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1.
Genomics ; 116(2): 110804, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38307485

RESUMEN

Litchi (Litchi chinensis Sonn.) is a valuable subtropical fruit tree with high-quality fruit. However, its economic benefits and sustainable development are restrained by a number of challenges. One major challenge is the lack of extremely early and late maturing high-quality varieties due to limited availability of varieties suitable for commercial cultivation and outdated breeding methods, resulting in an imbalanced supply and low price of litchi. Flowering time is a crucial genetic factor influencing the maturation period of litchi. Our previous research has highlighted the pivotal role of the LcFT1 gene in regulating the flowering time of litchi and identified a gene associated with LcFT1 (named as LcSOC1) based on RNA-Seq and weight gene co-expression network (WGCNA) analysis. This study further investigated the function of LcSOC1. Subcellular localization analysis revealed that LcSOC1 is primarily localized in the nucleus, where it acts as a transcription factor. LcSOC1 overexpression in Nicotiana tabacum and Arabidopsis thaliana resulted in significant early flowering. Furthermore, LcSOC1 was found to be expressed in various tissues, with the highest expression in mature leaves. Analysis of spatial and temporal expression patterns of LcSOC1 in litchi varieties with different flowering time under low temperature treatment and across an annual cycle demonstrated that LcSOC1 is responsive to low temperature induction. Interestingly, early maturing varieties exhibited higher sensitivity to low temperature, with significantly premature induction of LcSOC1 expression relative to late maturing varieties. Activation of LcSOC1 triggered the transition of litchi into the flowering phase. These findings demonstrate that LcSOC1 plays a pivotal role in regulating the flowering process and determining the flowering time in litchi. Overall, this study provides theoretical guidance and important target genes for molecular breeding to regulate litchi production period.


Asunto(s)
Litchi , Litchi/genética , Litchi/metabolismo , Frutas/genética , Fitomejoramiento , Hojas de la Planta/genética , Frío , Regulación de la Expresión Génica de las Plantas
2.
Lab Invest ; 104(6): 102058, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626874

RESUMEN

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inmunohistoquímica , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patología , Anciano de 80 o más Años , Adulto , Biomarcadores de Tumor/metabolismo
3.
BMC Cancer ; 24(1): 749, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902688

RESUMEN

BACKGROUND: To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months. CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.


Asunto(s)
Adenocarcinoma del Pulmón , Receptores ErbB , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Pulmonares , Terapia Molecular Dirigida , Mutación , Inhibidores de Proteínas Quinasas , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Terapia Molecular Dirigida/métodos , Adulto , Biopsia Líquida/métodos , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Citología
4.
Int J Mol Sci ; 24(8)2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37108143

RESUMEN

Diabetes is the most common metabolic disorder, with an extremely serious effect on health systems worldwide. It has become a severe, chronic, non-communicable disease after cardio-cerebrovascular diseases. Currently, 90% of diabetic patients suffer from type 2 diabetes. Hyperglycemia is the main hallmark of diabetes. The function of pancreatic cells gradually declines before the onset of clinical hyperglycemia. Understanding the molecular processes involved in the development of diabetes can provide clinical care with much-needed updates. This review provides the current global state of diabetes, the mechanisms involved in glucose homeostasis and diabetic insulin resistance, and the long-chain non-coding RNA (lncRNA) associated with diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , ARN Largo no Codificante , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
5.
Mol Cancer ; 21(1): 75, 2022 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-35296335

