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1.
Cell ; 187(16): 4261-4271.e17, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38964329

RESUMO

The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.


Assuntos
Serina Endopeptidases , Glicoproteína da Espícula de Coronavírus , Internalização do Vírus , Humanos , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Polissacarídeos/metabolismo , Polissacarídeos/química , Células HEK293 , Ligação Proteica , Receptores Virais/metabolismo , Receptores Virais/química , Coronavirus/metabolismo , Modelos Moleculares
2.
Plant J ; 119(2): 1014-1029, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38805573

RESUMO

Cassava, a pivotal tropical crop, exhibits rapid growth and possesses a substantial biomass. Its stem is rich in cellulose and serves as a crucial carbohydrate storage organ. The height and strength of stems restrict the mechanised operation and propagation of cassava. In this study, the triple helix transcription factor MeGT2.6 was identified through yeast one-hybrid assay using MeCesA1pro as bait, which is critical for cellulose synthesis. Over-expression and loss-of-function lines were generated, and results revealed that MeGT2.6 could promote a significant increase in the plant height, stem diameter, cell size and thickness of SCW of cassava plant. Specifically, MeGT2.6 upregulated the transcription activity of MeGA20ox1 and downregulated the expression level of MeGA2ox1, thereby enhancing the content of active GA3, resulting in a large cell size, high plant height and long stem diameter in cassava. Moreover, MeGT2.6 upregulated the transcription activity of MeCesA1, which promoted the synthesis of cellulose and hemicellulose and produced a thick secondary cell wall. Finally, MeGT2.6 could help supply additional substrates for the synthesis of cellulose and hemicellulose by upregulating the invertase genes (MeNINV1/6). Thus, MeGT2.6 was found to be a multiple regulator; it was involved in GA metabolism and sucrose decomposition and the synthesis of cellulose and hemicellulose.


Assuntos
Celulose , Regulação da Expressão Gênica de Plantas , Giberelinas , Manihot , Proteínas de Plantas , Manihot/genética , Manihot/metabolismo , Celulose/metabolismo , Celulose/biossíntese , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Giberelinas/metabolismo , Parede Celular/metabolismo , Crescimento Celular , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Caules de Planta/genética , Caules de Planta/metabolismo , Caules de Planta/crescimento & desenvolvimento , Polissacarídeos/metabolismo
3.
Mol Cancer ; 23(1): 125, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849860

RESUMO

BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.


Assuntos
Progressão da Doença , Exossomos , Regulação Neoplásica da Expressão Gênica , Glucose , RNA Circular , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Exossomos/metabolismo , RNA Circular/genética , Glucose/metabolismo , Camundongos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Animais , Prognóstico , Glicólise , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Reprogramação Metabólica , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização Intracelular
4.
Mol Cancer ; 23(1): 137, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970074

RESUMO

BACKGROUND: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. METHODS: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. RESULTS: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). CONCLUSIONS: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.


Assuntos
Carcinoma Hepatocelular , Quimiocina CCL2 , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Proteínas Serina-Treonina Quinases , Microambiente Tumoral , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Humanos , Animais , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Quimiocina CCL2/metabolismo , Linhagem Celular Tumoral , Tolerância a Radiação , Prognóstico , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , MicroRNAs/genética
5.
J Gene Med ; 26(7): e3715, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38962887

RESUMO

BACKGROUND: The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single-cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue. METHODS: We applied scRNA-sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein-protein interaction networks were constructed to identify crucial genes and pathways. RESULTS: Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level. CONCLUSIONS: Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.


Assuntos
Doença de Crohn , Análise de Célula Única , Ustekinumab , Doença de Crohn/genética , Doença de Crohn/tratamento farmacológico , Humanos , Ustekinumab/uso terapêutico , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas , Fibroblastos/metabolismo , Biomarcadores , Feminino , Transcriptoma , Adulto , Masculino , Linfócitos T/metabolismo , Linfócitos T/imunologia , Resultado do Tratamento , Análise de Sequência de RNA/métodos , Redes Reguladoras de Genes
6.
Toxicol Appl Pharmacol ; 486: 116947, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688426

RESUMO

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.


Assuntos
Apoptose , Cisplatino , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Células Ciliadas Auditivas , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Cisplatino/toxicidade , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Apoptose/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Linhagem Celular , Antineoplásicos/toxicidade , Masculino , Ototoxicidade/prevenção & controle
7.
Haematologica ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450521

RESUMO

Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.

8.
Brain Behav Immun ; 119: 607-620, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663772

RESUMO

The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines-including IL-6, IL-1ß, and TNF-α-in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy's beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy's protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities.


