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1.
Plant Cell ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092875

RESUMO

Xylem vessels function in the long-distance conduction of water in land plants. The NAC transcription factor VASCULAR-RELATED NAC-DOMAIN7 (VND7) is a master regulator of xylem vessel cell differentiation in Arabidopsis (Arabidopsis thaliana). We previously isolated suppressor of ectopic xylem vessel cell differentiation induced by VND7 (seiv) mutants. Here, we report that the responsible genes for seiv3, seiv4, seiv6, and seiv9 are protein ubiquitination-related genes encoding PLANT U-BOX46 (PUB46), an uncharacterized F-BOX protein (FBX), PUB36, and UBIQUITIN-SPECIFIC PROTEASE1 (UBP1), respectively. We also found decreased expression of genes downstream of VND7 and abnormal xylem transport activity in the seiv mutants. Upon VND7 induction, ubiquitination levels from 492 and 180 protein groups were up- and down-regulated, respectively. VND7 induction resulted in the ubiquitination of proteins for cell wall biosynthesis and protein transport, whereas such active protein ubiquitination did not occur in the seiv mutants. We detected the ubiquitination of three lysine residues in VND7: K94, K105, and K260. Substituting K94 with arginine significantly decreased the transactivation activity of VND7, suggesting that the ubiquitination of K94 is crucial for regulating VND7 activity. Our findings highlight the crucial roles of target protein ubiquitination in regulating xylem vessel activity.

2.
Front Cell Infect Microbiol ; 14: 1397717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157177

RESUMO

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results: The overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and ß diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion: Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.


Assuntos
Líquido da Lavagem Broncoalveolar , Microbiota , Humanos , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Pneumonia/microbiologia , Pneumonia/mortalidade , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão/microbiologia , Pulmão/patologia , Metagenômica , Aprendizado de Máquina
3.
Mil Med Res ; 11(1): 55, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138529

RESUMO

BACKGROUND: Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. METHODS: Age-specific mortality data for cervical and breast cancers among Chinese women aged 20-84 years were obtained from China's National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. RESULTS: From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35-64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5-7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: - 0.7%, 95% CI - 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI - 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: - 2.7%, 95% CI - 4.6 to - 0.7%, P = 0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35-54 age group across urban and rural areas, periods, and regions in China. CONCLUSIONS: Special attention should be given to women aged 35-54 years due to mortality trends and rural-urban disparities. Focusing on vulnerable age groups and addressing rural-urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.


Assuntos
Neoplasias da Mama , População Rural , População Urbana , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/mortalidade , Adulto , China/epidemiologia , Idoso , Neoplasias do Colo do Útero/mortalidade , População Rural/estatística & dados numéricos , População Rural/tendências , População Urbana/estatística & dados numéricos , População Urbana/tendências , Idoso de 80 Anos ou mais , Adulto Jovem , Mortalidade/tendências , Fatores Etários
4.
J Biochem Mol Toxicol ; 38(9): e23769, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39152098

RESUMO

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment (TME) and can induce functional polarization of tumor macrophages. This study aimed to explore the effect of CAFs-derived exosome LINC01833 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells and its mechanism. Tumor tissues (n = 3) and adjacent noncancerous tissues (n = 3) were collected from patients with NSCLC, and fibroblasts (CAF, NF) were isolated from the two tissues. Expression of LINC01833/miR-335-5p/VAPA in NSCLC clinical tissues and cell lines was detected by RT-qPCR. Exosomes of CAFs and NFs were isolated by ultracentrifugation. Cell proliferation, migration, invasion, and M2 macrophage polarization were detected by MTT, transwell, wound-healing assay, and flow cytometry assay, while western blot was used to verify the expression of M2 macrophage polarization-related proteins. Tumor volume weight and M2 macrophage polarization were detected by tumor xenografts in nude mice. LINC01833 was highly expressed in NSCLC tumor tissues and cells. Knockdown of LINC01833 exosomes could significantly inhibit proliferation, migration, invasion of NSCLC cells, and M2 macrophage polarization of THP-1 cells, while simultaneous knockdown of miR-335-5p on the above basis could reverse the effect of knockdown of LINC01833. In vivo experiments also indicated that knockdown of LINC01833 exosomes suppressed tumor growth and M2 macrophage polarization. CAF-derived LINC01833 exosomes can promote the proliferation, migration and invasion of NSCLC cells and M2 macrophage polarization by inhibiting miR-335-5p and regulating VAPA activity.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Camundongos Nus , MicroRNAs , RNA Longo não Codificante , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Exossomos/metabolismo , Exossomos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Proliferação de Células , Masculino , Feminino , Linhagem Celular Tumoral , Movimento Celular , Células A549 , Camundongos Endogâmicos BALB C
5.
Alzheimers Dement ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023044

