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1.
Dis Model Mech ; 16(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35855640

RESUMO

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3ß/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Remodelação Ventricular , Animais , Cardiomegalia/genética , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Isoproterenol/uso terapêutico , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo , Remodelação Ventricular/fisiologia
2.
Food Chem ; 400: 134007, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055149

RESUMO

On-site screening of biotoxins is of great importance for food safety. A new electrochemical-biosensing strategy was constructed for ochratoxin A (OTA) detection by direct using ready-made commercial portable-glucose-meter (PGM). Aptamer against OTA was adopted as the recognition probe and pre-immobilized onto the sensing interface. The complementary biotin-modified probe was further decorated by hybridization. Biotinylated invertase was further introduced onto the sensing system with streptavidin, which also acted as the signal amplification unit. The invertase, which was depended on the amount of OTA, produced the glucose from sucrose in the sensing solution. The glucose could be directly and conveniently measured with PGM. Quantitative analysis of OTA was achieved with a linear range from 0.5 ng/mL to 10 ng/mL and detection limit of 0.45 ng/mL. Of significance, it has been successfully applied for OTA analysis in rice with satisfied recoveries. This unique PGM-based electrochemical platform reveals prospective potential in food safety monitoring.

3.
Food Chem ; 399: 133999, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36037688

RESUMO

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.


Assuntos
Inibidores de Glicosídeo Hidrolases , Melastomataceae , Animais , Antocianinas , Glicemia/metabolismo , Frutas/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Melastomataceae/metabolismo , Camundongos , Extratos Vegetais/química , alfa-Glucosidases/metabolismo
4.
Front Plant Sci ; 13: 860101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371184

RESUMO

Akebia trifoliata is a perennial climbing woody liana plant with a high potential for commercial exploitation and theoretical research. Similarly, microsatellites (simple sequence repeats, SSRs) also have dual roles: as critical markers and as essential elements of the eukaryotic genome. To characterize the profile of SSRs and develop molecular markers, the high-quality assembled genome of A. trifoliata was used. Additionally, to determine the potential transferability of SSR loci, the genomes of Amborella trichopoda, Oryza sativa, Vitis vinifera, Arabidopsis thaliana, Papaver somniferum, and Aquilegia coerulea were also used. We identified 434,293 SSRs with abundant short repeats, such as 290,868 (66.98%) single-nucleotide repeats (SNRs) and 113,299 (26.09%) dinucleotide repeats (DNRs) in the A. trifoliata genome. 398,728 (91.81%) SSRs on 344,283 loci were physically mapped on the chromosomes, and a positive correlation (r = 0.98) was found between the number of SSRs and chromosomal length. Additionally, 342,916 (99.60%) potential SSR markers could be designed from the 344,283 physically mapped loci, while only 36,160 could be viewed as high-polymorphism-potential (HPP) markers, findings that were validated by PCR. Finally, SSR loci exhibited broad potential transferability, particularly DNRs such as the "AT/AT" and "AG/CT" loci, among all angiosperms, a finding that was not related to the genetic divergence distance. Practically, we developed a whole set of effective, polymorphic, and physically anchored molecular markers and found that, evolutionarily, DNRs could be responsible for microsatellite origin and protecting gene function.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36074966

RESUMO

Introduction: Nutrition treatment is important in the critically ill patient. Nutritional therapy should be instituted as soon as possible if indicated. Case presentation: A 64-year-old woman with malnutrition and intestinal obstruction with gastrointestinal bleeding came to our emergency room. She had a history of constipation. After CT scan, we found perforations in the digestive tract. Because she could not tolerate surgery and parenteral nutrition (PN), we chose to start enteral nutrition (EN). She recovered after the initiation of EN. Discussion: Chronic constipation may cause intestinal obstruction, which is rare but fatal. Providers should evaluate the nutritional status for the intensive care patient and start PN/EN at once if necessary. EN may help the closure of perforations. Conclusion: EN may play a vital important role even in the patients who have perforations in the digestive tract. Chronic constipation may cause obstruction and perforation, which are rare but fatal.

