Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Autophagy ; : 1-2, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38744666

RESUMO

Hematopoietic stem cells (HSC) emerge from hemogenic endothelial cells (HEC) in the aorta-gonad-mesonephros (AGM) region of embryos, which go through the pre-HSC process. Various intrinsic and extrinsic factors are involved in this process. We recently discovered that the existence of distinct macroautophagic/autophagic statuses in hematopoietic precursors is related to the hematopoietic potential of pre-HSCs and the depletion of the Atg5 (autophagy related 5) gene specifically in endothelial cells impaired in the transition of endothelial to pre-HSCs, by hampering the autophagic process, likely via the NCL (nucleolin) pathway.Abbreviation: Atg5: autophagy related 5; EGFP: enhanced green fluorescent protein; EHT: endothelial-to-hematopoietic transition; HEC: hemogenic endothelial cell; HSC: hematopoietic stem cell; NCL: nucleolin; RFP: red fluorescent protein.

2.
EBioMedicine ; 104: 105161, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772282

RESUMO

BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric illness affecting ∼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive. METHODS: In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies. FINDINGS: We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with changes to Na+ conductance. Whole transcriptome sequencing in BD neurons revealed altered gene expression pathways related to glutamate transmission, alterations in cell signalling and ion transport/channel activity. We found altered Akt signalling as a potential therapeutic effect of Li in LR neurons from patients with BD, and that Akt activation mimics Li effect in LR neurons. Furthermore, the increased neural network activity observed in both LR & LNR neurons from patients with BD were reversed by AMP-activated protein kinase (AMPK) activation. INTERPRETATION: These results suggest potential for new treatment strategies in BD, such as Akt activators in LR cases, and the use of AMPK activators for LNR patients with BD. FUNDING: Supported by funding from ERA PerMed, Bell Brain Canada Mental Research Program and Brain & Behavior Research Foundation.


Assuntos
Proteínas Quinases Ativadas por AMP , Transtorno Bipolar , Células-Tronco Pluripotentes Induzidas , Neurônios , Proteínas Proto-Oncogênicas c-akt , Transtorno Bipolar/metabolismo , Transtorno Bipolar/tratamento farmacológico , Humanos , Neurônios/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Lítio/farmacologia , Lítio/uso terapêutico , Transdução de Sinais , Perfilação da Expressão Gênica , Transcriptoma
3.
EMBO J ; 43(9): 1722-1739, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580775

RESUMO

Understanding the regulatory mechanisms facilitating hematopoietic stem cell (HSC) specification during embryogenesis is important for the generation of HSCs in vitro. Megakaryocyte emerged from the yolk sac and produce platelets, which are involved in multiple biological processes, such as preventing hemorrhage. However, whether megakaryocytes regulate HSC development in the embryonic aorta-gonad-mesonephros (AGM) region is unclear. Here, we use platelet factor 4 (PF4)-Cre;Rosa-tdTomato+ cells to report presence of megakaryocytes in the HSC developmental niche. Further, we use the PF4-Cre;Rosa-DTA (DTA) depletion model to reveal that megakaryocytes control HSC specification in the mouse embryos. Megakaryocyte deficiency blocks the generation and maturation of pre-HSCs and alters HSC activity at the AGM. Furthermore, megakaryocytes promote endothelial-to-hematopoietic transition in a OP9-DL1 coculture system. Single-cell RNA-sequencing identifies megakaryocytes positive for the cell surface marker CD226 as the subpopulation with highest potential in promoting the hemogenic fate of endothelial cells by secreting TNFSF14. In line, TNFSF14 treatment rescues hematopoietic cell function in megakaryocyte-depleted cocultures. Taken together, megakaryocytes promote production and maturation of pre-HSCs, acting as a critical microenvironmental control factor during embryonic hematopoiesis.


Assuntos
Células-Tronco Hematopoéticas , Megacariócitos , Animais , Megacariócitos/citologia , Megacariócitos/metabolismo , Camundongos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular , Hematopoese/fisiologia , Mesonefro/embriologia , Mesonefro/metabolismo , Mesonefro/citologia , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Técnicas de Cocultura
4.
Nat Commun ; 15(1): 2255, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490977

RESUMO

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.