RESUMO

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

6.
Chin J Integr Med ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028451

RESUMO

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS: CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.

7.
Food Res Int ; 191: 114727, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059923

RESUMO

Phages are a class of viruses that specifically infect host bacteria. Compared to other recognition elements, phages offer several advantages such as high specificity, easy to obtain and good environmental tolerance, etc. These advantages underscore the potential of phages as recognition elements in the construction of biosensors. Therefore, the phage-based biosensors are currently garnering widespread attention for detecting pathogens in recent years. However, the test performance such as detection limit, sensitivity and stability of exicting phage-based biosensors require enhancement. In the design of sensors, the selection of various materials and construction methods significantly influences the test performance of the sensor, and employing appropriate signal amplification strategies and construction methods to devise biosensors based on different principles is an effective strategy to enhance sensor performance. The manuscript primarily focuses on the signal amplification strategies and construction methods employed in phage-based biosensors recent ten years, and summarizes the advantages and disadvantages of different signal amplification strategies and construction methods. Meanwhile, the manuscript discusses the relationship between sensor performance and various materials and construction methods, and reviews the application progress of phage-based electrochemical biosensors in the detection of foodborne bacteria. Furthermore, the manuscript points out the present limitations and the future research direction for the field of phage-based biosensors, so as to provide the reference for developing high-performance phage-based biosensors.


Assuntos
Bacteriófagos , Técnicas Biossensoriais , Microbiologia de Alimentos , Técnicas Biossensoriais/métodos , Microbiologia de Alimentos/métodos , Bactérias/virologia , Bactérias/isolamento & purificação , Técnicas Eletroquímicas/métodos
8.
Medicine (Baltimore) ; 103(27): e38812, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968470

RESUMO

Acquired undescended testes were once considered a sporadic disease. In recent years, reports suggest that they are not uncommon, with an incidence rate about 3 times that of congenital undescended testes. The etiology of acquired undescended testes remains inconclusive, clinical diagnostic standards are unclear, and treatment approaches are still controversial. There is ongoing debate about the mechanism of testicular ascent. The prevailing view is that acquired undescended testes occur due to the partial absorption of the gubernaculum, which forms part of the parietal peritoneum. The residual gubernacular fibers continuously pull on the spermatic cord, preventing the spermatic cord from elongating proportionately to somatic growth, leading to a re-ascent of the testis. Acquired undescended testes may increase the risk of testicular cancer, but this is still debated. The preferred treatment method is also controversial. However, surgical fixation has an immediate effect; no studies have proven that early surgery improves fertility in patients. The etiology of acquired undescended testes is closely related to the continuous pull of the residual gubernacular fibers on the spermatic cord, which prevents the cord from extending proportionately to body growth. There are no clear diagnostic standards for acquired undescended testes yet, and spontaneous descent is possible, so testicular fixation surgery may not be the preferred treatment method.


