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1.
ACS Appl Mater Interfaces ; 16(15): 19529-19536, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564290

RESUMO

Flexible and stretchable transparent heaters (THs) have been widely used in various applications, including deicing and defogging of flexible screens as well as thermotherapy pads. Ionic THs based on ionogels have emerged as a promising alternative to conventional electronic THs due to their unique advantages in terms of transparency-conductance conflict, uniform heating, and interfacial adhesion. However, the commonly used hydrophilic ionogels inevitably introduce a moisture-sensitive issue. In this work, we present a stretchable and transparent hydrophobic ionogel-based heater that utilizes ionic current-induced Joule heating under high-frequency alternating current. This ionogel-based TH exhibits exceptional multifunctional properties with low hysteresis, a fracture strain of 840%, transmittance of 93%, conductivity of 0.062 S m-1, temperature resistance up to 165 °C, voltage resistance up to 120 V, heating rate of 0.1 °C s-1, steady-state temperature at 115 °C, and uniform heating even when bent or stretched (up to 200%). Furthermore, it maintains its heating performance when it is directly exposed to water. This hydrophobic ionogel-based TH expands the range of materials available for ionic THs and paves the way for their practical applications.

2.
J Hazard Mater ; 470: 134129, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38565019

RESUMO

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.


Assuntos
Rim , Parabenos , Fenóis , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Peixe-Zebra , Animais , Parabenos/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Células HEK293 , Transdução de Sinais/efeitos dos fármacos , Fenóis/toxicidade , Glucosídeos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nefropatias/metabolismo
3.
Vet Res ; 55(1): 33, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493160

RESUMO

Lumpy skin disease virus (LSDV) infection is a major socio-economic issue that seriously threatens the global cattle-farming industry. Here, a recombinant virus LSDV-ΔTK/EGFP, expressing enhanced green fluorescent protein (EGFP), was constructed with a homologous recombination system and applied to the high-throughput screening of antiviral drugs. LSDV-ΔTK/EGFP replicates in various kidney cell lines, consistent with wild-type LSDV. The cytopathic effect, viral particle morphology, and growth performance of LSDV-ΔTK/EGFP are consistent with those of wild-type LSDV. High-throughput screening allowed to identify several molecules that inhibit LSDV-ΔTK/EGFP replication. The strong inhibitory effect of theaflavin on LSDV was identified when 100 antiviral drugs were screened in vitro. An infection time analysis showed that theaflavin plays a role in the entry of LSDV into cells and in subsequent viral replication stages. The development of this recombinant virus will contribute to the development of LSDV-directed antiviral drugs and the study of viral replication and mechanisms of action.


Assuntos
Doenças dos Bovinos , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/veterinária , Replicação Viral , Linhagem Celular
4.
Plant Physiol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536032

RESUMO

Carotenoids are major pigments contributing to fruit coloration. We previously reported that the apple (Malus domestica Borkh.) mutant fruits of 'Beni Shogun' and 'Yanfu 3' show a marked difference in fruit coloration. However, the regulatory mechanism underlying this phenomenon remains unclear. In this study, we determined that carotenoid is the main factor influencing fruit flesh color. We identified an R1-type MYB transcription factor, MdMYBS1, which was found to be highly associated with carotenoids and abscisic acid (ABA) contents of apple fruits. Overexpression of MdMYBS1 promoted, and silencing of MdMYBS1 repressed, ß-branch carotenoids synthesis and ABA accumulation. MdMYBS1 regulates carotenoid biosynthesis by directly activating the major carotenoid biosynthetic genes encoding phytoene synthase (MdPSY2-1) and lycopene ß-cyclase (MdLCYb). 9-cis-epoxycarotenoid dioxygenase 1 (MdNCED1) contributes to ABA biosynthesis, and MdMYBS1 enhances endogenous ABA accumulation by activating the MdNCED1 promoter. In addition, the basic leucine zipper domain transcription factor ABSCISIC ACID-INSENSITIVE5 (MdABI5) was identified as an upstream activator of MdMYBS1, which promotes carotenoid and ABA accumulation. Furthermore, ABA promotes carotenoid biosynthesis and enhances MdMYBS1 and MdABI5 promoter activities. Our findings demonstrate that the MdABI5-MdMYBS1 cascade activated by ABA regulates carotenoid-derived fruit coloration and ABA accumulation in apple, providing avenues in breeding and planting for improvement of fruit coloration and quality.

