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1.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109943, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38810897

RESUMO

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

2.
Nanomaterials (Basel) ; 14(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38668156

RESUMO

In recent years, the phenomenon of optical second harmonic generation (SHG) has attracted significant attention as a pivotal nonlinear optical effect in research. Notably, in low-dimensional materials (LDMs), SHG detection has become an instrumental tool for elucidating nonlinear optical properties due to their pronounced second-order susceptibility and distinct electronic structure. This review offers an exhaustive overview of the generation process and experimental configurations for SHG in such materials. It underscores the latest advancements in harnessing SHG as a sensitive probe for investigating the nonlinear optical attributes of these materials, with a particular focus on its pivotal role in unveiling electronic structures, bandgap characteristics, and crystal symmetry. By analyzing SHG signals, researchers can glean invaluable insights into the microscopic properties of these materials. Furthermore, this paper delves into the applications of optical SHG in imaging and time-resolved experiments. Finally, future directions and challenges toward the improvement in the NLO in LDMs are discussed to provide an outlook in this rapidly developing field, offering crucial perspectives for the design and optimization of pertinent devices.

3.
Heliyon ; 10(5): e26552, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434403

RESUMO

Objectives: There are many available pharmaceutical and surgical management for Coronary artery disease (CAD) patients. However, coronary artery bypass grafting (CABG) is the preferred treatment modality for CAD patients with low ejection fraction (EF) in view of the more favorable outcomes. This study aimed to determine the associated factors of poor outcomes post-CABG for heart failure patients with reduced left ventricular ejection fraction who underwent on-pump and off-pump CABG. Methods: A retrospective review of CAD patients who underwent isolated on-pump CABG (ONCAB) or off-pump CABG (OPCAB) in Beijing Anzhen Hospital Affiliated with Capital Medical University from January 2013 to March 2021. Only those with confirmed reduced left ventricular ejection fraction (LVEF) ≤40% on preoperative echocardiography were included. By analyzing the clinical and surgical data, postoperative mortality and morbidity, as well as major cardiovascular and cerebrovascular adverse events (MACCE) as endpoints, certain risk factors of the postoperative complications were identified. Results: Out of the 500 patients, 64 developed MACCE, of which 14 (13.6%) occurred in the ONCAB group and 50 (14.0%) in the OPCAB group. Univariate COX regression analysis showed that age ≥65 years, history of diabetes, and preoperative renal insufficiency were independent risk factors for postoperative primary endpoint events in CAD patients with heart failure with reduced ejection fraction (HFrEF). Following the multivariate COX regression analysis, in addition to the above three risk factors, a history of previous percutaneous coronary angiography (PCI) intervention was also a risk factor for the occurrence of the primary endpoints post-CABG. Conclusion: Based on the analysis, significant predictors of post-CABG MACCE in patients with HFrEF included being older than 65 years old, having diabetes, preoperative renal insufficiency, and having previous PCI.

4.
Cell Signal ; 116: 111064, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38266744

RESUMO

Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233-1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro, human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1ß and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Animais , Humanos , Camundongos , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Camundongos Endogâmicos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Interferente Pequeno/metabolismo , Esfingomielina Fosfodiesterase/metabolismo
5.
ACS Appl Mater Interfaces ; 16(1): 907-914, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38146641

RESUMO

Entropy engineering is aneffective scheme to reduce the thermal conductivity of thermoelectric materials, but it inevitably deteriorates the carrier mobility. Here, we report the optimization of thermoelectric performance of PbTe by combining entropy engineering and nanoprecipitates. In the continuously tuned compounds of Pb0.98Na0.02Te(1-2x)SxSex, we show that the x = 0.05 sample exhibits an exceptionally low thermal conductivity relative to its configuration entropy. By introducing Mn doping, the produced temperature-dependent nanoprecipitates of MnSe cause the high-temperature thermal conductivity to be further reduced. A very low lattice thermal conductivity of 0.38 W m-1 K-1 is achieved at 825 K. Meanwhile, the carrier mobility of the samples is only slightly influenced, owing to the well-controlled configuration entropy and the size of nanoprecipitates. Finally, a high peak zT of ∼2.1 at 825 K is obtained in the Pb0.9Na0.04Mn0.06Te0.9S0.05Se0.05 alloy.

