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1.
Theranostics ; 14(9): 3634-3652, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948059

RESUMEN

Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.


Asunto(s)
Imagen Óptica , Nanomedicina Teranóstica , Animales , Nanomedicina Teranóstica/métodos , Humanos , Imagen Óptica/métodos , Ratones , Microambiente Tumoral , Línea Celular Tumoral , Colorantes Fluorescentes/química , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Ratones Desnudos , Cirugía Asistida por Computador/métodos
2.
J Am Chem Soc ; 146(28): 18967-18978, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38973592

RESUMEN

Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.


Asunto(s)
Adamantano , Aminobenzoatos , Aminofenoles , Anilidas , Compuestos Policíclicos , Aminofenoles/química , Aminofenoles/farmacología , Aminofenoles/síntesis química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/síntesis química , Adamantano/química , Adamantano/farmacología , Adamantano/síntesis química , Adamantano/análogos & derivados , Anilidas/farmacología , Anilidas/química , Anilidas/síntesis química , Aminobenzoatos/farmacología , Aminobenzoatos/química , Aminobenzoatos/síntesis química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Estructura Molecular , Reacción de Cicloadición , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química
3.
J Med Chem ; 67(11): 9318-9341, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38764175

RESUMEN

Interfering with sterol biosynthesis is an important strategy for developing safe and effective antifungal drugs. We previously identified compound H55 as an allosteric inhibitor of the fungal-specific C-24 sterol methyltransferase Erg6 for treating Candida albicans infections. Herein, 62 derivatives of H55 were designed and synthesized based on target-ligand interactions to identify more active candidates. Among them, d28 displayed the most potent antivirulence ability (MHIC50 = 0.25 µg/mL) by targeting Erg6, exhibiting an 8-fold increase in potency compared with H55. Moreover, d28 significantly outperformed H55 in inhibiting cell adhesion and biofilm formation, and exhibited minimal cytotoxicity and negligible potential to induce drug resistance. Of note, the coadministration of d28 and other sterol biosynthesis inhibitors, such as tridemorph or terbinafine, demonstrated a strong synergistic antifungal action in vitro and in vivo in a murine skin infection model. These results support the potential application of d28 in the treatment of C. albicans infections.


Asunto(s)
Antifúngicos , Candida albicans , Candidiasis , Metiltransferasas , Candida albicans/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/uso terapéutico , Animales , Relación Estructura-Actividad , Ratones , Candidiasis/tratamiento farmacológico , Metiltransferasas/antagonistas & inhibidores , Metiltransferasas/metabolismo , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Humanos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Femenino
5.
Int Nurs Rev ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477788

RESUMEN

AIM: To evaluate the mediating roles of occupational resilience and the moderationg role of perceived organizational support in the relationship between career calling and nurse burnout. BACKGROUND: Burnout is a frequent and serious problem in the field of nursing, and it poses a serious threat to both nurses' health and patient safety. Although many studies have described the links between burnout, career calling, and occupational resilience, little is known about the actual mechanisms between career calling and nurse burnout. METHODS: A cross-sectional study of 615 nurses in China was conducted using a convenience sampling method. The data were analyzed using descriptive statistics and Pearson correlation analysis. Hypotheses were tested using structural equation models and bootstrapping methods. STROBE guidelines were followed. RESULTS: Career calling was found to be negatively associated with nurse burnout, and occupational resilience mediated the relationship between career calling and burnout. Additionally, perceived organizational support was found to play a moderating role in the relationship between occupational resilience and burnout. CONCLUSION: Career calling can reduce burnout by increasing nurses' levels of occupational resilience, and perceived organizational support moderates this mechanism. Hence, policies focused on encouraging and sustaining career calling should be provided by nurse managers in order to enhance stress resistance and reduce burnout.

