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Solid mutant induction using specialized habituation and PBR (Plant bio-regulator) autotrophy-mediated suspension-based ISE system was the prime aim of present investigation. Based on survival of cell clumps after mutagen treatment, the probit analysis was calculated. The result revealed LD50 at 54.31 Gy in gamma, while for EMS (ethyl methanesulfonate), it was 0.1% for 3 h and 0.5% for 1 h. Based on embryogenesis efficiency, a dose rate of 100 Gy and 0.1% EMS for a 3-h exposure were selected for regeneration. As compared to control, significant decrease in the embryogenesis efficiency was recorded at 100 Gy (85.92%) with similar reduction trends in embryo production (79.49%), germination (13.43%), conversion (2.48%), establishment (15.78%) and acclimatization (60.92%). The growth-related parameters such as root and shoot length and number of leaves/regenerant were also significantly reduced to 67.29%, 30.19% and 5.03%, respectively, in the regenerated plants after gamma irradiation as compared to control. In the EMS treatment, at the dose rate of 0.1% for 3-h, the embryogenesis efficiency was reduced to 43.67% with similar diminution trends in embryo production (59.49%), germination (8.95%), conversion (1.94%), establishment (4.37%) and acclimatization (29.9%). The growth-related parameters in the EMS treatment, decreased to 91.00% (root length), 71.34% (shoot length) and 35.03% (no. of leaves). The molecular marker based varied amplifications confirmed the occurrence of mutations in both gamma and EMS induced M1 regenerants. The study highlights the alternative high frequency in vitro mutagenesis protocol for induction of solid mutants in Kinnow mandarin and related citrus species.

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Background: Neuroinflammation in Alzheimer's disease is known as an important process in the disease, yet how microglial activation affects disease progression remains unclear. Objective: The current study aims to interrogate the predictive value of neuroinflammation biomarker (11C-PBR28 PET), together with A/T/N imaging markers on disease deterioration in a cognitively impaired patient cohort. Methods: The study included 6 AD and 27 MCI patients, who had MRI, 11C-PBR28, 18F-flutemetamol (amyloid marker), 18F-AV1451 (tau marker) PET scans, and were followed up with multiple neuropsychological assessments for at least one year (1.6 and 2.8 years on average for AD and MCI). The predictive values of imaging biomarkers on baseline and longitudinal cognition were interrogated using linear regression to identify the biomarkers that could explain disease progression. Results: Linear mixed models found the average intercepts (baseline) MMSE were 23.5 for AD and 28.2 for MCI patients, and the slope of MMSE (annual change) were -0.74 for AD and -0.52 for MCI patients. White matter microstructural integrity was predictive of baseline cognition, while PET markers of amyloid, tau and neuroinflammation were predictive of longitudinal cognitive decline. Both amyloid and neuroinflammation PET markers were predictors independent of each other. And a sub-group analysis showed the predictive effect of neuroinflammation on cognitive decline is independent of amyloid and tau. Conclusions: Our study highlights the prognostic value of disease specific markers (amyloid, tau and neuroinflammation) in clinically diagnosed AD and MCI patients and suggests that the effects of these molecular markers are mediated by structural damage to the brain.

Asunto(s)

Enfermedad de Alzheimer , Biomarcadores , Disfunción Cognitiva , Progresión de la Enfermedad , Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Anciano , Biomarcadores/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Proteínas tau/metabolismo , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Persona de Mediana Edad , Anciano de 80 o más Años , Valor Predictivo de las Pruebas , Estudios Longitudinales , Péptidos beta-Amiloides/metabolismo

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Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

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Infecciones por VIH , Enfermedades Neuroinflamatorias , Receptores de GABA , Humanos , Masculino , Receptores de GABA/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Adulto , Persona de Mediana Edad , Estudios Transversales , Femenino , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/virología , Enfermedad Crónica , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Piridinas/uso terapéutico , Radioisótopos de Carbono , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/virología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/metabolismo , Sustancia Gris/efectos de los fármacos , Sustancia Gris/virología , Sustancia Gris/patología , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Radiofármacos

