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1.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166569, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243293

RESUMO

BACKGROUND: Hippocampus plays critical roles in drug addiction. Cocaine-induced modifications in dopamine receptor function and the downstream signaling are important regulation mechanisms in cocaine addiction. Rac regulates actin filament accumulation while Cdc42 stimulates the formation of filopodia and neurite outgrowth. Based on the region specific roles of small GTPases in brain, we focused on the hippocampal subregions to detect the regulation of Cdc42 signaling in long-term morphological and behavioral adaptations to cocaine. METHODS: Genetically modified mouse models of Cdc42, dopamine receptor D1 (D1R) and D2 (D2R) and expressed Cdc42 point mutants that are defective in binding to and activation of its downstream effector molecules PAK and N-WASP were generated, respectively, in CA1 or dentate gyrus (DG) subregion. RESULTS: Cocaine induced upregulation of Cdc42 signaling activity. Cdc42 knockout or mutants blocked cocaine-induced increase in spine plasticity in hippocampal CA1 pyramidal neurons, leading to a decreased conditional place preference (CPP)-associated memories and spatial learning and memory in water maze. Cdc42 knockout or mutants promoted cocaine-induced loss of neurogenesis in DG, leading to a decreased CPP-associated memories and spatial learning and memory in water maze. Furthermore, by using D1R knockout, D2R knockout, and D2R/Cdc42 double knockout mice, we found that D2R, but not D1R, regulated Cdc42 signaling in cocaine-induced neural plasticity and behavioral changes. CONCLUSIONS: Cdc42 acts downstream of D2R in the hippocampus and plays an important role in cocaine-induced neural plasticity through N-WASP and PAK-LIMK-Cofilin, and Cdc42 signaling pathway correlatively links specific brain regions (CA1, dentate gyrus) to cocaine-induced CPP behavior.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Camundongos , Animais , Transtornos Relacionados ao Uso de Cocaína/genética , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Hipocampo/metabolismo , Cocaína/farmacologia , Cocaína/metabolismo , Dopamina/metabolismo , Camundongos Knockout
2.
J Environ Sci (China) ; 125: 650-661, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375947

RESUMO

The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish (Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the mRNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase (COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae. Additionally, the AhR antagonist CH223191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity.


Assuntos
Cardiotoxicidade , Praguicidas , Poluentes Químicos da Água , Animais , Cardiotoxicidade/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Embrião não Mamífero , Larva , Praguicidas/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
3.
Medicine (Baltimore) ; 101(43): e31338, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316923

RESUMO

Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.


Assuntos
Hipofisite Autoimune , Doenças do Colágeno , Hipofisite , Hipopituitarismo , Lúpus Eritematoso Sistêmico , Doenças da Hipófise , Doenças Reumáticas , Humanos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Hipofisite/complicações , Doenças da Hipófise/complicações , Doenças da Hipófise/diagnóstico , Hipopituitarismo/etiologia , Hipófise/diagnóstico por imagem , Glucocorticoides/uso terapêutico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças do Colágeno/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Hipofisite Autoimune/complicações , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/tratamento farmacológico
4.
Front Cardiovasc Med ; 9: 966973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324750

RESUMO

Objective: Although chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are known to be accompanied by symptoms associated with sleep-disordered breathing (SDB) and nocturnal hypoxemia, the sex-specific differences of SDB and nocturnal hypoxemia in patients with CTEPH and CTEPD remain unknown. Methods: Between July 2020 and August 2022, data were retrieved from 57 males and 63 female patients with CTEPH and CTEPD who underwent sleep study at Shanghai Pulmonary Hospital. Nocturnal mean SpO2 (mean SpO2) < 90% was defined as nocturnal hypoxemia. Logistic and linear regression analysis was performed to assess the predictive value of sleep study indices to hemodynamic parameters. Receiver operating characteristic (ROC) curve was applied to analyze the specific parameters to predict the risk of CTEPH. Results: SDB was similarly present in males and females, and both sexes predominantly had obstructive sleep apnea (OSA); more women were diagnosed with nocturnal hypoxemia (32 vs. 7%, p = 0.002). SaO2 was negatively associated with mean pulmonary arterial pressure (mPAP) in men (p < 0.001), whereas the ratio of nocturnal SpO2 < 90% of the total monitoring time (T90%) was positively correlated with mPAP. Mean SpO2 was an independent predictor for pulmonary vascular resistance and cardiac output in women (p = 0.001, p < 0.001, p = 0.001, respectively). T90%, SaO2, and minimal SpO2 were combined to develop a new composite parameter: hypoxemia scoring index (HSI). ROC curve analysis indicated that HSI levels of 0.55 could discriminate CTEPH from CTEPD with a sensitivity of 92.3% and specificity of 87.5% in female patients (an area under the curve, 0.937; 95% CI: 0.879-0.995, p < 0.001). Conclusion: Sex-specific nocturnal hypoxemia was present in patients with CTEPH or CTEPD. In female patients, the HSI showed high capacity for predicting the risk of CTEPH. Clinical trials registration: Registry: chictr.org.cn; Identifier: ChiCTR-DDD-16009406.

