Hellebrigenin anti-pancreatic cancer effects based on apoptosis and autophage
Hellebrigenin is a natural product found in the toad skin secretions and plants of Urginea, including Hellebores and Kalanchoe genera. It has been shown to be active against Leishmania chagasi promastigotes and Trypanosoma cruzi trypomastigotes and also reported to play an anti-tumor effect on several cancer cell lines in vitro, including pancreatic cancer. This study is aimed to investigate the effects of Hellebrigenin on pancreatic carcinoma cells, SW1990 and BxPC-3 in vitro and its molecular mechanism involved in antitumor activities. Our results showed that Hellebrigenin effectively inhibited the proliferation of SW1990 and BxPC-3 cells in dose- and time-dependent manner. Flow cytometry results showed that Hellebrigenin induced the G0/G1 arrest in both of SW1990 and BxPC-3 cells and promoted cell early apoptosis and autophagy according to morphological observation. Immunofluorescence staining results further confirmed that cell apoptosis and autophagy also increased upon the Hellebrigenin treatment. Moreover, higher dose of Hellebrigenin further increased the cell apoptosis rate while decrease the mitochondrial membrane potential 24 h after treatment. The autophagy rate increased 48 h after treatment with significant difference (P < 0.05). Western blot analysis showed that the expression of caspase 3, 7, cleaved caspase 7, Atg 12, LC3 proteins were increased in SW1990 cell after treatment with Hellebrigenin. In addition, increasing expression of caspase 3, 7, 9, PARP, cleaved caspase 3, 7, 9, PARP, the sub basic protein of the PI3K family, Beclin-1, LC 3, Atg 3, 5, 12, 16 L were also observed after BxPC-3 cells treated with Hellebrigenin. In summary, this study reported for the first time that Hellebrigenin effectively induced autophagy and apoptosis especially the early apoptosis in SW1990 and BxPC-3 cells.
Wei et al. (2020) Hellebrigenin anti-pancreatic cancer effects based on apoptosis and autophage. PeerJ 8:e9011 https://doi.org/10.7717/peerj.9011
Characteristics of the soil microbial community in the forestland of Camellia oleifera
Characterizing soil microbial community is important for forest ecosystem management and microbial utilization. The microbial community in the soil beneath Camellia oleifera, an important woody edible oil tree in China, has not been reported before. Here, we used Illumina sequencing of 16S and ITS rRNA genes to study the species diversity of microorganisms in C. oleifera forest land in South China. The results showed that the rhizosphere soil had higher physicochemical properties, enzyme activities and microbial biomass than did the non-rhizosphere soil. The rhizosphere soil microorganisms had a higher carbon source utilization capacity than the non-rhizosphere soil microorganisms, and attained the highest utilization capacity in summer. The soil microbial community of C. oleifera was characterized by rich ester and amino acid carbon sources that played major roles in the principal functional components of the community. In summer, soil microbes were abundant in species richness and very active in community function. Rhizosphere microorganisms were more diverse than non-root systems in species diversity, which was associated with soil pH, Available phosphorous (AP) and Urease (URE). These results indicated that microbial resources were rich in rhizosphere soil. A priority should be given to the rhizosphere microorganisms in the growing season in developing and utilizing soil microorganisms in C. oleifera plantation. It is possible to promote the growth of C. oleifera by changing soil microbial community, including carbon source species, pH, AP, and URE. Our findings provide valuable information to guide microbial isolation and culturing to manage C. oleifera land.
Zhang et al. (2020) Characteristics of the soil microbial community in the forestland of Camellia oleifera. PeerJ 8:e9117 https://doi.org/10.7717/peerj.9117
Impact of electrocardiographic morphology on clinical outcomes in patients with non-ST elevation myocardial infarction receiving coronary angiography and intervention: a retrospective study
Background The impact of electrocardiography (ECG) morphology on clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving percutaneous coronary intervention (PCI) is unknown. This study investigated whether different ST morphologies had different clinical outcomes in patients with NSTEMI receiving PCI. Methods This retrospective study analyzed record-linked data of 362 patients who had received PCI for NSTEMI between January 2008 and December 2010. ECG revealed ST depression in 67 patients, inverted T wave in 91 patients, and no significant ST-T changes in 204 patients. The primary endpoint was long-term all-cause mortality. The secondary endpoint was long-term cardiac death and non-fatal major adverse cardiac events. Results Compared to those patients whose ECG showed an inverted T wave and non-specific ST-T changes, patients whose ECG showed ST depression had more diabetes mellitus, advanced chronic kidney disease (CKD) and left main artery disease, as well as more in-hospital mortality, cardiac death and pulmonary edema during hospitalization. Patients with ST depression had a significantly higher rate of long-term total mortality and cardiac death. Finally, multiple stepwise Cox regression analysis showed that an advanced Killip score, age, advanced CKD, prior percutaneous transluminal coronary angioplasty and ST depression were independent predictors of the primary endpoint. Conclusions Among NSTEMI patients undergoing coronary angiography, those with ST depression had more in-hospital mortality and cardiac death. Long-term follow-up of patients with ST depression consistently reveals poor outcomes.