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INTRODUCTION: The neuroimmune system performs a wide range of functions in the brain and the central nervous system. The microglial translocator protein (TSPO) has an established role as a cell marker in identification of the neuroimmune system. Previously, human studies have shown TSPO differences in neuropsychiatric disorders. Seasonal variability has also been demonstrated in multiple systems of healthy individuals. Therefore, in this study, we attempt to understand whether seasonal changes affect brain TSPO levels using [11C]PBR28 positron emission tomography (PET) imaging. METHODS: 46 healthy subjects (mean age ± SD = 32.5 ± 10); sex (M/F) = 32/14)) underwent PET imaging with [11C]PBR28 in a retrospectively conducted analysis. All PET scans were performed on the HRRT scanner. Volume of distribution (VT) values were generated for cortical and subcortical regions and the cerebellum. Spring/summer months were defined as March to August while fall/winter months were defined as September to February and were compared through 2-tailed t-tests (SciPy library v.1.10.1 and Pinguoin library on Python v.3.8.8). Average daylight hours and temperature in New Haven, CT were obtained online (www.wunderground.com) and compared to VT with Spearman's correlations. RESULTS: There were no significant differences observed between the TSPO levels of spring/summer and fall/winter months in the brain (t = 0.52, p = 0.61). Additional analysis on all individual brain regions also indicated non-significance. Likewise, no significant correlations were found between TSPO levels in the whole brain and brain regions against daylight hours (ρ= 0.05, p = 0.74), temperature (ρ = 0.04, p = 0.81), or month (ρ = 0.08, p = 0.60). Controlling TSPO gene polymorphisms and other variables had no significant effect on the outcome. CONCLUSION: To the best of our knowledge, this is the first human study to investigate seasonal changes in TSPO expression. Our results can be interpreted as the lack of seasonal variability in the neuroimmune system, but important limitations include high interindividual variability, test-retest variability, specificity of the tracer, and a limited sample size. Limitations notwithstanding, our results conclude that TSPO levels in the brain are not impacted by light and temperature changes in different seasons.

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Encéfalo , Receptores de GABA , Humanos , Estaciones del Año , Estudios Retrospectivos , Receptores de GABA/metabolismo , Encéfalo/metabolismo , Tomografía de Emisión de Positrones/métodos , Proteínas Portadoras/metabolismo

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The ability of bacteriophages to destroy bacteria has made them the subject of extensive research. Interest in bacteriophages has recently increased due to the spread of drug-resistant bacteria, although genomic research has not kept pace with the growth of genomic data. Genomic analysis and, especially, the taxonomic description of bacteriophages are often difficult due to the peculiarities of the evolution of bacteriophages, which often includes the horizontal transfer of genes and genomic modules. The latter is particularly pronounced for temperate bacteriophages, which are capable of integration into the bacterial chromosome. Xanthomonas phage PBR31 is a temperate bacteriophage, which has been neither described nor classified previously, that infects the plant pathogen Xanthomonas campestris pv. campestris. Genomic analysis, including phylogenetic studies, indicated the separation of phage PBR31 from known classified bacteriophages, as well as its distant relationship with other temperate bacteriophages, including the Lederbervirus group. Bioinformatic analysis of proteins revealed distinctive features of PBR31, including the presence of a protein similar to the small subunit of D-family DNA polymerase and advanced lysis machinery. Taxonomic analysis showed the possibility of assigning phage PBR31 to a new taxon, although the complete taxonomic description of Xanthomonas phage PBR31 and other related bacteriophages is complicated by the complex evolutionary history of the formation of its genome. The general biological features of the PBR31 phage were analysed for the first time. Due to its presumably temperate lifestyle, there is doubt as to whether the PBR31 phage is appropriate for phage control purposes. Bioinformatics analysis, however, revealed the presence of cell wall-degrading enzymes that can be utilised for the treatment of bacterial infections.

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Bacteriófagos , Xanthomonas , Bacteriófagos/genética , Xanthomonas/genética , Filogenia , ADN Polimerasa Dirigida por ADN/genética

