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1.
Food Res Int ; 164: 112334, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36737927

RESUMO

Tartary buckwheat (TB) sprout is a kind of novel nutritional vegetable, but its consumption was limited by low biomass and thin hypocotyl. The tetraploid TB sprouts was considered to be able to solve this issue. However, the nutritional quality of tetraploid TB sprouts and differences between conventional (diploid) and tetraploid TB sprouts remain unclear. In this study, the morphological traits, nutrient compositions and metabolome changes of diploid and tetraploid TB sprouts were analyzed. The water, pigments and minerals contents of TB sprouts increased during sprouting, while the contents of total soluble protein, reducing sugar, cellulose, and total phenol decreased. Compared with diploid sprouts, tetraploid sprouts had higher biomass and thicker hypocotyl. Tetraploid sprouts had higher ash and carotenoid contents, but had lower phenol and flavonoid accumulation. 677 metabolites were identified in TB sprouts by UPLC-MS analysis, including 62 diseases-resistance metabolites and 43 key active ingredients. Some key bioactive metabolites, such as rimonabant, quinapril, 1-deoxynojirimycin and miglitol, were identified. 562 differential expressed metabolites (DEMs) were identified during sprouting with seven accumulation patterns, and five hormones were found to be involved in sprout development. Additionally, 209 DEMs between diploid and tetraploid sprouts were found, and some key bioactive metabolites were induced by chromosome doubling such as mesoridazine, amaralin, atractyloside A, rhamnetin and Qing Hau Sau. This work lays a basis for the development and utilization of TB sprouts and provides evidence for the selection of tetraploid varieties to produce sprouts with high biomass and quality.

2.
Zhen Ci Yan Jiu ; 48(1): 95-101, 2023 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-36734505

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of moxibustion at Baihui (CV20) combined with acupuncture in treatment of cervical vertigo. METHODS: From the databases, such as CNKI, VIP, WanFang, CBM, PubMed, Cochrane Library and Embase, the studies of randomized controlled trials (RCTs) on moxibustion at CV20 combined with acupuncture for cervical vertigo were searched from inception to September 15th, 2021. The Cochrane risk of bias assessment tool was utilized to evaluate the quality of the included literature. Using RevMan5.3, Stata12.0 and TSA0.9.5.0 10 Beta software, the Meta-analysis and trial sequential analysis (TSA) were performed. RESULTS: Seventeen RCTs with 1 232 patients were included. Meta-analysis showed that in the trial group (moxibustion at CV20 combined with acupuncture), the total effective rate (RR=1.17, 95%CI[1.12, 1.22], P<0.000 1), the curative and remarkably-effective rate (RR=1.28,95%CI[1.20,1.36],P<0.000 1) and the score of cervical vertigo (WMD=2.88, 95%CI[1.87, 3.89], P<0.000 1) were all better when compared with the control group (simple acupuncture or electroacupuncture group). The results of trial sequential analysis indicated that for the cumulative Z-score of each RCT, the Z-curve crossed the conventional test boundary and TSA boundary, which further confirmed the clinical efficacy of moxibustion at CV20 combined with acupuncture on cervical vertigo. CONCLUSION: The clinical efficacy of moxibustion at CV20 combined with acupuncture is determined in treatment of cervical vertigo.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36733846

RESUMO

Background: Microvascular angina (MVA) has received increasing attention and interest in recent years, but there are still some shortcomings in the diagnosis and treatments at current stage. In recent years, several studies have confirmed the efficacy of proprietary Chinese medicines (PCMs) in improving MVA symptoms; however, there is no systematic review and meta-analysis to comprehensively assess the efficacy of PCMs in this area. Objective: Investigating the clinical efficacy of proprietary Chinese medicines for treating MVA and coronary microvascular function. Methods: We looked up articles from January 1, 2012, to the present from eight databases. Then, we screened the literature and followed the 2019 version 2 of Cochrane risk of bias tool for systematic review. The Stata/SE 15.0 software was used for the meta-analysis. Results: There are 21 studies, including 1,641 patients who were included in this review. According to the results, the combination of PCMs and conventional MVA treatment was able to further enhance clinical efficacy [RR = 1.28, 95% CI (1.20, 1.36), p < 0.001], prolong the time of duration on the treadmill exercise testing (TET) [SMD = 1.49, 95% CI (0.63, 2.36), p = 0.001] and improve levels of NO [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. At the same time, PCMs could also decrease the microvascular resistance index (IMR) [SMD = -1.79, 95% CI (-2.58, -1.00), p < 0.001)], serum level of hs-CRP [SMD = -1.21, 95% CI (-1.84, -0.58), p < 0.001] and ET-1 [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. Regards to medication safety, a total of 27 adverse events occurred, including 10 cases in the intervention group and 17 cases in the control group. Conclusion: The study suggests that the combination of PCMs and conventional MVA treatment enhances clinical efficacy and could better improve coronary microvascular function. In the future, we expect more high-quality, randomized, double-blind clinical studies to validate the safety, and efficacy of PCMs to provide valuable evidence-based medicine (EBM) for the treatment of MVA with PCMs.

