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1.
Chem Res Toxicol ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771988

RESUMEN

Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.

2.
Nat Commun ; 15(1): 4474, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796514

RESUMEN

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.


Asunto(s)
Algoritmos , Inteligencia Artificial , Odorantes , Olfato , Dispositivos Electrónicos Vestibles , Humanos , Olfato/fisiología , Interfaz Usuario-Computador , Adulto , Masculino
3.
Hepatology ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563629

RESUMEN

BACKGROUND AND AIMS: Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies. APPROACH AND RESULTS: We identified long noncoding RNA TILAM located near COL1A1 , expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog ( Tilam ), generated Tilam- deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam -deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-ß2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs. CONCLUSIONS: TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.

4.
Front Vet Sci ; 11: 1354548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38496312

RESUMEN

Mycoplasma synoviae (MS) is an economically important pathogen in the poultry industry. Vaccination is an effective method to prevent and control MS infections. Currently two live attenuated MS vaccines are commercially available, the temperature-sensitive MS-H vaccine strain and the NAD-independent MS1 vaccine strain. Differentiation of vaccine strains from wild-type (WT) strains is crucial for monitoring MS infection, especially after vaccination. In this study, we developed a Taqman duplex real-time polymerase chain reaction (PCR) method to identify MS1 vaccine strains from WT strains. The method was specific and did not cross-react with other avian pathogens. The sensitivity assay indicated that no inhibition occurred between probes or between mixed and pure templates in duplex real-time PCR. Compared with the melt-based mismatch amplification mutation assay (MAMA), our method was more sensitive and rapid. In conclusion, the Taqman duplex real-time PCR method is a useful method for the diagnosis and differentiation of WT-MS and MS1 vaccine strains in a single reaction.

5.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38396815

RESUMEN

The gaseous phytohormone ethylene plays a crucial role in plant growth, development, and stress responses. In the ethylene signal transduction cascade, the F-box proteins EIN3-BINDING F-BOX 1 (EBF1) and EBF2 are identified as key negative regulators governing ethylene sensitivity. The translation and processing of EBF1/2 mRNAs are tightly controlled, and their 3' untranslated regions (UTRs) are critical in these regulations. However, despite their significance, the exact mechanisms modulating the processing of EBF1/2 mRNAs remain poorly understood. In this work, we identified the gene DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1), which encodes an endoribonuclease and is induced by ethylene treatment, as a positive regulator of ethylene response. The loss of function mutant dne1-2 showed mild ethylene insensitivity, highlighting the importance of DNE1 in ethylene signaling. We also found that DNE1 colocalizes with ETHYLENE INSENSITIVE 2 (EIN2), the core factor manipulating the translation of EBF1/2, and targets the P-body in response to ethylene. Further analysis revealed that DNE1 negatively regulates the abundance of EBF1/2 mRNAs by recognizing and cleaving their 3'UTRs, and it also represses their translation. Moreover, the dne1 mutant displays hypersensitivity to 1,4-dithiothreitol (DTT)-induced ER stress and oxidative stress, indicating the function of DNE1 in stress responses. This study sheds light on the essential role of DNE1 as a modulator of ethylene signaling through regulation of EBF1/2 mRNA processing. Our findings contribute to the understanding of the intricate regulatory process of ethylene signaling and provide insights into the significance of ribonuclease in stress responses.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Arabidopsis/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Proteínas Nucleares/genética , Etilenos/farmacología , Etilenos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas F-Box/genética
6.
Sci Total Environ ; 917: 170415, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38278276

