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1.
Article En | MEDLINE | ID: mdl-38753528

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

2.
Cancer Control ; 31: 10732748241244929, 2024.
Article En | MEDLINE | ID: mdl-38607968

BACKGROUND: Black-White racial disparities in cancer mortality are well-documented in the US. Given the estimated shortage of oncologists over the next decade, understanding how access to oncology care might influence cancer disparities is of considerable importance. We aim to examine the association between oncology provider density in a county and Black-White cancer mortality disparities. METHODS: An ecological study of 1048 US counties was performed. Oncology provider density was estimated using the 2013 National Plan and Provider Enumeration System data. Black:White cancer mortality ratio was calculated using 2014-2018 age-standardized cancer mortality rates from State Cancer Profiles. Linear regression with covariate adjustment was constructed to assess the association of provider density with (1) Black:White cancer mortality ratio, and (2) cancer mortality rates overall, and separately among Black and White persons. RESULTS: The mean Black:White cancer mortality ratio was 1.12, indicating that cancer mortality rate among Black persons was on average 12% higher than that among White persons. Oncology provider density was significantly associated with greater cancer mortality disparities: every 5 additional oncology providers per 100 000 in a county was associated with a .02 increase in the Black:White cancer mortality ratio (95% CI: .007 to .03); however, the unexpected finding may be explained by further analysis showing that the relationship between oncology provider density and cancer mortality was different by race group. Every 5 additional oncologists per 100 000 was associated with a 1.6 decrease per 100 000 in cancer mortality rates among White persons (95% CI: -3.0 to -.2), whereas oncology provider density was not associated with cancer mortality among Black persons. CONCLUSION: Greater oncology provider density was associated with significantly lower cancer mortality among White persons, but not among Black persons. Higher oncology provider density alone may not resolve cancer mortality disparities, thus attention to ensuring equitable care is critical.


Our study provides timely information to address the growing concern about the need to increase oncology supply and the impact it might have on racial disparities in cancer outcomes. This analysis of counties across the US is the first study to estimate the association of oncology provider density with Black-White racial disparities in cancer mortality. We show that having more oncology providers in a county is associated with significantly lower cancer mortality among the White population, but is not associated with cancer mortality among the Black population, thereby leading to a disparity. Our findings suggest that having more oncology providers alone may be insufficient to overcome existing disadvantages for Black patients to access and use high-quality cancer care. These findings have important implications for addressing racial disparities in cancer outcomes that are persistent and well-documented in the US.


Neoplasms , Oncologists , Humans , White , Medical Oncology , Black People , Linear Models
3.
MedComm (2020) ; 5(4): e531, 2024 Apr.
Article En | MEDLINE | ID: mdl-38617435

Pyrogallol, a natural polyphenol compound (1,2,3-trihydroxybenzene), has shown efficacy in the therapeutic treatment of disorders associated with inflammation. Nevertheless, the mechanisms underlying the protective properties of pyrogallol against influenza A virus infection are not yet established. We established in this study that pyrogallol effectively alleviated H1N1 influenza A virus-induced lung injury and reduced mortality. Treatment with pyrogallol was found to promote the expression and nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Notably, the activation of Nrf2 by pyrogallol was involved in elevating the expression of PPAR-γ, both of which act synergistically to enhance heme oxygenase-1 (HO-1) synthesis. Blocking HO-1 by zinc protoporphyrin (ZnPP) reduced the suppressive impact of pyrogallol on H1N1 virus-mediated aberrant retinoic acid-inducible gene-I-nuclear factor kappa B (RIG-I-NF-κB) signaling, which thus abolished the dampening effects of pyrogallol on excessive proinflammatory mediators and cell death (including apoptosis, necrosis, and ferroptosis). Furthermore, the HO-1-independent inactivation of janus kinase 1/signal transducers and activators of transcription (JAK1/STATs) and the HO-1-dependent RIG-I-augmented STAT1/2 activation were both abrogated by pyrogallol, resulting in suppression of the enhanced transcriptional activity of interferon-stimulated gene factor 3 (ISGF3) complexes, thus prominently inhibiting the amplification of the H1N1 virus-induced proinflammatory reaction and apoptosis in interferon-beta (IFN-ß)-sensitized cells. The study provides evidence that pyrogallol alleviates excessive proinflammatory responses and abnormal cell death via HO-1 induction, suggesting it could be a potential agent for treating influenza.