6.
Eur J Health Econ ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083356

RESUMO

BACKGROUND: To compare measurement properties of the utility scores derived from various country-specific value sets of EQ-5D-5L (5L) and EORTC QLU-C10D (10D) in gastric cancer patient. METHODS: The study used cross-sectional data of 243 Chinese gastric cancer patients who completed both 5L and EORTC QLQ-C30. Utility score of QLU-C10D is generated from all the available QLU-C10D value sets currently; the score of 5L is derived from the corresponding 5L value sets for the countries with both the 5L and QLU-C10D value sets and the Chinese 5L value set. Convergent validity was evaluated by testing their correlations with the VAS score. Known-group validity was assessed by comparing the utility scores the patients with different severities. Their relative efficiency (RE) was also compared. RESULTS: Correlation coefficient of 5L and QLU-C10D utility scores with VAS ranged from 0.54 to 0.59, and 0.55 to 0.63, respectively. Both the utility scores were in general able to discriminate the patients with different severities; and 5L utility score had higher RE in the majority of known-groups. CONCLUSION: EQ-5D-5L and QLU-C10D utility scores were different and, thus, non-swappable. They possess similar convergent validity and known-group validity; while EQ-5D-5L scores may have better discriminative power.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36072401

RESUMO

The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2 antagonist group, and ALI + CXCR2 antagonist group. We estimated the lung injury by the hematoxylin and eosin staining, the neutrophil extracellular traps (NETs) formations by the immunofluorescence colocalization and enzyme-linked immunosorbent assay (ELISA), and the CXCR2/CXCL2 pathway by the flow cytometry, ELISA, and real-time polymerase chain reaction. We conducted the high-throughput sequencing and enrichment analyses to explore the potential mechanisms. The results showed that the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung injury and inflammatory response but failed to reduce the circulating and lung tissue NETs formation and the blood neutrophil percent. The high-dose RC decoction increased the plasma CXCL2 level, but the RC decoction had no effects on the neutrophilic CXCR2 levels. Under the inhibition of the CXCR2, the middle-dose RC decoction still decreased the lung injury score but as yet had unobvious influence on the NETs formation. Other potential mechanisms of the RC decoction against the ALI involved the pathways of ribosome and coronavirus disease 2019 (COVID-19); the target genes of inflammatory factors, such as Ccl17, Cxcl17, Cd163, Cxcr5, and Il31ra, and lncRNAs; and the regulations of the respiratory cilia. In conclusion, the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung inflammatory injury via upregulating the CXCL2/CXCR2 pathway but could not reduce the circulating or lung tissue NETs formation.

8.
Comput Intell Neurosci ; 2022: 5611456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072733

RESUMO

This paper designs a multimodal convolutional neural network model for the intelligent analysis of the influence of music genres on children's emotions by constructing a multimodal convolutional neural network model and profoundly analyzing the impact of music genres on children's feelings. Considering the diversity of music genre features in the audio power spectrogram, the Mel filtering method is used in the feature extraction stage to ensure the effective retention of the genre feature attributes of the audio signal by dimensional reduction of the Mel filtered signal, deepening the differences of the extracted features between different genres, and to reduce the input size and expand the model training scale in the model input stage, the audio power spectrogram obtained by feature extraction is cut the MSCN-LSTM consists of two modules: multiscale convolutional kernel convolutional neural network and long and short term memory network. The MSCNN network is used to extract the EEG signal features, the LSTM network is used to remove the temporal characteristics of the eye-movement signal, and the feature fusion is done by feature-level fusion. The multimodal signal has a higher emotion classification accuracy than the unimodal signal, and the average accuracy of emotion quadruple classification based on a 6-channel EEG signal, and children's multimodal signal reaches 97.94%. After pretraining with the MSD (Million Song Dataset) dataset in this paper, the model effect was further improved significantly. The accuracy of the Dense Inception network improved to 91.0% and 89.91% on the GTZAN dataset and ISMIR2004 dataset, respectively, proving that the Dense Inception network's effectiveness and advancedness of the Dense Inception network were demonstrated.


