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Introduction: Hypertension (HTN) is the third leading risk factor contributing to the disease burden in Southeast Asia. Understanding its underlying mechanism, such as endothelial dysfunction, is very important. Apelin is a recently discovered endogenous peptide hormone that, along with Nitric Oxide (NO), is implicated in endothelial dysfunction and the severity of HTN. This can significantly reduce renal function and lead to microalbuminuria/proteinuria in 5-15% of patients. Aim: To measure serum apelin and NO in patients with newly diagnosed primary HTN with or without microalbuminuria and to investigate the correlation of serum apelin with HTN in the same study population. Materials and Methods: This cross-sectional study was conducted from February 2019 to January 2021 in the Department of Biochemistry In collaboration with the Department of Medicine at SCB Medical College and Hospital, Cuttack, Odisha, India. A total of 180 participants were included in the present study. Among them, 90 were newly diagnosed hypertensive patients, and 90 were non hypertensive. The study comprised of 90 hypertensive patients, with 46 having microalbuminuria (Group-A), 44 without microalbuminuria (Group-B) and 90 normotensive controls (Group-C). All participants underwent evaluation of their biochemical profile which included Fasting Plasma Sugar (FBS), serum urea, creatinine, Total Cholesterol (TC), Triglyceride (TG), High-density Lipoprotein cholesterol (HDL-c), Low-density Lipoprotein cholesterol (LDL-c), Very Low-Density Lipoprotein (VLDL), serum apelin and NO levels, and urine albumin. The comparison between the three groups was done by using Analysis of Variance (ANOVA) test with post-hoc analysis. The Chi-square test was used to compare categorical variables. Results: The mean age of the participants was 50.48±9.73 years. study comprised of 90 hypertensive patients, with 46 having microalbuminuria, 44 without microalbuminuria, and 90 normotensive controls. The mean serum apelin levels were 394.45±84.2, 386.9±86.12, and 62.73±22.87 ng/L, respectively, among patients with microalbuminuria, without microalbuminuria, and normotensive patients. Similarly, the mean serum NO levels were 6.31±2.94, 8.32±2.63, and 20.15±4.37 μmol/L, respectively, among the three groups. The comparison of mean values indicated a significant (p

Introduction: Hypertension (HTN) is the third leading risk factor contributing to the disease burden in Southeast Asia. Understanding its underlying mechanism, such as endothelial dysfunction, is very important. Apelin is a recently discovered endogenous peptide hormone that, along with Nitric Oxide (NO), is implicated in endothelial dysfunction and the severity of HTN. This can significantly reduce renal function and lead to microalbuminuria/proteinuria in 5-15% of patients. Aim: To measure serum apelin and NO in patients with newly diagnosed primary HTN with or without microalbuminuria and to investigate the correlation of serum apelin with HTN in the same study population. Materials and Methods: This cross-sectional study was conducted from February 2019 to January 2021 in the Department of Biochemistry In collaboration with the Department of Medicine at SCB Medical College and Hospital, Cuttack, Odisha, India. A total of 180 participants were included in the present study. Among them, 90 were newly diagnosed hypertensive patients, and 90 were non hypertensive. The study comprised of 90 hypertensive patients, with 46 having microalbuminuria (Group-A), 44 without microalbuminuria (Group-B) and 90 normotensive controls (Group-C). All participants underwent evaluation of their biochemical profile which included Fasting Plasma Sugar (FBS), serum urea, creatinine, Total Cholesterol (TC), Triglyceride (TG), High-density Lipoprotein cholesterol (HDL-c), Low-density Lipoprotein cholesterol (LDL-c), Very Low-Density Lipoprotein (VLDL), serum apelin and NO levels, and urine albumin. The comparison between the three groups was done by using Analysis of Variance (ANOVA) test with post-hoc analysis. The Chi-square test was used to compare categorical variables. Results: The mean age of the participants was 50.48±9.73 years. study comprised of 90 hypertensive patients, with 46 having microalbuminuria, 44 without microalbuminuria, and 90 normotensive controls. The mean serum apelin levels were 394.45±84.2, 386.9±86.12, and 62.73±22.87 ng/L, respectively, among patients with microalbuminuria, without microalbuminuria, and normotensive patients. Similarly, the mean serum NO levels were 6.31±2.94, 8.32±2.63, and 20.15±4.37 µmol/L, respectively, among the three groups. The comparison of mean values indicated a significant (p<0.001) positive correlation between the level of serum apelin and HTN and its complications, such as microalbuminuria. Conclusion: The positive correlation between serum apelin levels and blood pressure underscores the potential role of apelin in hypertensive pathophysiology. [ABSTRACT FROM AUTHOR]

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Summary: Chromatin configuration is critical for establishing tissue identity and changes substantially during tissue identity transitions. The crucial scientific and agricultural technology of in vitro tissue culture exploits callus formation from diverse tissue explants and tissue regeneration via de novo organogenesis. We investigated the dynamic changes in H3ac and H3K4me3 histone modifications during leaf‐to‐callus transition in Arabidopsis thaliana.We analyzed changes in the global distribution of H3ac and H3K4me3 during the leaf‐to‐callus transition, focusing on transcriptionally active regions in calli relative to leaf explants, defined by increased accumulation of both H3ac and H3K4me3.Peptide signaling was particularly activated during callus formation; the peptide hormones RGF3, RGF8, PIP1 and PIPL3 were upregulated, promoting callus proliferation and conferring competence for de novo shoot organogenesis. The corresponding peptide receptors were also implicated in peptide‐regulated callus proliferation and regeneration capacity. The effect of peptide hormones in plant regeneration is likely at least partly conserved in crop plants.Our results indicate that chromatin‐dependent regulation of peptide hormone production not only stimulates callus proliferation but also establishes pluripotency, improving the overall efficiency of two‐step regeneration in plant systems. [ABSTRACT FROM AUTHOR]