Assuntos
Criptorquidismo , Humanos , Masculino , Criptorquidismo/terapia , Criptorquidismo/diagnóstico , Criptorquidismo/etiologia , Testículo , Orquidopexia
9.
Asia Pac J Ophthalmol (Phila) ; : 100086, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39053733

RESUMO

PURPOSE: To investigate the potential phases in myopic retinal vascular alterations for further elucidating the mechanisms underlying the progression of high myopia (HM). METHODS: For this retrospective study, participants diagnosed with high myopia at Beijing Tongren Hospital were recruited. Based on bionic mechanisms of human vision, an intelligent image processing model was developed and utilized to extract and quantify the morphological characteristics of retinal vasculatures in different regions measured by papilla-diameter (PD), including vascular caliber, arteriole-to-venule ratio (AVR), tortuosity, the angle of the vascular arch (AVA), the distance of the vascular arch (DVA), density, fractal dimension, and venular length. In addition, the optic disc and the area of peripapillary atrophy (PPA) were also quantified. The characteristics of the overall population, as well as patients aged less than 25 years old, were compared by different genders. Univariate and multiple linear regression analyses were conducted to investigate the correlation of retinal vasculature parameters with PPA width, and detailed trends of the vascular indicators were analyzed to explore the potential existence of staged morphological changes. FINDINGS: The study included 14,066 fundus photographs of 5775 patients (aged 41.2 ± 18.6 years), of whom 7379 (61.2 %) were female. The study included 12,067 fundus photographs of 5320 patients (aged 41.2 ± 18.6 years). Significant variations in the morphological parameters of retinal vessels were observed between males and females. After adjusting for age and sex, multiple linear regression analysis showed that an increased PPA width ratio was associated with lower AVA (1PD), DVA (1PD), vascular caliber (0.5-1.0 PD), tortuosity (0.5-1.0 PD), density and fractal dimension (all P < 0.001, Spearman's ρ < 0). Overall, the changes in retinal vascular morphology showed two phases: tortuosity (0.5-1.0PD) and AVA (1PD) decreased rapidly in the first stage but significantly more slowly in the second stage, while vascular density and fractal dimension showed a completely opposite trend with an initial slow decline followed by a rapid decrease. CONCLUSIONS: This study identified two distinct phases of retinal vascular morphological changes during the progression of HM. Traction lesions were predominant in the initial stage, while atrophic lesions were predominant in the later stage. These findings provide further insight into the development mechanism of HM from the perspective of retinal vasculature.

10.
Brain Behav Immun ; 120: 181-186, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825049

RESUMO

BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Células Produtoras de Anticorpos , Imunoglobulina G , Leucócitos Mononucleares , Receptores de N-Metil-D-Aspartato , Humanos , Receptores de N-Metil-D-Aspartato/imunologia , Receptores de N-Metil-D-Aspartato/metabolismo , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/metabolismo , Masculino , Feminino , Células Produtoras de Anticorpos/imunologia , Células Produtoras de Anticorpos/metabolismo , Adulto , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologia , Autoanticorpos/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança
11.
Epigenomics ; 16(10): 715-731, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38869474

RESUMO

Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.


Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age ­ essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system ­ which fights off diseases ­ react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.


Assuntos
Envelhecimento , Ácidos Nucleicos Livres , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Inflamação , Humanos , Envelhecimento/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Feminino , Inflamação/genética , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Biomarcadores/sangue , Idoso de 80 Anos ou mais
12.
Heliyon ; 10(10): e31526, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38831844

