Biomarkers of heart failure: current state of problem

There is constant increase in patients with heart failure every year worldwide. Early diagnosis and prediction of deterioration could upgrade management of patients and slow down the progression of heart failure.The brain natriuretic peptide precursor (NT-proBNP) is considered to be the universal biomarker, although it has several limitations. The search of ideal biomarker is directed into molecular biology and genetics. Microribonucleic acids (microRNAs) regulate different processes in human body, present myocardial specificity, and plasma stability. It has been proven in different trials that diagnostic and prognostic level of microRNAs is equal to NT-proBNP. Potential opportunities of the method are not only diagnosis but therapeutic targets for heart failure

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.

Evolution and Potential Function in Molluscs of Neuropeptide and Receptor Homologues of the Insect Allatostatins

The allatostatins (ASTs), AST-A, AST-B and AST-C, have mainly been investigated in insects. They are a large group of small pleotropic alloregulatory neuropeptides that are unrelated in sequence and activate receptors of the rhodopsin G-protein coupled receptor family (GPCRs). The characteristics and functions of the homologue systems in the molluscs (Buccalin, MIP and AST-C-like), the second most diverse group of protostomes after the arthropods, and of high interest for evolutionary studies due to their less rearranged genomes remains to be explored. In the present study their evolution is deciphered in molluscs and putative functions assigned in bivalves through meta-analysis of transcriptomes and experiments. Homologues of the three arthropod AST-type peptide precursors were identified in molluscs and produce a larger number of mature peptides than in insects. The number of putative receptors were also distinct across mollusc species due to lineage and species-specific duplications. Our evolutionary analysis of the receptors identified for the first time in a mollusc, the cephalopod, GALR-like genes, which challenges the accepted paradigm that AST-AR/buccalin-Rs are the orthologues of vertebrate GALRs in protostomes. Tissue transcriptomes revealed the peptides, and their putative receptors have a widespread distribution in bivalves and in the bivalve Mytilus galloprovincialis, elements of the three peptide-receptor systems are highly abundant in the mantle an innate immune barrier tissue. Exposure of M. galloprovincialis to lipopolysaccharide or a marine pathogenic bacterium, Vibrio harveyi, provoked significant modifications in the expression of genes of the peptide precursor and receptors of the AST-C-like system in the mantle suggesting involvement in the immune response. Overall, our study reveals that homologues of the arthropod AST-systems in molluscs are potentially more complex due to the greater number of putative mature peptides and receptor genes. In bivalves they have a broad and varying tissue distribution and abundance, and the elements of the AST-C-like family may have a putative function in the immune response.

Prolactin-releasing peptide receptor in GtoPdb v.2021.3

The precursor (PRLH, P81277) for PrRP generates 31 and 20-amino-acid versions. QRFP43 (43RFa) (named after a pyroglutamylated arginine-phenylalanine-amide peptide) is a 43 amino acid peptide derived from QRFP (P83859) and is also known as P518 or 26RFa. RFRP is an RF amide-related peptide [31] derived from a FMRFamide-related peptide precursor (NPVF, Q9HCQ7), which is cleaved to generate neuropeptide SF, neuropeptide RFRP-1, neuropeptide RFRP-2 and neuropeptide RFRP-3 (neuropeptide NPVF).

The ERAP1 active site cannot productively access the N-terminus of antigenic peptide precursors stably bound onto MHC class I

Processing of N-terminally elongated antigenic peptide precursors by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a key step in antigen presentation and the adaptive immune response. Although ERAP1 can efficiently process long peptides in solution, it has been proposed that it can also process peptides bound onto Major Histocompatibility Complex I molecules (MHCI). In a previous study, we suggested that the occasionally observed “ontο MHCI” trimming by ERAP1 is likely due to fast peptide dissociation followed by solution trimming, rather than direct action of ERAP1 onto the MHCI complex. However, other groups have proposed that ERAP1 can trim peptides covalently bound onto MHCI, which would preclude peptide dissociation. To explore this interaction, we constructed disulfide-linked MHCI-peptide complexes using HLA-B*08 and a 12mer kinetically labile peptide, or a 16mer carrying a phosphinic transition-state analogue N-terminus with high-affinity for ERAP1. Kinetic and biochemical analyses suggested that while both peptides could access the ERAP1 active site when free in solution, they were unable to do so when tethered in the MHCI binding groove. Our results suggest that MHCI binding protects, rather than promotes, antigenic peptide precursor trimming by ERAP1 and thus solution trimming is the more likely model of antigenic peptide processing.