RESUMEN

BACKGROUND: Histone lysine-specific demethylase 1 (LSD1) expression has been shown to be significantly elevated in gastric cancer (GC) and may be associated with the proliferation and metastasis of GC. It has been reported that LSD1 repressed tumor immunity through programmed cell death 1 ligand 1 (PD-L1) in melanoma and breast cancer. The role of LSD1 in the immune microenvironment of GC is unknown. METHODS: Expression LSD1 and PD-L1 in GC patients was analyzed by immunohistochemical (IHC) and Western blotting. Exosomes were isolated from the culture medium of GC cells using an ultracentrifugation method and characterized by transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), sucrose gradient centrifugation, and Western blotting. The role of exosomal PD-L1 in T-cell dysfunction was assessed by flow cytometry, T-cell killing and enzyme-linked immunosorbent assay (ELISA). RESULTS: Through in vivo exploration, mouse forestomach carcinoma (MFC) cells with LSD1 knockout (KO) showed significantly slow growth in 615 mice than T-cell-deficient BALB/c nude mice. Meanwhile, in GC specimens, expression of LSD1 was negatively correlated with that of CD8 and positively correlated with that of PD-L1. Further study showed that LSD1 inhibited the response of T cells in the microenvironment of GC by inducing the accumulation of PD-L1 in exosomes, while the membrane PD-L1 stayed constant in GC cells. Using exosomes as vehicles, LSD1 also obstructed T-cell response of other cancer cells while LSD1 deletion rescued T-cell function. It was found that while relying on the existence of LSD1 in donor cells, exosomes can regulate MFC cells proliferation with distinct roles depending on exosomal PD-L1-mediated T-cell immunity in vivo. CONCLUSION: LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in GC; this finding indicates a new mechanism with which LSD1 may regulate cancer immunity in GC and provides a new target for immunotherapy against GC.


Asunto(s)
Antígeno B7-H1 , Neoplasias Gástricas , Animales , Histona Demetilasas/genética , Humanos , Ratones , Ratones Desnudos , Neoplasias Gástricas/genética , Linfocitos T , Microambiente Tumoral
6.
Crit Rev Food Sci Nutr ; 62(30): 8388-8402, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34014123

RESUMEN

Whole grain cereals have been the basis of human diet since ancient times. Due to rich in a variety of unique bioactive ingredients, they play an important role in human health. This review highlights the contents and distribution of primary functional components and their health effects in commonly consumed whole grain cereals, especially dietary fiber, protein, polyphenols, and alkaloids. In general, cereals exert positive effects in the following ways: 1) Restoring intestinal flora diversity and increasing intestinal short-chain fatty acids. 2) Regulating plasma glucose and lipid metabolism, thereby the improvement of obesity, cardiovascular and cerebrovascular diseases, diabetes, and other chronic metabolic diseases. 3) Exhibiting antioxidant activity by scavenging free radicals. 4) Preventing gastrointestinal cancer via the regulation of classical signaling pathways. In summary, this review provides a scientific basis for the formulation of whole-grain cereals-related dietary guidelines, and guides people to form scientific dietary habits, so as to promote the development and utilization of whole-grain cereals.


Asunto(s)
Grano Comestible , Granos Enteros , Humanos , Fibras de la Dieta , Dieta , Obesidad/prevención & control
7.
Analyst ; 147(2): 358-365, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-34981079

RESUMEN

The detection of ultralow heavy metal ion concentration is highly significant for protecting human health and maintaining the stability of the ecological environment. Herein, a microfiber interferometer chemical sensor for the detection of Ni2+ ions was proposed and experimentally demonstrated. The microfiber sensor was coated with an ion-imprinted chitosan polymer using Ni2+ as the template ion. Experimental results demonstrated a high sensitivity of 0.0454 nm nM-M for detect-ing Ni2+ in the range of 10 nM to 100 nM, and a limit of detection as low as 6.5 nM was achieved. The microfiber sensor was verified using two different non-template heavy ions, Cu2+ and Cr3+, and was determined to be highly selective to Ni2+. Furthermore, the regeneration characteristics of the sensor were experimentally assessed by three repeated adsorption-desorption cycles, and the results showed that the microfiber sensor achieved good stability without a significant loss in sensitivity. Besides, the detecting tests of Ni2+ in lake water and industrial sewage samples demonstrated the sensor's practical application. This proposed sensor has the advantages of simple configuration, high selectivity and sensitivity, fast response, and the ability to serve as a platform for water safety monitoring and remote sensing.


Asunto(s)
Quitosano , Metales Pesados , Humanos , Iones , Polímeros , Tecnología
8.
Int J Mol Sci ; 23(7)2022 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-35408903

