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1.
Psychother Res ; : 1-11, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38590020

RESUMO

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

2.
J Environ Manage ; 357: 120829, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579474

RESUMO

The emergence and increasing prevalence of antibiotic resistance pose a global public risk for human health, and nonantimicrobial pharmaceuticals play an important role in this process. Herein, five nonantimicrobial pharmaceuticals, including acetaminophen (ACT), clofibric acid (CA), carbamazepine (CBZ), caffeine (CF) and nicotine (NCT), tetracycline-resistant strains, five ARGs (sul1, sul2, tetG, tetM and tetW) and one integrase gene (intI1), were detected in 101 wastewater samples during two typical sewage treatment processes including anaerobic-oxic (A/O) and biological aerated filter (BAF) in Harbin, China. The impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on both the resistance genotypes and resistance phenotypes were explored. The results showed that a significant impact of nonantibiotic pharmaceuticals at environmentally relevant concentrations on tetracycline resistance genes encoding ribosomal protection proteins (RPPs) was found, while no changes in antibiotic phenotypes, such as minimal inhibitory concentrations (MICs), were observed. Machine learning was applied to further sort out the contribution of nonantibiotic pharmaceuticals at environmentally relevant concentrations to different ARG subtypes. The highest contribution and correlation were found at concentrations of 1400-1800 ng/L for NCT, 900-1500 ng/L for ACT and 7000-10,000 ng/L for CF for tetracycline resistance genes encoding RPPs, while no significant correlation was found between the target compounds and ARGs when their concentrations were lower than 500 ng/L for NCT, 100 ng/L for ACT and 1000 ng/L for CF, which were higher than the concentrations detected in effluent samples. Therefore, the removal of nonantibiotic pharmaceuticals in WWTPs can reduce their selection pressure for resistance genes in wastewater.


Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Humanos , Eliminação de Resíduos Líquidos/métodos , Genes Bacterianos , Bactérias/genética , Antibacterianos/farmacologia , Tetraciclina/farmacologia , Genótipo , Resistência Microbiana a Medicamentos/genética , Aprendizado de Máquina , Preparações Farmacêuticas
3.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1154-1163, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621962

RESUMO

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , Medicina Tradicional Chinesa , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipófise-Suprarrenal/patologia , Sistema Nervoso Central , Isquemia Encefálica/terapia , Sistema Imunitário , Inflamação
4.
J Environ Sci (China) ; 143: 235-246, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38644021

RESUMO

Comprehensive Air Quality Model with extensions (CAMx)-Decoupled Direct Method (DDM) simulations of first-order ozone (O3) sensitivity to nitrogen oxides (NOx) and volatile organic compounds (VOCs) emissions were performed and combined with modelled [Formula: see text] ratios to obtain a range of thresholds for determining O3-sensitivity regimes for different areas of China. Utilising the new threshold ranges for photochemical indicators, the method for determining O3 formation in the Ozone Source Apportionment Technology (OSAT) module within CAMx was improved by a dynamically varied threshold of [Formula: see text] ratio. The O3 concentration contributions in the newly added transition regime were apportioned to NOx and VOCs emissions in proportion to the relationship between the [Formula: see text] ratio and first-order O3 sensitivity. The source contributions of O3 concentrations from different emission sectors from June to September 2019 were compared using the original and improved CAMx-OSAT. The results showed that the O3 concentration contributions changed significantly in the NOx-limited regime, with a maximum decrease of 21.89%, while the contributions increased by up to 7.57% in the VOC-limited regime, and were within 15 µg/m3 in the transition regime. The modified OSAT module enabled a more sophisticated attribution of O3 to precursor emissions and may have far-reaching implications for informing O3 pollution control policy.

5.
Adv Sci (Weinh) ; : e2309873, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482743

RESUMO

Metasurfaces have shown unparalleled controllability of electromagnetic (EM) waves. However, most of the metasurfaces need external spatial feeding sources, which renders practical implementation quite challenging. Here, a low-profile programmable metasurface with 0.05λ0 thickness driven by guided waves is proposed to achieve dynamic control of both amplitude and phase simultaneously. The metasurface is fed by a guided wave traveling in a substrate-integrated waveguide, avoiding external spatial sources and complex power divider networks. By manipulating the state of the p-i-n diodes embedded in each meta-atom, the proposed metasurface enables 1-bit amplitude switching between radiating and nonradiating states, as well as a 1-bit phase switching between 0° and 180°. As a proof of concept, two advanced functionalities, namely, low sidelobe-level beam scanning and Airy beam generation, are experimentally demonstrated with a single platform operating in the far- and near-field respectively. Such complex-amplitude, programmable, and low-profile metasurfaces can overcome integration limitations of traditional metasurfaces, and open up new avenues for more accurate and advanced EM wave control within an unprecedented degree of freedom.