4.
BMC Cancer ; 23(1): 31, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624407

RESUMO

OBJECTIVE: To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC). METHODS: We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. RESULTS: Data from 18,375 patients in 15 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.32-0.59) and total recurrence (OR 0.72, 95%CI 0.58-0.89). ACR was also associated with significantly better overall survival (HR 0.66, 95%CI 0.57-0.76), progression-free survival (HR 0.56, 95%CI 0.39-0.81) and disease-free survival (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer.


Assuntos
Neoplasias do Endométrio , Feminino , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/tratamento farmacológico , Quimioterapia Adjuvante , Quimiorradioterapia Adjuvante , Quimiorradioterapia , Radioterapia Adjuvante
6.
Org Lett ; 25(3): 549-554, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36637443

RESUMO

Herein, a mild and convenient defluorinative reductive cross coupling of gem-difluoroalkenes with aliphatic aldehydes has been developed to afford diverse silyl-protected ß-fluorinated allylic alcohols. The reaction is operationally simple and shows good functional group tolerance with moderate to excellent yields. The utility of this method is demonstrated by converting the products into various bioactive fluorinated compounds, showing its potential applications in drug discovery and biochemistry.

7.
Curr Probl Cardiol ; 48(4): 101592, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36632931

RESUMO

The association between disease-specific health quality of life (QoL) and adverse outcomes remains controversial in patients with heart failure (HF). This meta-analysis aimed to evaluate the association of QoL measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) or Kansas City Cardiomyopathy Questionnaire (KCCQ) with all-cause mortality in patients with HF. PubMed and Embase databases were comprehensively searched until December 30, 2022 to identify studies investigating the utility of QoL measured by the MLHFQ or KCCQ in predicting all-cause mortality patients with HF. Twenty-five studies reported on 24 articles enrolling 42,414 HF patients were identified. A comparison of the top with the bottom MLHFQ score, the pooled adjusted hazard ratios (HR) of all-cause mortality was 1.56 (95% confidence intervals [CI] 1.26-1.94). When analyzed the MLHFQ as continuous variable, each 10-point MLHFQ score increase conferred a 12% (95% CI 6%-18%) higher risk of all-cause mortality, which was consistently significant for physical component (HR 1.19; 95% CI 1.09-1.30) and mental component (HR 1.21; 95% CI 1.05-1.40). A comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10-2.60) for all-cause mortality. Furthermore, each 10-point KCCQ score decrease was associated with a 12% (95% CI 7%-16%) higher risk of all-cause mortality. Worse health-related QoL defined by the higher MLHFQ or lower KCCQ score was associated with an increased risk of all-cause mortality in patients with HF. Assessment of disease-specific health QoL at baseline may provide important prognostic information in these patients.