4.
Phytomedicine ; 129: 155534, 2024 Jul.
Article En | MEDLINE | ID: mdl-38583346

BACKGROUND: Severe respiratory system illness caused by influenza A virus infection is associated with excessive inflammation and abnormal apoptosis in alveolar epithelial cells (AEC). However, there are limited therapeutic options for influenza-associated lung inflammation and apoptosis. Pterostilbene (PTE, trans-3,5-dimethoxy-4-hydroxystilbene) is a dimethylated analog of resveratrol that has been reported to limit influenza A virus infection by promoting antiviral innate immunity, but has not been studied for its protective effects on virus-associated inflammation and injury in AEC. PURPOSE: Our study aimed to investigate the protective effects and underlying mechanisms of PTE in modulating inflammation and apoptosis in AEC, as well as its effects on macrophage polarization during influenza virus infection. STUDY DESIGN AND METHODS: A murine model of influenza A virus-mediated acute lung injury was established by intranasal inoculation with 5LD50 of mouse-adapted H1N1 viruses. Hematoxylin and eosin staining, immunofluorescence, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, Luminex and flow cytometry were performed. RESULTS: PTE effectively mitigated lung histopathological changes and injury induced by H1N1 viruses in vivo. These beneficial effects of PTE were attributed to the suppression of inflammation and apoptosis in AEC, as well as the modulation of M1 macrophage polarization. Mechanistic investigations revealed that PTE activated the phosphorylated AMP-activated protein kinase alpha (P-AMPKα)/sirtui1 (Sirt1)/PPARγ coactivator 1-alpha (PGC1α) signal axis, leading to the inhibition of nuclear factor kappa-B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling induced by H1N1 viruses, thereby attenuating inflammation and apoptosis in AEC. PTE also forced activation of the P-AMPKα/Sirt1/PGC1α signal axis in RAW264.7 cells, counteracting the activation of phosphorylated signal transducer and activator of transcription 1 (P-STAT1) induced by H1N1 viruses and the augment of P-STAT1 activation in RAW264.7 cells with interferon-gamma (IFN-γ) pretreatment before viral infection, thereby reducing H1N1 virus-mediated M1 macrophage polarization as well as the enhancement of macrophages into M1 phenotypes elicited by IFN-γ pretreatment. Additionally, the promotion of the transition of macrophages towards the M2 phenotype by PTE was also related to activation of the P-AMPKα/Sirt1/PGC1α signal axis. Moreover, co-culturing non-infected AEC with H1N1 virus-infected RAW264.7 cells in the presence of PTE inhibited apoptosis and tight junction disruption, which was attributed to the suppression of pro-inflammatory mediators and pro-apoptotic factors in an AMPKα-dependent manner. CONCLUSION: In conclusion, our findings suggest that PTE may serve as a promising novel therapeutic option for treating influenza-associated lung injury. Its ability to suppress inflammation and apoptosis in AEC, modulate macrophage polarization, and preserve alveolar epithelial cell integrity highlights its potential as a therapeutic agent in influenza diseases.


Acute Lung Injury , Apoptosis , Influenza A Virus, H1N1 Subtype , Orthomyxoviridae Infections , Sirtuin 1 , Stilbenes , Animals , Stilbenes/pharmacology , Acute Lung Injury/drug therapy , Acute Lung Injury/virology , Mice , Influenza A Virus, H1N1 Subtype/drug effects , Apoptosis/drug effects , Sirtuin 1/metabolism , Orthomyxoviridae Infections/drug therapy , RAW 264.7 Cells , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Macrophages/drug effects , Disease Models, Animal , Mice, Inbred C57BL , AMP-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/virology , Lung/drug effects , Lung/virology , Lung/pathology , Female
5.
Sci Rep ; 14(1): 808, 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38191680

Temperature as an important indicator of climate change, accurate temperature prediction has important guidance and application value for agricultural production, energy management and disaster warning. Based on the advantages of CEEMDAN model in effectively extracting the time-frequency characteristics of nonlinear and nonsmooth signals, BO algorithm in optimizing the objective function within a limited number of iterations, and BiLSTM model in revealing the connection between the current data, the previous data and the future data, a monthly average temperature prediction model based on CEEMDAN-BO-BiLSTM is established. A CEEMDAN-BO-BiLSTM-based monthly average temperature prediction model is developed and applied to the prediction of monthly average temperature in Jinan City, Shandong Province. The results show that the constructed monthly mean temperature prediction model based on CEEMDAN-BO-BiLSTM is feasible; the constructed CEEMDAN-BO-BiLSTM model has an average absolute error of 1.17, a root mean square error of 1.43, an average absolute percentage error of 0.31%, which is better than CEEMDAN-BiLSTM, EMD-BiLSTM, and BiLSTM models in terms of prediction accuracy and shows better adaptability; the constructed CEEMDAN-BO-BiLSTM model illustrates that the model is not over-modeled and adds complexity using Friedman's test and performance comparisons between model run speeds. The model provides insights for effective forecasting of monthly mean temperatures.

