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1.
ACS Omega ; 9(21): 22754-22763, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38826549

RESUMO

Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.

2.
Pediatr Cardiol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880798

RESUMO

This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous atrial septal defect (ASD) closure in children. An analysis was conducted on clinical data from children undergoing TEE-guided (n = 168) and X-ray-guided (n = 139) percutaneous ASD closure. Demographic characteristics, technical indices, acute complications, follow-up outcomes, and costs were compared between the groups. The results are that TEE-guided closure demonstrated shorter surgical times (20.3 ± 7.6 min vs. 32.8 ± 7.9 min, P < 0.001) and lower procedural costs ($3093.3 ± 451.5 vs. $3589.1 ± 219.4, P < 0.001) compared to X-ray guidance. Initial successful closure rates were similar between the groups (TEE: 98.2%, XR: 97.1%, P = 0.691). TEE guidance also resulted in fewer acute complications and reduced radiation exposure. TEE-guided percutaneous ASD closure offers advantages in terms of shorter surgical times, lower procedural costs, and reduced radiation exposure compared to X-ray guidance. These findings support the preference for TEE guidance in pediatric ASD closure procedures, with potential implications for improving patient outcomes and reducing healthcare costs.

3.
Clin Neuroradiol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922421

RESUMO

PURPOSE: To observe the regulation of cerebral circulation in vivo based on image segmentation algorithms for deep learning in medical imaging to automatically detect and quantify the neonatal deep medullary veins (DMVs) on susceptibility weighted imaging (SWI) images. To evaluate early cerebral circulation self-rescue for neonates undergoing risk of cerebral hypoxia-ischaemia in vivo. METHODS: SWI images and clinical data of 317 neonates with or without risk of cerebral hypoxia-ischaemia were analyzed. Quantitative parameters showing the number, width, and curvature of DMVs were obtained using an image segmentation algorithm. RESULTS: The number of DMVs was greater in males than in females (p < 0.01), and in term than in preterm infants (p = 0.001). The width of DMVs was greater in term than in preterm infants (p < 0.01), in low-risk than in high-risk group (p < 0.01), and in neonates without intracranial extracerebral haemorrhage (ICECH) than with ICECH (p < 0.05). The curvature of DMVs was greater in term than in preterm infants (P < 0.05). The width of both bilateral thalamic veins and anterior caudate nucleus veins were positively correlated with the number of DMVs; the width of bilateral thalamic veins was positively correlated with the width of DMVs. CONCLUSION: The DMVs quantification based on image segmentation algorithm may provide more detailed and stable quantitative information in neonate. SWI vein quantification may be an observable indicator for in vivo assessment of cerebral circulation self-regulation in neonatal hypoxic-ischemic brain injury.

4.
EFORT Open Rev ; 9(6): 556-566, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828976

RESUMO

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

5.
EMBO Rep ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839944

RESUMO

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.

6.
World J Clin Cases ; 12(17): 3027-3034, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898832

RESUMO

BACKGROUND: Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed. AIM: To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function (CPF) and prognosis. METHODS: In total, 160 patients with CHF admitted between June 2022 and June 2023 were selected, including 75 receiving perindopril (control group) and 85 receiving Luhong Formula (research group). We conducted comparative analyses on the curative effects of traditional Chinese medicine (TCM) syndromes and cardiac function, CPF [oxygen consumption at the anaerobic threshold (VO2 AT) and at peak exercise (peak VO2)], echocardiographic indexes [left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), left ventricular ejection fraction (LVEF)], and prognosis [major adverse cardiovascular events (MACEs) at 6 months follow-up]. RESULTS: The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group. In addition, post-treatment VO2 AT, peak VO2, LVMI and LVEF in the research group were significantly higher, whereas LAVI was significantly lower, than those of the control group. Furthermore, fewer patients in the research group developed MACEs at the 6-month follow-up. CONCLUSION: Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF, specifically in enhancing CPF and prognosis.

7.
Sci Rep ; 14(1): 14721, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926428

RESUMO

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia-ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia-ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia-ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.


Assuntos
Hipóxia-Isquemia Encefálica , Hemorragias Intracranianas , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Feminino , Imageamento por Ressonância Magnética/métodos , Incidência , Masculino , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/complicações , Fatores de Risco
8.
Front Immunol ; 15: 1388109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799451

RESUMO

Background: The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment. Methods: We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test. Results: A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001). Conclusion: Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.