RESUMEN

Astaxanthin (Axn), a feed additive, can improve growth performance and enhance the environmental stress tolerance of shrimp at all growth stages. High carbonate alkalinity is considered a major stressor that affects the survival, growth, and reproduction of aquatic animals in saline-alkaline waters. In this study, a combined analysis of physiology, transcriptomics, and metabolomics was performed to explore the effected mechanism of Axn on Exopalaemon carinicauda (E. carinicauda) under alkalinity stress. The results revealed that dietary Axn can inhibit oxidative stress damage caused by alkalinity stress and maintain the normal cell structure and mitochondrial membrane potential. Transcriptomic data indicated that differentially expressed genes (DEGs) under alkalinity stress and those under alkalinity stress after Axn feeding were associated with apoptosis. The metabolic data suggested that alkalinity stress has adverse effects on ammonia metabolism, unsaturated fatty acid metabolism, and TCA cycle, and dietary Axn can improve the metabolic processes in E. carinicauda. In addition, transcriptomics and metabolomics analyses showed that Axn could help maintain the cytoskeletal structure and inhibit apoptosis under alkalinity stress; a TUNEL assay further confirmed these effects. Lastly, metabolic responses to alkalinity stress included changes in multiple amino acids and unsaturated fatty acids, and pathways related to energy metabolism were downregulated in the hepatopancreas of E. carinicauda under alkalinity stress. Collectively, all these results provide new insights into the molecular mechanisms underlying alkalinity stress tolerance in E. carinicauda after Axn feeding.


Asunto(s)
Palaemonidae , Animales , Perfilación de la Expresión Génica , Transcriptoma , Estrés Fisiológico , Xantófilas
7.
Adv Sci (Weinh) ; 11(8): e2305608, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38095542

RESUMEN

As a vital project of forward chemical genetic research, target deconvolution aims to identify the molecular targets of an active hit compound. Chemoproteomics, either with chemical probe-facilitated target enrichment or probe-free, provides a straightforward and effective approach to profile the target landscape and unravel the mechanisms of action. Canonical methods rely on chemical probes to enable target engagement, enrichment, and identification, whereas click chemistry and photoaffinity labeling techniques improve the efficiency, sensitivity, and spatial accuracy of target recognition. In comparison, recently developed probe-free methods detect protein-ligand interactions without the need to modify the ligand molecule. This review provides a comprehensive overview of different approaches and recent advancements for target identification and highlights the significance of chemoproteomics in investigating biological processes and advancing drug discovery processes.


Asunto(s)
Descubrimiento de Drogas , Etiquetas de Fotoafinidad , Ligandos , Descubrimiento de Drogas/métodos , Etiquetas de Fotoafinidad/química , Química Clic
8.
J Biol Chem ; 300(1): 105535, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38072043

RESUMEN

Renal cell carcinoma (RCC) is a frequent malignancy of the urinary system with high mortality and morbidity. However, the molecular mechanisms underlying RCC progression are still largely unknown. In this study, we identified FOXA2, a pioneer transcription factor, as a driver oncogene for RCC. We show that FOXA2 was commonly upregulated in human RCC samples and promoted RCC proliferation, as evidenced by assays of cell viability, colony formation, migratory and invasive capabilities, and stemness properties. Mechanistically, we found that FOXA2 promoted RCC cell proliferation by transcriptionally activating HIF2α expression in vitro and in vivo. Furthermore, we found that FOXA2 could interact with VHL (von Hippel‒Lindau), which ubiquitinated FOXA2 and controlled its protein stability in RCC cells. We showed that mutation of lysine at position 264 to arginine in FOXA2 could mostly abrogate its ubiquitination, augment its activation effect on HIF2α expression, and promote RCC proliferation in vitro and RCC progression in vivo. Importantly, elevated expression of FOXA2 in patients with RCC positively correlated with the expression of HIF2α and was associated with shorter overall and disease-free survival. Together, these findings reveal a novel role of FOXA2 in RCC development and provide insights into the underlying molecular mechanisms of FOXA2-driven pathological processes in RCC.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Carcinoma de Células Renales , Factor Nuclear 3-beta del Hepatocito , Neoplasias Renales , Humanos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Factor Nuclear 3-beta del Hepatocito/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Factores de Transcripción/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Progresión de la Enfermedad
9.
Animals (Basel) ; 13(24)2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38136838

