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1.
Plant Cell Environ ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39262278

RESUMO

Plants have developed various resistance mechanisms against herbivorous insects through prolonged coevolution. Plant defence responses can be triggered by specific compounds present in insect saliva. Apyrase, a known enzyme that catalyzes the hydrolysis of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and inorganic phosphorus, has recently been identified in some herbivorous insects. However, whether insect salivary apyrase induces or inhibits plant responses remains poorly understood. In this study, we identified an apyrase-like protein in the salivary proteome of the fall armyworm, Spodoptera frugiperda, named Sfapyrase. Sfapyrase was primarily expressed in the salivary gland and secreted into plants during insect feeding. Transient expression of Sfapyrase in tobacco and maize enhanced plant resistance and resulted in decreased insect feeding. Knockdown of Sfapyrase through RNA interference led to increased growth and feeding of S. frugiperda. Furthermore, we showed that Sfapyrase activates the jasmonic acid signalling pathway and promotes the synthesis of secondary metabolites, especially benzoxazinoids, thereby enhancing resistance to S. frugiperda. In summary, our findings demonstrated that Sfapyrase acts as a salivary elicitor, inducing maize jasmonic acid defence responses and the production of insect-resistant benzoxazinoids. This study provides valuable insights into plant-insect interactions and offers potential targets for developing innovative insect pest management strategies.

2.
Chem Sci ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39246362

RESUMO

An unexpected, divergent and efficient approach toward furanoid-bridged fullerene dimers C120O and C120O2 was established under different solvent-free ball-milling conditions by simply using pristine C60 as the starting material, water as the oxygen source and FeCl3 as the mediator. The structures of C120O and C120O2 were unambiguously established by single-crystal X-ray crystallography. A plausible reaction mechanism is proposed on the basis of control experiments. Furthermore, C120O2 has been applied in organic solar cells as the third component and exhibits good performance.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39347931

RESUMO

BACKGROUND: The relationship between fat-free mass index (FFMI), fat mass index (FMI), and mortality in patients with asthma remains unknown. This study aimed to examine the associations between FFMI and FMI and all-cause mortality in a cohort of American adults diagnosed with asthma. METHODS: This study included 15,200 adults from NHANES. To assess mortality, we linked participant records to the National Death Index. FMI and FFMI were measured and evaluated using dual-energy X-ray absorptiometry (DXA). Survival differences across quintiles of FFMI and FMI were explored using Kaplan-Meier plots and log-rank tests, with the proportional hazards assumption assessed using Schoenfeld residuals. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for mortality associated with FFMI and FMI, adjusting for potential confounders including age, sex, smoking status, physical activity, and other relevant factors. Additionally, stratified analyses based on theoretical considerations were conducted to identify subgroups of individuals exhibiting an elevated risk of mortality. This study also examined the nonlinear relationships between FFMI, FMI, and mortality using restricted cubic splines (RCS). RESULTS: After a median follow-up of 184 months, 12.11% of individuals had died. Kaplan-Meier plots revealed significant differences in all-cause mortality among patients with asthma across the FFMI and FMI quintiles. Specifically, individuals in the lowest FFMI quintile (Q1, 10.4-16.0, representing the range of FFMI values) exhibited a significantly increased risk of all-cause mortality (HR: 4.63; 95% CI: 1.59, 13.5; p < 0.01). Similarly, elevated risks of all-cause mortality were observed in the upper three quintiles of FMI, with Q3 (4.8-6.1) having an HR of 2.9 (95% CI: 1.20, 7.00; p < 0.05), Q4 (6.2-8.3) having an HR of 3.37 (95% CI: 1.41, 8.03; p < 0.01), and Q5 (8.4-22.8) having an HR of 4.6 (95% CI: 1.31, 16.2; p < 0.05). Moreover, the risk of all-cause mortality increased with increasing FMI and decreasing FFMI (p for non-linearity < 0.001 in both cases). Subgroup analyses further elucidated these associations across different categories. In examining the association between FMI and all-cause mortality among asthma patients across various subgroups, a heightened mortality risk found among males, individuals with medium education levels, medium income levels, and those who consume alcohol. CONCLUSIONS: The study shows that both high FMI and low FFMI are associated with increased mortality in patients with asthma. These findings underscore the critical role of FMI and FFMI in the health management of asthma patients. Therefore, it is recommended that clinicians proactively monitor and adjust these indices to improve patient prognosis and enhance health outcomes for individuals with asthma..

