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1.
J Ethnopharmacol ; 325: 117807, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38280661

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease affecting the colon and rectum with an etiology that remains elusive. Traditional Chinese medicine (TCM) has been widely used on long-term UC treatment to better maintain the efficacy than traditional aminosalicylic acid or glucocorticosteroids and to ease financial burden of patients. Qingchang Wenzhong Decoction (QCWZD) is a modern TCM decoction with established clinical efficacy but the mechanism of its protection on intestinal barrier function remains unclear. AIM OF THE STUDY: Current findings highlight that the activation of the hypoxia inducible factor (HIF) pathway can facilitate the repair of intestinal epithelium barrier. This study is to investigate the protective effects of QCWZD and its HIF-targeted ingredients on hypoxia-dependent intestinal barrier. METHODS: The mice model of UC was induced by dextran sulfate sodium (DSS). Disease activity index (DAI) and histopathology scores and colon length were used to measure the severity of colitis. The DAO activity in serum and protein expression of tight junction (TJ) proteins were detected to explore the function of intestinal barrier. The protein levels of HIF-1α and its downstream gene heme oxygenase-1 (HO-1) were measured as well. HIF-targeted active ingredients in QCWZD were selected by network pharmacology and molecular docking. Protective effects of six constituents on HIF-related anti-oxidative and barrier protective pathway were evaluated by lipopolysaccharide (LPS)-induced HT29 and RAW264.7 cells, through the measurement of the production of ROS and mRNA level of pro-inflammatory cytokines. HIF-1α knockdown was carried out to explore the correlation of protection effects with HIF-related pathway of the active ingredients. RESULTS: QCWZD effectively alleviated colitis induced by DSS and demonstrated a protective effect on intestinal barrier function by upregulating HIF-related pathways. Six specific ingredients in QCWZD, targeting HIF, successfully reduced the production of cellular ROS and proinflammatory cytokines in LPS-induced cells. It is noteworthy that the barrier protection provided by these molecules is intricately linked with the HIF-related pathway. CONCLUSIONS: This study elucidates the HIF-related molecular mechanism of QCWZD in protecting the function of the epithelial barrier. Six compounds targeting the activation of the HIF-dependent pathway were demonstrated to unveil a novel therapeutic approach for managing UC.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Humanos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Espécies Reativas de Oxigênio , Simulação de Acoplamento Molecular , Lipopolissacarídeos , Colite/induzido quimicamente , Citocinas/metabolismo , Hipóxia
2.
J Pharm Biomed Anal ; 238: 115838, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-37948776

RESUMO

Euphorbia pekinensis (EP), known for its diuretic properties, is clinically utilized for treating conditions such as edema and malignant tumors. However, in its raw form, Euphorbia pekinensis is toxic, and oral administration of this crude medicine can lead to gastrointestinal stimulation, resulting in abdominal pain and diarrhea. In Mongolian medicine's ethnomedicinal system, a distinctive processing method called "Chebulae Fructus processing" is employed. Chebulae Fructus is used to mitigate the toxicity of EP and alleviate its purgative effects. Nevertheless, the detoxification mechanism associated with this processing method remains unexplored. It is hypothesized that processing with Chebulae Fructus may alter the chemical composition of EP, and the residual components of Chebulae Fructus within processed Chinese medicine might exhibit pharmacological antagonistic effects, thereby achieving the purpose of processing and reducing toxicity. To investigate this further, a combination of UPLC-QTOF-MS-based metabolomics technology and multivariate statistical analysis was employed to analyze and compare the chemical composition of raw and processed EP. Differential variables contributing to group separation were identified based on specific criteria, including VIP (Variable Importance in Projection) values of ≥ 1 in PLS-DA models, p-values < 0.05, and fold changes (FC) > 1.2 or < 0.8. The resulting differentially expressed features were then identified through database matching, literature review, or manual annotation. In total, 47 components were identified from the PEP samples in both positive and negative ionization modes, primarily belonging to flavonoids, terpenoids, organic acids, glycosides, and fatty acids. Among the raw EP group and PEP S4 group, 10 differential compounds were identified. Notably, one toxic terpene and one phenylpropanoid from EP were downregulated, while two bioactive components from Chebulae Fructus were upregulated in the processed group. The possible conversion reactions of these two processing Q-markers were also elucidated. The characteristic processing with Chebulae Fructus resulted in a change in the composition of this Mongolian medicine EP. Furthermore, this study provides a scientific foundation for optimizing the processing technology of EP and offers insights into the processing of other ethnomedicines with toxic properties.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbia , Plantas Medicinais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/análise , Euphorbia/química , Metabolômica , Extratos Vegetais , Plantas Medicinais/química
3.
Front Psychol ; 14: 1280871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849483