6.
Environ Toxicol ; 39(4): 2150-2165, 2024 Apr.
Article En | MEDLINE | ID: mdl-38108618

Pyrogallol (1,2,3-trihydroxybenzene), a polyphenolic natural compound, has attracted considerable attention with regard to its potential anticancer activity. However, further study is needed to elucidate the underlying mechanism related to the antiNSCLC activity of pyrogallol and provide a comprehensive theoretical basis for better clinical utilization of pyrogallol. Our current study aims to investigate the effects and potential underlying mechanisms of pyrogallol on the inhibition of NSCLC growth. Our results showed that pyrogallol treatment induced cell cycle arrest at the G2/M phase and apoptosis in two different NSCLC cell lines. Mechanistically, we found that the induction of cell cycle arrest in NSCLC cells at the G2/M phase by pyrogallol was due to the upregulation of p21 in a p53-dependent manner. And blockade of p53 and p21 effectively abolished the cell cycle arrest at the G2/M phase. Meanwhile, p53 inhibition has been found to abrogate the pyrogallol-induced apoptosis of the two NSCLC cells. Moreover, we revealed that the inhibitory effects of pyrogallol on ß-catenin signaling resulted from autophagy initiation depending on p53 activation, accompanied by an increase in p62/SQSTM1 expression, thus p62 subsequently interacting with ubiquitinated ß-catenin and facilitating autophagic destruction of ß-catenin. Furthermore, in vivo experiments demonstrated that pyrogallol exerted growth inhibition on NSCLC with low toxicity through the same molecular mechanism as observed in vitro. Our findings could contribute to the understanding of the mechanism by which pyrogallol negatively regulates NSCLC growth, which could be effective in treating NSCLC.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Pyrogallol/pharmacology , Pyrogallol/therapeutic use , Up-Regulation , Tumor Suppressor Protein p53/metabolism , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism , Lung Neoplasms/drug therapy , beta Catenin/metabolism , Cell Line, Tumor , Apoptosis , Cell Proliferation
7.
JAMA Health Forum ; 4(11): e233798, 2023 Nov 03.
Article En | MEDLINE | ID: mdl-37921746

Importance: Evidence suggests that racial disparities in health outcomes disappear or diminish when Black and White adults in the US live under comparable living conditions; however, whether racial disparities in health care expenditures concomitantly disappear or diminish is unknown. Objective: To examine whether disparities in health care expenditures are minimized when Black and White US adults live in similar areas of racial composition and economic condition. Design, Setting, and Participants: This cross-sectional study used a nationally representative sample of 7062 non-Hispanic Black or White adults who live in 2238 of 2275 US census tracts with a 5% or greater Black population and who participated in the Medical Expenditure Panel Study (MEPS) in 2016. Differences in total health care expenditures and 6 specific categories of health care expenditures were assessed. Two-part regression models compared expenditures between Black and White adults living in the same Index of Concentration at the Extremes (ICE) quintile, a measure of racialized economic segregation. Estimated dollar amount differences in expenditures were calculated. All analyses were weighted to account for the complex sampling design of the MEPS. Data analysis was performed from December 1, 2019, to August 7, 2023. Exposure: Self-reported non-Hispanic Black or non-Hispanic White race. Main Outcomes and Measures: Presence and amount of patient out-of-pocket and insurance payments for annual total health care expenditures; office-based, outpatient, emergency department, inpatient hospital, or dental visits; and prescription medicines. ICE quintile 5 (Q5) reflected tracts that were mostly high income with mostly White individuals, whereas Q1 reflected tracts that were mostly low income with mostly Black individuals. Results: A total of 7062 MEPS respondents (mean [SD] age, 49 [18] years; 33.1% Black and 66.9% White; 56.1% female and 43.9% male) who lived in census tracts with a 5% or greater Black population in 2016 were studied. In Q5, Black adults had 56% reduced odds of having any health care expenditures (odds ratio, 0.44; 95% CI, 0.27-0.71) compared with White adults, at an estimated $2145 less per year, despite similar health status. Among those in Q5 with any expenditures, Black adults spent 30% less on care (cost ratio, 0.70; 95% CI, 0.56-0.86). In Q3 (most racially and economically integrated), differences in total annual health care spending were minimal ($79 annually; 95% CI, -$1187 to $1345). Conclusions and Relevance: In this cross-sectional study of Black and White adults in the US, health care expenditure disparities diminished or disappeared under conditions of both racial and economic equity and equitable health care access; in areas that were mostly high income and had mostly White residents, Black adults spent substantially less. Results underscore the continuing need to recognize place as a contributor to race-based differences in health care spending.