RESUMEN

Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in the cure of colon cancer. Therefore, there is an urgent need to explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be of great significance for improving clinical efficacy. The dietary flavonoid kaempferol plays a key role in the progression of colorectal cancer and 5-Fu resistance. However, the molecular mechanism of kaempferol in reversing 5-Fu resistance in human colorectal cancer cells is still unclear. We found that kaempferol could reverse the drug resistance of HCT8-R cells to 5-Fu, suggesting that kaempferol alone or in combination with 5-Fu has the potential to treat colorectal cancer. It is well known that aerobic glycolysis is related to tumor growth and chemotherapy resistance. Indeed, kaempferol treatment significantly reduced glucose uptake and lactic acid production in drug-resistant colorectal cancer cells. In terms of mechanism, kaempferol promotes the expression of microRNA-326 (miR-326) in colon cancer cells, and miR-326 could inhibit the process of glycolysis by directly targeting pyruvate kinase M2 isoform (PKM2) 3'-UTR (untranslated region) to inhibit the expression of PKM2 or indirectly block the alternative splicing factors of PKM mRNA, and then reverse the resistance of colorectal cancer cells to 5-Fu. Taken together, our data suggest that kaempferol may play an important role in overcoming resistance to 5-Fu therapy by regulating the miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , MicroARNs , Proteínas Portadoras , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Glucólisis , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Humanos , Quempferoles , Proteínas de la Membrana , MicroARNs/metabolismo , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Hormonas Tiroideas , Proteínas de Unión a Hormona Tiroide
9.
Int J Mol Sci ; 23(20)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36292959

RESUMEN

Polyphenol-rich foods are gaining popularity due to their potential beneficial effects in the prevention and treatment of cancer. Foxtail millet is one of the important functional foods, riches in a variety of biologically active substance. Our previous study showed that ferulic acid (FA) and p-coumaric acid (p-CA) are the main anticancer components of foxtail millet bran, and the two have a significant synergistic effect. In the present study, the clinical application potential of FA and p-CA (FA + p-CA) were evaluated in vivo and in vitro. The FA and p-CA target gene enrichment analysis discovered that FA + p-CA were associated with aerobic glycolysis. It was further shown that FA + p-CA remodel aerobic glycolysis by inhibiting the glycolysis-associated lncRNA 495810 and the glycolytic rate-limiting enzyme M2 type pyruvate kinase (PKM2). Moreover, PKM2 expression was positively correlated with lncRNA 495810. More interestingly, the exogenous expression of lncRNA 495810 eliminated the inhibitory effects of FA + p-CA on aerobic glycolysis. Collectively, FA + p-CA obstruct the aerobic glycolysis of colorectal cancer cells via the lncRNA 495810/PKM2 axis, which provides a nutrition intervention and treatment candidate for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piruvato Quinasa/metabolismo , Polifenoles , Línea Celular Tumoral , Glucólisis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética
10.
Molecules ; 27(17)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36080360

RESUMEN

Background: Targeting the CD47/SIRPα signaling pathway represents a novel approach to enhance anti-tumor immunity. However, the crystal structure of the CD47/SIRPα has not been fully studied. This study aims to analyze the structure interface of the complex of CD47 and IMM01, a novel recombinant SIRPα-Fc fusion protein. Methods: IMM01-Fab/CD47 complex was crystalized, and diffraction images were collected. The complex structure was determined by molecular replacement using the program PHASER with the CD47-SIRPαv2 structure (PDB code 2JJT) as a search model. The model was manually built using the COOT program and refined using TLS parameters in REFMAC from the CCP4 program suite. Results: Crystallization and structure determination analysis of the interface of IMM01/CD47 structure demonstrated CD47 surface buried by IMM01. Comparison with the literature structure (PDB ID 2JJT) showed that the interactions of IMM01/CD47 structure are the same. All the hydrogen bonds that appear in the literature structure are also present in the IMM01/CD47 structure. These common hydrogen bonds are stable under different crystal packing styles, suggesting that these hydrogen bonds are important for protein binding. In the structure of human CD47 in complex with human SIRPα, except SER66, the amino acids that form hydrogen bonds are all conserved. Furthermore, comparing with the structure of PDB ID 2JJT, the salt bridge interaction from IMM01/CD47 structure are very similar, except the salt bridge bond between LYS53 in IMM01 and GLU106 in CD47, which only occurs between the B and D chains. However, as the side chain conformation of LYS53 in chain A is slightly different, the salt bridge bond is absent between the A and C chains. At this site between chain A and chain C, there are a salt bridge bond between LYS53 (A) and GLU104 (C) and a salt bridge bond between HIS56 (A) and GLU106 (C) instead. According to the sequence alignment results of SIRPα, SIRPß and SIRPγ in the literature of PDB ID 2JJT, except ASP100, the amino acids that form common salt bridge bonds are all conserved. Conclusion: Our data demonstrated crystal structure of the IMM01/CD47 complex and provides a structural basis for the structural binding interface and future clinical applications.