Assuntos
Hemangioblastos , Células-Tronco Hematopoéticas , Animais , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular , Embrião de Mamíferos , Hematopoese/genética , Fatores de Transcrição/metabolismo , Autofagia/genética , Mesonefro
5.
Cardiovasc Diabetol ; 23(1): 95, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486275

RESUMO

OBJECTIVE: The association of the triglyceride-glucose (TyG) index with intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) is unclear. This study aimed to investigate the relationship of TyG index with the distribution and severity of ICAS and ECAS. METHOD: Patients who underwent digital subtraction angiography (DSA) for evaluating ICAS/ECAS in Zhongnan Hospital of Wuhan University from January 2017 to October 2021 were retrospectively enrolled in our study. Clinical characteristics, DSA data, blood routine, lipid profile and fasting glucose were recorded. The association of TyG index and ICAS/ECAS status were investigated in four aspects: location and distribution of stenosis, stenosis severity and whether stenosis is symptomatic. Logistic regression models were used to evaluate the association. Restricted cubic splines were constructed to model the non-linear relationship between the TyG index and different arterial stenosis status. RESULTS: Among 1129 included patients, the median age was 62 (IQR 55-68) years, and 71.3% were male. The median TyG index was 8.81 (8.40, 9.21). Elevated TyG index was significantly associated with ICAS, combined ICAS/ECAS, anterior circulation stenosis, posterior circulation stenosis, combined anterior/posterior circulation stenosis, severe stenosis, both asymptomatic and symptomatic stenosis. This association was maintained after adjusting for age, sex, smoking, drinking, medical history of hypertension and stroke, platelet, total cholesterol, high-density lipoprotein, and low-density lipoprotein. Multivariable-adjusted spline regression models showed that a progressively increasing risk of arterial stenosis was related to an elevated TyG index. CONCLUSION: Elevated TyG index was associated with ICAS/ECAS. TyG index might be a useful indicator of ICAS and severe stenosis.


Assuntos
Glucose , Lipoproteínas HDL , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Triglicerídeos , Estudos Retrospectivos , Constrição Patológica
6.
Molecules ; 29(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38257381

RESUMO

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.


Assuntos
Ansiolíticos , Sesquiterpenos , Humanos , Ansiolíticos/farmacologia , Farmacologia em Rede , Microextração em Fase Sólida , Transtornos de Ansiedade , Cromatografia Gasosa-Espectrometria de Massas , Sesquiterpenos/farmacologia
7.
Heliyon ; 9(11): e22262, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38045129

RESUMO

Background: Cerebral venous sinus thrombosis (CVST) in pregnancy was common and endovascular treatment (EVT) could be an effective and safe treatment for patients with severe and refractory CVST. However, the efficacy and safety of hybrid EVT (craniotomy + endovascular treatment) for CVST were unknown. We represented a rare case of hybrid EVT through the incision of the superior sagittal sinus in a pregnant woman with CVST who failed to EVT through the femoral vein pathway. Case presentation: A 26-year-old woman, in her second month of pregnancy, complained of a headache for 5 days and aggravation with coma combined with convulsions for 2 days. She was diagnosed with CVST in the local hospital by digital subtraction angiography (DSA) and treated with anticoagulation. She had no history of illness and the biochemical tests were normal. Hybrid EVT (craniotomy + EVT) was attempted after failing to conduct EVT through the femoral vein pathway due to difficulty to reach the target cerebral venous sinus. Briefly, a small hole was made in the frontotemporal head to expose the superior sagittal sinus and a 6F sheath was inserted into 2cm of superior sagittal sinus incision and fixed on the scalp, after repeated aspiration by 5F intermediate catheter and balloon dilatation of stenosis in the right transverse sinus and right sigmoid sinus, the cerebral venous system got successful recanalization. No obvious complications were found and the patient recovered very well after the surgery. Conclusion: Anticoagulation was the standard treatment for CVST. EVT could rapidly restore venous flow and improve the prognosis for refractory and severe CVST. EVT by hybrid surgery through the superior sagittal sinus incision may be safe and effective for desperate patients with severe CVST.