4.
Immunopharmacol Immunotoxicol ; 46(5): 651-661, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39138614

RESUMO

OBJECTIVE: The study aimed to explore the role of the Wnt/ß-catenin signaling pathway in pancreatic cancer progression and chemoresistance, with a focus on identifying specific factors that distinguish between normal and tumor cells, thereby offering potential therapeutic targets. MATERIALS AND METHODS: We analyzed levels of total and phosphorylated eukaryotic translation initiation factor 4E (eIF4E) and ß-catenin in pancreatic cancer and normal pancreatic tissues. Functional assays were used to assess the impact of eIF4E phosphorylation on ß-catenin signaling, cell proliferation, and chemoresistance, with MNK kinase involvement determined through gene depletion studies. The MNK kinase inhibitor eFT508 was evaluated for its effects on eIF4E phosphorylation, ß-catenin activation, and cell viability in both in vitro and in vivo models of pancreatic cancer. RESULTS: Both total and phosphorylated eIF4E, along with ß-catenin, were significantly elevated in pancreatic cancer tissues compared to normal tissues. Phosphorylation of eIF4E at serine 209 was shown to activate ß-catenin signaling, enhance cell proliferation, and contribute to chemoresistance in pancreatic cancer. Importantly, these effects were dependent on MNK kinase activity. Depletion of eIF4E reduced cell viability in both pancreatic cancer and normal cells, while depletion of MNK selectively decreased viability in pancreatic cancer cells. Treatment with eFT508 effectively inhibited eIF4E phosphorylation, suppressed ß-catenin activation, and reduced pancreatic cancer cell growth and survival in vitro and in vivo, with minimal impact on normal cells.Conclusions: The MNK-eIF4E-ß-catenin axis plays a critical role in pancreatic cancer progression and chemoresistance, distinguishing pancreatic cancer cells from normal cells. Targeting MNK kinases with inhibitors like eFT508 presents a promising therapeutic strategy for pancreatic cancer, with potential for selective efficacy and reduced toxicity.


Assuntos
Fator de Iniciação 4E em Eucariotos , Neoplasias Pancreáticas , Proteínas Serina-Treonina Quinases , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Linhagem Celular Tumoral , Fator de Iniciação 4E em Eucariotos/metabolismo , Animais , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , beta Catenina/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos Nus , Feminino
5.
Environ Sci Technol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138130

RESUMO

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

6.
Transl Lung Cancer Res ; 13(7): 1450-1462, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39118895

RESUMO

Background: Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. Methods: E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. Conclusions: E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.

7.
Glob Chang Biol ; 30(8): e17466, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39152655

RESUMO

Global patterns in soil microbiomes are driven by non-linear environmental thresholds. Fertilization is known to shape the soil microbiome of terrestrial ecosystems worldwide. Yet, whether fertilization influences global thresholds in soil microbiomes remains virtually unknown. Here, utilizing optimized machine learning models with Shapley additive explanations on a dataset of 10,907 soil samples from 24 countries, we discovered that the microbial community response to fertilization is highly dependent on environmental contexts. Furthermore, the interactions among nitrogen (N) addition, pH, and mean annual temperature contribute to non-linear patterns in soil bacterial diversity. Specifically, we observed positive responses within a soil pH range of 5.2-6.6, with the influence of higher temperature (>15°C) on bacterial diversity being positive within this pH range but reversed in more acidic or alkaline soils. Additionally, we revealed the threshold effect of soil organic carbon and total nitrogen, demonstrating how temperature and N addition amount interacted with microbial communities within specific edaphic concentration ranges. Our findings underscore how complex environmental interactions control soil bacterial diversity under fertilization.