6.
J Nat Prod ; 87(4): 1124-1130, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38419347

RESUMEN

Seven new terpenoids, including six sacculatane diterpenoids plagiochilarins A-F (1-6), and one ent-2,3-seco-aromandrane sesquiterpenoid plagiochilarin H (8) with a 6/7/3/5 tetracyclic scaffold, alongside three known compounds, were obtained from the Chinese liverwort Plagiochila nitens Inoue. Plagiochilarin B (2) was unpredictably converted to the more stable artifact 7 under acid catalysis through cyclic ether formation. The reaction mechanism was reasonably deduced and experimentally verified. The structures of these terpenoids were determined by analysis of MS and NMR spectroscopic data and single-crystal X-ray diffraction. The inhibitory effect of all of the isolates was evaluated on the growth of two C. albicans strains, wild strain SC5314 and efflux pump-deficient strain DSY654. However, only plagiochilarin H (8) showed a MIC value of 16 µg/mL against C. albicans DSY654.


Asunto(s)
Candida albicans , Diterpenos , Hepatophyta , Hepatophyta/química , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , China , Candida albicans/efectos de los fármacos , Estructura Molecular , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Cristalografía por Rayos X
7.
Genes (Basel) ; 15(2)2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-38397239

RESUMEN

(1) Background: Copy number variation (CNV) is a critical component of genome structural variation and has garnered significant attention. High-throughput screening of the KCNJ15 gene has revealed a correlation between the CNV region and the growth traits of goats. We aimed to identify the CNV of the KCNJ15 gene in five goat breeds and analyze its association with growth characteristics. (2) Methods: We utilized 706 goats from five breeds: Guizhou black goat (GZB), Guizhou white goat (GZW), Bohuai goat (BH), Huai goat (HH), and Taihang goat (TH). To evaluate the number of copies of the KCNJ15 gene using qPCR, we analyzed the correlation between the CNV and growth characteristics and then used a universal linear model. The findings revealed variations in the distribution of different copy number types among the different goat breeds. (3) Results: Association analysis revealed a positive influence of the CNV in the KCNJ15 gene on goat growth. In GZB, individuals with duplication types exhibited superior performance in terms of cannon bone circumference (p < 0.05). In HH, individuals with duplication types exhibited superior performance in terms of body slanting length (p < 0.05). Conversely, normal TH demonstrated better body height and body weight (p < 0.05), while in GZW, when CN = 3, it performed better than other types in terms of body weight and chest circumference (p < 0.05). However, in BH, it had no significant effect on growth traits. (4) Conclusions: We confirmed that the CNV in the KCNJ15 gene significantly influences the growth characteristics of four distinct goat breeds. The correlation between KCNJ15 gene CNVs and goat growth traits offers valuable insights to breeders, enabling them to employ precise and efficient breeding methods that enhance livestock welfare, productivity, and overall economic benefits in the industry.


Asunto(s)
Cabras , Canales de Potasio de Rectificación Interna , Animales , Peso Corporal/genética , Variaciones en el Número de Copia de ADN/genética , Dosificación de Gen , Cabras/genética , Cabras/crecimiento & desarrollo , Fenotipo , Canales de Potasio de Rectificación Interna/genética
8.
Plant Biotechnol J ; 22(5): 1164-1176, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38070185

RESUMEN

Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome-wide association studies (GWAS) using two re-sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13-3, which encodes a protein homologous to the pseudo-response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13-3 in the natural population, with haplotype H4 (qFT13-3H4) being lost during domestication, while qFT13-3H1 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13-3H1 were located in high-latitude regions. Knockout of qFT13-3 accelerated flowering and maturity time under long-day conditions, indicating that qFT13-3 functions as a flowering inhibitor. Our results also showed that qFT13-3 directly downregulates the expression of GmELF3b-2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13-3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13-3 can be utilized for the breeding of high-yield cultivars with a short maturity time suitable for high latitudes.


