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1.
Pharmaceutics ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36678798

RESUMO

Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs. The aggregation-caused quenching (ACQ) probes P4 emitted intense fluorescence signals in intact NC while quenched after the degradation of NC, had been demonstrated the feasibility of label intact NC. In this study, P4 was loaded in solid lipid nanoparticles (SLNs), and further encapsulated into DMNs, to track the transdermal diffusion of SLNs delivered at different skin sites. The results showed that SLNs had excellent stability after being loaded into DMNs with no significant changes in morphology and fluorescence properties. The in vivo live and ex vivo imaging showed that the transdermal diffusion rate of NC-loaded DMNs was positively correlated with skin thickness, with the order ear > abdomen > back. In conclusion, this study confirmed the site-dependency of transdermal diffusion in NC-loaded DMNs.

2.
Food Res Int ; 163: 112194, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596132

RESUMO

Fermented peppers are usually obtained by the spontaneous fermentation of microorganisms attached to fresh peppers, and the variable microbial composition would lead to inconsistencies in flavor between batches. To demonstrate the roles of microorganisms in flavor formation, the core microbes closely associated with the key aroma compounds of fermented pepper paste were screened and validated in this study. Lactobacillus was the dominant bacterial genus in fermented pepper paste, whereas the main fungal genera were Alternaria and Kazachstania. Nine strains of the genera Lactobacillus, Weissella, Bacillus, Zygosaccharomyces, Kazachstania, Debaryomyces, and Pichia were isolated from fermented pepper paste. Eleven key aroma compounds were identified using gas chromatography combined with olfactometry and relative odor activity values. Correlation analysis showed that Zygosaccharomyces and Kazachstania were positively correlated with the majority of the key aroma compounds, whereas Lactobacillus was negatively correlated with them. Thus, Zygosaccharomyces and Kazachstania were identified as core genera associated with the key odorants. Finally, Zygosaccharomyces bisporus, Kazachstania humilis, and Lactiplantibacillus plantarum were used as starter cultures for fermented peppers, confirming that Z. bisporus and K. humilis were more beneficial for the key aroma compounds (e.g., acetate, linalool, and phenyl ethanol) rather than L. plantarum. This study contributed to understanding the flavor formation mechanism and provided references for the quality control of food fermentation.


Assuntos
Capsicum , Capsicum/química , Odorantes/análise , Fermentação , Verduras , Cromatografia Gasosa
3.
J Transl Med ; 21(1): 21, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635690

RESUMO

BACKGROUND: Growth arrest-specific 6 (GAS6) is a vitamin K-dependent protein related to inflammation, fibrosis, as well as platelet function. Genetic ablation of GAS6 in mice protects against cardiac hypertrophy and dysfunction. Nonetheless, the association between plasma GAS6 levels and acute heart failure (AHF) patients is still unknown. METHODS: We measured plasma GAS6 concentrations in 1039 patients with AHF who were enrolled in the DRAGON-HF trial (NCT03727828). Mean follow-up of the study was 889 days. The primary endpoint is all-cause death. RESULTS: In total, there were 195 primary endpoints of all-cause death and 135 secondary endpoints of cardiovascular death during the mean follow-up duration of 889 days. The higher levels of GAS6 were associated with higher rates of all-cause and cardiovascular death (P < 0.05). Baseline plasma GAS6 levels were still strongly correlated with clinical outcomes in different models after adjustment for clinical factors and N-terminal pro-brain natriuretic peptide (NT-proBNP, P < 0.05). GAS6 could further distinguish the risks of clinical outcomes based on NT-proBNP measurement. CONCLUSION: Elevated plasma GAS6 levels were associated with an increased risk of all-cause and cardiovascular death in patients with AHF. Trial registration NCT03727828 (DRAGON-HF trial) clinicaltrials.gov.


