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1.
J Pathol ; 263(2): 203-216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38551071

RESUMO

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.


Assuntos
Cistite Intersticial , Receptor 3 Toll-Like , Urotélio , Animais , Feminino , Humanos , Camundongos , Diferenciação Celular , Proliferação de Células , Cistite Intersticial/patologia , Cistite Intersticial/metabolismo , Cistite Intersticial/genética , Camundongos Endogâmicos C57BL , Transdução de Sinais , Análise de Célula Única , Receptor 3 Toll-Like/metabolismo , Receptor 3 Toll-Like/genética , Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Urotélio/patologia , Urotélio/metabolismo
2.
Am J Pathol ; 193(7): 899-912, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37068638

RESUMO

The accuracy and timeliness of the pathologic diagnosis of soft tissue tumors (STTs) critically affect treatment decision and patient prognosis. Thus, it is crucial to make a preliminary judgement on whether the tumor is benign or malignant with hematoxylin and eosin-stained images. A deep learning-based system, Soft Tissue Tumor Box (STT-BOX), is presented herein, with only hematoxylin and eosin images for malignant STT identification from benign STTs with histopathologic similarity. STT-BOX assumed gastrointestinal stromal tumor as a baseline for malignant STT evaluation, and distinguished gastrointestinal stromal tumor from leiomyoma and schwannoma with 100% area under the curve in patients from three hospitals, which achieved higher accuracy than the interpretation of experienced pathologists. Particularly, this system performed well on six common types of malignant STTs from The Cancer Genome Atlas data set, accurately highlighting the malignant mass lesion. STT-BOX was able to distinguish ovarian malignant sex-cord stromal tumors without any fine-tuning. This study included mesenchymal tumors that originated from the digestive system, bone and soft tissues, and reproductive system, where the high accuracy of migration verification may reveal the morphologic similarity of the nine types of malignant tumors. Further evaluation in a pan-STT setting would be potential and prospective, obviating the overuse of immunohistochemistry and molecular tests, and providing a practical basis for clinical treatment selection in a timely manner.


Assuntos
Aprendizado Profundo , Tumores do Estroma Gastrointestinal , Neoplasias Ovarianas , Neoplasias de Tecidos Moles , Feminino , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Amarelo de Eosina-(YS) , Hematoxilina , Estudos Prospectivos , Neoplasias de Tecidos Moles/diagnóstico
3.
New Phytol ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874377

RESUMO

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.

4.
Plant Physiol ; 194(1): 243-257, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37399189

RESUMO

Plant lignocellulosic biomass, i.e. secondary cell walls of plants, is a vital alternative source for bioenergy. However, the acetylation of xylan in secondary cell walls impedes the conversion of biomass to biofuels. Previous studies have shown that REDUCED WALL ACETYLATION (RWA) proteins are directly involved in the acetylation of xylan but the regulatory mechanism of RWAs is not fully understood. In this study, we demonstrate that overexpression of a Populus trichocarpa PtRWA-C gene increases the level of xylan acetylation and increases the lignin content and S/G ratio, ultimately yielding poplar woody biomass with reduced saccharification efficiency. Furthermore, through gene coexpression network and expression quantitative trait loci (eQTL) analysis, we found that PtRWA-C was regulated not only by the secondary cell wall hierarchical regulatory network but also by an AP2 family transcription factor HARDY (HRD). Specifically, HRD activates PtRWA-C expression by directly binding to the PtRWA-C promoter, which is also the cis-eQTL for PtRWA-C. Taken together, our findings provide insights into the functional roles of PtRWA-C in xylan acetylation and consequently saccharification and shed light on synthetic biology approaches to manipulate this gene and alter cell wall properties. These findings have substantial implications for genetic engineering of woody species, which could be used as a sustainable source of biofuels, valuable biochemicals, and biomaterials.


Assuntos
Populus , Populus/genética , Populus/metabolismo , Xilanos/metabolismo , Acetilação , Biomassa , Biocombustíveis/análise , Plantas/metabolismo , Parede Celular/metabolismo , Lignina/metabolismo
5.
Plant Cell Environ ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847345

RESUMO

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.