RESUMEN

Translocator protein (18 kDa) (Tspo), formerly known as peripheral benzodiazepine receptor is a highly conserved transmembrane protein primarily located in the outer mitochondrial membrane. In the central nervous system (CNS), especially in glia cells, Tspo is upregulated upon inflammation. Consequently, Tspo was used as a tool for diagnostic in vivo imaging of neuroinflammation in the brain and as a potential therapeutic target. Several synthetic Tspo ligands have been explored as immunomodulatory and neuroprotective therapy approaches. Although the function of Tspo and how its ligands exert these beneficial effects is not fully clear, it became a research topic of interest, especially in ocular diseases in the past few years. This review summarizes state-of-the-art knowledge of Tspo expression and its proposed functions in different cells of the retina including microglia, retinal pigment epithelium and Müller cells. Tspo is involved in cytokine signaling, oxidative stress and reactive oxygen species production, calcium signaling, neurosteroid synthesis, energy metabolism, and cholesterol efflux. We also highlight recent developments in preclinical models targeting Tspo and summarize the relevance of Tspo biology for ocular and retinal diseases. We conclude that glial upregulation of Tspo in different ocular pathologies and the use of Tspo ligands as promising therapeutic approaches in preclinical studies underline the importance of Tspo as a potential disease-modifying protein.

Asunto(s)

Receptores de GABA , Retina , Humanos , Receptores de GABA/metabolismo , Animales , Retina/metabolismo , Oftalmopatías/metabolismo , Enfermedades de la Retina/metabolismo , Microglía/metabolismo

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BACKGROUND: Minimal access breast surgery improves cosmetic outcomes over conventional breast surgery but still faces barriers in becoming standard procedure for breast reconstruction. This report introduces a novel technique of transaxillary reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) followed by direct-to-implant prepectoral breast reconstruction (DTI-PBR) and describes its clinical outcomes. METHODS: This prospective study enrolled patients who underwent R-E-NSM and DTI-PBR from March 2021 to December 2021 at a single institution. Perioperative data, surgical complications, oncologic outcomes, and patient- and surgeon-reported cosmetic results were noted. RESULTS: The 60 patients in this study who underwent 68 R-E-NSM and DTI-PBR had a mean age was 40.4 ± 10.3 years. The average durations of uni- and bilateral operations were 156.5 ± 48.3 min and 191.3 ± 36.1 min, respectively. The overall surgical complication rate was 13.3%, including 10.0% of patients with minor complications and 3.3% of patients with major complications. The study had one case (1.7%) of implant loss and one case (1.7%) of skin flap necrosis treated by reoperation. During the median follow-up period of 24 months, one patient (1.7%) who discontinued chemotherapy for myelosuppression experienced liver metastases 5 months postoperatively, and one patient experienced new-onset contralateral ductal carcinoma in situ 24 months postoperatively. The preoperative and 18-month postoperative Breast-Q scores for satisfaction with breasts, psychosocial well-being, sexual well-being, and chest well-being did not differ significantly, and the Scar-Q was 81.2 ± 14.5 points. The good-to-excellent rate in surgeon-reported cosmetic results reached 90%. CONCLUSIONS: Transaxillary R-E-NSM followed by DTI-PBR is a safe and efficient technique with high cosmetic outcomes and reliable medium-term oncologic results.

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Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Adulto , Persona de Mediana Edad , Femenino , Mastectomía/métodos , Estudios Prospectivos , Pezones/cirugía , Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Estudios Retrospectivos

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Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.

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Monitoreo Biológico , Plomo , Adsorción , Transporte Biológico , Biomineralización

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Purpose: This study aimed to evaluate changes in ocular surface parameters among obstructive sleep apnea syndrome (OSAS) patients. Methods: 44 healthy volunteers (88 eyes) and 27 OSAS patients (54 eyes) were recruited in our cross-sectional study. 14 patients were classified as mild&moderate OSAS, and 13 patients were classified as severe OSAS. For evaluating the ocular surface, the following tests were conducted: the height of tear meniscus (TMH), first non-invasive tear break-up time (FNITBUT), mean non-invasive tear break-up time (MNITBUT), the score of Meibomian gland dropout area (Meiboscore), the tear test of anesthesia-free Schirmer I (SIT), corneal fluorescein staining (CFS), partial blinks rate (PBR), the lipid layer thickness (LLT), ocular surface disease index (OSDI). The results obtained from the study were analyzed and compared among the groups. Results: FNITBUT, MNITBUT, and TMH were lower. OSDI, CFS, Meiboscore and PBR were higher in the OSAS group than those in the control group. The mild&moderate as well as the severe OSAS subgroups had statistically significantly lower TMH, and higher OSDI and PBR than the control group. Meanwhile, we found there were no significant differences between two OSAS subgroups. CFS was higher in the severe OSAS group than the mild&moderate OSAS group. Significantly lower FNITBUT, MNITBUT and higher Meiboscore were observed in the severe OSAS subgroup than in the control group, and MNITBUT was higher in severe OSAS objects than in the mild&moderate OSAS objects. LLT and SIT did not exhibit significant differences among control and OSAS subgroups. FNITBUT and MNITBUT showed significantly negative correlations with BMI, while Meiboscore showed a significant positive correlation with AHI. Conclusion: Patients with OSAS have a tendence of dry eyes, whereas control subjects do not. This indicates us that the OSAS patients should pay more attention to ocular surface care.

