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1.
Sci Total Environ ; 806(Pt 1): 150352, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555607

RESUMO

BACKGROUND: The effects of weather periods, race/ethnicity, and sex on environmental triggers for respiratory exacerbations are not well understood. This study linked the OneFlorida network (~15 million patients) with an external exposome database to analyze environmental triggers for asthma, bronchitis, and COPD exacerbations while accounting for seasonality, sex, and race/ethnicity. METHODS: This is a case-crossover study of OneFlorida database from 2012 to 2017 examining associations of asthma, bronchitis, and COPD exacerbations with exposures to heat index, PM 2.5 and O 3. We spatiotemporally linked exposures using patients' residential addresses to generate average exposures during hazard and control periods, with each case serving as its own control. We considered age, sex, race/ethnicity, and neighborhood deprivation index as potential effect modifiers in conditional logistic regression models. RESULTS: A total of 1,148,506 exacerbations among 533,446 patients were included. Across all three conditions, hotter heat indices conferred increasing exacerbation odds, except during November to March, where the opposite was seen. There were significant differences when stratified by race/ethnicity (e.g., for asthma in April, May, and October, heat index quartile 4, odds were 1.49 (95% confidence interval (CI) 1.42-1.57) for Non-Hispanic Blacks and 2.04 (95% CI 1.92-2.17) for Hispanics compared to 1.27 (95% CI 1.19-1.36) for Non-Hispanic Whites). Pediatric patients' odds of asthma and bronchitis exacerbations were significantly lower than adults in certain circumstances (e.g., for asthma during June - September, pediatric odds 0.71 (95% CI 0.68-0.74) and adult odds 0.82 (95% CI 0.79-0.85) for the highest quartile of PM 2.5). CONCLUSION: This study of acute exacerbations of asthma, bronchitis, and COPD found exacerbation risk after exposure to heat index, PM 2.5 and O 3 varies by weather period, age, and race/ethnicity. Future work can build upon these results to alert vulnerable populations to exacerbation triggers.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Transtornos Respiratórios , Adulto , Asma/epidemiologia , Big Data , Criança , Estudos Cross-Over , Humanos
2.
EMBO Rep ; : e53543, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842321

RESUMO

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for dissecting the complexity of normal and diseased tissues, enabling characterization of cell diversity and heterogeneous phenotypic states in unprecedented detail. However, this technology has been underutilized for exploring the interactions between the host cell and viral pathogens in latently infected cells. Herein, we use scRNA-seq and single-molecule sensitivity fluorescent in situ hybridization (smFISH) technologies to investigate host single-cell transcriptome changes upon the reactivation of a human neurotropic virus, herpes simplex virus-1 (HSV-1). We identify the stress sensor growth arrest and DNA damage-inducible 45 beta (Gadd45b) as a critical antiviral host factor that regulates HSV-1 reactivation events in a subpopulation of latently infected primary neurons. We show that distinct subcellular localization of Gadd45b correlates with the viral late gene expression program, as well as the expression of the viral transcription factor, ICP4. We propose that a hallmark of a "successful" or "aborted" HSV-1 reactivation state in primary neurons is determined by a unique subcellular localization signature of the stress sensor Gadd45b.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34806271

RESUMO

Owing to their unique electronic structure and maximum atom utilization efficiency, single-atom catalysts have received widespread attention and exhibited efficient activity. Herein, we report the preparation of non-metal Se single atoms embedded in nitrogen-doped carbon (NC) via a high-temperature reduction strategy for electrocatalytic oxygen reduction reaction (ORR). Selenium dioxide is reduced to selenium by NC at high temperature and partially anchored to form C-Se-C bond. Impressively, the obtained single-atom catalyst exhibits outstanding ORR activity and stability that even surpasses state-of-the-art noble metal catalysts and many previously reported nanocatalysts. Experimental and theoretical calculations reveal that the Se single atoms can serve as the ORR active sites and contribute to lowering the reaction barrier. Our discoveries demonstrate the promising prospects for utilizing metal-free single-atom-based materials for efficient electrocatalysis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34755424

