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1.
Sci Rep ; 12(1): 7731, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546169

RESUMO

Chlorophyll (Chl) is an essential component of the photosynthetic apparatus and pigments in plant greening. Leaf color is an important agronomic and commercial trait of Chinese cabbage. In this study, we identified a pale green mutant pgm created by ethyl methane sulfonate (EMS) mutagenesis in Chinese cabbage. Compared with wild-type (FT), pgm had a lower Chl content with a higher Chl a/b ratio, imperfect chloroplast structure, and lower non-photochemical quenching. However, its net photosynthetic rate and biomass showed no significant differences. Genetic analysis revealed that the pale green phenotype of pgm was controlled by a recessive nuclear gene, designated as Brpgm. We applied BSR-Seq, linkage analysis, and whole-genome resequencing to map Brpgm and predicted that the target gene was BraA10g007770.3C (BrCAO), which encodes chlorophyllide a oxygenase (CAO). Brcao sequencing results showed that the last nucleotide of its first intron changed from G to A, causing the deletion of the first nucleotide in its second CDS and termination of the protein translation. The expression of BrCAO in pgm was upregulated, and the enzyme activity of CAO in pgm was significantly decreased. These results provide an approach to explore the function of BrCAO and create a pale green variation in Chinese cabbage.

2.
Protoplasma ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35570202

RESUMO

Isolated microspore culture has been implemented in breeding programs to produce doubled haploid (DH) lines and thus accelerates the breeding process. However, low microspore embryogenesis frequency in flowering Chinese cabbage remains a key obstacle to the practical application of this technique. This study aimed to establish an efficient microspore culture protocol for flowering Chinese cabbage that would be applied for heterosis breeding. Microspores of five genotypes, 19AY05, 19AY06, 19AY10, 19AY12, and 19AY15, were successfully induced to produce embryos in NLN-13 medium. Microspores of two genotypes, 19AY05 and 19AY15, were cultivated in NLN-13 medium supplemented with different concentrations (0, 0.01, 0.05, 0.1, or 0.2 mg·L-1) of compound sodium nitrophenol (sodium nitrophenol, 5-nitrophenol) to enhance microspore embryogenesis and plant regeneration without an intervening callus phase. The results showed that 0.05 ~ 0.1 mg· L-1 sodium nitrophenol and 0.01 ~ 0.2 mg· L-1 of 5-nitrophenol significantly promoted the induction of microspore embryogenesis of two genotypes, and the best concentrations required for different genotypes are different. Moreover, 0.1 mg· L-1 sodium nitrophenol can significantly increase the plant regeneration rate of the two genetypes. The 5-nitrophenol at 0.01 mg·L-1 significantly increased rate of embryos directly convert to plant in 19AY15. In addition, the average doubled haploid rates in the five genotypes were close to 63%. Horticultural traits of DH lines from 19AY05 were identified and all of them were self-incompatible lines. They showed a high uniformity and consistency that can be directly used for hybrid breeding. Furthermore, the hybrid combination was prepared with the selected DH lines and the Guangdong nucleus genic sterile line GMS019 to screen the excellent hybrid combination for the flowering Chinese cabbage breeding program. This method accelerates the application of microspore culture in hybrid breeding of flowering Chinese cabbage.

3.
Theor Appl Genet ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35532733

RESUMO

KEY MESSAGE: qFT7.1, a major QTL for flowering time in Brassica rapa was fine-mapped to chromosome A07 in a 56.4-kb interval, in which the most likely candidate gene is BraA07g018240.3C. In Brassica rapa, flowering time (FT) is an important agronomic trait that affects the yield, quality, and adaption. FT is a complicated trait that is regulated by many genes and is affected greatly by the environment. In this study, a chromosome segment substitution line (CSSL), CSSL16, was selected that showed later flowering than the recurrent parent, a rapid-cycling inbred line of B. rapa (RcBr). Using Bulked Segregant RNA sequencing, we identified a late flowering quantitative trait locus (QTL), designated as qFT7.1, on chromosome A07, based on a secondary-F2 population derived from the cross between CSSL16 and RcBr. qFT7.1 was further validated by conventional QTL mapping. This QTL explained 39.9% (logarithm of odds = 32.2) of the phenotypic variations and was fine mapped to a 56.4-kb interval using recombinant analysis. Expression analysis suggested that BraA07g018240.3C, which is homologous to ATC (encoding Arabidopsis thaliana CENTRORADIALIS homologue), a gene for delayed flowering in Arabidopsis, as the most promising candidate gene. Sequence analysis demonstrated that two synonymous mutations existed in the coding region and numerous bases replacements existed in promoter region between BraA07g018240.3C from CSSL16 and RcBr. The results will increase our knowledge related to the molecular mechanism of late flowering in B. rapa and lays a solid foundation for the breeding of late bolting B. rapa.