RESUMO

Although successful educational practices (SEPs) in higher education institutions have well-established student outcomes, the vast majority do not meet physical education standards in schools. Despite the promising nature of policy initiatives supporting schools, there is scant evidence of how these SEPs affect student outcomes. This review aimed to determine the status of the literature and the type of evidence regarding school SEPs. Several studies have demonstrated that these SEPs contribute directly or indirectly to improving student outcomes. Three objectives were examined and synthesized in our review of SEP research findings. The first goal is to identify different types of impacts on students in schools. The second goal is to provide educators, principals, and policymakers with a unified and comprehensive framework. Lastly, we provide suggestions for future SEP research. The review identified 45 studies that met our inclusion criteria. Our reviewed studies documented impacts on the individual level. It encompasses both students' instrumental abilities and their sense of self-esteem and motivation. Secondly, improving interpersonal relationships, reducing conflict, and increasing group cohesion are important components at the group level. Finally, there are factors at the community level, including absenteeism reduction, parental involvement, and changes in attitudes toward school. Current research supports the effectiveness of successful school practices. It stresses the importance of implementing policies to maximize student outcomes. Finally, the review concludes by discussing findings implications and future research directions.

4.
Eur Radiol ; 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37875593

RESUMO

OBJECTIVES: The study of postoperative liver decompensation after microwave ablation (MWA) for hepatocellular carcinoma (HCC) in patients with clinically significant portal hypertension (CSPH) is still lacking. The purpose of the present study was to compare the postoperative liver decompensation after MWA and laparoscopic resection (LR) for HCC in patients with CSPH. METHODS: The present retrospective study enrolled 222 HCC patients with CSPH who underwent MWA (n = 67) or LR (n = 155). Postoperative liver decompensation, complications, postoperative hospital stays, and overall survival were analyzed. Factors associated with postoperative liver decompensation were identified. RESULTS: After propensity score matching, the postoperative liver decompensation rate was significantly lower in the MWA group than that in the LR group (15.5% versus 32.8%, p = 0.030). The multivariable regression analysis identified that type of treatment (MWA vs. LR, odds ratio [OR] 0.44; 95% confidence interval [CI], 0.21-0.91; p = 0.026) and Child-Pugh B (OR, 2.86; 95% CI, 1.24-6.61; p = 0.014) were independent predictors for postoperative liver decompensation. The rate of complications for patients in the MWA group was significantly lower than that in the LR group (p < 0.001). And MWA showed shorter postoperative hospital stays than LR (3 days vs. 6 days, p < 0.001). Overall survival rate between the two groups was not significantly different (p = 0.163). CONCLUSION: Compared with laparoscopic resection, microwave ablation has a lower rate of postoperative liver decompensation and might be a better option for HCC patients with CSPH. CLINICAL RELEVANCE STATEMENT: Microwave ablation exhibited a lower incidence of postoperative liver decompensation in comparison to laparoscopic resection, thereby conferring greater advantages to hepatocellular carcinoma patients with clinically significant portal hypertension. KEY POINTS: •Postoperative liver decompensation rate after microwave ablation was lower than that of laparoscopic resection for hepatocellular carcinoma in patients with clinically significant portal hypertension. •Microwave ablation showed shorter postoperative hospital stays than laparoscopic resection. •Microwave ablation had fewer complications than laparoscopic resection.