Black or African American , Health Expenditures , White , Adult , Female , Humans , Male , Middle Aged , Cross-Sectional Studies , Health Services Accessibility , United States , Aged
8.
Chin Med ; 18(1): 139, 2023 Oct 27.
Article En | MEDLINE | ID: mdl-37891648

BACKGROUND: Rosmarinic acid (RosA) is a natural phenolic compound that possesses a wide-range of pharmacological properties. However, the effects of RosA on influenza A virus-mediated acute lung injury remain unknown. In this study, we aimed to explore whether RosA could protect against H1N1 virus-mediated lung injury and elucidate the underlying mechanisms. METHODS: Mice were intragastrically administered with RosA for 2 days before intranasal inoculation of the H1N1 virus (5LD50) for the establishment of an acute lung injury model. At day 7 post-infection (p.i.), gross anatomic lung pathology, lung histopathologic, and lung index (lung weight/body weight) were examined. Luminex assay, multiple immunofluorescence and flow cytometry were performed to detect the levels of pro-inflammatory cytokines and apoptosis, respectively. Western blotting and plasmid transfection with hematopoietic-type PGD2 synthase (h-PGDS) overexpression were conducted to elucidate the mechanisms. RESULTS: RosA effectively attenuated H1N1 virus-triggered deterioration of gross anatomical morphology, worsened lung histopathology, and elevated lung index. Excessive pro-inflammatory reactions, aberrant alveolar epithelial cell apoptosis, and cytotoxic CD8+ T lung recruitment in the lung tissues induced by H1N1 virus infection were observed to be reduced by RosA treatment. In vitro experiments demonstrated that RosA treatment dose-dependently suppressed the increased levels of pro-inflammatory mediators and apoptosis through inhibition of nuclear factor kappa B (NF-κB) and P38 MAPK signaling pathways in H1N1 virus-infected A549 cells, which was accompanied by promoting activation of the h-PGDS-PGD2-HO-1 signal axis. Furthermore, we strikingly found that h-PGDS inhibition significantly abrogated the inhibitory effects of RosA on H1N1 virus-mediated activation of NF-κB and P38 MAPK signaling pathways, resulting in diminishing the suppressive effects on the increased levels of pro-inflammatory cytokines and chemokines as well as apoptosis. Finally, suppressing h-PGDS prominently abolished the protective effects of RosA on H1N1 virus-mediated severe pneumonia and lung injury. CONCLUSIONS: Taken together, our study demonstrates that RosA is a promising compound to alleviate H1N1 virus-induced severe lung injury through prompting the h-PGDS-PGD2-HO-1 signal axis.

9.
Food Chem ; 429: 136955, 2023 Dec 15.
Article En | MEDLINE | ID: mdl-37490817

Pectin extraction is generally an energy-intensive industrial process, while on the other hand their extraction methods vary from different sources. Starting with that perspective, pectin (WSP) containing ultra-low degree of methylation (31.08 ± 1.27%) from dragon fruit peel (DFP) was extracted by using pure water at room temperature. WSP, dominant in DFP (17.13 ± 1.01%), showed both a high molecular weight and a wide molecular weight distribution, while the yield of the rest acid-soluble pectin (HAP) from DFP residue was only 5.22 ± 0.76%. Furthermore, WSP can stabilize emulsions over a wide range of concentrations and oil phases, especially HIPE. Therefore, the hypothesis was verified that the pectin-rich extract from dragon fruit peel with excellent emulsifying properties could be simply extracted by pure water. This environmentally-friendly and energy-saving extraction method provides a new insight to increase the additional value of dragon fruit peel produced in food processing.


Fruit , Pectins , Emulsifying Agents , Emulsions , Camphor , Menthol , Water
10.
Food Funct ; 14(7): 3357-3378, 2023 Apr 03.
Article En | MEDLINE | ID: mdl-36942763

The severity of a viral respiratory illness was greatly exacerbated after exposure to a contaminant containing benzo[a]pyrene (B[a]P). Flavonoid-rich fruit intake has gained intense interest due to their health-promoting benefits for viral respiratory diseases, including influenza viruses. In our study, diosmetin (3',5,7-trihydroxy-4'-methoxyflavone), a naturally occurring hydroxylated methoxyflavone that is abundant in Citrus fruits, was explored for its effects on B[a]P-exacerbated H1N1 influenza virus-mediated inflammation and lung injury. Initially, in vivo results demonstrated that diosmetin protected against H1N1 virus-elicited acute lung injury. Simultaneously, H1N1 virus or B[a]P-stimulated A549 cells treated with diosmetin inhibited NF-κB and P-P38 activation, resulting in suppression of pro-inflammatory cytokines and apoptosis. Interestingly, diosmetin obviously promoted the expression of PPAR-γ as well as nuclear translocation of PPAR-γ, whereas, PPAR-γ inhibition by GW9662 weakened the inhibitory effects of diosmetin on H1N1 virus or B[a]P-mediated activation of NF-κB and P-P38, elevated expression of pro-inflammatory mediators as well as apoptosis. Furthermore, it was surprising to discover that mice exposed to both B[a]P and H1N1 viruses contributed to exacerbated acute lung injury, which were significantly ameliorated by diosmetin administration. In vitro studies showed that A549 cells with the combination of B[a]P and H1N1 virus augmented NF-κB and P-P38 activation, accompanied by higher levels of pro-inflammatory mediators and apoptosis, all of which were also significantly reduced by diosmetin treatment. Repressing PPAR-γ abrogated the inhibitory effects of diosmetin on B[a]P-exacerbated H1N1 virus-mediated NF-κB and P-P38 activation, inflammation, and apoptosis in A549 cells. Our findings suggest that diosmetin protected against B[a]P-exacerbated H1N1 virus-mediated lung injury by suppressing the exacerbation of NF-κB and P38 kinase activation in a PPAR-γ-dependent manner, suggesting potential benefits for B[a]P-exacerbated influenza-related illness therapeutics.


