An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice

Diabetic nephropathy (DN) is a common microvascular complication that easily leads to end-stage renal disease. It is important to explore the key biomarkers and molecular mechanisms relevant to diabetic nephropathy (DN). We used highthroughput RNA sequencing to obtain the genes related to DN glomerular tissues and healthy glomerular tissues of mice. Then we used LIMMA to analyze differentially expressed genes (DEGs) between DN and non-diabetic glomerular samples. And we performed KEGG, gene ontology functional (GO) enrichment, and gene set enrichment analysis to reveal the signaling pathway of the disease. The CIBERSORT algorithm based on support vector machine was used to determine the immune infiltration score. Random forest algorithm and Cytoscape obtained hub genes. Finally, we applied co-staining, immunohistochemical staining, RT-qPCR and western blotting to validate the protein and mRNA expression of both hub genes. We obtained 913 DEGs mainly related to inflammatory factors and immunity. GSEA results showed that differential genes were mainly enriched in IL-17 signaling pathway, lipid and atherosclerosis, rheumatoid arthritis, TNF signaling pathway, neutrophil extracellular trap formation, Staphylococcus aureus infection and other pathways. The intersection of the random forest algorithm and Cytoscape revealed both hub genes of CD300A and CXCL1. Experiments have shown that the both key genes of CD300A and CXCL1 shown increased expression in glomerular podocytes, and are related to the inflammation of diabetic nephropathy. And immunohistochemical staining and RT-qPCR further confirmed that the protein and mRNA expression level of CD300A or CXCL1 in glomeruli tissue in DN mice were increased. The expression levels of CD300A and CXCL1 increased significantly under HG (high glucose) stimulation, further confirming that diabetes can lead to increased levels of CD300A and CXCL1 at the cellular level. Through bioinformatics analysis, machine learning algorithms, and experimental research, CD300A and CXCL1 are confirmed as both potential biomarkers in diabetic nephropathy. And we further revealed the main pathways of differential genes and the differentially distributed immune infiltrating cells in diabetic nephropathy.     

Organic geochemistry of Cretaceous Lamza and Chikila coals, upper Benue trough, Nigeria

Some biomarkers and other compounds in the aliphatic and aromatic fractions of the Lamza and the Chikila coals were characterized and used in assessing the source input, maturity, hence the hydrocarbon generative potentials of the coals. The samples exhibit a slight n-alkanes odd carbon preference (CPI ∼ 1), high pristane/phytane ratios and a dominance of 20S epimer of C₂₉ sterane. The ratio of C₃₀ αβ/(αβ + βα) sterane and 22S/(22S + 22R) C₃₁-homohopane gave values of 0.77-0.83 and 0.58-0.60, respectively. The low Ts/Tm ratios are in agreement with the calculated vitrinite reflectance, R_c (0.60-0.70%). The methylphananthrenes maturity derived parameters (1-MP/9-MP; MPR; MPI-1; R_c) revealed a very slight variation and a consistent order of samples maturity with the exception of the R_c values. All these together with some other hopanoid ratios, show that the organic matter is terrestrially derived, deposited in an oxic environment and at marginal maturity for hydrocarbon generation.     

北部湾盆地迈陈凹陷徐闻X1井油气地球化学特征

通过对北部湾盆地迈陈凹陷徐闻X 1井所产天然气和原油样品的系统分析,指出该井天然气甲烷含量低、重烃气体含量高、干燥系数低,属于原油伴生气,而乙烷和丙烷的碳同位素值小于-30‰,是典型的油型气;该井原油的三环萜烷系列呈C19>C20>C21>C23>C24>C25>C26的阶梯状分布,呈煤成油的特征,但丰富的C27甾烷的存在表明该原油属于典型的湖相原油,而非煤成油,其生物标志物组成的重要特征是富含各种重排构型化合物,表明该原油的烃源岩形成于浅水、弱还原的淡水沉积环境。     

Biomarkers of meat tenderness: Present knowledge and perspectives in regards to our current understanding of the mechanisms involved

Biomarkers of the meat quality are of prime importance for meat industry, which has to satisfy consumers' expectations and, for them, meat tenderness is and will remain the primary and most important quality attribute. The tenderization of meat starts immediately after animal death with the onset of apoptosis followed by a cooperative action of endogenous proteolytic systems. Before consideration of the biomarkers identified so far, we present here some new features on the apoptotic process. Among them, the most important is the recent discovery of a complex family of serpins capable to inhibit, in a pseudo-irreversible manner, caspases, the major enzymes responsible of cell dismantling during apoptosis. The biomarkers so far identified have been then sorted and grouped according to their common biological functions. All of them refer to a series of biological pathways including glycolytic and oxidative energy production, cell detoxification, protease inhibition and production of Heat Shock Proteins. Some unusual biomarkers are also presented: annexins, galectins and peroxiredoxins. On this basis, a detailed analysis of these metabolic pathways allowed us to identify some domains of interest for future investigations. It was thus emphasized that mitochondria, an important organelle in the production of energy from carbohydrates, lipids and proteins are a central element in the initiation and development of apoptosis. It was therefore stressed forward that, in fact, very little is known about the postmortem fate of these organelles and their multiple associated activities. Other topics discussed here would provide avenues for the future in the context of identifying reliable predictors of the ultimate meat tenderness.     