Assuntos
Música , Algoritmos , Criança , Emoções , Humanos , Inteligência , Redes Neurais de Computação
9.
Dis Markers ; 2022: 2631852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061356

RESUMO

Objective: To assess and compare the effectiveness of immune checkpoint inhibitors vs. chemotherapy for KRAS-mutant or EGFR-mutant non-small-cell lung cancers. Methods: Until February 19, 2022, Cochrane Library, PubMed, Web of Science, and Embase were searched for relevant randomized controlled trials (RCTs) in NSCLC. Progression-free survival (PFS) and overall survival (OS) were used as outcome measures. The studies were conducted using the Cochrane methodology for meta-analyses, and all statistical analyses were made with Review Manager Software (RevMan version 5.4). Results: Our meta-analysis included nine clinical trials including 5633 participants with NSCLC. Immune checkpoint drugs extended OS (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.60-0.76) and PFS (HR, 0.44; 95% CI, 0.35-0.56) in patients with EGFR wild-type compared to chemotherapy alone, whereas programmed cell death 1 ligand 1 (PD-L1)/programmed cell death-1 (PD-1) inhibitors with chemotherapy versus chemotherapy extended PFS in NSCLC patients with EGFR mutations (HR, 0.63; 95% CI, 0.42-0.94). Meanwhile, immune checkpoint inhibitors vs. chemotherapy improved the OS (HR, 0.65; 95% CI, 0.48-0.88) and PFS (HR, 0.49; 95% CI, 0.36-0.66) of NSCLC patients with KRAS mutation. NSCLCs with KRAS G12C mutation had a much better PFS with ICIs than with chemotherapy (HR, 0.38; 95% CI, 0.21-0.71). Conclusion: This research revealed that individuals with EGFR wild-type NSCLC or KRAS mutation may benefit from PD-L1/PD-1 inhibitors and that PD-L1/PD-1 inhibitors in combination with chemotherapy seem to be more successful than chemotherapy alone in NSCLC patients with EGFR mutation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Front Public Health ; 10: 973832, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062090

RESUMO

Background: Trace metals have side-effect on human health. The association between trace metals exposure and hearing loss remains unclear. Methods: A total of 8,128 participants were exacted for analysis of association between trace metals and hearing loss from the database of the National Health and Nutrition Examination Survey (NHANES) (2013-2018). Multivariable logistic regression and restricted cubic spline models were used to examine the association between trace metals and hearing loss. Results: Participants with hearing loss had a higher level of lead, cadmium, molybdenum, tin, thallium, and tungsten (all p < 0.05). After adjusting for confounders, compared with the reference of the lowest quartile, the ORs with 95%CIs for hearing loss across quartiles were 1.14 (0.86, 1.51), 1.49 (1.12, 1.98), 1.32 (0.97, 1.80) for cobalt, and 1.35 (0.98, 1.87), 1.58 (1.15, 2.16), 1.75 (1.28, 2.40) for tin. Individuals with the level of cobalt at third quartile had 49% higher risks of hearing loss than those at lowest quartile. And participants with highest quartile of tin had 1.75-folds risks of hearing loss than those with lowest quartile of tin. There were increasing trends in risks of hearing loss with a raised level of thallium (p for trend <0.05). Restricted cubic spline regression analysis indicated that there was a nonlinear association between hearing loss and the levels of tin (p for nonlinearity = 0.021). Subgroup analysis showed that individuals of female, without hypertension and diabetes, and with a higher level of low-density lipoprotein cholesterol had modified effects on the associations between hearing loss and exposure to tin. Conclusions: Our study indicated that exposure to cobalt and tin were significantly associated with hearing loss.