Acute Lung Injury , Influenza A Virus, H1N1 Subtype , Influenza, Human , Animals , Mice , Humans , NF-kappa B/metabolism , Benzo(a)pyrene , PPAR gamma/genetics , PPAR gamma/metabolism , Inflammation/drug therapy , Flavonoids/pharmacology , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Influenza, Human/drug therapy , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , Inflammation Mediators
11.
Eng Life Sci ; 23(2): e2200034, 2023 Feb.
Article En | MEDLINE | ID: mdl-36751472

Clustering enzymes in the same metabolic pathway is a natural strategy to enhance productivity. Synthetic protein, RNA and DNA scaffolds have been designed to artificially cluster multiple enzymes in the cell, which require complex construction processes and possess limited slots for target enzymes. We utilized the Escherichia coli inner cell membrane as a native scaffold to cluster four fatty acid synthases (FAS) and achieved to improve the efficiency of fatty acid synthesis in vivo. The construction strategy is as simple as fusing target enzymes to the N-terminus or C-terminus of the membrane anchor protein (Lgt), and the number of anchored enzymes is not restricted. This novel device not only presents a similar efficiency in clustering multiple enzymes to that of other artificial scaffolds but also promotes the product secretion, driving the entire metabolic flux forward and further increasing the gross yield compared with that in a cytoplasmic scaffold system.

12.
J Inflamm (Lond) ; 19(1): 24, 2022 Nov 30.
Article En | MEDLINE | ID: mdl-36451220

BACKGROUND: Acute lung injury (ALI) arises from sepsis or bacterial infection, which are life-threatening respiratory disorders that cause the leading cause of death worldwide. 5-Methoxyflavone, a methylated flavonoid, is gaining increased attention for its various health benefits. In the current study, we investigated the potential effects of 5-methoxyflavone against LPS-mediated ALI and elucidated the corresponding possible mechanism. METHODS: A mouse model with ALI was established by intratracheal instillation of LPS, and lung pathological changes, signaling pathway related proteins and apoptosis in lung tissues were estimated by H&E staining, immunofluorescence and TUNEL assay, respectively. Cell viability was evaluated by MTT assay; protein levels of pro-inflammatory mediators were measured by ELISA assay; levels of ROS and M1 macrophage polarization were assayed by flow cytometry; the expression of Nrf2 signaling, NOX4/TLR4 axis and P-STAT1 were detected by western blotting. RESULTS: Our results showed that 5-methoxyflavone treatment inhibited LPS-induced expression of NOX4 and TLR4 as well as the activation of downstream signaling (NF-κB and P38 MAPK), which was accompanied by markedly decreased ROS levels and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1, and IL-8) in BEAS-2B cells. Moreover, we revealed that these effects of 5-methoxyflavone were related to its Nrf2 activating property, and blockade of Nrf2 prevented its inhibitory effects on NOX4/TLR4/NF-κB/P38 MAPK signaling, thus abrogating the anti-inflammatory effects of 5-methoxyflavone. Besides, the Nrf2 activating property of 5-methoxyflavone in RAW264.7 cells led to inhibition of LPS/IFN-γ-mediated STAT1 signaling, resulting in suppression of LPS/IFN-γ-induced M1 macrophage polarization and the repolarization of M2 macrophages to M1. In a mouse model of LPS-induced ALI, 5-methoxyflavone administration ameliorated LPS-mediated lung pathological changes, the increased lung index (lung/body weight ratio), and epithelial cell apoptosis. Meanwhile, we found 5-methoxyflavone effectively suppressed the hyperactive signaling pathways and the production of excessive pro-inflammatory mediators. Moreover, 5-methoxyflavone reduced LPS-mediated M1 macrophage polarization associated with elevated P-STAT1 activation in the lung tissues. In addition, 5-methoxyflavone improved the survival of LPS-challenged mice. CONCLUSION: These results indicated that 5-methoxyflavone might be suitable for the development of a novel drug for ALI therapeutic.