5.
Anal Chim Acta ; 1279: 341779, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37827677

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that devastatingly affects people's lives. Accumulating evidence indicates that the pathological progression of AD is inseparably connected with hypochlorous acid (HClO). However, further exploring the biological function remains an open challenging due to a lack of effective tools to image HClO in AD brains. To this end, a ruthenium(II) luminescence probe, Ru-HClO, is developed for quantitative detection and visualization of HClO in nerve cells and AD brains. Ru-HClO shows quenched luminescence due to the PET process (excited electron transfer from Ru(II) center to diaminomaleonitrile) and the CN bond isomerization in the excited state. The HClO-triggered specific cleavage reaction with Ru-HClO cleaves the CN bond to form highly luminescent Ru-COOH. Ru-HClO shows rapid response speed, high sensitivity and selectivity, excellent biocompatibility, which makes the probe to be applied to semi-quantitative analysis of HClO in nerve cells and high-throughput screening of anti-AD drugs in the AD cell model. Moreover, using Ru-HClO as a probe, present work further validated that the elevated levels of HClO secretion were accompanied by the AD progressed. These findings may provide valuable results for figuring out the biological roles that HClO played in AD but also for accelerating anti-AD therapeutic discovery.


Assuntos
Doença de Alzheimer , Rutênio , Humanos , Luminescência , Ácido Hipocloroso/análise , Rutênio/química , Doença de Alzheimer/diagnóstico por imagem , Corantes Fluorescentes/química
6.
Transl Neurosci ; 14(1): 20220298, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37719746

RESUMO

Background: Baicalin has been shown to promote spatial learning and neural regeneration, which might increase the differentiation of neural stem cells in Alzheimer's disease (AD) rat models. We aimed to study the role of baicalin on neuronal pentraxin-1 (NPTX-1), neuronal pentraxin-2 (NPTX-2), and C-reactive protein (CRP) in AD model rats. Methods: The 30 male Sprague Dawley rats were divided into three groups: the control group, the AD model group, and the AD + baicalin group. Then, the Morris water maze was used to verify the effect of baicalin on the memory and spatial learning of rats. Immunohistochemistry and immunofluorescence were used to observe the expression of NPTX-1, NPTX-2, and CRP in brain tissue. Results: Compared with the AD model group, the AD rats treated with baicalin spent significantly less time finding escape latencies (P = 0.008) and had longer cross-platform times in the target quadrant (P = 0.015). In addition, the AD + baicalin group had significantly higher numbers of hippocampal neurons compared with the AD model group (P < 0.05). Baicalin also obviously decreased the apoptosis of neurons. Moreover, compared with the AD model group, the NPTX-1 and CRP expression in the AD + baicalin group was significantly reduced (P = 0.000) while the expression of NPTX-2 in the brain tissue of AD rats was significantly increased (P = 0.000). Conclusions: Baicalin can play a therapeutic role by downregulating NPTX-1, upregulating NPTX-2, and downregulating CPR in AD model rats.