Assuntos
Dissecção Aórtica , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Fatores de Risco , Resultado do Tratamento , Biomarcadores/sangue , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/mortalidade , Estimativa de Kaplan-Meier , Doença Aguda , Período Pré-Operatório
9.
World J Clin Oncol ; 15(4): 531-539, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38689626

RESUMO

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

10.
Chemistry ; : e202401078, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752798

RESUMO

Hybridized local and charge-transfer (HLCT) with the utilization of both singlet and triplet excitons through the "hot excitons" channel have great application potential in highly efficient blue organic light-emitting diodes (OLEDs). The proportion of charge-transfer (CT) and locally excited (LE) components in the relevant singlet and triplet states makes a big difference for the high-lying reverse intersystem crossing process. Herein, three novel donor (D)-acceptor (A) type HLCT materials, 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-phenyl-1H-isochromen-1-one (pPh-7P), 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-7M), and 6-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-6M), were rationally designed and synthesized with diphenylamine derivative as donor and oxygen heterocyclic coumarin moiety as acceptors. The proportions of CT and LE components were fine controlled by changing the connection site of diphenylamine derivative at C6/C7-position and the substituent at C3-position of coumarin moiety. The HLCT characteristics of pPh-7P, pPh-7M, and pPh-6M were systematically demonstrated through photophysical properties and density functional theory calculations. The solution-processed doped OLEDs based on pPh-6M exhibited deep-blue electroluminescence with the maximum emission wavelength of 446 nm, maximum luminance of 8755 cd m-2, maximum current efficiency of 5.83 cd A-1, and maximum external quantum efficiency of 6.54 %. The results reveal that pPh-6M with dominant 1LE and 3CT components has better OLED performance.

11.
Nat Commun ; 15(1): 3884, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719909

RESUMO

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.


Assuntos
Antígeno B7-1 , Antígeno B7-H1 , Vesículas Extracelulares , Receptor de Morte Celular Programada 1 , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Humanos , Antígeno B7-1/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Camundongos , Linhagem Celular Tumoral , Feminino , Neoplasias/imunologia , Neoplasias/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Masculino , Microambiente Tumoral/imunologia
12.
Hortic Res ; 11(5): uhae073, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738212

RESUMO

The seasonal flowering Chinese Cymbidium produce an axillary floral meristem and require a dormancy period during cold conditions for flower development. However, the bud activation mechanism remains elusive. This study evaluates the multi-omics across six stages of flower development, along with functional analysis of core genes to decipher the innate mechanism of floral bud initiation and outgrowth in the Chinese orchid Cymbidium sinense. Transcriptome and proteome analyses identified 10 modules with essential roles in floral bud dormancy and activation. Gene clusters in the early stages of flower development were mainly related to flowering time regulation and meristem determination, while the late stages were correlated with hormone signaling pathways. The metabolome identified 69 potential hormones in which gibberellin (GA) and abscisic acid (ABA) were the main regulatory hubs, and GA4 and GA53 exhibited a reciprocal loop. Extraneous GA application caused rapid elongation of flower buds and promoted the expression of flower development genes. Contrarily, exogenous ABA application extended the dormancy process and ABA inhibitors induced dormancy release. Moreover, CsAPETALA1 (CsAP1) was identified as the potential target of ABA for floral bud activation. Transformation of CsAP1 in Arabidopsis and its transient overexpression in C. sinense protoplasts not only affected flowering time and floral organ morphogenesis in Arabidopsis but also orchestrated the expression of flowering and hormone regulatory genes. The presence of ABA response elements in the CsAP1 promoter, rapid downregulation of CsAP1 after exogenous ABA application, and the activation of the floral bud after ABA inhibitor treatment suggest that ABA can control bud outgrowth through CsAP1.

13.
Nat Commun ; 15(1): 4066, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744885

RESUMO

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.


Assuntos
Archaea , Genoma Arqueal , Fontes Termais , Metagenoma , Metagenômica , Filogenia , Fontes Termais/microbiologia , Archaea/genética , Archaea/classificação , China , Metagenômica/métodos , Biodiversidade , Concentração de Íons de Hidrogênio , Enxofre/metabolismo , Temperatura , Ecossistema
14.
Talanta ; 276: 126291, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38776774