6.
Plant Cell Environ ; 47(4): 1363-1378, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221855

RESUMO

Eucalyptus is a widely planted hardwood tree species due to its fast growth, superior wood properties and adaptability. However, the post-transcriptional regulatory mechanisms controlling tissue development and stress responses in Eucalyptus remain poorly understood. In this study, we performed a comprehensive analysis of the gene expression profile and the alternative splicing (AS) landscape of E. grandis using strand-specific RNA-Seq, which encompassed 201 libraries including different organs, developmental stages, and environmental stresses. We identified 10 416 genes (33.49%) that underwent AS, and numerous differentially expressed and/or differential AS genes involved in critical biological processes, such as primary-to-secondary growth transition of stems, adventitious root formation, aging and responses to phosphorus- or boron-deficiency. Co-expression analysis of AS events and gene expression patterns highlighted the potential upstream regulatory role of AS events in multiple processes. Additionally, we highlighted the lignin biosynthetic pathway to showcase the potential regulatory functions of AS events in the KNAT3 and IRL3 genes within this pathway. Our high-quality expression atlas and AS landscape serve as valuable resources for unravelling the genetic control of woody plant development, long-term adaptation, and understanding transcriptional diversity in Eucalyptus. Researchers can conveniently access these resources through the interactive ePlant browser (https://bar.utoronto.ca/eplant_eucalyptus).


Assuntos
Eucalyptus , Genes de Plantas , Genes de Plantas/genética , Eucalyptus/fisiologia , Processamento Alternativo/genética , Madeira , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas
7.
Microb Pathog ; 192: 106723, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823465

RESUMO

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.


Assuntos
Enterotoxinas , Proteínas Hedgehog , Transdução de Sinais , Linfócitos T , Timo , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Feminino , Gravidez , Ratos , Timo/metabolismo , Timo/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Receptor Patched-1/metabolismo , Receptor Patched-1/genética , Receptor Smoothened/metabolismo , Receptor Smoothened/genética , Efeitos Tardios da Exposição Pré-Natal/imunologia , Diferenciação Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Masculino
8.
J Eukaryot Microbiol ; 71(2): e13012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37975433

RESUMO

To determine the infection status and assess the zoonotic potential of Blastocystis spp. in Hotan Black chickens in southern Xinjiang, China, fecal samples were collected from 617 chickens on 18 large-scale farms. The presence of Blastocystis spp. was determined using polymerase chain reaction based on the small subunit rRNA (SSU rRNA) locus. The results revealed an overall infection rate of 26.3% (162/617). Samples from Farm 1 in Luopu County showed the highest infection rate (76.3%, 29/38). The highest and lowest infection rates were detected in the <30-day (34.4%, 43/125) and > 90-day age groups (12.4%, 11/89), respectively. The infection rate decreased with increasing age. Statistical analysis showed significant differences in the infection rates of Blastocystis spp. among the different sampling sites (p < 0.05) and age groups (p < 0.05). Four Blastocystis spp. subtypes (ST6, ST7, ST10, and ST23) were identified. The infection rates of the zoonotic subtypes, ST6 and ST7, were 3.2% (20/617) and 22.2% (137/617), respectively. The presence of Blastocystis spp. and zoonotic subtypes provided evidence for the potential transmission of this pathogen between Hotan Black chickens and humans, especially in animal handlers in this area.


Assuntos
Infecções por Blastocystis , Blastocystis , Humanos , Animais , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/veterinária , Galinhas , Variação Genética , Reação em Cadeia da Polimerase , Fezes , Prevalência , Filogenia
9.
J Pineal Res ; 76(2): e12948, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488331

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.


Assuntos
Ferroptose , Melatonina , Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Melatonina/farmacologia , Receptor MT1 de Melatonina/metabolismo , Sirtuína 1/metabolismo , Neurônios Dopaminérgicos , Ferro/metabolismo
10.
Neurourol Urodyn ; 43(2): 382-389, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38078752

RESUMO

PURPOSE: To design a quick checklist for urodynamic study (UDS), aiming to reduce the occurrence of errors in the process, which may help to increase the quality of UDS. And further to analyze the effectiveness of this quick checklist for UDS quality control. METHODS: First, a quick checklist for uroflow study and pressure-flow study was developed, based on the International Continence Society-Good Urodynamic Practice standards, our previous studies, and recent literature, as well as expert suggestions. Then, patients who underwent UDS between January 2023 to February 2023 were randomly assigned to a study group or a control group. For the study group, the quick checklist was used throughout the UDS process, while the control group did not. The main artefacts were chosen to verify the effectiveness of the quick checklist for improving the UDS quality. RESULTS: The quick checklist comprised three subtypes: checklist for patients, checklist for environment and device, and checklist for UDS test process. 38 UDS traces per group were included. The incidence of missing the standard cough test decreased significantly from 18.4% to 0 (p = 0.012), with the checklist implementation. The baseline drift frequency rate also declined significantly from 39.5% to 5.3% (p < 0.05). Volume < 150 mL on uroflow study occurred in 68.4% of cases and its frequency rate decreased significantly with checklist implementation (p < 0.05). CONCLUSION: A quick checklist for quality control of UDS was developed. The quick checklist as a convenient, quick, and easy used urodynamic quality control method, may help to reduce the technical artefacts and improve fundamental urodynamic quality control. Future research with a larger sample size is needed to confirm the effectiveness of the checklist.