Assuntos
Exposição Ambiental , Perda Auditiva , Cobalto/análise , Feminino , Perda Auditiva/epidemiologia , Humanos , Inquéritos Nutricionais , Tálio/análise , Estanho/efeitos adversos , Estanho/análise
11.
Front Public Health ; 10: 952075, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062107

RESUMO

Objective: Herein, we purposed to explore the association of sleep duration with chest pain among adults in US. Methods: This research work enrolled 13,274 subjects in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The association of sleep duration with chest pain among adults in US was evaluated by Multivariable logistic regression. Results: To elucidate the association, we made adjustments for gender, BMI, diabetes, smoking status, drinking status, race, marital status, annual family income, hyperlipoidemia, Hypertension. Chest pain incidence decreased by 5% [OR = 0.95 (0.93, 0.98), p = 0.0004] for an increase in sleep duration by 1 h. A generalized additive model (GAM) was used to reseal a U-shaped relationship of sleep duration with incident chest pain. When duration of sleep was <6.5 h, chest pain incidence negatively correlated to sleep duration [OR = 0.77 (0.72, 0.82) P < 0.0001]. However, when sleep duration was ≥6.5 h, chest pain incidence rose with escalating sleep duration [OR = 1.07 (1.03, 1.11) p = 0.0014]. Conclusions: Duration of sleep was established to be independently linked with an increase in the occurrence of chest pain. Excessive sleep, as much as insufficient sleep, increases the risk of chest pain. Both excessive sleep and insufficient sleep are associated with an increased risk of chest pain.


Assuntos
Privação do Sono , Sono , Adulto , Dor no Peito/epidemiologia , Estudos Transversais , Humanos , Inquéritos Nutricionais
12.
Artigo em Inglês | MEDLINE | ID: mdl-36073150

RESUMO

Selective electrocatalytic oxidation of alcohol to value-added aldehyde has attracted increasing attention. However, due to its higher reactivity than alcohol, the aldehyde is easily over-oxidized to acid in alkaline electrolytes. This work has successfully realized the selective electrooxidation of alcohol to aldehyde on NiO by tuning the local microenvironment to salt out the aldehyde intermediate product from the reaction system. The origin of the high selectivity was unveiled that inhibiting the hydration process of aldehyde and enabling the salting-out of aldehyde at the gas|electrolyte interface are the key to achieving high selectivity of aldehyde, which is the result of the decreased alkalinity and the increased cation and substrate concentration. This strategy could salt out the aldehyde from the electrooxidation of alcohol with 100% selectivity and be easily extended to other selective oxidation reactions, such as 5-hydroxymethyl furfural (HMF) to 2,5-furandicarboxaldehyde (DFF) and amine to an imine.

13.
J Phys Chem Lett ; 13(35): 8386-8396, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36047673

RESUMO

Defect engineering is an important means of improving the electrochemical performance of the Co3O4 electrocatalyst in the oxygen evolution reaction (OER). In this study, operando soft X-ray absorption spectroscopy (SXAS) is used to explore the electronic structure of Co3O4 under OER for the first time. The defect-rich Co3O4 (D-Co3O4) has a Co2.45+ state with Co2+ at both octahedral (Oh) and tetrahedral (Td) sites and Co3+ at Oh, whereas Co3O4 has Co2.6+ with Co2+ and Co3+ at Td and Oh sites, respectively. SXAS reveals that upon increasing the voltage, the Co2+ in D-Co3O4 is converted to low-spin Co3+, some of which is further converted to low-spin Co4+; most Co2+ in Co3O4 is converted to Co3+ but rarely to Co4+. When the voltage is switched off, Co4+ intermediates quickly disappear. These findings reveal Co(Oh) in D-Co3O4 can be rapidly converted to active low-spin Co4+ under operando conditions, which cannot be observed by ex situ XAS.

14.
J Acoust Soc Am ; 152(2): 933, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36050157

RESUMO

Formants in speech signals are easily identified, largely because formants are defined to be local maxima in the wideband sound spectrum. Sadly, this is not what is of most interest in analyzing speech; instead, resonances of the vocal tract are of interest, and they are much harder to measure. Klatt [(1986). in Proceedings of the Montreal Satellite Symposium on Speech Recognition, 12th International Congress on Acoustics, edited by P. Mermelstein (Canadian Acoustical Society, Montreal), pp. 5-7] showed that estimates of resonances are biased by harmonics while the human ear is not. Several analysis techniques placed the formant closer to a strong harmonic than to the center of the resonance. This "harmonic attraction" can persist with newer algorithms and in hand measurements, and systematic errors can persist even in large corpora. Research has shown that the reassigned spectrogram is less subject to these errors than linear predictive coding and similar measures, but it has not been satisfactorily automated, making its wider use unrealistic. Pending better techniques, the recommendations are (1) acknowledge limitations of current analyses regarding influence of F0 and limits on granularity, (2) report settings more fully, (3) justify settings chosen, and (4) examine the pattern of F0 vs F1 for possible harmonic bias.