Asunto(s)
Aminoácidos , Antígenos de Diferenciación , Antígeno CD47 , Receptores Inmunológicos , Aminoácidos/química , Antígenos de Diferenciación/química , Antígeno CD47/química , Humanos , Fagocitosis , Unión Proteica , Receptores Inmunológicos/química , Proteínas Recombinantes de Fusión/química
11.
Cancer Control ; 28: 10732748211040009, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34468231

RESUMEN

Gliomas are the most prevalent brain tumors among children and adolescents. The occurrence and development of various malignant tumors is closely related with LIN28A gene, but its relationship with glioma susceptibility has not been widely discovered. In this case-control study, we conducted four single nucleotide polymorphisms (SNPs) (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) of LIN28A gene to investigate whether they increase the risk of glioma. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate their relationship. There was no significant correlation between four SNPs and glioma risk in single polymorphism and conjoint analysis. However, in stratification analysis, we found that rs3811463 TC/CC may add to the risk of glioma with clinical stage III (adjusted OR = 3.16, 95% CI = 1.15-8.70, P = .026) or stage III+IV patients (adjusted OR = 2.05, 95% CI = 1.02-4.13, P = .044). Our research suggested that four SNPs of LIN28A gene have a weak relationship with the risk of glioma in Chinese children. LIN28A rs3811463 TC/CC may increase the possibility of glioma in clinical stage III or stage III+IV patients which need larger samples and further confirmation.


Asunto(s)
Neoplasias Encefálicas/genética , ADN de Neoplasias/análisis , Predisposición Genética a la Enfermedad , Glioma/genética , Polimorfismo de Nucleótido Simple , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Niño , China/epidemiología , Genotipo , Glioma/diagnóstico , Humanos , Estadificación de Neoplasias , Proteínas de Unión al ARN/genética
12.
Environ Res ; 202: 111605, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34197819

RESUMEN

In this study, a novel electrochemical sensor for simultaneous detection of Pb(II) and Cu(II) was constructed by using Zn/Ni-ZIF-8/XC-72/Nafion hybrid material as electrode surface modifier. XRD, FT-IR, XPS and SEM were used to study the crystal structure, functional groups, element types and morphologies of the prepared materials. The electrochemical performance of the Zn/Ni-ZIF-8/XC-72/Nafion/GCE sensor were investigated by CV, EIS and DPV. In addition, the effects of various conditions including pH, the type of buffer and the ratio of Zn/Ni-ZIF-8 to XC-72 were also explored for the determination of Pb(II) and Cu(II). Under the optimum conditions, the constructed sensor exhibited outstanding linear response of Pb(II) (0.794-39.6 ppm) and Cu(II) (0.397-19.9 ppm) with detection limits of 0.0150 and 0.0096 ppm, respectively. Finally, the fabricated sensor was further used to detect Pb(II) and Cu(II) in real samples, and the satisfactory recovery was obtained.


Asunto(s)
Plomo , Zinc , Electrodos , Polímeros de Fluorocarbono , Espectroscopía Infrarroja por Transformada de Fourier
13.
J Sep Sci ; 44(5): 1015-1025, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33355404

RESUMEN

Superparamagnetic core-shell structured molecularly imprinted polydopamine nanospheres were constructed via self-polymerization of dopamine to attach the template onto the surface of magnetic Fe3 O4 substrate in tris-HCl solution. Then they were used for the specific recognition and extraction of perfluorooctane sulfonate from environmental water and human serum samples. The structural features and morphological characterization of the magnetic imprinting nanospheres were assessed, indicating that the magnetic polydopamine imprinted composite was successfully prepared and featured excellent magnetic separation characteristics. Adsorption experiments revealed that the magnetic adsorbents exhibited rapid adsorption kinetics and highly selective recognition properties toward perfluorooctane sulfonate. The stability and regeneration experiments indicated the materials had repeatable activity retention after repeated reuse. As a magnetic solid-phase extraction adsorbent, it was successfully applied for the extraction and quantification of perfluorooctane sulfonate in environmental water and human serum samples combined with liquid chromatography tandem mass spectrometry, with recoveries of ∼70-101.5% obtained in real samples. These results demonstrate that the prepared magnetic imprinting nanospheres are effective for the selective separation of perfluorooctane sulfonate from real samples. The synthesis technique is an effective and facile method that is conducted in aqueous solution and at ambient temperature, which is low cost, environmentally benign, and easy for scaling-up.

