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1.
Front Plant Sci ; 15: 1377253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654905

RESUMO

159 wheat varieties obtained from ICARDA, CYR32, CYR33 and CYR34 were used to evaluate the stripe rust resistance in this study. Seedling resistance was carried out in the green house at the two-leaf stage. Adult-plant resistance was carried out between 2022 and 2023 in Xining and Guide, respectively. A total of 24,151 high-quality SNP loci were obtained from a 55K SNP chip data. Genome-wide association study was carried out between SNP loci and stripe rust resistance. Seedling resistance screening revealed that 91.8% (146) of wheat varieties were resistant to CYR32 and CYR33, while only 49.7% (79) of wheat varieties were resistant to CYR34. Adult-plant resistance showed 153 (96.2%) germplasms represented resistance in 2022, while only 85 (53.4%) showed resistance in 2023. An association study using the 55K SNP chip data results combined with disease ratings of 159 materials at both the seedling and adult stages discovered 593 loci related to stripe rust resistance (P ≤ 0.0001). These loci exhibited contribution rates ranging from 11.1% to 18.7%. Among them, 71 were significantly related to resistance against CYR32 at the seedling stage, with a contribution rate of 12.7%-17.2%. Constituting the vast majority, 518 loci distributed across 21 chromosomes were significantly related to CYR33 at the seedling stage, with a contribution rate of 12.6%-18.7%. Fewer loci were found to be associated with disease resistance in adult plants. In E1 environment, a sole locus was detected on chromosome 2B with a contribution rate of 14.4%. In E2 environment, however, exhibited three loci across chromosomes 2B, 4A, and 7B with contribution rates ranging from 11.1% to 16.9%. A total of 68 multi-effect loci were significantly related to resistance against both CYR32 and CYR33 at the seedling stage, and one stable locus was significantly associated with stripe rust resistance at the adult plant stage.

2.
Front Pharmacol ; 15: 1331138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655174

RESUMO

Background: This study aims to determine the efficacy and safety profile of aumolertinib in the real-word treatment setting for advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. Methods: We retrospectively analyzed the clinical data of 173 EGFR-mutated advanced NSCLC patients who received aumolertinib treatment at Henan Cancer Hospital from April 2020 to December 2022. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves, while a Cox regression model was used for multifactorial analysis and prognostic factor assessment. Results: Among patients administered first-line aumolertinib (n = 77), the objective remission rate (ORR) of 77.92% was observed, along with a disease control rate (DCR) of 100%. The median progression-free survival (mPFS) was 24.97 months, which did not reach the median overall survival (mOS). The patients treated with aumolertinib after progression on prior EGFR-tyrosine kinase inhibitor (TKI) therapy (n = 96) exhibited an ORR of 46.88%, a DCR of 89.58%, an mPFS of 15.17 months, and an mOS of 21.27 months. First-line treatment multivariate Cox regression analysis demonstrated a statistically significant impact of elevated creatine kinase on PFS (p = 0.016) and a similar significant influence of co-mutation on OS (p = 0.034). Furthermore, subsequent-line treatment multivariate Cox regression analysis showed a statistically significant impact of elevated creatine kinase on median PFS (p = 0.026) and a significant effect on the number of metastatic organs (p = 0.017), co-mutation (p = 0.035), and elevated creatine kinase (p = 0.014) on median OS. Conclusion: Aumolertinib has shown clinical significance and can safely be used in the real-world setting for patients with EGFR mutation-positive NSCLC.

3.
iScience ; 27(5): 109706, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38660398

RESUMO

SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.

4.
J Nat Med ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662303

RESUMO

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.

5.
BMC Ophthalmol ; 24(1): 107, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448947

RESUMO

PURPOSE: To evaluate the association of body stature with ocular biometrics and refraction in preschool children. METHODS: A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. RESULTS: A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters. CONCLUSION: Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers.