RESUMO

We report a facile and powerful strategy to prepare libraries of oligothienoacene diimides that include anti- and syn-isomers using palladium-catalyzed C-H activation and an unexpected 1,2-sulfur migration. Through this strategy, a series of oligothienoacene diimides containing 6, 8, and 10 fused rings were synthesized. The molecular geometry and extent of π-conjugation have dramatic effects on the electronic properties, degree of crystallinity, and charge-carrier transport properties. Notably, single-crystal microfibers of syn-3 c show electron mobilities up to 4.2 cm2 V-1 s-1 , illustrating the significant potential of these materials for organic electronic devices. Our work demonstrates the versatility of this strategy for the development of oligothienoacene diimide libraries, in particular complex and large syn-oligothienoacene diimides, which are difficult to prepare by present methods.

5.
Comput Math Methods Med ; 2021: 3634548, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34812268

RESUMO

Methods: Clinical information of 78 COPD patients treated with TC (intervention group) or routine care (control group) in Shanghai Pulmonary Hospital during March 2019 and August 2020 was gathered. Patients were followed up for 3 months after discharge. The intervention group (n = 39) was subjected to a TC plan for 3 months to help patients and their family caregivers for self-management of COPD. TC was provided by specially trained nurses, and patients were supported by standardized tools. Nursing measures in the control group (n = 79) included transitional support for 30 d after hospital discharge. In this way, patients were guaranteed to follow discharge plans and transit to outpatient nursing. Patient's anxiety and depression symptoms, sleep quality, survival quality, mobility, and life quality at admission and after 3 months of discharge were assessed by Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Quality of Life Scale Abbreviated Version, Activity of Daily Life Scale, St. George's Respiratory Questionnaire, and COPD Assessment Test. Results: Except for anxiety and depression, patient's sleep quality, survival quality, mobility, and life quality in two groups were significantly improved. Moreover, average change of total CAT score during 3 months of intervention was -5.44, while that in the control group was -1.74 (p = 0.011). Improvement of survival quality of patients in the intervention group (p = 0.001) was markedly greater than that in the control group (p = 0.016). Conclusion: Altogether, TC based on quantification by questionnaire survey is beneficial to COPD patient's life quality and self-management.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34767173

RESUMO

To analyze the association of long-term exposure to air pollution and its attributable risks with the number of tuberculosis (TB) cases notified, a quasi-Poisson regression model combined with a distributed lag nonlinear model (DLNM) was constructed using monthly data on air pollution and TB cases notified in Hong Kong from 1999 to 2018. Nonlinear relationships between PM10, PM2.5, and CO and TB cases notified were identified. The concentrations of PM10, PM2.5, and CO corresponding to the minimum numbers of TB cases notified (the minimum TB notification concentrations, MTNCs) were 58.3 µg/m3, 41.7 µg/m3, and 0.1 mg/m3, respectively. Compared with the MTNCs, the overall cumulative numbers of TB cases notified increased by 76.93% (95% CI: 13.08%, 176.83%), 88.81% (95% CI: 26.09%, 182.71%), and 233.43% (95% CI: 13.56%, 879.03%) for the 95th percentiles of PM10 and PM2.5 and for the 97.5th percentiles of CO, respectively. The TB notification rate attributed to concentration ranges above the 97.5th percentile of PM10, PM2.5, and CO was 3.38% (95% empirical confidence intervals [eCI]: 0.93%, 5.61%), 4.73% (95% eCI: 1.87%, 7.15%), and 3.34% (95% eCI: 0.29%, 5.83%), respectively. Long-term exposure to high concentrations of air pollution in Hong Kong may be associated with increases in the number of TB cases notified for this area.

7.
Front Cardiovasc Med ; 8: 750714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733895

RESUMO

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period. Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids. Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was -7.0 [0.6] kg vs. -6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was -7 [0.7] mmHg vs. -7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was -6 [0.5] mmHg vs. -5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial. Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2000040468.