4.
Langmuir ; 38(18): 5803-5811, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35499163

RESUMO

Through molecular structure design, modified polycarboxylate superplasticizers (PCEs) were synthesized via copolymerization using isoprenyl oxy poly(ethylene glycol) ether (TPEG), acrylic acid, and hydroxyethyl methacrylate phosphate. TPEG-PCEs were selected as potential dispersants for Na/Ca-bentonite containing cement mortar. Other two kinds of commercial PCE that were obtained based on methallyl ether (HPEG) and ethylene-glycol monovinyl polyethylene glycol (EPEG) as macromonomers were also applied in the mortar. The effects of the type of bentonite and its dosage, as well as the monomer structure of PCEs and the type of cement, on the dispersion properties of the bentonite-containing mortar were studied. According to the findings, the initial fluidity of the mortar was reduced by about 20 mm when two kinds of bentonite were used. Applying 3% Ca-bentonite resulted in 40% flow loss in the mortar after 1 h. The fluidity of the mortar with Na-bentonite exhibited lower dispersion ability than that with Ca-bentonite when HPEG-PCE and EPEG-PCE were chosen as dispersants. The TPEG-PCE exhibited superior dispersing performance over HPEG-PCE and EPEG-PCE and exerted a retarding effect on cement, being also weakly sensitive to clay content. Thus, TPEG-PCEs with phosphate groups present a viable alternative to conventional PCEs.

5.
Front Oncol ; 12: 851677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480091

RESUMO

Objective: The objective of the study is to investigate the feasibility of using the fractional order calculus (FROC) model to reflect tumor subtypes and histological grades of cervical carcinoma. Methods: Sixty patients with untreated cervical carcinoma underwent multi-b-value diffusion-weighted imaging (DWI) at 3.0T magnetic resonance imaging (MRI). The mono-exponential and the FROC models were fitted. The differences in the histological subtypes and grades were evaluated by the Mann-Whitney U test. Receiver operating characteristic (ROC) analyses were performed to assess the diagnostic performance and to determine the best predictor for both univariate analysis and multivariate analysis. Differences between ROC curves were tested using the Hanley and McNeil test, while the sensitivity, specificity, and accuracy were compared using the McNemar test. P-value <0.05 was considered as significant difference. The Bonferroni corrections were applied to reduce problems associated with multiple comparisons. Results: Only the parameter ß, derived from the FROC model could differentiate cervical carcinoma subtypes (P = 0.03) and the squamous cell carcinoma (SCC) lesions exhibited significantly lower ß than that in the adenocarcinoma (ACA) lesions. All the individual parameters, namely, ADC, ß, D, and µ derived from the FROC model, could differentiate low-grade cervical carcinomas from high-grade ones (P = 0.022, 0.009, 0.004, and 0.015, respectively). The combination of all the FROC parameters showed the best overall performance, providing the highest sensitivity (81.2%) and AUC (0.829). Conclusion: The parameters derived from the FROC model were able to differentiate the subtypes and grades of cervical carcinoma.

6.
3 Biotech ; 12(4): 104, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35463043

RESUMO

The promoter of the male sterile gene is important for studying male sterility. In this study, BraA08g014780.3C which differentially expressed between male sterile and fertile plants was identified from a genetic male sterile AB line of Chinese cabbage by RNA-seq. qRT-PCR revealed that BraA08g014780.3C was mainly expressed in the early stage of floral bud development in fertile plants, and preferentially expressed in their anthers. The promoter of BraA08g014780.3C was cloned and analyzed. Cis acting element analysis showed that the promoter of BraA08g014780.3C contains POLLEN1LELAT52 and GTGANTG10, which are both pollen-specific expression elements. The BraA08g014780.3Cp::GUS vector was constructed, then transformed to Arabidopsis thaliana Col-0. PCR analysis and sequencing of the transgenic Arabidopsis revealed that the GUS gene driven by the BraA08g014780.3C promoter was successfully transformed to the Arabidopsis. GUS staining indicated that the promoter of BraA08g014780.3C was an anther-specific promoter. Identifying the anther-specific promoter laid a foundation for revealing BraA08g014780.3C function in male sterility of Chinese cabbage. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03160-z.