6.
Sci Total Environ ; 926: 171629, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513862

RESUMO

Changes in water yield are influenced by many intersecting biophysical elements, including climate, on-land best management practices, and landcover. Large-scale reductions in water yield may present a significant threat to water supplies globally. Many of these intersecting factors are intercorrelated and confounded, making it challenging to separate the factors' individual contributions to shaping local streamflow dynamics. Comprehensive hydrological models constructed based on a well-established understanding of biophysical processes are often employed to address these matters. However, these models rarely incorporate all relevant factors influencing local hydrological processes, due to the reliance of these models on the latest, albeit limited, state-of-the-art research. For instance, complexities inherent in watershed hydrology, which involve multilayered interactions among potentially many biophysical factors, leave the direct analysis of subtle impacts on water yields measured in-situ largely intractable. Therefore, we propose an innovative approach to assess impacts of elevated atmospheric CO2 concentrations and flow diversion terraces (FDTs) on stream discharge rates at the watershed scale. Initially, we use a comprehensive hydrological model to account for the impacts of major climatic and landuse/landcover factors on changes in field-acquired measurements of water yield. Next, we employ conventional and advanced statistical methods to decompose the residuals of model predictions to facilitate the identification of subtle influences promoted by increases in atmospheric CO2 concentrations and the application of FDTs in an agriculture-dominated watershed. Through this innovative approach, we find that FDTs contributed to a watershed-wide, net water-yield reduction of 188.0 mm (or 28.9 %) from 1992 to 2014. Ongoing increases in ambient CO2 concentrations, which are responsible for an overall reduction in a watershed-level assessment of stomatal conductance, have led to a minor increase in stream discharge rates during the same 23-year period, i.e., 0.45 mm of water yield per year, or 1.6 % overall. Streamflow reductions explicitly caused by regional warming in the area alone, on account of increased evapotranspiration, may be overestimated due to the opposing, synergistic effects on water yield associated with CO2-enrichment of the lower atmosphere and the annual application of FDTs.

7.
Front Immunol ; 15: 1339971, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426096

RESUMO

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.


Assuntos
Anemia Aplástica , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Humanos , Anemia Aplástica/terapia , Medula Óssea , Síndromes Mielodisplásicas/genética , Leucemia Mieloide Aguda/genética
8.
Nat Commun ; 15(1): 1974, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438350

RESUMO

Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

9.
Diabetes Metab Syndr Obes ; 17: 997-1011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435631

RESUMO

Background: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis. Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified. Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein-Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD. Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.

10.
Opt Express ; 32(4): 6277-6290, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439335

RESUMO

In this study, a novel method that can detect carbon dioxide (CO2) concentration and realize temperature immunity based on only one fiber Bragg grating (FBG) is proposed. The outstanding contribution lies in solving the temperature crosstalk issue of FBG and ensuring the accuracy of detection results under the condition of anti-temperature interference. To achieve immunity to temperature interference without changing the initial structure of FBG, the optical fiber cladding of FBG and adjacent optical fiber cladding at both ends of FBG are modified by a polymer coating. Moreover, a universal immune temperature demodulation algorithm is derived. The experimental results demonstrate that the temperature response sensitivity of the improved FBG is controlled within the range of 0.00407 nm/°C. Compared with the initial FBG (the temperature sensitivity of the initial FBG is 0.04 nm/°C), it decreases by nearly 10 times. Besides, the gas response sensitivity of FBG reaches 1.6 pm/ppm and has overwhelmingly ideal linearity. The detection error results manifest that the gas concentration error in 20 groups of data does not exceed 3.16 ppm. The final reproducibility research shows that the difference in detection sensitivity between the two sensors is 0.08 pm/ppm, and the relative error of linearity is 1.07%. In a word, the proposed method can accurately detect the concentration of CO2 gas and is efficiently immune to temperature interference. The sensor we proposed has the advantages of a simple production process, low cost, and satisfactory reproducibility. It also has the prospect of mass production.