Asunto(s)
Estudio de Asociación del Genoma Completo , Glycine max , Glycine max/genética , Fitomejoramiento , Haplotipos/genética , Fotoperiodo , Flores/genética , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética
9.
J Nat Prod ; 87(1): 132-140, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-38157445

RESUMEN

Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.


Asunto(s)
Alcanos , Hepatophyta , Sesquiterpenos de Guayano , Sesquiterpenos , Hepatophyta/química , Estructura Molecular , Sesquiterpenos/farmacología , Sesquiterpenos/química , China
10.
J Agric Food Chem ; 71(49): 19551-19567, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38032113

RESUMEN

Liverworts provide valuable ecological services to improve the sustainability of agriculture, encompassing soil health maintenance and natural pest management. Some liverworts have potential applications in medicine and as food additives. Twenty-two novel diterpenoids (anajoerins A-V), of which anajoerins B-G are rearranged labdanes featuring an unprecedented 6/5 fused ring system, were isolated from the Chinese liverwort Anastrophyllum joergensenii Schiffn. The absolute configurations of all compounds were identified based on high-resolution electrospray ionization mass spectroscopy data, NMR spectra, and ECD calculations. Plausible biogenetic pathways for unprecedented rearranged labdanes were proposed. Seven diterpenoids exhibited anti-inflammatory activity by reducing nitric oxide production in LPS-stimulated RAW264.7 murine macrophages in a dose-dependent manner with IC50s between 9.71 and 56.56 µM. All tested compounds showed no cytotoxicity at the tested concentrations. Western blot analyses of NF-κB p65 downregulation showed that anajoerin L could inhibit the NF-κB signaling pathway. Furthermore, anajoerin L also suppressed the secretion of the ConA-induced proinflammatory cytokines IFN-γ, TNF-α, and IL-6.


Asunto(s)
Diterpenos , Hepatophyta , Animales , Ratones , FN-kappa B/metabolismo , Hepatophyta/metabolismo , Células RAW 264.7 , Antiinflamatorios/farmacología , Citocinas/metabolismo , China , Lipopolisacáridos/farmacología , Óxido Nítrico/metabolismo
11.
JACS Au ; 3(10): 2749-2762, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37885576

RESUMEN

Inducing paraptosis, a nonapoptotic form of cell death, has great therapeutic potential in cancer therapy, especially for drug-resistant tumors. However, the specific molecular target(s) that trigger paraptosis have not yet been deciphered yet. Herein, by using activity-based protein profiling, we identified the GDP-dissociation inhibitor beta (GDI2) as a manipulable target for inducing paraptosis and uncovered benzo[a]quinolizidine BQZ-485 as a potent inhibitor of GDI2 through the interaction with Tyr245. Comprehensive target validation revealed that BQZ-485 disrupts the intrinsic GDI2-Rab1A interaction, thereby abolishing vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus and initiating subsequent paraptosis events including ER dilation and fusion, ER stress, the unfolded protein response, and cytoplasmic vacuolization. Based on the structure of BQZ-485, we created a small benzo[a]quinolizidine library by click chemistry and discovered more potent GDI2 inhibitors using a NanoLuc-based screening platform. Leveraging the engagement of BQZ-485 with GDI2, we developed a selective GDI2 degrader. The optimized inhibitor (+)-37 and degrader 21 described in this study exhibited excellent in vivo antitumor activity in two GDI2-overexpressing pancreatic xenograft models, including an AsPc-1 solid tumor model and a transplanted human PDAC tumor model. Altogether, our findings provide a promising strategy for targeting GDI2 for paraptosis in the treatment of pancreatic cancers, and these lead compounds could be further optimized to be effective chemotherapeutics.