5.
ACS Sens ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36384296

RESUMO

As a common toxic gas, nitrogen dioxide (NO2) seriously threatens the environment and human respiratory system even at part per billion (ppb) level. Covalent organic frameworks (COFs) have gained widespread attention in sensing applications because of the benefits of designability, environmental stability, and a large number of active sites. However, the competitive adsorption of water molecules and the target gas molecules at room temperature as well as the weak interaction between COFs and gas molecules hinder their practical applications. Here, we introduce ion-in-conjugation (IIC) into a covalent organic framework (COF) by preparing a condensate of squaraine (SA) with 1,3,5-tris(4-aminophenyl)benzene (TAPB) to form a mesoporous macrocyclic material (SA-TAPB). Layers of SA-TAPB, drop cast onto interdigitated Ag-Pd alloy electrodes, show a statistically significant conductivity response to NO2 at concentrations as low as 30 ppb and a theoretical detection limit of 10.9 ppb. The sensor displays a lower sensitivity to variations in humidity when operated at 80 °C compared to room temperature. The density functional theory (DFT) calculations indicated that the main adsorption site of NO2 is dual hydrogen bonds formed between two amide hydrogen atoms of SA-TAPB and the NO2 molecule. Gas adsorption experiments revealed that SA-TAPB has the largest adsorption capacity of NO2 versus other interference gases, which were responsible for the excellent selectivity toward NO2.

6.
Blood Adv ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350716

RESUMO

For participants receiving experimental gene therapy or gene editing clinical trials, the FDA requires contemporaneous controls to compare clinical outcomes. However, developing a contemporaneous cohort of rare diseases is costly and requires multiple person-hours. In a single referral center for sickle cell disease, we tested the hypothesis that we could create an automated contemporaneous cohort of children and adults with sickle cell anemia (SCA) to predict mortality. Data were obtained between 1/1/2004 and 4/30/2021. We identified 419 individuals with SCA with consistent medical care (i.e., followed continuously for >0.5 years with no visit gaps ≥3.0 years). The median age was 10.2 years (IQR 1.0 - 24.0 years), with a median follow-up of 7.4 years (IQR 3.6-13.5 years) and 47 deaths. A total of 98% (274 of 277) of the children remained alive at 18 years of age, and 34.3% (94 of 274) of those children were followed into adulthood. For adults, the median age of survival was 49.3 years of age. Treatment groups were mutually exclusive and in a hierarchical order: hematopoietic stem cell transplant (n=22)>regular blood transfusion for at least two years (n=56)>hydroxyurea for at least one year (n=243)>no disease-modifying therapy (n=98). Compared to those receiving no disease-modifying treatment, those treated with hydroxyurea therapy had significantly lower hazard of mortality (hazard ratio=0.38, p=0.016), but no statistical difference for those receiving regular blood transfusions compared to no disease-modifying therapy (hazard ratio=0.71, p=0.440). An automated contemporaneous SCA cohort can be generated to estimate mortality in children and adults with SCA.

7.
ISA Trans ; 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36344355

RESUMO

When analyzing the stability of time-varying delay systems in view of the Lyapunov-Krasovskii functional, a quadratic polynomial function with regard to time-varying delay is always generated. And it is particularly crucial to determine the negativeness of the matrix of such a quadratic form function for obtaining an analysis result expressed in linear matrix inequalities. This paper proposes a method of tangent intersection in the delay interval segmentation, producing the generalized quadratic convex conditions by further utilizing the cross point between every two tangent lines. It reduces the conservatism of the existing conditions remarkably without requiring unexplainable adjustable parameters and additional decision variables. Benefiting from the newly proposed quadratic convex conditions, the novel stability conditions are derived, the superiority of which is demonstrated through several widely used numerical instances and single area power system PI control example.