6.
Polymers (Basel) ; 15(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37688224

RESUMO

Silicone rubber insulators are widely used in power grids because of their excellent performance, but aging has been an inevitable problem of silicone rubber, especially in extreme conditions, such as acidic conditions. In order to clarify the performance changes in silicone rubber in an acidic environment, this paper uses the developed acid-resistant silicone rubber sheet and common silicone rubber samples as the research objects, and conducts an aging comparison test on them in a natural acidic environment. The electrical properties, physical properties, and chemical properties of the two types of silicone rubber specimens with different aging times are analyzed to obtain the performance characteristics of silicone rubber under a natural acidic environment. The research results show that the dry flash voltage and pollution flashover voltage of the acid-resistant silicone rubber after one year of aging are greater than those of the common type; the water repellency of both types of silicone rubber remains in good condition. The silicone rubber produced by our team according to the self-developed acid-resistant silicone rubber formula has indeed played a role in delaying aging in an acidic environment compared with the common-type silicone rubber.

8.
Exp Cell Res ; 430(2): 113735, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37517590

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary morphology, affecting more and more women of reproductive age. Our study aimed to explore the molecular mechanism and effect of exosomal miR-4449 on granulosa cells (GCs). Two immortalized human ovarian granulosa cells (KGN and COV434 cells) were used for in vitro functional studies. Our study found that follicular fluid (FF) derived exosomal miR-4449 was significantly decreased in women with PCOS compared with the control patients. And exosomal miR-4449 could alleviate GCs oxidative stress (OS) and promote GCs proliferation, while the opposite trend was observed after inhibiting the expression of miR-4449. In addition, we demonstrated that Kelch-like ECH-associated protein 1(KEAP1) was a direct target of miR-4449 through dual-luciferase reporter assay, and the expression patterns of KEAP1 and miR-4449 in PCOS FF-derived exosomes were exactly opposite. In addition, KEAP1/NRF2 signaling pathway may play an important role in GCs proliferation and OS. Our results demonstrated that the decreased FF-derived exosomal miR-4449 expression in PCOS might aggravate the OS of GCs and inhibit GCs proliferation via KEAP1/NRF2 signaling pathway. Exosomal miR-4449 might be a potential biomarker for the diagnosis of PCOS. Our study contributes to a new understanding of the pathogenesis of PCOS.


Assuntos
MicroRNAs , Síndrome do Ovário Policístico , Humanos , Feminino , MicroRNAs/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Líquido Folicular/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Células da Granulosa , Proliferação de Células/genética , Apoptose
9.
Opt Express ; 31(6): 9481-9495, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157518

RESUMO

Multi-mode converters, which can achieve spatial mode conversion in multimode waveguide, play a key role in multi-mode photonics and mode-division multiplexing (MDM). However, rapid design of high-performance mode converters with ultra-compact footprint and ultra-broadband operation bandwidth is still a challenge. In this work, through combining adaptive genetic algorithm (AGA) and finite element simulations, we present an intelligent inverse design algorithm and successfully designed a set of arbitrary-order mode converters with low excess losses (ELs) and low crosstalk (CT). At the communication wavelength of 1550 nm, the footprint of designed TE0-n (n = 1, 2, 3, 4) and TE2-n (n = 0, 1, 3, 4) mode converters are only 1.8 × 2.2 µm2. The maximum and minimum conversion efficiency (CE) is 94.5% and 64.2%, and the maximum and minimum ELs/CT are 1.92/-10.9 dB and 0.24/-20 dB, respectively. Theoretically, the smallest bandwidth for simultaneously achieving ELs ≤ 3 dB and CT ≤ -10 dB exceeds 70 nm, which can be as large as 400 nm for the case of low-order mode conversion. Moreover, the mode converter in conjunction with a waveguide bend allows for mode-conversion in ultra-sharp waveguide bends, significantly increasing the density of on-chip photonic integration. This work provides a general platform for the realization of mode converters and has good prospect in application of multimode silicon photonics and MDM.