8.
Anal Methods ; 15(4): 419-429, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36606523

RESUMO

As the "mother of antioxidants", glutathione (GSH) plays an important role in physiological functions. Rapid and accurate monitoring of GSH is of great significance for medicinal chemistry, food chemistry, and clinical medicine. We herein report a visual ratiometric fluorescence sensor based on MnO2 nanowires (MnO2 NWs) as an oxidant, quencher and recognition unit for the determination of GSH. The powerful ratiometric fluorescent probe was constructed by mixing thiamine (VB1) and rhodamine B (RhB) with the help of MnO2 NWs. MnO2 NWs could not only effectively quench the fluorescence of RhB due to the inner filter effect (IFE), but also oxidized non-fluorescent VB1 to blue fluorescent thiochrome (oxVB1). Upon interaction with GSH, the quenched RhB fluorescence could be rapidly restored through decomposition of MnO2 NWs into Mn2+, while the oxVB1 fluorescence decreased, showing an apparent color change from blue to red. The concentration of GSH was proportional to the ratio of fluorescence intensities of RhB and oxVB1, and the detection linear range was 1 to 10 000 µM with comparable selectivity. This ratio fluorescence sensor was successfully applied to GSH determination in whitening capsules and glutathione tablets with satisfactory results, and the sensor may be a potentially powerful tool for the detection of GSH.


Assuntos
Nanofios , Fluorescência , Oxidantes , Compostos de Manganês/química , Óxidos/química , Glutationa
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 198-202, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647667

RESUMO

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.


Assuntos
Neoplasias da Mama , Sincalida , Humanos , Camundongos , Animais , Feminino , Distribuição Tecidual , Sincalida/metabolismo , Membrana Celular/metabolismo , Linhagem Celular Tumoral , Lipossomos , Neoplasias da Mama/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-36634261

RESUMO

BACKGROUND: Following the rapid spread of the novel coronavirus SARS-CoV-2, short-term and long-term mental health impacts on the public, in particular for vulnerable individuals, have been reported worldwide. Although digital mental health expands accessibility while removing many barriers to in-person therapy, its usability, feasibility, acceptability, and efficacy has been examined during the initial phase of pandemic and its aftermath. OBJECTIVE: To understand what mental health services are offered, whether they are practical or acceptable, and to what extent digital mental health services are effective in response to COVID-19 across high-income countries and middle-income countries. METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and scoping review extension. We implemented searches in PubMed (MEDLINE), EMBASE, PsycINFO, and Cochrane between December 2019 and November 2021 for studies that involve the use of digital mental health services. Two review authors screened, assessed, and extracted studies independently. The protocol was registered on the PROSPERO (CRD42022307695). RESULTS: This review identified 7506 articles through database searching. Sixty-five studies from 18 countries with 67,884 participants were eligible for the scoping review, and sixteen studies were included in the meta-analysis. A total of 15 studies (23.1%) measured usability, 31 studies (47.7%) evaluated feasibility, 29 (44.6%) considered acceptability, and 51 (78.5%) assessed efficacy. Web-based programs (32.3%), videoconferencing platforms (24.6%), smartphone applications (21.5%), and text messaging (7.7%) were the main techniques. Psychotherapy (67.7%) followed by psychoeducation (9.2%) and psychological support (7.7%) were commonly used. The results of meta-analysis showed digital mental health interventions were associated with a small reduction in depressive symptoms (SMD=-0.49 [-0.74 to -0.24], P<0.001), and a moderate reduction in anxiety symptoms (SMD=-0.66 [-1.23 to -1.0], P=0.02) significantly. CONCLUSIONS: Findings suggested that digital mental health intervention may be practical and helpful for the general population, at-risk individuals, and patients with pre-existing mental disorders across high-income and middle-income countries. An expanded research agenda is needed to apply different strategies for addressing diverse psychological needs and develop integrated mental health services in the post-COVID-19 era. CLINICALTRIAL: Not applicable.

11.
Mol Biotechnol ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656498

RESUMO

Alterations in the M1/M2 polarization phenotype significantly affect disease progression. Antioxidant and anti-inflammatory protective effects of resveratrol (Res) have been demonstrated. This paper tested the hypothesis that Res could protect against cerebral ischemia-reperfusion injury (CI/RI) by modulating microglial polarization via the miR-450b-5p/KEAP1/Nrf2 pathway. Rats were first treated with Res and adenovirus that interfered with miR-450b-5p or KEAP1, and then established a middle cerebral artery occlusion-reperfusion model using modified nylon sutures. Rats were then evaluated for neurological and behavioral functions, and markers of M2 microglia were detected by immunofluorescence staining. Additionally, the signature patterns of miR-450b-5p, KEAP1, and Nrf2 were determined. The collected data demonstrated that Res exerted neuroprotective effects in CI/RI by promoting microglial M2 polarization. Additionally, Res could regulate the Nrf2 pathway by targeting KEAP1 by up-regulating miR-450b-5p. Up-regulating miR-450b-5p or down-regulating KEAP1 could further promote the protective effect of Res, while down-regulating miR-450b-5p or up-regulating KEAP1 worked oppositely. Our study demonstrates that Res exerts neuroprotective effects on microglial M2 polarization through the miR-450b-5p/KEAP1/Nrf2 pathway during CI/RI.