13.
Medicine (Baltimore) ; 101(37): e30582, 2022 Sep 16.
Article En | MEDLINE | ID: mdl-36123856

OBJECTIVE: To retrospectively analyze the preoperative endoscopic evaluation of the size, nature, and depth of lesions in endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, determine whether the lesions can be completely resected, and reduce the risk of additional surgery after ESD. METHODS: A total of 114 patients with high-grade intraepithelial neoplasia(HGIN) and early gastric cancer treated with ESD in Hebei General Hospital from January 2016 to April 2021 were enrolled in this study. The lesions were evaluated preoperatively according to the endoscopic findings of white light, magnifying endoscopy, endoscopic features of narrow band imaging, and preoperative pathology. Lesion size, positive resection margin, lesion depth, and vascular invasion of postoperative pathology were used as criteria. RESULTS: There were 121lesions in 114 patients. The coincidence rates of preoperative and postoperative pathology were 87.21% (75/86) for HGIN and 92.1% (35/38) for adenocarcinoma. There was no significant difference in the coincidence rate between preoperative pathological evaluation and postoperative pathology among the 3 lesions (χ2 = 10.614, P = .005). The type and malignancy of the lesion were not related to its location or size. Magnifying endoscopy combined with narrow-band imaging showed that HGIN and early gastric cancer had clear borders, irregular microvessels, and irregular surface microarchitecture on endoscopic features. Lesions > 3 cm, surface ulcers and spontaneous bleeding may be risk factors for deeper lesions. CONCLUSION: ESD is not only a method for the treatment of early gastric cancer and precancerous lesions, but is also an important method for definite pathological diagnosis. Accurate preoperative assessment of lesion type, lesion extent and depth of invasion is helpful to improve the complete resection rate of ESD and reduce the risk of additional surgery.


Endoscopic Mucosal Resection , Precancerous Conditions , Stomach Neoplasms , Humans , Narrow Band Imaging/methods , Precancerous Conditions/surgery , Retrospective Studies , Stomach Neoplasms/pathology
14.
Cell Mol Biol Lett ; 27(1): 82, 2022 Sep 30.
Article En | MEDLINE | ID: mdl-36180831

Influenza-related acute lung injury (ALI) is a life-threatening condition that results mostly from uncontrolled replication of influenza virus (IV) and severe proinflammatory responses. The methoxy flavonoid compound 5-methoxyflavone (5-MF) is believed to have superior biological activity in the treatment of cancer. However, the effects and underlying mechanism of 5-MF on IV-mediated ALI are still unclear. Here, we showed that 5-MF significantly improved the survival of mice with lethal IV infection and ameliorated IV-mediated lung edema, lung histological changes, and inflammatory cell lung recruitment. We found that 5-MF has antiviral activity against influenza A virus (IAV), which was probably associated with increased expression of radical S-adenosyl methionine domain containing 2 (RSAD2) and suppression of endosomal acidification. Moreover, IV-infected A549 cells with 5-MF treatment markedly reduced proinflammatory mediator expression (IL-6, CXCL8, TNF-α, CXCL10, CCL2, CCL3, CCL4, GM-CSF, COX-2, and PGE2) and prevented P-IKBα, P-P65, and P-P38 activation. Interestingly, we demonstrated that 5-MF treatment could trigger activation of AMP-activated protein kinase (AMPK)α in IV-infected A549 cells, as evidenced by activation of the AMPKα downstream molecule P53. Importantly, the addition of AMPKα blocker compound C dramatically abolished 5-MF-mediated increased levels of RSAD2, the inhibitory effects on H1N1 virus-elicited endosomal acidification, and the suppression expression of proinflammatory mediators (IL-6, TNF-α, CXCL10, COX-2 and PGE2), as well as the inactivation of P-IKBα, P-P65, and P-P38 MAPK signaling pathways. Furthermore, inhibition of AMPKα abrogated the protective effects of 5-MF on H1N1 virus-mediated lung injury and excessive inflammation in vivo. Taken together, these results indicate that 5-MF alleviated IV-mediated ALI and suppressed excessive inflammatory responses through activation of AMPKα signaling.