Assuntos
Lista de Checagem , Urodinâmica , Humanos , Estudos Prospectivos , Controle de Qualidade , Padrões de Referência
11.
BMC Public Health ; 24(1): 1660, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907219

RESUMO

BACKGROUND: Comprehensive data has shown that adolescents often suffer from depression, anxiety, and low self-esteem, and are in a particularly fragile stage of psychological, physiological, and social development. Left-behind children in particular tend to have significantly higher, state anxiety and depression compared to non-left-behind children. The Depression, Anxiety, and Stress Scale (DASS-21) is an effective tool for evaluating depression, anxiety, and stress, and is used to measure levels of depression, anxiety, and stress in groups from a variety of backgrounds. The purpose of this study was to determine the effectiveness, reliability, and measurement invariance of the DASS-21 in Chinese left-behind children. METHOD: The test and re-test method was used (N = 676), and the exploratory structural equation model (Mplus v.8.3) used to verify basic measurement models. For measurement invariance, the configural, weak, strong, and strict models were tested. The reliability of the DASS-21 was also tested using the collected data. RESULTS: Analysis results showed that the DASS-21 had a stable three-factor structure in the sample of left-behind children in China. The measurement invariance test showed that gender and time not only had strong invariance, but also strict invariance. The results of cross left and non-left invariance indicated a lack of strict invariance. Finally, the McDonald's omega coefficient of the DASS-21 total scale was 0.864, and the internal consistency of each subscale was also good. CONCLUSIONS: The DASS-21 is shown to be an effective and reliable tool for measuring depression, anxiety and stress in Chinese left-behind children.


Assuntos
Ansiedade , Depressão , Separação da Família , Estresse Psicológico , Adolescente , Criança , Feminino , Humanos , Masculino , Ansiedade/diagnóstico , China , Depressão/diagnóstico , Depressão/psicologia , População do Leste Asiático , Análise Fatorial , Análise de Classes Latentes , Escalas de Graduação Psiquiátrica/normas , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/diagnóstico , Migrantes/psicologia , Migrantes/estatística & dados numéricos
12.
J Am Chem Soc ; 145(32): 17700-17709, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37527512

RESUMO

In photoelectrochemical cells (PECs) the photon-to-current conversion efficiency is often governed by carrier transport. Most metal oxides used in PECs exhibit thermally activated transport due to charge localization via the formation of polarons or the interaction with defects. This impacts catalysis by restricting the charge accumulation and extraction. To overcome this transport bottleneck nanostructuring, selective doping and photothermal treatments have been employed. Here we demonstrate an alternative approach capable of directly activating localized carriers in bismuth vanadate (BiVO4). We show that IR photons can optically excite localized charges, modulate their kinetics, and enhance the PEC current. Moreover, we track carriers bound to oxygen vacancies and expose their ∼10 ns charge localization, followed by ∼60 µs transport-assisted trapping. Critically, we demonstrate that localization is strongly dependent on the electric field within the device. While optical modulation has still a limited impact on overall PEC performance, we argue it offers a path to control devices on demand and uncover defect-related photophysics.

13.
New Phytol ; 238(4): 1479-1497, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36797656

RESUMO

The acquisition of dormancy capabilities has enabled plants to survive in adverse terrestrial environmental conditions. Dormancy accumulation and release is coupled with light signaling, which is well studied in Arabidopsis, but it is unclear in the distant nonvascular relative. We study the characteristics and function on dormancy regulation of a blue light receptor cryptochrome in Marchantia polymorpha (MpCRY). Here, we identified MpCRY via bioinformatics and mutant complement analysis. The biochemical characteristics were assessed by multiple protein-binding assays. The function of MpCRY in gemma dormancy was clarified by overexpression and mutation of MpCRY, and its mechanism was analyzed via RNA sequencing and quantitative PCR analyses associated with hormone treatment. We found that the unique MpCRY protein in M. polymorpha undergoes both blue light-promoted interaction with itself (self-interaction) and blue light-dependent phosphorylation. MpCRY has the specific characteristics of blue light-induced nuclear localization and degradation. We further demonstrated that MpCRY transcriptionally represses abscisic acid (ABA) signaling-related gene expression to suppress gemma dormancy, which is dependent on blue light signaling. Our findings indicate that MpCRY possesses specific biochemical and molecular characteristics, and modulates ABA signaling under blue light conditions to regulate gemma dormancy in M. polymorpha.


