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The extensive utilization of bismuth and its derivatives in many industries, such as chemical, semiconductor, pharmaceutical, and cosmetics, leads to their accumulation in wastewater, posing a risk to both human health and the environment. Carbon nanorods (CNR) are fluorescent nanoparticles with an ability to detect various analytes as sensing probes. This study focuses on the production, structure, and chemical composition characterization of silkworm-derived CNR (swCNR) and their ability to detect bismuth ions (Bi3+) and inhibit radicals. The optimum wavelength for exciting the fluorescence of swCNR was 370 nm, and the resulting emission peak was observed at 436 nm. The prepared swCNR showed static fluorescence quenching mechanism-based sensing of Bi3+ ions with a limit of detection of 175 nM and two linear ranges from 0.5 to 5 µM (R2 = 0.9997) and 10-50 µM (R2 = 0.9995). The swCNR demonstrated high selectivity in detecting Bi3+ ions in the spiked river water samples, thus establishing the swCNR's role as a nano fluorescence probe designed for the selective detection of Bi3+ ions among other metal ions. Favorable results for the antiradical ability of swCNR were obtained against hydroxyl, 2,2 diphenyl-1 picrylhydrazyl, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with scavenging percentages of 15, 32, and 90, respectively. The possible applications of swCNR in the environmental and antioxidant sectors are proposed in this study.
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Rhinocerebralmucormycosis, is a progressive fungal invasion of a hard palate, paranasal sinuses, orbit, and brain. Post covid the huge number of mucor cases reported in our institute. To combat them a uniform assessment scale was needed as multiple healthcare workers were involved. Thus, a novel linear grading system on nasal endoscopy was developed for the early management of patients to prevent morbidity and mortality. A Prospective study of 650 patients in Epidemic duration from April to June 2021 in a tertiary health center, Central India. Patients subjected to Nasal Endoscopy with 0degree 4 mm Telescope and classified into 5 categories according to the severity of the disease. In a novel grading system, minimum patients were of grade 0, maximum was in Grade I. Maxillary sinus was most commonly involved. This novel grading system on nasal endoscopy makes the management of patients much easier in an epidemic, reducing human errors, morbidity, and mortality of the fulminant disease.
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Macroalgae, particularly red seaweeds, have attracted significant attention due to their economic and health benefits. Chondrus, a red algae genus, despite its economic importance, seems to be undervalued. Among all its species, Chondrus crispus has been meticulously documented for its biological properties, and little is known about other species. No comprehensive review of the biological properties of this genus has been acknowledged. Thus, this review aimed to summarize the available information on the chemical constituents and biological properties of a few selected species, including Chondrus crispus, Chondrus ocellatus, Mazzaella canaliculata, and Chondrus armatus. We compiled and discovered that the genus is offering most of the important health-promoting benefits evidenced from in vitro and in vivo studies focused on antimicrobial, immunomodulation, neuroprotection, anti-atopic, anti-inflammatory, anti-viral, anti-diabetic, cytoprotective, antioxidant, anti-coagulation, nephroprotective, anti-tumor, and anti-venom activity, which speaks about the potential of this genus. Data on clinical studies are limited. Further, around 105 chemical constituents have been reported from Chondrus spp. Given its significance, further investigation is warranted, in the form of meticulously planned cell, animal, and clinical studies that concentrate on novel health-enhancing endeavors, in order to unveil the full potential of this genus. The review also outlines challenges and future directions.
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Chondrus , Hipersensibilidad Inmediata , Algas Marinas , Animales , Antioxidantes/farmacología , AntivenenosRESUMEN
PURPOSE: The aim of this study was to directly evaluate glucose, amino-acid and membrane metabolism in tumor cells for diagnosis and prognostication of recurrent gliomas. METHODS: Fifty-five patients (median age = 36 years; 33 men) with histologically proven gliomas and suspected recurrence were prospectively recruited and underwent 18F-FDG (Fluorodeoxyglucose), 18F-FDOPA (fluorodopa) and 18F-Fluorocholine-PET/CT. Images were evaluated by two physicians visually and quantitatively [lesion-SUVmax, tumor (T) to gray-matter (G) and metabolically-active tumor volumes (MTV)]. After median follow-up of 51.5 months, recurrence was diagnosed in 49 patients. Thirty-one patients died with a median survival of 14 months. RESULTS: Diagnostic-accuracies for 18F-FDOPA, 18F-Fluorocholine,18F-FDG and contrast-enhanced-MRI were 92.7% (95% CI 82.7-97.1), 81.8% (69.7-89.8), 45.5% (33.0-58.5) and 44.7% (30.2-60.3), respectively. Among the 20 lesions, missed by MRI; 18F-FDOPA, 18F-Fluorocholine and 18F-FDG were able to detect 19, 14 and 4 lesions. Corresponding area-under-the-curves (T/G ratios) were 0.817 (0.615-1.000), 0.850 (0.736-0.963) and 0.814 (0.658-0.969), when differentiating recurrence from treatment-induced changes. In univariate-survival-analysis, 18F-FDOPA-T/G, visually detectable recurrence in 18F-FDG, 18F-FDOPA-MTV, cell-lineage and treatment-type were significant parameters. In Multivariate-Cox-regression analysis, 18F-FDOPA-MTV [HRâ =â 1.009 (1.001-1.017); P â =â 0.024 (~0.9% increase in hazard for every mL increase of MTV)] and cell-lineage [3.578 (1.447-8.846); P â =â 0.006] remained significant. 18F-FDOPA-MTV cutoff <29.59â mL predicted survival higher than 2 years. At cutoff ≥29.59â mL, HR at 2 years was 2.759 (1.310-5.810). CONCLUSION: 18F-FDOPA-PET/CT can diagnose recurrence with high accuracy and MTV predicts survival. 18F-Fluorocholine is a good alternative. Higher 18F-FDG uptake is an adverse prognostic indicator.
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Glioma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Masculino , Humanos , Adulto , Fluorodesoxiglucosa F18 , Recurrencia Local de Neoplasia/diagnóstico por imagen , Glioma/diagnóstico por imagen , Pronóstico , Estudios Retrospectivos , Radiofármacos , Carga TumoralRESUMEN
Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for ~10-20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2-targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range of patients, and the emerging resistance further adds to the difficulties. Furthermore, TNBC exhibits a higher mutational burden and is acknowledged as the most immunogenic of all BC subtypes. Consequently, the application of immune checkpoint inhibition has been investigated in TNBC, yielding promising outcomes. Recent evidence identified extracellular vesicles (EVs) as an important contributor in the context of TNBC immunotherapy. In view of the extraordinary ability of EVs to transfer bioactive molecules, such as proteins, lipids, DNA, mRNAs, and small miRNAs, between the cells, EVs are considered a promising diagnostic biomarker and novel drug delivery system among the prospects for immunotherapy. The present review provides an in-depth understanding of how EVs influence TNBC progression, its immune regulation, and their contribution as a predictive biomarker for TNBC. The final part of the review focuses on the recent key advances in immunotherapeutic strategies for better understanding the complex interplay between EVs and the immune system in TNBC and further developing EV-based targeted immunotherapies.
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OBJECTIVE: We compared diagnostic quality of 68 Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. MATERIAL AND METHODS: A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68 Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68 Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. RESULTS: Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points ( P â >â 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P â <â 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P â =â 0.002). CONCLUSION: The simultaneous furosemide and 68 Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.