RESUMEN

To investigate the shifts in the biochemical composition of hybrid grouper during the early larval stages, we collected samples at various developmental milestones, spanning from newly hatched larvae (stage I) to 4 days after hatching (stage V). Our findings revealed several notable trends: (1) The total length of hybrid grouper larvae exhibited a significant increase as the yolk-sac absorption progressed from stage I to V. Concurrently, there was a marked decrease in yolk volume and oil volume during the transition from stage I to III, followed by a gradual decline from stage III to V. (2) Dry weight and total lipid content displayed a rapid reduction throughout the larval development period, while the total protein content exhibited a declining trend. (3) The concentrations of triacylglycerols and wax esters/steryl esters decreased considerably, particularly at stage V. However, no differences were observed among the contents of ketones, hydrocarbons, and sterols. (4) As yolk-sac larvae developed from stage I to V, a significant reduction was observed in the levels of essential amino acids (EAAs), such as leucine, valine, isoleucine, phenylalanine, glycine, alanine, serine, proline, and tyrosine. This trend was also observed for non-EAAs and total amino acids, with fluctuations in the content of other amino acids. (5) There was a significant decrease in the levels of specific fatty acids, including C16:0, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), C18:0, 18:1n-9, and C20:4n-6. In contrast, the contents of C22:6n-3, polyunsaturated fatty acids (PUFAs), n-3 PUFA, n-6 PUFA, and the combination of docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), as well as the DHA/EPA ratio, remained stable from stage I to III but declined thereafter. (6) During the early developmental stages, the utilization sequence of fatty acids followed a pattern of prioritizing SFAs, followed by MUFAs, n-6 PUFA, and n-3 PUFA. These findings provide further insights into the nutritional priorities of hybrid grouper larvae during their early development, with a particular emphasis on lipids and fatty acids as vital energy sources. Additionally, our results highlight variations in the efficiency of utilization among different types of fatty acids, while protein utilization remained relatively stable, characterized by the selective consumption of amino acid content.

10.
ACS Nano ; 17(21): 21947-21961, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37917185

RESUMEN

Deaf-blindness limits daily human activities, especially interactive modes of audio and visual perception. Although the developed standards have been verified as alternative communication methods, they are uncommon to the nondisabled due to the complicated learning process and inefficiency in terms of communicating distance and throughput. Therefore, the development of communication techniques employing innate sensory abilities including olfaction related to the cerebral limbic system processing emotions, memories, and recognition has been suggested for reducing the training level and increasing communication efficiency. Here, a skin-integrated and wireless olfactory interface system exploiting arrays of miniaturized odor generators (OGs) based on melting/solidifying odorous wax to release smell is introduced for establishing an advanced communication system between deaf-blind and non-deaf-blind. By optimizing the structure design of the OGs, each OG device is as small as 0.24 cm3 (length × width × height of 11 mm × 10 mm × 2.2 mm), enabling integration of up to 8 OGs on the epidermis between nose and lip for direct and rapid olfactory drive with a weight of only 24.56 g. By generating single or mixed odors, different linked messages could be delivered to a user within a short period in a wireless and programmable way. By adopting the olfactory interface message delivery system, the recognition rates for the messages have been improved 1.5 times that of the touch-based method, while the response times were immensely decreased 4 times. Thus, the presented wearable olfactory interface system exhibits great potential as an alternative message delivery method for the deaf-blind.