12.
J Clin Anesth ; 85: 111047, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36599219

RESUMO

STUDY OBJECTIVE: Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB). DESIGN: Prospective, randomized, double-blind, parallel-group clinical trial. SETTING: University-affiliated teaching hospital. PATIENTS: We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021. INTERVENTIONS: Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure. MEASUREMENTS: The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes. MAIN RESULTS: The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups. CONCLUSIONS: Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol.


Assuntos
Anestesia , Propofol , Humanos , Propofol/efeitos adversos , Estudos Prospectivos , Anestésicos Intravenosos/efeitos adversos , Colonoscopia , Hipnóticos e Sedativos/efeitos adversos , Sedação Consciente/efeitos adversos , Sedação Consciente/métodos
13.
J Sci Food Agric ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36620949

RESUMO

BACKGROUND: Harpadon nehereus is a high-protein marine fish. A valuable way to add value to H. nehereus is to convert it into protein hydrolysate. The Maillard reaction is an effective way to improve the functional properties of peptides and proteins, which are affected by many factors such as reactant concentration, water activity, pH, temperature, and heating time. However, the traditional Maillard reaction method is inefficient. The purpose of this study was therefore to explore the effect of the ultrasound-assisted wet heating method on the Maillard reaction of H. nehereus protein hydrolysate (HNPH) in a new-type green solvent - a natural hypereutectic solvent (NADES). RESULTS: Harpadon nehereus protein hydrolysate-xylose (Xy) conjugates were prepared via a Maillard reaction in a NADES system using an ultrasound-assisted wet heating method. The effects of different treatment conditions on the Maillard reaction were studied. The optimized glycation degree (DG) of HNPH-Xy conjugates was obtained with a water content of 10%, a reaction temperature of 80 °C, a reaction time of 35 min, and an ultrasonic power level of 300 W. Compared with HNPH, the structure of HNPH-Xy conjugates were significantly changed. Moreover, the functional properties and antioxidant activity of HNPH-Xy were all superior to the HNPH. CONCLUSIONS: An ultrasound-assisted wet-heating Maillard reaction between HNPH and Xy in the NADES system could be a promising way to improve the functional properties of HNPH. © 2023 Society of Chemical Industry.

14.
Cancers (Basel) ; 15(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36672395

RESUMO

BACKGROUND: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. METHODS: Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile. RESULTS: We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45+CD11b+Ly6G- mononuclear myeloid cells. CONCLUSIONS: Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer.

15.
J Neurosci ; 43(5): 803-811, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36564185

RESUMO

Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH-abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the designer receptors exclusively activated by designer drugs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduced anxiety-like behaviors, whereas it did not induce depression-like behaviors in male mice after prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms from METH with few side effects.SIGNIFICANCE STATEMENT Prolonged abstinence from METH triggers IPN GABAergic neurons and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduces anxiety in mice.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Núcleo Interpeduncular , Metanfetamina , Síndrome de Abstinência a Substâncias , Camundongos , Masculino , Animais , Metanfetamina/farmacologia , Núcleo Interpeduncular/metabolismo , Ansiedade/metabolismo , Neurônios GABAérgicos/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo
16.
Neural Regen Res ; 18(3): 560-567, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018178

RESUMO

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage (ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase VII into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell (BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3 (NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