Assuntos
Arabidopsis , Marchantia , Marchantia/metabolismo , Criptocromos/genética , Criptocromos/metabolismo , Plantas/metabolismo , Luz , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo
14.
Ann Hematol ; 102(4): 907-916, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36757444

RESUMO

The rate of intensive care unit (ICU) mortality in patients with hematologic malignancies is high. The risk factors for this were inconsistent across several previous studies, and there is currently no accepted consensus around risk factors for these patients. We aimed to identify which prognostic factors were associated with ICU mortality in critically ill patients with hematologic malignancies, nearly half of which were allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. In addition, we aimed to compare the characteristics and clinical outcomes of patients with and without allogenic allo-HSCT. In total, 217 patients with hematologic malignancies were enrolled consecutive, 119 (54.8%) of whom underwent HSCT (allo-HSCT: n = 115). All survivors were followed up with until August 1, 2022. The rate of ICU mortality in this cohort was 54.4%: 55.5 and 53.1% for the patients with and without HSCT, respectively (p = 0.724). The probabilities of survival after ICU admission were also comparable between the patients who had allo-HSCT and those who did not. A multivariable analysis revealed that cerebrovascular disease, hyperlactic acidemia on the day of ICU admission, lower platelet count, use of vasoactive drugs, and absence of noninvasive ventilation on the day of ICU admission were independent risk factors for ICU mortality. For patients with three to five of these risk factors, the rate of ICU mortality was as high as 84.6%, which was significantly higher than that of other patients. In this study, the ICU mortality rate in patients with hematologic malignancies was still high, particularly for those with multiple risk factors. However, allo-HSCT was not found to be a risk factor for ICU mortality.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Prognóstico , Estudos Retrospectivos , Unidades de Terapia Intensiva , Transplante Homólogo , Fatores de Risco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
15.
Inflamm Res ; 72(3): 443-462, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36598534

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process. OBJECTIVES: Further studies are needed to determine how α-syn works in microglia. METHODS: A keyword-based search was performed using the PubMed database for published articles. CONCLUSION: In this review, we discuss the interaction between microglia and α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Autofagia , Inflamassomos/metabolismo , Microglia/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neuroinflamatórias , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fagocitose
16.
J Integr Plant Biol ; 65(5): 1134-1146, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36647609

RESUMO

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.


Assuntos
Lignina , Populus , Lignina/metabolismo , Populus/metabolismo , Xilema/metabolismo , Madeira/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Diferenciação Celular , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo
17.
Int Ophthalmol ; 43(4): 1175-1184, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36112256

RESUMO

PURPOSE: Evaluate the efficacy and safety of LipiFlow® thermal pulsation treatment system compared with lid massage combined warm compress in Chinese patients with meibomian gland dysfunction (MGD). METHODS: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow® thermal pulsation system treatment. In warm compress group, patients (n = 50 eyes) underwent warm compress daily for two weeks after an initial manual lid massage. Patients' symptoms were evaluated using Standard Patient Evaluation for Eye Dryness (SPEED) questionnaire. Safety parameters included best-corrected visual acuity (BCVA), intraocular pressure (IOP) and objective parameters including meibomian glands yielding lipid secretion (MGYLS) number, meibomian glands secretion (MGS) score, lipid layer thickness (LLT), tear-film breakup time (TBUT), corneal fluorescein staining (CFS) were measured and presented from baseline and to 3 months post-treatment. RESULTS: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number. CONCLUSION: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months.