RESUMO

Background and objectives: The intercornual distance in the sacral hiatus has yet to be studied precisely in children. This age-stratified, observational study aimed to clarify the changes in sacral hiatus dimensions and to quantify the correlations between the intercornual distance of the sacral hiatus and age, height, weight, and head circumference by using real-time ultrasonography. Methods: The patients were stratified into three groups: neonates and infants, toddlers, and schoolchildren. In the operating room, the ultrasonic probe was placed at the sacral cornua to obtain a transverse view of the sacral hiatus, and the intercornual distance was measured three times in millimetres. Results: The study included a total of 156 patients. The mean ± SD (95%CI) of intercornual distance in neonates and infants (<12 months) was 11.58 ± 1.79 (11.11-12.04) mm, 13.29 ± 1.97 (12.71-13.86) mm in toddlers (13-36 months), and 13.36 ± 2.49 (12.64-14.08) mm in schoolchildren (>36 months).The mean values of neonates and infants were different from those of toddlers and schoolchildren (p < 0.001), but it was similar between toddlers and schoolchildren (p > 0.05, 95 % CI mean difference -1.10 to 0.95).Intercornual distance was correlated with age, height, weight, and head circumference before one year of age (Spearman's R values > 0.7), but there was no correlation thereafter (Spearman's p value > 0.05). Conclusion: In the first year after birth, the intercornual distance increases rapidly with body growth; after one year of age, the sacral hiatus dimension changes significantly. Ultrasound is superior for assessing the gradually ossified cartilage components in older children.

13.
Mol Med Rep ; 30(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38785160

RESUMO

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.


Assuntos
Ferroptose , Transdução de Sinais , Acidente Vascular Cerebral , Ferroptose/efeitos dos fármacos , Humanos , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Terapia de Alvo Molecular , Medicina Tradicional Chinesa/métodos
14.
Front Neurosci ; 18: 1181670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737099

RESUMO

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

15.
Food Chem ; 452: 139572, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733686

RESUMO

The discarded longan shell-derived porous carbon material (LPC) served as a scaffold for synthesizing bismuth nanoparticle-loaded longan porous carbon nanocomposite (BiNPs@LPC) via a hydrothermal method. Then BiNPs@LPC was utilized to modify screen-printed carbon electrodes (SPCE) for simultaneous detection of Pb(II) and Cd(II) by square wave anodic stripping voltammetry (SWASV). The material was thoroughly characterized by scanning electron microscopy, X-ray diffraction, Raman spectra, Brunauer-Emmett-Teller analysis, electrochemical impedance spectroscopy and cyclic voltammetry. BiNPs@LPC exhibited abundant porous structures, high surface area, and numerous active sites, which could improve significantly response sensitivity. Under optimal conditions, the peak currents of Pb(II) and Cd(II) exhibited favorable linear relationships with the concentration within a range of 0.1-150 µg L-1, with detection limits (S/N = 3) of 0.02 µg L-1 and 0.03 µg L-1, respectively. BiNPs@LPC/SPCE demonstrated remarkable selectivity, stability and repeatability. The proposed method was successfully applied for the detection of Pb(II) and Cd(II) in seafoods achieving satisfying recovery of 97.8%-108.3% and 96.7%-106.4%. These excellent test properties were coupled with convenience for batch preparation of the modified electrodes, highlighting its potential for practical applications in heavy metal detection of real samples.


Assuntos
Bismuto , Cádmio , Carbono , Técnicas Eletroquímicas , Contaminação de Alimentos , Chumbo , Alimentos Marinhos , Bismuto/química , Chumbo/análise , Chumbo/química , Cádmio/química , Cádmio/análise , Alimentos Marinhos/análise , Carbono/química , Contaminação de Alimentos/análise , Porosidade , Animais , Nanopartículas Metálicas/química , Limite de Detecção , Eletrodos
16.
Plant Mol Biol ; 114(3): 45, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630407

RESUMO

The recent growth in global warming, soil contamination, and climate instability have widely disturbed ecosystems, and will have a significant negative impact on the growth of plants that produce grains, fruits and woody biomass. To conquer this difficult situation, we need to understand the molecular bias of plant environmental responses and promote development of new technologies for sustainable maintenance of crop production. Accumulated molecular biological data have highlighted the importance of RNA-based mechanisms for plant stress responses. Here, we report the most advanced plant RNA research presented in the 33rd International Conference on Arabidopsis Research (ICAR2023), held as a hybrid event on June 5-9, 2023 in Chiba, Japan, and focused on "Arabidopsis for Sustainable Development Goals". Six workshops/concurrent sessions in ICAR2023 targeted plant RNA biology, and many RNA-related topics could be found in other sessions. In this meeting report, we focus on the workshops/concurrent sessions targeting RNA biology, to share what is happening now at the forefront of plant RNA research.