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Carcinoma , Neoplasias de la Próstata , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Furosemida , Estudios Retrospectivos , Radioisótopos de Galio , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Diuresis , Ácido EdéticoRESUMEN
The anti-obesity effect of milk intake has been suggested via a variety of designed studies, but findings of obesity interventions for Korean adults are scarcely reported. The study aimed to investigate the anti-obesity effect of cow milk in Korean adults with an 8-wk randomized intervention. A total of 121 adults overweight aged 19 to 60 yr old were randomly assigned to 1 of the 2 groups: milk or control. During the intervention, both groups were encouraged 500 kcal of restriction a day, and the milk group consumed 200 mL of milk twice a day; the same energy intake as the control group, including milk intake, was recommended for 8 wk. We detected no significant differences in body weight (BW) and body mass index (BMI) between the milk and control groups during the 8-wk intervention, although the changes in BW and BMI of those within the milk group were significant. High-density lipoprotein cholesterol levels and serum calcium levels increased significantly in the milk group compared with the control group. Calcium, phosphorus, vitamin A, and riboflavin intakes increased significantly, when compared with the control. In conclusion, 8-wk milk consumption had no effect on weight loss and BMI change but improved some blood biomarkers and nutrient intake in Korean adults who were overweight. To evaluate the effect of milk on obesity reduction, well-designed, long-term, and large-scale studies are needed.
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Enfermedades de los Bovinos , Sobrepeso , Femenino , Bovinos , Animales , Sobrepeso/veterinaria , Leche , Calcio , Obesidad/veterinaria , Peso Corporal , Índice de Masa Corporal , Ingestión de Energía , República de CoreaRESUMEN
Breast cancer is a devastating disease that affects women worldwide, and computer-aided algorithms have shown potential in automating cancer diagnosis. Recently Generative Artificial Intelligence (GenAI) opens new possibilities for addressing the challenges of labeled data scarcity and accurate prediction in critical applications. However, a lack of diversity, as well as unrealistic and unreliable data, have a detrimental impact on performance. Therefore, this study proposes an augmentation scheme to address the scarcity of labeled data and data imbalance in medical datasets. This approach integrates the concepts of the Gaussian-Laplacian pyramid and pyramid blending with similarity measures. In order to maintain the structural properties of images and capture inter-variability of patient images of the same category similarity-metric-based intermixing has been introduced. It helps to maintain the overall quality and integrity of the dataset. Subsequently, deep learning approach with significant modification, that leverages transfer learning through the usage of concatenated pre-trained models is applied to classify breast cancer histopathological images. The effectiveness of the proposal, including the impact of data augmentation, is demonstrated through a detailed analysis of three different medical datasets, showing significant performance improvement over baseline models. The proposal has the potential to contribute to the development of more accurate and reliable approach for breast cancer diagnosis.
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Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell-cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.
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INTRODUCTION: Heterogeneous and nonspecific symptoms make invasive endometriosis a difficult entity to diagnose. Small lesions with absent associated changes can be easily missed in cross-sectional imaging. Even when the lesions satisfy the thresholds for various investigations, their appearance changes with cyclical fluctuations in the hormonal levels. Therefore, newer approaches are needed to achieve correct diagnosis. METHODS: Six females in reproductive age group (mean age = 32.5â ±â 4.3 years) were retrospectively selected, wherein the diagnosis of invasive endometriosis was confirmed after 18F-FDG-PET/CT. Indications for PET/CT were staging in 4 patients, suspected progression in 1 and suspected inflammatory bowel disease in one patient. The study was repeated in proliferative phase in two patients and in the menstrual phase in another patient. FNAC was available in two patients and a drop in CA125 was documented in the last patient. RESULTS: In five patients metabolically active lesions were seen in PET/CT and in the last, activity was absent despite symptoms. Repeat menstrual phase imaging in the last patient confirmed the diagnosis. In two patients with metabolically active lesions at baseline, resolution was seen in proliferative phase PET/CT. In the other two patients, repeat study was not indicated as FNAC revealed normal endometrial tissue and in the last patient, significant drop in CA125 was documented after just 2 weeks. In all of these patients, the final diagnosis was of invasive endometriosis. CONCLUSION: In reproductive-age women, PET/CT acquisition should be optimized in the context of menstrual cycle. This approach can be used to non-invasively rule in/rule out endometriosis, especially with repeat imaging in proper menstrual phase.