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Intensive use of chemical pesticides in agriculture poses environmental risks and may have negative impacts on agricultural productivity. The potential phytotoxicity of two chemical pesticides, chlorpyrifos (CPS) and fensulfothion (FSN), were evaluated using Cicer arietinum and Allium cepa as model crops. Different concentrations (0-100 µgmL-1) of both CPS and FSN decreased germination and biological attributes of C. arietinum. High pesticide doses significantly (p ≤ 0.05) caused membrane damage by producing thiobarbituric acid reactive substances (TBARS) and increasing proline (Pro) content. Pesticides elevated ROS levels and substantially increased the superoxide anions and H2O2 concentrations, thus aggravating cell injury. Plants exposed to high pesticide dosages displayed significantly higher antioxidant levels to combat pesticide-induced oxidative stress. Ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) increased by 48%, 93%, 71%, 52% and 94%, respectively, in C. arietinum roots exposed to 100 µgFSNmL-1. Under CLSM, pesticide-exposed C. arietinum and 2',7'-dichlorodihydrofluorescein diacetate (2'7'-DCF) and 3,3'-diaminobenzidine stained roots exhibited increased ROS production in a concentration-dependent manner. Additionally, enhanced Rhodamine 123 (Rhd 123) and Evan's blue fluorescence in roots, as well as changes in mitochondrial membrane potential (ΔΨm) and cellular apoptosis, were both associated with high pesticide dose. Allium cepa chromosomal aberration (CAs) assay showed a clear reduction in mitotic index (MI) and numerous chromosomal anomalies in root meristematic cells. Additionally, a-dose-dependent increase in DNA damage in root meristematic cells of A. cepa and conversion of the super-coiled form of DNA to open circular in pBR322 plasmid revealed the genotoxic potential of pesticides. The application of CPS and FSN suggests phytotoxic and cyto-genotoxic effects that emphasize the importance of careful monitoring of current pesticide level in soil before application and addition at optimal levels to soil-plant system. It is appropriate to prepare both target-specific and slow-release agrochemical formulations for crop protection with concurrent safeguarding of agroecosystems.

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Cloropirifos , Insecticidas , Plaguicidas , Insecticidas/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/farmacología , Antioxidantes/farmacología , Plaguicidas/toxicidad , Cebollas , Cloropirifos/metabolismo , Cloropirifos/farmacología , Daño del ADN , Suelo , Raíces de Plantas

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We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.

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Neoplasias del Sistema Nervioso Central , Enfermedades del Nervio Facial , Linfoma , Neuropatía Ciática , Humanos , Masculino , Persona de Mediana Edad , Encéfalo/inmunología , Enfermedades del Nervio Facial/etiología , Enfermedades del Nervio Facial/inmunología , Enfermedades del Nervio Facial/terapia , Fluorodesoxiglucosa F18 , Inmunoglobulina G/inmunología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Receptores de GABA/metabolismo , Neuropatía Ciática/etiología , Neuropatía Ciática/inmunología , Neuropatía Ciática/terapia , Neoplasias del Sistema Nervioso Central/complicaciones , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/inmunología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Linfoma/complicaciones , Linfoma/diagnóstico por imagen , Linfoma/inmunología , Polineuropatía Paraneoplásica/etiología , Polineuropatía Paraneoplásica/inmunología , Prednisona/uso terapéutico , Glucocorticoides/uso terapéutico , Intercambio Plasmático , Proteínas del Tejido Nervioso/inmunología

