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1.
J Hazard Mater ; 460: 132318, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37672995

RESUMO

Biodegradable microplastics (BMPs) and cadmium (Cd) are posing threats to agro-systems especially to plants and current studies mostly used virgin BMPs to explore their ecological effects. However, effects of naturally aged BMPs and their combined effects with Cd on pakchoi are yet to be unraveled. Therefore, this study incubated naturally aged polylactic acid (PLA) MPs through soil aging process and investigated the single and combined effects of Cd and PLA MPs (virgin and aged) on pakchoi (Brassica rapa subsp. chinensis) morphology, antioxidant systems and soil microbial activities. Our results found that after being deposited in soil for six months, aged PLA (PLAa) MPs formed with a fractured surface, demonstrating more detrimental effects on pakchoi than virgin ones. PLA/PLAa MPs and Cd stunted pakchoi growth, caused oxidative stress and altered the biophysical environment in soil, separately. Moreover, co-existence of PLA/PLAa MPs and Cd caused greater damages to pakchoi than applied alone. The co-presence of PLAa MPs and Cd inhibited pakchoi biomass accumulation rate by 92.2 % compared with the no-addition group. The results unraveled here emphasized BMPs, especially aged BMPs, could trigger negative effects on agro-systems with heavy metals. These findings will give reference to future holistic assessments of BMPs' ecological effects.


Assuntos
Brassica rapa , Cádmio , Cádmio/toxicidade , Microplásticos , Plásticos , Poliésteres , Solo
2.
Brain Res ; 1820: 148578, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37709161

RESUMO

The α-amino-3-hydroxy-5-methylisoxazole-4-isoxazolepropionic acid receptor (AMPAR) has been recognized to play a vital role in the development of neuropathic pain. Recent studies have indicated that protein kinase C (PKC) and protein interacting with C-kinase 1 (PICK1) are involved in the phosphorylation of AMPARs. However, whether PKC and PICK1 were involved in the AMPAR phosphorylation in the trigeminal ganglion (TG) to participate in orofacial neuropathic pain remains enigmatic. A behavioral test was utilized to evaluate the head withdrawal threshold (HWT) after chronic constriction injury of the infraorbital nerve (CCI-ION). The distribution and expression of GluA1, GluA2, PKC, and PICK1 were examined in the trigeminal ganglion (TG) by immunofluorescence, real-time reverse transcription-quantitative polymerase chain reaction, immunoblotting, and co-immunoprecipitation. Intra-ganglionic injections of drugs were performed to investigate the regulation mechanism. The present study demonstrated that CCI-ION-induced mechanical allodynia was maintained over at least 21 days. GluA1 and GluA2 were mainly expressed in the neurons. Trigeminal nerve injury potentiated the phosphorylation of GluA1, GluA2, and PKC in the TG, which was prevented by inhibiting PKC with chelerythrine chloride. Additionally, PICK1 colocalized and interacted with GluA2 in the TG. Following blocking PICK1 with FSC-231, the phosphorylation of GluA2 decreased. Finally, inhibition of PKC and PICK1 both alleviated mechanical allodynia in the whisker pad of CCI-ION mice. In conclusion, activation of PKC and PICK1 contribute to orofacial allodynia by regulating AMPAR phosphorylation in the TG of male mice, which provides potential therapeutic targets for alleviating orofacial neuropathic pain.

3.
Cardiology ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37708863

RESUMO

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHOD: A systematic literature review of PubMed, Embase, and Cochrane library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiac event (MACE). Pooled effects were calculated using random-effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, P < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, P = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, P<0.00001; HR: 4.01, 95% CI, 2.59-6.20, P < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated a consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.

4.
Pharmacology ; : 1-7, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37742623

RESUMO

BACKGROUND: The most prevalent kind of RNA methylation modification existing in eukaryotes is N6-methyladenosine (m6A), which is a reversible type of posttranscriptional modification. SUMMARY: Many studies have reported that m6A participates in cell differentiation, self-renewal, invasion, and apoptosis by modifying protein synthesis. Furthermore, m6A modification is also involved in disease progression and pulmonary vascular remodeling in pulmonary hypertension. However, very few researchers have investigated the effect of m6A modifications on pulmonary hypertension. KEY MESSAGES: Here, we have reviewed the latest research advances in the field of m6A RNA methylation in pulmonary hypertension and explored its regulatory role in pulmonary hypertension development and progression.