Assuntos
Insuficiência Cardíaca , Peptídeos e Proteínas de Sinalização Intercelular , Biomarcadores , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Volume Sistólico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue
4.
Headache ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651491

RESUMO

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

5.
BMC Neurol ; 23(1): 10, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624392

RESUMO

BACKGROUND: We investigated the influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of patients with acute ischemic stroke who received intravenous thrombolytic therapy (ITT) in Dalian, China, in 2020. METHODS: This retrospective descriptive study, conducted from February 1, 2020, to August 31, 2020, examined 13 hospitals in Dalian that participated in the "stroke emergency map". To use this "stroke emergency map" of China, patients followed the official "Stroke Map" WeChat account and dialed 120 for emergency medical services. We analyzed the number of patients with acute ischemic stroke who underwent ITT. In particular, we examined the onset-to-door time (ODT), door-to-needle time (DNT), onset-to-needle time (ONT), mode of transportation to the hospital, and National Institutes of Health Stroke Scale (NIHSS) scores before and after ITT. Data were collected for the aforementioned period and compared with the 2021 baseline data from the same time of year. The Mann‒Whitney U test was performed for data analysis. RESULTS: Compared with the data from 2020, the number of patients with acute ischemic stroke who underwent ITT increased (from 735 to 1719 cases) in 2021, but the DNT decreased (from 59 to 45 min; P = 0.002). Moreover, 83.9% of patients in 2020 presented to the hospital without ambulance transport, compared to 81.1% of patients in the 2021 non-COVID-19 pandemic period. Patients with NIHSS scores of 6-14 were more likely to call an ambulance for transport to the hospital than to transport themselves to the emergency department. CONCLUSIONS: During the 2020 COVID-19 pandemic, the DNT was prolonged as a result of strengthened fever surveillance. In 2021, the number of patients with acute ischemic stroke who underwent ITT increased compared to the previous year. Notably, the growth in the number of patients with acute ischemic stroke who underwent ITT benefited from both the "stroke emergency map" of China and the "green channel," a novel treatment approach that focuses on the rational design of the rescue process. TRIAL REGISTRATION: Our study was a retrospective descriptive study, not a clinical trial, thus we did not have to register for clinical trials.


Assuntos
Isquemia Encefálica , COVID-19 , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/epidemiologia , Pandemias , Estudos Retrospectivos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Resultado do Tratamento , Fibrinolíticos/uso terapêutico , Terapia Trombolítica , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento
6.
Int J Cardiol ; 373: 118-123, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36476671

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a chronic progressive disease that may lead to right heart failure (RHF) and early death. Balloon atrial septostomy (BAS) may be used for the palliative treatment of RHF from PAH. We present our contemporary institutional experience of utilizing BAS in idiopathic PAH (IPAH) patients with refractory RHF to investigate the effect on the safety, efficacy and long-term survival. METHODS: This retrospective analysis included 12 IPAH patients with severe RHF from March 2017 to May 2019 who were assessed as high risk. All patients received standard treatment including combination of PAH-specific drugs. Graded BAS was performed on these patients due to unsatisfactory clinical response. Clinical, functional and hemodynamic variables before and immediately after the procedure were collected. 1-year follow-up outcomes and 3-year survival rate were further analyzed. RESULTS: Successful septostomy was achieved in cases with no procedure-related complications. All patients obtained hemodynamic improvement immediately after the procedure. The WHO functional class and exercise endurance improved at 1-year follow-up, 7 of 12 patients achieved intermediate-low risk status, while the rest remained at intermediate-high risk. 2 patients died at 18 and 20 months due to malignant arrhythmia and advanced heart failure, respectively. Survival at 1 year and 3 years was 100% and 83.3%. CONCLUSIONS: In selected IPAH patients with refractory RHF, BAS is an additional therapeutic strategy, especially when PAH-specific drugs could not achieve the treatment target. BAS can improve hemodynamic variables, bring clinical and cardiac functional benefits and increase the 3-year survival.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Pulmonar Primária Familiar , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Estudos Retrospectivos
7.
Aging Clin Exp Res ; 34(3): 679-685, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34570316