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Endometriosis , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Femenino , Adulto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Endometriosis/diagnóstico por imagen , Diagnóstico Erróneo , Estudios Retrospectivos , Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18RESUMEN
In the current study, synthesis and use of a novel adsorbent (composite in nature) are presented for treatment of one of the most commonly found pharmaceutical compound, viz, diclofenac sodium (DCF) in waste water. Synthesis of the composite adsorbent was done by hydrothermal method metal organic framework (MOF) based on Zr metal and multi-walled carbon nanotube (MWCNT). The composite adsorbent is termed as UiO-66/MWCNT. The confirmation of successful synthesis of the adsorbent is done with the help of sophisticated characterization techniques like FTIR, XRD, zeta potential analyser, and SEM. The synthesized composite adsorbent is found to have good adsorption capacity for DCF. The experiments related to the process of adsorption were done in batch mode and the significance of various operating parameters affecting the specific uptake of DCF. Maximum adsorption is observed at 3 pH (acidic condition) when the initial concentration of DCF and adsorbent dose was 30 mg/L and 100 mg/L, respectively. The Langmuir isotherm model best describes the process of adsorption with a maximum adsorption capacity of 256.41 mg/g. Experimental results obtained through the studies conducted related to the kinetics displayed that the process followed pseudo-second order model, and intraparticle studies suggested that diffusion through pores controls the rate. Thermodynamic studies suggest that the adsorption of DCF on UiO-66/MWCNT was completely spontaneous with ΔH = -22.089 kJ/mol. The possible mechanism for the adsorptive removal of DCF through UiO-66/MWCNT as found from this study is electrostatic interaction.
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In recent decades, several studies demonstrating various applications of carbon dots (C-dots), including metal sensing, bioimaging, pH sensing, and antimicrobial activities, have been published. Recent developments have shifted this trend toward biomedical applications that target various biomarkers relevant to chronic diseases. However, relevant developments and research results regarding the anti-inflammatory properties of C-dots against inflammation-associated diseases have not been systematically reviewed. Hence, this review discusses the anti-inflammatory effects of C-dots in in vivo and in vitro models of LPS-induced inflammation, gout, cartilage tissue engineering, drug-induced inflammation, spinal cord injury, wound healing, liver diseases, stomach cancer, gastric ulcers, acute kidney and lung injury, psoriasis, fever or hypothermia, and bone tissue regeneration. The compiled studies demonstrate the promising potential of C-dots as anti-inflammatory agents for the development of new drugs.
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Carbono , Úlcera Gástrica , Humanos , Carbono/uso terapéutico , Carbono/química , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
Chronic Rhinosinusitis (CRS) is a common health problem with an estimated prevalence of 6.8% in Asia. The treatment of CRS involves an initial course of maximal medical therapy followed by Functional Endoscopic Sinus Surgery (FESS). Here, we are assessing the outcomes of FESS on CRS using most recent Sino Nasal Outcome Test (SNOT-22) questionnaire, for quantifying changes in symptoms and predicting extent of postoperative improvement. 75 patients who reported in the tertiary health care centre in Department of ENT, MGM Medical College & M.Y. Hospital, Indore and were diagnosed with CRS that did not relieve on medication were selected on the basis of inclusion and exclusion criteria. The selected cases were asked to answer the SNOT-22 questionnaire before the surgery. FESS was done and after three months, the patients were again subjected to the SNOT-22 questionnaire. There was 83.67% overall improvement in postsurgical SNOT-22 evaluations, which was statistically significant (p value < 0.00001). Most common SNOT-22 symptom was the need to blow nose, which was seen in 28 (93.34%) cases, while ear pain was found in 10 (50%) patients and was the least common SNOT-22 symptom. FESS seems to be effective treatment of CRS patients. We observed SNOT-22 to be very effective and reliable in assessing the Quality of Life in CRS patients and to measure the improvement after FESS.