8.
eNeurologicalSci ; 32: 100471, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37435445

RESUMO

Introduction: Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines and studies mainly focused on pediatric patients. The rarity and also insufficient knowledge of LCH in adults, especially central neuvous system (CNS) involvement of LCH, often resulted in missed and delayed diagnosis. Case presentation: A 35-year-old woman presented with cognitive impairment, anxietydepression, decreased eyesight, skin rash, hypernatremia, gonadal hormone deficiency and hypothyroidism. She had experienced menstrual disturbance and infertility since 10 years ago. MRI examination showed a mass lesion in the hypothalamic-pituitary region. Sighs of radiologic neurodegeneration were not found on brain MRI scans, however. Biopsy of skin rash confirmed the the diagnosis of multisystem LCH. BRAF V600E mutation was detected in the peripheral blood mononuclear cells. She accepted combination chemotherapy of vindesine and prednisone and accquired partial remission. The patient died of severe pneumonia during the second course of chemotherapy. Conclusion: Given the complicated differential diagnoses of neuroendocrine disorders, it was essential to be aware of CNS involvement of LCH at first, especially in adults. BRAF V600E mutation may participated in disease progression.

9.
Front Oncol ; 13: 1102853, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124528

RESUMO

Purpose: The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population. Materials and methods: Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan-Meier method. Results: In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively. Conclusions: De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.

10.
CNS Neurosci Ther ; 29(7): 1817-1829, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36852451

RESUMO

AIMS: Multiple guidance cues, such as netrin-1 (NTN-1)/deleted in colorectal carcinoma (DCC), control the guidance of axons and help establish functional neural circuits during development. However, the function of these guidance molecules during the neurodegenerative process is unclear. METHODS: To access the alterations of NTN-1 and DCC during the onset and progression of PD, we first established two subacute and one chronic PD model. Then, we investigated the relationship between the NTN-1/DCC pathway and cell death in SH-SY5Y cells. Finally, we conducted correlation studies between plasma NTN-1 and parkinsonian symptoms in patients to understand how this pathway contributes to PD. RESULTS: We found that the imbalance of NTN-1 and DCC was a common feature of nigral DA neuron injury in PD mouse models. We investigated that MPP+ inhibited NTN-1 expression and increased DCC expression in a concentration- and time-dependent manner. We further discovered a significant decrease in plasma NTN-1 levels and a positive correlation with UPDRS scores in PD patients. CONCLUSION: Our findings confirmed the imbalance of NTN-1/DCC signaling during nigral degeneration in experimental PD models and found for the first time a correlation of plasma NTN-1 with PD symptoms in patients.


Assuntos
Neuroblastoma , Doença de Parkinson , Camundongos , Animais , Humanos , Fatores de Crescimento Neural/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Netrina-1 , Células Cultivadas , Axônios/metabolismo , Receptor DCC
11.
Int J Gynaecol Obstet ; 161(2): 367-385, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36786495

