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Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately â¼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.
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Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems.
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Sistemas de Liberação de Medicamentos , Inaladores de Pó Seco , Inaladores de Pó Seco/métodos , Humanos , Administração por Inalação , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Nanomedicina/métodos , Tamanho da Partícula , Nanotecnologia/métodosRESUMO
RATIONALE: Home mechanical ventilation (HMV) is an advanced medical therapy offered to children with medical complexity. Despite the growing pediatric HMV population in North America, there are limited studies describing healthcare utilization and predictors of highest costs using robust health administrative data. OBJECTIVES: To describe patterns of healthcare utilization and costs in children receiving HMV over a 14-year period in Ontario, Canada. METHODS: We conducted a retrospective population-based cohort study (April 1, 2003 to March 31, 2017) of children aged 0-18 years receiving HMV via invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV). Paired t-tests compared healthcare system utilization and costs two years before and two years after HMV approval. We developed linear models to analyze variables associated with children in the top quartile of health service utilization and costs. RESULTS: We identified 835 children receiving HMV. In the two years after HMV approval compared to the 2 years prior, children had decreased hospitalization days (median 9 (IQR 3-30) versus 29 (6-99), p<0.0001) and ICU admission days (6.6 (1.9-18.0) versus 17.1 (3.3-70.9), p<0.0001) but had increased homecare service approvals (195 (24-522) versus 40 (12-225), p<0.0001) and outpatient Pulmonology visits (3 (1-4) versus 2 (1-3), p<0.0001). Total healthcare costs were higher in the two years after HMV approval (mean $164,892 (SD $214,187) versus $128,941 ($194,199), p<0.0001). However, all-cause hospital admission costs were reduced ($66,546 ($142,401) versus $81,578 ($164,672), p<0.0001). Highest total 2-year costs were associated with IMV (OR 3.45, 95% CI 2.24-5.31; reference NIV), number of medical devices at home (OR 1.63, 95% CI 1.35-1.96; reference no technology), and increased healthcare costs in the year prior to HMV initiation (OR 2.23, 95% CI 1.84-2.69). CONCLUSIONS: Children progressing to the need for HMV represent a worsening in their respiratory status that will undoubtedly increase healthcare utilization and costs. We found that the initiation of HMV in these children can reduce inpatient healthcare utilization and costs but can still increase overall healthcare expenditures, especially in the outpatient setting.
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Dirac fermions, particles with zero rest mass, are observed in topological materials and are believed to play a key role in the exotic phenomena in fundamental science and the advancement of quantum technology. Most of the topological systems studied so far are weakly correlated systems and the study of their properties in the presence of electron correlation is an interesting emerging area of research, where the electron correlation is expected to enhance the effective mass of the particles. Here, we studied the properties of Dirac bands in a non-symmorphic layered Kondo lattice system, CeAgSb2, employing high-resolution angle-resolved photoemission spectroscopy and first-principles calculations. In addition to the Dirac cones due to non-symmorphic symmetry, this material hosts Dirac fermions in the squarenet layer in the proximity of a strongly correlated Ce layer exhibiting Kondo behavior. Experimental results reveal crossings of the highly dispersive linear bands at the Brillouin zone boundary due to non-symmorphic symmetry. In addition, there are anisotropic Dirac cones constituted by the squarenet Sb 5p states forming a diamond-shaped nodal line. These Dirac bands are linear in a wide energy range with an unusually high slope. Interestingly, near the local Ce 4f bands, these bands exhibit a change in the slope akin to the formation of a 'kink' observed in other materials due to electron-phonon coupling. The emergence of such exotic properties in proximity to strongly correlated electronic states has significant implications in the study of complex quantum materials including unconventional superconductors.
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Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtb-associated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.
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Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz , Mycobacterium tuberculosis , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Animais , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose/tratamento farmacológico , Progressão da DoençaRESUMO
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.
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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
Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer's disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.
