In search of novel immune-modulatory compounds from British Columbia wild mushrooms and their effectiveness in inflammatory micro-circulation of mice

Natural products have been an integral component of people's health and health outcomes for thousands of years. In particular, several mushroom species have demonstrated beneficial therapeutic potential. The goals of this research are to explore the immune-stimulatory and anti-inflammatory potential of wild mushrooms native to the North Central region of British Columbia. Out of 42 mushroom extracts examined, four exhibited strong immune-stimulatory activity as assessed by induction of tumor-necrosis factor alpha (TNF-a) production in macrophage cells. Out of thirty-three extracts tests, nineteen demonstrated potent anti-inflammatory activity as determined by inhibition of lipopolysaccharide-induced TNF-a production in macrophage cells. Sodium hydroxide extract of Echinodontium trinctorium exhibited potent anti-inflammatory activity and was selected for further study. A small molecular weight (~5-25 kDa) carbohydrate was successfully purified using sequential size-exclusion and ion-exchange chromatography. GC-MS analysis showed that the polysaccharide has glucose (89.7%) as the major back-bone monosaccharide, and also the presence of other monosaccharides such as mannose (3.1%), galactose (2.8%), fucose (2.4%), and xylose (2.0%). The study also revealed the presence of 1,3-linked glucose linkages. Both the semi-purified anti-inflammatory compound(s) from E. tinctorium and the methanol extract of Inonotus obliquus can ameliorate histamine-induced vasodilation in the 2A arterioles (gluteus maximus muscle) in mice. This is the first study to demonstrate the anti-inflammatory activity of purified compounds and extracts from mushroom in an animal microcirculation model using intravital microscopy

Crisis Communication in China: Strategies taken by the Chinese Government and Online Public Opinion

Crisis communication strategies play an important role in determining whether an organisation is able to survive a crisis affecting the public. The 2003 severe acute respiratory syndrome, or SARS, outbreak in China is considered the beginning of modern crisis management and communication in the country. Ten years later, when a similar public health crisis occurred in 2013 with the H7N9 outbreak, the Chinese government pursued a variety of strategies to avoid a potential pandemic. Much of the previous research on crisis communication in China adopted Coombs’ Situational Crisis Communication Theory. However, as a theory proposed and developed in the West, its application in a non-Western culture requires testing. In addition, cultural influences and the role of digital technology have been discussed in some existing literature, but few studies have attempted to integrate these elements into crisis communication theories.In order to fill these two gaps, this research analyses the Chinese government’s crisis communication strategies during the H7N9 crisis, examining not only the government’s management of the crisis but also the public’s reaction to the official communication process. It also explores the cultural context and the development of digital media as critical actors underlying the strategies adopted. The analysis contributes to development of a comprehensive theory that incorporates these two elements, which shows and identifies related crisis communication strategies emerged from cultural traditions and the development of digital media. This research analyses five media sources representing different perspectives – government newspaper reports, press conferences and Weibo posts representing the government perspective and metropolitan newspaper reports and public Weibo posts representing public perspective. It aims to identify the strategies taken by the Chinese government during the H7N9 crisis and to examine the role of cultural factors and digital technology. This research uses the case study method and includes content analysis and critical discourse analysis. Content analysis is used to describe patterns and trends in strategies used during the H7N9 crisis, as represented in the government media sources. Critical discourse analysis is used for in-depth analysis of press conference transcripts to identify cultural factors relevant to the crisis communication strategies. Content analysis of metro newspapers reports and public Weibo posts, as well as critical discourse analysis of public Weibo postings are conducted to examine how the public responded to the strategies taken by the Chinese government. </div

Insomnia is related to long-term atrial fibrillation recurrence following radiofrequency ablation

Atrial fibrillation (AF), the most common cardiac arrhythmia, presents significant health challenges, and the intricate connection between insomnia and AF has garnered substantial attention. This cohort study aims to investigate the relationship between insomnia and AF recurrences following radiofrequency ablation. Data were retrieved from an electronic database of patients who underwent radiofrequency ablation for AF. The primary endpoint was AF recurrence. We utilized a multivariable Cox model, coupled with three propensity score methods, for analysis. Between January 1, 2017, and June 1, 2022, 541 patients who underwent radiofrequency ablation for AF were recorded in the database. After excluding 185 patients, the final cohort comprised 356 patients. Among them, 68 were afflicted by insomnia, while 288 were not. Over a median follow-up of 755 days, one patient died, and 130 (36.5%) experienced AF recurrence. Multivariate Cox regression analysis revealed that the insomnia group had a higher risk of AF recurrence compared to the non-insomnia group (HR: 1.83, 95% CI: 1.16–2.89). Further landmark analysis showed no significant difference in AF recurrence rates during the initial 1-year follow-up. However, beyond 1 year, the insomnia group demonstrated a significantly higher AF recurrence rate. As the number of insomnia symptoms increased, the risk of AF recurrence also rose significantly, indicating a dose-response relationship. This study establishes a significant link between insomnia and long-term AF recurrence following radiofrequency ablation. It underscores the importance of identifying and addressing insomnia in patients with AF undergoing radiofrequency ablation.</p

Dual-Responsive Controlled Drug Delivery Based on Ionically Assembled Nanoparticles

Ionically assembled nanoparticles (INPs) have been formed from poly­(ionic liquid-<i>co</i>-<i>N</i>-isopropylacrylamide) with deoxycholic acid through electrostatic interaction. The structure and properties of the INPs were investigated by using ¹H NMR, Fourier transform infrared (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), and so on. Due to pH-responsive deoxycholic acid (p<i>K</i>_a = 6.2) and thermo responsive <i>N</i>-isopropylacrylamide included in the ionic complex, the INPs exhibit highly pH and thermal dual-responsive properties. The potential practical applications as drug delivery carriers were demonstrated using doxorubicin (DOX) as a model drug. With a lower pH (pH 5.2) and higher temperature (above 37 °C), structural collapse of the INPs occurred as well as release of DOX owing to protonated DA departure from the INPs and a lower LCST (lower critical solution temperature) at the pathological conditions. The result shows that 80% of DOX molecules were released from INPs within 48 h at pH 5.2, 43 °C, but only 30% of the drug was released within 48 h at 37 °C and pH 7.4. Moreover, drug-loaded INPs exhibit an inhibitory effect on cell growth

Image_4_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.pdf

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p

Table_4_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.xlsx

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p

Table_5_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.xlsx

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p

Image_3_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.pdf

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p

Image_6_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.pdf

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p

Table_2_Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.xlsx

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.</p