8.
Front Oncol ; 11: 705929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722250

RESUMO

Background: Alternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC). Methods: AS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established. Results: We identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC. Conclusion: Through the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

9.
Cancer Med ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723436

RESUMO

PURPOSE: Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. PATIENTS AND METHODS: We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer-specific survival (CSS) between married and unmarried via the Kaplan-Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. RESULTS: There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59-2.92) rate and CSS (HR: 1.70, 95% CI: 1.17-2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. CONCLUSION: Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

10.
Front Immunol ; 12: 763831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777380

RESUMO

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1ß/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

11.
Plant Physiol ; 187(2): 917-930, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34608955

RESUMO

Cell cycle is one of the most fundamentally conserved biological processes of plants and mammals. Casein kinase1s (CK1s) are critical for cell proliferation in mammalian cells; however, how CK1s coordinate cell division in plants remains unknown. Through genetic and biochemical studies, here we demonstrated that plant CK1, Arabidopsis (Arabidopsis thaliana) EL1-like (AELs), regulate cell cycle/division by modulating the stability and inhibitory effects of Kip-related protein6 (KRP6) through phosphorylation. Cytological analysis showed that AELs deficiency results in suppressed cell-cycle progression mainly due to the decreased DNA replication rate at S phase and increased period of G2 phase. AELs interact with and phosphorylate KRP6 at serines 75 and 109 to stimulate KRP6's interaction with E3 ligases, thus facilitating the KRP6 degradation through the proteasome. These results demonstrate the crucial roles of CK1s/AELs in regulating cell division through modulating cell-cycle rates and elucidate how CK1s/AELs regulate cell division by destabilizing the stability of cyclin-dependent kinase inhibitor KRP6 through phosphorylation, providing insights into the plant cell-cycle regulation through CK1s-mediated posttranslational modification.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34616484

RESUMO

Background: Cutoff scores of the Montreal cognitive assessment (MoCA) for screening mild cognitive impairment in older adults differ across the world and within the Chinese culture. It is argued that to seek a cutoff score is essential to classify test participants. It was unknown how taking a classifying approach might reveal the cutoff score for identifying mildly cognitively impaired older adults. Methods: Participants, selected from 13 communities in Wuhan, China, were tested with the Chinese version of MoCA and rated with the Activities of Daily Living and the Clinical Dementia Rating scales. Mixture modeling was applied to the data with certain covariates and MoCA sum scores as the outcome of the latent class. Models with different numbers of classes were compared in terms of information criteria, likelihood ratio test, entropy, and interpretability. Results: A 3-class model (normal, mildly impaired, and severely impaired) was found to fit the data best. The normal class averaged a MoCA score of 24, while the severely impaired class averaged a score below 18. For those cases with MoCA scores above 18 and below 24, it is not certain if they are in the normal or the severely impaired classes. Conclusion: Latent variable classification modeling provides another option to identify MCI in older adults. Some categorically different cases of MCI cannot be captured with any single MoCA sum score. A range of 18-24 MoCA scores might serve as a better screening criterion of MCI. Older adults who scored within this gray zone should be monitored for potential interventions.