Wu et al. (2020) Impact of electrocardiographic morphology on clinical outcomes in patients with non-ST elevation myocardial infarction receiving coronary angiography and intervention: a retrospective study. PeerJ 8:e8796 https://doi.org/10.7717/peerj.8796
Integrated analysis of lymphocyte infiltration-associated lncRNA for ovarian cancer via TCGA, GTEx and GEO datasets
Background Abnormal expression of long non-coding RNAs (lncRNA) play a significant role in the incidence and progression of high-grade serous ovarian cancer (HGSOC), which is a leading cause of mortality among gynecologic malignant tumor patients. In this study, our aim is to identify lncRNA-associated competing endogenous RNA (ceRNA ) axes that could define more reliable prognostic parameters of HGSOC, and to investigate the lncRNAs’ potential mechanism of in lymphocyte infiltration. Methods The RNA-seq and miRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database; while for obtaining the differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs), we used edgeR, limma and DESeq2. After validating the RNA, miRNA and gene expressions, using integrated three RNA expression profiles (GSE18520, GSE27651, GSE54388) and miRNA profile (GSE47841) from the Gene Expression Omnibus (GEO) database, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses through ClusterProfiler. The prognostic value of these genes was determined with Kaplan–Meier survival analysis and Cox regression analysis. The ceRNA network was constructed using Cytoscape. The correlation between lncRNAs in ceRNA network and immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource (TIMER), and gene markers of tumor-infiltrating immune cells were identified using Spearman’s correlation after removing the influence of tumor purity. Results A total of 33 DELs (25 upregulated and eight downregulated), 134 DEMs (76 upregulated and 58 downregulated), and 1,612 DEGs (949 upregulated and 663 downregulated) were detected that could be positively correlated with overall survival (OS) of HGSOC. With the 1,612 analyzed genes, we constructed a ceRNA network, which indicated a pre-dominant involvement of the immune-related pathways. Furthermore, our data revealed that LINC00665 influenced the infiltration level of macrophages and dendritic cells (DCs). On the other hand, FTX and LINC00665, which may play their possible roles through the ceRNA axis, demonstrated a potential to inhibit Tregs and prevent T-cell exhaustion. Conclusion We defined several prognostic biomarkers for the incidence and progression of HGSOC and constructed a network for ceRNA axes; among which three were indicated to have a positive correlation with lymphocyte infiltration, namely: FTX-hsa-miR-150-5p-STK11, LINC00665-hsa-miR449b-5p-VAV3 and LINC00665-hsa-miR449b-5p-RRAGD.
Wu et al. (2020) Integrated analysis of lymphocyte infiltration-associated lncRNA for ovarian cancer via TCGA, GTEx and GEO datasets. PeerJ 8:e8961 https://doi.org/10.7717/peerj.8961
Association of heart rate trajectories with the risk of adverse outcomes in a community-based cohort in Taiwan
Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18–2.76]) and 1.45 (95% CI [0.67–3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.
Wei et al. (2020) Association of heart rate trajectories with the risk of adverse outcomes in a community-based cohort in Taiwan. PeerJ 8:e8987 https://doi.org/10.7717/peerj.8987
Understanding PM2.5 concentration and removal efficiency variation in urban forest park—Observation at human breathing height
To increase our knowledge of PM2.5 concentrations near the surface in a forest park in Beijing, an observational study measured the concentration and composition of PM2.5 in Beijing Olympic Forest Park from 2014 to 2015. This study analyzed the meteorological factors and removal efficiency at 1.5 m above the ground (human breathing height) over the day in the forest. The results showed that the average concentrations of PM2.5 near the surface peaked at 07:00–09:30 and reached their lowest at 12:00–15:00. Besides, the results showed that the annual concentration of PM2.5 in the forest was highest during winter, followed by spring and fall, and was lowest during summer. The main chemical components of PM2.5 near the surface in the forest were SO42− and NO3−, which accounted for 68.72% of all water-soluble ions that we observed. The concentration of PM2.5 in the forest had a significant positive correlation with relative humidity and a significant negative correlation with temperature. The removal efficiency near the surface showed no significant variation through the day or year. In the forest, the highest removal efficiency occurred between 07:00 and 09:30 in summer, while the lowest occurred between 09:30 and 12:00 in winter.
Yan et al. (2020) Understanding PM2.5 concentration and removal efficiency variation in urban forest park—Observation at human breathing height. PeerJ 8:e8988 https://doi.org/10.7717/peerj.8988
Tetrandrine alleviates cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via Sirt-1
Background & Aims Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome. Methods C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, i.p.) was administered for seven days and 30 min before and after MCAO. Their brain tissues were evaluated for NLRP3 inflammasome and Sirtuin-1 (Sirt-1) expression. An intracerebroventricular injection of Sirt-1 siRNA was administered to assess the activation of the NLRP3 inflammasome. Results Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation. Conclusion Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.