RESUMO

BACKGROUND: Peripheral artery disease (PAD) is a common syndrome in elderly people. Recently, artificial intelligence (AI) algorithms, in particular machine-learning algorithms, have been increasingly used in disease diagnosis. AIM: In this study, we designed an effective diagnostic model of PAD in the elderly patients using artificial intelligence. METHODS: The study was performed with 539 participants, all over 80 years in age, who underwent the measurements of Doppler ultrasonography and ankle-brachial pressure index (ABI). Blood samples were collected. ABI and two machine-learning algorithms (MLAs)-logistic regression and a random forest (RF) model-were established to diagnose PAD. The sensitivity and specificity of the models were analyzed. An additional RF model was designed based on the most significant features of the original RF model and a prospective study was conducted to demonstrate its external validity. RESULTS: Thirteen of the 28 features introduced to the MLAs differed significantly between PAD and non-PAD participants. The respective sensitivities and specificities of logistic regression, RF, and ABI were as follows: logistic regression (81.5%, 83.8%), RF (89.3%, 91.6%) and ABI (85.1%, 84.5%). In the prospective study, the newly designed RF model based on the most significant seven features exhibited an acceptable performance rate for the diagnosis of PAD with 100.0% sensitivity and 90.3% specificity. CONCLUSIONS: An RF model was a more effective method than the logistic regression and ABI for the diagnosis of PAD in an elderly cohort.


Assuntos
Inteligência Artificial , Doença Arterial Periférica , Idoso , Algoritmos , Índice Tornozelo-Braço/métodos , Humanos , Aprendizado de Máquina , Doença Arterial Periférica/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Prospectivos
8.
J Control Release ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464062

RESUMO

Microneedles (MNs) with enhanced delivery efficiency have revolutionized the transdermal drug delivery system for treating systemic illness. However, the bioavailability of MNs was still far from the clinical requirements by only overcoming the stratum corneum barrier. Herein, hyaluronidase (HAase)-powered MNs were developed as a top-down permeation-enhancement strategy to hijack the sequential transdermal barriers for improved bioavailability. HAase MNs with robust mechanical strength showed excellent skin penetration ability and significantly enhanced the transdermal delivery efficacy of macromolecular drugs as compared to that of HAase-absent MNs, resulting in considerable effect to subcutaneous injection in terms of biodistribution, bioavailability, and therapeutical efficacy. As evidenced from the distribution of trypan blue and fluorescence underlying skin, the positive effects exerted by HAase MNs could be ascribed to the depolymerization of HA that would loosen the subcutaneous space and destruct the extracellular matrix barrier to promote drug diffusion and permeation in larger area and greater depth. Notably, the transient interconversion of keratin from α-helix to ß-sheet that might assist the drug residues on the skin surface permeate across the stratum corneum during administration might be another reason not to be ignored. As a labor-saving strategy, HAase-powered MNs offers a promising and painless administration route for macromolecules.

9.
ACS Nano ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455073

RESUMO

Two-dimensional (2D) materials with the atomically thin thickness have attracted great interest in the post-Moore's Law era because of their tremendous potential to continue transistor downscaling and offered advances in device performance at the atomic limit. However, the metal-semiconductor contact is the bottleneck in field-effect transistors (FETs) integrating 2D semiconductors as channel materials. A robust and tunable doping method at the source and drain region of 2D transistors to minimize the contact resistance is highly sought after. Here we report a stable carrier doping method via the mild covalent grafting of maleimides on the surface of 2D transition metal dichalcogenides. The chemisorbed interaction contributes to the efficient carrier doping without degrading the high-performance carrier transport. Density functional theory results further illustrate that the molecular functionalization leads to the mild hybridization and the negligible impact on the conduction bands of monolayer MoS2, avoiding the random scattering from the dopants. Differently from reported molecular treatments, our strategy displays high thermal stability (above 300 °C) and it is compatible with micro/nano processing technology. The contact resistance of MoS2 FETs can be greatly reduced by ∼12 times after molecular functionalization. The Schottky barrier of 44 meV is achieved on monolayer MoS2 FETs, demonstrating efficient charge injection between metal and 2D semiconductor. The mild covalent functionalization of molecules on 2D semiconductors represents a powerful strategy to perform the carrier doping and the device optimization.