7.
Int J Pharm ; 641: 122987, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37207860

RESUMO

Diabetic retinopathy (DR) is one of the serious complications of diabetes, which has become the fourth leading cause of vision loss worldwide. Current treatment of DR relies on intravitreal injections of antiangiogenic agents, which has made considerable achievements in reducing visual impairment. However, long-term invasive injections require advanced technology and can lead to poor patient compliance as well as the incidence of ocular complications including bleeding, endophthalmitis, retinal detachment and others. Hence, we developed non-invasive liposomes (EA-Hb/TAT&isoDGR-Lipo) for efficiency co-delivery of ellagic acid and oxygen, which can be administered intravenously or by eye drops. Among that, ellagic acid (EA), as an aldose reductase inhibitor, could remove excessive reactive oxygen species (ROS) induced by high glucose for preventing retinal cell apoptosis, as well as reduce retinal angiogenesis through the blockage of VEGFR2 signaling pathway; carried oxygen could ameliorate DR hypoxia, and further enhanced the anti-neovascularization efficacy. Our results showed that EA-Hb/TAT&isoDGR-Lipo not only effectively protected retinal cells from high glucose-induced damage, but also inhibited VEGF-induced vascular endothelial cells migration, invasion, and tube formation in vitro. In addition, in a hypoxic cell model, EA-Hb/TAT&isoDGR-Lipo could reverse retinal cell hypoxia, thereby reducing the expression of VEGF. Significantly, after being administered as an injection or eye drops, EA-Hb/TAT&isoDGR-Lipo obviously ameliorated the structure (central retinal thickness and retinal vascular network) of retina by eliminating ROS and down-regulating the expression of GFAP, HIF-1α, VEGF and p-VEGFR2 in a DR mouse model. In summary, EA-Hb/TAT&isoDGR-Lipo holds great potentials in improvement of DR, which provides a novel approach for the treatment of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Neovascularização Retiniana , Camundongos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Retinopatia Diabética/prevenção & controle , Neovascularização Retiniana/tratamento farmacológico , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/prevenção & controle , Lipossomos/farmacologia , Ácido Elágico/metabolismo , Ácido Elágico/farmacologia , Ácido Elágico/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Retina/metabolismo , Hipóxia , Glucose/farmacologia , Soluções Oftálmicas/farmacologia
8.
Eur J Radiol ; 164: 110860, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37178491

RESUMO

OBJECTIVES: The efficacy of microwave ablation (MWA) for hepatocellular carcinoma (HCC) as bridge therapy has been gradually confirmed. We aimed to compare the recurrence beyond the Milan criteria (RBM) rates in potentially transplantable patients with HCC receiving MWA or radiofrequency ablation (RFA) as bridge therapy. METHODS: In total, 307 potentially transplantable patients with single HCC ≤ 3 cm who initially received MWA (n = 82) or RFA (n = 225) were included. RBM, recurrence-free survival (RFS), and overall survival (OS) were compared between MWA and RFA groups by using propensity score matching (PSM). Competing risks Cox regression was used to identify predictors of RBM. RESULTS: After PSM, the 1-, 3-, and 5-year cumulative RBM rates were 6.8%, 18.3%, and 39.3% in the MWA group (n = 75), and 7.4%,18.5%, and 27.7% in the RFA group (n = 137), respectively, with no significant difference (p = 0.386). MWA and RFA were not the independent risk factors of RBM, and patients with higher alpha-fetoprotein, non-antiviral treatment, and higher MELD score were at greater risk of RBM. Neither corresponding RFS rates (66.7%, 39.2% and 21.4% vs. 70.8%, 47% and 34.7%, p = 0.310) nor OS rates (97.3%, 88.0%, and 75.4% vs. 97.8%, 85.1%, and 70.7%, p = 0.384) for 1-, 3- and 5-years were significantly different between the MWA and RFA groups. The MWA group showed more frequent major complications (21.4% vs. 7.1%, p = 0.004) and longer hospital stays (4 days vs. 2 days, p < 0.001) compared with the RFA group. CONCLUSION: MWA showed comparable RBM, RFS, and OS rates to RFA in potentially transplantable patients with single HCC ≤ 3 cm. Compared to RFA, MWA might provide the same effect as bridge therapy.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Terapia Ponte , Resultado do Tratamento , Estudos Retrospectivos
9.
J Colloid Interface Sci ; 645: 882-894, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37178565

RESUMO

Photodynamic therapy (PDT), as a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species, has been widely used for eliminating cancer cells under specific wavelength light irradiation. However, the low aqueous solubility of PSs and special tumor microenvironments (TME), such as high glutathione (GSH) and tumor hypoxia remain challenges towards PDT for hypoxic tumor treatment. To address these problems, we constructed a novel nanoenzyme for enhanced PDT-ferroptosis therapy by integrating small Pt nanoparticles (Pt NPs) and near-infrared photosensitizer CyI into iron-based metal organic frameworks (MOFs). In addition, hyaluronic acid was adhered to the surface of the nanoenzymes to enhance the targeting ability. In this design, MOFs act not only as a delivery vector for PSs, but also a ferroptosis inducer. Pt NPs stabilized by MOFs were functioned as an oxygen (O2) generator by catalyzing hydrogen peroxide into O2 to relieve tumor hypoxia and increase singlet oxygen generation. In vitro and in vivo results demonstrated that under laser irradiation, this nanoenzyme could effectively relive the tumor hypoxia and decrease the level of GSH, resulting in enhanced PDT-ferroptosis therapy against hypoxic tumor. The proposed nanoenzymes represent an important advance in altering TME for improved clinical PDT-ferroptosis therapy, as well as their potential as effective theranostic agents for hypoxic tumors.