7.
Am J Bot ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35419829

RESUMO

PREMISE OF THE STUDY: The phylogeography of coastal plant species is shaped by contemporary and historical biogeographic processes. In this study, we aim to decipher the phylogeography of Derris trifoliata, a woody legume of relatively recent origin and wide distribution, in coastal areas in the Indo-West Pacific (IWP) region. METHODS: Genetic diversity and population structure were assessed by analyzing six nuclear and three chloroplast DNA sequences from 30 populations across the species' range. Phylogeography was inferred by estimating gene flow, divergence time, historical population size changes, and historical habitat suitability using paleoclimatic niche-modeling. KEY RESULTS: High genetic diversity was observed at the species-level. The populations of three oceanic regions included in this study (i.e., Indian Ocean, South China Sea, and Pacific Ocean) formed distinct clades, and likely diverged during the late Pleistocene. Potential barriers to gene flow were identified, including the Sunda and Sahul shelves, geographic distance, and current patterns of oceanic circulation. Analysis of changes in population size supported the bottleneck model, which was strengthened by estimates of habitat suitability across paleoclimatic conditions. CONCLUSIONS: The once widespread distribution of D. trifoliata was fragmented by changes in climatic suitability and biogeographic barriers that arose following sea-level changes during the Pleistocene. In addition, contemporary patterns of oceanic circulation and geographic distance between populations appear to maintain genetic differentiation across its distribution in the IWP. This article is protected by copyright. All rights reserved.

8.
Food Funct ; 13(9): 5050-5060, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35403637

RESUMO

Due to the rapid evolution of antibiotic resistance in Staphylococcus aureus, antivirulence therapy may be a promising alternative for the effective control of the spread of resistant pathogens. The Chinese Materia Medica has been widely used for the treatment of diseases and production of health foods, and it remains a valuable resource for the discovery of compounds possessing antivirulence activity. Through a Caenorhabditis elegans infection model, an EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus. Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 µg mL-1, reducing hemolytic activity and α-hemolysin expression in S. aureus. Furthermore, at 100 mg kg-1, SMEA reduced abscess formation in the main organs of mice challenged with S. aureus. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo. Furthermore, at 24 µg mL-1, TNB significantly reduced the expression of RNAIII and psmα, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. In conclusion, TNB's antivirulence properties make it a promising candidate for drug development against S. aureus infections.


Assuntos
Anti-Infecciosos , Salvia miltiorrhiza , Infecções Estafilocócicas , Animais , Antibacterianos/metabolismo , Anti-Infecciosos/farmacologia , Camundongos , Percepção de Quorum , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Virulência
9.
Protoplasma ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476157

RESUMO

Isolated Microspore Culture (IMC) is an efficient method to obtain the homozygous strain; however, it is difficult to apply in ornamental kale due to its low rate of microspore embryogenesis. Histone acetylation is an important epigenetic mechanism and may affect the changes of the microspore development pathway, promoting microspore embryogenesis. Here, microspores from three cut-flower ornamental kales, namely Crane Feather Queen (CFQ), Crane Pink (CP), and Crane Bicolor (CB), were treated with the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) to induce embryogenesis. The haploid 'CFQ' microspore plantlets were doubled with colchicine. The results for 'CFQ' revealed that, the appropriate concentration of SAHA was 0.03 µM and obtained 17.27 embryos per bud. For 'CP,' the appropriate concentration of SAHA was 0.045 µM and obtained 11.19 embryos per bud. For 'CB,' the appropriate concentration of SAHA was 0.045 µM and obtained 6.10 embryos per bud. Haploid 'CFQ' microspore plantlets were treated with 75 mg/L colchicine for 7 d and the doubling rate was 41.7%. Haploid 'CFQ' plantlets were treated with 1000 mg/L colchicine by root-soaking for 4 h and the doubling rate was 64.3%. SAHA could promote microspore embryogenesis, and colchicine root soaking was more effective than adding colchicine to the medium for haploid plantlet doubling in cut-flower ornamental kale.