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In this study, we report the preparation of bio-inspired binary CuO/ZnO nanocomposite (bb-CuO/ZnO nanocomposite) via the biological route using Bauhinia variegata flower extract following hydrothermal treatment. The prepared bb-CuO/ZnO nanocomposite was electrophoretically deposited (EPD) on indium tin oxide (ITO) substrate to develop bb-CuO/ZnO/ITO biosensing electrode which is employed for the determination of vitamin B2 (Riboflavin) through electrochemical techniques. Physicochemical assets of the prepared bb-CuO/ZnO nanocomposite have been extensively evaluated and make use of different characterization techniques including powder XRD, FT-IR, AFM, SEM, TEM, EDX, XPS, Raman, and TGA. Electrochemical characteristics of the bb-CuO/ZnO/ITO biosensing electrode have been studied towards vitamin B2 determination. Furthermore, different biosensing parameters such as response time, reusability, stability, interference, and real sample analysis were also estimated. From the linear plot of scan rate, charge transfer rate constant (Ks), surface concentration of electrode (γ), and diffusion coefficient (D) have been calculated, and these are found to be 6.56 × 10-1 s-1, 1.21 × 10-7 mol cm-2, and 6.99 × 10-3 cm2 s-1, respectively. This biosensor exhibits the linear range of vitamin B2 detection from 1 to 40 µM, including sensitivity and limit of detection (LOD) of 1.37 × 10-3 mA/µM cm2 and 0.254 µM, respectively. For higher concentration range detection linearity is 50-100 µM, with sensitivity and the LOD of 1.26 × 10-3 mA/µM cm2 and 0.145 µM, respectively. The results indicate that the bio-inspired nanomaterials are promising sustainable biosensing platforms for various food and health-based biosensing devices.
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Bauhinia , Técnicas Biossensoriais , Cobre , Técnicas Eletroquímicas , Flores , Nanocompostos , Extratos Vegetais , Riboflavina , Óxido de Zinco , Cobre/química , Cobre/análise , Extratos Vegetais/química , Nanocompostos/química , Técnicas Eletroquímicas/métodos , Flores/química , Técnicas Biossensoriais/métodos , Óxido de Zinco/química , Bauhinia/química , Riboflavina/análise , Riboflavina/química , Eletrodos , Limite de DetecçãoRESUMO
Patients with rheumatoid arthritis (RA) often have one or more painfuljoints despite adequate medicine. Local drug delivery to the synovial cavity bids for high drug concentration with minimal systemic adverse effects. However, anti-RA drugs show short half-lives in inflamed joints after intra-articular delivery. To improve the therapeutic efficacy, it is essential to ensure that a drug is only released from the formulation when it is needed. In this work, we developed an intelligent "Self-actuating" drug delivery system where Disease-modifying anti-rheumatic Drug (DMARD) methotrexate is incorporated within a matrix intended to be injected directly into joints. This formulation has the property to sense the need and release medication only when joints are inflamed in response to inflammatory enzyme Matrix metalloproteinases (MMP). These enzymes are important proteases in RA pathology, and several MMP are present in augmented levels in synovial fluid and tissues. A high level of MMP present in synovial tissues of RA patients would facilitate the release of drugs in response and ascertain controlled drug release. The formulation is designed to be stable within the joint environment, but to dis-assemble in response to inflammation. The synthesized enzyme-responsive methotrexate (Mtx) encapsulated micron-sized polymer-lipid hybrid hydrogel microspheres (Mtx-PLHM) was physiochemically characterized and tested in synovial fluid, Human Fibroblast like synoviocytes (h-FLS) (derived from RA patients) and a rat arthritic animal model. Mtx-PLHM can self-actuate and augment the release of Mtx drug upon contact with either exogenously added MMP or endogenous MMP present in the synovial fluid of patients with RA. The drug release from the prepared formulation is significantly amplified to several folds in the presence of MMP-2 and MMP-9 enzymes. In the rat arthritic model, Mtx-PLHM showed promising therapeutic results with the significant alleviation of RA symptoms through decrease in joint inflammation, swelling, bone erosion, and joint damage examined by X-ray analysis, histopathology and immune-histology. This drug delivery system would be nontoxic as it releases more drug only during the period of exacerbation of inflammation. This will simultaneously protect patients from unwanted side effects when the disease is inactive and lower the need for repeated joint injections.
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Antirreumáticos , Artrite Reumatoide , Preparações de Ação Retardada , Hidrogéis , Metotrexato , Microesferas , Sinoviócitos , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Humanos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Metotrexato/química , Metotrexato/administração & dosagem , Hidrogéis/química , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Ratos , Antirreumáticos/farmacologia , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacocinética , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Inflamação/tratamento farmacológico , Inflamação/patologia , Metaloproteinases da Matriz/metabolismo , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismoRESUMO
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.
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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.