Assuntos
Ferroptose , Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Estruturas Metalorgânicas/farmacologia , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes , Neoplasias/tratamento farmacológico , Oxigênio , Peróxido de Hidrogênio/farmacologia , Microambiente Tumoral
10.
J Cardiothorac Surg ; 18(1): 184, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208736

RESUMO

Sternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.


Assuntos
Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/etiologia , Esterno/cirurgia , Esternotomia/efeitos adversos , Fatores de Risco , Estudos Retrospectivos
11.
J Clin Med ; 12(7)2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37048805

RESUMO

As society ages, it is important to understand the prevalence of dementia and the difficulties of inserting prostheses in patients with maxillofacial defects in order to clarify issues in supportive care. We screened 183 patients for dementia using the revised Hasegawa's dementia scale (HDS-R) at the Clinic for Maxillofacial prosthetics, Tokyo Medical and Dental University, and investigated age and sex differences in HDS-R score. We asked 47 of the 183 participants about the difficulty of inserting a maxillofacial obturator prosthesis and collected subjective comments, information about the prosthesis, and data from five assessments. Multiple regression analysis was used to reveal factors associated with insertion difficulty. Overall, 8.7% of the participants were judged to have possible dementia. Men were more likely than women to have possible dementia, and the risk increased with age. Of the 47 participants, 26 reported difficulty inserting their prosthesis, 12 of whom attributed it to their oral defect. Fourteen patients advised following doctor's instructions to practice insertion in order to become accustomed to it. A lower HDS-R score had a significant impact on insertion difficulty. Cognitive function and difficulty inserting maxillary obturator prostheses should be considered in the provision of continuous supportive care to patients with maxillary defects.

12.
Nanoscale Adv ; 5(5): 1271-1290, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36866253

RESUMO

Ferroptosis, an iron-dependent mode of regulated cell death, is induced by lipid peroxidation, whose occurrence and execution are primarily controlled by metabolism of iron, lipids, amino acids and glutathione. In recent years, the fast-growing studies of ferroptosis in cancer have promoted its application in cancer therapy. So, this review focuses on the feasibility and characteristics of initiating ferroptosis for cancer therapy, as well as the main mechanism of ferroptosis. And various emerging strategies of cancer therapy based on ferroptosis are then highlighted to describe their design, mechanism of action, and anticancer applications. In addition ferroptosis in diverse cancer types is summarized, some considerations for the research of various preparations that can cause ferroptosis are introduced, and this emerging field is discussed in terms of its challenges and future development directions.

13.
Chemistry ; 29(25): e202203363, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-36826395

RESUMO

Acetylcholinesterase (AChE) is a key target for the current symptomatic treatment of Alzheimer's disease, and galantamine is a clinical anticholinesterase drug with transiently acting characteristic and good selectivity for AChE. The present theoretical-experimental work improves the drug's residence time without reducing the inhibition effect, thus providing a crucial breakthrough for modifying the inhibitor of AChE with better kinetic behavior. The static binding and dynamic delivery properties acquired from atomic view reveal that the galantamine simply occupies a catalytic anionic site, and its release from AChE needs only ∼8.6 kcal/mol. Both of these may cause the short residence time of galantamine. The hotspots and most favorable transport mechanism are identified, and the hydrogen bond and aromatic stacking interactions are observed to play crucial roles for galantamine binding and release in AChE. The typical peripheral anionic site arisen at the delivery process would provide another key occupation to enhance the anti-release ability for inhibitors. The compound with "specific-ring-chain-ring" framework with detailed beneficial modification scheme is summarized, which may improve the residence time of the inhibitor in AChE. The thermodynamic and dynamic properties of galantamine derivatives are also studied. Based on dictamnine, a natural alkaloid, two novel eligible derivatives are designed, synthesized and evaluated, which verifies our prediction. Multiple computational approaches and experimental combinations probably provide a train of thought from both static and dynamic views to modify or design appropriate inhibitors on the basis of specific binding and transportation features.