RESUMO

Developing a Surface-enhanced Raman spectroscopy (SERS) method with excellent detecting ability, good recyclability and analyzing multiple pollutants rapidly are critical for evaluation of water quality in emergency pollution affairs. While constructing a multifunctional substrate with these characteristics to realize the application of SERS in water quality monitoring remains a challenge. In this work, a reusable Au@R-Fe3O4/g-C3N4 SERS substrate is prepared by loading Au nanoparticles (Au NPs) on Fe3O4 nanorings (R-Fe3O4) and the formed Au@R-Fe3O4 is further combined with g-C3N4 nanosheets through a simple electrostatic assembly method. The Au@R-Fe3O4/g-C3N4 nanocomposite presents multifunction of magnetic enrichment, SERS signal enhancement, multiple pollutants analyzing, and photocatalytic activity, which achieves quantitative detection of rhodamine B (RhB), tetracycline hydrochloride (TC), and 4-chlorophenol (4-CP), with detection limits of 5.30 × 10-9, 7.50 × 10-8, 7.69 × 10-8 mol/L, respectively. Furthermore, the recyclable detection capability of Au@R-Fe3O4/g-C3N4 for multi components is demonstrated by the strong SERS signal after 9 cycles of "detection-degradation" processes. Combined with good uniformity and stability, this SERS method based on Au@R-Fe3O4/g-C3N4 substrate provides a new strategy for the multi-pollutants detection and degradation in water environment.

15.
J Med Chem ; 67(11): 9054-9068, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38781403

RESUMO

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.


Assuntos
Apoptose , Fluoruracila , Gálio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Fluoruracila/farmacologia , Fluoruracila/química , Fluoruracila/uso terapêutico , Humanos , Gálio/química , Gálio/farmacologia , Animais , Porfirinas/farmacologia , Porfirinas/química , Porfirinas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Apoptose/efeitos dos fármacos , Células Hep G2 , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos Endogâmicos BALB C , Camundongos Nus
16.
Plant Physiol Biochem ; 211: 108518, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744085

RESUMO

The Chinese orchids symbolise nobility and gentility in China, and the variation of leaf color makes Cymbidium sinense more diversified and valuable. However, its color variations especially at the protein level still remain largely unexplored. In this study, the proteomics and phosphoproteomics of Cymbidium sinense leaf color variation mutants were studied. A total of 1059 differentially abundant proteins (DAPs) and 1127 differentially abundant phosphorylation sites belonging to 644 phosphoproteins (DAPPs) were identified in the yellow section of leaf variegation mutant of Cymbidium sinense (MY) compared with the green section (MG). Moreover, 349 co-expressing proteins were found in both omics' datasets, while only 26 proteins showed the same expression patterns in the two omics. The interaction network analysis of kinases and phosphatases showed that DAPs and DAPPs in photosynthesis, response to hormones, pigment metabolic process, phosphorylation, glucose metabolic process, and dephosphorylation might contribute to leaf color variation. The abundance of 28 Hsps and 28 phosphorylation sites belonging to 10 Hsps showed significant differences between MG and MY. CsHsp70 was selected to explore the function in Cymbidium sinense leaf variegation. The results showed CsHsp70 is essential for maintaining photosynthetic pigment content and the 399S phosphorylation site is crucial to the function of CsHsp70. Collectively, our findings construct a comprehensive coverage of protein and protein phosphorylation in leaf variegation of C. sinense, providing valuable insights into its formation mechanisms.


Assuntos
Clorofila , Orchidaceae , Proteínas de Plantas , Orchidaceae/metabolismo , Orchidaceae/genética , Clorofila/metabolismo , Fosforilação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteômica
17.
Nature ; 629(8014): 1158-1164, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750355

RESUMO

Plant pattern-recognition receptors perceive microorganism-associated molecular patterns to activate immune signalling1,2. Activation of the pattern-recognition receptor kinase CERK1 is essential for immunity, but tight inhibition of receptor kinases in the absence of pathogen is crucial to prevent autoimmunity3,4. Here we find that the U-box ubiquitin E3 ligase OsCIE1 acts as a molecular brake to inhibit OsCERK1 in rice. During homeostasis, OsCIE1 ubiquitinates OsCERK1, reducing its kinase activity. In the presence of the microorganism-associated molecular pattern chitin, active OsCERK1 phosphorylates OsCIE1 and blocks its E3 ligase activity, thus releasing the brake and promoting immunity. Phosphorylation of a serine within the U-box of OsCIE1 prevents its interaction with E2 ubiquitin-conjugating enzymes and serves as a phosphorylation switch. This phosphorylation site is conserved in E3 ligases from plants to animals. Our work identifies a ligand-released brake that enables dynamic immune regulation.


