Construction and validation of a novel apoptosis-associated prognostic signature related to osteosarcoma metastasis and immune infiltration

BackgroundApoptosis played vital roles in the formation and progression of osteosarcoma. However, no studies elucidated the prognostic relationships between apoptosis-associated genes (AAGs) and osteosarcoma.MethodsThe differentially expressed genes associated with osteosarcoma metastasis and apoptosis were identified from GEO and MSigDB databases. The apoptosis-associated prognostic signature was established through univariate and multivariate cox regression analyses. The Kaplan–Meier (KM) survival curve, ROC curve and nomogram were constructed to investigate the predictive value of this signature. CIBERSORT algorithm and ssGSEA were used to explore the relationships between immune infiltration and AAG signature. The above results were validated in another GEO dataset and the expression of AAGs was also validated in osteosarcoma patient samples by immunohistochemistry.ResultsHSPB1 and IER3 were involved in AAG signature. In training and validation datasets, apoptosis-associated risk scores were negatively related to patient survival rates and the AAG signature was regarded as the independent prognostic factor. ROC and calibration curves demonstrated the signature and nomogram were reliable. GSEA revealed the signature related to immune-associated pathways. ssGSEA indicated that one immune cell and three immune functions were significantly dysregulated. The immunohistochemistry analyses of patients’ samples revealed that AAGs were significantly differently expressed between metastasis and non-metastasis osteosarcomas.ConclusionsThe present study identified and validated a novel apoptosis-associated prognostic signature related to osteosarcoma metastasis. It could serve as the potential biomarker and therapeutic targets for osteosarcoma in the future.     

The role of amino acid metabolism alterations in pancreatic cancer: From mechanism to application

The incidence of pancreatic cancer is increasing in both developed and developing Nations. In recent years, various research evidence suggested that reprogrammed metabolism may play a key role in pancreatic cancer tumorigenesis and development. Therefore, it has great potential as a diagnostic, prognostic and therapeutic target. Amino acid metabolism is deregulated in pancreatic cancer, and changes in amino acid metabolism can affect cancer cell status, systemic metabolism in malignant tumor patients and mistakenly involved in different biological processes including stemness, proliferation and growth, invasion and migration, redox state maintenance, autophagy, apoptosis and even tumor microenvironment interaction. Generally, the above effects are achieved through two pathways, energy metabolism and signal transduction. This review aims to highlight the current research progress on the abnormal alterations of amino acids metabolism in pancreatic cancer, how they affect tumorigenesis and development of pancreatic cancer and the application prospects of them as diagnostic, prognostic and therapeutic targets.     

Remembrance of things past: maintaining gene expression patterns with altered chromatin

Eukaryotic organisms have evolved mechanisms to stably preserve the gene expression patterns that determine cell fate. Recent advances have been made in understanding the DNA sequences and protein factors required to propagate gene activation or silencing. These studies suggest that, after gene activity states are selected during development, maintenance protein complexes provide a molecular memory of those states by altering a local domain of chromatin structure.     

Assessing the climate change effects on the distribution pattern of the Azerbaijan Mountain Newt (Neurergus crocatus)

Climate change is a grave danger for humans and a looming threat to Earth's biodiversity in the twenty-first century. Assessing the vulnerability of species to climate change is critical for practical conservation efforts. Due to their limited dispersal ability, amphibians are one of the most vulnerable groups of vertebrates to climate change. Among them, the species that inhabit mountains suffer a tremendous amount of climate change-induced pressures. We, therefore, adopted the Azerbaijan Mountain Newt (Neurergus crocatus), which currently inhabits Northwest Iran, North Iraq, and Southeast Turkey, as a case study for assessing the effects of climate change on the distribution patterns of mountain amphibians. By applying the species distribution models (SDMs) in this study, we tried to hindcast the species distribution area in the past and illustrate the impacts of climate change on its distribution in the present and future (the 2050s and 2070s) climate conditions. Also, the patch metrics have been deployed for identifying habitat fragmentation. Our results indicate a more than 50% rise in the species’ current suitable habitats compared to its glacial refugia. The suitable habitat is expected to gradually decrease in RCP 2.6 and RCP 8.5. Among the three countries in which the species occurs, its distribution overlaps with protected areas only in Iraq. The number of habitat patches will grow and reach approximately 20 to 60 patches by 2070 and the average area of the patches will decrease throughout this time. Aside from the numerous threats that endanger the species, climate change puts the long-term existence of Azerbaijan Newt in jeopardy. The results of this study stress the urgent need for taking extreme measures on the species management and conserving its remnant habitat patches.     

SOD mimics: From the tool box of the chemists to cellular studies

Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O₂⁻) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.     

Helminth infections: Enabling the World Health Organization Road Map

Helminthiases are considered among the most persistent public health problems. Control and/or elimination remains a global health challenge and the World Health Organization Road Map highlights critical gaps and actions required to reach the 2030 targets, among them the need for new and more effective treatment options. Stronger collaborations across different fields are required to reach these goals. The helminth elimination platform is one example of how knowledge of two different disease areas can be aligned to fuse expertise and break disease silos.