13.
Radiol Artif Intell ; 3(5): e200237, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34617025

RESUMO

Purpose: To develop and evaluate a diffusion-weighted imaging (DWI) deep learning framework based on the generative adversarial network (GAN) to generate synthetic high-b-value (b =1500 sec/mm2) DWI (SYNb1500) sets from acquired standard-b-value (b = 800 sec/mm2) DWI (ACQb800) and acquired standard-b-value (b = 1000 sec/mm2) DWI (ACQb1000) sets. Materials and Methods: This retrospective multicenter study included 395 patients who underwent prostate multiparametric MRI. This cohort was split into internal training (96 patients) and external testing (299 patients) datasets. To create SYNb1500 sets from ACQb800 and ACQb1000 sets, a deep learning model based on GAN (M0) was developed by using the internal dataset. M0 was trained and compared with a conventional model based on the cycle GAN (Mcyc). M0 was further optimized by using denoising and edge-enhancement techniques (optimized version of the M0 [Opt-M0]). The SYNb1500 sets were synthesized by using the M0 and the Opt-M0 were synthesized by using ACQb800 and ACQb1000 sets from the external testing dataset. For comparison, traditional calculated (b =1500 sec/mm2) DWI (CALb1500) sets were also obtained. Reader ratings for image quality and prostate cancer detection were performed on the acquired high-b-value (b = 1500 sec/mm2) DWI (ACQb1500), CALb1500, and SYNb1500 sets and the SYNb1500 set generated by the Opt-M0 (Opt-SYNb1500). Wilcoxon signed rank tests were used to compare the readers' scores. A multiple-reader multiple-case receiver operating characteristic curve was used to compare the diagnostic utility of each DWI set. Results: When compared with the Mcyc, the M0 yielded a lower mean squared difference and higher mean scores for the peak signal-to-noise ratio, structural similarity, and feature similarity (P < .001 for all). Opt-SYNb1500 resulted in significantly better image quality (P ≤ .001 for all) and a higher mean area under the curve than ACQb1500 and CALb1500 (P ≤ .042 for all). Conclusion: A deep learning framework based on GAN is a promising method to synthesize realistic high-b-value DWI sets with good image quality and accuracy in prostate cancer detection.Keywords: Prostate Cancer, Abdomen/GI, Diffusion-weighted Imaging, Deep Learning Framework, High b Value, Generative Adversarial Networks© RSNA, 2021 Supplemental material is available for this article.

14.
Proc Natl Acad Sci U S A ; 118(42)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34635597

RESUMO

A field campaign was carried out to investigate ice accretion features on large turbine blades (50 m in length) and to assess power output losses of utility-scale wind turbines induced by ice accretion. After a 30-h icing incident, a high-resolution digital camera carried by an unmanned aircraft system was used to capture photographs of iced turbine blades. Based on the obtained pictures of the frozen blades, the ice layer thickness accreted along the blades' leading edges was determined quantitatively. While ice was found to accumulate over whole blade spans, outboard blades had more ice structures, with ice layers reaching up to 0.3 m thick toward the blade tips. With the turbine operating data provided by the turbines' supervisory control and data acquisition systems, icing-induced power output losses were investigated systematically. Despite the high wind, frozen turbines were discovered to rotate substantially slower and even shut down from time to time, resulting in up to 80% of icing-induced turbine power losses during the icing event. The research presented here is a comprehensive field campaign to characterize ice accretion features on full-scaled turbine blades and systematically analyze detrimental impacts of ice accumulation on the power generation of utility-scale wind turbines. The research findings are very useful in bridging the gaps between fundamental icing physics research carried out in highly idealized laboratory settings and the realistic icing phenomena observed on utility-scale wind turbines operating in harsh natural icing conditions.

15.
Front Cell Infect Microbiol ; 11: 597431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671567

RESUMO

A close relationship between knee osteoarthritis (KOA) and gut microbiota has recently been described. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with KOA. We conducted a study of 60 participants with KOA and 30 matched healthy controls (HCs). Sixty participants were allocated to either EA group (n=30) or sham acupuncture (SA) group (n=30). Five obligatory acupoints and three adjunct acupoints were punctured in the EA group. Eight non-acupoints that were separated from conventional acupoints or meridians were used for the SA group. Participants in both groups received 24 sessions within eight weeks. Fecal microbial analyses by 16S ribosomal RNA gene sequencing were carried out after collecting stools at T 0 and T 8 weeks (Four samples with changed defecation habits were excluded). The results showed that both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (P=0.043) and NRS score (P=0.002) decreased more in EA group than those in SA group. Moreover, EA could reverse more KOA-related bacteria including Bacteroides, [Eubacterium]_hallii_group, Agathobacter and Streptococcus. The number of significantly different genera between KOA patients and HCs were less after EA treatment than that after SA treatment. This meant that EA modified the composition of the gut microbiome, making it closer to healthy people, while not significantly affecting the microbial diversity. Two genera including Agathobacter (P=0.0163), Lachnoclostridium (P=0.0144) were statistically increased than baseline in EA group (paired Wilcoxon rank sum test). After EA treatment, Bacteroides (P=0.0394) was more abundant and Streptococcus (P=0.0306) was significantly reduced in patients who demonstrated adequate response than in those with inadequate response (Wilcoxon rank-sum test). Spearman correlation test between gut microbe and KOA clinical outcomes indicated that Bacteroides and Agathobacter was negatively correlated with NRS score, WOMAC total score, and WOMAC pain, stiffness and pain scores (P<0.001 or 0.05 or 0.01), while Streptococcus was positively correlated with them (P<0.05 or 0.01). Our study suggests that EA contributes to the improvement of KOA and gut microbiota could be a potential therapeutic target.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Microbioma Gastrointestinal , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Resultado do Tratamento
16.
J Interferon Cytokine Res ; 41(10): 375-384, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34612721