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Turkey is the world's leading producer of figs, a typical Mediterranean fruit. The fig, Ficus carica L. (Moraceae), has been widely cultivated since ancient times due to the nutritional value of its fruits. It was aimed to investigate the phytochemical characterization and biological properties of F. carica leaf extracts in order to determine their potential for use in the treatment of various diseases. F. carica leaves were extracted in 70% methanol at 40 °C under reflux. To obtain extracts of different polarities, the crude extract was fractionated with n-hexane, dichloromethane, and n-butanol. Phenolic content was determined using liquid chromatography-high resolution mass spectrometry (LC-HRMS). 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and antityrosinase activities of all extracts were investigated using spectrophotometric methods. Furthermore, the DNA-damage protective properties of extracts were investigated using electrophoretic methods. The n-butanol extract was found to have the highest total phenolic content, with 72.58 ± 4.52 mg GAE/g dry weight. According to LC-HRMS analysis, rutin (40.13 g/kg) was the most abundant compound in the n-butanol extract. The n-butanol extract, which was found to have the highest tyrosinase inhibitory effects among the extracts, demonstrated radical scavenging activity of 37.01 ± 1.15% and 82.57 ± 0.88% at 80 and 200 µg/mL, respectively. The n-butanol extract had the highest protective effects against Fenton's reagent, UV radiation, and singlet oxygen. Given these findings, it is possible to argue that F. carica leaves can be evaluated for developing products that could be used to treat various diseases.

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BACKGROUND: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. OBJECTIVES: We sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. METHODS: Using baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. RESULTS: There was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). CONCLUSION: We revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.

Asunto(s)

Enfermedad Coronaria , Obesidad , Persona de Mediana Edad , Humanos , Masculino , Femenino , Países Bajos/epidemiología , Microcirculación/fisiología , Obesidad/diagnóstico , Obesidad/epidemiología , Coagulación Sanguínea , Fibrinógeno

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BACKGROUND: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging. METHODS: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation. RESULTS: A total of 50 articles was identified. Twelve papers were selected from the included studies' bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment. CONCLUSION: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18F makes this isotope a preferable choice to 11C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers' effects and increasing the noise ratio in images.

Asunto(s)

Demencia , Imagen Molecular , Enfermedades Neuroinflamatorias , Tomografía de Emisión de Positrones , Radiofármacos , Receptores de GABA-A , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Demencia/diagnóstico por imagen , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Medicina Nuclear , Radioisótopos de Flúor/química , Receptores de GABA-A/análisis , Radiofármacos/química , Cerebelo/diagnóstico por imagen , Animales , Imagen Molecular/métodos

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Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington's disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller-Gartner algorithm) were applied. Differences were sought in Unified Huntington's Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period.

RESUMEN

In this study, computational fluid dynamics were employed to examined clockwise and anticlockwise vortexes in the rising and down coming sections of novel nested-bottle photobioreactor. The radial velocity was increased by four times which significantly reduced dead zones compared to traditional PBR. The (NB-PBR) comprised of integrated bottles connected by curved tubes (d = 4 cm) that generated dominant vortices as the microalgae solution flows through each section (h = 10 cm). The (NB-PBR) was independent of the inner and outer sections which increased the mixing time and mass-transfer coefficient by 13.33 % and 42.9 %, respectively. Furthermore, the results indicated that the (NB-PBR) showed higher photosynthesis efficiency preventing self-shading and photo-inhibition, resulting in an increase in biomass yield and carbon dioxide fixation by 35 % and 35.9 %, respectively.

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Microalgas , Spirulina , Fotobiorreactores , Fotosíntesis , Biomasa

RESUMEN

The 18 kDa translocator protein (TSPO/PBR) is a multifunctional evolutionary highly conserved outer mitochondrial membrane protein. Decades of research has reported an obligatory role of TSPO/PBR in both mitochondrial cholesterol transport and, thus, steroid production. However, the strict dependency of steroidogenesis on TSPO/PBR has remained controversial. The aim of this study was to provide insight into the steroid profile in complete C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout male mice (TSPO-KO) under basal conditions. The steroidome in the brain, adrenal glands, testes and plasma was measured by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). We found that steroids present in wild-type (WT) mice were also detected in TSPO-KO mice, including pregnenolone (PREG), progestogens, mineralo-glucocorticosteroids and androgens. The concentrations of PREG and most metabolites were similar between genotypes, except a significant decrease in the levels of the 5α-reduced metabolites of progesterone (PROG) in adrenal glands and plasma and of the 5α-reduced metabolites of corticosterone (B) in plasma in TSPO-KO compared to WT animals, suggesting other regulatory functions for the TSPO/PBR. The expression levels of the voltage-dependent anion-selective channel (VDAC-1), CYP11A1 and 5α-reductase were not significantly different between both groups. Thus, the complete deletion of the tspo gene in male mice does not impair de novo steroidogenesis in vivo.