Asunto(s)
Odorantes , Olfato , Humanos , Olfato/fisiología , Aprendizaje , Piel , Electrónica
11.
Anim Biotechnol ; : 1-9, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870116

RESUMEN

Fibroblast growth factor 7 (FGF7) is involved in lipid metabolism, which is considered as a candidate gene with close relation with muscle development by eGWAs and RNA-Seq analyses. To date, limited research has been conducted on the relationship between FGF7 gene and growth traits. The main objective of this work was to further investigate the association between novel InDel within FGF7 gene and growth traits in goat. Herein, FGF7 mRNA expression levels were investigated in various Fuqing goat tissues. We found that FGF7 gene was expressed in six adult goat tissues with the highest mRNA levels in adipose tissue. This result suggested that FGF7 gene might play a critical role in fat deposition. We also detected potential polymorphisms in Fuqing, Nubian and Jianyang Daer breeds. A 22-bp InDel polymorphism in FGF7 gene was detected in 396 goats and the three genotypes were designated as II, ID, and DD. Correlation analysis revealed that InDel polymorphism was significantly associated with growth traits (P < 0.05). Goats with genotypes ID and/or II had superior growth traits compared to those with genotype DD. In summary, our findings suggested that the 22-bp InDel within FGF7 gene could act as a molecular marker to improve the growth traits of goats in breeding programs.

12.
bioRxiv ; 2023 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-37546982

RESUMEN

Background & Aims: Fibrosis is the common endpoint for all forms of chronic liver injury, and progression of fibrosis leads to the development of end-stage liver disease. Activation of hepatic stellate cells (HSCs) and their transdifferentiation to myofibroblasts results in the accumulation of extracellular matrix (ECM) proteins that form the fibrotic scar. Long noncoding (lnc) RNAs regulate the activity of HSCs and may provide targets for fibrotic therapies. Methods: We identified lncRNA TILAM as expressed near COL1A1 in human HSCs and performed loss-of-function studies in human HSCs and liver organoids. Transcriptomic analyses of HSCs isolated from mice defined the murine ortholog of TILAM . We then generated Tilam -deficient GFP reporter mice and quantified fibrotic responses to carbon tetrachloride (CCl 4 ) and choline-deficient L-amino acid defined high fat diet (CDA-HFD). Co-precipitation studies, mass spectrometry, and gene expression analyses identified protein partners of TILAM . Results: TILAM is conserved between human and mouse HSCs and regulates expression of ECM proteins, including collagen. Tilam is selectively induced in HSCs during the development of fibrosis in vivo . In both male and female mice, loss of Tilam results in reduced fibrosis in the setting of CCl 4 and CDA-HFD injury models. TILAM interacts with promyelocytic leukemia protein (PML) to stabilize PML protein levels and promote the fibrotic activity of HSCs. Conclusion: TILAM is activated in HSCs and interacts with PML to drive the development of liver fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end stage liver disease.

13.
Plant J ; 115(6): 1514-1527, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37269223

RESUMEN

The signaling pathways for the phytohormones ethylene and abscisic acid (ABA) have antagonistic effects on seed germination and early seedling establishment. However, the underlying molecular mechanisms remain unclear. In Arabidopsis thaliana, ETHYLENE INSENSITIVE 2 (EIN2) localizes to the endoplasmic reticulum (ER); although its biochemical function is unknown, it connects the ethylene signal with the key transcription factors EIN3 and EIN3-LIKE 1 (EIL1), leading to the transcriptional activation of ethylene-responsive genes. In this study, we uncovered an EIN3/EIL1-independent role for EIN2 in regulating the ABA response. Epistasis analysis demonstrated that this distinct role of EIN2 in the ABA response depends on HOOKLESS 1 (HLS1), the putative histone acetyltransferase acting as a positive regulator of ABA responses. Protein interaction assays supported a direct physical interaction between EIN2 and HLS1 in vitro and in vivo. Loss of EIN2 function resulted in an alteration of HLS1-mediated histone acetylation at the ABA-INSENSITIVE 3 (ABI3) and ABI5 loci, which promotes gene expression and the ABA response during seed germination and early seedling growth, indicating that the EIN2-HLS1 module contributes to ABA responses. Our study thus revealed that EIN2 modulates ABA responses by repressing HLS1 function, independently of the canonical ethylene pathway. These findings shed light on the intricate regulatory mechanisms underling the antagonistic interactions between ethylene and ABA signaling, with significant implications for our understanding of plant growth and development.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Plantones/metabolismo , Germinación , Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas , Semillas/genética , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo
14.
Front Oncol ; 13: 1172670, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37346071