Assuntos
Segmento Anterior do Olho , Estatura , Pré-Escolar , Humanos , Estudos Transversais , Biometria , China/epidemiologia
6.
Biofactors ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551331

RESUMO

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.

7.
Sci Rep ; 14(1): 6971, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521855

RESUMO

Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy-both of which contribute to cardiac atrophy and failure after doxorubicin treatment.


Assuntos
Cardiomiopatias , Miócitos Cardíacos , NADPH Oxidase 2 , Animais , Camundongos , Autofagia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Doxorrubicina/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/metabolismo , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Estresse Oxidativo , Simpatectomia
8.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 877-894, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38545984

RESUMO

Daqu is the saccharifying, fermenting, and aroma-producing agent used in Baijiu brewing, and its maturation is crucial for obtaining high-quality Daqu. Previous studies have explored the microbial community composition and diversity before and after maturation. However, little is known about the changes in the functions of microbial community. In this study, based on the analyses of enzyme activities and volatile compounds of medium-temperature Daqu before and after maturation, metagenomics was used to analyze the differences in the composition of microbial community and the potential functions, with the aim to explore the microorganisms involved in changes in enzyme activities and important volatiles. The results showed that the moisture (P≤0.05), starch content, liquefying activity, saccharifying activity (P≤0.05), and fermentative activity decreased, while the acidity and esterifying activity (P≤0.05) increased after Daqu maturation. In the meantime, the composition of volatile compounds changed significantly (P=0.001), with significant decreases in the contents of aromatic alcohols and esters as well as significant increases in the contents of pyrazines, ketones, and higher fatty alcohols. The relative abundances of Mucorales (34.8%-23.0%) and Eurotiales (34.3%-20.1%) decreased in matured Daqu, and functional predictions showed these changes decreased the gene abundances of α-amylase, α-glucosidase, alcohol dehydrogenase, and alcohol dehydrogenase (NADP+) (P > 0.05), resulting in lower levels of liquefying activity (P > 0.05), saccharifying activity (P≤0.05), fermentative activity (P > 0.05), as well as aromatic alcohols such as phenylethyl alcohol (P≤0.05). In addition, higher relative abundances of Saccharomycetales (2.9%-16.6%), Lactobacillales (14.9%-23.6%), and Bacillales (0.8%-3.8%) were observed after maturation, and they were conducive to improving the gene abundances of alcohol O-acetyltransferase, carboxylesterase, acetolactate decarboxylase, (R)-acetoin dehydrogenase, and (S)-acetoin dehydrogenase (P≤0.05), resulting in significantly higher levels of esterifying activity and pyrazines (P≤0.05). The microorganisms involved in the changes in enzyme activities and important volatiles before and after Daqu maturation were studied at the gene level in this work, which may facilitate further rational regulation for Daqu production.


Assuntos
Bactérias , Microbiota , Bactérias/genética , Temperatura , Acetoína Desidrogenase , Álcool Desidrogenase , Microbiota/fisiologia , Fermentação , Pirazinas
9.
Exp Ther Med ; 27(4): 136, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476884

RESUMO

[This retracts the article DOI: 10.3892/etm.2020.8623.].

10.
China CDC Wkly ; 6(6): 100-104, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38406636

RESUMO

What is already known about this topic?: Echinococcosis is classified as a Class C infectious disease in China. It is endemic in 370 counties located in the agricultural and pastoral regions of western China. What is added by this report?: This report provides a comprehensive overview of the cases of echinococcosis reported in China in 2022. Following a thorough evaluation conducted by provincial CDCs, it was identified that 105 new cases were not reported through the National Notifiable Disease Reporting System. Furthermore, there were 1,051 cases that were reported among patients who had been previously diagnosed with echinococcosis. What are the implications for public health practice?: The reported cases of echinococcosis in non-endemic counties of provincial-level administrative divisions where the disease is endemic need to be given more attention, as there is a potential risk of it spreading within the non-endemic areas. Inadequate reporting practices by clinical medical institutions are hindering the subsequent investigations carried out by CDCs. It is important to implement enhanced health promotion efforts that focus on high-risk populations to address unhealthy lifestyles.