11.
Biopharm Drug Dispos ; 45(2): 83-92, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492211

RESUMO

AST-001 is a chemically synthesized inactive nitrogen mustard prodrug that is selectively cleaved to a cytotoxic aziridine (AST-2660) via aldo-keto reductase family 1 member C3 (AKR1C3). The purpose of this study was to investigate the pharmacokinetics and tissue distribution of the prodrug, AST-001, and its active metabolite, AST-2660, in mice, rats, and monkeys. After single and once daily intravenous bolus doses of 1.5, 4.5, and 13.5 mg/kg AST-001 to Sprague-Dawley rats and once daily 1 h intravenous infusions of 0.5, 1.5, and 4.5 mg/kg AST-001 to cynomolgus monkeys, AST-001 exhibited dose-dependent pharmacokinetics and reached peak plasma levels at the end of the infusion. No significant accumulation and gender differences were observed after 7 days of repeated dosing. In rats, the half-life of AST-001 was dose independent and ranged from 4.89 to 5.75 h. In cynomolgus monkeys, the half-life of AST-001 was from 1.66 to 5.56 h and increased with dose. In tissue distribution studies conducted in Sprague-Dawley rats and in liver cancer PDX models in female athymic nude mice implanted with LI6643 or LI6280 HepG2-GFP tumor fragments, AST-001 was extensively distributed to selected tissues. Following a single intravenous dose, AST-001 was not excreted primarily as the prodrug, AST-001 or the metabolite AST-2660 in the urine, feces, and bile. A comprehensive analysis of the preclinical data and inter-species allometric scaling were used to estimate the pharmacokinetic parameters of AST-001 in humans and led to the recommendation of a starting dose of 5 mg/m2 in the first-in-human dose escalation study.


Assuntos
Pró-Fármacos , Ratos , Camundongos , Humanos , Feminino , Animais , Ratos Sprague-Dawley , Macaca fascicularis , Membro C3 da Família 1 de alfa-Ceto Redutase , Camundongos Nus
12.
Fitoterapia ; 175: 105924, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38537886

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

13.
Heliyon ; 10(3): e25066, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38314292

RESUMO

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel.

14.
Nat Prod Res ; : 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303493

RESUMO

Two new guaiane sesquiterpenoids were isolated from the dried aerial parts of Dracocephalum tanguticum Maxim., named as dracotangusions A (1) and B (2), together with four known sesquiterpenoids, which were identified as Curcumenone (3), (4Z,7Z,9Z)-11-Hydroxy-4,7,9-germacratriene-1,6-dione (4), Kobusone (5), and (1S,10S), (4S, 5S)-(+)-germacrone-1(10)-4-diepoxide (6). The structures of isolates were determined by UV, IR, HR-ESI-MS, and NMR analysis. What is noteworthy is that four known sesquiterpenoids were isolated for the first time from the genus of Dracocephalum L. All compounds inhibited the extremely significant difference (p < 0.01) in anti-inflammatory activity, suggesting that these compounds may be promising candidates as an anti-inflammatory agent.

15.
Rev Sci Instrum ; 95(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376384

RESUMO

The incidence of infectious diseases has risen in recent years, leading to a significant surge in the demand for medical molecular detection. High-throughput molecular detection platforms play a crucial role in facilitating rapid and efficient molecular detection. Among the various techniques employed in high-throughput molecular detection, microliquid transfer stands out as one of the most frequently utilized methods. However, ensuring the accuracy of liquid transfer poses a challenge due to variations in the physical and chemical properties of different samples and reagents. In this study, a pipetting complementation model was developed specifically for the serum, paraffin oil, and throat swabs. The aim was to enhance the transfer accuracy of diverse liquids in the context of high-throughput molecular detection, ultimately ensuring detection reliability and stability. The experimental findings revealed notable improvements in pipetting accuracy after compensating for the three liquids. In particular, the pipetting error rates decreased by 52.5, 96, and 71.4% for serum, paraffin oil, and throat swabs, respectively. These results underscore the model's effectiveness in providing reliable support for the precise transfer of liquids on the high-throughput molecular detection platform.


Assuntos
Óleos , Parafina , Reprodutibilidade dos Testes
16.
J Agric Food Chem ; 72(8): 4155-4169, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38366990

RESUMO

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.


Assuntos
Imunoglobulina G , Doenças Vasculares , Humanos , Feminino , Gravidez , Animais , Bovinos , Farmacologia em Rede , Espectrometria de Massas em Tandem , Células CACO-2 , Colostro/metabolismo , Peróxido de Hidrogênio , Peptídeos/química , Peptidil Dipeptidase A/química , Hidrolisados de Proteína/química , Simulação de Acoplamento Molecular
17.
CNS Neurosci Ther ; 30(2): e14577, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38421107