14.
Drug Resist Updat ; 48: 100663, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31785545

RESUMEN

Drug resistance is a major obstacle in the field of pre-clinical and clinical therapeutics. The development of novel technologies and targeted therapies have yielded new modalities to overcome drug resistance, but multidrug resistance (MDR) remains one of the major challenges in the treatment of cancer. The ubiquitin-proteasome system (UPS) has a central role in regulating the levels and activities of a multitude of proteins as well as regulation of cell cycle, gene expression, response to oxidative stress, cell survival, cell proliferation and apoptosis. Therefore, inhibition of the UPS could represent a novel strategy for the treatment and overcoming of drug resistance in chemoresistant malignancies. In 2003, bortezomib was approved by the FDA for the treatment of multiple myeloma (MM). However, due to its limitations, second generation proteasome inhibitors (PIs) like carfilzomib, ixazomib, oprozomib, delanzomib and marizomib were introduced which displayed clinical activity in bortezomib-resistant tumors. Past studies have demonstrated that proteasome inhibition potentiates the anti-cancer efficacy of other chemotherapeutic drugs by: i) decreasing the expression of anti-apoptotic proteins such as TNF-α and NF-kB, ii) increasing the levels of Noxa, a pro-apoptotic protein, iii) activating caspases and inducing apoptosis, iv) degrading the pro-survival protein, induced myeloid leukemia cell differentiation protein (MCL1), and v) inhibiting drug efflux transporters. In addition, the mechanism of action of the immunoproteasome inhibitors, ONX-0914 and LU-102, suggested their therapeutic role in the combination treatment with PIs. In the current review, we discuss various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents.


Asunto(s)
Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina/metabolismo , Animales , Humanos , Neoplasias/metabolismo , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/uso terapéutico , Transducción de Señal/efectos de los fármacos
15.
BMC Genet ; 20(1): 54, 2019 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-31272371

RESUMEN

BACKGROUND: Overgrazing is a major factor that causes steppe degradation in Inner Mongolian, resulting in extensive ecosystem damage. Scarcity of grass means sheep are smaller and therefore mutton and cashmere production is greatly reduced, which has resulted in massive annual economic losses. Liver is the primary metabolic organ in mammals. It is also the key source of energy supply and detoxification of metabolites in animals, has a close relationship with animal growth. However, investigations on the responses of sheep induced by consequence of overgrazing, particularly those relating to liver-related molecular mechanisms and related metabolic pathways, remain elusive. RESULTS: The body weight daily gain of sheep, immune organ indices (liver and spleen), and serum parameters related to immune response, protein synthesis and energy supply (IgG, albumin, glucose and non-esterified fatty acid) were significantly lower in the overgrazing group. Other serum parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen and interleukin-6 were significantly higher in the overgrazing group. For the RNA-Seq results, we identified approximately 50 differentially expressed genes, of which half of were up-regulated and the other half were down-regulated (overgrazing group versus light grazing group). Bioinformatics analysis identified two enriched KEGG pathways including peroxisome proliferator-activated receptor (PPAR) signaling pathway (related to lipolysis) and ECM-receptor interaction (related to liver injury and apoptosis). Additionally, several of the down-regulated genes were related to detoxification and immune response. CONCLUSIONS: Overall, based on the high-throughput RNA sequencing profile integrated with the results of serum biochemical analyses, consequences of lower forage availability and quality under overgrazing condition induced altered expression levels of genes participating in energy metabolism (particularly lipid metabolism) and detoxification and immune responses, causing lipolysis and impaired health status, which might be key reasons for the reduced growth performance of sheep. This investigation provides a novel foundation for the development of sheep hepatic gene interactive networks that are a response to the degraded forage availability under overgrazing condition.