Assuntos
Oryza , Imunidade Vegetal , Proteínas de Plantas , Ubiquitina , Animais , Quitina/metabolismo , Homeostase , Ligantes , Oryza/enzimologia , Oryza/imunologia , Oryza/metabolismo , Oryza/microbiologia , Fosforilação , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Fosfosserina/metabolismo , Sequência Conservada
18.
J Hematol Oncol ; 17(1): 36, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783389

RESUMO

Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening. In models of glioblastoma (GBM) and triple-negative breast cancer (TNBC), we showed that the combination of OV and a PARP inhibitor (PARPi) exhibited superior efficacy compared to either monotherapy. Additionally, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy sensitized TNBC to immune checkpoint blockade, and the incorporation of an immune checkpoint inhibitor (ICI) further increased the survival rate of tumor-bearing mice. The combination of PARPi and ICI synergistically enhanced the ability of OV to establish durable tumor-specific immune responses. Our study effectively overcomes the inherent limitations of OV therapy, providing valuable insights for the clinical treatment of TNBC, GBM, and other malignancies.


Assuntos
Terapia Viral Oncolítica , Terapia Viral Oncolítica/métodos , Animais , Humanos , Camundongos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Glioblastoma/terapia , Glioblastoma/genética , Vírus Oncolíticos/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/genética , Feminino , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Herpesvirus Humano 1/genética , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , MicroRNAs/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Sistemas CRISPR-Cas
19.
Aging (Albany NY) ; 16(7): 6334-6347, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38575308

RESUMO

BACKGROUND: The purpose of this study is to observe LP45 (Lactobacillus plantarum 45) to investigate the mechanism by which LP45 attenuates oxidative stress-induced damage and regulates the osteoblast-osteoclast balance. MATERIALS AND METHODS: The oxidative stress level and osteoblast- and osteoclast-related proteins were detected by immunofluorescence staining, Western blotting, ROS fluorescent probe and ELISA. Osteoblast cell proliferation capacity was determined by the CCK-8 assay. X-ray observation and HE staining were used to detect the effect of LP45 on osteoporosis. RESULTS: The expression level of SHP2 and Src was significantly increased, and the expression levels of NOX4, P22, P47, IL-1ß, NLRP3, IRF3, RANK, ß-catenin and INF-ß were inhibited in LP45 group and LPS + LP45 group as compared to those in LPS group. Compared with that in LPS group, the concentration of SOD was increased and the concentration of MDA was decreased in LPS + LP45 group. The protein expressions of OPG, RANKL, RUNX3, RANK and ß-catenin in LP45 group and LPS + LP45 group increased. The protein expressions of NF-κB, CREB and AP-1 in LP45 group and LPS + LP45 group decreased significantly. The results were also confirmed by immunofluorescence staining and ROS fluorescent probe. X-ray observation and HE staining showed that LP45 could inhibit the progression of osteoporosis. CONCLUSION: LP45 can exert its antioxidant effect by inhibiting the production of oxidative stress to activate the SHP2 signaling pathway, thus promoting osteoblast differentiation and repressing osteoclast formation to maintain bone homeostasis and improve bone metabolism.


Assuntos
Diferenciação Celular , Lactobacillus plantarum , Osteoblastos , Osteoclastos , Estresse Oxidativo , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Osteoblastos/metabolismo , Animais , Osteoclastos/metabolismo , Camundongos , Osteoporose/metabolismo , Transdução de Sinais , Proliferação de Células
20.
Front Immunol ; 15: 1366489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660314

RESUMO

Cancer ranks among the foremost causes of mortality worldwide, posing a significant threat to human lives. The advent of tumor immunotherapy has substantially transformed the therapeutic landscape for numerous advanced malignancies, notably non-small cell lung cancer and melanoma. However, as immune checkpoint inhibitors (ICIs) are increasingly applied in clinical settings, a spectrum of undesired reactions, termed immune-related adverse events (irAEs), has emerged. These adverse reactions are associated with immunotherapy and can result in varying degrees of harm to the human body. Among these reactions, Immune checkpoint inhibitor-induced colitis (ICIIC) stands out as one of the most prevalent clinical adverse events. In contemporary times, traditional Chinese medicine (TCM) has demonstrated remarkable efficacy in addressing various maladies. Consequently, investigating the potential application and mechanisms of Chinese medicine in countering immune checkpoint inhibitor-induced colitis assumes significant importance in the treatment of this condition.


Assuntos
Colite , Inibidores de Checkpoint Imunológico , Medicina Tradicional Chinesa , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Colite/induzido quimicamente , Colite/imunologia , Colite/terapia , Animais , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos
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