10.
Front Cardiovasc Med ; 9: 853583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35445093

RESUMO

Background: Patients with lower extremity arteriosclerosis obliterans (LEASO) are more likely to appear to be associated with adverse cardiovascular outcomes. Currently, few studies have reported the sex-specific characteristics and risk of major cardiovascular and cerebrovascular adverse events (MACCEs) in LEASO. Our study was conducted to determine the characteristics and contributions of LEASO to MACCEs in males and females. Methods: We conducted a single-center retrospective study of consecutively enrolled patients with first-diagnosed LEASO at Renmin Hospital of Wuhan University from November 2017 to November 2019. The ratio of patients between the LEASO and control groups was 1 to 1 and based on age, sex, comorbid diabetes mellitus and hypertension, current smoking and medications. The occurrence of MACCEs was used as the primary endpoint of this observational study. Results: A LEASO group (n = 430) and control group (n = 430) were enrolled in this study. A total of 183 patients experienced MACCEs during an average of 38.83 ± 14.28 months of follow-up. Multivariate Cox regression analysis indicated that LEASO was an independent predictor of the occurrence of MACCEs in all patients (HR: 2.448, 95% CI: 1.730-3.464, P < 0.001). Subgroup analysis by sex subgroup was conducted for sex, and LEASO was also an independent predictor of the occurrence of MACCEs in both male cases (HR: 2.919, 95% CI: 1.776-4.797, P < 0.001) and female cases (HR: 1.788, 95% CI: 1.110-2.880, P = 0.017). Moreover, Kaplan-Meier analysis indicated no significant difference in event-free survival between patients of different sexes with LEASO (χ2 = 0.742, P = 0.389). Conclusion: LEASO tended to a useful risk stratified indicator for MACCEs in both male and female patients in our study. Notably, attention should be given to patients with LEASO who should undergo comprehensive cardiovascular evaluation and intervention, even if there is a lack of traditional cardiovascular risk factors.

11.
Anal Chem ; 94(13): 5406-5414, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35315662

RESUMO

Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca2+ by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells.


Assuntos
Cálcio , Esterases , Diagnóstico por Imagem , Corantes Fluorescentes/química , Íons , Raízes de Plantas
12.
Neurosci Bull ; 38(4): 440-452, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35249185

RESUMO

Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.


Assuntos
Dor Crônica , Optogenética , Encéfalo , Humanos , Neurônios , Medula Espinal
13.
Immunopharmacol Immunotoxicol ; : 1-10, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35238277

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is a life-threatening disorder associated with multisystem organ failure. This study aimed to investigate the function of high mobility group box 1 (HMGB1) in SAP-induced myocardial injury. METHODS: A rat model with SAP was induced. The pathological changes in rat pancreatic and cardiac tissues were examined by HE staining. Cardiomyocyte apoptosis in rat cardiac tissues, and the serum levels of myocardial injury markers and pro-inflammatory cytokines were examined. Rat primary cardiomyocytes were treated with H2O2 for in vitro experiments. The regulatory molecules of HMGB1 were predicted by bioinformatics analysis. Altered expression of HMGB1, microRNA (miR)-340-5p and CCCTC-binding factor (CTCF) was introduced in rats or cells to investigate their roles in myocardial injury. RESULTS: CTCF and HMGB1 were highly expressed but miR-340-5p was poorly expressed in cardiac tissues of rats with SAP. HMGB1 silencing reduced toll-like receptor 4 (TLR4) expression to promote proliferation and reduce apoptosis of H2O2-treated cardiomyocytes. miR-340-5p targeted HMGB1 mRNA, while CTCF suppressed miR-340-5p transcription. CTCF upregulation or miR-340-5p downregulation blocked the effects of HMGB1 silencing on cardiomyocytes. In vivo, CTCF silencing alleviated injury in rat pancreatic and cardiac tissues and reduced the expression of creatine kinase-MB (CK-MB), lactic dehydrogenase, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) in rat serum. But further overexpression of HMGB1 or inhibition of miR-340-5p aggravated the symptoms in rats. CONCLUSION: This study demonstrated that CTCF reduces transcription of miR-340-5p to promote HMGB1 expression, which activates TLR4 expression and promotes myocardial injury in rats with SAP.