10.
Pharmaceuticals (Basel) ; 15(12)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36558956

RESUMO

Selaginella doederleinii Hieron. is a common pharmacological plant, and this folk herbal medicine and its complex preparations have been widely used for the treatment of throat carcinoma (TC) and several associated complications in traditional Chinese medicine. This study was aimed at investigating the specific anti-throat carcinoma impacts and potential mechanisms of a biflavonoid-rich extract from S. doederleinii (SD-BFRE). The phytochemical profiling of SD-BFRE was performed by HPLC-ESI-QTOF-MS and UPLC-PDA, and the detailed pharmacological effects and mechanisms were respectively evaluated in vitro and in vivo. MTT assay, the Transwell assay and flow cytometry were performed to evaluate the abilities of SD-BFRE on inhibiting cell infiltrative growth in TC cells (Hep-2 and FaDu) in in vitro experiments. In vivo experiments used Hep-2 tumor-bearing nude mice to evaluate the anti-TC effect of SD-BFRE. Western blotting was used to explore the potential apoptotic pathway of TC cells. Here, we found that SD-BFRE exhibited anti-proliferation and pro-apoptotic effects in TC cells. Mechanistic studies have identified that SD-BFRE can suppress the activity of IKKß and IκB-α kinase and then down-regulate the effector proteins of NF-κB/COX-2 signaling. Moreover, SD-BFRE induced apoptosis partly by regulating the Akt/Bad/caspase signaling pathway. Taken together, this study firstly demonstrated that SD-BFRE exerted its anti-TC effects by way of IKKß/NF-κB/COX-2 and Akt/Bad pathways and might represent a potential chemotherapeutic agent for throat carcinoma.

11.
AAPS PharmSciTech ; 24(1): 21, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526883

RESUMO

Azithromycin (AZI) is a commonly used antibiotic with extremely bitter taste that severely decreases the compliance of patients. Besides, the poor solubility of AZI in alkaline pH makes it difficult to be absorbed in the small intestine. To achieve the dual effects of taste masking and enhanced absorption, AZI-loaded pellets were coated by polymer blend of Eudragit®RL30D and Eudragit®L30D-55. The coated pellets could avoid drug release in the oral environment (pH 5-7) but release rapidly in the gastric environment (pH 1-3). Then, the coated pellets were further formulated into dry suspension to address the problem of dysphagia. The taste-masking effect tests by electronic tongue and human volunteers revealed that the dry suspension was more effective to improve the bitter taste of AZI than the commercial product. Therefore, this study provided an economical and feasible approach for taste masking with good practical application prospect.


Assuntos
Azitromicina , Paladar , Humanos , Liberação Controlada de Fármacos , Química Farmacêutica/métodos , Suspensões , Solubilidade , Implantes de Medicamento/farmacologia , Concentração de Íons de Hidrogênio
12.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36555490

RESUMO

As one of the most studied mesoporous silica nanoparticles (MSNs) in drug delivery systems, Mobil Composition of Matter No. 41 (MCM-41) possesses unique properties including perfect channel architecture, excellent load capacity, and good biocompatibility. However, the applications of MCM-41 nanoparticles in drug delivery have not yet been industrialized, due to the interaction between MCM-41 and biomolecules (especially proteins) that affect their in vivo behaviors after dosing. To investigate the interactions between MCM-41 and proteins, this study selected bovine serum albumin (BSA), lysozyme (Lyso), and bovine hemoglobin (BHb) as model proteins and characterized the ultraviolet-visible, fluorescence, circular dichroism spectra and the protein adsorption of MCM-41-protein complex. The UV-Vis spectra exhibited the different absorption increment degrees of three proteins. The fluorescence spectra showed that the fluorescence intensity of proteins changed by different trends. The CD spectra indicated that the secondary structure changes were ranked as BSA > Lyso > BHb, which is consistent with the protein's adsorption capability on MCM-41. It was shown that there were three different patterns of MCM-41-proteins interactions. The hydrophilic and low-charged BSA followed the strong interaction pattern, the hydrophilic but heavily charged Lyso followed the moderate interaction pattern, and the hydrophobic BHb followed the weak interaction pattern. Different interaction patterns would lead to different effects on the structural properties of proteins, the surface chemistry of MCM-41, and the absorption capability of proteins on MCM-41. We believe our study will provide a better insight into the application of MCM-41 nanoparticles in drug delivery systems.


Assuntos
Hemoglobinas , Dióxido de Silício , Dicroísmo Circular , Dióxido de Silício/química , Hemoglobinas/química , Soroalbumina Bovina/química , Espectrometria de Fluorescência
13.
Sci Rep ; 12(1): 22604, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585458

RESUMO

Precision radiotherapy needs to manage organ movements to prevent critical organ injury. The purpose of this study is to examine the feasibility of motion control of the lung by suppressing respiratory motion. The non-invasive high frequency oscillatory ventilation (NIHFOV) is a technique commonly used in the protection of lung for patients with acute lung disease. By using a very high respiratory frequency and a low tidal volume, NIHFOV allows gas exchange, maintains a constant mean airway pressure and minimizes the respiratory movements. We tested healthy volunteers NIHFOV to explore the optimal operational parameter setting and the best possible motion suppression achievable. This study was conducted with the approval of Institutional Review Boards of the Wuwei Cancer hospital (approval number: 2021-39) and carried out in accordance with Declaration of Helsinki. The study comprises two parts. Twenty three healthy volunteers participated in the first part of the study. They had 7 sessions of training with the NIHFOV. The duration of uninterrupted, continuous breathing under the NIHFOV and the optimal operational machine settings were defined. Eight healthy volunteers took part in the second part of the study and underwent 4-dimensional CT (4DCT) scanning with and without NIHFOV. Their respiratory waveform under free breathing (FB) and NIHFOV were recorded. The maximum range of motion of the diaphragm from the two scannings was compared, and the variation of bilateral lung volume was obtained to evaluate the impact of NIHFOV technique on lung volume. The following data were collected: comfort score, transcutaneous partial pressure of oxygen (PtcO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), and pulse rate. Data with and without NIHFOV were compared to evaluate its safety, physiological impacts and effect of lung movement suppression. All the volunteers completed the training sessions eventlessly, demonstrating a good tolerability of the procedure. The median NIHFOV-on time was 32 min (22-45 min), and the maximum range of motion in the cephalic-caudal direction was significantly reduced on NIHFOV compared with FB (1.8 ± 0.8 cm vs 0.3 ± 0.1 cm, t = - 3.650, P = 0.003); the median range of motion was only 0.3 ± 0.1 cm on NIHFOV with a good reproducibility. The variation coefficient under NIHFOV of the right lung volume was 2.4% and the left lung volume was 9.2%. The PtcO2 and PtcCO2 were constantly monitored during NIHFOV. The medium PtcCO2 under NIHFOV increased lightly by 4.1 mmHg (interquartile range [IQR], 4-6 mmHg) compared with FB (t = 17.676, P < 0.001). No hypercapnia was found, PtcO2 increased significantly in all volunteers during NIHFOV (t = 25.453, P < 0.001). There was no significant difference in pulse rate between the two data sets (t = 1.257, P = 0.233). NIHFOV is easy to master in healthy volunteers to minimize respiratory movement with good tolerability and reproducibility. It is a feasible approach for lung motion control and could potentially be applied in accurate radiotherapy including carbon-ion radiotherapy through suppression of respiratory movement.