Assuntos
Doença de Alzheimer , Produtos Biológicos , Humanos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Galantamina/química , Galantamina/farmacologia , Simulação de Acoplamento Molecular
14.
Toxicology ; 486: 153430, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669722

RESUMO

Pinellia ternata, a widely used traditional Chinese medicine, contains a strong mucosal irritant that is connected with Pinellia ternata lectin (PTL) in its tubers. The purpose of this study was to explore the mechanisms by which PTL induces inflammation. We found that in RAW264.7 cells, PTL activated the PI3K/Akt/mTOR and NF-κB pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal microscopy analysis showed that FITC-labeled PTL bound to the macrophages' surface. Based on kinetic analyses and protein-protein docking simulations, PTL was shown to bind toll-like receptor 4 (TLR4).it was demonstrated that PTL binds highly to Toll-like receptor 4 (TLR4). TLR4 knock-down or knockout resulted in a decrease in both cytokine release and PI3K/Akt/mTOR and NF-κB pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upregulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflammatory effect of PTL in RAW264.7 cells. These findings reveal that PTL can mediate inflammation through TLR4 and activating the PI3K/Akt/mTOR to regulate NF-κB signaling pathways.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , Animais , Camundongos , Citocinas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Serina-Treonina Quinases TOR/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-36395131

RESUMO

Transcranial direct current stimulation (tDCS) has become a new method of rehabilitation treatment for stroke and is gradually gaining acceptance. However, the neurophysiological mechanisms of tDCS in the treatment of stroke still need to be further explored. In our research, we aimed to investigate the effects of tDCS on neural oscillation power and brain functional network (BFN) connectivity in stroke patients based on electroencephalogram (EEG). Fifteen patients with ischemic stroke attended two experimental sessions in a randomized crossover trial and received real and sham tDCS. Resting-state EEG signals were acquired before and after stimulation. First, the power of EEG delta, theta, alpha, beta, and gamma bands were analyzed before and after stimulation. Then, BFNs in different bands were constructed, and network characteristic parameters such as degree, clustering coefficient, characteristic path length, global efficiency, and small-world attribute were analyzed. The results showed that the delta power decreased significantly ( ) and the alpha power increased significantly ( ) after real tDCS, whereas the theta, beta, and gamma power did not change significantly ( ). The degree and global efficiency of the delta band BFN decreased significantly after real tDCS ( ), the characteristic path length increased significantly ( ), and the clustering coefficient and small-world attribute decreased but not statistically significant ( ). The degree, clustering coefficient, global efficiency, and small-world attribute of the alpha band BFN increased significantly after real tDCS ( ), and the characteristic path length decreased significantly ( ). The BFN characteristic parameters in theta, beta, and gamma bands did not change significantly after real tDCS ( ). There was no significant difference in sham tDCS group ( ). Our study found that the power of delta oscillations decreased and the global connectivity of delta band BFN weakened after tDCS in stroke patients, whereas the power of alpha oscillations increased and the global and local connectivity of alpha band BFN was enhanced. The findings implied that one of the neurophysiological mechanisms of tDCS treatment in stroke patients may be the modulation of the power of delta and alpha oscillations, as well as the improvement of the connectivity of delta and alpha oscillation networks.