6.
Kaohsiung J Med Sci ; 40(2): 161-174, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37873881

RESUMO

Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer-related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT-PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug-resistant glioma cells. Cell viability was assessed using the CCK-8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co-immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si-KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Histonas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Linhagem Celular Tumoral , Glioma/genética , Metilação , Resistencia a Medicamentos Antineoplásicos/genética , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
7.
Plant Physiol ; 194(2): 634-661, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37770070

RESUMO

Lysine acetylation is a conserved regulatory posttranslational protein modification that is performed by lysine acetyltransferases (KATs). By catalyzing the transfer of acetyl groups to substrate proteins, KATs play critical regulatory roles in all domains of life; however, no KATs have yet been identified in cyanobacteria. Here, we tested all predicted KATs in the cyanobacterium Synechococcus sp. PCC 7002 (Syn7002) and demonstrated that A1596, which we named cyanobacterial Gcn5-related N-acetyltransferase (cGNAT2), can catalyze lysine acetylation in vivo and in vitro. Eight amino acid residues were identified as the key residues in the putative active site of cGNAT2, as indicated by structural simulation and site-directed mutagenesis. The loss of cGNAT2 altered both growth and photosynthetic electron transport in Syn7002. In addition, quantitative analysis of the lysine acetylome identified 548 endogenous substrates of cGNAT2 in Syn7002. We further demonstrated that cGNAT2 can acetylate NAD(P)H dehydrogenase J (NdhJ) in vivo and in vitro, with the inability to acetylate K89 residues, thus decreasing NdhJ activity and affecting both growth and electron transport in Syn7002. In summary, this study identified a KAT in cyanobacteria and revealed that cGNAT2 regulates growth and photosynthesis in Syn7002 through an acetylation-mediated mechanism.


Assuntos
Lisina Acetiltransferases , Synechococcus , Lisina Acetiltransferases/genética , Lisina Acetiltransferases/metabolismo , Lisina/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Synechococcus/genética , Synechococcus/metabolismo , Acetilação
8.
J Alzheimers Dis ; 96(4): 1579-1592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38007666

RESUMO

BACKGROUND: Emerging evidence has revealed that dysregulation of the hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), contributes to the pathogenesis of Alzheimer's disease (AD). Specifically, defective GHSR function and resultant hippocampal ghrelin resistance are linked to hippocampal synaptic injury in AD paradigms. Also, AD patients exhibit elevated ghrelin activation. However, the detailed molecular mechanisms of hippocampal GHSR dysfunction and the relevance of ghrelin elevation to hippocampal ghrelin resistance in AD-relevant pathological settings are not fully understood. OBJECTIVE: In the current study, we employed a recently established mouse line of AD risk [humanized amyloid beta knockin (hAß KI mice), also referred to as a mouse model of late-onset AD in previous literature] to further define the role of ghrelin system dysregulation in the development of AD. METHODS: We employed multidisciplinary techniques to determine the change of plasma ghrelin and the functional status of GHSR in hAß KI mice as well as primary neuron cultures. RESULTS: We observed concurrent plasma ghrelin elevation and hippocampal GHSR desensitization with disease progression. Further examination excluded the possibility that ghrelin elevation is a compensatory change in response to GHSR dysfunction. In contrast, further in vitro and in vivo results show that agonist-mediated overstimulation potentiates GHSR desensitization through enhanced GHSR internalization. CONCLUSIONS: These findings suggest that circulating ghrelin elevation is a pathological event underlying hippocampal GHSR dysfunction, culminating in hippocampal ghrelin resistance and resultant synaptic injury in late-onset AD-related settings.


Assuntos
Doença de Alzheimer , Grelina , Humanos , Camundongos , Animais , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Peptídeos beta-Amiloides , Hipocampo/metabolismo , Envelhecimento/genética , Doença de Alzheimer/genética
9.
Medicine (Baltimore) ; 102(44): e35442, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37932973

RESUMO

OBJECTIVE: Systematic evaluation of the efficacy and safety of conservative hemodynamic cure for venous insufficiency (CHIVA) compared with high ligation and stripping (HLS) in the treatment of varicose veins of lower extremities. METHODS: We conducted a systematic literature search and compared the randomized controlled trial and retrospective cohort study of CHIVA and HLS in the treatment of varicose veins of lower extremities in several databases, including China National Knowledge Infrastructure, Wanfang database, cqvip datebase, PubMed, Cochrane library and EMBASE, to identify articles that might meet the criteria. Meta-analysis was performed using Revman 5.3 and Stata 13.0 software. RESULTS: This Meta-analysis included a total of 14 research articles. This meta-analysis shows that CHIVA requires shorter operation time than HLS [mean difference (MD) = -13.57, 95% confidence interval (CI) (-21.05, -6.10), P = .0004]. There is less blood loss with CHIVA surgery [MD = -21.72, 95% CI (-30.35, -13.09), P < .00001]. The number of incisions made by the CHIVA technique is less [MD = -3.67, 95% CI (-4.03, -3.31), P < .00001]. Patients who underwent CHIVA had a shorter hospital stay [MD = -3.40, 95% CI (-4.72, -2.09), P < .00001]. The relapse rate was lower after CHIVA [OR = 0.36, 95% CI (0.18, 0.70), P = .003]. In terms of postoperative complications, CHIVA has a lower total complication rate [MD = 0.26, 95% CI (0.15, 0.46), P < .00001]. The incidence of deep vein thrombosis was lower after CHIVA [MD = 0.23, 95% CI (0.06, 0.92), P = .04]. CHIVA has a lower incidence of sensory disturbance than HLS [OR = 0.39, 95% CI (0.25, 0.60), P < .0001]. CHIVA technique has less nerve injury rate than HLS [OR = 0.11, 95% CI (0.02, 0.62), P = .01]. The incidence of hematoma was lower after CHIVA [OR = 0.48, 95% CI (0.27, 0.87), P = .02]. Among other metrics, the comparison results of the 2 techniques were similar. CONCLUSION: By comparison, it is found that CHIVA has shorter operation time, less blood loss, and fewer surgical incisions. Patients who underwent CHIVA surgery had shorter hospital stays and lower relapse rates. In terms of complications, the incidence of total complications after CHIVA is lower, and the incidence of postoperative deep vein thrombosis, postoperative sensory, nerve injury, and postoperative hematoma is also lower than that of HLS.


Assuntos
Varizes , Trombose Venosa , Humanos , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares/métodos , Varizes/cirurgia , Extremidade Inferior , Complicações Pós-Operatórias , Ultrassonografia de Intervenção , Hematoma , Recidiva , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
JCI Insight ; 8(22)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37991017

RESUMO

Mitochondria are critical for neurophysiology, and mitochondrial dysfunction constitutes a characteristic pathology in both brain aging and Alzheimer disease (AD). Whether mitochondrial deficiency in brain aging and AD is mechanistically linked, however, remains controversial. We report a correlation between intrasynaptosomal amyloid ß 42 (Aß42) and synaptic mitochondrial bioenergetics inefficiency in both aging and amnestic mild cognitive impairment, a transitional stage between normal aging and AD. Experiments using a mouse model expressing nonmutant humanized Aß (humanized Aß-knockin [hAß-KI] mice) confirmed the association of increased intramitochondrial sequestration of Aß42 with exacerbated synaptic mitochondrial dysfunction in an aging factor- and AD risk-bearing context. Also, in comparison with global cerebral Aß, intramitochondrial Aß was relatively preserved from activated microglial phagocytosis in aged hAß-KI mice. The most parsimonious interpretation of our results is that aging-related mitochondrial Aß sequestration renders synaptic mitochondrial dysfunction in the transitional stage between normal aging and AD. Mitochondrial dysfunction in both brain aging and the prodromal stage of AD may follow a continuous transition in response to escalated intraneuronal, especially intramitochondrial Aß, accumulation. Moreover, our findings further implicate a pivotal role of mitochondria in harboring early amyloidosis during the conversion from normal to pathological aging.


Assuntos
Doença de Alzheimer , Humanos , Animais , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Mitocôndrias/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças
11.
Wei Sheng Yan Jiu ; 52(5): 721-725, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802894

RESUMO

OBJECTIVE: To evaluate the chronic health risk of heavy metals and metalloid in drinking water through oral ingestion in a typical area. METHODS: Monitoring data of seven heavy metals and metalloid elements(Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd) in drinking water in a typical area of Huaihe River Basin were collected from 2015 to 2019. The health risks of heavy metals and metalloid in drinking water in the area were assessed using the classic four-step health risk assessment model. RESULTS: The average concentrations of Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd in drinking water in the typical area of Huaihe River Basin were(0.13±0.45), (0.49±0.49), (0.34±0.99), (1.10±2.49), (32.29±126.64), (2.13±0.50) and(0.03±0.04) µg/L, respectively. In which, Hg, Mn and Ni exceeded the limit of the Standard for Drinking Water(GB 5749-2006), the exceedance rates were 2.14%, 6.79% and 0.3%, respectively, and the maximum exceedance times were 2.61, 8.90 and 0.34, respectively. The chronic non-carcinogenic risks of Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd were 1.32×10~(-2), 4.99×10~(-2), 2.97×10~(-3), 1.68×10~(-3), 7.04×10~(-3), 2.17×10~(-2) and 1.83×10~(-3), respectively. The carcinogenic risks of As, Pb, Cr~(6+) and Cd were 2.24×10~(-5), 8.82×10~(-8), 3.25×10~(-5) and 5.86×10~(-7), respectively. CONCLUSION: Hg, Mn and Ni in drinking water exceeded the standard in a typical area of Huaihe River Basin from 2015 to 2019. The chronic non-carcinogenic risks of Hg, As and other 7 heavy metals and metalloid are at an acceptable level(HQ≤1), while As and Cr~(6+) have certain carcinogenic risks(10~(-6)≤CR≤10~(-4)).


Assuntos
Água Potável , Metaloides , Metais Pesados , Poluentes Químicos da Água , Cádmio , China , Água Potável/análise , Água Potável/química , Monitoramento Ambiental , Chumbo , Mercúrio , Metaloides/análise , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análise , Humanos
12.
World J Gastrointest Surg ; 15(9): 2003-2011, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37901745

RESUMO

BACKGROUND: Esophageal gastric anastomosis is a common surgical technique used to treat patients with gastric cancer who undergo total gastrectomy. However, using simple anastomosis techniques alone may not meet the needs of patients in some cases and can lead to complications such as anastomotic stenosis and ulceration. In order to overcome these issues and improve patient prognosis, muscle flap reconstruction technique has emerged. Muscle flap reconstruction is a method of improving gastric-esophageal anastomosis by transplanting muscle tissue. By covering the anastomotic site with muscle tissue, it not only enhances the stability of the anastomosis site but also increases blood supply, promoting healing and recovery of the anastomosis. Therefore, the use of muscle flap reconstruction technique in esophageal gastric anastomosis during total gastrectomy for gastric cancer is increasingly widely applied. AIM: To determine the effectiveness of esophagogastric anastomosis using the muscle flap reconstruction technology in total abdominal gastrectomy for gastric cancer and perform follow-up experiments to understand the factors affecting patients' prognosis. METHODS: The study subjects were 60 patients with gastric cancer who were admitted to our hospital between October 2018 and January 2022. All patients underwent esophagogastric anastomosis using the double muscle flap reconstruction technology in total abdominal gastrectomy. Perioperative indicators were determined, and patients were followed up for 1 year. Furthermore, patient outcomes were observed within 1 year, followed by patient classification based on different outcomes. Moreover, clinicopathological parameters were observed and relevant factors affecting patient prognosis were analyzed. RESULTS: The operation time was 318 ± 43 min, the formation time of esophageal double muscle flap anastomosis was 110 ± 13 min, the number of lymph node dissections was 26 ± 6, the incision length was 3 ± 0.6 cm, intraoperative bleeding volume was 48 ± 15 mL, first anal exhaust time was 5.3 ± 1.8 d, first meal time was 6.0 ± 1.6 d, length of hospital stay was 11.8 ± 2.5, and treatment cost was 5.8 ± 0.7 thousand yuan. The patient experienced three postoperative complications: 2 cases of pulmonary infection and 1 case of respiratory discomfort. During 1-year follow-up, 50 patients survived and 10 died. Univariate analysis revealed that histological types, tumor size, tumor-node-metastasis staging, vascular invasion, and postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting the prognosis of surviving patients. Furthermore, Cox regression analysis revealed that postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting patient prognosis. The survival time of the survival group was significantly higher than that of the death group (P < 0.05). CONCLUSION: Esophagogastric anastomotic using muscle flap reconstruction exhibits good effects on patients who undergo total abdominal gastrectomy for cancer. Postoperative adjuvant radiotherapy and chemotherapy are the main factors affecting patient prognosis.

