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In this study, an efficient stabilizer material for cadmium (Cd2+) treatment was successfully prepared by simply co-milling olivine with magnesite. Several analytical methods including XRD, TEM, SEM and FTIR, combined with theoretical calculations (DFT), were used to investigate mechanochemical interfacial reaction between two minerals, and the reaction mechanism of Cd removal, with ion exchange between Cd2+ and Mg2+ as the main pathway. A fixation capacity of Cd2+ as high as 270.61 mg/g, much higher than that of the pristine minerals and even the individual/physical mixture of milled olivine and magnesite, has been obtained at optimized conditions, with a neutral pH value of the solution after treatment to allow its direct discharge. The as-proposed Mg-based stabilizer with various advantages such as cost benefits, green feature etc., will boosts the utilization efficiency of natural minerals over the elaborately prepared adsorbents.
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Cadmio , Compuestos de Hierro , Compuestos de Magnesio , Silicatos , Contaminantes Químicos del Agua , Cadmio/química , Contaminantes Químicos del Agua/química , Compuestos de Magnesio/química , Silicatos/química , Compuestos de Hierro/química , Adsorción , Modelos Químicos , Purificación del Agua/métodosRESUMEN
Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.
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Oxígeno , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Oxígeno/química , Catálisis , Manganeso/química , Compuestos de Bencidrilo/química , Nitrilos/química , Adsorción , Especies Reactivas de Oxígeno , Restauración y Remediación Ambiental/métodos , Fenoles/químicaRESUMEN
Background: There are limited studies exploring the relationship between physical activity (PA), cognitive function, and the brain processing characteristics in healthy older adults. Methods: A total of 41 participants (42.7 ± 20.5 years, 56.1% males) were included in the data analysis. The International Physical Activity Questionnaire Short Form was used to assess PA levels, and the Chinese version of the Montreal Cognitive Assessment-Basic and the Flanker task were employed to evaluate cognitive function. Furthermore, fMRI technology was utilized to examine brain activation patterns. Results: The cognitive function of the older adults was found to be significantly lower compared to the young adults. Within the older adults, those with high levels of PA exhibited significantly higher cognitive function than those with low and medium PA levels. The fMRI data showed significant differences in brain activation patterns among young adults across the different PA levels. However, such difference was not observed among older adults. Conclusion: A decline in cognitive function was observed among older adults. There was a significant correlation between the levels of PA and cognitive function in healthy older adults. The study demonstrated significant effects of PA levels on brain activation patterns in inhibitory control-related regions among young adults, while not significant among older adults. The findings suggest that neurological mechanisms driving the relationship between PA and cognitive function may differ between older and young adults.
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Cognición , Ejercicio Físico , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Cognición/fisiología , Proyectos Piloto , Ejercicio Físico/fisiología , Adulto , Persona de Mediana Edad , Anciano , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Encuestas y Cuestionarios , Adulto Joven , Factores de EdadRESUMEN
Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumor-selective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [18F]FDG (2-[18F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide 18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note, an OxaliPt(IV) linker is designed to construct an [18F]FDG-activated antibody-drug conjugate (Pt-ADC). Sequential injection of Pt-ADC and [18F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation, and we find that [18F]FDG is capable of deprotecting various radiotherapy-removable protecting groups (RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.
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A bisphosphirane-fused anthracene (5) was prepared by treatment of a sterically encumbered amino phosphorus dichloride (3) with MgAâ¢3THF (A = anthracene). X-ray diffraction analysis revealed a pentacyclic framework consisting of 5 with two phosphirane rings fused to the anthracene in a trans-fashion. Compound 5 has been shown to be an efficient phosphinidene synthon, readily liberating two transient phosphinidene units for subsequent downstream bond activation via the reductive elimination of anthracene under mild conditions. The formal oxidative addition of H2 and E-H (E = Si, N, P) bonds by the liberated phosphinidene provided diphosphine and substituted phosphines. Furthermore, phosphinidene transfer to alkenes and alkynes smoothly yielded the corresponding phosphiranes and phosphirenes. The mechanism of the H2 activation by 5 was investigated by density functional theory (DFT) calculations.
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Oocyte activation is a fundamental event in mammalian fertilization and is initiated by a cascade of calcium signaling and oscillation pathways. Phospholipase C zeta (PLCζ) is involved in modulating cortical granule exocytosis, releasing oocyte meiotic arrest, regulating gene expression, and early embryogenesis. These processes are considered to be initiated and controlled by PLCζ activity via the inositol-1,4,5-triphosphate pathway. The decrease or absence of functional PLCζ due to mutational defects in protein expression or maintenance can impair male fertility. In this literature review, we highlight the significance of PLCζ as a sperm factor involved in oocyte activation, its mechanism of action, the signaling pathway involved, and its close association with oocyte activation. Finally, we discuss the relationship between male infertility and PLCζ deficiency.