12.
Eur J Med Chem ; 259: 115693, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37531745

RESUMEN

Epothilone B (Epo B) is a potent antitumor natural product with sub-nanomolar anti-proliferation action against several human cancer cells. However, poor selectivity to tumor cells and unacceptable therapeutic windows of Epo B and its analogs are the major obstacles to their development into clinical drugs. Herein, we present self-assembled nanomicelles based on an amphiphilic carbohydrate-Epo B conjugate that is inactive until converted to active Epo B within the tumor. Four Epo B-Rhamnose conjugates linked via two linkers containing a disulfide bond that is sensitive to GSH were synthesized. Conjugate 34 can self-assemble into nanomicelles with a high concentration of Rha on the surface, allowing for better tumor targeting. After internalization by cancer cells, the disulfide bond can be cleaved in the presence of high levels of GSH to release active Epo B, thereby exhibiting significant anticancer efficiency and selectivity in vitro and in vivo.


Asunto(s)
Epotilonas , Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Carbohidratos/uso terapéutico , Disulfuros , Línea Celular Tumoral , Nanopartículas/química
13.
Phytochemistry ; 214: 113796, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37499849

RESUMEN

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.


Asunto(s)
Antifúngicos , Antineoplásicos , Hepatophyta , Sesquiterpenos de Eudesmano , Sesquiterpenos , Antifúngicos/farmacología , Antifúngicos/química , China , Hepatophyta/química , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/farmacología , Sesquiterpenos de Eudesmano/química , Células Hep G2/efectos de los fármacos , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología
14.
Plant Physiol Biochem ; 201: 107890, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37454467

RESUMEN

Drought stress is an important constraint for the germination of soybean (Glycine max [L.] Merr.) seeds and seedling establishment. A pot experiment was conducted to determine the effects of priming soybean seeds with 5 µM α-naphthaleneacetic acid (NAA) and the mechanism responsible for the induced tolerance of drought stress (soil relative water content of 55%). NAA priming inhibited drought-induced oxidative damage in seeds, and further analysis indicated that it induced an early spike in hydrogen peroxide content by the upregulation of abscisic acid-dependent GmRbohC2, resulting in an enhancement of antioxidant capacity. Moreover, NAA priming also improved the hydrolysis of triacylglycerol (TAG) to sucrose in stressed cotyledons by causing a 2- to 5-fold increase in the transcript levels of GmSDP1, GmACX2, GmMFP2, GmICL, GmMLS, GmGLI1, GmPCK1, GmFBPase1, GmSPS1 and GmSPS2. Consistently, it upregulated the expression levels of GmSUT1, GmCWINV1 and GmMST2 under drought stress, thus enhancing the transport of sucrose from cotyledons to embryonic axes, providing carbon skeletons and energy for axis growth. The seed germination percentage increased by 208.1% at 21 h after sowing, and seedling establishment percentage increased by 47.8% at 14 days after sowing. Collectively, the positive effects of NAA priming on seed germination and seedling establishment can be attributed to enhanced antioxidant ability in seeds, TAG mobilization in cotyledons and sucrose transport from cotyledons to embryonic axes under drought stress.


Asunto(s)
Germinación , Plantones , Glycine max/metabolismo , Antioxidantes/metabolismo , Sequías , Semillas , Sacarosa/metabolismo
15.
Microbiol Spectr ; 11(3): e0512122, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37191506