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Rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) poses enormous challenge in the development of broad-spectrum antivirals that are effective against the existing and emerging viral strains. Virus entry through endocytosis represents an attractive target for drug development, as inhibition of this early infection step should block downstream infection processes, and potentially inhibit viruses sharing the same entry route. In this study, we report the identification of 1,3-diphenylurea (DPU) derivatives (DPUDs) as a new class of endocytosis inhibitors, which broadly restricted entry and replication of several SARS-CoV-2 and IAV strains. Importantly, the DPUDs did not induce any significant cytotoxicity at concentrations effective against the viral infections. Examining the uptake of cargoes specific to different endocytic pathways, we found that DPUDs majorly affected clathrin-mediated endocytosis, which both SARS-CoV-2 and IAV utilize for cellular entry. In the DPUD-treated cells, although virus binding on the cell surface was unaffected, internalization of both the viruses was drastically reduced. Since compounds similar to the DPUDs were previously reported to transport anions including chloride (Cl-) across lipid membrane and since intracellular Cl- concentration plays a critical role in regulating vesicular trafficking, we hypothesized that the observed defect in endocytosis by the DPUDs could be due to altered Cl- gradient across the cell membrane. Using in vitro assays we demonstrated that the DPUDs transported Cl- into the cell and led to intracellular Cl- accumulation, which possibly affected the endocytic machinery by perturbing intracellular Cl- homeostasis. Finally, we tested the DPUDs in mice challenged with IAV and mouse-adapted SARS-CoV-2 (MA 10). Treatment of the infected mice with the DPUDs led to remarkable body weight recovery, improved survival and significantly reduced lung viral load, highlighting their potential for development as broad-spectrum antivirals.
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COVID-19 , Virus de la Influenza A , Animales , Ratones , SARS-CoV-2 , Virus de la Influenza A/fisiología , Endocitosis , Internalización del Virus , Antivirales/farmacología , Antivirales/químicaRESUMEN
Overweight and obesity are significant global public health concerns that are increasing in prevalence at an alarming rate. Numerous studies have demonstrated the benefits of probiotics against obesity. Postbiotics are the next generation of probiotics that include bacteria-free extracts and nonviable microorganisms that may be advantageous to the host and are being increasingly preferred over regular probiotics. However, the impact of postbiotics on obesity has not been thoroughly investigated. Therefore, the goal of this review is to gather in-depth data on the ability of postbiotics to combat obesity. Postbiotics have been reported to have significant potential in alleviating obesity. This review comprehensively discusses the anti-obesity effects of postbiotics in cellular, animal, and clinical studies. Postbiotics exert anti-obesity effects via multiple mechanisms, with the major mechanisms including increased energy expenditure, reduced adipogenesis and adipocyte differentiation, suppression of food intake, inhibition of lipid absorption, regulation of lipid metabolism, and regulation of gut dysbiosis. Future research should include further in-depth studies on strain identification, scale-up of postbiotics, identification of underlying mechanisms, and well-defined clinical studies. Postbiotics could be a promising dietary intervention for the prevention and management of obesity.
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Obesidad , Probióticos , Animales , Obesidad/prevención & control , Sobrepeso , Adipogénesis , Diferenciación Celular , Probióticos/uso terapéutico , PercepciónRESUMEN
Silver nanoparticles (AgNPs) have inconsistent findings against inflammation. Although a wealth of literature on the beneficial effects of green-synthesized AgNPs has been published, a detailed mechanistic study of green AgNPs on the protective effects against lipopolysaccharide (LPS)-induced neuroinflammation using human microglial cells (HMC3) has not yet been reported. For the first time, we studied the inhibitory effect of biogenic AgNPs on inflammation and oxidative stress induced by LPS in HMC3 cells. X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and transmission electron microscopy were used to characterize AgNPs produced from honeyberry. Co-treatment with AgNPs significantly reduced mRNA expressions of inflammatory molecules such as interleukin (IL)-6 and tumor necrosis factor-α, while increasing the expressions of anti-inflammatory markers such as IL-10 and transforming growth factor (TGF)-ß. HMC3 cells were also switched from M1 to M2, as shown by lower expression of M1 markers such as cluster of differentiation (CD)80, CD86, and CD68 and higher expression of M2 markers such as CD206, CD163, and triggering receptors expressed on myeloid cells (TREM2). Furthermore, AgNPs inhibited LPS-induced toll-like receptor (TLR)4 signaling, as evidenced by decreased expression of myeloid differentiation factor 88 (MyD88) and TLR4. In addition, AgNPs reduced the production of reactive oxygen species (ROS) and enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while decreasing the expression of inducible nitric oxide synthase. The docking score of the honeyberry phytoconstituents ranged from -14.93 to - 4.28 KJ/mol. In conclusion, biogenic AgNPs protect against neuroinflammation and oxidative stress by targeting TLR4/MyD88 and Nrf2/HO-1 signaling pathways in a LPS-induced in vitro model. Biogenic AgNPs could be utilized as potential nanomedicine against LPS-induced inflammatory disorders.