Assuntos
Bactérias , Fertilizantes , Microbiota , Nitrogênio , Microbiologia do Solo , Solo , Temperatura , Nitrogênio/análise , Nitrogênio/metabolismo , Fertilizantes/análise , Concentração de Íons de Hidrogênio , Solo/química , Carbono/análise , Carbono/metabolismo , Aprendizado de Máquina , Biodiversidade
8.
Clin Transl Oncol ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153177

RESUMO

PURPOSE: This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. METHODS: This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. RESULTS: Multivariate analysis revealed that an alpha-fetoprotein (AFP) level ⩾ 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) ⩽ 65.43 (HR 0.50; 95% CI 0.30-0.84; P < 0.01 ) and SII ⩽ 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP ⩾ 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII > 303.66 were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). CONCLUSION: SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39189800

RESUMO

Bronchial airways and lung parenchyma undergo both static and dynamic stretch in response to normal breathing but also in the context of insults such as mechanical ventilation (MV) or in diseases such as asthma and COPD which lead to airway remodeling involving increased extracellular matrix (ECM) production. Here, the role of fibroblasts is critical, but the relationship between stretch and fibroblast induced ECM remodeling under these conditions is not well-explored. Piezo (PZ) channels play a role in mechanotransduction in many cell and organ systems, but their role in mechanical stretch-induced airway remodeling is not known. To explore this, we exposed human lung fibroblasts to 10% static stretch on a background of 5% oscillations for 48 hours, with no static stretch considered controls. Collagen I, Fibronectin, α-SMA, and Piezo 1 (PZ1) expression were determined in the presence or absence of Yoda1 (PZ1 agonist) or GsMTx4 (PZ1 inhibitor). Collagen I, Fibronectin, and α-SMA expression was increased by stretch and Yoda1 while pretreatment with GsMTx4 or knockdown of PZ1 by siRNA blunted this effect. Acute stretch in the presence and absence of Yoda1 demonstrated activation of ERK pathway but not Smad. Measurement of [Ca2+] i responses to histamine showed significantly greater responses following stretch: effects that were blunted by knockdown of PZ1.Our findings identify an essential role for PZ1 in mechanical stretch-induced production of ECM mediated by ERK phosphorylation and Ca2+ influx in lung fibroblasts. Targeting PZ channels in fibroblasts may constitute a novel approach to ameliorate airway remodeling by decreasing ECM deposition.

10.
Poult Sci ; 103(9): 103947, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986358

RESUMO

Chickens exhibit extensive genetic diversity and are distributed worldwide. Different chicken breeds have evolved to thrive in diverse environmental conditions. However, research on the genetic mechanisms underlying chicken adaptation to extreme environments, such as tropical, frigid and drought-prone regions, remains limited. In this study, we conducted whole-genome sequencing of 240 individuals from six native chicken breeds in Xinjiang, China, as well as 4 publicly available chicken breeds inhabiting regions with varying annual precipitations, temperatures, and altitudes. Our analysis revealed several genetic variants among the examined breeds. Furthermore, we investigated the genetic diversity and population structure of breeds residing in extreme drought and temperature environments by comparing them. Notably, native chicken breeds exhibited different genetic diversity and population structures. Moreover, we identified candidate genes associated with chicken adaptability to the environment, such as CORO2A, CTNNA3, AGMO, GRID2, BBOX1, COL3A1, INSR, SOX5, MAP2 and PLPPR1. Additionally, pathways such as lysosome, cysteine and methionine metabolism, glycosaminoglycan degradation, and Wnt signaling may be play crucial roles in regulating chicken adaptation to drought environments. Overall, these findings contribute to our understanding of the genetic mechanisms governing chicken adaptation to extreme environments, and also offer insights for enhancing the resilience of chicken breeds to different climatic conditions.


Assuntos
Adaptação Fisiológica , Galinhas , Secas , Animais , Galinhas/genética , Galinhas/fisiologia , China , Adaptação Fisiológica/genética , Sequenciamento Completo do Genoma/veterinária , Variação Genética , Clima Tropical
11.
Environ Sci Technol ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39079029

RESUMO

Wastewater discharge from wastewater treatment plants continuously pumps microplastics into rivers, yet their transport distances within these waterways remain unknown. Herein, we developed a conceptual framework by synthesizing the microplastic data from the Yangtze River Basin to evaluate its transport distances, quantifying a significant spatial dependence between large-scale wastewater discharge and riverine microplastics (p < 0.05). The presence of microplastics at a specific sampling site could be attributed to wastewater discharge within a large-scale range spanning >1000 km upstream, encompassing a substantial portion equivalent to one-third of the Yangtze River Basin. The dominance analysis indicated that the contribution of wastewater discharge in rivers with higher discharge (>100 m3/s) to riverine microplastic pollution exceeded 65% within the Yangtze River Basin. The spatial dependence framework of riverine microplastics on wastewater discharge advances our prior understanding of the prevention and control of riverine microplastics by demonstrating that such pollution is not limited to nearby environmental factors.