Wang et al. (2020) Tetrandrine alleviates cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via Sirt-1. PeerJ 8:e9042 https://doi.org/10.7717/peerj.9042
Public perspectives and media reporting of wolf reintroduction in Colorado
In the state of Colorado, a citizen ballot initiative to reintroduce gray wolves (Canis lupus) is eliciting polarization and conflict among multiple stakeholder and interest groups. Given this complex social landscape, we examined the social context surrounding wolf reintroduction in Colorado as of 2019. We used an online survey of 734 Coloradans representative in terms of age and gender, and we sampled from different regions across the state, to examine public beliefs and attitudes related to wolf reintroduction and various wolf management options. We also conducted a content analysis of media coverage on potential wolf reintroduction in 10 major daily Colorado newspapers from January 2019, when the signature-gathering effort for the wolf reintroduction initiative began, through the end of January 2020, when the initiative was officially added to the ballot. Our findings suggest a high degree of social tolerance or desire for wolf reintroduction in Colorado across geographies, stakeholder groups, and demographics. However, we also find that a portion of the public believes that wolves would negatively impact their livelihoods, primarily because of concerns over the safety of people and pets, loss of hunting opportunities, and potential wolf predation on livestock. These concerns—particularly those related to livestock losses—are strongly reflected in the media. We find that media coverage has focused only on a few of the many perceived positive and negative impacts of wolf reintroduction identified among the public. Our findings highlight the need to account for this diversity of perspectives in future decisions and to conduct public outreach regarding likely impacts of wolf reintroduction.
Niemiec et al. (2020) Public perspectives and media reporting of wolf reintroduction in Colorado. PeerJ 8:e9074 https://doi.org/10.7717/peerj.9074
Ecological data often violate common assumptions of traditional parametric statistics (e.g., that residuals are Normally distributed, have constant variance, and cases are independent). Modern statistical methods are well equipped to handle these complications, but they can be challenging for non-statisticians to understand and implement. Rather than default to increasingly complex statistical methods, resampling-based methods can sometimes provide an alternative method for performing statistical inference, while also facilitating a deeper understanding of foundational concepts in frequentist statistics (e.g., sampling distributions, confidence intervals, p-values). Using simple examples and case studies, we demonstrate how resampling-based methods can help elucidate core statistical concepts and provide alternative methods for tackling challenging problems across a broad range of ecological applications.
Fieberg et al. (2020) Resampling-based methods for biologists. PeerJ 8:e9089 https://doi.org/10.7717/peerj.9089
Evaluation of a novel syndromic surveillance system for the detection of the 2007 melamine-related nephrotoxicosis foodborne outbreak in dogs and cats in the United States
The 2007 nephrotoxicosis outbreak associated with melamine and cyanuric acid adulteration of pet foods in the United States sparked an urgent need for a nationwide companion animal surveillance program. In 2016, we introduced a syndromic surveillance system based on a novel epidemiological algorithm, the proportionate diagnostic outcome ratio (PDOR). The PDOR procedure was validated using simulated outbreaks of foodborne illness (i.e., aflatoxicosis and gastrointestinal illness) in dogs and cats. In this study, we further evaluated the PDOR procedure using the 2007 melamine-related outbreak of nephrotoxicosis. The performance of the PDOR procedure was assessed by the time to alert and positive predictive value (PPV). Electronic medical records of dogs and cats seen at networked primary care veterinary hospitals across the United States were retrieved from a centralized database. The data of four relevant syndromic components: elevated serum creatinine concentration, vomiting, anorexia, and lethargy from July 28, 2006 to May 31, 2007 were prospectively analyzed using the PDOR algorithm. The results showed that the alerts generated from the analysis of elevated serum creatinine concentration could have led to an early detection of this nephrotoxicosis foodborne outbreak and were well matched to the reported timeline of the outbreak. Additionally, we also observed variations in the performance of the PDOR procedure across age of animals and syndromic components, with the PPVs ranged from 0.61 to 1.0. Combined with the findings from previous evaluations using simulated outbreak scenarios, this study provided additional evidence that the PDOR procedure can be applied in syndromic surveillance to effectively and accurately detect various types of foodborne illness outbreaks in companion animals. However, the interpretations of and responses to alerts require an understanding of clinical veterinary medicine and relevant syndromic knowledge, and should not be based solely on quantitative measures.
Weng et al. (2020) Evaluation of a novel syndromic surveillance system for the detection of the 2007 melamine-related nephrotoxicosis foodborne outbreak in dogs and cats in the United States. PeerJ 8:e9093 https://doi.org/10.7717/peerj.9093