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Selective hydroboration of C-C single bonds presents a fundamental challenge in the chemical industry. Previously, only catalytic systems utilizing precious metals Ir and Rh, in conjunction with N- and P- ligands, could achieve this, ensuring bond cleavage and selectivity. In sharp contrast, we discovered an unprecedented and general transition-metal-free system for the hydroboration of C-C single bonds. This methodology is transition-metal and ligand-free and surpasses the transition-metal systems regarding chemo- and regioselectivities, substrate versatility, or yields. In addition, our system tolerates various functional groups such as Ar-X (X = halides), heterocyclic rings, ketones, esters, amides, nitro, nitriles, and C=C double bonds, which are typically susceptible to hydroboration in the presence of transition metals. As a result, a diverse range of γ-boronated amines with varied structures and functions has been readily obtained. Experimental mechanistic studies, density functional theory (DFT), and intrinsic bond orbital (IBO) calculations unveiled a hydroborane-promoted C-C bond cleavage and hydride-shift reaction pathway. The carbonyl group of the amide suppresses dehydrogenation between the free N-H and hydroborane. The lone pair on the nitrogen of the amide facilitates the cleavage of C-C bonds in cyclopropanes.
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N-nitrosamines and nitrosamine drug substance related impurities (NDSRIs) became a critical topic for the development and safety of small molecule medicines following the withdrawal of various pharmaceutical products from the market. To assess the mutagenic and carcinogenic potential of different N-nitrosamines lacking robust carcinogenicity data, several approaches are in use including the published carcinogenic potency categorization approach (CPCA), the Enhanced Ames Test (EAT), in vivo mutagenicity studies as well as read-across to analogue molecules with robust carcinogenicity data. We employ quantum chemical calculations as a pivotal tool providing insights into the likelihood of reactive ion formation and subsequent DNA alkylation for a selection of molecules including e.g., carcinogenic N-nitrosopiperazine (NPZ), N-nitrosopiperidine (NPIP), together with N-nitrosodimethylamine (NDMA) as well as non-carcinogenic N-nitrosomethyl-tert-butylamine (NTBA) and bis (butan-2-yl) (nitros)amine (BBNA). In addition, a series of nitroso-methylaminopyridines is compared side-by-side. We draw comparisons between calculated reaction profiles for structures representing motifs common to NDSRIs and those of confirmed carcinogenic and non-carcinogenic molecules with in vivo data from cancer bioassays. Furthermore, our approach enables insights into reactivity and relative stability of intermediate species that can be formed upon activation of several nitrosamines. Most notably, we reveal consistent differences between the free energy profiles of carcinogenic and non-carcinogenic molecules. For the former, the intermediate diazonium ions mostly react, kinetically controlled, to the more stable DNA adducts and less to the water adducts via transition-states of similar heights. Non-carcinogenic molecules yield stable carbocations as intermediates that, thermodynamically controlled, more likely form the statistically preferred water adducts. In conclusion, our data confirm that quantum chemical calculations can contribute to a weight of evidence approach for the risk assessment of nitrosamines.
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The fouling resistance of zwitterionic coatings is conventionally explained by the strong hydrophilicity of such polymers. Here, the in vitro biocompatibility of a set of systematically varied amphiphilic, zwitterionic copolymers is investigated. Photocrosslinkable, amphiphilic copolymers containing hydrophilic sulfobetaine methacrylate (SPe) and butyl methacrylate (BMA) were systematically synthesized in different ratios (50:50, 70:30, and 90:10) with a fixed content of photo-crosslinker by free radical copolymerization. The copolymers were spin-coated onto substrates and subsequently photocured by UV irradiation. Pure pBMA and pSPe as well as the prepared amphiphilic copolymers showed BMA content-dependent wettability in the dry state, but overall hydrophilic properties a fortiori in aqueous conditions. All polysulfobetaine-containing copolymers showed high resistance against non-specific adsorption (NSA) of proteins, platelet adhesion, thrombocyte activation, and bacterial accumulation. In some cases, the amphiphilic coatings even outperformed the purely hydrophilic pSPe coatings.
