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1.
Luminescence ; 39(10): e4913, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39350655

RESUMO

The biosynthesis of nanoparticles is a crucial research area aimed at developing innovative, cost-effective, and eco-friendly synthesis techniques for various applications. Herein, we synthesized copper oxide nanoparticles (CuNPs) using Couroupita guianensis flower extract via a simple green synthesis method. These green CuNPs demonstrate promising antimicrobial activity and anticancer activity against A549 nonsmall cell lung cancer (NSCLC) cells. We comprehensively characterized the CuNPs using UV spectrum, XRD, FTIR, SEM, and EDS analyses. The antibacterial and anticancerous performance is attributed to their spherical-like morphology, which enhances effective interaction with bacterial and cancer cells. Moreover, CuNPs proved effective in inactivating Escherichia coli, achieving 2%, 52%, and 99% inactivation at 0, 30, and 60 min, respectively, and Listeria monocytogenes, achieving 1%, 48%, and 98% inactivation at 0, 30, and 60 min, respectively, under visible light. Furthermore, the CuNPs exhibited significant anticancer activity against A549 NSCLC cells, achieving cell viability reductions of 10%, 30%, 50%, 70%, 83%, and 91% at concentrations of 25, 50, 100, 150, 200, and 250 µg/mL, respectively. The green synthesized CuNPs demonstrate their potential in biomedical applications.


Assuntos
Antibacterianos , Antineoplásicos , Cobre , Escherichia coli , Flores , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Humanos , Cobre/química , Cobre/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Nanopartículas Metálicas/química , Flores/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Escherichia coli/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Células A549 , Listeria monocytogenes/efeitos dos fármacos , Luminescência , Relação Dose-Resposta a Droga , Química Verde , Proliferação de Células/efeitos dos fármacos
2.
Korean J Pain ; 37(4): 285-287, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39322311
3.
Korean J Pain ; 37(4): 310-319, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39344359

RESUMO

Background: This study aimed to investigate the analgesic and preventive effect of low-level laser therapy (LLLT) on the incisional pain model and spinal nerve ligation (SNL) model in rats and identify the possible mechanisms of action. Methods: Male Sprague-Dawley rats were used, divided into different treatment groups. The single application group received LLLT before or after skin incision or SNL. The consecutive application group received LLLT for six consecutive days post-incision, three days pre-incision, or three consecutive days pre-SNL. The control group underwent skin incision or SNL without LLLT. The von Frey test was used to quantify the pain associated with mechanical allodynia. Pro-inflammatory cytokine level and alterations in nerve growth factor (NGF) expression were measured by using ELISA and immunohistochemistry, respectively in the skin, muscle of the paw, and spinal cord dorsal horn (SCDH). Results: In the incisional pain model, LLLT showed significant analgesic and preventive effect. LLLT ameliorated SNL-induced mechanical allodynia but LLLT had no preventive effect. LLLT decreased interleukin-1ß (IL-1ß) expression levels in the skin, muscle, and SCDH and reduced the optical density of skin and spinal cord NGF in the incisional pain model. Conclusions: LLLT alleviated incisional pain and neuropathic pain caused by SNL in rats, and reduced the levels of IL-1ß and NGF in the peripheral tissue and SCDH in the incisional pain model. LLLT might be effective in patients with post-operative pain and peripheral neuropathic pain.

4.
Biosens Bioelectron ; 264: 116646, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39142231

RESUMO

Hg2+ is a highly toxic heavy metal ion that poses serious risks to human health and the environment. Due to its tendency to accumulate, it can easily enter the human body through the food chain, making it crucial to develop detection sensors that mimic real environmental conditions. To achieve this, our study employed a surface-enhanced Raman scattering (SERS) sensor using two strategies. First, we designed a highly selective probe by optimizing the probe and reporter DNA strands to bind Hg2+ within a thymine-thymine mismatch. Second, we used the double coffee ring effect to concentrate the optimized probe DNA. These two strategies greatly enhanced the SERS signal, resulting in a sensor with exceptional sensitivity, a low detection limit of 208.71 fM, and superior selectivity for Hg2+. The practical application of the sensor was demonstrated by successfully detecting Hg2+ in drinking water, tap water, canned tuna, and tuna sashimi. Additionally, the experimental results were presented in a pizza-shaped SERS mapping image, allowing users to estimate Hg2+ concentrations through color, providing a user-friendly and intuitive method for data comprehension and analysis. Our study presents a promising approach for sensitive and reliable Hg2+ detection, with potential implications for environmental monitoring and food safety.


Assuntos
Técnicas Biossensoriais , DNA , Limite de Detecção , Mercúrio , Análise Espectral Raman , Mercúrio/análise , Mercúrio/química , Análise Espectral Raman/métodos , Técnicas Biossensoriais/métodos , DNA/química , DNA/análise , Humanos , Contaminação de Alimentos/análise , Água Potável/análise , Nanopartículas Metálicas/química , Poluentes Químicos da Água/análise , Ouro/química , Animais , Monitoramento Ambiental/métodos
5.
Anim Cells Syst (Seoul) ; 28(1): 381-391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100550

RESUMO

Allergic asthma, a type of chronic airway inflammation, is a global health concern because of its increasing incidence and recurrence rates. Camellia sinensis L. yields a variety type of teas, which are also used as medicinal plants in East Asia and are known to have antioxidant, anti-inflammatory, and immune-potentiating properties. Here, we examined the constituents of C. sinensis L. extract (CSE) and evaluated the protective effects of CSE on allergic asthma by elucidating the underlying mechanism. To induce allergic asthma, we injected the sensitization solution (mixture of ovalbumin (OVA) and aluminum hydroxide) into mice intraperitoneally on days 0 and 14. Then, the mice were exposed to 1% OVA by a nebulizer on days 21 to 23, while intragastric administration of CSE (30 and 100 mg/kg) was performed each day on days 18 to 23. We detected five compounds in CSE, including (-)-epigallocatechin, caffeine, (-)-epicatechin, (-)-epigallocatechin gallate, and (-)-epicatechin gallate. Treatment with CSE remarkably decreased the airway hyperresponsiveness, OVA-specific immunoglobulin E level, and inflammatory cell and cytokine levels of mice, with a decrease in inflammatory cell infiltration and mucus production in lung tissue. Treatment with CSE also decreased the phosphorylation of nuclear factor-κB (NF-κB) and the expression of matrix-metalloproteinase (MMP)-9 in asthmatic mice. Our results demonstrated that CSE reduced allergic airway inflammation caused by OVA through inhibition of phosphorylated NF-κB and MMP-9 expression.

6.
Antioxidants (Basel) ; 13(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39199218

RESUMO

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

7.
J Korean Neurosurg Soc ; 67(5): 541-549, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39139023

RESUMO

OBJECTIVE: Advancements in AVM surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. METHODS: We retrospectively reviewed 55 patients (36 males and 19 females; average age 37.4 years) with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2022. RESULTS: In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow coma scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms through multivariate logistic regression. Postoperative seizures noted in nine patients, were exclusive to the ruptured AVM group. CONCLUSION: Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis.

8.
Brain ; 147(9): 3059-3069, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39049445

RESUMO

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and two groups treated for 20-30 days with low- (10 mg/kg/day) or high- (30 mg/kg/day) dose BLZ945. With the high-dose BLZ945 treatment, there was a significant reduction in cells expressing CD163 and CD206 across all four brain areas examined, compared with the low-dose treatment and control groups. In 9 of 11 tested regions, tissue viral DNA (vDNA) loads were reduced by 95%-99% following at least one of the two doses, and even to undetectable levels in some instances. Decreased numbers of CD163+ and CD206+ cells correlated significantly with lower levels of vDNA in all four corresponding brain areas. In contrast, BLZ945 treatment did not significantly affect the number of microglia. Our results indicate that doses as low as 10 mg/kg/day of BLZ945 are sufficient to reduce the tissue vDNA loads in the brain with no apparent adverse effect. This study provides evidence that infected PVMs are highly sensitive to CSF1R inhibition, opening new possibilities to achieve viral clearance.


Assuntos
Encéfalo , Macaca mulatta , Macrófagos , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/virologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Carga Viral/efeitos dos fármacos , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Antígenos CD/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/virologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores de Superfície Celular/metabolismo , Anisóis
9.
Investig Clin Urol ; 65(4): 378-390, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978218

RESUMO

PURPOSE: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. MATERIALS AND METHODS: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. RESULTS: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. CONCLUSIONS: Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.


Assuntos
Cistite , Microbiota , Recidiva , Humanos , Feminino , Cistite/microbiologia , Cistite/urina , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Urina/microbiologia , República da Coreia , Sequenciamento de Nucleotídeos em Larga Escala , Doença Aguda , Infecções Urinárias/microbiologia , Idoso , Relevância Clínica
11.
Environ Res ; 258: 119395, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38909944

RESUMO

In this study, we report the development of a novel CuOx(3 wt%)/CoFe2O4 nanocubes (NCs) photocatalyst through simple co-precipitation and wet impregnation methods for the efficient photocatalytic degradation of triclosan (TCS) pollutants. Initially, rod-shaped bare CoFe2O4 was synthesized using a simple co-precipitation technique. Subsequently, CuOx was loaded in various percentages (1, 2, and 3 wt%) onto the surface of bare CoFe2O4 nanorods (NRs) via the wet impregnation method. The synthesized materials were systematically characterized to evaluate their composition, structural and electrical characteristics. The CuOx(3 wt%)/CoFe2O4 NCs photocatalyst exhibited superior photocatalytic degradation efficiency of TCS (89.9%) compared to bare CoFe2O4 NRs (62.1 %), CuOx(1 wt%)/CoFe2O4 (80.1 %), CuOx(2 wt%)/CoFe2O4 (87.0 %) under visible light (VL) irradiation (λ ≥ 420 nm), respectively. This enhanced performance was attributed to the improved separation effectiveness of photogenerated electron (e-) and hole (h+) in CuOx(3 wt%)/CoFe2O4 NCs. Furthermore, the optimized CuOx(3 wt%)/CoFe2O4 NCs exhibited strong stability and reusability in TCS degradation, as demonstrated by three successive cycles. Genetic screening on Caenorhabditis elegans showed that CuOx(3 wt%)/CoFe2O4 NCs reduced ROS-induced oxidative stress during TCS photocatalytic degradation. ROS levels decreased at 30, 60, and 120-min intervals during TCS degradation, accompanied by improved egg hatching rates. Additionally, expression levels of stress-responsible antioxidant proteins like SOD-3GFP and HSP-16.2GFP were significantly normalized. This study demonstrates the efficiency of CuOx(3 wt%)/CoFe2O4 NCs in degrading TCS pollutants, offers insights into toxicity dynamics, and recommends its use for future environmental remediation.


Assuntos
Cobalto , Cobre , Triclosan , Triclosan/química , Triclosan/toxicidade , Animais , Cobre/química , Catálise , Cobalto/química , Compostos Férricos/química , Compostos Férricos/toxicidade , Luz , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/efeitos da radiação , Fotólise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade
12.
Parasites Hosts Dis ; 62(2): 169-179, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38835258

RESUMO

Naegleria fowleri invades the brain and causes a fatal primary amoebic meningoencephalitis (PAM). Despite its high mortality rate of approximately 97%, an effective therapeutic drug for PAM has not been developed. Approaches with miltefosine, amphotericin B, and other antimicrobials have been clinically attempted to treat PAM, but their therapeutic efficacy remains unclear. The development of an effective and safe therapeutic drug for PAM is urgently needed. In this study, we investigated the anti-amoebic activity of Pinus densiflora leaf extract (PLE) against N. fowleri. PLE induced significant morphological changes in N. fowleri trophozoites, resulting in the death of the amoeba. The IC50 of PLE on N. fowleri was 62.3±0.95 µg/ml. Alternatively, PLE did not significantly affect the viability of the rat glial cell line C6. Transcriptome analysis revealed differentially expressed genes (DEGs) between PLE-treated and non-treated amoebae. A total of 5,846 DEGs were identified, of which 2,189 were upregulated, and 3,657 were downregulated in the PLE-treated amoebae. The DEGs were categorized into biological process (1,742 genes), cellular component (1,237 genes), and molecular function (846 genes) based on the gene ontology analysis, indicating that PLE may have dramatically altered the biological and cellular functions of the amoeba and contributed to their death. These results suggest that PLE has anti-N. fowleri activity and may be considered as a potential candidate for the development of therapeutic drugs for PAM. It may also be used as a supplement compound to enhance the therapeutic efficacy of drugs currently used to treat PAM.


Assuntos
Naegleria fowleri , Pinus , Extratos Vegetais , Folhas de Planta , Naegleria fowleri/efeitos dos fármacos , Naegleria fowleri/genética , Extratos Vegetais/farmacologia , Pinus/química , Folhas de Planta/química , Animais , Ratos , Antiprotozoários/farmacologia , Linhagem Celular , Trofozoítos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/parasitologia , Encéfalo/metabolismo , Encéfalo/patologia , Perfilação da Expressão Gênica , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Concentração Inibidora 50 , Sobrevivência Celular/efeitos dos fármacos
13.
Nanomicro Lett ; 16(1): 219, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884690

RESUMO

Doped two-dimensional (2D) materials hold significant promise for advancing many technologies, such as microelectronics, optoelectronics, and energy storage. Herein, n-type 2D oxidized Si nanosheets, namely n-type siloxene (n-SX), are employed as Li-ion battery anodes. Via thermal evaporation of sodium hypophosphite at 275 °C, P atoms are effectively incorporated into siloxene (SX) without compromising its 2D layered morphology and unique Kautsky-type crystal structure. Further, selective nucleophilic substitution occurs, with only Si atoms being replaced by P atoms in the O3≡Si-H tetrahedra. The resulting n-SX possesses two delocalized electrons arising from the presence of two electron donor types: (i) P atoms residing in Si sites and (ii) H vacancies. The doping concentrations are varied by controlling the amount of precursors or their mean free paths. Even at 2000 mA g-1, the n-SX electrode with the optimized doping concentration (6.7 × 1019 atoms cm-3) delivers a capacity of 594 mAh g-1 with a 73% capacity retention after 500 cycles. These improvements originate from the enhanced kinetics of charge transport processes, including electronic conduction, charge transfer, and solid-state diffusion. The approach proposed herein offers an unprecedented route for engineering SX anodes to boost Li-ion storage.

15.
ACS Appl Mater Interfaces ; 16(25): 32375-32384, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38869189

RESUMO

Colloidal PbS quantum dot solar cells (QDSCs) have been primarily demonstrated in n-i-p structures by incorporating a solution-processed ZnO electron transporting layer (ETL). Nevertheless, the inherent energy barrier for the electron extraction at the ZnO/PbS junction along with the defective nature significantly diminishes the performance of the PbS QDSCs. In this study, by employing Sn-doped ZnO (ZTO) ETL, we have tuned the conduction band offset at the junction from spike-type to cliff-type so that the electron extraction barrier can be eliminated and the overall photovoltaic parameters can be enhanced (open-circuit voltage of 0.7 V, fill factor over 70%, and efficiency of 11.3%) as compared with the counterpart with the undoped ZnO ETL. The X-ray photoelectron spectroscopy (XPS) analysis revealed a mitigation of oxygen vacancies in the ZTO ETL of our PbS QDSCs. Our work signifies the importance of Sn doping into the conventional ZnO ETL for the superior electron extraction in PbS QDSCs.

16.
BMC Complement Med Ther ; 24(1): 213, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835032

RESUMO

BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer's disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats. METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1ß (IL-1ß) and cellular expression were examined in the spinal cord and dorsal root ganglion. RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1ß were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS. CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1ß is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.


Assuntos
Álcoois Benzílicos , Modelos Animais de Doenças , Glucosídeos , Hiperalgesia , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Álcoois Benzílicos/farmacologia , Glucosídeos/farmacologia , Masculino , Ratos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Nervos Espinhais/efeitos dos fármacos , Injeções Espinhais
17.
Brain Pathol ; : e13282, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38932696

RESUMO

Although the concept that the blood-brain barrier (BBB) plays an important role in the etiology and pathogenesis of Alzheimer's disease (AD) has become increasingly accepted, little is known yet about how it actually contributes. We and others have recently identified a novel functionally distinct subset of BBB pericytes (PCs). In the present study, we sought to determine whether these PC subsets differentially contribute to AD-associated pathologies by immunohistochemistry and amyloid beta (Aß) peptidomics. We demonstrated that a disease-associated PC subset (PC2) expanded in AD patients compared to age-matched, cognitively unimpaired controls. Surprisingly, we found that this increase in the percentage of PC2 (%PC2) was correlated negatively with BBB breakdown in AD patients, unlike in natural aging or other reported disease conditions. The higher %PC2 in AD patients was also correlated with a lower Aß42 plaque load and a lower Aß42:Aß40 ratio in the brain as determined by immunohistochemistry. Colocalization analysis of multicolor confocal immunofluorescence microscopy images suggests that AD patient with low %PC2 have higher BBB breakdown due to internalization of Aß42 by the physiologically normal PC subset (PC1) and their concomitant cell death leading to more vessels without PCs and increased plaque load. On the contrary, it appears that PC2 can secrete cathepsin D to cleave and degrade Aß built up outside of PC2 into more soluble forms, ultimately contributing to less BBB breakdown and reducing Aß plaque load. Collectively our data shows functionally distinct mechanisms for PC1 and PC2 in high Aß conditions, demonstrating the importance of correctly identifying these populations when investigating the contribution of neurovascular dysfunction to AD pathogenesis.

18.
Clin Chim Acta ; 561: 119819, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38901629

RESUMO

Metabolic syndrome (MetS) represents a significant public health concern due to its association with an increased risk of cardiovascular disease, type 2 diabetes, and other serious health conditions. Despite extensive research, the underlying molecular mechanisms contributing to MetS pathogenesis remain elusive. This review aims to provide a comprehensive overview of the molecular mechanisms linking MetS and cluster of differentiation (CD) markers, which play critical roles in immune regulation and cellular signaling. Through an extensive literature review with a systematic approach, we examine the involvement of various CD markers in MetS development and progression, including their roles in adipose tissue inflammation, insulin resistance, dyslipidemia, and hypertension. Additionally, we discuss potential therapeutic strategies targeting CD markers for the management of MetS. By synthesizing current evidence, this review contributes to a deeper understanding of the complex interplay between immune dysregulation and metabolic dysfunction in MetS, paving the way for the development of novel therapeutic interventions.


Assuntos
Síndrome Metabólica , Síndrome Metabólica/metabolismo , Humanos , Biomarcadores/metabolismo
19.
AIDS Res Hum Retroviruses ; 40(9): 531-542, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38787309

RESUMO

Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and interleukin (IL)-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies versus (CVD-path) alone or simian immunodeficiency virus encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies, and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, p = 0.11; gal-9, p = 0.001; IL-18, p = 0.007; sCD163, p < 0.001; %BrdU p = 0.02). Although gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlated strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a marker of monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (p = 0.02) and increased sCD163 in late infection (p = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE.


Assuntos
Biomarcadores , Galectina 3 , Galectinas , Interleucina-18 , Ativação de Macrófagos , Monócitos , Síndrome de Imunodeficiência Adquirida dos Símios , Galectinas/sangue , Interleucina-18/sangue , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Monócitos/metabolismo , Monócitos/imunologia , Galectina 3/sangue , Biomarcadores/sangue , Humanos , Macaca mulatta , Masculino , Receptores de Superfície Celular/sangue , Antígenos CD/sangue , Vírus da Imunodeficiência Símia , Doenças Cardiovasculares , Macrófagos/metabolismo , Macrófagos/virologia , Antígenos de Diferenciação Mielomonocítica/sangue , Proteínas Sanguíneas/metabolismo
20.
Sci Prog ; 107(2): 368504241253692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38780474

RESUMO

The brain regulates every physiological process in the body, including metabolism. Studies investigating brain metabolism have shown that stress can alter major metabolic processes, and that these processes can vary between regions. However, no study has investigated how metabolic pathways may be altered by stressor perception, or whether stress-responsive brain regions can also regulate metabolism. The basolateral amygdala (BLA), a region important for stress and fear, has reciprocal connections to regions responsible for metabolic regulation. In this study, we investigated how BLA influences regional metabolic profiles within the hippocampus (HPC) and medial prefrontal cortex (mPFC), regions involved in regulating the stress response and stress perception, using optogenetics in male C57BL/6 mice during footshock presentation in a yoked shuttlebox paradigm based on controllable (ES) and uncontrollable (IS) stress. RNA extracted from HPC and mPFC were loaded into NanoString® Mouse Neuroinflammation Panels, which also provides a broad view of metabolic processes, for compilation of gene expression profiles. Results showed differential regulation of carbohydrate and lipid metabolism, and insulin signaling gene expression pathways in HPC and mPFC following ES and IS, and that these differences were altered in response to optogenetic excitation or inhibition of the BLA. These findings demonstrate for the first time that individual brain regions can utilize metabolites in a way that are unique to their needs and function in response to a stressor, and that vary based on stressor controllability and influence by BLA.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Hipocampo , Camundongos Endogâmicos C57BL , Optogenética , Córtex Pré-Frontal , Estresse Psicológico , Animais , Masculino , Complexo Nuclear Basolateral da Amígdala/metabolismo , Camundongos , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Córtex Pré-Frontal/metabolismo , Hipocampo/metabolismo , Encéfalo/metabolismo , Metabolismo dos Lipídeos
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