17.
Addict Biol ; 28(1): e13255, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36577725

RESUMO

Methamphetamine (METH) is a commonly abused addictive psychostimulant, and METH-induced neurotoxic and behavioural deficits are in a sex-specific manner. However, there is lack of biomarkers to evaluate METH addiction in clinical practice, especially for gender differences. We utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to detect the serum metabolomics in METH addicts and controls, specially exploring the sex-specific metabolic alterations by METH abuse. We found that many differently expressed metabolites in METH addicts related to metabolisms of amino acid, energy, vitamin and neurological disorders. Further, METH abuse caused different patterns of metabolomics in a sex-specific manner. As to amino acid metabolism, L-phenylalanine, L-tryptophan and L-histidine in serum of male addicts and betaine in serum of female addicts were significantly changed by METH use. In addition, it seemed that purine and pyrimidine-related metabolites (e.g., xanthosine and adenosine 5'-monophosphate) in male and the metabolites of hormone (e.g., cortisol) and folate biosynthesis (e.g., 7,8-dihydrobiopterin and 4-hydroxybenzoic acid) in female were more sensitive to METH addiction. Our findings revealed that L-glutamic acid, L-aspartic acid, alpha-ketoglutarate acid and citric acid may be potential biomarkers for monitoring METH addiction in clinic. Considering sex-specific toxicity by METH, the metabolites of purine and pyrimidine metabolism in male and those of stress-related hormones in female may be used to facilitate the accurate diagnosis and treatment for METH addicts of different genders.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Feminino , Masculino , Humanos , Metanfetamina/farmacologia , Espectrometria de Massas em Tandem , Biomarcadores/metabolismo , Purinas , Aminoácidos , Pirimidinas
18.
Brain Res ; 1801: 148203, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36521514

RESUMO

The neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) present significant morbidity and mortality due to frequent non-response or adverse effects of the current clinical drugs. The disruption of the blood-brain barrier (BBB) contributes to inflammatory NPSLE disease progression. K-7174, a highly piperazine-derived compound, inhibits leukocyte adhesion and inflammatory factor expression. The present study aimed to comprehensively assess the treatment effect of neurobehavioral deficits in MRL/lpr mice, a validated neuropsychiatric lupus model. The intraperitoneal injection of K-7174 alleviated lupus-like symptoms and improved cognitive dysfunction in MRL/lpr mice. Also, it significantly attenuated neuronal degeneration and decreased serum albumin deposition in the hippocampus. Furthermore, K-7174 acted directly on the brain microvascular endothelial bEnd.3 cells and reduced the BBB permeability, manifested by inhibiting the activation of brain microvascular endothelial cells and increasing the expression of tight junctions (TJs). Notably, in vitro experiments showed that K-7174 alleviates the decreased ZO1 and Occludin expression in bEnd.3 cells caused by lactate increase, improving cell permeability via the MCT4/NKAP/CREB signaling pathway. These findings suggested that K-7174 mediates the attenuation of NPSLE in MRL/lpr mice, indicating a promising therapeutic strategy for NPSLE.


Assuntos
Células Endoteliais , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Animais , Camundongos , Depressão/tratamento farmacológico , Camundongos Endogâmicos MRL lpr
19.
Food Chem ; 407: 135133, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493492

RESUMO

The binding mechanism between tea polyphenols and sturgeon myofibrillar protein (SMP) in the early stage (0, 2, 4 min), middle stage (6, 10 min) and late stage (15 min) of low temperature vacuum heating (LTVH) in an in vitro anti-glycation model was investigated. The result indicated that the protein cross-linking during LTVH treatment were mainly induced by tea polyphenols. The loss rate of free arginine (Arg) and free lysine (Lys) of SMP at the late stage of LTVH treatment (15 min) was 73.95 % and 83.16 %, respectively. The hydrophobic force and disulfide bond were the main force between tea polyphenols and SMP in the middle and late stage of LTVH treatment. The benzene ring and phenolic hydroxyl group of tea polyphenols can interact with the amino acid residues of SMP, which was exothermic and entropy-increasing. This study provides new insights in the interaction mechanisms between tea polyphenols-protein during heat treatment process.


Assuntos
Polifenóis , Chá , Polifenóis/farmacologia , Polifenóis/química , Chá/química , Vácuo , Calefação , Temperatura
20.
J Nanobiotechnology ; 20(1): 509, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463199

RESUMO

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Neoplasias , Estados Unidos , Sistemas de Liberação de Medicamentos , Meia-Vida , Disponibilidade Biológica , Neoplasias/tratamento farmacológico
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