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Collagen, the most abundant protein in the body, is a key component of the extracellular matrix (ECM), which plays a crucial role in the structure and support of connective tissues. Abnormalities in collagen associated with connective tissue disorders (CTD) can lead to neuroinflammation and weaken the integrity of the blood-brain barrier (BBB), a semi-permeable membrane that separates the brain's extracellular fluid from the bloodstream. This compromise in the BBB can result from disruptions in ECM components, leading to neuroinflammatory responses, neuronal damage, and increased risks of neurological disorders. These changes impact central nervous system homeostasis and may exacerbate neurological conditions linked to CTD, manifesting as cognitive impairment, sensory disturbances, headaches, sleep issues, and psychiatric symptoms. The Ehlers-Danlos syndromes (EDS) are a group of heritable CTDs that result from varying defects in collagen and the ECM. The most prevalent subtype, hypermobile EDS (hEDS), involves clinical manifestations that include joint hypermobility, skin hyperextensibility, autonomic dysfunction, mast cell activation, chronic pain, as well as neurological manifestations like chronic headaches and cerebrospinal fluid (CSF) leaks. Understanding the connections between collagen, CSF, inflammation, and the BBB could provide insights into neurological diseases associated with connective tissue abnormalities and guide future research.
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The development and progression of temporal lobe epilepsy (TLE) are heavily influenced by inflammation, excessive activation of glial cells, and neuronal cell death. This study aimed to investigate the effects of treatment with alpha-pinene (APN) on pro-and anti-inflammatory cytokine levels, astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE induced by kainic acid (KA). Male Wistar rats were employed, and TLE was induced by intracerebroventricular injection of KA. APN (50 mg/kg) was intraperitoneally administered for 19 days, including two weeks before and five days after the administration of KA. After full recovery from anesthesia and KA injection, the seizure-related behavioral expressions were evaluated. On day 19, the hippocampal levels of IL-1ß, TNF-α, progranulin, IL-10, ERK1/2, phospho-ERK1/2, NF-κB, GFAP, S100-B, NLRP1, NLRP3, caspase-1, and becline-1 were examined. The results revealed that treatment with APN significantly diminished the heightened levels of IL-1ß, TNF-α, progranulin, ERK1/2, and NF-κB and reversed the reduced levels of the anti-inflammatory cytokine, IL-10, in the hippocampus caused by KA. Furthermore, administration of APN significantly reduced the levels of astrogliosis, pyroptosis, and autophagy markers in the hippocampus that were elevated by KA. It can be concluded that treatment with APN for 19 days alleviated neuroinflammation by inhibiting ERK1/2 and NF-κB signaling pathways and prevented increases in astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE.
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In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease.
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BACKGROUND: Inadequate nerve regeneration and an inhibitory local microenvironment are major obstacles to the repair of spinal cord injury (SCI). The activation and differentiation fate regulation of endogenous neural stem cells (NSCs) represent one of the most promising repair approaches. Metformin has been extensively studied for its antioxidative, anti-inflammatory, anti-aging, and autophagy-regulating properties in central nervous system diseases. However, the effects of metformin on endogenous NSCs remains to be elucidated. METHODS: The proliferation and differentiation abilities of NSCs were evaluated using CCK-8 assay, EdU/Ki67 staining and immunofluorescence staining. Changes in the expression of key proteins related to ferroptosis in NSCs were detected using Western Blot and immunofluorescence staining. The levels of reactive oxygen species, glutathione and tissue iron were measured using corresponding assay kits. Changes in mitochondrial morphology and membrane potential were observed using transmission electron microscopy and JC-1 fluorescence probe. Locomotor function recovery after SCI in rats was assessed through BBB score, LSS score, CatWalk gait analysis, and electrophysiological testing. The expression of the AMPK pathway was examined using Western Blot. RESULTS: Metformin promoted the proliferation and neuronal differentiation of NSCs both in vitro and in vivo. Furthermore, a ferroptosis model of NSCs using erastin treatment was established in vitro, and metformin treatment could reverse the changes in the expression of key ferroptosis-related proteins, increase glutathione synthesis, reduce reactive oxygen species production and improve mitochondrial membrane potential and morphology. Moreover, metformin administration improved locomotor function recovery and histological outcomes following SCI in rats. Notably, all the above beneficial effects of metformin were completely abolished upon addition of compound C, a specific inhibitor of AMP-activated protein kinase (AMPK). CONCLUSION: Metformin, driven by canonical AMPK-dependent regulation, promotes proliferation and neuronal differentiation of endogenous NSCs while inhibiting ferroptosis, thereby facilitating recovery of locomotor function following SCI. Our study further elucidates the protective mechanism of metformin in SCI, providing new mechanistic insights for its candidacy as a therapeutic agent for SCI.