Assuntos
Acústica , Acústica da Fala , Algoritmos , Canadá , Humanos , Idioma
15.
Dis Markers ; 2022: 1360954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051356

RESUMO

Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.


Assuntos
Antineoplásicos , Neoplasias Colorretais , MicroRNAs , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico
16.
J Oncol ; 2022: 9390912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046364

RESUMO

Estrogen receptor-positive (ER+) breast cancer (BC) is a common subtype of BC with a relatively good prognosis. However, recurrence and death from ER+ BC occur because of tumor heterogeneity. This study aimed to explore tumor heterogeneity using next-generation sequencing (NGS) and tumor-organoid models to promote BC precise therapy. We collected needle biopsy, surgical excision, and cerebrospinal fluid (CSF) samples to establish tumor organoids. We found that the histological characteristics of organoids were consistent with original lesions and recapitulated their heterogenicity. In addition, the NGS results showed that PIK3CA and TP53 genes had detrimental mutations. BAP1, RET, AXIN2, and PPP2R2A genes had mutations with unknown function. The score for homologous recombination deficiency (HRD) of genome was 56, indicating that the tumor was likely sensitive to PARPi. The mutant-allele tumor heterogeneity (MATH) value of the tumor genome was 68.03, indicating high tumor heterogeneity. At last, we performed a drug screening on organoids. The toxicity of different drugs toward BC organoids originated from needle biopsy and surgical excision was tested, respectively. The IC50 values in the needle biopsy groups were paclitaxel 2.83 µM, carboplatin 61.47 µM, neratinib 0.8 µM, lapatinib >100 µM; in the surgical excision groups: trastuzumab >100 µM, docetaxel 0.036 µM, tamoxifen 20.54 µM, olaparib 5.478 µM, BYL719 < 0.1 µM. The toxicity data showed that the BC organoids could show dynamic characteristics of tumor progression and reflect the heterogeneity of BC. Our study demonstrates that the combined use of tumor organoids and NGS is a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributes to the development of personalized therapy.

17.
Int Urol Nephrol ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050583

RESUMO

PURPOSE: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide. However, the effect of the degree of tubulointerstitial lesions (TIL) on the renal prognosis of these patients is uncertain. METHODS: All biopsy-proven primary IgAN patients from a single center (≥ 14 years old) were retrospectively examined from January 2006 to December 2011. According to the Oxford classification for tubulointerstitial lesions in IgAN, eligible patients were assigned to T0 or T1/2 groups. The clinicopathological features of these groups were compared and multivariate models were used to identify the effect of tubulointerstitial lesions on renal prognosis. The composite endpoint was end-stage renal disease or doubling of serum creatinine. RESULTS: We initially identified 1570 patients with IgAN and examined 988 patients who completed follow-up examinations (mean: 49 months). There were 506 patients in the T0 group (51.2%) and 482 in the T1/2 group (48.8%). The 1-year, 3-year, and 5-year incidences of the composite endpoint were 0.2%, 1.5%, 7.7% in the T0 group, and 1.9%, 9.9%, 18.1% in the T1/2 group. An adjusted multivariate model indicated the hazard ratio for reaching the composite endpoint was 9.3 for patients with T1/2 rather than T0 (reference group). A multivariate logistic analysis of the T1/2 group indicated the independent risk factors for reaching the composite endpoint were decreased eGFR, hypertension, hyperlipidemia, proteinuria, global glomerulosclerosis, and segmental glomerulosclerosis. CONCLUSION: More severe tubulointerstitial lesions (> 25%, T1/2) were an independent predictor of poor renal prognosis in patients with IgAN.