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Mitochondrial morphology dynamics regulate signaling pathways during epithelial cell formation and differentiation. The mitochondrial fission protein Drp1 affects the appropriate activation of EGFR and Notch signaling-driven differentiation of posterior follicle cells in Drosophila oogenesis. The mechanisms by which Drp1 regulates epithelial polarity during differentiation are not known. In this study, we show that Drp1-depleted follicle cells are constricted in early stages and present in multiple layers at later stages with decreased levels of apical polarity protein aPKC. These defects are suppressed by additional depletion of mitochondrial fusion protein Opa1. Opa1 depletion leads to mitochondrial fragmentation and increased reactive oxygen species (ROS) in follicle cells. We find that increasing ROS by depleting the ROS scavengers, mitochondrial SOD2 and catalase also leads to mitochondrial fragmentation. Further, the loss of Opa1, SOD2 and catalase partially restores the defects in epithelial polarity and aPKC, along with EGFR and Notch signaling in Drp1-depleted follicle cells. Our results show a crucial interaction between mitochondrial morphology, ROS generation and epithelial cell polarity formation during the differentiation of follicle epithelial cells in Drosophila oogenesis.
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Drosophila , Dinâmica Mitocondrial , Animais , Drosophila/genética , Drosophila/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Dinâmica Mitocondrial/genética , Catalase , Receptores ErbB/genética , Receptores ErbB/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
Insulin resistance (IR) is the key pathophysiological cause of type 2 diabetes, and inflammation has been implicated in it. The death domain (DD) of the adaptor protein, MyD88 plays a crucial role in the transduction of TLR4-associated inflammatory signal. Herein, we have identified a 10-residue peptide (M10), from the DD of MyD88 which seems to be involved in Myddosome formation. We hypothesized that M10 could inhibit MyD88-dependent TLR4-signaling and might have effects on inflammation-associated IR. Intriguingly, 10-mer M10 showed oligomeric nature and reversible self-assembly property indicating the peptide's ability to recognize its own amino acid sequence. M10 inhibited LPS-induced nuclear translocation of NF-κB in L6 myotubes and also reduced LPS-induced IL-6 and TNF-α production in peritoneal macrophages of BALB/c mice. Remarkably, M10 inhibited IL-6 and TNF-α secretion in diabetic, db/db mice. Notably, M10 abrogated IR in insulin-resistant L6 myotubes, which was associated with an increase in glucose uptake and a decrease in Ser307-phosphorylation of IRS1, TNF-α-induced JNK activation and nuclear translocation of NF-κB in these cells. Alternate day dosing with M10 (10 and 20â mg/kg) for 30 days in db/db mice significantly lowered blood glucose and improved glucose intolerance after loading, 3.0 g/kg glucose orally. Furthermore, M10 increased insulin and adiponectin secretion in db/db mice. M10-induced glucose uptake in L6 myotubes involved the activation of PI3K/AKT/GLUT4 pathways. A scrambled M10-analog was mostly inactive. Overall, the results show the identification of a 10-mer peptide from the DD of MyD88 with anti-inflammatory and anti-diabetic properties, suggesting that targeting of TLR4-inflammatory pathway, could lead to the discovery of molecules against IR and diabetes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Glicemia , Domínio de Morte , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/tratamento farmacológico , Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The advent of drug resistance in response to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI) targeted therapy represents a serious challenge in the management of non-small cell lung cancer (NSCLC). These acquired resistance mutations, attributed to several advanced EGFR mutations and, necessitated the development of new-generation TKIs. Nanomedicine approaches provide a plausible way to address these problems by providing targeted delivery and sustained release, which have demonstrated success in preclinical trials. This review article provides a summary of nano-formulations designed for EGFR-TKI-resistant NSCLC, highlighting their efficacy in both in vitro and in vivo models. These findings reveal insights into the design of nanoparticles and multifunctional nanosystems, offering a potential avenue for efficacious treatment of EGFR-TKIresistant NSCLC.
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A propitious biosensor for adrenaline (AD) detection in bovine serum albumin (BSA) real samples, which can be used for diagnosis and treatment of neurodegenerative disorders, is reported here. The biosensor consists of a La/ZF/rGO/ITO bioelectrode, which is fabricated by electrophoretic deposition of zinc ferrite/reduced graphene oxide (ZF/rGO) nanohybrid followed by drop casting of laccase (La) enzymes. The material characterization and electrochemical studies revealed that the ZF/rGO nanohybrid enhanced the electroactive surface and facilitated direct electron transfer between the electrode and electrolyte interface, resulting in enhanced electrocatalytic performance. The cyclic voltammetry and electrochemical impedance spectroscopy results asserted that the ZF/rGO nanohybrid decreased the charge-transfer resistance (Rct) and increased the surface adsorption, leading to a high diffusion coefficient (D) of 0.192 cm2/s. The biosensor exhibited a high sensitivity of 0.71 Ω/µM cm2, a good linear range (0.1 to 140 µM with R2 = 0.98), and a low limit of detection (LOD) is 12.5 µM, demonstrating the synergic effect of ZF and rGO in the La/ZF/rGO/ITO bioelectrode with AD. The biosensor also exhibited high selectivity and stability (55 days) in the presence of interfering substances and in BSA samples, with a recovery percentage close to 100 ± 5% RSD, indicating its potential biosensing applications for real-world applications in disease diagnostics, monitoring, and treatment.