Acute Lung Injury , Influenza A Virus, H1N1 Subtype , Influenza A virus , AMP-Activated Protein Kinases/metabolism , Acute Lung Injury/metabolism , Animals , Antiviral Agents/pharmacology , Cyclooxygenase 2 , Flavones , Flavonoids/pharmacology , Flavonoids/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Inflammation/drug therapy , Influenza A Virus, H1N1 Subtype/metabolism , Influenza A virus/metabolism , Interleukin-6/metabolism , Methionine/pharmacology , Methionine/therapeutic use , Mice , NF-kappa B/metabolism , Prostaglandins E/pharmacology , Prostaglandins E/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Tumor Suppressor Protein p53 , p38 Mitogen-Activated Protein Kinases/metabolism
15.
Omega (Westport) ; : 302228221121493, 2022 Sep 20.
Article En | MEDLINE | ID: mdl-36127158

This study aimed to examine coping strategies used by advanced colorectal cancer (CRC-A) survivors to manage death anxiety and fear of cancer progression, and links between these strategies and quality of life (QoL), distress, and death acceptance. Qualitative semi-structured interviews of 38 CRC-A survivors (22 female) were analysed via framework analysis. QoL and distress were assessed through the FACT-C and Distress Thermometer. Eleven themes were identified and mapped to active avoidance (keeping busy and distracted), passive avoidance (hoping for a cure), active confrontation (managing negative emotions; reaching out to others; focusing on the present; staying resilient), meaning-making (redefining one's identity; contributing to society; gaining perspective; remaining spiritual), and acceptance (accepting one's situation). Active confrontation (specifically utilising informal support networks) and meaning-making appeared beneficial coping strategies; more research is needed to develop and evaluate interventions which increase CRC-A survivors' use of these strategies to manage and cope with their death anxiety.

16.
Free Radic Biol Med ; 191: 66-81, 2022 10.
Article En | MEDLINE | ID: mdl-36028178

The main challenges in clinical applications of mesenchymal stem cells (MSCs) are attributed to their heterogeneity. It is believed that preconditioning of MSCs with active compounds may enhance the expression of potentially therapeutic molecules and thus achieve stable and effective therapeutic outcomes. In the present study, we investigated the mechanism by which pyrogallol increased the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) against LPS-induced acute lung injury (ALI). hUCMSCs with pyrogallol treatment increased expression of HO-1 at both mRNA and protein levels, accompanied by Kelch-Like ECH-Associated Protein 1 (Keap1) degradation, and upregulation of the Nrf2 protein levels as well as nuclear translocation of Nrf2. Moreover, the modulation of Keap1 and Nrf2 as well as HO-1 upregulation by pyrogallol was reversed by pretreatment with N-acetylcysteine (NAC) and a P38 kinase inhibitor (SB203580). Whereas, NAC pretreatment abrogated pyrogallol-mediated activation of P38 kinase, indicating that pyrogallol-derived ROS led to P38 kinase activation, thus promoting Nrf2/HO-1 signaling. Additionally, we found that the induction of p62 by the pyrogallol-mediated ROS/P38/Nrf2 axis interacted with Keap1 and resulted in autophagic degradation of Keap1, which created a positive feedback loop to further release of Nrf2. Furthermore, the increased expression of HO-1 in pyrogallol-pretreated hUCMSCs led to enhanced inhibitory effects on LPS-mediated TLR4/P-P65 signaling in BEAS-2B cells, resulting in increasing suppression of LPS-indued expression of a series of pro-inflammatory mediators. Compared to untreated hUCMSCs, Sprague-Dawley (SD) rats with pyrogallol-primed hUCMSCs transplantation showed enhanced improvements in LPS-mediated lung pathological alterations, the increased lung index (lung/body ratio), apoptosis of epithelial cells, the activation of TLR4/NF-κB signaling as well as the release of pro-inflammatory mediators. Together, these results suggested that hUCMSCs with pyrogallol pretreatment enhanced the therapeutic efficacy of hUCMSCs, which may provide a promising therapeutic strategy to maximize the therapeutic efficacy of hUCMSC-based therapy for treating LPS-associated ALI.


Acute Lung Injury , Mesenchymal Stem Cell Transplantation , Pyrogallol , Acetylcysteine/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/therapy , Animals , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Humans , Inflammation/drug therapy , Inflammation/therapy , Inflammation Mediators/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Lipopolysaccharides , Mesenchymal Stem Cells/cytology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Pyrogallol/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Umbilical Cord/cytology
17.
Support Care Cancer ; 30(11): 9057-9069, 2022 Nov.
Article En | MEDLINE | ID: mdl-35972645