11.
J Clin Lab Anal ; 38(4): e25012, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305509

RESUMO

BACKGROUND: RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. METHODS: The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro. RESULTS: We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. CONCLUSIONS: Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.


Assuntos
Neoplasias do Colo do Útero , Humanos , Camundongos , Feminino , Animais , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores de Quinase C Ativada/genética , Receptores de Quinase C Ativada/farmacologia
12.
Front Plant Sci ; 15: 1339417, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348268

RESUMO

Proper water and fertilizer management strategies are essential for alfalfa cultivation in arid areas. However, at present, the optimal amounts of subsurface irrigation and nitrogen (N) supply for alfalfa (Medicago sativa L.) cultivation are still unclear. Therefore, a field experiment was conducted in 2022 in Yinchuan, Ningxia, China, to explore the effects of different subsurface irrigation levels (W1, 50% of ETC (crop evapotranspiration); W2, 75% of ETC; W3, 100% of ETC) and N application rates (N0, 0 kg/ha; N1, 75 kg/ha; N2, 150 kg/ha; N3, 225 kg/ha; N4, 300 kg/ha) on alfalfa yield, crop water productivity (CWP), N use efficiency (NUE), quality, and economic benefits. Besides, the least squares method and multiple regression analysis were used to explore the optimal water and N combination for alfalfa cultivation under subsurface irrigation. The results showed that the alfalfa yield, crude ash content, and partial factor productivity from applied N (PFPN) were the highest under W2 level, but there was no difference in PFPN compared with that under W3 level. The branch number (BN), leaf area index (LAI), yield, CWP, irrigation water productivity (IWP), crude protein content (CPC), and economic benefits increased and then decreased with the increase of N application rate, reaching a maximum at the N2 or N3 level, while the NUE and PFPN decreased with the increase of N application rate. Considering the yield, CWP, NUE, quality, and economic benefits, W2N2 treatment was the optimal for alfalfa cultivation under subsurface irrigation. Besides, when the irrigation volume and N application rate were 69.8 ~ 88.7% of ETC and 145 ~ 190 kg/ha, respectively (confidence interval: 85%), the yield, CPC, and economic benefits reached more than 85% of the maximum. This study will provide technique reference for the water and N management in alfalfa cultivation in Northwest China.

13.
Phytomedicine ; 125: 155239, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308917

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a demyelination disorder caused by an overactive immune response. Its pathological characteristics include CNS inflammation, white matter demyelination, glial cell proliferation, and so on. Huangqi-Guizhi-Wuwu Decoction (HGWD), which is recorded in the Synopsis of the Golden Chamber, is used clinically for the therapy of MS, but its mechanism is still elusive. PURPOSE: This study was aimed to investigate the impact of HGWD on the classical animal model for MS, experimental autoimmune encephalomyelitis (EAE), and explore the underlying action mechanism. RESULTS: HGWD ameliorated the pathogenesis of EAE mice, and improved their neurobehavior and pathological tissue damage. Network pharmacology predictions revealed the action mechanism of HGWD in EAE mice might be related to its effect on the immune system of mice. HGWD effectively suppressed the inflammatory infiltration in CNS, while also preventing the elevation of CD4+T cells of mice with EAE. HGWD could increase the ratio of Treg cells, up-regulate the secretion of IL-10 and Foxp3 mRNA expression, inhibit the ratio of Th1 and Th17 cells, down-regulate the IFN-γ and IL-17 protein expression, as well as the RORγT and T-bet gene expression in EAE mice. In addition, HGWD-containing serum modulated Th1/Th17/Treg cell differentiation in vitro. Moreover, HGWD inhibited the p-JAK1, p-JAK2, p-STAT1, p-STAT3 and p-STAT4 proteins and elevated the p-STAT5 protein in lymphoid tissues of EAE mice. CONCLUSION: HGWD improved the progress of EAE by regulating the proportion of CD4+T cell subtype differentiation, which might be exerted through JAK/STAT signaling pathway, providing a pharmacological basis for the clinical treatment of MS.