RESUMEN

Introduction: The occurrence of metastasis is a threat to patients with colon cancer (CC), and the liver is the most common metastasis organ. However, the role of the extrahepatic organs in patients with liver metastasis (LM) has not been distinctly demonstrated. Therefore, this research aimed to explore the prognostic value of extrahepatic metastases (EHMs). Methods: In this retrospective study, a total of 13,662 colon patients with LM between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results database (SEER). Fine and Gray's analysis and K-M survival analysis were utilized to explore the impacts of the number of sites of EHMs and different sites of EHMs on prognosis. Finally, a prognostic nomogram model based on the number of sites of EHMs was constructed, and a string of validation methods was conducted, including concordance index (C-index), receiver operating characteristic curves (ROC), and decision curve analysis (DCA). Results: Patients without EHMs had better prognoses in cancer-specific survival (CSS) and overall survival (OS) than patients with EHMs (p < 0.001). Varied EHM sites of patients had different characteristics of primary location site, grade, and histology. Cumulative incidence rates for CSS surpassed that for other causes in patients with 0, 1, 2, ≥ 3 EHMs, and the patients with more numbers of sites of EHMs revealed worse prognosis in CSS (p < 0.001). However, patients with different EHM sites had a minor difference in cumulative incidence rates for CSS (p = 0.106). Finally, a nomogram was constructed to predict the survival probability of patients with EHMs, which is based on the number of sites of EHMs and has been proven an excellent predictive ability. Conclusion: The number of sites of EHMs was a significant prognostic factor of CC patients with LM. However, the sites of EHMs showed limited impact on survival. Furthermore, a nomogram based on the number of sites of EHMs was constructed to predict the OS of patients with EHMs accurately.

15.
CNS Neurosci Ther ; 29(8): 2292-2307, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36987665

RESUMEN

OBJECTIVE: Temozolomide is extensively applied in chemotherapy for glioblastoma with unclear exact action mechanisms. This article seeks to address the potential molecular mechanisms in temozolomide therapy for glioblastoma involving LINC00470. METHODS: Bioinformatics analysis was conducted to predict the potential mechanism of LINC00470 in glioblastoma, which was validated by dual-luciferase reporter, RIP, ChIP, and RNA pull-down assays. LINC00470 expression and the predicted downstream transcription factor early growth response 2 (EGR2) were detected in the collected brain tissues from glioblastoma patients. Following temozolomide treatment and/or gain- and loss-of-function approaches in glioblastoma cells, cell viability, invasion, migration, cycle distribution, angiogenesis, autophagy, and apoptosis were measured. In addition, the expression of mesenchymal surface marker proteins was assessed by western blot. Tumor xenograft in nude mice was conducted for in vivo validation. RESULTS: Mechanistic analysis and bioinformatics analysis revealed that LINC00470 transcriptionally activated SRY-related high-mobility-group box 4 (SOX4) through the transcription factor EGR2. LINC00470 and EGR2 were highly expressed in brain tissues of glioblastoma patients. LINC00470 and EGR2 mRNA expression gradually decreased with increasing concentrations of temozolomide in glioblastoma cells, and SOX4 expression was reduced in cells by temozolomide and LINC00470 knockdown. Temozolomide treatment induced cell cycle arrest, diminished cell viability, migration, invasion, and angiogenesis, and increased apoptosis and autophagy in glioblastoma, which was counteracted by overexpressing LINC00470 or SOX4 but was further promoted by LINC00470 knockdown. Temozolomide restrained glioblastoma growth and angiogenesis in vivo, while LINC00470 or SOX4 overexpression nullified but LINC00470 knockdown further facilitated these trends. CONCLUSION: Conclusively, temozolomide repressed glioblastoma progression by repressing the LINC00470/EGR2/SOX4 axis.