10.
Nanomedicine ; 51: 102686, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37121459

RESUMO

Sonodynamic therapy (SDT) can noninvasively focus sound energy to deep tumor tissues and activate sonosensitizer (such as chlorin e6(Ce6)) to produce antitumor effects. However, due to the hypoxic microenvironment of the tumor, the effect of sonodynamic therapy is limited. In this work, we successfully synthesized Platinum-Boron-Phosphorus ternary nanoparticles (Pt-B-P NPs) for the first time to efficiently catalyze the decomposition of hydrogen peroxide (H2O2) in tumor tissues to produce sufficient oxygen (O2) and improve the effect of sonodynamic treatment of ovarian cancer. In vitro studies, we found that compared with Platinum nanoparticles (Pt NPs), Pt-B-P NPs have the significantly increased ability to catalyze the decomposition of H2O2 to produce oxygen and thus the hypoxic environment of tumor cells could be improved efficiently. Meanwhile, the bio-distribution, therapeutic effect and bio-safety of Pt-B-P NPs in vivo were evaluated using BALB/c-nu mouse model of ovarian cancer and the desired result had been achieved.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Nanopartículas Metálicas/uso terapêutico , Platina/farmacologia , Peróxido de Hidrogênio , Neoplasias Ovarianas/tratamento farmacológico , Oxigênio , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio , Linhagem Celular Tumoral , Microambiente Tumoral
11.
BMJ Open ; 13(3): e069465, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36889830

RESUMO

OBJECTIVES: The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA). DESIGN: Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III). SETTING: We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China. PARTICIPANTS: 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months. RESULTS: Among the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months. CONCLUSIONS: The LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.


Assuntos
Isquemia Encefálica , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , LDL-Colesterol , Sistema de Registros , China/epidemiologia
12.
Sci Rep ; 13(1): 4081, 2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906716

RESUMO

Phosphoserine aminotransferase 1 (PSAT1) has been associated with the occurrence and development of various carcinomas; however, its function in uterine corpus endometrial carcinoma (UCEC) is unknown. We aimed to explore the relationship between PSAT1 and UCEC using The Cancer Genome Atlas database and functional experiments. PSAT1 expression levels in UCEC were employed using the paired sample t-test, Wilcoxon rank-sum test, the Clinical Proteomic Tumor Analysis Consortium database, and the Human Protein Atlas database, while survival curves were constructed using the Kaplan-Meier plotter. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the possible functions and related pathways of PSAT1. Furthermore, single-sample gene set enrichment analysis was performed to detect the relationship between PSAT1 and tumor immune infiltration. StarBase and quantitative PCR were used to predict and verify the interactions between miRNAs and PSAT1. The Cell Counting Kit-8, EdU assay, clone formation assay, western blotting and flow cytometry were used to evaluate cell proliferation. Finally, Transwell and Wound healing assays were used to assess cell invasion and migration. Our study found that PSAT1 was significantly overexpressed in UCEC, and this high expression was associated with a worse prognosis. A high level of PSAT1 expression was associated with a late clinical stage and, histological type. In addition, the results of GO and KEGG enrichment analysis showed that PSAT1 was mainly involved in the regulation of cell growth, immune system and cell cycle in UCEC. In addition, PSAT1 expression was positively correlated with Th2 cells and negatively correlated with Th17 cells. Furthermore, we also found that miR-195-5P negatively regulated the expression of PSAT1 in UCEC. Finally, the knockdown of PSAT1 resulted in the inhibition of cell proliferation, migration, and invasion in vitro. Overall, PSAT1 was identified as a potential target for the diagnosis and immunotherapy of UCEC.


Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Transaminases , Feminino , Humanos , Carcinoma Endometrioide/genética , Proliferação de Células , Bases de Dados de Proteínas , Regulação para Baixo , Neoplasias do Endométrio/genética , Proteômica , Transaminases/genética
13.
Front Plant Sci ; 14: 1097846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36844052

RESUMO

Translation is a crucial process during plant growth and morphogenesis. In grapevine (Vitis vinifera L.), many transcripts can be detected by RNA sequencing; however, their translational regulation is still largely unknown, and a great number of translation products have not yet been identified. Here, ribosome footprint sequencing was carried out to reveal the translational profile of RNAs in grapevine. A total of 8291 detected transcripts were divided into four parts, including the coding, untranslated regions (UTR), intron, and intergenic regions, and the 26 nt ribosome-protected fragments (RPFs) showed a 3 nt periodic distribution. Furthermore, the predicted proteins were identified and classified by GO analysis. More importantly, 7 heat shock-binding proteins were found to be involved in molecular chaperone DNA J families participating in abiotic stress responses. These 7 proteins have different expression patterns in grape tissues; one of them was significantly upregulated by heat stress according to bioinformatics research and was identified as DNA JA6. The subcellular localization results showed that VvDNA JA6 and VvHSP70 were both localized on the cell membrane. Therefore, we speculate that DNA JA6 may interact with HSP70. In addition, overexpression of VvDNA JA6 and VvHSP70, reduced the malondialdehyde (MDA) content, improved the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), increased the content of proline, an osmolyte substance, and affected the expression of the high-temperature marker genes VvHsfB1, VvHsfB2A, VvHsfC and VvHSP100. In summary, our study proved that VvDNA JA6 and the heat shock protein VvHSP70 play a positive role in the response to heat stress. This study lays a foundation for further exploring the balance between gene expression and protein translation in grapevine under heat stress.

14.
ACS Appl Mater Interfaces ; 15(9): 11631-11641, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36852882

RESUMO

Composition optimization, structural design, and introduction of external magnetic fields into the catalytic process can remarkably improve the oxygen evolution reaction (OER) performance of a catalyst. NiFe2O4@(Ni, Fe)S/P materials with a heterogeneous core-shell structure were prepared by the sulfide/phosphorus method based on spinel-structured NiFe2O4 nanomicrospheres. After the sulfide/phosphorus treatment, not only the intrinsic activity of the material and the active surface area were increased but also the charge transfer resistance was reduced due to the internal electric field. The overpotential of NiFe2O4@(Ni, Fe)P at 10 mA cm-2 (iR correction), Tafel slope, and charge transfer resistance were 261 mV, 42 mV dec-1, and 3.163 Ω, respectively. With an alternating magnetic field, the overpotential of NiFe2O4@(Ni, Fe)P at 10 mA cm-2 (without iR correction) declined by 45.5% from 323 mV (0 mT) to 176 mV (4.320 mT). Such enhancement of performance is primarily accounted for the enrichment of the reactive ion OH- on the electrode surface induced by the inductive electric potential derived from the Faraday induction effect of the AMF. This condition increased the electrode potential and thus the charge transfer rate on the one hand and weakened the diffusion of the active substance from the electrolyte to the electrode surface on the other hand. The OER process was dominantly controlled by the charge transfer process under low current conditions. A fast charge transfer rate boosted the OER performance of the catalyst. At high currents, diffusion exerted a significant effect on the OER process and low OH- diffusion rates would lead to a decrease in the OER performance of the catalyst.

15.
Neurotox Res ; 41(1): 1-15, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36598679

RESUMO

Lead (Pb) is a common heavy metal contaminant in the environment, and it may perturb autophagy and cause neurodegeneration. Although sodium para-aminosalicylic (PAS-Na) has been shown to protect the brain from lead-induced toxicity, the mechanisms associated with its efficacy have yet to be fully understood. In this study, we evaluated the efficacy of PAS-Na in attenuating the neurotoxic effects of lead, as well as the specific mechanisms that mediate such protection. Lead exposure resulted in weight loss and injury to the liver and kidney, and PAS-Na had a protective effect against this damage. Both short-term and subchronic lead exposure impaired learning ability, and this effect was reversed by PAS-Na intervention. Lead exposure also perturbed autophagic processes through the modulation of autophagy-related factors. Short-term lead exposure downregulated LC3 and beclin1 and upregulated the expression of p62; subchronic lead exposure upregulated the expression of LC3, beclin1, and P62. It follows that PAS-Na had an antagonistic effect on the activation of the above autophagy-related factors. Overall, our novel findings suggest that PAS-Na can protect the rat cortex from lead-induced toxicity by regulating autophagic processes. (1) Short-term lead exposure inhibits autophagy, whereas subchronic lead exposure promotes autophagy. (2) PAS-NA ameliorated the abnormal process of lead-induced autophagy, which had a protective effect on the cerebral cortex.