Assuntos
Ventilação de Alta Frequência , Humanos , Voluntários Saudáveis , Reprodutibilidade dos Testes , Pulmão/diagnóstico por imagem , Respiração
14.
J Bone Oncol ; 37: 100458, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36388640

RESUMO

Purpose: To investigate the prognostic value and function of six-transmembrane epithelial antigen of prostate 1 (STEAP1) in osteosarcoma and determine whether EFEMP1 mediates its effects. Methods: IHC (immunohistochemistry)/ICC (immunocytochemistry) in conjunction with RT-qPCR (quantitative real-time polymerase chain reaction) were employed to assess the expression of STEAP1 in paratumoral tissues, osteosarcoma, benign fibrous dysplasia, osteosarcoma cells, normal osteoblastic hFOB cells, as well as various invasive subclones. The association of STEAP1 with outcome was examined with Kaplan-Meier graph among the osteosarcoma population. The effects of the down-regulation and up-regulation of STEAP1 on the biological behavior of osteosarcoma cells were studied through in-vitro and in-vivo functional tests. Results: Up-regulation of STEAP1 in the osteosarcoma tissues, whose correlations with the malignant osteosarcoma phenotype and the poor patient outcome were positive. In addition, STEAP1 induced the epithelial-mesenchymal transition (EMT) via the Wnt/ß-catenin and TGF-ß/Smad2/3 pathways and facilitated the osteosarcoma cell infiltration and migration. An increase or decrease in EFEMP1 expression directly promoted or inhibited the expression of STEAP1. In osteosarcoma cells overexpressing EFEMP1, STEAP1 knockdown significantly inhibited cell invasion, EMT process, and increased activity of Wnt/ß-catenin and TGF-ß/Smad2/3 signaling pathways. Although exogenous EFEMP1 could stimulate the Wnt/ß-catenin and TGF-ß/Smad2/3 pathways to promote the EMT, it had not effect on osteosarcoma cells with STEAP1 knockdown. Collectively, similar to EFEMP1, STEAP1 acted like an oncogene in the osteosarcoma progression. Conclusion: EFEMP1 enabled the Wnt/ß-catenin and TGF-ß/Smad2/3 axises initiation and EMT elicitation by targeting STEAP1, thereby facilitating the osteosarcoma cell infiltration and migration. These results are expected to contribute to the search for new targeted drugs able to effectively inhibit invasion and metastasis and improve prognosis in osteosarcoma.

15.
Prostate ; 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36373171

RESUMO

BACKGROUND: Evaluating the complex interplay of cell types in the tissue microenvironment is critical to understanding the origin and progression of diseases in the prostate and potential opportunities for intervention. Mouse models are an essential tool to investigate the molecular and cell-type-specific contributions of prostate disease at an organismal level. While there are well-documented differences in the extent, timing, and nature of disease development in various genetically engineered and exposure-based mouse models in different mouse strains and prostate lobes within each mouse strain, the underlying molecular phenotypic differences in cell types across mouse strains and prostate lobes are incompletely understood. METHODS: In this study, we used single-cell RNA-sequencing (scRNA-seq) methods to assess the single-cell transcriptomes of 6-month-old mouse prostates from two commonly used mouse strains, friend virus B/NIH jackson (FVB/NJ) (N = 2) and C57BL/6J (N = 3). For each mouse, the lobes of the prostate were dissected (anterior, dorsal, lateral, and ventral), and individual scRNA-seq libraries were generated. In situ and pathological analyses were used to explore the spatial and anatomical distributions of novel cell types and molecular markers defining these cell types. RESULTS: Data dimensionality reduction and clustering analysis of scRNA-seq data revealed that basal and luminal cells possessed strain-specific transcriptomic differences, with luminal cells also displaying marked lobe-specific differences. Gene set enrichment analysis comparing luminal cells by strain showed enrichment of proto-Oncogene targets in FVB/NJ mice. Additionally, three rare populations of epithelial cells clustered independently of strain and lobe: one population of luminal cells expressing Foxi1 and components of the vacuolar ATPase proton pump (Atp6v0d2 and Atp6v1g3), another population expressing Psca and other stem cell-associated genes (Ly6a/Sca-1, Tacstd2/Trop-2), and a neuroendocrine population expressing Chga, Chgb, and Syp. In contrast, stromal cell clusters, including fibroblasts, smooth muscle cells, endothelial cells, pericytes, and immune cell types, were conserved across strain and lobe, clustering largely by cell type and not by strain or lobe. One notable exception to this was the identification of two distinct fibroblast populations that we term subglandular fibroblasts and interstitial fibroblasts based on their strikingly distinct spatial distribution in the mouse prostate. CONCLUSIONS: Altogether, these data provide a practical reference of the transcriptional profiles of mouse prostate from two commonly used mouse strains and across all four prostate lobes.