Assuntos
Arabidopsis , Agricultura , Arabidopsis/genética , Ecossistema , RNA de Plantas/genética , Solo
17.
Biosci Trends ; 18(2): 116-126, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38658363

RESUMO

As the population ages, the prevalence of dysphagia among older adults is a growing concern. Age-related declines in physiological function, coupled with neurological disorders and structural changes in the pharynx associated with aging, can result in weakened tongue propulsion, a prolonged reaction time of the submental muscles, delayed closure of the laryngeal vestibule, and delayed opening of the upper esophageal sphincter (UES), increasing the risk of dysphagia. Dysphagia impacts the physical health of the elderly, leading to serious complications such as dehydration, aspiration pneumonia, malnutrition, and even life-threatening conditions, and it also detrimentally affects their psychological and social well-being. There is a significant correlation between frailty, sarcopenia, and dysphagia in the elderly population. Therefore, older adults should be screened for dysphagia to identify both frailty and sarcopenia. A reasonable diagnostic approach for dysphagia involves screening, clinical assessment, and instrumental diagnosis. In terms of treatment, multidisciplinary collaboration, rehabilitation training, and the utilization of new technologies are essential. Future research will continue to concentrate on these areas to enhance the diagnosis and treatment of dysphagia, with the ultimate aim of enhancing the quality of life of the elderly population.


Assuntos
Transtornos de Deglutição , Humanos , Transtornos de Deglutição/terapia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/fisiopatologia , Idoso , Sarcopenia/diagnóstico , Sarcopenia/terapia , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Idoso de 80 Anos ou mais , Qualidade de Vida , Fragilidade/diagnóstico , Fragilidade/complicações , Avaliação Geriátrica/métodos
18.
Biosci Trends ; 18(2): 195-197, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38631884

RESUMO

APOE4 is widely recognized as a genetic risk factor for Alzheimer's disease (AD), implicated in 60-80% of all AD cases. Recent research suggests that microglia carrying the APOE4 genotype display abnormal lipid metabolism and accumulate lipid droplets, which may exacerbate the pathology of AD. Microglia play a critical role in immune surveillance within the central nervous system and are responsible for removing harmful particles and preserving neuronal function. The APOE4 genotype causes abnormal lipid metabolism in microglia, resulting in excessive accumulation of lipid droplets. This accumulation not only impairs the phagocytic and clearance capabilities of microglia but also disrupts their interactions with neurons, resulting in disorganization and neurodegenerative alterations at the neuronal network level. In addition, the presence of APOE4 modifies the metabolic landscape of microglia, particularly affecting purinergic signaling and lipid metabolism, thereby exacerbating the pathological processes of AD. In conclusion, the accumulation of lipid droplets and abnormal lipid metabolism may be critical mechanisms in the progression of AD in microglia carrying the APOE4 genotype.


Assuntos
Doença de Alzheimer , Apolipoproteína E4 , Genótipo , Metabolismo dos Lipídeos , Microglia , Microglia/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Animais
19.
Eur J Pharmacol ; 972: 176553, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38574838

RESUMO

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.


Assuntos
Benzamidas , Ferroptose , Microglia , Fator 2 Relacionado a NF-E2 , Pirróis , Traumatismo por Reperfusão , Animais , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/efeitos dos fármacos , Modelos Animais de Doenças , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Linhagem Celular , Transporte Ativo do Núcleo Celular/efeitos dos fármacos
20.
Ying Yong Sheng Tai Xue Bao ; 35(2): 457-468, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523104

RESUMO

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.


Assuntos
Ecossistema , Rios , Conservação dos Recursos Naturais/métodos , Solo , Carbono , Nitrogênio , Fósforo , China
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