Asunto(s)
Herbivoria , Hígado/metabolismo , Ovinos/genética , Transcriptoma , Animales , Biomarcadores , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Redes y Vías Metabólicas , Ovinos/metabolismo , Transducción de Señal
16.
BMC Vet Res ; 15(1): 469, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31878922

RESUMEN

BACKGROUND: Overgrazing is a primary contributor to severe reduction in forage quality and production in Inner Mongolia, leading to extensive ecosystem degradation, sheep health impairment and growth performance reduction. Further studies to identify serum biomarkers that reflect changes in sheep health and nutritional status following overgrazing would be beneficial. We hereby hypothesize that reduced sheep growth performance under overgrazing conditions would be associated with metabolic and immune response alterations. This study used an untargeted metabolomics analysis by conducting ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) of sheep serum under overgrazing and light grazing conditions to identify metabolic disruptions in response to overgrazing. RESULTS: The sheep body weight gains as well as serum biochemical variables associated with immune responses and nutritional metabolism (immunoglobulin G, albumin, glucose, and nonesterified fatty acids) were significantly decreased with overgrazing compared with light grazing condition. In contrast, other serum parameters such as alanine and aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, and interleukin-8 were markedly higher in the overgrazing group. Principal component analysis discriminated the metabolomes of the light grazing from the overgrazing group. Multivariate and univariate analyses revealed changes in the serum concentrations of 15 metabolites (9 metabolites exhibited a marked increase, whereas 6 metabolites showed a significant decrease) in the overgrazing group. Major changes of fatty acid oxidation, bile acid biosynthesis, and purine and protein metabolism were observed. CONCLUSIONS: These findings offer metabolic evidence for putative biomarkers for overgrazing-induced changes in serum metabolism. Target-identification of these particular metabolites may potentially increase our knowledge of the molecular mechanisms of altered immune responses, nutritional metabolism, and reduced sheep growth performance under overgrazing conditions.


Asunto(s)
Dieta/veterinaria , Metaboloma , Oveja Doméstica/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Biomarcadores/sangre , China , Pradera , Herbivoria , Masculino , Oveja Doméstica/sangre , Oveja Doméstica/inmunología , Aumento de Peso
17.
Hereditas ; 156: 34, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31708719

RESUMEN

BACKGROUND: Cadmium (Cd) is a ubiquitous environmental toxicant for aquatic animals. The freshwater crab, Sinopotamon henanense (S. henanense), is a useful model for monitoring Cd exposure since it is widely distributed in sediments whereby it tends to accumulate several toxicants, including Cd. In the recent years, the toxic effects of Cd in the hepatopancreas of S. henanense have been demonstrated by a series of biochemical analysis and ultrastructural observations as well as the deep sequencing approaches and gene expression profile analysis. However, the post-transcriptional regulatory network underlying Cd toxicity in S.henanense is still largely unknown. RESULTS: The miRNA transcriptional profile of the hepatopancreas of S. henanense was used to investigate the expression levels of miRNAs in response to Cd toxicity. In total, 464 known miRNAs and 191 novel miRNAs were identified. Among these 656 miRNAs, 126 known miRNAs could be matched with the miRNAs of Portunus trituberculatus, Eriocheir sinensis and Scylla paramamosain. Furthermore, a total of 24 conserved miRNAs were detected in these four crab species. Fifty-one differentially expressed miRNAs were identified in the Cd-exposed group, with 31 up-regulated and 20 down-regulated. Eight of the differentially expressed miRNAs were randomly selected and verified by the quantitative real-time PCR (qRT-PCR), and there was a general consistency (87.25%) between the qRT-PCR and miRNA transcriptome data. A total of 5258 target genes were screened by bioinformatics prediction. GO term analysis showed that, 17 GO terms were significantly enriched, which were mainly related to the regulation of oxidoreductase activity. KEGG pathway analysis showed that 18 pathways were significantly enriched, which were mainly associated with the biosynthesis, modification and degradation of proteins. CONCLUSION: In response to Cd toxicity, in the hepatopancreas of S. henanense, the expressions of significant amount of miRNAs were altered, which may be an adaptation to resist the oxidative stress induced by Cd. These results provide a basis for further studies of miRNA-mediated functional adaptation of the animal to combat Cd toxicity.