5.
Food Chem ; 434: 137466, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37741247

RESUMO

The empty cup aroma in soy sauce aroma type baijiu (SSB) is distinct, but the specific compounds responsible for its unique aroma remain unknown. The aroma characteristics of SSB and the empty cup were investigated using molecular sensory science. Fifty-three and 27 aroma active compounds were identified in SSB and empty cup aroma, respectively. AEDA of the empty cup showed ethyl 3-phenylpropanoate, phenylethyl alcohol, sotolon, p-cresol, and 2,3-dimethyl-5-ethyl pyrazine could be the most important aroma contributors to the empty cup aroma due to their high FD values. Sotolon, characterized by its seasoning-like and herbal aroma, was identified as a crucial aroma compound for the empty cup aroma for the first time. Lactic acid was found to decrease the olfactory threshold of sotolon markedly in both 53% ethanol water solution and empty cup, promoting the contribution of sotolon to the empty cup aroma.

6.
Molecules ; 28(17)2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37687249

RESUMO

Traditional natural products in China have a long history and a vast pharmacological repertoire that has garnered significant attention due to their safety and efficacy in disease prevention and treatment. Among the bioactive components of traditional natural products in China, bioactive peptides (BPs) are specific protein fragments that have beneficial effects on human health. Despite many of the traditional natural products in China ingredients being rich in protein, BPs have not received sufficient attention as a critical factor influencing overall therapeutic efficacy. Therefore, the purpose of this review is to provide a comprehensive summary of the current methodologies for the preparation, isolation, and identification of BPs from traditional natural products in China and to classify the functions of discovered BPs. Insights from this review are expected to facilitate the development of targeted drugs and functional foods derived from traditional natural products in China in the future.


Assuntos
Produtos Biológicos , Peptídeos , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , China , Sistemas de Liberação de Medicamentos , Alimento Funcional
7.
J Phys Chem Lett ; 14(38): 8620-8629, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37728520

RESUMO

Engineering the buried interfaces of perovskite solar cells (PSCs) is crucial for optimizing the device performance. We herein report a novel strategy by modifying the ETL-FTO interface with MgO, as well as the interface between the perovskite layer (PVKL) and the SnO2 electron transfer layer (ETL) with formamidine bromide (FABr). The dual-interface ETL engineering substantially improved the photoelectric conversion efficiency (19.62 → 22.04%) and suppressed the hysteresis index (14.98 → 1.09%). The structure-activity relationship was explored by using transient photoelectric and time-of-flight secondary-ion mass spectroscopic analyses. It was found that the FABr treatment enhanced the PVKL crystallinity and the PVKL-ETL interaction and that the MgO modification dramatically retarded the ion migration, which together optimized the ETL function. The mechanism underlying the influence of ion distribution on the dynamics of ions and free carriers is discussed, which may be helpful for the rational design of high-performance PSCs.

8.
Biomed Pharmacother ; 165: 115253, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37542855

RESUMO

Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50-400 µM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.


Assuntos
Angiotensina II , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Animais , Ratos , Angiotensina II/efeitos adversos , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteína X Associada a bcl-2/metabolismo , Cardiomegalia/metabolismo , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo
9.
Front Plant Sci ; 14: 1173962, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593047

RESUMO

Linkages between microbial communities and multiple ecosystem functions are context-dependent. However, the impacts of different restoration measures on microbial communities and ecosystem functioning remain unclear. Here, a 14-year long-term experiment was conducted using three restoration modes: planting mixed grasses (MG), planting shrub with Salix cupularis alone (SA), and planting shrub with Salix cupularis plus planting mixed grasses (SG), with an extremely degraded grassland serving as the control (CK). Our objective was to investigate how ecosystem multifunctionality and microbial communities (diversity, composition, and co-occurrence networks) respond to different restoration modes. Our results indicated that most of individual functions (i.e., soil nutrient contents, enzyme activities, and microbial biomass) in the SG treatment were significantly higher than in the CK treatment, and even higher than MG and SA treatments. Compared with the CK treatment, treatments MG, SA, and SG significantly increased the multifunctionality index on average by 0.57, 0.23 and 0.76, respectively. Random forest modeling showed that the alpha-diversity and composition of bacterial communities, rather than fungal communities, drove the ecosystem multifunctionality. Moreover, we found that both the MG and SG treatments significantly improved bacterial network stability, which exhabited stronger correlations with ecosystem multifunctionality compared to fungal network stability. In summary, this study demonstrates that planting shrub and grasses altogether is a promising restoration mode that can enhance ecosystem multifunctionality and improve microbial diversity and stability in the alpine degraded grassland.