Asunto(s)
Proteína 2 de la Respuesta de Crecimiento Precoz , Glioblastoma , ARN Largo no Codificante , Factores de Transcripción SOXC , Animales , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Proteína 2 de la Respuesta de Crecimiento Precoz/genética , Proteína 2 de la Respuesta de Crecimiento Precoz/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Ratones Desnudos , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Temozolomida/farmacología , Factores de Transcripción/genética , ARN Largo no Codificante/genética
16.
New Phytol ; 238(2): 765-780, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36653958

RESUMEN

Metabolites including antibiotics, enzymes, and volatiles produced by plant-associated bacteria are key factors in plant-microbiota interaction that regulates various plant biological processes. There should be crucial mediators responsible for their entry into host plants. However, less is known about the identities of these plant transporters. We report that the Arabidopsis Nitrate Transporter1 (NRT1)/NPF protein NPF2.13 functions in plant uptake of tunicamycin (TM), a natural antibiotic produced by several Streptomyces spp., which inhibits protein N-glycosylation. Loss of NPF2.13 function resulted in enhanced TM tolerance, whereas NPF2.13 overexpression led to TM hypersensitivity. Transport assays confirmed that NPF2.13 is a H+ /TM symporter and the transport is not affected by other substrates like nitrate. NPF2.13 exclusively showed TM transport activity among tested NPFs. Tunicamycin uptake from TM-producing Streptomyces upregulated the expression of nitrate-related genes including NPF2.13. Moreover, nitrate allocation to younger leaves was promoted by TM in host plants. Tunicamycin could also benefit plant defense against the pathogen. Notably, the TM effects were significantly repressed in npf2.13 mutant. Overall, this study identifies NPF2.13 protein as an important TM transporter in plant-microbe interaction and provides insights into multiple facets of NPF proteins in modulating plant nutrition and defense by transporting exterior bacterial metabolites.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Tunicamicina/farmacología , Nitratos/metabolismo , Proteínas de Transporte de Anión/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas
17.
Anim Biotechnol ; 34(7): 2571-2581, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36047452

RESUMEN

The Alternative splicing (AS) of Carnitine palmitoyltransferase 1a (CPT1a) and their expression profiles had never been illuminated in goats until now. Herein, a novel splice transcript in the CPT1a gene that is predicted to result in the skipping of exons 6-19 (CPT1a-sv1) has been isolated in addition to the full-length transcript in goats. The result of RT-PCR showed that CPT1a-sv1 is 606 bp in length and consists of 6 exons. A novel exon 6 was consisted of partial exon 5 and partial exon 19, compared to that in CPT1a. RT-qPCR analysis showed that the expression patterns of CPT1a and CPT1a-sv1 are spatially different. In both kid and adult goats, the CPT1a transcript is strongly expressed in the liver, spleen, lung, kidney, and brain tissues. However, CPT1a-sv1 has a strong tissue-specific expression pattern, with moderate RNA levels in the liver and brain of kids, while highly expressed in the liver and minimally expressed in the brain of adults. We observed two transcripts to be involved in brain development. These findings improve our understanding of the function of the CPT1a gene in goats and provide information on the molecular mechanism of AS events.