12.
CNS Neurosci Ther ; 30(7): e14849, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39075660

RESUMO

BACKGROUND: Angong Niuhuang Wan (AGNHW, ), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated. AIMS: This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW's multifaceted immunomodulation effects in-depth, emphasizing previously underexplored areas. RESULTS: AGNHW mitigated monocyte-derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW-treated group attenuated their expressions, indicating AGNHW's potential to temper the post-ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post-stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries. CONCLUSION: This study offers a comprehensive portrait of AGNHW's immunomodulation effects on ischemic stroke, illuminating its dual sites of action-both cerebral and systemic-and its nuanced modulation of cellular and molecular dynamics.


Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , AVC Isquêmico/imunologia , AVC Isquêmico/tratamento farmacológico , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Citometria de Fluxo/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo
14.
Sci Rep ; 14(1): 17273, 2024 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068277

RESUMO

Investigate the effect of long-term COVID-19 on maternal and fetal complications. A retrospective cohort study was conducted. A total of 623 pregnant women who delivered in Kunming First People's Hospital from November 1, 2022 to July 31, 2023 were selected. By employing statistical methods, we compared the associations between maternal and fetal complications in pregnant women with acute COVID-19 during pregnancy, long-term COVID-19, and non-COVID-19 pregnant women. In the final 623 samples, there were 209 pregnant women with acute COVID-19, 72 pregnant women with long-term COVID-19, and 342 pregnant women without COVID-19. The epidemiological and clinical characteristics of all subjects were similar. Pregnant individuals who developed long-term COVID-19 during their pregnancy had an increased risk of experiencing gestational hypertension (OR 3.344, 95% CI 1.544-7.243), gestational diabetes mellitus (OR 2.301, 95% CI 1.290-4.102), and fetal intrauterine growth restriction (OR 2.817, 95% CI 1.385-5.952). Multivariate binary logistic regression analysis showed that this association remained consistent even after adjusting for confounders and performing subgroup analyses. Other maternal and fetal complications, such as premature rupture of membranes, preterm delivery, neonatal asphyxia, and transfer of neonates to NICU, did not exhibit statistically significant associations. After linear regression analysis, the platelet count (ß: - 0.127, 95% CI - 0.001-0.000) of pregnant women with long-term COVID-19 was slightly lower than that of non-COVID-19 pregnant women, and the other coagulation parameters were not statistically significant. The incidence of gestational hypertension, gestational diabetes mellitus and fetal intrauterine growth restriction in pregnant women with long-term COVID-19 is significantly increased, but it does not further increase the coagulation status.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Humanos , Gravidez , Feminino , COVID-19/epidemiologia , COVID-19/complicações , Estudos Retrospectivos , China/epidemiologia , Adulto , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Hipertensão Induzida pela Gravidez/epidemiologia , SARS-CoV-2/isolamento & purificação , Diabetes Gestacional/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Fatores de Risco
15.
Am J Case Rep ; 25: e943112, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39054886

RESUMO

BACKGROUND Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a recently described inflammatory demyelinating disease of the central nervous system (CNS), which needs to be distinguished from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). CASE REPORT A 42-year-old woman presenting with loss of vision due to optic neuritis was admitted to the Naval Medical Center in October 2022. She had optic disc edema, blurred visual margins, optic disc pallor, and deficient visual field in both eyes. Cranial magnetic resonance imaging (MRI) showed bilateral optic nerve thickening, tortuosity, and swelling, especially on the right side. Orbital MRI T2 sequence showed the typical "double track sign" change. The titers of MOG-IgG in CSF and serum were 1: 1 (+) and 1: 32 (+) separately, so MOGAD was diagnosed. The primary treatment was intravenous methylprednisolone for 2 weeks, after which the blurred vision improved and MRI showed the optic nerve lesions disappeared. She was discharged and oral corticosteroids were tapered gradually, and 1 month later, the symptom had vanished without recurrence, cranial MRI was normal, and MOG-IgG in CSF and serum were negative. Low-dose oral corticosteroids were continued for 6 months, with no relapse and normal cranial MRI, so we stopped corticosteroid therapy. At 1-year follow-up, the symptoms had not recurred. CONCLUSIONS A 42-year-old woman presented with loss of vision due to optic neuritis and positive antibody testing for MOG. MOGAD was diagnosed, and timely immunotherapy was effective.