RESUMO

BACKGROUND: Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient and excessive GCs impair these functions. Although this phenomenon could be explained by the U-shape of GC effects, the underlying mechanisms are still not clear. Therefore, understanding the underlying mechanisms of GCs may provide insight into the treatments for cognitive and mood-related disorders. METHODS: Consecutive administration of corticosterone (CORT, 10 mg/kg, i.g.) proceeded for 28 days to mimic excessive GCs condition. Adrenalectomy (ADX) surgery was performed to ablate endogenous GCs in mice. Microinjection of 1 µL of Ad-mTERT-GFP virus into mouse hippocampus dentate gyrus (DG) and behavioral alterations in mice were observed 4 weeks later. RESULTS: Different concentrations of GCs were shown to affect the cell growth and development of neural stem cells (NSCs) in a U-shaped manner. The physiological level of GCs (0.01 µM) promoted NSC proliferation in vitro, while the stress level of GCs (10 µM) inhibited it. The glucocorticoid synthesis blocker metyrapone (100 mg/kg, i.p.) and ADX surgery both decreased the quantity and morphological development of doublecortin (DCX)-positive immature cells in the DG. The physiological level of GCs activated mineralocorticoid receptor and then promoted the production of telomerase reverse transcriptase (TERT); in contrast, the stress level of GCs activated glucocorticoid receptor and then reduced the expression of TERT. Overexpression of TERT by AD-mTERT-GFP reversed both chronic stresses- and ADX-induced deficiency of TERT and the proliferation and development of NSCs, chronic stresses-associated depressive symptoms, and ADX-associated learning and memory impairment. CONCLUSION: The bidirectional regulation of TERT by different GCs concentrations is a key mechanism mediating the U-shape of GC effects in modulation of hippocampal NSCs and associated brain function. Replenishment of TERT could be a common treatment strategy for GC dysfunction-associated diseases.


Assuntos
Glucocorticoides , Células-Tronco Neurais , Camundongos , Animais , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Hipocampo/metabolismo , Corticosterona/farmacologia , Células-Tronco Neurais/metabolismo , Transtornos da Memória/metabolismo
18.
Gastroenterology ; 166(4): 605-619, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176660

RESUMO

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Criança , Adolescente , Humanos , Incidência , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Infecções por Helicobacter/tratamento farmacológico , Prevalência
19.
Materials (Basel) ; 17(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38255493

RESUMO

With the advancement of industrial economies, incidents involving spills of petroleum products have become increasingly frequent. The resulting pollutants pose significant threats to air, water, soil, plant and animal survival, as well as human health. In this study, microcrystalline cellulose served as the matrix and benzoyl peroxide (BPO) as the initiator, while butyl acrylate (BA) and N,N'-methylene bisacrylamide (MBA) were employed as graft monomers. Through free radical graft polymerization, cellulose-graft-poly(butyl acrylate-N,N'-methylene bisacrylamide) [Cell-g-P(BA-MBA)], possessing oil-adsorbing properties, was synthesized. The chemical structure, elemental composition, surface morphology and wetting properties of the graft polymerization products have been characterized, using infrared spectroscopy, elemental analysis, scanning electron microscopy and contact angle testing. The adsorption properties of Cell-g-P(BA-MBA) for various organic solvents and oils were then assessed. The experimental results demonstrated that Cell-g-P(BA-MBA) exhibited a maximum adsorption capacity of 37.55 g/g for trichloromethane. Adsorption kinetics experiments indicated a spontaneous and exothermic process involving physical adsorption, conforming to the Freundlich isotherm model. Furthermore, adsorption kinetics experiments revealed that Cell-g-P(BA-MBA) displayed favorable reuse and regeneration performance, maintaining its adsorption capacity essentially unchanged over fifteen adsorption-desorption cycles.

20.
BMC Pediatr ; 24(1): 2, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172699

RESUMO

This study aimed at determining the intra- and inter-rater reliability in ultrasound body composition measurements and investigating the differences between malnourished and non-malnourished infants. Sonographic images for measurements of fat and muscle thickness were compared between 9 malnourished and 9 non-malnourished hospitalized infants. The mean of fat and muscle thickness sums were 12.44 ± 7.58 mm and 28.98 ± 7.18 mm, respectively. The intra- and inter-rater intraclass correlation coefficient were above 0.9 for both measurements, indicating high intra- and inter-rater reliability. Compared to non-malnourished infants, malnourished infants have 45% of fat thickness sum and 71% of muscle thickness sum. Ultrasound measurements of body composition in infants were different between hospitalized malnourished and non-malnourished infants. This approach has the potential to be utilized more broadly, from assessing the nutritional status of critically ill infants in intensive care units to screening for malnutrition in high-risk infant populations.


Assuntos
Desnutrição , Lactente , Humanos , Reprodutibilidade dos Testes , Estudos de Casos e Controles , Desnutrição/diagnóstico por imagem , Estado Nutricional , Composição Corporal , Ultrassonografia/métodos
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