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Técnicas Biossensoriais , Doenças Neurodegenerativas , Humanos , Lacase , Técnicas Eletroquímicas/métodos , Epinefrina , Impedância Elétrica , Técnicas Biossensoriais/métodos , EletrodosRESUMO
BACKGROUND OBJECTIVES: The seroprevalence of the hepatitis C virus (HCV) in general population is higher than that of human immunodeficiency virus (HIV) in India. People who inject drugs (PWIDs) constitute a high-risk group for all blood-borne infections. Multiple behavioural surveillance surveys have provided a rich typology of HIV-infected PWIDs, but this information is missing for HCV infection. We describe awareness, transmission risk factors and the treatment continuum for HCV infection among PWID. We also report spatial clustering of HCV infection in PWIDs residing in Bengaluru. METHODS: Information from clinical records was collected and telephonic interviews of retrospectively identified PWIDs who received treatment at a tertiary-level addiction treatment facility between 2016 and 2021 were conducted. RESULTS: We identified 391 PWIDs; 220 (56.26%) received an anti-HCV antibody test (4 th Generation HCV-Tridot). Individuals reporting unsafe injection practices were more often tested than those who did not ( χ2 =44.9, df=1, P <0.01). Almost half of the tested and more than a quarter of the whole sample (109/220, 49.9%; 109/391, 27.9%) were seropositive for HCV infection. The projected seropositivity in this group was between 27.9 per cent (best case scenario, all untested assumed negative) and 71.6 per cent (worst case scenario, all untested assumed positive). Only a minority of participants interviewed were aware of HCV (27/183, 14.7%). HCV infection and its associated risk behaviour (PWID) were clustered in certain localities (Diggle and Chetwynd Test; P =0.001) in Bengaluru in the southern district of Karnataka. INTERPRETATION CONCLUSIONS: Undetected HCV infection is common in PWIDs; awareness and treatment uptake is poor in this group. Spatial clustering of infections in a district shows transmission in close networks and provides opportunities for targeted interventions.
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Usuários de Drogas , Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Hepacivirus , Abuso de Substâncias por Via Intravenosa/epidemiologia , Infecções por HIV/epidemiologia , Estudos Soroepidemiológicos , Estudos Retrospectivos , Índia/epidemiologia , Hepatite C/epidemiologia , HIV , PrevalênciaRESUMO
Purpose: Neonatal skin care practices guided by personal experience and preferences might be substantially different across different hospital settings. The aim of this consensus recommendation is to provide clinical practice guidance to healthcare practitioners on evidence-based neonatal skin care practices from delivery-to-discharge, in hospital settings. Patients and Methods: A Scientific Advisory Board meeting on "Evidence-based Neonatal Skin Care Practices and Protocols" was held in December 2020 with an expert panel comprising neonatologists, pediatricians, obstetricians and gynecologists and pediatric dermatologist. Comprehensive literature search was performed up to 23 March 2021 using PubMed and Google Scholar to retrieve relevant evidence. Results: Recommendations were developed on critical aspects of skin care in healthy full-term neonates including cleansing at birth, skin-to-skin care, cord care, diaper area care, initial and routine bathing, cleansers and emollients use, and criteria to choose appropriate skin care products. Recommendations include inclusion of skin assessment in routine neonatal care, first bath timing after cardio-respiratory and thermal stabilization, 6-24 hours after birth; bathing with water alone or adding a mild liquid cleanser could be considered appropriate as it does not impact the developing skin barrier; use of emollients is recommended for neonates with higher risk of development of eczema to maintain and enhance skin barrier function and integrity; and inclusion of skin care advice in neonatal discharge checklist. Importance of rigorous quality control, high-quality clinical trials for assessment of baby products, usage of products that are formulated appropriately for newborns, and full label transparency for baby products were highlighted. The panel identified gaps in literature and discussed the scope for future research. Conclusion: These recommendations may help to standardize evidence-based skin care for healthy full-term neonates in Indian hospital settings to improve the quality of care that neonates receive in hospital and facilitate improvement in overall neonatal health outcomes.