Assuntos
Ácido Aminossalicílico , Autofagia , Córtex Cerebral , Animais , Ratos , Ácido Aminossalicílico/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1 , Chumbo/toxicidade , Ratos Sprague-Dawley , Sódio , Córtex Cerebral/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/patologia
16.
Toxicol Lett ; 375: 48-58, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586703

RESUMO

Lead (Pb) is a developmental neurotoxin that can disrupt brain development and damage the brain regions responsible for executive function, behavioral regulation and fine motor control. Sodium para-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that can cross the blood-brain barrier. The purpose of this study was to examine the effects of juvenile rat Pb exposure on behavioral changes and brain inflammation, and the efficacy of PAS-Na in ameliorating these effects. The results showed that Pb exposure during the juvenile period (from weaning to adult period) delayed rats' growth development and impaired their motor learning. Pb exposure not only increased Pb concentrations in several brain regions (including hippocampus, striatum and substantia nigra), but also disrupted metal-homeostasis in the brain, as higher levels of iron (Fe) and calcium (Ca) were observed in the substantia nigra. Moreover, Pb activated the MAPK pathway and increased levels of inflammatory factors such as IL-1ß, TNF-α and IL-6 in the hippocampus, striatum and substantia nigra. Furthermore, Pb increased the levels of alpha-synuclein (α-syn) in these brain sites. PAS-Na improved the motor deficits and brain inflammation in the Pb-exposed rats. Moreover, the elevated Pb, Fe and Ca concentrations in the brain were significantly reduced by PAS-Na, which contains amino, carboxyl and hydroxyl functional groups, suggesting that it may act as a chelator of brain metals. In addition, PAS-Na inhibited the Pb-induced MAPK pathway activation and α-syn accumulation in the same brain regions. Taken together, our novel study suggest that PAS-Na shows efficacy in improving the Pb-induced behavioral changes in rats by inhibiting MAPK-dependent inflammatory pathways and reducing α-syn accumulation.


Assuntos
Ácido Aminossalicílico , Encefalite , Ratos , Animais , Ácido Aminossalicílico/farmacologia , Ácido Aminossalicílico/uso terapêutico , alfa-Sinucleína , Chumbo/toxicidade , Doenças Neuroinflamatórias , Sódio , Encéfalo , Encefalite/induzido quimicamente , Encefalite/tratamento farmacológico , Sistema de Sinalização das MAP Quinases
17.
Neurochem Res ; 48(1): 238-249, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36063295

RESUMO

Lead (Pb) is considered to be a major environmental pollutant and occupational health hazard worldwide which may lead to neuroinflammation. However, an effective treatment for Pb-induced neuroinflammation remains elusive. The aim of this study was to investigate the mechanisms of Pb-induced neuroinflammation, and the therapeutic effect of sodium para-aminosalicylic acid (PAS-Na, a non-steroidal anti-inflammatory drug) in rat cerebral cortex. The results indicated that Pb exposure induced pathological damage in cerebral cortex, accompanied by increased levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Moreover, Pb decreased the expression of silencing information regulator 2 related enzyme 1 (SIRT1) and brain-derived neurotrophic factor (BDNF), and increased the levels of high mobile group box 1 (HMGB1) expression and p65 nuclear factor-κB (NF-κB) phosphorylation. PAS-Na treatment ameliorated Pb-induced histopathological changes in rat cerebral cortex. Moreover, PAS-Na reduced the Pb-induced increase of TNF-α and IL-1ß levels concomitant with a significant increase in SIRT1 and BDNF levels, and a decrease in HMGB1 and the phosphorylation of p65 NF-κB expression. Thus, PAS-Na may exert anti-inflammatory effects by mediating the SIRT1/HMGB1/NF-κB pathway and BDNF expression. In conclusion, in this novel study PAS-Na was shown to possess an anti-inflammatory effect on cortical neuroinflammation, establishing its efficacy as a potential treatment for Pb exposures.