14.
Transl Lung Cancer Res ; 11(1): 87-99, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242630

RESUMO

BACKGROUND: The incidence of bone metastases in non-small cell lung cancer (NSCLC) patients is about 30-40% and bone-related events can seriously affect quality of life. Immune checkpoint inhibitor (ICI) therapy has become the standard treatment for advanced NSCLC patients. However, the specific efficacy of ICIs in NSCLC patients with bone metastases remains unclear. The aim of the present study was to explore the prognosis of immunotherapy in this population and to find potential biomarkers. METHODS: In this retrospective study, a total of 110 advanced NSCLC patients with bone metastases who received pembrolizumab therapy were enrolled. Patient characteristics; palliative bone radiotherapy or bone-targeted therapy; serum levels of lactate dehydrogenase (LDH), and the neutrophil-to-lymphocyte ratio (NLR) at baseline were assessed. The correlation of these factors with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) was analyzed. RESULTS: The ORR of the total population was 29.1%, and PFS and OS were 7.0 and 14.8 months, respectively. Fifty-eight patients (52.7%) received pembrolizumab treatment as first-line therapy, and 52 patients (47.3%) as second-line therapy or beyond [ORR: 41.4% vs. 15.4%, P=0.011; PFS: 9.0 vs. 4.0 months, P=0.004; OS: not reached (NR) vs. 11.5 months, P<0.0001]. Bone therapy, including palliative bone radiotherapy and bone-targeted therapy, increased the ORR (34.9% vs. 11.1%, P<0.0001) and prolonged PFS (8.5 vs. 2.0 months, P=0.002). Eastern Cooperative Oncology Group performance status score of 0-1 [OS: hazard ratio (HR) =0.117, P<0.0001] and first-line pembrolizumab therapy (OS: HR =0.372, P=0.004) were independent predictors of OS. Patients whose baseline serum LDH level was ≤240.5 IU/L (NR vs. 10.0 months, P<0.0001) or NLR ≤5.55 (NR vs. 18.0 months, P=0.039) showed longer OS. CONCLUSIONS: The efficacy of Pembrolizumab therapy is confirmed in advanced NSCLC patients with bone metastases, particularly when palliative bone radiotherapy or bone-targeted therapy is delivered. Baseline serum LDH level ≤240.5 IU/L and NLR ≤5.55 might predict the prognosis of patients with bone metastases from advanced NSCLC treated with immunotherapy.

15.
Adv Sci (Weinh) ; 9(13): e2104850, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35239999

RESUMO

The Bcr/Abl plays a central role in Philadelphia chromosome-positive (Ph+) leukemia because of the constitutively activated Abl tyrosine kinase and its downstream pathways. Currently, the clinical treatment of imatinib-resistant patients with tyrosine kinase inhibitors is severely limited by drug resistance and adverse effects. Herein, a dual-targeting proteolysis-targeting chimera (PROTAC) protein drug, termed PMI Bcr/Abl-R6, is designed by engrafting an MDM2/p53 inhibition peptide sequence onto the Bcr/Abl tetramerization domain. PMI Bcr/Abl-R6, harboring a Bcr/Abl targeting sequence and an MDM2 binding sequence, acts as a PROTAC drug in Ph+ leukemia cells. Its dual-targeting constitution suggests that PMI Bcr/Abl-R6 designs to target the tetramerization domain instead of the Abl kinase domain, therefore has the potential to overcome drug resistance mutations in the kinase domain. The efficient ability of PMI Bcr/Abl-R6 is demonstrated to simultaneously induce Bcr/Abl degradation and activate the p53 pathway. PMI Bcr/Abl-R6 has the potential to overcome drug resistance in Ph+ leukemias by multiple mechanisms.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/uso terapêutico
16.
Eur J Med Chem ; 233: 114214, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35231829

RESUMO

The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. It was documented previously that co-administration of a cholecystokinin receptor-1 receptor (CCK-1R) agonist with a glucagon-like peptide-1 receptor (GLP-1R) agonist exerted improved effects on metabolic improvements in obese rodents. Here, we reported a series of novel GLP-1R/CCK-1R co-agonists constructed by linking the C-terminus of a GLP-1R agonist (native GLP-1 or Xenopus GLP-1) to the N-terminus of a CCK-1R selective agonist NN9056. The stability of co-agonists was further enhanced by introducing an albumin binding motif. In vitro functional assays revealed that the co-agonists retained full agonism potency on GLP-1R and CCK-1R. Particularly, 2a and 2c showed higher hypoglycemic and insulinotropic activities than NN9056 and semaglutide. The glucose-lowering durations and PK profiles of 2a and 2c were comparable to those of semaglutide. Desirably, in diet induced obesity (DIO) mice, 2a and 2c exhibited superior metabolic benefits to NN9056 and semaglutide in reducing food intake, inducing body weight loss, and regulating lipid metabolism. In short- and long-term studies in diabetic db/db mice, 2a and 2c showed enhanced effects on HbA1c, glucose tolerance, and pancreas function restoration compared with semaglutide. Importantly, no side effects, toxicities, or pancreatic inflammation were caused by 2a and 2c treatments. These preclinical studies suggest that the pharmacological effects of CCK-1 and GLP-1 pathways can be harnessed in a single fusion peptide, yielding a promising combination therapy strategy for treating metabolic disorders.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Perda de Peso , Animais , Colecistocinina , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Peptídeos/farmacologia , Receptores da Colecistocinina
17.
Oxid Med Cell Longev ; 2022: 9021474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265266

RESUMO

Neural stem cell (NSC) proliferation is the initial step for NSC participating in neurorehabilitation after central nervous system (CNS) injury. During this process, oxidative stress is always involved in restricting the regenerative ability of NSC. Tetrahydrofolate (THF) is susceptible to oxidative stress and exhibits a high antioxidant activity. While its effect on NSC proliferation under oxidative stress condition remains obscure. Here, NSC were isolated from embryonic mice and identified using immunofluorescent staining. Meanwhile, the results showed that THF (5 µM and 10 µM) attenuated oxidative stress induced by 50 µM hydrogen peroxide (H2O2) in NSC using mitochondrial hydroxyl radical detection and Western blotting assays. Afterward, administration of THF markedly alleviated the inhibitory effect of oxidative stress on NSC proliferation, which was evidenced by Cell Counting Kit-8 (CCK8), neurosphere formation, and immunofluorescence of Ki67 assays. Thereafter, the results revealed that PTEN/Akt/mTOR signaling pathway played a pivotal role in counteracting oxidative stress to rescue the inhibitory effect of oxidative stress on NSC proliferation using Western blotting assays and gene knockdown techniques. Collectively, these results demonstrate that THF mitigates the inhibitory effect of oxidative stress on NSC proliferation via PTEN/Akt/mTOR signaling pathway, which provides evidence for administrating THF to potentiate the neuro-reparative capacity of NSC in the treatment of CNS diseases with the presence of oxidative stress.


Assuntos
Células-Tronco Neurais/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tetra-Hidrofolatos/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Animais , Proliferação de Células , Humanos , Camundongos , Estresse Oxidativo , Tetra-Hidrofolatos/farmacologia , Complexo Vitamínico B/farmacologia
18.
Ann Palliat Med ; 11(2): 513-520, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35249329

RESUMO

BACKGROUND: Chronic respiratory insufficiency is mainly the result of ventilatory dysfunction due to various causes, which results in decreased respiratory function. The most important cause of chronic respiratory insufficiency is chronic obstructive pulmonary disease, which has a high incidence and places a great burden on families and society. Therefore, it is important to find an effective treatment for this disease. METHODS: This study was a retrospective self-controlled study. Thirty-eight patients receiving home oxygen therapy who visited the outpatient oxygen therapy clinic from November 2020 to August 2021 were selected. After a comprehensive and systematic diagnosis and treatment, home oxygen therapy as standardized, and 38 patients were followed up for 6 months. Oxygen therapy compliance, the average daily oxygen therapy duration, arterial blood gas analysis, activities of daily living (ADL), and modified Medical Research Council Dyspnea Scale (mMRC) scores before and 6 months after outpatient oxygen therapy intervention were compared. The number of hospital visits for acute exacerbation of chronic respiratory insufficiency and the medical costs incurred within 6 months before and after the outpatient oxygen therapy intervention were also compared. RESULTS: After 6 months of outpatient oxygen therapy intervention, the compliance with oxygen therapy was significantly improved, the average daily oxygen therapy duration was significantly prolonged, the oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) values were significantly increased, and the mMRC score was significantly decreased (P<0.05), while the differences in the ADL scores were not statistically significant (P>0.05). The number of hospital visits and the medical expenses due to acute exacerbation of chronic respiratory insufficiency within 6 months after the outpatient oxygen therapy intervention were significantly lower than those in the 6 months before the intervention (P<0.05). CONCLUSIONS: As a relatively new clinical service in China, outpatient oxygen therapy can improve the efficacy of home oxygen therapy for patients with chronic respiratory insufficiency through patient assessment, personalized selection of oxygen therapy equipment, and standardization of the implementation of home oxygen therapy. It provides an economically valuable treatment.