Assuntos
Astragalus propinquus , Medicamentos de Ervas Chinesas , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Linfócitos T Reguladores/metabolismo , Diferenciação Celular , Camundongos Endogâmicos C57BL , Células Th17
14.
Nat Commun ; 15(1): 1512, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374204

RESUMO

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética
15.
Microb Biotechnol ; 17(2): e14416, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381051

RESUMO

Many traditional fermented foods and beverages industries around the world request the addition of multi-species starter cultures. However, the microbial community in starter cultures is subject to fluctuations due to their exposure to an open environment during fermentation. A rapid detection approach to identify the microbial composition of starter culture is essential to ensure the quality of the final products. Here, we applied single-cell Raman spectroscopy (SCRS) combined with machine learning to monitor Oceanobacillus species in Daqu starter, which plays crucial roles in the process of Chinese baijiu. First, a total of six Oceanobacillus species (O. caeni, O. kimchii, O. iheyensis, O. sojae, O. oncorhynchi subsp. Oncorhynchi and O. profundus) were detected in 44 Daqu samples by amplicon sequencing and isolated by pure culture. Then, we created a reference database of these Oceanobacillus strains which correlated their taxonomic data and single-cell Raman spectra (SCRS). Based on the SCRS dataset, five machine-learning algorithms were used to classify Oceanobacillus strains, among which support vector machine (SVM) showed the highest rate of accuracy. For validation of SVM-based model, we employed a synthetic microbial community composed of varying proportions of Oceanobacillus species and demonstrated a remarkable accuracy, with a mean error was less than 1% between the predicted result and the expected value. The relative abundance of six different Oceanobacillus species during Daqu fermentation was predicted within 60 min using this method, and the reliability of the method was proved by correlating the Raman spectrum with the amplicon sequencing profiles by partial least squares regression. Our study provides a rapid, non-destructive and label-free approach for rapid identification of Oceanobacillus species in Daqu starter culture, contributing to real-time monitoring of fermentation process and ensuring high-quality products.


Assuntos
Algoritmos , Análise Espectral Raman , Reprodutibilidade dos Testes , Bases de Dados Factuais , Aprendizado de Máquina
16.
Eur J Pharmacol ; 967: 176351, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38290568

RESUMO

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every other day, 6 times) or doxorubicin plus GSK2795039 (2.5 mg/kg, twice a day, 9 weeks). Left ventricular (LV) total wall thickness and LV ejection fraction were decreased in doxorubicin-treated mice compared with saline-treated mice and the decreases were prevented by the treatment of the specific Nox2 inhibitor GSK2795039. The ratio of total heart weight to tibia length and myocyte cross-sectional area were decreased in doxorubicin-treated mice, and the decreases were attenuated by the GSK2795039 treatment. In doxorubicin-treated mice, myocardial Nox2 and 4-hydroxynonenal levels were increased, myocardial expression of GAP43, tyrosine hydroxylase and norepinephrine transporter, markers of sympathetic nerve terminals, was decreased, and these changes were prevented by the GSK2795039 treatment. The ratio of LC3 II/I, a marker of autophagy, and Atg5, Atg12 and Atg12-Atg5 conjugate proteins were increased in doxorubicin-treated mice, and the increases were attenuated by the GSK2795039 treatment. These findings suggest that inhibition of Nox2 by GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, thereby ameliorating cardiac atrophy and dysfunction after chronic doxorubicin treatment.