16.
Front Immunol ; 13: 1021102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341363

RESUMO

Acute lung injury (ALI) is significantly associated with morbidity and mortality in patients with critical diseases. In recent years, studies have identified that mesenchymal stem/stromal cells (MSCs) ameliorate ALI and pulmonary fibrosis. However, the mechanism underlying this outcome in ALI has not yet been investigated. In this study, RNA sequencing technology was used to analyze the gene expression profile of lung tissue in lipopolysaccharide (LPS)-induced ALI rats following treatment with human umbilical cord MSC (HUCMSC). Differential expression analyses, gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction network identification, and hub gene analysis were also performed. HUCMSC treatment decreased inflammatory factor production and alveolar exudates, and attenuated lung damage in LPS-induced ALI rats. The RNA-Seq data indicated that HUCMSC treatment activated the IL-17, JAK-STAT, NF-κB, and TNF-α signaling pathways, increased oxygen transport, and decreased extracellular matrix organization. HUCMSC exert beneficial effects on ALI via these signaling pathways by reducing inflammation, inhibiting pulmonary fibrosis, and improving lung ventilation. Moreover, our study further revealed the hub genes (Tbx2, Nkx2-1, and Atf5) and signaling pathways involved in HUCMSC treatment, thus providing novel perspectives for future research into the molecular mechanisms underlying cell treatment of ALI. HUCMSC can regulate multiple genes and signaling pathways, which can prevent LPS-induced lung damage in an ALI rat model.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Fibrose Pulmonar , Humanos , Ratos , Animais , Lipopolissacarídeos/efeitos adversos , Fibrose Pulmonar/metabolismo , Cordão Umbilical , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/terapia , Células-Tronco Mesenquimais/metabolismo , Análise de Sequência de RNA , RNA/metabolismo
17.
Int J Lab Hematol ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36358022

RESUMO

INTRODUCTION: AML patients with KMT2A-MLLT3 and other 11q23 abnormalities belong to the intermediate and high-risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site-1 (EVI1) overexpression suits either the subtypes of KMT2A-MLLT3 or Non-KMT2A-MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. METHODS: We retrospectively analyzed the clinical characteristics of 166 KMT2A-r and KMT2A-PTD AML patients. RESULTS: For the Non-KMT2A-MLLT3 group, patients in the EVI1-high subgroup had shorter OS and DFS and higher CIR than those in the EVI1-low subgroup (p = .027, p = .018, and p = .020, respectively). Additionally, both KMT2A-MLLT3 and Non-KMT2A-MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo-HSCT) regardless of their EVI1 expression level (all p < .001). For transplanted patients with KMT2A-MLLT3 or Non-KMT2A-MLLT3 rearrangement, the EVI1-high subgroup had worse prognosis than the EVI1-low subgroup (all p < .05). The 2-year CIR of the KMT2A-MLLT3 and Non-KMT2A-MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2-year CIR of transplanted patients with KMT2A-MLLT3 and Non-KMT2A-MLLT3 was relatively low. CONCLUSIONS: Our study showed that for the Non-KMT2A-MLLT3 group, the EVI1-high group had shorter OS and DFS than the EVI1-low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1-high patients with non-KMT2A-MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration.