Plasma Unesterified Fatty‐Acid Profile Is Dramatically and Acutely Changed under Ischemic Stroke in the Mouse Model

Although plasma biomarkers would facilitate rapid and accurate diagnosis of ischemic stroke for immediate treatment, no such biomarkers have been developed to date. In the present study, we tested our hypothesis that plasma unesterified fatty acids (FFA) are altered at early stages of acute ischemic stroke. Plasma was collected from mice 2 h after the permanent middle cerebral artery occlusion (pMCAo) onset, as well as from sham operated and control animals. After 2 h, pMCAo significantly changed the plasma FFA profile with the most dramatic 2‐ to 3‐fold relative increase in very long n‐3 and n‐6 FFA including 20:4n‐6, 22:4n‐6, 22:5n‐6, and 22:6n‐3. Changes in the plasma FFA profile are consistent with FFA liberation from brain phospholipid hydrolyzed under ischemic insult. These results identify, for the first time, the plasma FFA profile as a potential biomarker for an early ischemic stroke within the therapeutic window for thrombolytic treatment. Further studies are required to confirm its specificity and sensitivity in clinical settings.     

Biomarkers for cardiovascular risk assessment in autoimmune diseases

Autoimmune diseases, such as antiphospholipid syndrome, systemic lupus erythematosus, and rheumatoid arthritis, are characterized by a high prevalence of cardiovascular (CV) disease (CVD), which constitutes the leading causes of morbidity and mortality among such patients. Although such effects are partly explained by a higher prevalence of traditional CV risk factors, many studies indicate that such factors do not fully explain the enhanced CV risk in these patients. In addition, risk stratification algorithms based upon traditional CV risk factors are not as predictive in autoimmune diseases as in the general population. For these reasons, the timely and accurate assessment of CV risk in these high-risk populations still remains an unmet clinical need. An enhanced contribution of different inflammatory components of the immune response, as well as autoimmune elements (e.g. autoantibodies, autoantigens, and cellular response), has been proposed to underlie the incremental CV risk observed in these populations. Recent advances in proteomic tools have contributed to the discovery of proteins involved in CVDs, including some that may be suitable to be used as biological markers. In this review we summarize the main markers in the field of CVDs associated with autoimmunity, as well as the recent advances in proteomic technology and their application for biomarker discovery in autoimmune disease.     

Vitreous humor in the pathologic scope: Insights from proteomic approaches

The vitreous humor (VH) is the largest component of the eye. It is a colorless, gelatinous, highly hydrated matrix that fills the posterior segment of the eye between the lens and retina in vertebrates. In VH, a diversity of proteins that can influence retinal physiology is present, including growth factors, hormones, proteins with transporter activity, and enzymes. More importantly, the protein composition of VH has been described as being altered in a number of disease states. Therefore, attempts aiming at establishing a map of VH proteins and detecting putative biomarkers for ocular illness or protein fluctuations with putative physiologic significance were conducted over the last two decades, using proteomic approaches. Proteomic strategies often involve gel-based or LC techniques as sample fractioning approaches, subsequently coupled with MS procedures. This set of studies resulted in the proteomic characterization of a range of ocular disease samples, with particular incidence on diabetic retinopathy. However, practical therapeutic applications arising from these studies are scarce at the moment. A pertinent example of therapeutic targets arising from VH proteomics has emerged concerning vasoproliferative factors present in the vitreous, which should be involved in neovascularization and subsequent fibrovascular proliferation of the retina, in ocular disease context. Therefore, this review attempts to sum up the information acquired from the proteomic approaches to ocular disease conducted in VH samples, highlighting its clinical potential for disclosing ocular disease mechanisms and engendering pharmacological therapeutic treatments.     

State-of-the-art nanoplatform-integrated MALDI-MS impacting resolutions in urinary proteomics

Urine proteomics has become a subject of interest, since it has led to a number of breakthroughs in disease diagnostics. Urine contains information not only from the kidney and the urinary tract but also from other organs, thus urinary proteome analysis allows for identification of biomarkers for both urogenital and systemic diseases. The following review gives a brief overview of the analytical techniques that have been in practice for urinary proteomics. MALDI-MS technique and its current application status in this area of clinical research have been discussed. The review comments on the challenges facing the conventional MALDI-MS technique and the upgradation of this technique with the introduction of nanotechnology. This review projects nano-based techniques such as nano-MALDI-MS, surface-assisted laser desorption/ionization, and nanostructure-initiator MS as the platforms that have the potential in trafficking MALDI-MS from the lab to the bedside.     

Urine proteomic studies in preeclampsia

Preeclampsia (PE) is a multisystem disorder of pregnancy that develops after 20 wk of gestation in previously normotensive women and complicates 5–8% of pregnancies. This rapidly progressive syndrome is usually diagnosed when the mother develops hypertension and proteinuria. The only effective treatment is delivery of the baby although early low-dose aspirin has been shown to significantly reduce the risk for PE. Recent advances in proteomic methods of protein separation, identification, and quantitation may allow for the identification of proteins and peptides that could facilitate early detection of disease, improve assessment of prognosis, and allow closer monitoring of women at risk for PE. This review summarizes all currently available markers for prediction and diagnosis of PE and presents urine proteomic studies performed for the identification of novel biomarkers.