RESUMO

BACKGROUND: Stress urinary incontinence (SUI) is a global problem. It can significantly adversely impact a woman's quality of life. The use of synthetic mesh in vaginal surgery is controversial, especially when used for pelvic organ prolapse surgery. Although negative effects have been reported, the synthetic mesh midurethral sling (MUS) is considered to be safe and effective in the surgical treatment of SUI. OBJECTIVES: To provide evidence-based data and recommendations for the obstetrician/gynecologist who treats women with SUI and performs or plans to perform MUS procedures. METHODS: Academic searches of MEDLINE, the Cochrane Library, Embase, and Google Scholar articles published between 1987 and March 2020 were performed by a subgroup of the Urogynecology and Pelvic Floor Committee, International Federation of Gynecology and Obstetrics (FIGO). SELECTION CRITERIA: The obtained scientific data were associated with a level of evidence according to the Oxford University Centre for Evidence-Based Medicine and GRADE Working Group system. In the absence of concrete scientific evidence, the recommendations were made via professional consensus. RESULTS: The FIGO Urogynecology and Pelvic Floor Committee reviewed the literature and prepared this evidence-based recommendations document for the use of MUS for women with SUI. CONCLUSIONS: Despite the extensive literature, there is a lack of consensus in the optimal surgical treatment of SUI. These recommendations provide a direction for surgeons to make appropriate decisions regarding management of SUI. The MUS is considered safe and effective in the treatment of SUI, based on many high-quality scientific publications and professional society recommendations. Comprehensive long-term data and systemic reviews are still needed, and these data will become increasingly important as women live longer. These recommendations will be continuously updated through future literature reviews.


Assuntos
Prolapso de Órgão Pélvico , Slings Suburetrais , Incontinência Urinária por Estresse , Humanos , Feminino , Incontinência Urinária por Estresse/cirurgia , Qualidade de Vida , Prolapso de Órgão Pélvico/cirurgia , Consenso
12.
Sci Rep ; 12(1): 16899, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207462

RESUMO

CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Invasividade Neoplásica/genética , RNA Mensageiro/metabolismo
13.
ACS Omega ; 7(27): 23695-23707, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35847291

RESUMO

A three-dimensional numerical simulation of oil shale in situ conversion processing by applying the downhole burner heating technology was conducted. The evolution of the fluid vector and temperature field and the characteristic of kerogen decomposition and oil and gas production were analyzed. The effects of different burning temperatures and gas injection velocities on the thermal evolution processing of oil shale in situ conversion were investigated. The stress-strain and deformation of the oil shale stratum during in situ processing were studied. The results show that kerogen decomposition is a thermo-kinetically controlled mechanism. Both the gas injection velocity and burning temperature can enhance the kerogen decomposition and oil production, especially for the latter one. In addition, the stratum-deformation of oil shale should be considered for oil shale in situ conversion processing, especially for the long-term operational lifetime.

14.
J Inflamm Res ; 15: 2509-2521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479830

RESUMO

Purpose: This study aimed to evaluate the influence of hepatitis B virus (HBV) infection status on the initial metastatic pattern and prognosis in metastatic breast cancer (MBC). Methods: MBC patients admitted to Chongqing University Cancer Hospital between January 2011 and December 2019 were enrolled. The association of HBV infection status with clinicopathological features was analyzed. The impact of HBV infection status on initial metastatic pattern and survival was evaluated. Results: A total of 1124 patients with MBC, including 310 with de novo (cohort A) and 814 with relapsed metastatic disease (cohort B), were eligible for this study. Seropositive HBsAg was identified in 28 (9.0%) and 68 (8.4%) patients in cohort A and B, respectively. The clinicopathological features are similar between HBsAg-positive and HBsAg-negative patients. There was no significant association of HBV infection status with the rate of metastasis at each site in de novo and relapsed MBC. HBsAg-positive patients tended to have longer metastasis-free survival (MFS) and/or overall survival (OS) time, but it was not the independent prognostic factor. Conclusion: In conclusion, HBV infection status does not influence the initial metastatic pattern and the prognosis of MBC patients.

15.
Front Pharmacol ; 13: 770411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359846

RESUMO

Our objective was to explore the mechanism of essential oil that was extracted from Cinnamomum camphora chvar. Borneol (Borneol essential oil) for improving learning and memory impairment in mice. Brain tissue and plasma samples of a normal group, a model group, a Borneol essential oil group and a reference group were detected using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) in order to find differential metabolites and analyze metabolic pathways. Results showed that there were 11 different metabolites --including glycine and azelaic acid --in plasma samples, and that there were 26 different metabolites--including adenine and aspartic acid --in brain tissue samples. These metabolites are involved in phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, beta-alanine metabolism, glyoxylate acid and dicarboxylate metabolism, and aminoacyl-tRNA biosynthesis. Thus, Borneol essential oil may improve learning and memory impairment by regulating amino acid metabolism and/or neurotransmitter changes.