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Proteínas Quinasas Activadas por AMP , Diferenciación Celular , Proliferación Celular , Ferroptosis , Metformina , Células-Madre Neurales , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Metformina/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/metabolismo , Animales , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Proliferación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Recuperación de la Función/efectos de los fármacosRESUMEN
Objective: Falls are a major challenge to public health, particularly among older adults. Understanding factors that influence fall risk is pivotal in the prevention of falls and fall-related injuries. This study evaluated the timing of emergency medical service (EMS) activations for falls and transport patterns for adults age ≥65. Methods: A patient care report system at a single fire-based emergency medical service agency in a suburban, Midwest city was retrospectively reviewed. Type of call (lift assist/fall), time of injury (time, day, and month), and demographics (sex, age) were collected for residents age ≥65 who activated 9-1-1 for a lift assist or fall. Results: 1169 calls met inclusion criteria. Mornings and afternoons were the time of day associated with falls (33 % and 36 % of EMS activations, respectively, vs. 21 % and 10 % for evenings and nights, respectively; p = 0.002) while day of the week and month were not associated with falls or lift assists. More males requested lift assists than females (256 vs. 238) and more females called for falls than males (408 vs. 267; p < 0.001). Falls were more likely to be associated with transport to the hospital than lift assists (78% vs. 7 %). Female sex was associated with increased risk for transport to the hospital (60 % of females vs. 40 % of males; p < 0.001). Conclusions: Mornings and afternoons were associated with increased risk for falls and sex (female) with increased risk for transport to the hospital.
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Temperature-dependent plastic deformation behaviors of single crystals of quaternary and ternary equiatomic medium-entropy alloys (MEAs) belonging to the Cr-Mn-Fe-Co-Ni system were investigated in compression at temperatures in the range 9 K to 1373 K. Their critical resolved shear stresses (CRSSs) increase with decreasing temperature below room temperature. There is also a dulling of the temperature dependence of CRSS below 77 K due to dislocation inertial effects that we attribute to a decrease in the phonon drag coefficient. These behaviors were compared with those of previously investigated single crystals of the equiatomic Cr-Co-Ni and Cr-Fe-Co-Ni MEAs, and the equiatomic Cr-Mn-Fe-Co-Ni high-entropy alloy (HEA). The temperature dependence of CRSS and the apparent activation volumes below room temperature can be well described by conventional thermal activation theories of face-centered cubic (FCC) alloys. Above 673 K, there is a small increase in CRSS, which we believe is due to elastic interactions between solutes and mobile dislocations, the so-called Portevin-Le Chatelier (PL) effect. The CRSS at 0 K was obtained by extrapolation of fitted CRSS vs. temperature curves and compared with predictions from solid solution strengthening models of HEA and MEAs.
The novelty of our work entitled 'Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system' can be summarized as follows: The temperature dependences of CRSS were experimentally deduced from bulk single crystals of the six MEAs for the first time, so that fair comparison among the FCC HEA/MEAs is made.
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Parkinson's disease (PD) is associated with a reduction in 26/20S proteasome and mitochondrial function and depletion of dopamine. Activation of mitochondrial function with the NAD+ precursor nicotinamide riboside (NR) is a potential therapeutic for PD. However, despite recently started clinical trials, analysis of NR in mammalian animal PD models is lacking and data in simpler PD models is limited. We analyzed the effect of NR in C. elegans and in mouse 26/20S proteasome inhibition models of PD. In C. elegans, NR rescued α-synuclein overexpression induced phenotypes likely by activating the mitochondrial unfolded protein response. However, in a proteasome inhibitor-induced mouse model of PD, NR first partially rescued behavioural dysfunction, but later resulted in decrease in dopamine and its related gene expression in the substantia nigra. Our results suggest that reduction in 26/20S function with long term NR treatment may increase risk for developing reduced nigrostriatal DA function.
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Evaluating stroke campaigns and associated behavioural changes is crucial to assess intervention effectiveness and inform future strategies. We aimed to evaluate patient's and bystanders' foreknowledge of stroke signs and symptoms and their response at stroke onset. We interviewed stroke patients using a validated questionnaire or their bystanders if the stroke patient had disabling stroke. The questionnaire was administered to 165 participants, 142 (86.1%) stroke patients and 23 (13.9%) bystanders. The mean age was 52.6 (SD = 11.7), and male-female ratio was 7:1. Among the participants, 33 (20.1%) had foreknowledge of stroke signs, and of these, 27 (16.5%) were aware of the stroke campaign in Qatar. The behavioural responses at stroke onset included; activating Emergency Medical Services (EMS) (n = 55, 33.3%), calling friends/relatives (n = 69, 41.8%), driving to hospital (n = 33, 20%), waiting for improvement in condition (n = 21, 12.7%). There was no association of ethnicity, marital status, or campaign awareness with EMS activation. Despite limited community awareness of stroke signs and campaign, help-seeking behaviour through EMS activation was generally high, underscoring the need for focused educational efforts and public health interventions.