Asunto(s)

Receptores de GABA , Espectrometría de Masas en Tándem , Masculino , Ratones , Animales , Receptores de GABA/genética , Receptores de GABA/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Esteroides , Proteínas Portadoras , Pregnenolona

RESUMEN

Microalgae biofilm-based culture provides an efficient CO2 reduction and wastewater treatment method for its high photosynthetic efficiency and density. As supporting substrates for microalgae biofilm, porous materials have a big available adsorption area, but mutual shading makes it difficult to transmit external light to the internal surface for attached cells' photosynthesis. Thus, light-guided particles (SiO2) were introduced into photosensitive resin to fabricate a light-guided ordered porous photobioreactor (PBR) by 3D printing technology in this study. The space utilization of the PBR was significantly enhanced and the effective microalgae adsorption area was increased by 13.6 times. Further, a thermo-responsive hydrogel was grafted onto the surface of the substrate to form a smart temperature-controllable interface that could enhance microalgae adsorption and desorption in both directions. When the thermo-responsive layer received light, it would generate heat due to the hydrogel's photo-thermal effect. And the surface temperature would then raise to 33 °C, higher than the hydrogel phase transition point of 32 °C, making the surface shrinking and more hydrophobicity for microalgae cells attachment. The microalgae cells' adsorption capacity increased by 103%, resulting in a high microalgae growth rate of 3.572 g m-2 d-1. When turning off the light, the surface temperature would cool down to below 20 °C, the surface would shrink. And the biofilm shows a 564.7% increase in desorption ability, realizing temperature-controlled microalgae harvesting.

Asunto(s)

Microalgas , Dióxido de Carbono , Adsorción , Temperatura , Porosidad , Dióxido de Silicio , Fotobiorreactores , Biopelículas , Hidrogeles , Biomasa

RESUMEN

The present study is focused on the antimicrobial, antioxidant, cytotoxic, and DNA protective effects of methanol extract obtained from R. digitellata, R. fastigiata, R. fraxinea, and R. polymorpha species that are distributed in Turkey. The highest total phenol content was determined in R. digitellata (144.6 mgGAE/gextract ), and the highest total amount of flavonoids was found in R. fastigiata (20.40 mgGAE/gextract ). The content of usnic acid was determined by High-Performance Liquid Chromatography (HPLC) and the highest amount was found in R. digitellata. DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS [2,2'-azinobis(3-ethylbenzathiazoline-6-sulfonic acid)] radical scavenging methods were used for antioxidant activity. R. fraxinea showed the highest DPPH⋅ and ABTS+ ⋅ scavenging activity. In addition, the DNA protective effect was investigated using pBR322 plasmid DNA, and; all studied species were found to have DNA protective effects. The antibacterial activity was investigated using the disc diffusion method, and the R. digitellata methanol extract showed the best results with a 12.35 mm zone on Proteus mirabilis. On the human lung cancer (A549) and breast cancer (MDA-MB-231) cell lines, cytotoxic activity was assessed using an MTT assay. All lichen extracts were found to have a significant cytotoxic effect on both cancer cell lines at 1000 µg/mL concentration. These results suggest that Ramalina species may be potential candidates for developing new phytopharmaceuticals and functional components.

Asunto(s)

Antiinfecciosos , Antineoplásicos , Humanos , Antioxidantes/química , Metanol , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinfecciosos/farmacología , ADN

RESUMEN

BACKGROUND: Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge. METHODS: Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([11C]PBR28 - for microglial activation and [18F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia. MicroPET imaging data were subjected to advanced conjunction and individual analyses, followed by post-hoc analysis. RESULTS: There were significant increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus of C57BL/6 J mice 6 h following LPS (2 mg/kg) intraperitoneal (i.p.) administration compared with saline administration. These results confirmed previous postmortem observations. In addition, patterns of significant simultaneous activation were demonstrated in the hippocampus, the thalamus, and the hypothalamus in parallel with other tracer-specific and region-specific alterations. These changes were observed in the presence of robust systemic inflammatory responses manifested by significantly increased serum cytokine levels. CONCLUSIONS: Together, these findings demonstrate the applicability of [11C]PBR28 - [18F]FDG dual tracer microPET imaging for assessing neuroinflammation and brain metabolic alterations in conditions "classically" characterized by peripheral inflammatory and metabolic pathogenesis.