16.
J Exp Bot ; 73(8): 2698-2713, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-35137020

RESUMO

Phytosulfokine-α (PSK-α), a tyrosine-sulfated pentapeptide with the sequence YSO3IYSO3TQ, is widely distributed across the plant kingdom and plays multiple roles in plant growth, development, and immune response. Here, we report a novel type of phytosulfokine, PSK-δ, and its precursor proteins (MtPSKδ, LjPSKδ, and GmPSKδ1), specifically from legume species. The sequence YSO3IYSO3TN of sulfated PSK-δ peptide is different from PSK-α at the last amino acid. Expression pattern analysis revealed PSK-δ-encoding precursor genes to be expressed primarily in legume root nodules. Specifically, in Medicago truncatula, MtPSKδ expression was detected in root cortical cells undergoing nodule organogenesis, in nodule primordia and young nodules, and in the apical region of mature nodules. Accumulation of sulfated PSK-δ peptide in M. truncatula nodules was detected by LC/MS. Application of synthetic PSK-δ peptide significantly increased nodule number in legumes. Similarly, overexpression of MtPSKδ in transgenic M. truncatula markedly promoted symbiotic nodulation. This increase in nodule number was attributed to enhanced nodule organogenesis induced by PSK-δ. Additional genetic evidence from the MtPSKδ mutant and RNA interference assays suggested that the PSK-δ and PSK-α peptides function redundantly in regulating nodule organogenesis. These results suggest that PSK-δ, a legume-specific novel type of phytosulfokine, promotes symbiotic nodulation by enhancing nodule organogenesis.


Assuntos
Medicago truncatula , Proteínas de Plantas , Regulação da Expressão Gênica de Plantas , Medicago truncatula/metabolismo , Peptídeos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nodulação/genética , Nódulos Radiculares de Plantas/metabolismo , Simbiose/fisiologia
17.
ASN Neuro ; 14: 17590914211073276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023760

RESUMO

Long-term stable cell culture is a critical tool to better understand cell function. Most adherent cell culture models require a polymer substrate coating of poly-lysine or poly-ornithine for the cells to adhere and survive. However, polypeptide-based substrates are degraded by proteolysis and it remains a challenge to maintain healthy cell cultures for extended periods of time. Here, we report the development of an enhanced cell culture substrate based on a coating of dendritic polyglycerol amine (dPGA), a non-protein macromolecular biomimetic of poly-lysine, to promote the adhesion and survival of neurons in cell culture. We show that this new polymer coating provides enhanced survival, differentiation and long-term stability for cultures of primary neurons or neurons derived from human induced pluripotent stem cells (hiPSCs). Atomic force microscopy analysis provides evidence that greater nanoscale roughness contributes to the enhanced capacity of dPGA-coated surfaces to support cells in culture. We conclude that dPGA is a cytocompatible, functionally superior, easy to use, low cost and highly stable alternative to poly-cationic polymer cell culture substrate coatings such as poly-lysine and poly-ornithine. Summary statementHere, we describe a novel dendritic polyglycerol amine-based substrate coating, demonstrating superior performance compared to current polymer coatings for long-term culture of primary neurons and neurons derived from induced pluripotent stem cells.


Assuntos
Aminas , Células-Tronco Pluripotentes Induzidas , Técnicas de Cultura de Células , Diferenciação Celular , Glicerol , Humanos , Neurônios , Polímeros
18.
Environ Res ; 203: 111792, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333009