Assuntos
Aminopiridinas , Doxorrubicina , Células Musculares , Sulfonamidas , Animais , Camundongos , Atrofia/induzido quimicamente , Autofagia , Doxorrubicina/efeitos adversos , NADPH Oxidase 2
17.
JMIR Hum Factors ; 11: e43943, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285496

RESUMO

BACKGROUND: To improve the engagement and effectiveness of traditional health programs, it is necessary to explore alternative models of health education including video-assisted lectures and peer education. OBJECTIVE: This study aimed to evaluate the effects of a combination of video-assisted lectures and peer education on health literacy related to infectious diseases among students. METHODS: Third-grade classes from 11 pilot schools in Longgang District of Shenzhen, China, were randomized to the intervention and control groups. In the intervention group, a video-assisted interactive health education program was conducted twice over a time span of 5 months. Each of the 2 sessions included a 40-minute lecture on COVID-19 and other common infectious diseases in schools and a 5-minute science video. In addition, 5 "little health supervisors" at the end of the first session were elected in each class, who were responsible for helping class members to learn health knowledge and develop good hygiene habits. Students answered the same quiz before the first and after the second session. Models based on item response theory (IRT) were constructed to score the students' knowledge of infectious diseases based on the quiz. RESULTS: In total, 52 classes and 2526 students (intervention group: n=1311; control group: n=1215) were enrolled. Responses of the baseline survey were available for 2177 (86.2%; intervention group: n=1306; control group: n=871) students and those of the postintervention survey were available for 1862 (73.7%; intervention group: n=1187; control group: n=675). There were significant cross-group differences in the rates of correctly answering questions about influenza symptoms, transmission, and preventive measures; chicken pox symptoms; norovirus diarrhea symptoms; mumps symptoms; and COVID-19 symptoms. Average IRT scores of questions related to infectious diseases in the intervention and control groups were, respectively, -0.0375 (SD 0.7784) and 0.0477 (SD 0.7481) before the intervention (P=.01), suggesting better baseline knowledge in the control group. After the intervention, the average scores of the intervention and control groups were 0.0543 (SD 0.7569) and -0.1115 (SD 0.7307), respectively (P<.001), suggesting not only significantly better scores but also greater improvement in the intervention group. CONCLUSIONS: After the health education project, the correct answer rate of infectious disease questions in the intervention group was higher than that of the control group, which indicates significant effects of the combination of video-assisted lectures and peer education for the promotion of health literacy. In addition, the intervention effect of the first session persisted for at least 4 months up to the second session. As such, the proposed program was effective in improving the health literacy of school children in relation to infectious diseases and should be considered for massive health promotion campaigns during pandemics. TRIAL REGISTRATION: ISRCTN ISRCTN49297995; https://www.isrctn.com/ISRCTN49297995.


Assuntos
COVID-19 , Letramento em Saúde , Criança , Humanos , COVID-19/epidemiologia , Educação em Saúde , Escolaridade , Promoção da Saúde
18.
PLoS One ; 19(1): e0296416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166022

RESUMO

In sorghum [Sorghum bicolor (L.) Moench], combining ability and heterosis analysis are commonly used to evaluate superior parental lines and to screen for strongly heterotic hybrids, which helps in sorghum variety selection and breeding. In this context, combining ability and heterosis analysis were assessed using 14 restorer lines and seven cytoplasmic male sterile (CMS) lines in 2019 and 2020. The analysis of variance of all cross combinations had highly significant differences for all characters studied, which indicated a wide variation across the parents, lines, testers, and crosses. Combining ability analysis showed that the general combining ability (GCA) and specific combining ability (SCA) of the different parents were differed significantly among different traits. Most combinations with high SCA also showed high GCA in their parent lines. The heritability in the narrow sense of grain weight per panicle and grain yield was relatively low, indicating that the ability of these traits to be directly inherited by offspring was weak, that they were greatly affected by the environment. The better-parent heterosis for plant height, grain weight per panicle, panicle length, and 1000-grain weight was consistent with the order of mid-parent heterosis from strong to weak. The GCA effects of two lines 10480A, 3765A and three testers 0-30R, R111, and JY15R were significant for the majority of the agronomic traits including grain yield and might be used for improving the yield of grains in sorghum as parents of excellent specific combining ability. Seven strongly heterotic F1 hybrids were screened; of these, hybrids 3765A × R111, 1102A × L2R, and 3765A × JY15R showed significant increases in seed iristectorigenin A content and will feature into the creation of new sorghum varieties rich in iristectorigenin A.