18.
Biomolecules ; 12(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36358972

RESUMO

The antioxidant activity of protein-derived peptides was one of the first to be revealed among the more than 50 known peptide bioactivities to date. The exploitation value associated with food-derived antioxidant peptides is mainly attributed to their natural properties and effectiveness as food preservatives and in disease prevention, management, and treatment. An increasing number of antioxidant active peptides have been identified from a variety of renewable sources, including terrestrial and aquatic organisms and their processing by-products. This has important implications for alleviating population pressure, avoiding environmental problems, and promoting a sustainable shift in consumption. To identify such opportunities, we conducted a systematic literature review of recent research advances in food-derived antioxidant peptides, with particular reference to their biological effects, mechanisms, digestive stability, and bioaccessibility. In this review, 515 potentially relevant papers were identified from a preliminary search of the academic databases PubMed, Google Scholar, and Scopus. After removing non-thematic articles, articles without full text, and other quality-related factors, 52 review articles and 122 full research papers remained for analysis and reference. The findings highlighted chemical and biological evidence for a wide range of edible species as a source of precursor proteins for antioxidant-active peptides. Food-derived antioxidant peptides reduce the production of reactive oxygen species, besides activating endogenous antioxidant defense systems in cellular and animal models. The intestinal absorption and metabolism of such peptides were elucidated by using cellular models. Protein hydrolysates (peptides) are promising ingredients with enhanced nutritional, functional, and organoleptic properties of foods, not only as a natural alternative to synthetic antioxidants.


Assuntos
Antioxidantes , Peptídeos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Disponibilidade Biológica , Peptídeos/química , Hidrolisados de Proteína , Manipulação de Alimentos , Aditivos Alimentares
19.
Artigo em Inglês | MEDLINE | ID: mdl-36441318

RESUMO

Rainfall runoff and combined sewer overflow (CSO) converge with organic waste, nutrients, and microbes from the ground and wastewater. These pollutants promote the spread and transformation of antibiotic resistance genes (ARGs). In this study, four rainfall runoff and one CSO outfall were chosen, and samples were collected to explore the occurrence and distribution of ARGs. The ARGs were extracted from suspended solids and analyzed using metagenomic sequencing. A total of 888 ARG subtypes, belonging to 17 ARG types, were detected in all samples. Eleven ARG types were shared by all the samples. Multidrug resistance genes had the highest relative abundance. Their total relative abundance reached 1.07 ratio (ARG copy number/16S rRNA gene copy number) and comprised 46.6% of all the ARGs. In all samples, the CSO outfall had the highest total relative abundance (8.25 × 10-1 ratio) of ARGs, with a ratio ranging ND (not detected)-3.78 × 10-1 ratio. Furthermore, the relationship between ARG types and environmental factors was determined using redundancy analysis. The results showed that chemical organic demand (COD) and bacterial abundance were positively correlated with most ARG types, including multidrug, bacitracin, aminoglycoside, ß-lactam, tetracycline, and sulfonamide. NH3-N, TN, and TP were positively correlated with rifamycin, fosmidomycin, and vancomycin resistance genes. The relationship among the ARG subtypes was investigated using network analyses. The multidrug resistance gene subtypes had the highest frequency of co-occurrence. This study provides insights into the occurrence and distribution of ARGs under non-point source pollution and may contribute to the control of ARGs.

20.
ESC Heart Fail ; 2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36436827

RESUMO

BACKGROUND: Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. METHODS: This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan-Meier methods. RESULTS: A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow-up of 32 months (IQR: 26-41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P < 0.001). Cox regression showed that 1-SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024-1.242)], cardiovascular mortality [1.112 (1.032-1.198)], all-cause mortality [1.142 (1.057-1.234)], and HF rehospitalization [1.122 (1.030-1.224)] after adjustment for potential confounders including NT-proBNP. Kaplan-Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all-cause mortality (all P values < 0.001). Furthermore, both Kaplan-Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT-proBNP were more likely to predict all-cause or cardiovascular mortality (both P < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. CONCLUSIONS: Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT-proBNP, suggesting that sAXL is a promising prognostic marker for further study.

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