Assuntos
Glicoproteína Mielina-Oligodendrócito , Neurite Óptica , Humanos , Feminino , Neurite Óptica/etiologia , Neurite Óptica/diagnóstico , Adulto , Glicoproteína Mielina-Oligodendrócito/imunologia , Metilprednisolona/uso terapêutico , Imageamento por Ressonância Magnética , Imunoterapia/efeitos adversos , Cegueira/etiologia
16.
Org Lett ; 26(30): 6341-6346, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39024314

RESUMO

Described here is a visible-light-promoted cascade carboxylation/arylation of indole-tethered unactivated alkenes with CO2 to access various carboxylated indole-fused heterocycles. This reaction is initiated by the addition of a CO2 radical anion to the alkene motif toward an alkyl carbon radical, followed by its addition to the aromatic ring, and then rearomatization to afford the final products. This reaction provides a facile and sustainable protocol for the construction of carboxylated indole-fused heterocycles using CO2 as the carboxylic source.

17.
Sci Transl Med ; 16(752): eabq7074, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896602

RESUMO

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.


Assuntos
Receptores ErbB , Exantema , Inibidores de Janus Quinases , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Ratos , Administração Tópica , Afatinib/farmacologia , Afatinib/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Exantema/induzido quimicamente , Exantema/patologia , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Janus Quinases/antagonistas & inibidores , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Prospectivos
18.
J Am Chem Soc ; 146(26): 17600-17605, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38869355

RESUMO

Coupling two magnetic anisotropic lanthanide ions via a direct covalent bond is an effective way to realize high magnetization blocking temperature of single-molecule magnets (SMMs) by suppressing quantum tunneling of magnetization (QTM), whereas so far only single-electron lanthanide-lanthanide bonds with relatively large bond distances are stabilized in which coupling between lanthanide and the single electron dominates over weak direct 4f-4f coupling. Herein, we report for the first time synthesis of short Dy(II)-Dy(II) single bond (3.61 Å) confined inside a carbon cage in the form of an endohedral metallofullerene Dy2@C82. Such a direct Dy(II)-Dy(II) covalent bond renders a strong Dy-Dy antiferromagnetic coupling that effectively quenches QTM at zero magnetic field, thus opening up magnetic hysteresis up to 25 K using a field sweep rate of 25 Oe/s, concomitant with a high 100 s magnetization blocking temperature (TB,100s) of 27.2 K.

19.
Nutrients ; 16(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931200

RESUMO

Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome.


Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Hidrolisados de Proteína , Síndrome Metabólica/microbiologia , Síndrome Metabólica/dietoterapia , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/administração & dosagem , Animais , Proteínas de Plantas
20.
Nutrients ; 16(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38892535

RESUMO

Rice bean [Vigna umbellata (Thunb.) Ohwi and Ohashi], an annual legume in the genus Vigna, is a promising crop suitable for cultivation in a changing climate to ensure food security. It is also a medicinal plant widely used in traditional Chinese medicine; however, little is known about the medicinal compounds in rice bean. In this study, we assessed the diuretic effect of rice bean extracts on mice as well as its relationship with the contents of eight secondary metabolites in seeds. Mice gavaged with rice bean extracts from yellow and black seeds had higher urinary output (5.44-5.47 g) and water intake (5.8-6.3 g) values than mice gavaged with rice bean extracts from red seeds. Correlation analyses revealed significant negative correlations between urine output and gallic acid (R = -0.70) and genistein (R = -0.75) concentrations, suggesting that these two polyphenols negatively regulate diuresis. There were no obvious relationships between mice diuresis-related indices (urine output, water intake, and weight loss) and rutin or catechin contents, although the concentrations of both of these polyphenols in rice bean seeds were higher than the concentrations of the other six secondary metabolites. Our study findings may be useful for future research on the diuretic effects of rice bean, but they should be confirmed on the basis of systematic medical trials.


Assuntos
Diuréticos , Polifenóis , Sementes , Animais , Camundongos , Diuréticos/farmacologia , Sementes/química , Polifenóis/farmacologia , Polifenóis/análise , Masculino , Extratos Vegetais/farmacologia , Vigna/química , Ácido Gálico/farmacologia , Genisteína/farmacologia , Catequina/farmacologia , Catequina/análise , Rutina/farmacologia , Rutina/análise , Diurese/efeitos dos fármacos
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