Assuntos
Vigor Híbrido , Sorghum , Vigor Híbrido/genética , Sorghum/genética , Melhoramento Vegetal , Fenótipo , Grão Comestível
19.
Food Funct ; 15(3): 1612-1626, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38240339

RESUMO

Juice fermented with lactic acid bacteria (LAB) has received attention due to its health benefits, such as antioxidant and anti-inflammatory. Previous research on LAB-fermented goji juice mainly focused on exploring the changes in the metabolite profile and antioxidant activity in vitro, whereas the liver protection properties of LAB-fermented goji juice in vivo are still unknown. This study aimed to investigate the effects of Lacticaseibacillus paracasei E10-fermented goji juice (E10F), Lactiplantibacillus plantarum M-fermented goji juice (MF), Lacticaseibacillus rhamnosus LGG-fermented goji juice (LGGF) on preventing acute alcoholic liver injury with physiology, gut microbial, and metabolic profiles in mice. Compared with goji juice, E10F, MF, and LGGF enhanced the protective effect against liver injury by reducing serum alanine transaminase (ALT) levels, improving the hepatic glutathione (GSH) antioxidant system, and attenuating inflammation by decreasing the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß. Furthermore, E10F, MF, and LGGF increased intestinal integrity, restructured the gut microbiota including Bacteroides and Lactobacillus, and altered gut microbial metabolites including kyotorphin, indolelactic acid, and N-methylserotonin. Pretreatment of different LAB-fermented goji juice in mice showed significant differences in gut microbiota and metabolism. The correlation analysis demonstrated that the increase of Lactobacillus, indolelactic acid, and N-methylserotonin by E10F, MF, and LGGF was positively correlated with reduced inflammation and improved liver and gut function. Taken together, E10F, MF, and LGGF all have the potential to be converted into dietary interventions to combat acute alcoholic liver injury. It provided a reference for the study of the hepatoprotective effect of LAB-fermented goji juice.


Assuntos
Microbioma Gastrointestinal , Lactobacillales , Lycium , Serotonina/análogos & derivados , Camundongos , Animais , Lycium/metabolismo , Antioxidantes/metabolismo , Fermentação , Ácido Láctico/metabolismo , Lactobacillus/metabolismo , Lactobacillales/metabolismo , Fígado/metabolismo , Inflamação/metabolismo , Etanol/metabolismo
20.
Biotechnol J ; 19(1): e2300136, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971189

RESUMO

The L-serine exporters ThrE and SerE play important roles in L-serine production by Corynebacterium glutamicum. Deletion of both thrE and serE decreased L-serine titer by 60%, suggesting the existence of other L-serine exporters. A comparative transcriptomics identified NCgl0254 and NCgl0255 as novel L-serine exporters. Further analysis of the contributions of ThrE, SerE, NCgl0254, and NCgl0255 found that SerE was the major L-serine exporter in C. glutamicum and these four L-serine exporters were responsible for 79.7% of L-serine export. Deletion of one L-serine exporter upregulated the transcription levels of the other three, which might be coursed by increased intracellular concentrations of L-serine. Overexpression of NCgl0254 and NCgl0255 increased L-serine titer by 20.8% in C. glutamicum A36, while overexpression of the four L-serine exporters increased L-serine production by 31.9% (41.1 g·L-1 ) in C. glutamicum A36. The identification of novel L-serine exporters in C. glutamicum will help to improve industrial production of L-serine.


Assuntos
Corynebacterium glutamicum , Corynebacterium glutamicum/genética , Serina , Proteínas de Bactérias/genética , Engenharia Metabólica
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