RESUMEN

Newcastle disease virus (NDV) is an avian paramyxovirus that causes major economic losses to the poultry industry around the world, with NDV pathogenicity varying due to strain virulence differences. However, the impacts of intracellular viral replication and the heterogeneity of host responses among cell types are unknown. Here, we investigated the heterogeneity of lung tissue cells in response to NDV infection in vivo and that of the chicken embryo fibroblast cell line DF-1 in response to NDV infection in vitro using single-cell RNA sequencing. We characterized the NDV target cell types in the chicken lung at the single-cell transcriptome level and classified cells into five known and two unknown cell types. The five known cell types are the targets of NDV in the lungs with virus RNA detected. Different paths of infection in the putative trajectories of NDV infection were distinguished between in vivo and in vitro, or between virulent Herts/33 strain and nonvirulent LaSota strain. Gene expression patterns and the interferon (IFN) response in different putative trajectories were demonstrated. IFN responses were elevated in vivo, especially in myeloid and endothelial cells. We distinguished the virus-infected and non-infected cells, and the Toll-like receptor signaling pathway was the main pathway after virus infection. Cell-cell communication analysis revealed the potential cell surface receptor-ligand of NDV. Our data provide a rich resource for understanding NDV pathogenesis and open the way to interventions specifically targeting infected cells. IMPORTANCE Newcastle disease virus (NDV) is an avian paramyxovirus that causes major economic losses to the poultry industry around the world, with NDV pathogenicity varying due to strain virulence differences. However, the impacts of intracellular viral replication and the heterogeneity of host responses among cell types are unknown. Here, we investigated the heterogeneity of lung tissue cells in response to NDV infection in vivo and that of the chicken embryo fibroblast cell line DF-1 in response to NDV infection in vitro using single-cell RNA sequencing. Our results open the way to interventions specifically targeting infected cells, suggest principles of virus-host interactions applicable to NDV and other similar pathogens, and highlight the potential for simultaneous single-cell measurements of both host and viral transcriptomes for delineating a comprehensive map of infection in vitro and in vivo. Therefore, this study can be a useful resource for the further investigation and understanding of NDV.


Asunto(s)
Enfermedad de Newcastle , Enfermedades de las Aves de Corral , Embrión de Pollo , Animales , Virus de la Enfermedad de Newcastle , Pollos , Transcriptoma , Enfermedad de Newcastle/patología , Células Endoteliales
16.
Phytochemistry ; 212: 113702, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37149119

RESUMEN

Three unprecedented ent-labdane and pallavicinin based dimers pallamins A-C formed via [4 + 2] Diels-Alder cycloaddition, together with eight biosynthetically related monomers were isolated from Pallavicinia ambigua. Their structures were determined by the extensive analysis of HRESIMS and NMR spectra. The absolute configurations of the labdane dimers were determined by single crystal X-ray diffraction of the homologous labdane units, and 13C NMR and ECD calculations. Moreover, a preliminary evaluation of the anti-inflammatory activities of the isolated compounds was performed using the zebrafish model. Three of the monomers demonstrated significant anti-inflammatory activity.


Asunto(s)
Diterpenos , Hepatophyta , Animales , Diterpenos/farmacología , Diterpenos/química , Hepatophyta/química , Estructura Molecular , Pez Cebra , China
17.
Am J Cancer Res ; 13(3): 802-817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034207

RESUMEN

Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment.

18.
Apoptosis ; 28(5-6): 860-880, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36997733

RESUMEN

Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are particularly important for tumor cell growth and migration, and recurrence and drug resistance, including head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to explore stemness-related lncRNAs (SRlncRNAs) that could be used for prognosis of patients with HNSCC. HNSCC RNA sequencing data and matched clinical data were obtained from TCGA database, and stem cell characteristic genes related to HNSCC mRNAsi were obtained from the online database by WGCNA analysis, respectively. Further, SRlncRNAs were obtained. Then, the prognostic model was constructed to forecast patient survival through univariate Cox regression and LASSO-Cox method based on SRlncRNAs. Kaplan-Meier, ROC and AUC were used to evaluate the predictive ability of the model. Moreover, we probed the underlying biological functions, signalling pathways and immune status hidden within differences in prognosis of patients. We explored whether the model could guide personalized treatments included immunotherapy and chemotherapy for HNSCC patients. At last, RT-qPCR was performed to analyze the expressions levels of SRlncRNAs in HNSCC cell lines. A SRlncRNAs signature was identified based on 5 SRlncRNAs (AC004943.2, AL022328.1, MIR9-3HG, AC015878.1 and FOXD2-AS1) in HNSCC. Also, risk scores were correlated with the abundance of tumor-infiltrating immune cells, whereas HNSCC-nominated chemotherapy drugs were considerably different from one another. The final finding was that these SRlncRNAs were abnormally expressed in HNSCCCS according to the results of RT-qPCR. These 5 SRlncRNAs signature, as a potential prognostic biomarker, can be utilized for personalized medicine in HNSCC patients.