Electrochemical Immunosensors for Quantification of Procalcitonin: Progress and Prospects

Human procalcitonin (PCT) is a peptide precursor of the calcium-regulating hormone calcitonin. Traditionally, PCT has been used as a biomarker for severe bacterial infections and sepsis. It has also been recently identified as a potential marker for COVID-19. Normally, serum PCT is intracellularly cleaved to calcitonin, which lowers the levels of PCT (<0.01 ng/mL). In severe infectious diseases and sepsis, serum PCT levels increase above 100 ng/mL in response to pro-inflammatory stimulation. Development of sensors for specific quantification of PCT has resulted in considerable improvement in the sensitivity, linear range and rapid response. Among the various sensing strategies, electrochemical platforms have been extensively investigated owing to their cost-effectiveness, ease of fabrication and portability. Sandwich-type electrochemical immunoassays based on the specific antigen–antibody interactions with an electrochemical transducer and use of nanointerfaces has augmented the electrochemical response of the sensors towards PCT. Identification of a superior combination of electrode material and nanointerface, and translation of the sensing platform into flexible and disposable substrates are under active investigation towards development of a point-of-care device for PCT detection. This review provides an overview of the existing detection strategies and limitations of PCT electrochemical immunosensors, and the emerging directions to address these lacunae.

A Novel Clinical Nomogram to Predict Transient Symptomatic Associated with Infarction: The ABCD3-SLOPE Score

Background. It is hard to differentiate transient symptoms associated with infarction (TSI) from transient ischemic stroke (TIA) without MRI in the early onset. However, they have distinct clinical outcomes and respond differently to therapeutics. Therefore, we aimed to develop a risk prediction model based on the clinical features to identify TSI. Methods. We enrolled 230 consecutive patients with transient neurologic deficit in the Department of Neurology, Tongji University Affiliated Tenth People’s Hospital from March 2014 to October 2019. All the patients were assigned into TIA group (DWI-negative) or TSI group (DWI-positive) based on MRI conducted within five days of onset. We summarized the clinical characteristics of TSI by univariate and multivariate analyses. And then, we developed and validated a nomogram to identify TSI by the logistic regression equation. Results. Of the 230 patients, 41.3% were diagnosed with TSI. According to the multivariate analysis, four independent risk factors, including smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score, were incorporated into a nomogram. We developed a predictive model named ABCD3-SLOPE. The calibration curve showed good agreement between nomogram prediction and observation. The concordance index (C-index) of the nomogram for TSI prediction was 0.77 (95% confidence interval, 0.70-0.83), and it was well-calibrated. Conclusions. Smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score were reliable risk factors for TSI. ABCD3-SLOPE was a potential tool to quantify the likelihood of TSI.

Correlation Networks Provide New Insights into the Architecture of Testicular Steroid Pathways in Pigs

Steroid metabolism is a fundamental process in the porcine testis to provide testosterone but also estrogens and androstenone, which are essential for the physiology of the boar. This study concerns boars at an early stage of puberty. Using a RT-qPCR approach, we showed that the transcriptional activities of several genes providing key enzymes involved in this metabolism (such as CYP11A1) are correlated. Surprisingly, HSD17B3, a key gene for testosterone production, was absent from this group. An additional weighted gene co-expression network analysis was performed on two large sets of mRNA-seq to identify co-expression modules. Of these modules, two containing either CYP11A1 or HSD17B3 were further analyzed. This comprehensive correlation meta-analysis identified a group of 85 genes with CYP11A1 as hub gene, but did not allow the characterization of a robust correlation network around HSD17B3. As the CYP11A1-group includes most of the genes involved in steroid synthesis pathways (including LHCGR encoding for the LH receptor), it may control the synthesis of most of the testicular steroids. The independent expression of HSD17B3 probably allows part of the production of testosterone to escape this control. This CYP11A1-group contained also INSL3 and AGT genes encoding a peptide hormone and an angiotensin peptide precursor, respectively.

Identification and characterization of a peptidoglycan hydrolase from Rhodobacter johrii

The bacterial whole genome sequences are available in the database therefore explored for the varieties of known and unknown proteins. Bacteria harbor various peptidoglycan hydrolases that cleave peptidoglycan and play an important role in the cell division, growth, spore differentiation and development. In the present study, we report a peptidoglycan hydrolase in an endospore producing phototrophic proteobacterium Rhodobacter johrii. The Peptidoglycan Hydrolase of Rba. johrii (PgHR) can actively hydrolyze the intact spore cortex peptidoglycan (sacculi). The protein contains a pre-peptide precursor which has a Hydrolase-2 (PF07486) family conserved domain. PgHR protein has SleB like properties which are spore cortex-lytic enzymes involved in the depolymerization of cortex peptidoglycan present and characterized in Bacillus spp. The expression pattern of PgHR through qRT-PCR suggests its role in stationary phase of Rba. johrii. This is a new type of peptidoglycan hydrolase reported from a proteobacterium.