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A 10-year-old spayed female Dachshund presented with abdominal pain and generalized severe ileus. An exploratory laparotomy was performed, confirming a severe ileus of undetermined origin. Multiple intestinal biopsy results confirmed acute intestinal leiomyositis. Immunohistochemistry (IHC) stains confirmed a T-cell predominant inflammatory infiltrate. Intravenous immunoglobulin (hIVIG) was administered prior to immunosuppressive therapy. Within 10 days of hIVIG treatment, functional peristaltic activity returned, and symptoms resolved. Long-term management, including the use of mycophenolate, resulted in sustained functional peristaltic recovery. Further studies are needed to explore the potential benefits of hIVIG treatment in the stabilization phase of this commonly fatal, treatment-refractory disease.
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OBJECTIVE: This study assessed the cellular composition and effects of leukocyte-platelet-rich fibrin (L-PRF) exudate on whole blood platelets from healthy volunteers. Key objectives included evaluating leukocyte subpopulations, platelet activation markers, platelet-leukocyte interactions and quantifying inflammatory cytokines within the L-PRF exudate. MATERIALS AND METHODS: L-PRF was obtained from 20 healthy donors. Flow cytometry methodologies were used to assess intracellular calcium kinetics and activated GPIIbIIIa, and P-selectin expression. Leukocyte subpopulations and platelet-leukocyte interactions were characterized using monoclonal antibodies. Inflammatory cytokines (IL-8, IL-1ß, IL-6, IL-10, TNF, IL-12p70) within L-PRF exudate were quantified using a cytometric bead array. RESULTS: The expression of activated GPIIbIIIa, and P-selectin exhibited a significant increase (p < 0.001) when L-PRF exudate was added to platelets of whole blood. Regarding intracellular Ca2+ mobilization, the L-PRF exudate elicited significant responses (p < 0.001). L-PRF exudate contained different leukocytes populations, being TCD4 + the most representative of T cells. It was possible to stablish a profile of cytokines produced by the L-PRF exudate, with human IL-8 cytokine exhibiting the highest average (16.90 pg/mL). CONCLUSIONS: Despite the study limitations, the research yielded important insights: 1- L-PRF exudate can stimulate platelet activation, essential in healing, tissue inflammation and remodeling. 2-The presence of leukocyte subpopulations within L-PRF exudate reflexes its complexity and potential to enhance immune responses. 3-The analysis of inflammatory cytokines within L-PRF exudate revealed its immunomodulatory potential. These findings are valuable evidences for understanding the potential role of L-PRF exudate in regenerative dentistry and medicine, offering innovative therapeutic strategies. CLINICAL RELEVANCE: This research highlights crucial aspects that could significantly influence the clinical use of L-PRF exudate in the oral cavity. The findings support the application of L-PRF exudate in both surgical and regenerative dentistry, facilitating the development of innovative therapeutic strategies to enhance patient outcomes.
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Plaquetas , Citocinas , Exudados y Transudados , Citometría de Flujo , Fibrina Rica en Plaquetas , Humanos , Masculino , Citocinas/metabolismo , Femenino , Adulto , Voluntarios Sanos , Activación Plaquetaria , Leucocitos , Biomarcadores/sangreRESUMEN
Background: Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) pathogenesis. Persistent upregulation of interferons (IFNs) and interferon-stimulated genes (ISGs) has previously been associated with chronic immune activation and HIV progression. Here a longitudinal analysis of the IFN and ISG response during HIV infection was performed to gain insights into the ongoing immune activation during HIV infection. Methods: IFN and ISG levels were determined using quantitative polymerase chain reaction in peripheral blood mononuclear cells of people with HIV at pre-seroconversion, during acute and chronic HIV infection, and during suppressive antiretroviral therapy (ART). Results: HIV infection induced the expression of a set of 4 ISGs-RSAD2, ISG15, IFI44L, and IFI27-which remained upregulated during chronic infection. This set of ISGs showed no clear correlations with T-cell activation as determined by co-expression of CD38 and HLA-DR. However, a strong correlation with monocyte activation marker soluble CD163 in serum was found. Furthermore, the expression of this ISG cluster was predictive of viral load before ART initiation and, on ART, expression levels normalized to pre-seroconversion levels. Conclusions: The results presented here suggests that ISG expression is linked to monocyte activation, possibly driven by viral replication.