8.
Nanoscale ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36342434

RESUMO

The properties of nanoparticle (NP) carriers, such as size, shape and surface state, have been proven to dramatically affect their uptake by tumor cells, thereby influencing and determining the effect of nanomedicine on tumor theranostics. However, the effect of the stiffness of NPs on their cellular internalization remains unclear, especially for circumstances involving active or passive NP targeting. In this work, we constructed eutectic gallium indium liquid metal NPs with the same particle size, shape and surface charge properties but distinct stiffness via tailoring the surface oxidation and silica coating. It has been found that the softer NPs would be endocytosed much slower than their stiffer counterparts in the presence of specific ligand-receptor interaction. Interestingly, once the interaction is eliminated, softer NPs are internalized faster than the stiffer ones. Based on experimental observations and theoretical verification, we demonstrate that this phenomenon is mainly caused by varying degrees of deformation of soft NPs induced by ligand-receptor interactions. Such a finding of the stiffness effect of NPs implies great potential for fundamental biomedical applications, such as the rational design of nanomedicines.

9.
Am J Transl Res ; 14(10): 7217-7225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398203

RESUMO

OBJECTIVE: To investigate the effect of comprehensive nursing intervention in the management of pediatric patients with respiratory failure. METHODS: A total of 60 pediatric patients were selected as research subjects, and the clinical data were collected and retrospectively investigated. The patients were divided either into a control group (n=30) or an observation group (n=30) according to the nursing care methods. Pediatric patients from the observation group underwent comprehensive nursing intervention, while those in the control group received conventional nursing care intervention. The clinical effects, negative emotions, SF-36 scores, hospital stays, clinical symptom indicators, blood gas indices, lung function indicators and the nursing satisfaction rates were compared between the two groups. RESULTS: The clinical effect in the observation group was significantly better than that in the control group. Compared with those in the control group, significantly lower scores of the Self-Rating Anxiety Scale and the Self-Rating Depression Scale were observed in the observation group. The indicators associated with blood gas and lung function in the observation group were significantly improved in contrast to those in the control group. Moreover, the disappearance time of pulmonary rales, disappearance time of cyanochroia, alleviation time of dyspnea and hospital stays in the observation group were significantly shorter than those in the control group, while the SF-36 scores and the nursing satisfaction rate in the observation group were significantly higher than those in the control group (all P<0.05). CONCLUSION: Comprehensive nursing intervention significantly improved clinical treatment effects and patient satisfaction, alleviated the clinical symptoms, increased life quality and shortened hospital stay. So, it is worth being promoted in clinical practice.

10.
Small ; : e2205341, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399645

RESUMO

Chloramphenicol (CAP) has long been used extensively in agriculture and is severely toxic to the biological environment. Microwave catalysis appears a promising method for soil remediation due to its fast and effective heat transfer, but it is challenging to prepare catalysts with good electromagnetic wave absorption and robust catalytic activity. In this study, atomically dispersed Fe on three-dimensional N-doped carbon supports (3D Fe-NC) is firstly used for microwave remediation of soil. Thanks to the synergistic effect of microwave "hot spots" and reactive oxygen species (•OH, •O2 - ), 3D Fe-NC can completely remove 99.9% of CAP in 5 min. The removal rate constant is nearly twice that of commercial activated carbon. Significantly, the germination rate of lettuce seeds in microwave-repaired soil contaminated by CAP reaches 70%. This work demonstrates the application of Fe single-atom catalyst in microwave remediation of contaminated soil, providing a novel insight for agricultural soil remediation.

11.
Lupus Sci Med ; 9(1)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36351697

RESUMO

OBJECTIVE: Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC). METHODS: Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared. RESULTS: Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027). CONCLUSIONS: SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.


Assuntos
Imunossupressores , Lúpus Eritematoso Sistêmico , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Glucocorticoides
12.
Front Public Health ; 10: 1021104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388333