19.
Physiol Plant ; : e13766, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36053893

RESUMO

Heat stress is a major abiotic stress for temperate plant species with characteristic symptoms of premature leaf senescence. The objectives of this study were to evaluate the physiological effects of cytokinins (CK) and an ethylene inhibitor, aminoethoxyvinylglycine (AVG) on heat-induced leaf senescence in the temperate perennial grass species, perennial ryegrass (Lolium perenne), and to investigate whether WRKY transcriptional factors (TFs) could be associated with CK- or ethylene-mediated regulation of heat-induced leaf senescence by exogenously applying CK or AVG to perennial ryegrass. Perennial ryegrass plants foliar-sprayed with 6-benzylaminopurine (6-BA), and AVG exhibited prolonged stay-green phenotypes and a lesser degree of leaf senescence under heat stress (35/30°C), as shown by a decline in electrolyte leakage, malondialdehyde content, hydrogen peroxide and superoxide content, and increased chlorophyll (Chl) content along with reduced activities of Chl-degrading enzymes (pheophytinase and chlorophyllase) and increased activity of Chl-synthesizing enzyme (porphobilinogen deaminase) due to 6-BA or AVG application. The suppression of heat-induced leaf senescence by 6-BA or AVG treatment corresponded with the up-regulation of LpWRKY69 and LpWRKY70. The LpWRKY69 and LpWRKY70 promoters were predicted to share conserved cis-elements potentially recognized by transcription factors (TFs) in the cytokinin or ethylene pathways. These results indicate that LpWRKY69 and LpWRKY70 may negatively regulate heat-induced leaf senescence through cytokinin or ethylene pathways, conferring heat tolerance in perennial ryegrass.

20.
Am J Kidney Dis ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058429

RESUMO

RATIONALE AND OBJECTIVE: Belimumab improved renal outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the USA and EU. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup. STUDY DESIGN: Pre-specified subgroup analysis of BLISS-LN, a Phase 3, placebo-controlled, randomized 104-week trial. SETTING AND PARTICIPANTS: Adults with biopsy-proven, active LN were randomized (1:1) to belimumab or placebo, plus standard therapy. INTERVENTION: Patients were administered intravenous belimumab 10 mg/kg, or placebo, plus standard therapy (oral glucocorticoids and either cyclophosphamide for induction followed by azathioprine for maintenance, or mycophenolate mofetil for both induction and maintenance). At the investigator's discretion, 1-3 intravenous pulses of methylprednisolone, 500-1000 mg each, could be administered during induction. OUTCOMES: The primary endpoint was Primary Efficacy Renal Response (PERR; urine protein:creatinine ratio [uPCR] ≤0.7, eGFR no more than 20% below pre-flare value or ≥60 ml/min/1.73 m2, and no treatment failure) at week 104. Key secondary endpoints included: Complete Renal Response (CRR; uPCR <0.5, eGFR no more than 10% below pre-flare value or ≥90 ml/min/1.73 m2, and no treatment failure) at week 104; PERR at week 52; time to renal-related event or death; safety. ANALYTICAL APPROACH: PERR and CRR were analyzed using a logistic regression model, and time to a renal-related event or death were analyzed using a multivariable Cox proportional-hazards regression model. RESULTS: 142 patients from mainland China, Hong Kong, South Korea, and Taiwan were included (belimumab: n=74; placebo: n=68). At week 104, more belimumab than placebo patients achieved PERR (52.7% vs 36.8%, OR [95% CI] 1.76 [0.88, 3.51]) and CRR (35.1% vs 25.0%, OR [95% CI] 1.73 [0.80, 3.74]). At Week 52, more belimumab than placebo patients achieved PERR (62.2% vs 36.8%; OR [95% CI] 2.74 [1.33, 5.64]). Belimumab reduced the risk of a renal-related event or death compared to placebo at any time (HR [95% CI] 0.37 [0.15, 0.91]). Safety was similar across treatment groups. LIMITATIONS: Small sample size and lack of formal significance testing. CONCLUSION: Safety and efficacy profiles were consistent with BLISS-LN overall population, supporting benefits of belimumab treatment in the East Asian population with LN.

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