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The rise of tuberculosis (TB) superbugs has impeded efforts to control this infectious ailment, and new treatment options are few. Paradoxical Inflammation (PI) is another major problem associated with current anti-TB therapy, which can complicate the treatment and leads to clinical worsening of disease despite a decrease in bacterial burden in the lungs. TB infection is generally accompanied by an intense local inflammatory response which may be critical to TB pathogenesis. Clofazimine (CLF), a second-line anti-TB drug, delineated potential anti-mycobacterial effects in-vitro and in-vivo and also demonstrated anti-inflammatory potential in in-vitro experiments. However, clinical implications may be restricted owing to poor solubility and low bioavailability rendering a suboptimal drug concentration in the target organ. To unravel these issues, nanocrystals of CLF (CLF-NC) were prepared using a microfluidizer® technology, which was further processed into micro-sized CLF nano-clusters (CLF-NCLs) by spray drying technique. This particle engineering offers combined advantages of micron- and nano-scale particles where micron-size (â¼5 µm) promise optimum aerodynamic parameters for the finest lung deposition, and nano-scale dimensions (â¼600 nm) improve the dissolution profile of apparently insoluble clofazimine. An inhalable formulation was evaluated against virulent mycobacterium tuberculosis in in-vitro studies and in mice infected with aerosol TB infection. CLF-NCLs resulted in the significant killing of virulent TB bacteria with a MIC value of â¼0.62 µg/mL, as demonstrated by Resazurin microtiter assay (REMA). In TB-infected mice, inhaled doses of CLF-NCLs equivalent to â¼300 µg and â¼ 600 µg of CLF administered on every alternate day over 30 days significantly reduced the number of bacteria in the lung. With an inhaled dose of â¼600 µg/mice, reduction of mycobacterial colony forming units (CFU) was achieved by â¼1.95 Log10CFU times compared to CLF administered via oral gavage (â¼1.18 Log10CFU). Lung histology scoring showed improved pathogenesis and inflammation in infected animals after 30 days of inhalation dosing of CLF-NCLs. The levels of pro-inflammatory mediators, including cytokines, TNF-α & IL-6, and MMP-2 in bronchoalveolar lavage fluid (BAL-F) and lung tissue homogenates, were attenuated after inhalation treatment. These pre-clinical data suggest inhalable CLF-NCLs are well tolerated, show significant anti-TB activity and apparently able to tackle the challenge of paradoxical chronic lung inflammation in murine TB model.
Assuntos
Pneumonia , Tuberculose , Camundongos , Animais , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Aerossóis e Gotículas Respiratórios , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Pneumonia/tratamento farmacológico , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Drought stress is a major constraint for rice production worldwide. Reproductive stage drought stress (RSDS) leads to heavy yield losses in rice. The prospecting of new donor cultivars for identification and introgression of QTLs of major effect (Quantitative trait locus) for drought tolerance is crucial for the development of drought-resilient rice varieties. METHODS AND RESULTS: Our study aimed to map QTLs associated with yield and its related traits under RSDS conditions. A saturated linkage map was constructed using 3417 GBS (Genotyping by sequencing) derived SNP (Single nucleotide polymorphism) markers spanning 1924.136 cM map length with an average marker density of 0.56 cM, in the F3 mapping population raised via cross made between the traditional ahu rice cultivar, Koniahu (drought tolerant) and a high-yielding variety, Disang (drought susceptible). Using the Inclusive composite interval mapping approach, 35 genomic regions governing yield and related traits were identified in pooled data from 198 F3 and F4 segregating lines evaluated for two consecutive seasons under both RSDS and irrigated control conditions. Of the 35 QTLs, 23 QTLs were identified under RSDS with LOD (Logarithm of odds) values ranging between 2.50 and 7.83 and PVE (phenotypic variance explained) values of 2.95-12.42%. Two major QTLs were found to be linked to plant height (qPH1.29) and number of filled grains per panicle (qNOG5.12) under RSDS. Five putative QTLs for grain yield namely, qGY2.00, qGY5.05, qGY6.16, qGY9.19, and qGY10.20 were identified within drought conditions. Fourteen QTL regions having ≤ 10 Mb QTL interval size were further analysed for candidate gene identification and a total of 4146 genes were detected out of these 2263 (54.63%) genes were annotated to at least one gene ontology (GO) term. CONCLUSION: Several QTLs associated with grain yield and yield components and putative candidate genes were identified. The putative QTLs and candidate genes identified could be employed to augment drought resilience in rice after further validation through MAS strategies.