10.
Front Microbiol ; 14: 1225469, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621401

RESUMO

Introduction: African swine fever (ASF) is an acute and highly contagious disease and its pathogen, the African swine fever virus (ASFV), threatens the global pig industry. At present, management of ASF epidemic mainly relies on biological prevention and control methods. Moreover, due to the large genome of ASFV, only half of its genes have been characterized in terms of function. Methods: Here, we evaluated a previously uncharacterized viral gene, L60L. To assess the function of this gene, we constructed a deletion strain (SY18ΔL60L) by knocking out the L60L gene of the SY18 strain. To evaluate the growth characteristics and safety of the SY18ΔL60L, experiments were conducted on primary macrophages and pigs, respectively. Results: The results revealed that the growth trend of the recombinant strain was slower than that of the parent strain in vitro. Additionally, 3/5 (60%) pigs intramuscularly immunized with a 105 50% tissue culture infectious dose (TCID50) of SY18ΔL60L survived the 21-day observation period. The surviving pigs were able to protect against the homologous lethal strain SY18 and survive. Importantly, there were no obvious clinical symptoms or viremia. Discussion: These results suggest that L60L could serve as a virulence- and replication-related gene. Moreover, the SY18ΔL60L strain represents a new recombinant live-attenuated ASFV that can be employed in the development of additional candidate vaccine strains and in the elucidation of the mechanisms associated with ASF infection.

11.
J Hazard Mater ; 459: 132185, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37531760

RESUMO

The exposure characteristics of per- and polyfluoroalkyl substances (PFAS) in blood and their associations with hypertension have been well investigated in high-exposure populations, yet limited information is available concerning low-exposure populations. We conducted a cross-sectional study in a low-exposure population in China. A total of 394 females, including 162 with hypertension, were recruited and 30 PFAS were measured in whole blood samples. General linear model, generalized additive model, and logistic model were used to identify the associations with hypertension. Additionally, a Bayesian kernel machine regression model was conducted to test the mixture effects. Fourteen PFAS, including two novel species, 6:2 and 8:2 chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), were detected, among which PFOS predominated with the highest median level of 1.47 ng/mL. The median levels of individual PFAS were, however, below the 25th, and even the 5th percentile of previous reports, except for PFHxA, which was above the 50th percentile (median of 0.10 ng/mL). After adjusting for covariates, PFHxA showed a positive association with hypertension (OR=1.54, 95% CI: 1.25, 1.89), while 6:2 Cl-PFESA showed a negative association (OR=0.73, 95% CI: 0.56, 0.95). PFAS didn't show significant mixture effects. We proposed that PFHxA may contribute to hypertension and 6:2 Cl-PFESA may have a hormesis effect.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Hipertensão , Feminino , Humanos , Ácidos Alcanossulfônicos/toxicidade , Teorema de Bayes , Estudos Transversais , Fluorocarbonos/toxicidade , Fluorocarbonos/análise , China/epidemiologia , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia
13.
J Agric Food Chem ; 71(35): 13054-13065, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37619532

RESUMO

One of the main reasons for consumer rejection of plant-based meat alternatives is the lack of meaty flavor after cooking. In this study, a platform was developed to generate meaty flavors solely from Allium substrates (chives, leeks, ramsons, and onions) using basidiomycete-mediated submerged fermentations. Polyporus umbellatus-mediated fermentation of onions resulted in an intense meaty and liver sausage-like flavor under proper fermentation parameters. Using multisolvent and solvent-free aroma extractions coupled with gas chromatography-mass spectrometry-olfactometry, 5 odorants with high assigned flavor dilution (FD) factors (≥ 256) were identified in the fermented sample that have been reported in the literature as important aroma compounds of meat products: methyl palmitate, bis(2-methyl-furyl) disulfide, (E,E)-2,4-decadienal, γ-nonalactone, and eugenol. Using selected ion monitoring, the presence of bis(2-methyl-furyl) disulfide (meaty, savory, FD 256) after fermentation was confirmed. It was proposed that P. umbellatus enzymatically forms bis(2-methyl-furyl) disulfide from intermediates derived from the thermal degradation of thiamine.


