Enhydrin suppresses the malignant phenotype of GBM via Jun/Smad7/TGF-ß1 signaling pathway.

GBM is the most threatening form of brain tumor. The advancement of GBM is propelled by the growth, infiltration, and movement of cancer cells. Understanding the underlying mechanisms and identifying new therapeutic agents are crucial for effective GBM treatment. Our research focused on examining the withhold influence of Enhydrin on the destructive activity of GBM cells, both in laboratory settings and within living organisms. By employing network pharmacology and bioinformatics analysis, we have determined that Jun serves as the gene of interest, and EMT as the critical signaling pathway. Mechanistically, Enhydrin inhibits the activity of the target gene Jun to increase the expression of Smad7, which is infinitively regulated by the transcription factor Jun, and as the inhibitory transcription factor, Smad7 can down-regulate TGF-ß1 and the subsequent Smad2/3 signaling pathway. Consequently, this whole process greatly hinders the EMT mechanism of GBM, leading to the notable decline in cell proliferation, invasion, and migration. In summary, our research shows that Enhydrin hinders EMT by focusing on the Jun/Smad7/TGF-ß1 signaling pathway, presenting a promising target for treating GBM. Moreover, Enhydrin demonstrates encouraging prospects as a new medication for GBM treatment.

Effect of luteolin on glioblastoma's immune microenvironment and tumor growth suppression.

BACKGROUND: Glioblastoma is the most malignant and prevalent primary human brain tumor, and the immunological microenvironment controlled by glioma stem cells is one of the essential elements contributing to its malignancy. The use of medications to ameliorate the tumor microenvironment may give a new approach for glioma treatment. METHODS: Glioma stem cells were separated from clinical patient-derived glioma samples for molecular research. Other studies, including CCK8, EdU, Transwell, and others, supported luteolin's ability to treat glioma progenitor cells. Network pharmacology and molecular docking models were used to study the drug target, and qRT-PCR, WB, and IF were used to evaluate the molecular mechanism. Intracranial xenografts were examined using HE and IHC, while macrophage polarization was examined using FC. RESULTS: We originally discovered that luteolin inhibits glioma stem cells. IL6 released by glioma stem cells is blocked during medication action and inhibits glioma stem cell proliferation and invasion via the IL6/STAT3 signaling pathway. Additionally, luteolin inhibits the secretion of TGFß1, affects the polarization function of macrophages in the microenvironment, inhibits the polarization of M2 macrophages in TAM, and further inhibits various functions of glioma stem cells by affecting the IL6/STAT3 signaling pathway, luteolin crosstalk TGFß1/SMAD3 signaling pathway, and so on. CONCLUSIONS: Through the suppression of the immunological microenvironment and inhibition of the IL6/STAT3 signaling pathway, our study determined the inhibitory effect of luteolin on glioma stem cells. This medication's dual inhibitory action, which has a significant negative impact on the glioma stem cells' malignant process, makes it both a viable anti-glioma medication and a candidate for targeted glioma microenvironment therapy.

CircGNB1 facilitates the malignant phenotype of GSCs by regulating miR-515-5p/miR-582-3p-XPR1 axis.

Glioma is the most common and aggressive primary malignant brain tumor. Circular RNAs (circRNAs) and RNA-binding proteins (RBPs) have been verified to mediate diverse biological behaviors in various human cancers. Therefore, the aim of this study was to explore a novel circRNA termed circGNB1 and elucidate relative molecular mechanism in functional phenotypes, which might be a potential prognostic biomarker and therapeutic approach for glioma. CircGNB1 was upregulated in glioma and closely associated with the low poor prognosis. Functional assays demonstrated that circGNB1 overexpression promoted glioma stem cells (GSCs) viability proliferation, invasion, and neurosphere formation. Mechanistically, circGNB1 upregulated the expression of oncogene XPR1 via sponging miR-515-5p and miR-582-3p. The following experiments proved XPR1 could promote the malignant phenotype of GSCs via upregulating IL6 expression and activating JAK2/STAT3 signaling. Moreover, the RNA binding protein IGF2BP3 could bind to and maintain the stability of circGNB1, thus promoting the effects of circGNB1 on GSCs. Our study reveals that circGNB1 plays a crucial role in promoting tumorigenesis and malignant progression in glioma, which provides a promising cancer biomarker.

Optimal financing decision with financial constraints for a manufacturer in a low-carbon supply chain.