Asunto(s)
Empalme Alternativo , Cabras , Animales , Cabras/genética , Cabras/metabolismo , Secuencia de Bases , Exones/genética , Empalme Alternativo/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
18.
Mitochondrial DNA B Resour ; 8(11): 1285-1289, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38188445

RESUMEN

Acalypha hispida Burm. f. (1768) is an evergreen shrub native to New Guinea and the Bismarck Archipelago. Currently, it is widely cultivated as an ornamental and medicinal plant in tropical and subtropical areas worldwide. This study characterized the complete chloroplast genome of A. hispida, which is 172,122 bp in length and consists of large single-copy (LSC) and small single-copy (SSC) regions of 97,025 bp and 19,787 bp, respectively, that are separated by a pair of 27,655 bp inverted repeat (IR) regions. The overall GC content of the genome is 34.22%. The genome contains 131 genes, including 86 protein-coding, 37 tRNA, and eight rRNA genes. Phylogenetic analysis indicates that A. hispida is closely related to Ricinus communis and Cleidiocarpon cavaleriei in the Euphorbiaceae family. The complete chloroplast genome of A. hispida provides genomic resources and potential markers suitable for future species identification and speciation studies of the genus Acalypheae and will also provide important information on the phylogenetic relationships of the Euphorbiaceae family.

19.
Am J Transl Res ; 14(11): 7726-7743, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36505285

RESUMEN

OBJECTIVE: To investigate the role of Osteopontin (OPN) in mediating macroautophagy, autophagy, and neuroplasticity in the ipsilateral hemisphere after stroke. METHODS: Focal stroke was induced by photothrombosis in adult mice. Spatiotemporal expression of endogenous OPN and BECN1 was assessed by immunohistochemistry. Motor function was determined by the grid-walking and cylinder tasks. We also evaluated markers of neuroplasticity and autophagy using biochemical and histology analyses. RESULTS: Herein, we showed that endogenous OPN and beclin1 were increased in the peri-infarct area of stroked patients and mice. Intracerebral administration of OPN (0.1 mg/ml; 3 ml) significantly improved performance in motor behavioral tasks compared with non-OPN-treated stroke mice. Furthermore, the neural repair was induced in OPN-treated stroke mice. We found that OPN treatment resulted in a significantly higher density of a presynaptic marker (vesicular glutamate transporter 1, VgluT1) and synaptic plasticity marker (synaptophysin, SYN) within the peri-infarct region. OPN treatment in stroke mice not only increased protein levels of integrin ß1 but also promoted the expression of beclin1 and LC3, two autophagy-related proteins in the peri-infarct area. Additionally, OPN-induced neuroplasticity and autophagy were blocked by an integrin antagonist. CONCLUSION: Our findings indicate that OPN may enhance neuroplasticity via autophagy, providing a new therapeutic strategy for ischemic stroke.

20.
Fish Shellfish Immunol ; 131: 480-486, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36195268

RESUMEN

Astaxanthin (Axn), a common aquatic feed additive, can enhance immunity, improve the antioxidant capacity of the crustacean and then improve the anti-stress ability of crustaceans. Exopalaemon carinicauda (E. carinicauda) is an economically important fishery species in China that has been found that dietary Axn can significantly increase ACP and AKP compared to a control diet for shrimp hepatopancreas in this study. RNA-sequencing and comparative transcriptomic analyses were utilized to explore changes in E. carinicauda gene expression following Axn feeding. Differential gene expression analyses comparing the control and Axn groups identified 631 transcripts that were differentially expressed following Axn feeding, of which 314 and 317 were respectively upregulated and downregulated. Functional enrichment analyses of these genes revealed their enrichment in 22 Gene Ontology categories and 11 KEGG pathways. In the GO and KEGG enrichment analysis, it was found that dietary astaxanthin can regulate the gene expression level of adult E. carinicauda. Many of the signal pathways enriched by these genes are related to immunity, apoptosis and anti-stress. In addition, through KEGG enrichment analysis, it was found that dietary Axn could also regulate the amino acid metabolism of hepatopancreas of adult E. carinicauda. The comprehensive comparative transcriptomic analysis showed that Axn could improve the hepatopancreatic immunity and anti-apoptosis ability of adult E. carinicauda.


Asunto(s)
Decápodos , Palaemonidae , Animales , Transcriptoma , Palaemonidae/genética , Decápodos/genética , Perfilación de la Expresión Génica/veterinaria
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