Assuntos
Odorantes , Cebolas , Fermentação , Carne , Dissulfetos , Órgãos dos Sentidos
14.
Chemistry ; : e202302397, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37583100

RESUMO

Inkless and erasable printing (IEP) based on chromic materials holds great promise to alleviate environmental and sustainable problems. Metal-organic polymers (MOPs) are bright platforms for constructing IEP materials. However, it is still challenging to design target MOPs with excellent specific functions rationally due to the intricate component-structure-property relationships. Herein, an effective strategy was proposed for the rational design IEP-MOP materials. The stimuli-responsive viologen moiety was introduced into the construction of MOPs to give it potential chromic behaviors and two different coordination models (i. e. bilateral coordination model, M1 ; unilateral coordinated model, M2 ) based on the same viologen ligand were designed. Aided by theoretical calculations, model M1 was recommended secondarily as a more suitable system for IEP materials. Along this line, two representative viologen-ZnII MOPs 1 and 2 with models M1 and M2 were synthesized successfully. Experiments exhibit that 1 does have quicker stimuli response, stronger color contrast and longer radical lifetime compared to 2. Significantly, the obtained 1-IEP media brightly inherits the excellent chromic characteristics of 1 and the flexibility of the paper at the same time, which achieves most daily printing requirements, as well as enough resolution and durability to be used in identification by smart device.

15.
Sleep Med ; 110: 146-153, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37591029

RESUMO

OBJECTIVE: /Background: This study aimed to explore the clinical, polysomnographic, and heart rate variability (HRV) characteristics of highland obstructive sleep apnea (OSA) patients receiving one-night nocturnal oxygen supplementation (NOS) and to identify factors predicting response. PATIENTS/METHODS: Thirty-four highland OSA patients living in Shangri-La were randomly assigned to receive NOS and sham oxygen in a randomized, placebo-controlled, crossover trial. Clinical assessments, polysomnography, and HRV were measured. A responder was defined as a ≥50% reduction in apnea-hypopnea index (AHI) with NOS compared with sham oxygen. RESULTS: Eighteen participants responded and 16 did not respond, with a median (interquartile range [IQR]) age of 46.5 (36.5-53.0) and 48.0 (44.3-53.3) years, respectively. The median treatment effect (95% CI) on total AHI was -23.2/h (-30.0 to -17.5) and -12.0/h (-16.6 to -7.6) in responders and non-responders (p = 0.004), with similar effects on oxygen desaturation index. The mean OAH duration was prolonged by 7 s in responders together with improved sleep quality and daytime blood pressure. The mean OAH duration at baseline predicted responses to NOS with a sensitivity and specificity of 88.9% and 68.7% (AUC 0.809) at a cut-off point of 24.9 s. Changes in HRV parameters were negatively correlated with changes in mean oxygen saturation and daytime systolic blood pressure only in responders. CONCLUSIONS: NOS significantly improved OSA severity and clinical outcomes in responders, which was related to improvements in parasympathetic activity. Highlanders with shorter mean OAH may be suitable candidates for NOS. These findings provide new information about tailored treatment strategies for highland OSA patients.


Assuntos
Oxigênio , Apneia Obstrutiva do Sono , Humanos , Frequência Cardíaca , Estudos Cross-Over , Apneia Obstrutiva do Sono/terapia , Oxigenoterapia
17.
J Chromatogr A ; 1705: 464183, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37454456

RESUMO

We report on the successful development of a magnetic molecularly imprinted polymer (MMIP) for the separation and detection of catalpol in Rehmannia glutinosa extract and biological samples. Catalpol was used as the template molecule for the MMIPs, which were synthesized using the reverse prediction approach and differential UV-visible spectra to optimize the synthesis conditions. The resulting MMIPs were characterized using techniques including scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry, which confirmed their excellent nuclear shell construction and simple rapid magnetic separation. Static and dynamic adsorption experiments were performed to assess the sensitivity, repeatability, and adsorption capacity of the MMIPs. Adsorption capacity was found to be high (59.09 µg/mg). The MMIPs also exhibited strong identification specificity for catalpol analogs (IF = 2.41). Magnetic solid phase extraction (MSPE) was optimized to establish an MSPE-HPLC approach based on the MMIPs. Under ideal conditions, the new method showed excellent determination coefficient (R2 > 0.99) in the ranges of 0.1-1.0 mg/mL and 0.03-0.18 mg/mL for R. glutinosa extract and biological material, respectively, with limits of detection of 5.4 ng/mL and 1.7 ng/mL. The novelty of this research lies in the preparation of magnetic surface MMIPs using a magnetic carrier. These MMIPs exhibit excellent magnetic properties and possess specific adsorption capability for catalpol, enabling rapid separation. They offer advantages such as low cost, high specificity, chemical stability, physical robustness, and recyclability (97.09%-106.53%, 91.32%-100.99%). The application of these polymers in the pretreatment method for determining the catalpol content in R. glutinosa extract and biological samples enhances the extraction efficiency and detection accuracy for catalpol. It eliminates interference and influences from other components in catalpol determination while exhibiting high sensitivity, good enrichment effects, excellent reusability, and a high recovery rate.


