs , Doenças Neuroinflamatórias , Receptores de Orexina , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Interleucina-6/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Doenças Neuroinflamatórias/metabolismo , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The regeneration of critical-sized bone defects with biomimetic scaffolds remains clinically challenging due to avascular necrosis, chronic inflammation, and altered osteogenic activity. Two confounding mechanisms, efficacy manipulation, and temporal regulation dictate the scaffold's bone regenerative ability. Equally critical is the priming of the mesenchymal stromal cells (MSCs) toward lineage-specific differentiation into bone-forming osteoblast, which particularly depends on varied mechanochemical and biological cues during bone tissue regeneration. This study sought to design and develop an optimized osteogenic scaffold, adenosine/epigallocatechin gallate-N,O-carboxymethyl chitosan/collagen type I (AD/EGCG-g-NOCC@clgn I), having osteoinductive components toward swift bone regeneration in a calvarial defect BALB/c mice model. The ex vivo findings distinctly establish the pro-osteogenic potential of adenosine and EGCG, stimulating MSCs toward osteoblast differentiation with significantly increased expression of alkaline phosphatase, calcium deposits, and enhanced osteocalcin expression. Moreover, the 3D matrix recapitulates extracellular matrix (ECM) properties, provides a favorable microenvironment, structural support against mechanical stress, and acts as a reservoir for sustained release of osteoinductive molecules for cell differentiation, proliferation, and migration during matrix osteointegration observed. Evidence from in vivo experiments, micro-CT analyses, histology, and histomorphometry signify accelerated osteogenesis both qualitatively and quantitatively: effectual bone union with enhanced bone formation and new ossified tissue in 4 mm sized defects. Our results suggest that the optimized scaffold serves as an adjuvant to guide bone tissue regeneration in critical-sized calvarial defects with promising therapeutic efficacy.
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Osteogênese , Alicerces Teciduais , Adenosina , Animais , Regeneração Óssea , Catequina/análogos & derivados , Diferenciação Celular , Quitosana , Colágeno , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Two bacterial species with the ability to produce biosurfactants were isolated from a pesticide contaminated soil and identified as Planococcus rifietoensis IITR53 and Planococcus halotolerans IITR55. Formation of froth indicating the surfactant production was observed when grown in basal salt medium containing 2% glucose. The culture supernatant after 72 h showed reduction in surface tension from 72 N/m to 46 and 42 N/m for strain IITR53 and IITR55 with emulsification index of 51 and 54% respectively. The biosurfactant identified as rhamnolipid based on liquid chromatography-mass spectrometry analysis, was found to inhibit the growth of both gram- positive and negative pathogenic bacteria. Both the rhamnolipids at 40 mg/mL exhibited the release of extracellular DNA and protein content. Also at one third of the MIC, a significant generation of reactive oxygen species was recorded. These rhamnolipids effectively emulsified different vegetable oils suggesting their possible utilization as antimicrobial agent.
Assuntos
Glicolipídeos , Planococcus (Bactéria) , Bactérias , Pseudomonas aeruginosa , TensoativosRESUMO
As the world is striving hard towards sustainable agricultural practices for a better tomorrow, one of the primary focuses is on effective pest management for enhanced crop productivity. Despite newer and potent chemicals as pesticides, there are still substantial crop losses, and if by any means this loss can be tackled; it will alleviate unwanted excessive use of chemical pesticides. Scientific surveys have already established that pesticides are not being utilized by the crops completely rather a significant amount remains unused due to various limiting factors such as leaching and bioconversion, etc., resulting in an adverse effect on human health and ecosystems. Concerted efforts from scientific diaspora toward newer and innovative strategies are already showing promise, and one such viable approach is controlled release systems (CRS) of pesticides. Moreover, to bring these smart formulations within the domain of current pesticide regulatory framework is still under debate. It is thus, paramount to discuss the pros and cons of this new technology vis-à-vis the conventional agrarian methods. This review deliberates on the developmental updates in this innovative field from the past decades and also appraises the challenges encumbered. Additionally, critical information and the foreseeable research gaps in this emerging area are highlighted.
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INTRODUCTION: An ideal wound dressing material needs to be predisposed with desirable attributes like anti-infective effect, skin hydration balance, adequate porosity and elasticity, high mechanical strength, low wound surface adherence, and enhanced tissue regeneration capability. In this work, we have synthesized hydrogel-based wound patches having antibacterial silver nanoparticles and antioxidant epigallocatechin gallate (EGCG) and showed fast wound closure through their synergistic interaction without any inherent toxicity. METHODS AND RESULTS: Wound patches were synthesized from modified guar gum polymer and assessed to determine accelerated wound healing. The modified polymer beget chemical-free in-situ synthesis of monodispersed silver NPs (~12 nm), an antimicrobial agent, besides lending ionic surface charges. EGCG impregnated during ionotropic gelation process amplified the efficacy of wound patches that possess apt tensile strength, porosity, and swellability for absorbing wound exudates. Further, in vitro studies endorsed them as non-cytotoxic and the post agent effect following exposure to the patch showed an unbiased response to E coli K12 and B. subtilis. In vivo study using sub-cutaneous wounds in Wistar rats validated its accelerated healing properties when compared to a commercially available wound dressing material (skin graft; Neuskin-F®) through better wound contraction, promoted collagen deposition and enhanced vascularization of wound region by modulating growth factors and inflammatory cytokines. CONCLUSION: Synthesized wound patches showed all the desired attributes of a clinically effective dressing material and the results were validated in various in vitro and in vivo assays.