Assuntos
Ansiedade , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Vagotomia , Nervo Vago , Ácido gama-Aminobutírico , Animais , Ansiedade/metabolismo , Camundongos , Nervo Vago/metabolismo , Masculino , Ácido gama-Aminobutírico/metabolismo , Salmonella typhimurium , Citocinas/metabolismo , Eixo Encéfalo-Intestino , Encéfalo/metabolismo , Infecções por Salmonella/metabolismo , Comportamento Animal , Hipocampo/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Inflamação/metabolismo , Tonsila do Cerebelo/metabolismo
9.
Kidney Blood Press Res ; 49(1): 100-113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38237563

RESUMO

INTRODUCTION: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. METHODS: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. RESULTS: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = -0.374) and 6-min walk distance (r = -0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. CONCLUSION: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.


Assuntos
Síndrome Cardiorrenal , Insuficiência Cardíaca , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Doença Crônica , Peptídeo Natriurético Encefálico/sangue , Taxa de Filtração Glomerular , Células Endoteliais/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/farmacologia , Relevância Clínica
10.
Acta Pharmacol Sin ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811774

RESUMO

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise, in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex (mPFC). In particular, exercise was proposed to modulate the phosphorylation of Nogo-A protein, which drives the ras homolog family member A (RhoA)/ Rho-associated coiled-coil-containing protein kinases 1(ROCK1) signaling cascade. Further mechanistic studies found that liver-derived kynurenic acid (KYNA) can affect the kynurenine metabolism within the mPFC, to modulate this RhoA/ROCK1 pathway for conferring stress resilience. In sum, we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC, and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

11.
Biosci Biotechnol Biochem ; 88(3): 283-293, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38115610

RESUMO

Cytochrome P450s represent one of the largest protein families across all domains of life. In plants, biotic stress can regulate the expression of some P450 genes. However, the CYPome (cytochrome P450 complement) in Solanum tuberosum and its response to Phytophthora infestans infection remains unrevealed. In this study, 488 P450 genes were identified from potato genome, which can be divided into 41 families and 57 subfamilies. Responding to the infection of P. infestans, 375 potato P450 genes were expressed in late blight resistant or susceptible cultivars. A total of 14 P450 genes were identified as resistant related candidates, and 81 P450 genes were identified as late blight responsive candidates. Several phytohormone biosynthesis, brassinosteroid biosynthesis, and phenylpropanoid biosynthesis involved P450 genes were differentially expressed during the potato-pathogen interactions. This study firstly reported the CYPome in S. tuberosum, and characterized the expression patterns of these P450 genes during the infection of P. infestans.


Assuntos
Phytophthora infestans , Solanum tuberosum , Phytophthora infestans/genética , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Genoma , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Doenças das Plantas/genética
12.
BMC Anesthesiol ; 24(1): 278, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123151

RESUMO

BACKGROUND: Dexmedetomidine is a selective α2 receptor agonist with sedative, analgesic, anxiolytic, and anti-sympathetic effects. Dexmedetomidine is widely used for various surgical procedures performed under general anaesthesia and sedation in the intensive care unit. Dexmedetomidine was known to relieve or improve the symptoms of delirium. Schizophrenia is a common psychiatric disease, and the number of surgical patients with schizophrenia is increasing gradually. Dexmedetomidine-induced delirium in patients with schizophrenia is a particular case. CASE PRESENTATION: This patient was a 75-year-old woman (height: 156 cm; weight: 60 kg) with a 5-year history of schizophrenia. Her schizophrenia was well controlled with medications. She was scheduled for open reduction and internal fixation for a patellar fracture. Spinal anaesthesia was administered for surgery, and dexmedetomidine was administered intravenously to maintain sedation. The patient became delirious half an hour after the surgery began. The intravenous infusion of dexmedetomidine was discontinued immediately, intravenous propofol was subsequently administered, and the patient stopped experiencing dysphoria and fell asleep. After surgery, the patient stopped using propofol and recovered smoothly. She was transferred back to the general ward and was discharged from the hospital without any abnormal conditions on the 9th day after surgery. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with schizophrenia who developed delirium during the infusion of a normal dose of dexmedetomidine without an intravenous injection of any other sedative. The exact mechanism causing dexmedetomidine-induced delirium remains unclear, and this adverse reaction is rare and easy to ignore. Clinicians and pharmacists should be vigilant in identifying this condition.


Assuntos
Dexmedetomidina , Hipnóticos e Sedativos , Esquizofrenia , Humanos , Dexmedetomidina/efeitos adversos , Dexmedetomidina/administração & dosagem , Feminino , Idoso , Esquizofrenia/tratamento farmacológico , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Delírio/induzido quimicamente , Propofol/efeitos adversos , Propofol/administração & dosagem
13.
Orthod Craniofac Res ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967085