Assuntos
Síndromes do Olho Seco , Doenças Palpebrais , Hipertermia Induzida , Disfunção da Glândula Tarsal , Humanos , Disfunção da Glândula Tarsal/terapia , Doenças Palpebrais/terapia , Estudos Prospectivos , Glândulas Tarsais , Lágrimas , Síndromes do Olho Seco/terapia , Lipídeos
18.
Planta ; 255(5): 101, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397691

RESUMO

MAIN CONCLUSION: PdeHCA2 regulates the transition from primary to secondary growth, plant architecture, and affects photosynthesis by targeting PdeBRC1 and controlling the anatomy of the mesophyll, and intercellular space, respectively. Branching, secondary growth, and photosynthesis are vital developmental processes of woody plants that determine plant architecture and timber yield. However, the mechanisms underlying these processes are unknown. Here, we report that the Populus transcription factor High Cambium Activity 2 (PdeHCA2) plays a role in the transition from primary to secondary growth, vascular development, and branching. In Populus, PdeHCA2 is expressed in undifferentiated provascular cells during primary growth, in phloem cells during secondary growth, and in leaf veins, which is different from the expression pattern of its homolog in Arabidopsis. Overexpression of PdeHCA2 has pleiotropic effects on shoot and leaf development; overexpression lines showed delayed growth of shoots and leaves, reduced photosynthesis, and abnormal shoot branching. In addition, auxin-, cytokinin-, and photosynthesis-related genes were differentially regulated in these lines. Electrophoretic mobility shift assays and transcriptome analysis indicated that PdeHCA2 directly up-regulates the expression of BRANCHED1 and the MADS-box gene PdeAGL9, which regulate plant architecture, by binding to cis-elements in the promoters of these genes. Taken together, our findings suggest that HCA2 regulates several processes in woody plants including vascular development, photosynthesis, and branching by affecting the proliferation and differentiation of parenchyma cells.


Assuntos
Arabidopsis , Populus , Arabidopsis/metabolismo , Biomassa , Câmbio , Regulação da Expressão Gênica de Plantas , Fotossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Populus/metabolismo
19.
J Exp Bot ; 73(22): 7298-7311, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36001042

RESUMO

Adventitious root (AR) development is an extremely complex biological process that is affected by many intrinsic factors and extrinsic stimuli. Some WUSCHEL-related homeobox (WOX) transcription factors have been reported to play important roles in AR development, but their functional relationships with auxin signaling are poorly understood, especially the developmental plasticity of roots in response to adversity stress. Here, we identified that the WOX11/12a-SMALL AUXIN UP RNA36 (SAUR36) module mediates AR development through the auxin pathway in poplar, as well as under salt stress. PagWOX11/12a displayed inducible expression during AR development, and overexpression of PagWOX11/12a significantly promoted AR development and increased salt tolerance in poplar, whereas dominant repression of PagWOX11/12a produced the opposite phenotype. PagWOX11/12a proteins directly bind to the SAUR36 promoter to regulate SAUR36 transcription, and this binding was enhanced during salt stress. Genetic modification of PagWOX11/12a-PagSAUR36 expression revealed that the PagWOX11/12a-PagSAUR36 module is crucial for controlling AR development via the auxin pathway. Overall, our results indicate that a novel WOX11-SAUR-auxin signaling regulatory module is required for AR development in poplar. These findings provide key insights and a better understanding of the involvement of WOX11 in root developmental plasticity in saline environments.

20.
Xenobiotica ; 52(6): 625-632, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36102168

RESUMO

Cadmium (Cd) is a toxic element, which is associated with preeclampsia (PE).We treated pregnant rats with cadmium chloride from gestational days (GDs) 9-12 to introduce the PE-like animal model. Maternal systolic blood pressures (SBPs) and body weights were measured on GDs 0, 5, 10, 15, and 20. Foetuses were delivered by Caesarean section on GD20. Then, the dams were sacrificed and the specimens were obtained. The morphological analysis of the placentae was carried out by haematoxylin and eosin staining examination and immunohistochemistry assay.Our study showed that Cd-treated rats developed PE-like phenotypes, such as hypertension, albuminuria, and foetal growth restriction. Moreover, Cd-injected rats displayed abnormal placental angiogenesis and lower progesterone (P4) levels. We further demonstrated that Cd also inhibited the mRNA and protein expressions of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1), and 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1), which are involved in P4 synthesis in the rat placenta.Our study demonstrates that maternal Cd exposure disrupts the local synthesis of P4 in the placenta, which contributes to the onset of PE in pregnant rats. Supplementing P4 at the early gestational stage may be a promising therapeutic strategy to prevent PE, which requires further investigation.


Assuntos
Placenta , Pré-Eclâmpsia , Animais , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Cesárea , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Feminino , Humanos , Fenótipo , Placenta/química , Placenta/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/metabolismo , Gravidez , Progesterona , RNA Mensageiro/metabolismo , Ratos
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