13.
Dalton Trans ; 52(37): 13358-13366, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37671899

RESUMO

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

14.
Fish Shellfish Immunol ; 141: 109062, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37678480

RESUMO

Neuroinflammation is prevalent in multiple brain diseases and may also lead to dementia, cognitive impairment, and impaired spatial memory function associated with neurodegenerative diseases. A neuroprotective and antioxidant flavonoid, rutin hydrate (RH), was evaluated for the anti-neuroinflammatory activity mediated by copper sulfate (CuSO4) solution and lipopolysaccharide (LPS) in zebrafish. The results showed that 100 mg/L RH significantly reduced the ratio of neutrophil mobility in caudal hematopoietic tissue (CHT) region caused by CuSO4 and the number of neutrophils co-localized with facial peripheral nerves. In the LPS model, RH co-injection significantly diminished neutrophil and macrophage migration. Therefore, RH exhibited a significant rescue effect on both models. In addition, RH treatment remarkably reduced the effects of neuroinflammation on the locomotor ability, expression levels of genes associated with behavioral disorders, and acetylcholinesterase (AChE) activity. Furthermore, network pharmacology techniques were employed to investigate the potential mechanisms, and the associated genes and enzyme activities were validated in order to elucidate the underlying mechanisms. Network pharmacological analysis and zebrafish model indicated that RH regulated the expressions of NF-κB pathway-related targets (Toll-like receptor 9 (tlr9), nuclear factor kappa B subunit 1 (nfkb1), RELA proto-oncogene (RelA), nitric oxide synthase 2a, inducible (nos2a), tumour necrosis factor alpha-like (tnfα), interleukin 6 (il6), interleukin 1ß (il1ß), chemokine 8 (cxcl8), and macrophage migration inhibitory factor (mif)) as well as six key factors (arachidonic acid 4 alpha-lipoxygenase (alox4a), arachidonate 5-lipoxygenase a (alox5), prion protein a (prnpa), integrin, beta 2 (itgb2), catalase (CAT), and alkaline phosphatase (ALP) enzymes). Through this study, a thorough understanding of the mechanism underlying the therapeutic effects of RH in neuroinflammation has been achieved, thereby establishing a solid foundation for further research on the potential therapeutic applications of RH in neuroinflammatory disorders.