PURPOSE: Continuing employment or returning to work (RTW) as a cancer survivor can be meaningful and financially necessary, yet challenging. However, there is a lack of qualitative research on RTW experiences and financial wellbeing of people with advanced colorectal cancer (CRC-A). This study aimed to fill this gap. METHODS: Adults treated for CRC-A were recruited 0.5-2 years post-surgery (or post-diagnosis of CRC-A for palliative chemotherapy participants). Semi-structured telephone interviews, exploring RTW and finances, were subjected to framework analysis. Demographic, clinical, and quality of life data (FACT-C, Distress Thermometer, COST measure) were collected to characterise the sample and inform the framework analysis. RESULTS: Analysis of 38 interviews revealed five overarching themes: work as a struggle, work as my identity, work as my saviour, work as a financial necessity, and employer and colleague response. Many survivors with CRC-A desired to, and had the capacity to, continue work or RTW, yet faced unique challenges from compounded stigma of both cancer and toileting issues. Inability to RTW negatively impacted financial and psychosocial wellbeing. Workplace support was an important facilitator of RTW. CONCLUSION: For survivors with CRC-A, continuing or RTW is fraught with challenges, including physical functioning challenges, financial anxiety, and unsupportive workplace environments. Survivors require psychosocial, financial, and employer support to manage these difficulties. This paper recommends a multiprong approach, including education programmes (facilitated through workers' union groups, human resource institutions, and/or large consumer CRC groups) and policies, to support workers and for employers to understand the unique challenges of employees with CRC-A.


Cancer Survivors , Colorectal Neoplasms , Adult , Humans , Cancer Survivors/psychology , Quality of Life , Employment/psychology , Survivors/psychology , Qualitative Research , Workplace/psychology
18.
Stem Cell Res Ther ; 13(1): 373, 2022 07 28.
Article En | MEDLINE | ID: mdl-35902972

BACKGROUND: Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-ß1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. METHOD: HK-2, a human RTEC line, was co-treated with TGF-ß1 and hucMSC-derived exosomes. Additionally, TGF-ß1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. RESULTS: TGF-ß1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-ß1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-ß1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3'-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-ß1 induction. CONCLUSIONS: HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-ß1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.


Mesenchymal Stem Cells , MicroRNAs , ADAM Proteins/metabolism , Cell Transdifferentiation/genetics , Epithelial Cells/metabolism , Epithelial-Mesenchymal Transition/genetics , Fibrosis , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/therapy , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Myofibroblasts/metabolism , Transforming Growth Factor beta1/metabolism , Umbilical Cord
19.
J Acquir Immune Defic Syndr ; 90(5): 567-575, 2022 08 15.
Article En | MEDLINE | ID: mdl-35585664

OBJECTIVES: This study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions. METHODS: Data consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions. RESULTS: Study participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates. CONCLUSIONS: This study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations.


COVID-19 , HIV Infections , Stress Disorders, Post-Traumatic , Aged , COVID-19/epidemiology , Cohort Studies , Female , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/psychology , Humans , Male , Middle Aged , Pandemics , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , United States/epidemiology
20.
BMC Med ; 20(1): 57, 2022 02 10.
Article En | MEDLINE | ID: mdl-35139840

BACKGROUND: The World Health Organization's (WHO) 25X25 goal aims for a 25% relative reduction in premature death due to four non-communicable diseases (NCD4)-cancer, cardiovascular disease, chronic respiratory diseases and diabetes-by 2025 compared to 2010. This study aimed to quantify the premature mortality in the Australian population due to NCD4, quantify the variation in mortality rates by age and sex, predict the premature mortality due to NCD4 in 2025 and evaluate the progress towards the WHO 25X25 goal. METHODS: A population-based study using cause-specific mortality data of all deaths which occurred in Australia from 2010 to 2016 and registered up to 2017, for adults aged 30-69 years, was conducted. Age-specific and age-standardised mortality rates (ASMR) and probability of death for NCD4 were calculated for each year. ASMRs in 2016 were calculated for men and women. Deaths and the probability of death in 2025 were predicted using Poisson regression based on data from 2006 to 2016. To assess the progress against the WHO 25X25 goal, the relative reduction in the probability of death from NCD4 conditions in 2025 compared to 2010 was calculated. RESULTS: ASMRs for NCD4 decreased from 2010 to 2016, except for diabetes which increased on average by 2.5% per year. Across sociodemographic factors, ASMRs were highest in males and increased with age. The projected probability of premature death in 2025 was 7.36%, equivalent to a relative reduction of 25.16% compared to 2010 levels. CONCLUSIONS: Premature mortality due to cancer, cardiovascular disease, respiratory diseases and diabetes declined in Australia from 2010 to 2016. This trend is consistent across age groups and by sex, and higher mortality rates were observed in males and at older ages. Nationally, if the current trends continue, we estimate that Australia will achieve a 25.16% relative reduction in premature deaths due to NCD4 in 2025 compared to 2010, signifying substantial progress towards the WHO 25X25 goal. Concerted efforts will need to continue to meet the 25X25 goal, especially in the context of the COVID-19 pandemic.


COVID-19 , Noncommunicable Diseases , Adult , Aged , Australia/epidemiology , Cause of Death , Female , Goals , Humans , Male , Middle Aged , Mortality , Mortality, Premature , Pandemics , SARS-CoV-2 , World Health Organization
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