Asunto(s)
Braquiuros/efectos de los fármacos , Braquiuros/genética , Cadmio/toxicidad , Hepatopáncreas/efectos de los fármacos , Hepatopáncreas/metabolismo , MicroARNs/genética , Animales , Braquiuros/metabolismo , Cadmio/metabolismo , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Transcriptoma
18.
Mikrochim Acta ; 186(6): 380, 2019 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-31134351

RESUMEN

Nitrogen-doped carbon dots (NCDs) were synthesized via hydrothermal treatment of vitamin B1 and triethylamine. The NCDs exhibit strong blue fluorescence (with a peak at 437 nm at an excitation wavelength of 370 nm), good water solubility and excellent fluorescence stability in the pH 3~12 range, at ionic strengths between 0.01 and 1 M, and under UV illumination for 6 h, as well as incubation temperature of 15~60 °C. The nanoparticles respond selectively and sensitively to trace concentrations of perfluorooctane sulfonate (PFOS) through electrostatic interactions between PFOS and NCDs. This is accompanied by the aggregation of NCDs to yield enhanced fluorescence. The nanoprobe has high selectivity for PFOS even in presence of other common ions such as metal ions, anions, and structural analogues such as surfactants. Under the optimal conditions, the response is linear in the 0.3 to 160 nM PFOS concentration range with a detection limit of 0.3 nM. Satisfactory results were achieved for determination of PFOS in spiked real water samples. Graphical abstract Schematic presentation of the synthetic route to nitrogen-doped carbon dots (NCDs) starting from vitamin B1 and triethylamine, and its application for selective and sensitive fluorometric determination of perfluorooctane sulfonate (PFOS).

19.
Genet Mol Biol ; 42(3): 624-634, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31424071

RESUMEN

Drought and cold are the primary factors limiting plant growth worldwide. The Ammopiptanthus mongolicus NAC11 (AmNAC11) gene encodes a stress-responsive transcription factor. Expression of the AmNAC11 gene was induced by drought, cold and high salinity. The AmNAC11 protein was localized in the nucleus and plays an important role in tolerance to drought, cold and salt stresses. We also found that differential expression of AmNAC11 was induced in the early stages of seed germination and was related to root growth. When the AmNAC11 gene was introduced into Arabidopsis thaliana by an Agrobacterium-mediated method, the transgenic lines expressing AmNAC11 displayed significantly enhanced tolerance to drought and freezing stresses compared to wild-type Arabidopsis thaliana plants. These results indicated that over-expression of the AmNAC11 gene in Arabidopsis could significantly enhance its tolerance to drought and freezing stresses. Our study provides a promising approach to improve the tolerance of crop cultivars to abiotic stresses through genetic engineering.

20.
BMC Plant Biol ; 18(1): 81, 2018 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-29739327

RESUMEN

BACKGROUND: This study was designed to reveal potential molecular mechanisms of long-term overgrazing-induced dwarfism in sheepgrass (Leymus chinensis). METHODS: An electrospray ionisation mass spectrometry system was used to generate proteomic data of dwarf sheepgrass from a long-term overgrazed rangeland and normal sheepgrass from a long-term enclosed rangeland. Differentially expressed proteins (DEPs) between dwarf and normal sheepgrass were identified, after which their potential functions and interactions with each other were predicted. The expression of key DEPs was confirmed by high-performance liquid chromatography mass spectrometry (HPLC-MS) using a multiple reaction monitoring method. RESULTS: Compared with normal sheepgrass, a total of 51 upregulated and 53 downregulated proteins were identified in dwarf sheepgrass. The amino acids biosynthesis pathway was differentially enriched between the two conditions presenting DEPs, such as SAT5_ARATH and DAPA_MAIZE. The protein-protein interaction (PPI) network revealed a possible interaction between RPOB2_LEPTE, A0A023H9M8_9STRA, ATPB_DIOEL, RBL_AMOTI and DNAK_GRATL. Four modules were also extracted from the PPI network. The HPLC-MS analysis confirmed the upregulation and downregulation of ATPB_DIOEL and DNAK_GRATL, respectively in dwarf samples compared with in the controls. CONCLUSIONS: The upregulated ATPB_DIOEL and downregulated DNAK_GRATL as well as proteins that interact with them, such as RPOB2_LEPTE, A0A023H9M8_9STRA and RBL_AMOTI, may be associated with the long-term overgrazing-induced dwarfism in sheepgrass.


Asunto(s)
Proteínas de Plantas/metabolismo , Poaceae/crecimiento & desarrollo , Aminoácidos/metabolismo , Crianza de Animales Domésticos , Cromatografía Líquida de Alta Presión , Regulación de la Expresión Génica de las Plantas , Espectrometría de Masas , Redes y Vías Metabólicas , Proteínas de Plantas/fisiología , Poaceae/metabolismo , Poaceae/fisiología , Proteómica , Espectrometría de Masa por Ionización de Electrospray
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