In this paper, bank financing (BF) and trade credit financing (TCF) are viable. We investigate the financing choice problem for an emission-dependent manufacturer with capital constraints. Each supply chain member pursues its profit maximization. In the literature on the financing supply chain, enterprises and consumers become increasingly aware of environmental protection. A growing number of manufacturers produce low-carbon products, such as environmentally friendly bags, through a green supply chain system. We use the Stackelberg game to study the equilibrium financing choice and optimal decisions. We also perform numerical analysis to verify the impact of certain parameters on financing decisions. The results show no direct relationship between the degree of carbon reduction and the total amount of carbon emissions as defined by the government. In addition, when the trade credit interest rate is higher than the bank interest rate, the manufacturer chooses bank financing. When the credit interest rate is lower than a certain threshold, the retailer provides trade credit financing. Our study also provides useful insights for managers to understand and make financing decisions in a low-carbon supply chain with a capital-constrained manufacturer.

The U2AF65/circNCAPG/RREB1 feedback loop promotes malignant phenotypes of glioma stem cells through activating the TGF-ß pathway.

Glioma is the most aggressive and common malignant neoplasms in human brain tumors. Numerous studies have showed that glioma stem cells (GSCs)drive the malignant progression of gliomas. Recent studies have revealed that circRNAs can maintain stemness and promote malignant progression of glioma stem cells. We used bioinformatics analysis to identify circRNAs and potential RNA-binding proteins (RBPs) in glioma. qRT-PCR, western blotting, RNA FISH, RNA pull-down, RNA immunoprecipitation assay, ChIP, immunohistochemistry, and immunofluorescence methods were used to quantified the expression of circNCAPG, U2AF65, RREB1 and TGF-ß1, and the underlying mechanisms between them. MTS, EDU, neurosphere formation, limiting dilution neurosphere formation and transwell assays examined the proliferation and invasive capability of GSCs, respectively. We identified a novel circRNA named circNCAPG was overexpressed and indicated the poor prognosis in glioma patients. Upregulating circNCAPG promoted the malignant progression of GSCs. RNA binding protein U2AF65 could stabilize circNCAPG by direct binding. Mechanically, circNCAPG interacted with and stabilized RREB1, as well as stimulated RREB1 nuclear translocation to activate TGF-ß1 signaling pathway. Furthermore, RREB1 transcriptionally upregulated U2AF65 expression to improve the stability of circNCAPG in GSCs, which established a feedback loop involving U2AF65, circNCAPG and RREB1. Since circRNA is more stable than mRNA and can execute its function continuously, targeting circNCAPG in glioma may be a novel promising therapeutic.

UPF1/circRPPH1/ATF3 feedback loop promotes the malignant phenotype and stemness of GSCs.

Glioblastoma multiforme (GBM) is the most lethal type of craniocerebral gliomas. Glioma stem cells (GSCs) are fundamental reasons for the malignancy and recurrence of GBM. Revealing the critical mechanism within GSCs' self-renewal ability is essential. Our study found a novel circular RNA (circRPPH1) that was up-regulated in GSCs and correlated with poor survival. The effect of circRPPH1 on the malignant phenotype and self-renewal of GSCs was detected in vitro and in vivo. Mechanistically, UPF1 can bind to circRPPH1 and maintain its stability. Therefore, more existing circRPPH1 can interact with transcription factor ATF3 to further transcribe UPF1 and Nestin expression. It formed a feedback loop to keep a stable stream for stemness biomarker Nestin to strengthen tumorigenesis of GSCs continually. Besides, ATF3 can activate the TGF-ß signaling to drive GSCs for tumorigenesis. Knocking down the expression of circRPPH1 significantly inhibited the proliferation and clonogenicity of GSCs both in vitro and in vivo. The overexpression of circRPPH1 enhanced the self-renewal of GSCs. Our findings suggest that UPF1/circRPPH1/ATF3 maintains the potential self-renewal of GSCs through interacting with RNA-binding protein and activating the TGF-ß signal pathway. Breaking the feedback loop against self-renewing GSCs may represent a novel therapeutic target in GBM treatment.

Lag effect of air temperature on the incidence of respiratory diseases in Lanzhou, China.