Assuntos
NF-kappa B , Peixe-Zebra , Animais , NF-kappa B/metabolismo , Peixe-Zebra/metabolismo , Doenças Neuroinflamatórias , Rutina/farmacologia , Rutina/metabolismo , Rutina/uso terapêutico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Acetilcolinesterase/metabolismo , Microglia , Fator de Necrose Tumoral alfa/metabolismo
15.
Inorg Chem ; 62(40): 16294-16298, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37772803

RESUMO

It is desired to design and construct more efficient enzymes with better performance to catalyze carbene N-H insertions for the synthesis of bioactive molecules. To this end, we exploited and designed a series of human neuroglobin (Ngb) mutants. As shown in this study, a double mutant, A15C/H64G Ngb, with an additional disulfide bond and a modified heme active site, exhibited yields up to >99% and total turnover numbers up to 33000 in catalyzing the carbene N-H insertions for aromatic amine derivatives, including those with a large size such as 1-aminopyrene. Moreover, for o-phenylenediamine derivatives, they underwent two cycles of N-H insertions, followed by cyclization to form quinoxalinones, as confirmed by the X-ray crystal structures. This study suggests that Ngb can be designed into a functional carbene transferase for efficiently catalyzing carbene N-H insertion reactions with a range of substrates. It also represents the first example of the formation of quinoxalinones catalyzed by an engineered heme enzyme.

16.
Perfusion ; : 2676591231205124, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37776228

RESUMO

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

17.
Ecotoxicol Environ Saf ; 265: 115523, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37776822

RESUMO

Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.

18.
Transplant Proc ; 55(9): 2232-2240, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37777366

RESUMO

The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.


Assuntos
Leucemia , Pinellia , Humanos , Camundongos , Animais , Caspase 3/genética , Caspase 3/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Pinellia/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Apoptose , Leucemia/tratamento farmacológico , Proliferação de Células
19.
Int J Biometeorol ; 67(11): 1789-1802, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37561207

RESUMO

COVID-19 has ravaged Brazil, and its spread showed spatial heterogeneity. Changes in the environment have been implicated as potential factors involved in COVID-19 transmission. However, considerable research efforts have not elucidated the risk of environmental factors on COVID-19 transmission from the perspective of infectious disease dynamics. The aim of this study is to model the influence of the environment on COVID-19 transmission and to analyze how the socio-ecological factors affecting the probability of virus transmission in 10 states dramatically shifted during the early stages of the epidemic in Brazil. First, this study used a Pearson correlation to analyze the interconnection between COVID-19 morbidity and socio-ecological factors and identified factors with significant correlations as the dominant factors affecting COVID-19 transmission. Then, the time-lag effect of dominant factors on the morbidity of COVID-19 was investigated by constructing a distributed lag nonlinear model and standard two-stage meta-analytic model, and the results were considered in the improved SEIR model. Lastly, a machine learning method was introduced to explore the nonlinear relationship between the environmental propagation probability and socio-ecological factors. By analyzing the impact of environmental factors on virus transmission, it can be found that population mobility directly caused by human activities had a greater impact on virus transmission than temperature and humidity. The heterogeneity of meteorological factors can be accounted for by the diverse climate patterns in Brazil. The improved SEIR model was adopted to explore the interconnection of COVID-19 transmission and the environment, which revealed a new strategy to probe the causal links between them.

20.
J Colloid Interface Sci ; 650(Pt A): 47-57, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37392499

RESUMO

"Thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" are the new standards of contemporary science and technology for microwave absorption(MA) material. In this study, N-doped-rGO/g-C3N4 MA material was prepared for the first time by simple heat treatment, which the N atoms were doped into rGO and g-C3N4 was dispersed on the surface of N-doped-rGO, and its density is only 0.035 g/cm3. The impedance matching of the N-doped-rGO/g-C3N4 composite was well adjusted by decreasing the dielectric constant and attenuation constant due to the g-C3N4 semiconductor property and the graphite-like structure. Moreover, the distribution of g-C3N4 among N-doped-rGO sheets can produce more polarization effect and relaxation effect by increasing the lamellar spacing. Furthermore, the polarization loss of N-doped-rGO/g-C3N4 could be increased successfully by doping N atoms and g-C3N4. Ultimately, the MA property of N-doped-rGO/g-C3N4 composite was optimized significantly, with a loading of 5 wt%, the N-doped-rGO/g-C3N4 composite exhibited the RLmin of -49.59 dB and the effective absorption bandwidth could reach 4.56 GHz when the thickness was only 1.6 mm. The "thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" of MA material are actually achieved by the N-doped-rGO/g-C3N4.

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