Assuntos
Ácido Aminossalicílico , Proteína HMGB1 , Ratos , Animais , NF-kappa B/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína HMGB1/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Doenças Neuroinflamatórias , Sódio , Sirtuína 1/metabolismo , Chumbo/toxicidade , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Anti-Inflamatórios
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989082

RESUMO

Objective:To investigate the effects of neonatal respiratory distress syndrome(NRDS)on thymus of premature infants.Methods:We collected baseline data from premature infants with gestational age of 28~32 weeks in neonatal intensive care unit of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2019 to December 31, 2019.The largest transverse diameter and the sagittal of thymus were measured by ultrasonography within 24 h of birth, then, the thymic index(TI)and thymic weight index(TWI)were calculated to assess the size of thymus.The preterm neonates were divided into NRDS group and non-NRDS group according to the diagnosic criteria of NRDS, and the two groups were then divided into antenatal corticosteroid administration(ACS)group and non-ACS group according to ACS exposure.We then compared the TI and TWI between these groups.Results:One hundred and sixty-three preterm neonates were enrolled in our study, including 98 NRDS preterm neonates and 65 non NRDS preterm neonates.After matching gestational age and birth weight of the preterm neonates from two groups, 65 preterm neonates with NRDS comprised the NRDS group, and 65 preterm neonates without NRDS served as controls.Preterm neonates in NRDS group had significantly smaller TI[(1.788 ± 0.803)cm 3 vs.(2.420±1.068)cm 3, t=3.818, P<0.01] and TWI[(1.278 ± 0.380)cm 3/kg vs.(1.695 ± 0.491)cm 3/kg, t=5.401, P<0.01] than those in non-NRDS group.Besides, preterm neonates in NRDS group had smaller lymphocytes count[(3.729 ± 1.263)×10 9/L vs.(4.437 ± 1.608)×10 9/L, t=2.789, P<0.01] than that in non-NRDS group.For NRDS preterm neonates, TI[(1.487 ± 0.515)cm 3 vs(2.185 ± 0.942)cm 3, t=3.542, P<0.01] ]and TWI[(1.134± 0.311)cm 3/kg vs(1.469± 0.385)cm 3/kg, t=3.882, P<0.01] in ACS group were significantly smaller than those in non-ACS group.For non-NRDS preterm neonates, TI and TWI in ACS group also were significantly smaller than those in non-ACS group( t=2.676、3.659, P<0.05). Conclusion:NRDS is associated with thymic involution of preterm neonates, and ACS exposure affected the size of thymic in premature infants.

19.
Acta Pharmaceutica Sinica ; (12): 1232-1244, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978701

RESUMO

Human hormones at trace levels play a vital role in the regulation of a variety of functions and systems in the body, and an imbalance in hormone levels can lead to the emergence and development of diverse diseases. Therefore, the development of reliable sample pretreatment methods and sensitive and accurate analytical techniques for human hormone detection could contribute to the prevention, diagnosis and treatment of diseases, providing significant improvement for human health. Human samples which are usually used to detecting hormones, such as blood, saliva, urine and other matrix are more complex, so sample pretreatment is an important step to ensure the accuracy and reliability in the detection of hormones. In this review three common sample pretreatment methods including solid phase extraction (SPE), liquid-liquid extraction (LLE) and protein precipitation (PP) methods are discussed. Then, recent research progress in conventional techniques like liquid/gas chromatography and liquid/gas chromatography-mass spectrometry (LC/GC-MS/MS), as well as some novel strategies, such as immunoassay including chemiluminescence immunoassay (CLIA), lateral-flow immunoassay (LFIA) and time-resolved fluoroimmunoassay (TRFIA), and sensor technology including electrochemical (EC), fluorescent (FL) and surface-enhanced Raman scattering (SERS) sensors, and microfluidic chip analysis are discussed for human hormone detection. Finally, the future perspective on the use of these methods for hormone detection is considered. It is hoped to provide powerful insights to researchers for the relevant researches.

20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-977139

RESUMO

Background@#Antibiotic resistance is a significant public health concern around the globe.Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. @*Objective@#This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. @*Methods@#Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. @*Results@#The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). @*Conclusions@#Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.

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