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Lipopolisacáridos , Nanopartículas del Metal , Humanos , Lipopolisacáridos/toxicidad , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Simulación del Acoplamiento Molecular , Plata/farmacología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , Enfermedades Neuroinflamatorias , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/farmacología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Nanopartículas del Metal/uso terapéutico , Transducción de Señal , Fenotipo , Línea Celular , Inflamación/inducido químicamente , Inflamación/metabolismo , Encéfalo/metabolismoRESUMEN
PURPOSE: PACG is one of the leading causes of blindness where lens thickness is a major risk factor for narrow-angle individuals. To our knowledge, no literature has been reported on candidate gene for lens thickness as a quantitative trait (QT). Here, we performed a genome-wide association analysis on lens thickness in the narrow-angle individuals. MATERIALS AND METHODS: We conducted a genome-wide association study (GWAS) in the narrow angle individuals to investigate comprehensive genetic insights on lens thickness. RESULTS: In QT-GWAS, we identified 145 genome-wide suggestive significant loci in the discovery cohort. Subsequently, we observed 13 SNPs that showed statistical significance around the region of PTRRM. Regional association analysis for top significant genotyped variants identified PTPRM as the most likely candidate for increased LT. Integrative bioinformatic analyses confirmed that the associated genomic region has potential regulatory roles for modulating transcription as enhancers. In the replication cohort, the sentinel genotype SNP was further associated significantly (P-value =0.000448) with high LT individuals. In both cohorts, the T allele of rs1941137 in the PTPRM gene indicates as a risk allele for the increased LT. CONCLUSION: In this study, we discovered evidence of a genomic association between chromosomal areas around the PTPRM and increased lens thickness, resulting in a narrow angle. The regulatory components corresponding to PTPRM variations might have a role in the thicker lens. We report that the genomic region near PTPRM, a gene of potential interest, is associated with increased lens thickness.
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Oftalmopatías , Estudio de Asociación del Genoma Completo , Humanos , Estudio de Asociación del Genoma Completo/métodos , Predisposición Genética a la Enfermedad , Fenotipo , Genotipo , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genéticaRESUMEN
AIM: This study was aimed to determine antimicrobial and antiviral activity of a novel lanthipeptide from a Brevibacillus sp. for disinfectant application. METHODS AND RESULTS: The antimicrobial peptide (AMP) was produced by a bacterial strain AF8 identified as a member of the genus Brevibacillus representing a novel species. Whole genome sequence analysis using BAGEL identified a putative complete biosynthetic gene cluster involved in lanthipeptide synthesis. The deduced amino acid sequence of lanthipeptide named as brevicillin, showed >30% similarity with epidermin. Mass determined by MALDI-MS and Q-TOF suggested posttranslational modifications like dehydration of all Ser and Thr amino acids to yield Dha and Dhb, respectively. Amino acid composition determined upon acid hydrolysis is in agreement with core peptide sequence deduced from the putative biosynthetic gene bvrAF8. Biochemical evidence along with stability features ascertained posttranslational modifications during formation of the core peptide. The peptide showed strong activity with 99% killing of pathogens at 12 µg ml-1 within 1 minute. Interestingly, it also showed potent anti-SARS-CoV-2 activity by inhibiting â¼99% virus growth at 10 µg ml-1 in cell culture-based assay. Brevicillin did not show dermal allergic reactions in BALB/c mice. CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.