Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma

N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern in specific malignancies. We found two independent patterns of m6A alteration in ACC patients. The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns. The m6Ascore also served as an independent predictive factor in ACC patients. The somatic copy number variation (CNV) and patients prognosis can be predicted by m6A alteration patterns. Moreover, the ACC patients with high m6A scores had better overall survival (OS) and higher efficiency in immune checkpoint blockade therapy. Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy. The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice

Five EMT-Related Gene Signatures Predict Acute Myeloid Leukemia Patient Outcome

Background. The epithelial mesenchymal transition (EMT) gene has been shown to be significantly associated with the prognosis of solid tumors; however, there is a lack of models for the EMT gene to predict the prognosis of AML patients. Methods. First, we downloaded clinical data and raw transcriptome sequencing data from the TCGA database of acute myeloid leukemia (AML) patients. All currently confirmed EMT-related genes were obtained from the dbEMT 2.0 database, and 30% of the TCGA data were randomly selected as the test set. Univariate Cox regression analysis, random forest, and lasso regression were used to optimize the number of genes for model construction, and multivariate Cox regression was used for model construction. Area under the ROC curve was used to assess the efficacy of the model application, and the internal validation set was used to assess the stability of the model. Results. A total of 173 AML samples were downloaded, and a total of 1184 EMT-related genes were downloaded. The results of univariate batch Cox regression analysis suggested that 212 genes were associated with patient prognosis, random forest and lasso regression yielded 18 and 8 prognosis-related EMT genes, respectively, and the results of multifactorial COX regression model suggested that 5 genes, CBR1, HS3ST3B1, LIMA1, MIR573, and PTP4A3, were considered as independent risk factors affecting patient prognosis. The model ROC results suggested that the area under the curve was 0.868 and the internal validation results showed that the area under the curve was 0.815. Conclusion. During this study, we constructed a signature model of five EMT-related genes to predict overall survival in patients with AML; it will provide a useful tool for clinical decision making

Environmental and anthropogenic drivers of watercress (Nasturtium officinale) communities in char-lands and water channels across the Swat River Basin: implication for conservation planning

Recent anthropogenic sources and excess usage have immensely threatened the communities and habitat ecology of this region’s medicinally and economically significant crops. Therefore, our study aims to evaluate the community structure and related environmental characteristics sustaining Nasturtium officinale communities along the river basin (RB) in Northwest Pakistan, using the clustering procedure (Ward’s method) and Redundancy analysis (RDA). From 340 phytosociological plots (34 × 10 = 340), we identified four ecologically distinct assemblages of N. officinale governed by different environmental and anthropogenic factors for the first time. The floristic structure shows the dominance of herbaceous (100%), native (77%), and annual (58.09%) species indicating relatively stable communities; however, the existence of the invasive plants (14%) is perturbing and may cause instability in the future, resulting in the replacement of herbaceous plant species. Likewise, we noticed apparent variations in the environmental factors, i.e., clay percentage (p = 3.1 × 10−5), silt and sand percentage (p< 0.05), organic matter (p< 0.001), phosphorus and potassium (p< 0.05), and heavy metals, i.e., Pb, Zn, and Cd (p< 0.05), indicating their dynamic role in maintaining the structure and composition of these ecologically distinct communities. RDA has also demonstrated the fundamental role of these factors in species–environment correlations and explained the geospatial variability and plants’ ecological amplitudes in the Swat River wetland ecosystem. We concluded from this study that N. officinale communities are relatively stable due to their rapid colonization; however, most recent high anthropogenic interventions especially overharvesting and sand mining activities, apart from natural enemies, water deficit, mega-droughts, and recent flood intensification due to climate change scenario, are robust future threats to these communities. Our research highlights the dire need for the sustainable uses and conservation of these critical communities for aesthetics, as food for aquatic macrobiota and humans, enhancing water quality, breeding habitat, fodder crop, and its most promising medicinal properties in the region

Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures

Background: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. Methods: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. Results: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. Conclusions: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer

Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma

N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern in specific malignancies. We found two independent patterns of m6A alteration in ACC patients. The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns. The m6Ascore also served as an independent predictive factor in ACC patients. The somatic copy number variation (CNV) and patients prognosis can be predicted by m6A alteration patterns. Moreover, the ACC patients with high m6A scores had better overall survival (OS) and higher efficiency in immune checkpoint blockade therapy. Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy. The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis

Altered renal immune complexes deposition in female BWF1 lupus mice following Plasmodium chabaudi infection

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that has a mysterious relationship with malaria infection. The current study was designated to compare between the effect of the live and the gamma irradiated Plasmodium chabaudi infection on BWF1 lupus murine model. A total of 30 female BWF1 mice were randomly divided into three groups (10 mice/group) as follows: group (I) lupus group (lupus non infected); group (II) live malaria infected group (lupus + live malaria infection); and group (III) irradiated malaria-infected group (lupus + gamma irradiated malaria infection). Live P. chabaudi infection was accompanied with a decrease in survival rate and food consumption in comparison to the control group of mice while gamma irradiated P. chabaudi -infection was unable to do this effect. Additionally, live P. chabaudi infection was accompanied with an increased level of proteinuria and increased rate of immune complexes deposition in kidney. Moreover, infection with live, but not gamma-irradiated P. chabaudi was accompanied with an increase in nitric oxide (NO), hydrogen peroxide (H2O2), and malondialdehyde (MDA) levels in plasma of lupus mice. The levels of both total cholesterol and triglycerides in plasma of lupus mice after live P. chabaudi infection were obviously decreased in comparison to the control group. On the other hand, gamma-irradiated P. chabaudi infection resembled the control group. Our data revealed that infection of lupus mice with live but not gamma-irradiated P. chabaudi has several histological and biochemical effects. Keywords: Lipid peroxidation, Oxidative stress, Plasmodium chabaudi, Redox imbalance, SL