Assuntos
Impressão Molecular , Rehmannia , Impressão Molecular/métodos , Microesferas , Adsorção , Fenômenos Magnéticos , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão
18.
Sci Adv ; 9(27): eadf8412, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37418527

RESUMO

State-of-the-art ion-selective membranes with ultrahigh precision are of significance for water desalination and energy conservation, but their development is limited by the lack of understanding of the mechanisms of ion transport at the subnanometer scale. Herein, we investigate transport of three typical anions (F-, Cl-, and Br-) under confinement using in situ liquid time-of-flight secondary ion mass spectrometry in combination with transition-state theory. The operando analysis reveals that dehydration and related ion-pore interactions govern anion-selective transport. For strongly hydrated ions [(H2O)nF- and (H2O)nCl-], dehydration enhances ion effective charge and thus the electrostatic interactions with membrane, observed as an increase in decomposed energy from electrostatics, leading to more hindered transport. Contrarily, weakly hydrated ions [(H2O)nBr-] have greater permeability as they allow an intact hydration structure during transport due to their smaller size and the most right-skewed hydration distribution. Our work demonstrates that precisely regulating ion dehydration to maximize the difference in ion-pore interactions could enable the development of ideal ion-selective membranes.


Assuntos
Desidratação , Água , Humanos , Transporte de Íons , Íons , Ânions/química , Água/química
19.
J Nanobiotechnology ; 21(1): 207, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37403095

RESUMO

In recent years, cancer immunotherapy has emerged as an exciting cancer treatment. Immune checkpoint blockade brings new opportunities for more researchers and clinicians. Programmed cell death receptor-1 (PD-1) is a widely studied immune checkpoint, and PD-1 blockade therapy has shown promising results in a variety of tumors, including melanoma, non-small cell lung cancer and renal cell carcinoma, which greatly improves patient overall survival and becomes a promising tool for the eradication of metastatic or inoperable tumors. However, low responsiveness and immune-related adverse effects currently limit its clinical application. Overcoming these difficulties is a major challenge to improve PD-1 blockade therapies. Nanomaterials have unique properties that enable targeted drug delivery, combination therapy through multidrug co-delivery strategies, and controlled drug release through sensitive bonds construction. In recent years, combining nanomaterials with PD-1 blockade therapy to construct novel single-drug-based or combination therapy-based nano-delivery systems has become an effective mean to address the limitations of PD-1 blockade therapy. In this study, the application of nanomaterial carriers in individual delivery of PD-1 inhibitors, combined delivery of PD-1 inhibitors and other immunomodulators, chemotherapeutic drugs, photothermal reagents were reviewed, which provides effective references for designing new PD-1 blockade therapeutic strategies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico , Melanoma/tratamento farmacológico , Imunoterapia/métodos
20.
Front Endocrinol (Lausanne) ; 14: 1219194, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37501791

RESUMO

Maternal exercise during pregnancy has emerged as a potentially promising approach to protect offspring from cardiovascular disease, including hypertension. Although endothelial dysfunction is involved in the pathophysiology of hypertension, limited studies have characterized how maternal exercise influences endothelial function of hypertensive offspring. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were assigned either to a sedentary lifestyle or to swimming training daily, and fetal histone deacetylase-mediated epigenetic modification and offspring vascular function of mesenteric arteries were analyzed. Maternal exercise ameliorated the impairment of acetylcholine-induced vasodilation without affecting sodium nitroprusside-induced vasodilation in mesenteric arteries from the hypertensive offspring. In accordance, maternal exercise reduced NADPH oxidase-4 (Nox4) protein to prevent the loss of nitric oxide generation and increased reactive oxygen species production in mesenteric arteries of hypertensive offspring. We further found that maternal exercise during pregnancy upregulated vascular SIRT1 (sirtuin 1) expression, leading to a low level of H3K9ac (histone H3 lysine 9 acetylation), resulting in the transcriptional downregulation of Nox4 in mesenteric arteries of hypertensive fetuses. These findings show that maternal exercise alleviates oxidative stress and the impairment of endothelium-dependent vasodilatation via SIRT1-regulated deacetylation of Nox4, which might contribute to improved vascular function in hypertensive offspring.


Assuntos
Hipertensão , Hipotensão , NADPH Oxidase 4 , Condicionamento Físico Animal , Sirtuína 1 , Animais , Feminino , Gravidez , Ratos , Endotélio Vascular , Hipertensão/prevenção & controle , NADPH Oxidase 4/genética , Estresse Oxidativo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sirtuína 1/genética
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