RESUMO

Inflammatory cytokines has been of great interest in the field of colorectal cancer (CRC) tumor immunology in recent years. As an anti-inflammatory interleukin (IL), IL-38 may contribute to the early diagnosis of CRC and improve the prognosis of CRC patients. This study was designed to investigate the role of circulating IL-38 and the regulatory mechanism of IL-38 in CRC. Expression of IL-38 were detected by ELISA and immunohistochemical staining. The influence of IL-38 on CRC were evaluated by Western blot and cell biology assays after CRC cells were treated by rhIL-38 or LM22B-10. We also verified the anti-tumor activity of IL-38 in transgenic mouse model. The expression of IL-38 was found to be correlated with progression of CRC. IL-38 inhibits CRC metastasis, proliferation and facilitates apoptosis through suppressing the activation of extracellular signal-regulated kinases (ERK) signaling pathway inducing the decrease of downstream genes, which were partially abrogated by ERK activator LM22B-10 in vitro. We also found that IL-38 overexpression inhibits tumorigenesis in vivo. Our findings indicate that IL-38 may serve as a serum prediction marker to identify the prognosis of CRC patients. IL-38 may inhibit the progression of CRC by negatively regulation on ERK signaling pathway.

17.
Front Pharmacol ; 12: 735812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630111

RESUMO

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging-related neurodegenerative diseases. However, the mechanisms underlying QJD's improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD's effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1ß, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

18.
J Exp Med ; 218(11)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34586363

RESUMO

MicroRNAs (miRNAs, miRs) regulate cell fate decisions by post-transcriptionally tuning networks of mRNA targets. We used miRNA-directed pathway discovery to reveal a regulatory circuit that influences Ig class switch recombination (CSR). We developed a system to deplete mature, activated B cells of miRNAs, and performed a rescue screen that identified the miR-221/222 family as a positive regulator of CSR. Endogenous miR-221/222 regulated B cell CSR to IgE and IgG1 in vitro, and miR-221/222-deficient mice exhibited defective IgE production in allergic airway challenge and polyclonal B cell activation models in vivo. We combined comparative Ago2-HITS-CLIP and gene expression analyses to identify mRNAs bound and regulated by miR-221/222 in primary B cells. Interrogation of these putative direct targets uncovered functionally relevant downstream genes. Genetic depletion or pharmacological inhibition of Foxp1 and Arid1a confirmed their roles as key modulators of CSR to IgE and IgG1.

19.
Materials (Basel) ; 14(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576487

RESUMO

A trifunctional photoinitiator based on commercial photoinitiators 2-hydroxy-2-methylpropiophenone (Irgacure1173) and 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure2959) was synthesized by an esterization reaction. Its structure was characterized by UV-Vis spectrometry, Infrared Transformed Fourier, Proton Nuclear Magnetic Resonance Spectra, 13 Carbon Nuclear Magnetic Resonance Spectra, Mass Spectrometry, and Thermogravimetry. In addition, its photoinitiating activity was investigated. The results showed that the novel photoinitiator had good photoinitiating activity and thermal stability compared to commercial photoinitiators. The migration of the residual photoinitiator in the cured film was lower than that of 1173 and 2959.

20.
J Cancer ; 12(19): 5923-5928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476006

RESUMO

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

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