RESUMO

High-quality products in sustainable agriculture require both limited health risks and sufficient dietary nutrients. Phosphorus (P) as a finite and non-renewable resource is widely used in agriculture, usually exerting influence on the accumulation of heavy metals (HMs) in soil and crops. The present research explores, for the first time, the combined effects of long-term P fertilizer and repeated zinc (Zn) application in field on the human health risks and nutritional yield regarding trace elements in maize grain. A field experiment was conducted using maize with six P application rates (0, 12.5, 25, 50, 100, and 200 kg P ha-1) and two Zn application rates (0 and 11.4 kg Zn ha-1). The results showed that the concentrations of Zn, copper (Cu), and lead (Pb) in the maize grain were significantly affected by P application and can be further affected by Zn application. The concentrations of chromium (Cr) and arsenic (As) showed opposite tendency as affected by P fertilizer rates while did not affected by additional Zn application. Zn application decreased the cadmium (Cd) concentration at high P levels and Pb concentration at low P levels, particularly. No HMs contamination or direct health risk was found in maize grain after receiving long-term P and repeated Zn fertilizer. The threshold hazard quotient of an individual and all investigated HMs in this study were acceptable for human digestion of maize grain. While the carcinogenic risk of Cr was non-negligible in case of maize was taken as one of daily staple food for local residents. Combination use of P (25 kg ha-1) and Zn fertilizer on maize enhanced its nutritional supply ability regarding Zn and Cu, and simultaneously mitigated potential human health risks associated with Cd and Pb.


Assuntos
Metais Pesados , Poluentes do Solo , Agricultura , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Fósforo , Medição de Risco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Zea mays
19.
Front Surg ; 9: 1077826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36700015

RESUMO

Carotid artery stent implantation (CAS) plays an important role in preventing cerebral infarction associated with carotid stenosis. The postoperative complications of CAS include cerebral hyperperfusion syndrome (CHS), cerebral infarction, vascular injury, carotid sinus reaction, and stent restenosis. Hyperperfusion syndrome (CHS) is a serious complication that arises after the performance of carotid endarterectomy (CEA) or CAS and is characterized by high blood pressure, headache, epilepsy, and focal neurological deficit. Therefore, it is very important to evaluate and diagnose CHS. Cerebral infarction after CAS is often caused by distal embolism due to the shedding of microemboli. With the application of distal brain protection devices, the risk of distal embolism is significantly reduced. In this study, we report a rare case of hypoperfusion cerebral infarction after carotid artery stenting in a patient with severe carotid stenosis complicated with contralateral common carotid artery occlusion.

20.
Front Neurol ; 12: 630681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746885

RESUMO

Objectives: This present study aimed to examine the effects of adiponectin-transfected endothelial progenitor cells (LV-APN-EPCs) on cerebral ischemia-reperfusion injury in rats with type 2 diabetes mellitus (T2DM) and to explore the underlying mechanisms. Methods: Seventy male Sprague-Dawley rats with T2DM were randomly divided into sham, phosphate-buffered saline (PBS), LV-APN-EPCs, LV-EPCs, and EPCs groups. Transient middle cerebral artery occlusion (MCAO) was induced by the intraluminal suture method. After 1 h of reperfusion, the five interventions were performed by tail-vein injections. The modified neurological severity score (mNSS) was used to assess neurological function before and on days 1, 7, and 14 after MCAO. After 14 days, magnetic resonance imaging scanning, hematoxylin and eosin staining, terminal dUTP nick-end labeling staining, Western blotting analysis, cluster of differentiation (CD) 31 immunofluorescence, and enzyme-linked immunosorbent assay were used to evaluate infarct rate, morphological damage, cell apoptosis, and microvessel density. Results: Compared with PBS, LV-EPCs, and EPCs groups, the LV-APN-EPCs group showed significantly lower mNSS score, lower infarct rate, and less morphological damage (all P < 0.05). In addition, compared with other groups, the LV-APN-EPCs group had significantly increased levels of B cell lymphoma/leukemia-2 (Bcl-2) protein, CD31+ microvessels, endothelial nitric oxide synthase, and vascular endothelial growth factor, and decreased levels of Bcl-2-associated X protein and neuronal apoptosis in the peri-infarct cortex (all P < 0.05). Conclusion: These results suggest that LV-APN-EPCs exert protective effects against cerebral ischemia-reperfusion injury in T2DM rats by increasing angiogenesis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA