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1.
Cell ; 185(16): 2975-2987.e10, 2022 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-35853453

RESUMEN

Horizontal gene transfer (HGT) is an important evolutionary force shaping prokaryotic and eukaryotic genomes. HGT-acquired genes have been sporadically reported in insects, a lineage containing >50% of animals. We systematically examined HGT in 218 high-quality genomes of diverse insects and found that they acquired 1,410 genes exhibiting diverse functions, including many not previously reported, via 741 distinct transfers from non-metazoan donors. Lepidopterans had the highest average number of HGT-acquired genes. HGT-acquired genes containing introns exhibited substantially higher expression levels than genes lacking introns, suggesting that intron gains were likely involved in HGT adaptation. Lastly, we used the CRISPR-Cas9 system to edit the prevalent unreported gene LOC105383139, which was transferred into the last common ancestor of moths and butterflies. In diamondback moths, males lacking LOC105383139 courted females significantly less. We conclude that HGT has been a major contributor to insect adaptation.


Asunto(s)
Mariposas Diurnas , Transferencia de Gen Horizontal , Animales , Mariposas Diurnas/genética , Cortejo , Evolución Molecular , Masculino , Filogenia
2.
PLoS Biol ; 22(3): e3002515, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38512963

RESUMEN

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.


Asunto(s)
Proteínas de Drosophila , MicroARNs , Animales , Femenino , Drosophila/genética , Drosophila/metabolismo , Ovario/metabolismo , Proteínas de Drosophila/metabolismo , Nicho de Células Madre/genética , Diferenciación Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Células Madre/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Comunicación , Drosophila melanogaster/metabolismo , Células Germinativas/metabolismo
3.
BMC Biol ; 22(1): 113, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750524

RESUMEN

BACKGROUND: Protein posttranslational modifications (PTMs) are fast and early responses to environmental changes, including pathogen infection. Jujube witches' broom (JWB) is a phytoplasma disease causing great economic loss in jujube production. After phytoplasma infection, the transcriptional, translational, and metabolic levels in jujube were activated, enabling it to survive during phytoplasma invasion. However, no study has yet reported on PTMs in jujube. Lysine crotonylation (Kcr) and lysine succinylation (Ksu) have been popular studies in recent years and their function in plant phytoplasma-stress responses remains unclear. RESULTS: Here, 1656 crotonylated and 282 succinylated jujube proteins were first identified under phytoplasma-stress, of which 198 were simultaneously crotonylated and succinylated. Comparative analysis revealed that 656 proteins, 137 crotonylated and 43 succinylated proteins in jujube were regulated by phytoplasma infection, suggesting that Kcr was more universal than Ksu. Kcr differentially expressed proteins (DEPs) were related to ribosomes, photosynthetic and carbon metabolism, while Ksu DEPs were mainly involved in carbon metabolism, the TCA cycle and secondary metabolite biosynthesis. The crosstalk network among proteome, crotonylome and succinylome showed that DEPs related to ribosomal, peroxidases and glutathione redox were enriched. Among them, ZjPOD51 and ZjPHGPX2 significantly increased at the protein and Kcr level under phytoplasma-stress. Notably, 7 Kcr sites were identified in ZjPHGPX2, a unique antioxidant enzyme. After inhibitor nicotinamide (NAM) treatment, GPX enzyme activity in jujube seedlings was reduced. Further, site-directed mutagenesis of key Kcr modification sites K130 and/or K135 in ZjPHGPX2 significantly reduced its activity. CONCLUSIONS: This study firstly provided large-scale datasets of Kcr and Ksu in phytoplasma-infected jujube and revealed that Kcr modification in ZjPHGPX2 positively regulates its activity.


Asunto(s)
Phytoplasma , Enfermedades de las Plantas , Proteínas de Plantas , Ziziphus , Ziziphus/microbiología , Ziziphus/metabolismo , Phytoplasma/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Enfermedades de las Plantas/microbiología , Procesamiento Proteico-Postraduccional , Estrés Fisiológico , Lisina/metabolismo
4.
Curr Issues Mol Biol ; 46(3): 1886-1903, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38534739

RESUMEN

Kidney renal papillary cell carcinoma (KIRP) is a highly heterogeneous type of kidney cancer, resulting in limited effective prognostic targets for KIRP patients. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the regulation of ferroptosis and iron metabolism, making them potential targets for the treatment and prognosis of KIRP. In this study, we constructed a ferroptosis-related lncRNA risk score model (FRM) based on the TCGA-KIRP dataset, which represents a novel subtype of KIRP not previously reported. The model demonstrated promising diagnostic accuracy and holds potential for clinical translation. We observed significant differences in metabolic activities, immune microenvironment, mutation landscape, ferroptosis sensitivity, and drug sensitivity between different risk groups. The high-risk groups exhibit significantly higher fractions of cancer-associated fibroblasts (CAFs), hematopoietic stem cells (HSC), and pericytes. Drugs (IC50) analysis provided a range of medication options based on different FRM typing. Additionally, we employed single-cell transcriptomics to further analyze the impact of immune invasion on the occurrence and development of KIRP. Overall, we have developed an accurate prognostic model based on the expression patterns of ferroptosis-related lncRNAs for KIRP. This model has the potential to contribute to the evaluation of patient prognosis, molecular characteristics, and treatment modalities, and can be further translated into clinical applications.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38972436

RESUMEN

BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

6.
Plant Cell Environ ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119795

RESUMEN

Phytoplasmas can induce complex and substantial phenotypic changes in their hosts in ways that favour their colonisation, but the mechanisms underlying these changes remain largely unknown. Jujube witches' broom (JWB) disease is a typical phytoplasma disease causing great economic loss in Chinese jujube (Ziziphus jujuba Mill.). Here, we reported an effector, PHYL1JWB from Candidatus Phytoplasma ziziphi, which implicated in inducing abnormal floral organogenesis. Utilising a combination of in vivo and in vitro methods, we investigated the influence of PHYL1JWB on the proteins associated with floral development. Our findings reveal that PHYL1JWB facilitates the proteasome-mediated degradation of essential flower morphogenetic regulators, including AP1, SEP1, SEP2, SEP3, SEP4, CAL, and AGL6, through a distinctive pathway that is dependent on the activity of the 26S proteasome, thus obviating the requirement for lysine ubiquitination of the substrates. Further, the Y2H analysis showed that the leucine at position 75th in second α helix of PHYL1JWB is fundamental for the interactions of PHYL1JWB with AP1 and SEP1-4 in jujube and Arabidopsis. Our research carry profound implications for elucidating the contribution of PHYL1JWB to the aberrant floral development in diseased jujube, and help to establish a robust theoretical underpinning for the prophylaxis and therapy of JWB disease.

7.
Toxicol Appl Pharmacol ; 487: 116958, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735591

RESUMEN

Acute lung injury (ALI) remains a significant clinical challenge due to the absence of effective treatment alternatives. This study presents a new method that employs a screening platform focusing on MyD88 affinity, anti-inflammatory properties, and toxicity. This platform was used to evaluate a 300-compound library known for its anti-inflammatory potential. Among the screened compounds, Bicyclol emerged as a standout, exhibiting MyD88 binding and a significant reduction in LPS-stimulated pro-inflammatory factors production in mouse primary peritoneal macrophages. By targeting MyD88, Bicyclol disrupts the MyD88/TLR4 complex and MyD88 polymer formation, thereby mitigating the MAPKs and NF-κB signaling pathways. In vivo experiments further confirmed Bicyclol's efficacy, demonstrating alleviated ALI symptoms, decreased inflammatory cytokines level, and reduced inflammatory cells presence in lung tissues. These findings were associated with a decrease in mortality in LPS-challenged mice. Overall, Bicyclol represents a promising treatment option for ALI by specifically targeting MyD88 and limiting inflammatory responses.


Asunto(s)
Lesión Pulmonar Aguda , Compuestos de Bifenilo , Lipopolisacáridos , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide , Animales , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/prevención & control , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lipopolisacáridos/toxicidad , Factor 88 de Diferenciación Mieloide/metabolismo , Ratones , Masculino , Compuestos de Bifenilo/farmacología , Antiinflamatorios/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo
8.
Eur J Nucl Med Mol Imaging ; 51(11): 3161-3175, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38713298

RESUMEN

PURPOSE: The unsatisfactory efficacy of PD-L1 antibodies in glioblastoma (GBM) is largely due to the temporal and spatial heterogeneity of PD-L1 expression. Molecular imaging can enhance understanding of the tumor immune microenvironment and guide immunotherapy. However, highly sensitive imaging agents capable of effectively visualizing PD-L1 heterogeneity are limited. This study introduces a novel PET tracer, offering improved imaging of PD-L1 heterogeneity in GBM xenografts, with a comparative analysis to [18F]AlF-NOTA-WL12. METHODS: [18F]AlF-NOTA-PCP2 was synthesized with high purity and its affinity for PD-L1 was characterized using surface plasmon resonance (SPR) and cell binding assays. Its specificity for PD-L1 was evaluated both in vitro using various cell lines and in vivo with GBM xenograft models in NOD/SCID mice. PET/CT imaging was conducted to evaluate the tracer's biodistribution, pharmacokinetics, and ability to quantify tumoral spatial heterogeneity of PD-L1 expression. A focused comparative analysis between [18F]AlF-NOTA-PCP2 and [18F]AlF-NOTA-WL12 was conducted, examining binding affinity, biodistribution, pharmacokinetics, and imaging effectiveness in GBM xenografts. Additionally, human radiation dosimetry estimates compared the safety profiles of both tracers. RESULTS: [18F]AlF-NOTA-PCP2 demonstrated high radiochemical purity (> 95%) and a strong affinity for PD-L1, comparable to [18F]AlF-NOTA-WL12. In vitro and in vivo studies confirmed its specificity for PD-L1, with increased uptake in PD-L1 expressing cells and tumors. Toxicological profiles indicated no significant abnormalities in serum biochemical indicators or major organ tissues. MicroPET/CT imaging showed [18F]AlF-NOTA-PCP2's effectiveness in visualizing PD-L1 expression levels and spatial heterogeneity in GBM xenografts. Comparative studies revealed [18F]AlF-NOTA-PCP2's improved pharmacokinetic properties, including higher tumor-to-blood ratios and lower nonspecific liver uptake, as well as reduced radiation exposure compared to [18F]AlF-NOTA-WL12. CONCLUSION: [18F]AlF-NOTA-PCP2 distinguishes itself as an exceptionally sensitive PET/CT tracer, adept at non-invasively and accurately quantifying PD-L1 expression and its spatial heterogeneity in tumors, especially in GBM. Its favorable pharmacokinetic properties, safety profile, and high affinity for PD-L1 highlight its potential for enhancing the precision of cancer immunotherapy and guiding individualized treatment strategies. While promising, its clinical translation, especially in brain imaging, necessitates further validation in clinical trials.


Asunto(s)
Antígeno B7-H1 , Glioblastoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Animales , Ratones , Humanos , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Distribución Tisular , Trazadores Radiactivos , Compuestos Heterocíclicos con 1 Anillo/química , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacocinética , Radiofármacos/farmacocinética , Radiofármacos/química
9.
J Nutr ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880175

RESUMEN

BACKGROUND: The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites. OBJECTIVES: This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice. METHODS: Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition. RESULTS: The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism. CONCLUSIONS: The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.

10.
Mol Pharm ; 21(3): 1515-1525, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38291578

RESUMEN

Immune checkpoint inhibitors (ICIs) are a powerful treatment modality for various types of cancer. The effectiveness of ICIs is intimately connected to the binding status of antibodies to receptors. However, validated means to accurately evaluate target specificity and predict antibody efficacy in vivo are lacking. A novel peptide-based probe called Al[18F]F-NOTA-PCP1 was developed and validated for its specificity to PD-L1 in A549, U87MG, GL261, and GL261-iPDL1 cell lines, as well as in xenograft models. Then the probe was used in PET/CT scans to determine the binding status of PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) in U87MG xenograft model mice. Moreover, Al[18F]F-NOTA-PCP1 was used to evaluate the impact of different treatment times and doses. Al[18F]F-NOTA-PCP1 PET/CT can be used to evaluate the interaction between PD-L1 and antibodies to determine the effectiveness of immunotherapy. By quantifying target engagement, the probe has the potential to predict the efficacy of immunotherapy and optimize the dose and treatment schedules for PD-L1 immunotherapy. This imaging agent could be a valuable tool in guiding personalized treatment strategies and improving cancer patient outcomes.


Asunto(s)
Compuestos Heterocíclicos con 1 Anillo , Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Neoplasias/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Péptidos
11.
Artículo en Inglés | MEDLINE | ID: mdl-38904989

RESUMEN

TwoGram-stain-positive and rod-shaped actinomycetes (strains CDC186T and CDC192) were isolated from sputum samples of a patient in Chongqing, PR China, and were investigated to determine their taxonomic status. The results of phylogenetic analysis based on the 16S rRNA gene indicated that CDC186T and CDC192 represented members of the genus Nocardia, and the sequence similarity with Nocardia beijingensis DSM 44636T was the highest, at 99.71 and 99.78 %, respectively. The DNA G+C content of both CDC186T and CDC192 was 69.1 %. Genomic diversity analysis revealed that the average nucleotide identity and in silico DNA‒DNA hybridisation values between the two novel strains and closely related species were significantly below the thresholds of 95-96 and 70 %, respectively, but these values between the two novel strains were 99.96 and 99.90 %, respectively. The phylogenetic relationship based on the dapb1 gene and the single-copy core genes further indicated that the two novel strains were clustered in separate branch adjacent to N. beijingensis DSM 44636T. Growth occurred within the ranges of 20-42 °C, pH 6.0-9.0 and NaCl concentrations of 0.5-4.5 % (w/v). The major fatty acids of CDC186T and CDC192 were C16 : 0 and C18 : 0 10-methyl [tuberculostearic acid (TBSA)]. The predominant respiratory menaquinone was MK-9. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and one unidentified phosphoglycolipid. All the genomes of the studied strains were annotated with virulence factor (VF)-associated genes homologous to those of Mycobacterium tuberculosis, and the results of susceptibility testing indicated that CDC186T and CDC192 were resistant to amoxicillin-clavulanic acid and tigecycline. On the basis of chemotaxonomic characteristics and the results of phylogenetic analyses, strains CDC186T and CDC192 represent a novel species within the genus Nocardia, for which the name Nocardia implantans sp. nov. is proposed. The type strain is CDC186T (=GDMCC 4.206T= JCM 34959T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Nocardiosis , Nocardia , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Esputo , Nocardia/aislamiento & purificación , Nocardia/genética , Nocardia/clasificación , Humanos , ARN Ribosómico 16S/genética , China , ADN Bacteriano/genética , Ácidos Grasos/análisis , Ácidos Grasos/química , Nocardiosis/microbiología , Esputo/microbiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Genoma Bacteriano
12.
Bioorg Chem ; 151: 107700, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128245

RESUMEN

A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.


Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Pirimidinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Animales , Descubrimiento de Drogas , Ratones , Movimiento Celular/efectos de los fármacos , Diaminas/química , Diaminas/farmacología , Diaminas/síntesis química , Ratones Desnudos
13.
Acta Pharmacol Sin ; 45(6): 1276-1286, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38438580

RESUMEN

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.


Asunto(s)
Senescencia Celular , Neoplasias Hepáticas , Acortamiento del Telómero , Proteína 2 de Unión a Repeticiones Teloméricas , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/antagonistas & inhibidores , Proteína 2 de Unión a Repeticiones Teloméricas/genética , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Animales , Acortamiento del Telómero/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Ratones , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Masculino , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Surg Endosc ; 38(1): 148-157, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37945708

RESUMEN

BACKGROUND: The pink-color sign (PCS) has been widely used for diagnosing esophageal squamous cell carcinoma (ESCC) during Lugol's iodine chromoendoscopy. However, the identification of the PCS only relies on the subjective assessments made by the endoscopist, which could lead to bias and disagreement. Previous research has indicated that the V' variable can, as an objective index, define the PCS in the LU'V' color space. We aimed to validate the diagnostic performance of the PCS defined by the V' variable alone and attempt to improve the diagnostic performance by combining the V' and U' variables. METHODS: We re-examined 231 subjects with Lugol's unstained lesions (LULs) from a previously reported prospective trial. The diagnostic performance of the method using V' variable alone (V' alone method), the combination method using V' and U' variables (V' + U' method), and the endoscopists were calculated and compared. RESULTS: A total of 236 LULs were included, among which 46 were histologically confirmed to be cancerous lesions. The sensitivity, specificity, and accuracy of the V' alone method were 73.91% (95% CI 58.87-85.73%), 79.47% (95% CI 73.03-84.98%), and 78.39% (95% CI 72.59-83.47%) in the external validation cohort, respectively. It is inferior to endoscopists in terms of specificity and accuracy. The V' + U' method demonstrated a diagnostic performance comparable to the experienced endoscopists, with sensitivity, specificity, and accuracy of 76.74% (95% CI 61.37-88.25%), 88.64% (95% CI 83.00-92.92%), and 86.30% (95% CI 81.03-90.56%), respectively. CONCLUSION: The V' alone method exhibited lower specificity and accuracy than the experienced endoscopist and the V' + U' method. However, the modified V' + U' method demonstrated a diagnostic performance comparable to experienced endoscopists. Utilizing the objective index of the PCS could provide valuable support in clinical decision-making.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Esofagoscopía/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Estudios Prospectivos
15.
Ecotoxicol Environ Saf ; 281: 116596, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38896899

RESUMEN

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.


Asunto(s)
Nicotiana , Nicotiana/química , Nicotiana/genética , Nicotiana/crecimiento & desarrollo , Nicotiana/metabolismo , Cadmio/toxicidad , Resistencia a Medicamentos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Antioxidantes/metabolismo , Proteínas de Transporte de Catión/metabolismo
16.
BMC Biol ; 21(1): 143, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37340484

RESUMEN

BACKGROUND: How stem cell populations are organized and regulated within adult tissues is important for understanding cancer origins and for developing cell replacement strategies. Paradigms such as mammalian gut stem cells and Drosophila ovarian follicle stem cells (FSC) are characterized by population asymmetry, in which stem cell division and differentiation are separately regulated processes. These stem cells behave stochastically regarding their contributions to derivative cells and also exhibit dynamic spatial heterogeneity. Drosophila FSCs provide an excellent model for understanding how a community of active stem cells maintained by population asymmetry is regulated. Here, we use single-cell RNA sequencing to profile the gene expression patterns of FSCs and their immediate derivatives to investigate heterogeneity within the stem cell population and changes associated with differentiation. RESULTS: We describe single-cell RNA sequencing studies of a pre-sorted population of cells that include FSCs and the neighboring cell types, escort cells (ECs) and follicle cells (FCs), which they support. Cell-type assignment relies on anterior-posterior (AP) location within the germarium. We clarify the previously determined location of FSCs and use spatially targeted lineage studies as further confirmation. The scRNA profiles among four clusters are consistent with an AP progression from anterior ECs through posterior ECs and then FSCs, to early FCs. The relative proportion of EC and FSC clusters are in good agreement with the prevalence of those cell types in a germarium. Several genes with graded profiles from ECs to FCs are highlighted as candidate effectors of the inverse gradients of the two principal signaling pathways, Wnt and JAK-STAT, that guide FSC differentiation and division. CONCLUSIONS: Our data establishes an important resource of scRNA-seq profiles for FSCs and their immediate derivatives that is based on precise spatial location and functionally established stem cell identity, and facilitates future genetic investigation of regulatory interactions guiding FSC behavior.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Femenino , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Diferenciación Celular/genética , Folículo Ovárico , Células Madre/metabolismo , Mamíferos
17.
J Environ Manage ; 367: 121979, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39088904

RESUMEN

Cadmium (Cd) is readily absorbed by tobacco and accumulates in the human body through smoke inhalation, posing threat to human health. While there have been many studies on the negative impact of cadmium in tobacco on human health, the specific adaptive mechanism of tobacco roots to cadmium stress is not well understood. In order to comprehensively investigate the effects of Cd stress on the root system of tobacco, the combination of transcriptomic, biochemical, and physiological methods was utilized. In this study, tobacco growth was significantly inhibited by 50 µM of Cd, which was mainly attributed to the destruction of root cellular structure. By comparing the transcriptome between CK and Cd treatment, there were 3232 up-regulated deferentially expressed genes (DEGs) and 3278 down-regulated DEGs. The obvious differential expression of genes related to the nitrogen metabolism, metal transporters and the transcription factors families. In order to mitigate the harmful effects of Cd, the root system enhances Cd accumulation in the cell wall, thereby reducing the Cd content in the cytoplasm. This result may be mediated by plant hormones and transcription factor (TF). Correlational statistical analysis revealed significant negative correlations between IAA and GA with cadmium accumulation, indicated by correlation coefficients of -0.91 and -0.93, respectively. Conversely, ABA exhibited a positive correlation with a coefficient of 0.96. In addition, it was anticipated that 3 WRKY TFs would lead to a reduction in Cd accumulation. Our research provides a theoretical basis for the systematic study of the specific physiological processes of plant roots under Cd stress.


Asunto(s)
Cadmio , Reguladores del Crecimiento de las Plantas , Factores de Transcripción , Transcriptoma , Cadmio/toxicidad , Cadmio/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Transcriptoma/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/metabolismo , Nicotiana/genética , Nicotiana/efectos de los fármacos , Estrés Fisiológico , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos
18.
Plant Foods Hum Nutr ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150636

RESUMEN

The fruit of the jujube tree is high in nutrients and has various health benefits. China is a major producer of jujube, and it is now cultivated all around the world. Numerous studies have demonstrated the nutritional value and potential health advantages of bioactive compounds found in the jujube tree. Furthermore, the jujube tree has a remarkable 7000-year agricultural history. The jujube plant has developed a rich gene pool, making it a valuable resource for germplasm. Different studies have focused on the developmental stages of jujube fruits to identify the optimal time for harvest and to assess the changes in their bioactive natural compounds or products during the process of development but the molecular mechanism underlying the production of bioactive natural products in Z. jujuba is still poorly understood. Moreover, the potential differential expressed genes (DEGs) identified as responsible for the synthesis of these compounds should be further functionally verified. It has been noticed that the contents of total flavonoids, total phenolic, and vitamin C increase significantly during the ripening process, while the contents of soluble sugars and organic acids decrease gradually. In this review, we have also scrutinized the challenges that hinder the utilization of jujube fruit resources and suggested potential areas for further research. As such, our review serves as a valuable resource for the future development of jujube-based nutritional compounds and the incorporation of their nutritional elements into the functional foods industry.

19.
BMC Genomics ; 24(1): 648, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891463

RESUMEN

BACKGROUND: The Begonia species are common shade plants that are mostly found in southwest China. They have not been well studied despite their medicinal and decorative uses because gene penetration, decreased adaptability, and restricted availability are all caused by frequent interspecific hybridization. RESULT: To understand the patterns of mutation in the chloroplast genomes of different species of Begonia, as well as their evolutionary relationships, we collected seven Begonia species in China and sequenced their chloroplast genomes. Begonia species exhibit a quadripartite structure of chloroplast genomes (157,634 - 169,694 bp), consisting of two pairs of inverted repeats (IR: 26,529 - 37,674 bp), a large single copy (LSC: 75,477 - 86,500 bp), and a small single copy (SSC: 17,861 - 18,367 bp). 128-143 genes (comprising 82-93 protein-coding genes, 8 ribosomal RNAs, and 36-43 transfer RNAs) are found in the chloroplast genomes. Based on comparative analyses, this taxon has a relatively similar genome structure. A total of six substantially divergent DNA regions (trnT-UGU-trnL-UAA, atpF-atpH, ycf4-cemA, psbC-trnS-UGA, rpl32-trnL-UAG, and ccsA-ndhD) are found in the seventeen chloroplast genomes. These regions are suitable for species identification and phylogeographic analysis. Phylogenetic analysis shows that Begonia species that were suited to comparable environments grouped in a small clade and that all Begonia species formed one big clade in the phylogenetic tree, supporting the genus' monophyly. In addition, positive selection sites were discovered in eight genes (rpoC1, rpoB, psbE, psbK, petA, rps12, rpl2, and rpl22), the majority of which are involved in protein production and photosynthesis. CONCLUSION: Using these genome resources, we can resolve deep-level phylogenetic relationships between Begonia species and their families, leading to a better understanding of evolutionary processes. In addition to enhancing species identification and phylogenetic resolution, these results demonstrate the utility of complete chloroplast genomes in phylogenetically and taxonomically challenging plant groupings.


Asunto(s)
Begoniaceae , Genoma del Cloroplasto , Humanos , Filogenia , Begoniaceae/genética , Genómica/métodos , Cloroplastos/genética , Secuencia de Bases
20.
BMC Genomics ; 24(1): 80, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36803656

RESUMEN

BACKGROUND: Ribonuclease (RNase T2) plays crucial roles in plant evolution and breeding. However, there have been few studies on the RNase T2 gene family in Ziziphus jujuba Mill., one of important dried fruit tree species. Recently, the released sequences of the reference genome of jujube provide a good chance to perform genome-wide identification and characterization of ZjRNase gene family in the jujube. RESULTS: In this study, we identified four members of RNase T2 in jujube distributed on three chromosomes and unassembled chromosomes. They all contained two conserved sites (CASI and CASII). Analysis of the phylogenetic relationships revealed that the RNase T2 genes in jujube could be divided into two groups: ZjRNase1 and ZjRNase2 belonged to class I, while ZjRNase3 and ZjRNase4 belonged to class II. Only ZjRNase1 and ZjRNase2 expression were shown by the jujube fruit transcriptome analysis. So ZjRNase1 and ZjRNase2 were selected functional verification by overexpression transformation of Arabidopsis. The overexpression of these two genes led to an approximately 50% reduction in seed number, which deserve further attention. Moreover, the leaves of the ZjRNase1 overexpression transgenic lines were curled and twisted. Overexpression of ZjRNase2 resulted in shortened and crisp siliques and the production of trichomes, and no seeds were produced. CONCLUSION: In summary, these findings will provide new insights into the molecular mechanisms of low number of hybrid seeds in jujube and a reference for the future molecular breeding of jujube.


Asunto(s)
Ziziphus , Ziziphus/genética , Frutas/genética , Filogenia , Fitomejoramiento
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