Assuntos
Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Encéfalo , Eletroencefalografia
16.
J Mater Chem B ; 11(2): 415-429, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36512437

RESUMO

Ferroptosis, a type of programmed cell death induced by the iron-dependent lipid hydroperoxide pathway, has attracted widespread attention. However, Fenton response-dependent ferroptosis has many limitations, such as insufficient reaction conditions in the tumor micro-environment. Here, we propose an all-in-one phototherapy nanoplatform consisting of iron-polydopamine (Fe-PDA), a folic acid-modified red blood cell membrane (FA-RBCm), and epirubicin (EPI), namely, Fe-PDA-EPI@FA-RBCm NPs, to achieve enhanced photothermal-ferroptosis effects via overcoming the limitations of the Fenton-like reaction. The results showed that the synthesized biomimetic nanoparticles could decompose hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH), and further induce the non-apoptotic ferroptosis pathway. After irradiation with near-infrared (NIR) light, the uptake of Fe-PDA-EPI@FA-RBCm NPs by cells could be effectively promoted, and it presented impressive in vitro and in vivo photothermal properties. In vitro and in vivo results showed that laser irradiation could enhance ferroptosis by promoting the production of reactive oxygen species (ROS) and lipid peroxides, down-regulating the expression of glutathione peroxidase 4 (GPX4), and reducing the mitochondrial membrane potential. Furthermore, the photothermal-promoted ferroptosis and apoptosis pathways (photothermal therapy and chemotherapy) exhibited outstanding synergistic antitumor efficacy in vitro and in vivo, with an in vivo tumor inhibition rate as high as 76.95%. In conclusion, the construction of tumor-targeted biomimetic nanocarriers utilizing the advantageous properties of RBCm has been investigated as a potential anticancer strategy.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Peróxido de Hidrogênio/farmacologia , Nanopartículas/uso terapêutico , Apoptose , Epirubicina/farmacologia , Ferro/farmacologia
17.
Nutrients ; 14(24)2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36558438

RESUMO

We aimed to assess the effects of an 8-week, online high-intensity interval training (HIIT) program on the parameters related to the anaerobic threshold (AT), body weight, and body composition in pregnant women. A total of 69 Caucasian women with an uncomplicated singleton pregnancy (age: 31 ± 4 years; gestational age: 22 ± 5 weeks; mean ± standard deviation) were randomly allocated to either an 8-week HIIT program (HIIT group) or to a comparative 8-week educational program (EDU group). Our most important finding was that even with the 8-week progression of pregnancy and physiological weight gain, the HIIT group maintained the same level of parameters related to AT: volume of oxygen at the AT (VO2/AT), percentage of maximal oxygen uptake at the AT (%VO2max/AT), and heart rate at the AT (HR/AT). In contrast, in the EDU group we observed a substantial deterioration of parameters related to the AT. The HIIT intervention substantially reduced the fat mass percentage (median: 30 to 28%; p < 0.01) and improved the total fat-free mass percentage (median: 70% to 72%; p < 0.01). In the EDU group, the body composition did not change significantly. An online, supervised HIIT program may be used to prevent the pregnancy-related risk of excessive weight gain and reduction in exercise capacity without yielding adverse obstetric or neonatal outcomes.


Assuntos
Limiar Anaeróbio , Treinamento Intervalado de Alta Intensidade , Recém-Nascido , Feminino , Humanos , Gravidez , Adulto , Lactente , Peso Corporal , Composição Corporal/fisiologia , Aumento de Peso
18.
Front Med (Lausanne) ; 9: 1040168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582294

RESUMO

Background: Emergence agitation (EA) is common in patients after general anesthesia (GA) and is associated with poor outcomes. Patients with thoracic surgery have a higher incidence of EA compared with other surgery. This study aimed to investigate the impact of pre-anesthetic butorphanol infusion on the incidence of EA in patients undergoing thoracic surgery with GA. Materials and methods: This prospective randomized controlled trial (RCT) was conducted in 20 tertiary hospitals in China. A total of 668 patients undergoing elective video-assisted thoracoscopic lobectomy/segmentectomy for lung cancer were assessed for eligibility, and 620 patients were enrolled. In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. Patients in the intervention group received butorphanol 0.02 mg/kg 15 min before induction of anesthesia. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of EA after 5 min of extubation, and EA was evaluated using the Riker Sedation-Agitation Scale (RSAS). The incidence of EA was determined by the chi-square test, with a significance of P < 0.05. Results: In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. The incidence of EA 5 min after extubation was lower with butorphanol treatment: 9.8% (29 of 296) vs. 24.5% (75 of 306) in the control group (P = 0.0001). Patients who received butorphanol had a lower incidence of drug-related complications (including injecting propofol pain and coughing with sufentanil): 112 of 296 vs. 199 of 306 in the control group (P = 0.001) and 3 of 296 vs. 35 of 306 in the control group (P = 0.0001). Conclusion: The pre-anesthetic administration of butorphanol reduced the incidence of EA after thoracic surgery under GA. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=42684], identifier [ChiCTR1900025705].