Previous studies have found that ambient temperature was associated with respiratory disease. However, little evidence is available in Lanzhou, a semi-arid region in northwest China, and respiratory disease is not well understood. This study evaluated the risk of outpatient visits for respiratory diseases associated with ambient temperatures from 2007 to 2016 in Lanzhou. We used a distributed lag non-linear model coupled with a generalized additive model to estimate the association between daily temperature and hospital visits for respiratory diseases in age- and sex-specific groups. Over 10 years, 1,042,656 hospital visits were recorded for respiratory disease, the ratio between males and females was 1.21:1. The peak period of onset occurs from November of the current year to March of the following year. Both low and high temperatures were associated with an increased risk of hospital visits for respiratory illness. The results showed that a large temperature decrease was associated with a significant risk for respiratory disease, the maximum effect of a temperature drop was reached at lag 1~2 days, the extreme low temperature (- 16 °C) had the maximum RR at lag 1, and the RR value was 1.082 (95 % CI 1.025-1.142). The high temperatures (23 °C) had maximum RR for respiratory disease on the current day, and the RR value was 1.099 (95 % CI 1.049-1.152). The high temperatures had acute and short-term effects and declined quickly over time, while the effects in low-temperature ranges were persistent over longer lag periods. Females suffered more from cold-associated morbidity than males. The effects of both hot and cold temperatures were greater among adolescents aged 6-14 years. Our study suggests that ambient temperatures are associated with hospital visits for respiratory illness in Lanzhou, particularly for those who are female and young. Caregivers and health practitioners should be made aware of the potential threat posed by cold and hot temperatures.

Comparison of air pollution in Shanghai and Lanzhou based on wavelet transform.

For a long-period comparative analysis of air pollution in coastal and inland cities, we analyzed the continuous Morlet wavelet transform on the time series of a 5274-day air pollution index in Shanghai and Lanzhou during 15 years and studied the multi-scale variation characteristic, main cycle, and impact factor of the air pollution time series. The analysis showed that (1) air pollution in the two cities was non-stationary and nonlinear, had multiple timescales, and exhibited the characteristics of high in winter and spring and low in summer and autumn. (2) The monthly variation in air pollution in Shanghai was not significant, whereas the seasonal variation of air pollution in Lanzhou was obvious. (3) Air pollution in Shanghai showed an ascending tendency, whereas that in Lanzhou presented a descending tendency. Overall, air pollution in Lanzhou was higher than that in Shanghai, but the situation has reversed since 2015. (4) The primary cycles of air pollution in these two cities were close, but the secondary cycles were significantly different. The aforementioned differences were mainly due to the impact of topographical and meteorological factors in Lanzhou, the weather process and the surrounding environment in Shanghai. These conclusions have reference significance for Shanghai and Lanzhou to control air pollution. The multi-timescale variation and local features of the wavelet analysis method used in this study can be applied to varied aspects of air pollution analysis. The identification of cycle characteristics and the monitoring, forecasting, and controlling of air pollution can yield valuable reference.

Effect of PM2.5 on daily outpatient visits for respiratory diseases in Lanzhou, China.

The present study assessed the effect of short-term exposure to PM2.5 of daily outpatient visits for respiratory diseases. Electronic records of daily outpatient visits were collected from two large general hospitals in Lanzhou, China from 01 January 2007 to 31 December 2016. Daily air pollution data from the Lanzhou Environmental Monitoring Station and daily meteorological data from the Lanzhou Meteorological Bureau were collected in the same period. A distributed lag non-linear model, based on a gender and age groups, was applied to analyse the exposure-response relationship between the air pollutants, and the daily outpatient visits for respiratory diseases. From 2007 to 2016, the PM2.5 concentrations were associated with an increase in the daily outpatient visits for respiratory diseases in Lanzhou. In addition, a lag effect was observed and this effect was the strongest on day 1. For every 10 µg/m3 increase in the PM2.5 concentration, the daily outpatient visits for respiratory diseases increased by 0.53% (95% CI: 0.22%-0.84%). People aged 18 years or younger were most sensitive to PM2.5, and the influence of PM2.5 was more significant for females than for males. The cumulative effect of the PM2.5 concentration for the number of outpatient visits was greater than its daily effect, and the cumulative effect peaked on day 12. From day 0 to day 14, every 10-µg/m3 increase in the PM2.5 concentration had a statistically significant cumulative effect on the outpatient visits for respiratory diseases among individuals aged 18 years or younger (p < 0.05), reaching a maximum value on day 14 (PM2.5: RR = 1.0213, 95% CI: 1.0128-1.0299).