RESUMO

Background and aims: Along with an aging population, exploring the impact of oral health on holistic health and determining exact outcomes in elderly individuals are important in both scientific research and clinical practice. Significant increase in the number of systematic reviews shows that oral health can directly or indirectly affect the overall health of elderly people physically, mentally and socially. To systematically collate, appraise, and synthesize the current evidence, we carried out an umbrella review of the impacts of oral health on holistic health in elderly individuals. Methods: A systematic reviews and meta-analyses search was performed in the major databases PubMed, MEDLINE, Web of Science and the Cochrane Library from inception to February 1, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The JBI (Joanna Briggs Institute) Critical Appraisal Checklist for Systematic Reviews and Research Syntheses was referred to assess methodological quality, and the GRADE (Grading of Recommendations, assessment, Development, and Evaluation working group classification) was used to assess the quality of evidence for each outcome included in the umbrella review. Results: Out of 1,067 records, a total of 35 systematic reviews were included. Respiratory diseases, malnutrition, age-related oral changes, frailty, cognitive impairment, depression and poor quality of life were identified as seven key outcomes that affect the physical, mental and social health of elderly individuals. Meanwhile, three intervention measures of oral health were summarized as (i) more rigorous and universal scales, (ii) dental cleaning and denture installation, and (iii) improving self-awareness regarding oral care. Conclusions: Evidence showed that oral health can significantly affect holistic health, and the diverse oral diseases directly lead to multiple health outcomes in elderly individuals. Clear high-quality evidence revealed that oral health is strongly associated with seven health outcomes covering physical, mental, and social levels, which directly corresponds to holistic health, and impacts the quality of life of elderly individuals. Such the results remind the importance of oral care in public health, and further studies need to be conducted to verity more specific association between oral health and other chronic diseases. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42022315315.


Assuntos
Saúde Holística , Saúde Bucal , Idoso , Humanos , Metanálise como Assunto , Saúde Pública , Qualidade de Vida , Relatório de Pesquisa , Revisões Sistemáticas como Assunto
13.
J Pharm Biomed Anal ; 223: 115130, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36335849

RESUMO

Zhi-Zi-Chi decoction (ZZCD), comprising of Gardenia jasminoides Ellis (GJE) and Semen sojae preparatum (SSP), is a classical Chinese medicine formula. A novel analysis strategy was set up to obtain an evaluation of ZZCD on attenuation and synergy of compatibility. High-resolution ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) was used for qualitative analysis. Variant ingredients were analyzed to compare the componential differences between ZZCD formula and single herbs. Based on our previous fingerprint studies that combined with chemometric methods, 13 remarkable chemical markers were selected and evaluated for quantitative determination by high performance liquid chromatography (HPLC) in three different ratios of ZZCD. 62 compounds in ZZCD, 55 compounds in GJE and 16 compounds in SSP were characterized. The compatibility of GJE and SSP may lead to the undetection of hepatotoxic components such as genipin and the emergence of protective components such as jasminoside A, which was not found in single herbs. Meanwhile, 13 selected chemical markers were successfully determined in three ratios of ZZCD. The compatibility may lead to the decrease of toxic ingredients and the increase of beneficial ingredients. By comparing the dissolution of chemical markers, iridoids in GJE and flavonoids in SSP had the best dissolution when the compatibility ratio was 1:1. This strategy would be a valuable reference for further study on the compatibility of traditional Chinese medicine formula.

14.
Neural Netw ; 157: 147-159, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36334536

RESUMO

Compared with relatively easy feature creation or generation in data analysis, manual data labeling needs a lot of time and effort in most cases. Even if automated data labeling​ seems to make it better in some cases, the labeling results still need to be checked and verified by manual. The High Dimension and Low Sample Size (HDLSS) data are therefore very common in data mining and machine learning. For classification problems with the HDLSS data, due to data piling and approximate equidistance between any two input points in high-dimension space, some traditional classifiers often give poor predictive performance. In this paper, we propose a Maximum Decentral Projection Margin Classifier (MDPMC) in the framework of a Support Vector Classifier (SVC). In the MDPMC model, the constraints of maximizing the projection distance between decentralized input points and their supporting hyperplane are integrated into the SVC model in addition to maximizing the margin of two supporting hyperplanes. On ten real HDLSS datasets, the experiment results show that the proposed MDPMC approach can deal well with data piling and approximate equidistance problems. Compared with SVC with Linear Kernel (SVC-LK) and Radial Basis Function Kernel (SVC-RBFK), Distance Weighted Discrimination (DWD), weighted DWD (wDWD), Distance-Weighted Support Vector Machine (DWSVM), Population-Guided Large Margin Classifier (PGLMC), and Data Maximum Dispersion Classifier (DMDC), MDPMC obtains better predictive accuracy and lower classification errors than the other seven classifiers on the HDLSS data.