Assuntos
Atividades Cotidianas , Insuficiência Respiratória , Humanos , Pacientes Ambulatoriais , Oxigênio/uso terapêutico , Insuficiência Respiratória/terapia , Estudos Retrospectivos
19.
Adv Clin Exp Med ; 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275452

RESUMO

BACKGROUND: Mosapride significantly improves intestinal motility in liver cirrhosis, ultimately leading to the reduction in plasma endotoxin levels and bacterial translocation. OBJECTIVES: To investigate the effects of mosapride on intestinal microecology in cirrhotic rats and its potential mechanisms. MATERIAL AND METHODS: Forty-five healthy male Sprague-Dawley rats that were pathogen-free (weight 200-220 g) were randomly divided into a control group (n = 15), model group (n = 15) and mosapride group (n = 15). Then, the pathological changes in the liver and intestine were determined through tissue staining and using transmission electron microscope (TEM). Bacterial translocation was examined. High throughput 16S rRNA sequencing was performed to determine the changes of gut microbiota in each group. RESULTS: Compared with the model group, mosapride treatment induced no attenuation in hepatic morphology and pathology changes. The TEM indicated no differences in intestinal structure in both groups. There was a significant decline in the rate of gut microbiota translocation in the mosapride group compared with the model group. There were intestinal microbiota changes in the mosapride group compared with that of the model group, including Bacteroidetes, Prevotellaceae, Alloprevotella, Ruminiclostridium, Negativicutes, Selenomonadales, Veillonellaceae, Anaerovibrio, Campylobacterales, Epsilonbacteraeota, Helicobacter, Oscillibacter, Verrucomicrobiales, Akkermansia, Intestinimonas, Eubacterium, Clostridiaceae, Clostridium, Bacteroides, Tyzzerella, Actinobacteria, and Bifidobacteriales. Among these bacteria, Alloprevotella showed a strong correlation with the other bacteria. CONCLUSIONS: Taken together, we concluded that mosapride may reduce intestinal bacterial translocation through regulating the gut microbiota in rats with hepatic cirrhosis.

20.
Ying Yong Sheng Tai Xue Bao ; 33(2): 304-310, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229502

RESUMO

Water use efficiency (WUE) of five dominant tree species (Pinus koraiensis, Fraxinus mandshurica, Acer mono, Quercus mongolica, and Tilia amurensis) was estimated using the stable carbon isotope method in a broadleaved Korean pine forest in Changbai Mountains. Leaf carbon (C), nitrogen (N), and phosphorus (P) contents were measured to analyze nutrient utilization of the dominant species. The relationship between WUE and leaf nutrient contents was systematically assessed. WUE was different due to the variations of micrometeorological factors at different locations in the canopy. The four broadleaved tree species showed upper layer > middle layer > lower layer, while P. koraiensis showed upper layer > lower layer > middle layer. WUE of evergreen coniferous P. koraiensis was higher than that of two broadleaved species with diffuse-porous wood (T. amurensis and A. mono) and lower than that of two broadleaved species with ring-porous wood (F. mandshurica and Q. mongolica). The compound-leaved species (F. mandshurica) had the highest WUE. The WUE of new leaves was significantly higher than old leaves in P. koraiensis. The carbon content and C/N of the old and new leaves of evergreen coniferous P. koraiensis were significantly higher than those of the other four broadleaved tree species, while nitrogen content and N/P were significantly lower than those of the four broadleaved tree species. P content of old leaves of P. koraiensis was significantly lower than that of the four broadleaved tree species. P content of new leaves of current year was not significantly different from that of the broadleaved tree species. The WUE of five tree species had a poor correlation with leaf C content, but a positive correlation with leaf N content. The WUE of evergreen coniferous and deciduous broadleaved tree species was correlated with leaf P content but in opposite direction.


Assuntos
Pinus , Árvores , China , Florestas , Nutrientes , Folhas de Planta , República da Coreia , Água
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