19.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6076-6081, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471932

RESUMO

To determine the content of endogenous toxic substance Pinellia ternata lectin(PTL) protein in Pinelliae Rhizoma and the related processed products, this study prepared specific monoclonal antibodies against PTL by hybridoma cell technology, and established a quantitative double-antibody sandwich enzyme linked immunosorbent assay(ELISA) for PTL antigen. The detection conditions were 2.5 µg·mL~(-1) working concentration of the captured antibody and 1∶450 of the dilution multiple of detected antibody. The coating condition was staying overnight at 4 ℃. The blocking time and incubation times of antigen and detected antibody were all 90 minutes. The incubation time of horseradish peroxidase conjugated streptavidin-horseradish peroxidase(SA-HRP) was 15 minutes. The quantitative limit of the method for PTL antigen was 0.375 ng·mL~(-1). The linear range was 75.000-4 800.000 pg·mL~(-1), and R~2=0.997 1. The recovery rate was 90.0%-110.0%, and the variation coefficients of intra-test and inter-test precision were 2.0%-3.0% and 2.0%-8.5%.The content of PTL in three batches of Pinelliae Rhizoma and the related processed products was determined by the method, and the average content of PTL in Pinelliae Rhizoma was 35.42 mg·g~(-1). The average content of PTL in Pinelliae Rhizoma Praeparatum Cum Alumine, Pinelliae Rhizoma Praeparatum, and Pinelliae Rhizoma Praeparatum Cum Zingibere Et Alumine were 1.15 mg·g~(-1), 16.53 µg·g~(-1), and 122.63 ng·g~(-1), respectively, indicating that the content of PTL decreased significantly after processing. The quantitative double-antibody sandwich ELISA for PTL antigen established in this paper had good linearity, sensitive response, and high accuracy, which provided a simple and effective monitoring method for the detection of PTL content in the processing of Pinelliae Rhizoma.


Assuntos
Medicamentos de Ervas Chinesas , Pinellia , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Peroxidase do Rábano Silvestre
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(5): 966-973, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36310485

RESUMO

As an emerging non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS) has received increasing attention in the field of stroke disease rehabilitation. However, its efficacy needs to be further studied. The tDCS has three stimulation modes: bipolar-stimulation mode, anode-stimulation mode and cathode-stimulation mode. Nineteen stroke patients were included in this research (10 with left-hemisphere lesion and 9 with right). Resting electroencephalogram (EEG) signals were collected from subjects before and after bipolar-stimulation, anodal-stimulation, cathodal-stimulation, and pseudo-stimulation, with pseudo-stimulation serving as the control group. The changes of multi-scale intrinsic fuzzy entropy (MIFE) of EEG signals before and after stimulation were compared. The results revealed that MIFE was significantly greater in the frontal and central regions after bipolar-stimulation ( P< 0.05), in the left central region after anodal-stimulation ( P< 0.05), and in the frontal and right central regions after cathodal-stimulation ( P< 0.05) in patients with left-hemisphere lesions. MIFE was significantly greater in the frontal, central and parieto-occipital joint regions after bipolar-stimulation ( P< 0.05), in the left frontal and right central regions after anodal- stimulation ( P< 0.05), and in the central and right occipital regions after cathodal-stimulation ( P< 0.05) in patients with right-hemisphere lesions. However, the difference before and after pseudo-stimulation was not statistically significant ( P> 0.05). The results of this paper showed that the bipolar stimulation pattern affected the largest range of brain areas, and it might provide a reference for the clinical study of rehabilitation after stroke.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Eletroencefalografia , Acidente Vascular Cerebral/terapia , Eletrodos
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