15.
Int J Bioprint ; 8(4): 619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404784

RESUMO

Vessel-on-a-chips, which can be used to study microscale fluid dynamics, tissue-level biological molecules delivery and intercellular communication under favorable three-dimensional (3D) extracellular matrix microenvironment, are increasingly gaining traction. However, not many of them can allow for long-term perfusion and easy observation of angiogenesis process. Since angiogenesis is necessary for the expansion of tumor, antiangiogenic drugs play a significant role in cancer treatment. In this study, we established an innovative and reliable antiangiogenic drug screening chip that was highly modularly integrated for long-term perfusion (up to 10 days depending on the hydrogel formula) and real-time monitoring. To maintain an unobstructed flow of cell-laden tubes for subsequent perfusion culture on the premise of excellent bioactivities, a polycaprolactone stent inspired by coronary artery stents was introduced to hold up the tubular lumen from the inside, while the perfusion chip was also elaborately designed to allow for convenient observation. After 3 days of perfusion screening, distinct differences in human umbilical vein endothelial cell sprouting were observed for a gradient of concentrations of bevacizumab, which pointed to the effectiveness and reliability of the drug screening perfusion system. Overall, a perfusion system for antiangiogenic drug screening was developed, which can not only conduct drug evaluation, but also be potentially useful in other vessel-mimicking scenarios in the area of tissue engineering, drug screening, pharmacokinetics, and regenerative medicine.

16.
J Environ Manage ; 326(Pt A): 116754, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375439

RESUMO

The overuse of phosphate fertilizer causes waste of resources and is detrimental to the sustainability of agriculture and aquatic systems. Effective management of phosphorus (P) in agricultural systems is important. Lack of understanding on the temporal and spatial variations of P utilization in farmland systems would constrain the development of more precise and effective policies as well as management practices. Here, we used two indicators, P use efficiency (PUE) and P surplus (Psur), to evaluate changes in P utilization in crop production on both national and regional scale in China during 2005-2018. Great heterogeneity of PUE and Psur were found across different regions, with Northeast of China showing the highest PUE (0.67) and lowest Psur (11.0 kg/ha). For temporal trends, our study showed that China crossed the turning point of the environmental Kuznets curve in 2007, which indicates that China has reached a new development stage of P use that is resource-saving and environmentally friendly. Along with the processes of industrialization and urbanization in China, the development of agricultural mechanization has further resulted in an increase of PUE and decrease of Psur. Although great efforts were made, China still has a relative low PUE and high Psur compared to developed countries. Our results suggest a regionalized perspective for developing policies for the sustainable use of P resources.

17.
JAMA Netw Open ; 5(11): e2241451, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36355371

RESUMO

Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches. Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People's Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020. Interventions: Patients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up. Main Outcomes and Measures: The primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24. Results: Sixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, -18.33 points; 95% CI, -28.46 to -8.21 points; P = .001; pain: difference, -10.33 points; 95% CI, -19.38 to -1.29 points; P = .03; fatigue: difference, -11.67 points; 95% CI, -20.65 to -2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells. Conclusions and Relevance: In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells. Trial Registration: ClinicalTrials.gov Identifier: NCT02464319.


Assuntos
Síndrome de Sjogren , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/complicações , Interleucina-2/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento , Fadiga/tratamento farmacológico , Dor/complicações
18.
Medicine (Baltimore) ; 101(46): e31911, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401434

RESUMO

Adjuvant endocrine therapy (AET) is known to reduce the risk of hormone receptor-positive (HR+) breast cancer (BC) recurrence and mortality rates, but its impact on cardiovascular disease (CVD) events is unclear. The primary objective of this study was to analyze the association of HR status with CVD mortality in patients with stage I to III BC. A retrospective study of patients with stage I to III BC was conducted using the 2004 to 2016 Surveillance, Epidemiology, and End Results (SEER) database, and patients were grouped according to their HR status. Propensity score matching (PSM) was used to adjust for heterogeneity between the groups. The cumulative incidence rate of CVD mortality was evaluated via a cumulative incidence curve. Univariate and multivariate Fine and Gray's competing risk regression models were used to identify risk factors associated with CVD mortality. In total, 399,209 patients with BC were included in this study, and 329,958 patients (82.65%) were HR-positive. The cumulative incidence of CVD death was 8.28% in stage I to III BC patients. In the constituent ratio analysis, primary BC was the leading cause of death (45.29%, N = 31,465), followed by heart disease (16.07%, N = 11,166). Compared to the second year following BC diagnosis, the risk of CVD-specific death gradually increased. After PSM, 65,952 pairs of patients were matched, which led to the equilibrium of all variables between the HR-negative cohort and HR+ cohort. Multivariate analysis indicated that HR status was not significantly associated with the risk of CVD mortality, with a hazard ratio of 1.01 (P = .895). This study highlights the importance of understanding the associations between risk factors and CVD for BC patients. HR status was not associated with the risk of CVD mortality in this study.


Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Humanos , Feminino , Estudos Retrospectivos , Recidiva Local de Neoplasia/complicações , Hormônios
19.
Medicine (Baltimore) ; 101(46): e31668, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401440

RESUMO

Erectile dysfunction (ED) is a male disease, which is easy to cause disharmony in sexual life. However, at present, there are few drugs with small side effects in clinic. Jin Gui Shen Qi Pill (JGSQP) is a traditional Chinese medicine compound with obvious clinical effect in treating ED. Therefore, it is imperative to explore clinical drugs based on inhibiting the pathological characteristics of ED. First, the active ingredients and action targets in JGSQP were screened by applying Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SWISS Target Prediction. Further, a systematic pharmacological analysis platform for traditional Chinese medicine, and the ED targets were screened by applying Gene Cards and Online Mendelian Inheritance in Man databases to construct drug active ingredient-target-disease mapping, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis. Finally, Molecular docking and molecular dynamics simulations were used to screen the active ingredients of JGSQP acting on PDE-5, and analyze the ligand-receptor interaction relationship and binding free energy. The results showed that there were 212 potential targets of JGSQP for ED disease, and GO analysis revealed that the main pathways were positive regulation of DNA-binding transcription factor activity, regulation of vascular diameter, and negative regulation of vascular diameter, etc. KEGG analysis revealed that the main pathways were HIF-1 signaling pathway, prolactin signaling pathway, fluid shear stress, and atherosclerosis, etc. PPI network analysis revealed that the core targets TGFB1 and EGFR have important roles. Molecular docking and molecular dynamics simulations showed that the main components acting on PDE-5 were MOL000546, MOL011169, MOL000279, MOL000273 and Sildenafil. MOL000546 was able to bind stably to PDE-5. The multi-component, multi-target, and multi-pathway action characteristics of JGSQP were confirmed by network pharmacology, which predicted the possible mechanism of action of JGSQP in the treatment of ED and provided a theoretical reference for further experimental validation.


Assuntos
Medicamentos de Ervas Chinesas , Disfunção Erétil , Humanos , Masculino , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Disfunção Erétil/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa
20.
Oxid Med Cell Longev ; 2022: 7435754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406768

RESUMO

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, for which elevated intraocular pressure (IOP) is a major risk factor. IOP is mainly regulated by dynamic balance of aqueous humor (AH) production and outflow via the conventional trabecular meshwork/Schlemm's canal (TM/SC) pathway. Dysfunctions of TM cells due to endoplasmic reticulum (ER) stress have been demonstrated to increase the resistance of AH outflow, resulting in IOP elevation. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic component in green tea, has been shown to alleviate ER stress in several diseases while its potential roles in alleviating ER stress in TM cells have not been determined. In this study, we investigate the mitigation of tunicamycin-induced ER stress in TM cells by EGCG. MTT assay was used to measure the cell viability of human TM (HTM) cells and primary porcine TM (PTM) cells. ER stress levels in both HTM cells and primary PTM cells were detected by quantitative real-time PCR. The primary PTM cells isolated from porcine TM tissues were characterized by immunostaining. We found that 40 µM and 80 µM EGCG pretreatment substantially promoted HTM cell survival under 3 µM tunicamycin-induced ER stress. Pretreatment of 40 µM EGCG markedly reduced the expression of ER stress markers ATF4, HSPA5, and DDIT3, evoked by 3 µM tunicamycin in HTM cells. Furthermore, 40 µM EGCG pretreatment significantly decreased the expressions of ATF4, HSPA5, and DDIT3 at the mRNA level induced by 3 µM tunicamycin and improved cell viability in primary PTM cells. Our results show that EGCG is capable of protecting TM cells from ER stress. EGCG provides a promising therapeutic option for POAG treatment.


Assuntos
Glaucoma de Ângulo Aberto , Malha Trabecular , Humanos , Suínos , Animais , Malha Trabecular/metabolismo , Estresse do Retículo Endoplasmático , Tunicamicina/farmacologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/metabolismo
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