RESUMO

BACKGROUND: To establish the automatic soft-tissue analysis model based on deep learning that performs landmark detection and measurement calculations on orthodontic facial photographs to achieve a more comprehensive quantitative evaluation of soft tissues. METHODS: A total of 578 frontal photographs and 450 lateral photographs of orthodontic patients were collected to construct datasets. All images were manually annotated by two orthodontists with 43 frontal-image landmarks and 17 lateral-image landmarks. Automatic landmark detection models were established, which consisted of a high-resolution network, a feature fusion module based on depthwise separable convolution, and a prediction model based on pixel shuffle. Ten measurements for frontal images and eight measurements for lateral images were defined. Test sets were used to evaluate the model performance, respectively. The mean radial error of landmarks and measurement error were calculated and statistically analysed to evaluate their reliability. RESULTS: The mean radial error was 14.44 ± 17.20 pixels for the landmarks in the frontal images and 13.48 ± 17.12 pixels for the landmarks in the lateral images. There was no statistically significant difference between the model prediction and manual annotation measurements except for the mid facial-lower facial height index. A total of 14 measurements had a high consistency. CONCLUSION: Based on deep learning, we established automatic soft-tissue analysis models for orthodontic facial photographs that can automatically detect 43 frontal-image landmarks and 17 lateral-image landmarks while performing comprehensive soft-tissue measurements. The models can assist orthodontists in efficient and accurate quantitative soft-tissue evaluation for clinical application.

14.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39062957

RESUMO

The AT-hook motif nuclear-localized (AHL) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis-acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Manihot , Reguladores de Crescimento de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Estresse Fisiológico , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico/genética , Manihot/genética , Manihot/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Secas , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Acetatos/farmacologia
15.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731930

RESUMO

Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the MeSSIII-1 gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the MeSSIII-1 gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots. MeSSIII-1 expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava. MeSSIII-1 expression patterns were further confirmed in proMeSSIII-1 transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp MeSSIII-1 promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the MeSSIII-1 gene and for further in-depth exploration of the regulatory network of its internal functional elements.


Assuntos
Regulação da Expressão Gênica de Plantas , Manihot , Proteínas de Plantas , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Manihot/genética , Manihot/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Sintase do Amido/genética , Sintase do Amido/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Etilenos/metabolismo
16.
J Sci Food Agric ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822620

RESUMO

BACKGROUND: Java tea is widely consumed and has multiple health effects. This study established a steam explosion (SE) pretreatment method to prepare Java tea-leaf powders. The physicochemical, functional properties, phenolic extraction, and antioxidant activity of Java tea-leaf powders produced by simple and SE-assisted milling methods were investigated. RESULTS: In comparison with simple milling, SE pretreatment broke the cell wall effectively and reduced the particle size of Java tea-leaf powders. Steam explosion-treated powders showed higher values for sensory signals, bulk and tap density, and for the water solubility index. After SE treatment, the adsorption capacities to glucose, soybean oil, and cholesterol of leaf powders were increased by up to 55, 95, and 80% respectively. The extracts from SE-treated powders also showed higher total polyphenol content and antioxidant activity. CONCLUSION: Steam explosion treatment is helpful for the improvement of functional properties and antioxidant activity, which can benefit the development and application of Java tea-leaf powders. © 2024 Society of Chemical Industry.

17.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2222-2229, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812237

RESUMO

This study aims to investigate the effect and mechanism of Stellera chamaejasme extract(SCL) on multidrug resistance(MDR) in breast cancer. Human triple-negative breast cancer cell line MDA-MB-231 and its adriamycin-resistant cell line MDA-MB-231/ADR were used in the experiment. Cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay, and cell apoptosis was detected by DAPI staining and Annexin-V/Pi double staining. Western blot(WB) was used to detect the expression levels of Keap1, Nrf2, HO-1, Bcl-2, Bax, caspase-9, and caspase-3. Immunofluorescence staining was used to observe the distribution of Nrf2 in the cell, and flow cytometry was used to detect the level of reactive oxygen species(ROS) in the cell. The results showed that the resis-tance factor of SCL was 0.69, and that of adriamycin and paclitaxel was 8.40 and 16.36, respectively. DAPI staining showed that SCL could cause nuclear shrinkage and fragmentation of breast cancer cells. Annexin-V/Pi double staining showed that the average apoptosis rate of the drug-resistant cells was 32.64% and 50.29%, respectively under medium and high doses of SCL. WB results showed that SCL could significantly reduce the expression levels of anti-apoptotic proteins Bcl-2, caspase-9, and caspase-3 and significantly increase the expression level of pro-apoptotic protein Bax. Further studies showed that SCL could significantly promote the expression of Keap1, significantly inhibit the expression of Nrf2 and HO-1, and significantly reduce the expression level of Nrf2 in the nucleus. Correspondingly, flow cytometry showed that the intracellular ROS level was significantly increased. In conclusion, SCL can significantly inhibit the proliferation of MDA-MB-231 multidrug-resistant cells of triple-negative breast cancer and cause cell apoptosis, and the mechanism is related to inhibiting Keap1/Nrf2 signaling pathway, leading to ROS accumulation in drug-resistant cells and increasing the expression of apoptosis-related proteins.


Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Fator 2 Relacionado a NF-E2 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Feminino , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Thymelaeaceae/química , Medicamentos de Ervas Chinesas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Doxorrubicina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proliferação de Células/efeitos dos fármacos , Células MDA-MB-231
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