Asunto(s)
Productos Biológicos , Neoplasias de Cabeza y Cuello , ARN Largo no Codificante , Humanos , Pronóstico , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Apoptosis , Neoplasias de Cabeza y Cuello/genética
19.
BMC Genomics ; 24(1): 116, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922782

RESUMEN

BACKGROUND: Cross breeding is an important way to improve livestock performance. As an important livestock and poultry resource in Henan Province of China, Bohuai goat was formed by crossing Boer goat and Huai goat. After more than 20 years of breeding, BoHuai goats showed many advantages, such as fast growth, good reproductive performance, and high meat yield. In order to better develop and protect Bohuai goats, we sequenced the whole genomes of 30 BoHuai goats and 5 Huai goats to analyze the genetic diversity, population structure and genomic regions under selection of BoHuai goat. Furthermore, we used 126 published genomes of world-wide goat to characterize the genomic variation of BoHuai goat. RESULTS: The results showed that the nucleotide diversity of BoHuai goats was lower and the degree of linkage imbalance was higher than that of other breeds. The analysis of population structure showed that BoHuai goats have obvious differences from other goat breeds. In addition, the BoHuai goat is more closely related to the Boer goat than the Huai goat and is highly similar to the Boer goat. Group by selection signal in the BoHuai goat study, we found that one region on chromosome 7 shows a very strong selection signal, which suggests that it could well be the segment region under the intense artificial selection results. Through selective sweeps, we detected some genes related to important traits such as lipid metabolism (LDLR, STAR, ANGPTL8), fertility (STAR), and disease resistance (CD274, DHPS, PDCD1LG2). CONCLUSION: In this paper, we elucidated the genomic variation, ancestry composition, and selective signals related to important economic traits in BoHuai goats. Our studies on the genome of BoHuai goats will not only help to understand the characteristics of the crossbred but also provide a basis for the improvement of cross-breeding programs.


Asunto(s)
Genoma , Cabras , Animales , Cabras/genética , Fenotipo , Secuenciación Completa del Genoma/veterinaria , Variación Genética , Polimorfismo de Nucleótido Simple , Selección Genética
20.
Anim Biotechnol ; 34(4): 1095-1101, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35236249

RESUMEN

Copy number variant (CNV), a common genetic polymorphism, is closely related to the phenotypic variation traits of organisms. Vesicle-associated membrane protein 7 gene (VAMP7) codes a protein, which is a member of the SNARE proteins family and plays an important role in the process of intracellular vesicle transport. In this study, a total of four cattle breeds (Yunling cattle, Xianan cattle, Pinan cattle, Jiaxian red cattle) were used to investigate the copy numbers, and we found an association relationship between CNV of VAMP7 gene and growth traits of cattle by SPSS 20.0 software. The results showed that the CNV type of VAMP7 gene in four cattle breeds had the same distribution, Duplication type occupies a dominant position among the four varieties. In Yunling cattle, the Duplication type of VAMP7 is significantly related to the height at the hip cross (p < 0.05), Individuals with Duplication type commonly have less performance on growth and development, which indicates that the Duplication type of the VAMP7 gene may have a negative effect on cattle growth. Individuals with the other two CNV types may become the breeding direction of the VAMP7 gene. This study provided a new perspective and basic material for the molecular genetics of the CNV of the VAMP7 gene, and also promoted the breeding progress of Chinese local cattle.


Asunto(s)
Variaciones en el Número de Copia de ADN , Polimorfismo de Nucleótido Simple , Animales , Bovinos/genética , Variaciones en el Número de Copia de ADN/genética , Fenotipo
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