The discovery of fibroblast growth factor 21 (FGF21) as an important metabolic regulator with multiple salutary effects in animals sparked intense interest in the biopharmaceutical development of FGF21-based therapies. Several genetically engineered FGF21 analogues and antibody-based mimetics with improved pharmacokinetic and pharmacodynamic properties have been tested clinically for the treatment of obesity-related metabolic comorbidities. Significant amelioration of dyslipidaemia, hepatic steatosis, liver injury, resolution of metabolic dysfunction-associated steatohepatitis (MASH) has been consistently demonstrated in most clinical trials of different forms of FGF21 analogues/mimetics. The potent antidiabetic and antiobesity effects of FGF21 analogues observed in mice cannot be translated to humans, highlighting the interspecies differences in FGF21 actions. Combinatorial therapy with FGF21 and glucagon-like peptide-1 analogues, which act synergistically to exert their pharmacological benefits, holds great therapeutic potential for a cluster of obesity-related comorbid conditions. Recent advances in fibroblast growth factor 21 (FGF21) biology and pharmacology have led to the development of several long-acting FGF21 analogues and antibody-based mimetics now in various phases of clinical trials for the treatment of obesity-related metabolic comorbidities. The efficacy of these FGF21 analogues/mimetics on glycaemic control and weight loss is rather mild and inconsistent; nevertheless, several promising therapeutic benefits have been reproducibly observed in most clinical studies, including amelioration of dyslipidaemia (particularly hypertriglyceridaemia) and hepatic steatosis, reduction of biomarkers of liver fibrosis and injury, and resolution of metabolic dysfunction-associated steatohepatitis (MASH). Evidence is emerging that combination therapy with FGF21 analogues and other hormones (such as glucagon-like peptide 1; GLP-1) can synergise their pharmacological benefits, thus maximising the therapeutic efficacy for obesity and its comorbidities. Recent advances in fibroblast growth factor 21 (FGF21) biology and pharmacology have led to the development of several long-acting FGF21 analogues and antibody-based mimetics now in various phases of clinical trials for the treatment of obesity-related metabolic comorbidities. The efficacy of these FGF21 analogues/mimetics on glycaemic control and weight loss is rather mild and inconsistent; nevertheless, several promising therapeutic benefits have been reproducibly observed in most clinical studies, including amelioration of dyslipidaemia (particularly hypertriglyceridaemia) and hepatic steatosis, reduction of biomarkers of liver fibrosis and injury, and resolution of metabolic dysfunction-associated steatohepatitis (MASH). Evidence is emerging that combination therapy with FGF21 analogues and other hormones (such as glucagon-like peptide-1; GLP-1) can synergise their pharmacological benefits, thus maximising the therapeutic efficacy for obesity and its comorbidities. [ABSTRACT FROM AUTHOR]

Dr. Roger Guillemin was a French physiologist who won the Nobel Prize in 1977. His pioneering research and fierce competition led to the isolation and identification of hypothalamic hormones, including thyrotropin-releasing factor (TRF), luteinizing hormone-releasing factor (LRF), and somatostatin. These discoveries transformed the knowledge of the role of the hypothalamus in endocrine control. His work not only helped in the advancement of scientific understanding but also directed the field for decades. His research continues to resonate today, shaping modern endocrinology and impacting the global treatment of endocrine disorders., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Baranwal et al.)

Categories: Cardiovascular Pharmacology. [Display omitted] Calcitonin gene-related peptides alpha and beta (αCGRP, βCGRP), adrenomedullin (AM), and adrenomedullin 2/intermedin (AM2/IMD) function in pain signaling, neuroimmune communication, and regulation of the cardiovascular and lymphatic systems by activating either of two class B GPCRs, CLR and CTR, in complex with a RAMP1, −2, or −3 modulatory subunit. Inspired by our recent discovery that AM2/IMD(1–47) activation of CLR-RAMP3 elicits long duration cAMP signaling, here we used a live-cell cAMP biosensor assay to characterize the signaling kinetics of the two CGRP peptides and several bioactive AM and AM2/IMD fragments with variable N-terminal extensions. Remarkably, AM2/IMD(8–47) and AM2/IMD-53 exhibited even longer duration signaling than the 1–47 fragment. AM2/IMD(8–47) was a striking 8-fold longer acting than AM(13–52) at CLR-RAMP3. In contrast, the N-terminal extension of AM had no effect on signaling duration. AM(1–52) and (13–52) were equally short-acting. Analysis of AM2/IMD-AM mid-region chimeras and AM2/IMD R23 and R33 point mutants showed the importance of these residues for long-duration signaling and identified AM2/IMD peptides that exhibited up to 17-fold diminished signaling duration at CLR-RAMP3, while retaining near wildtype signaling potencies. βCGRP was ∼ 3-fold longer acting than αCGRP at the CGRP (CLR-RAMP1) and the amylin 1 (CTR-RAMP1) receptors. Chimeric CGRP peptides showed that the single residue difference near the N-terminus, and the two differences in the mid-region, equally contributed to the longer duration of βCGRP signaling. This work uncovers key temporal differences in cAMP signaling among the CGRP family peptides, elucidates the structural bases thereof, and provides pharmacological tools for studying long-duration AM2/IMD signaling. [ABSTRACT FROM AUTHOR]

The function of endogenous cell-cell signaling peptides relies on their interactions with cognate receptors, which in turn are influenced by the peptides' structures, necessitating a comprehensive understanding of the suite of post-translational modifications of the peptide. Herein, we report the initial characterization of putative peptide isomerase enzymes extracted from R. norvegicus, A. californica, and B. taurus tissues. These enzymes are both tissue and substrate-specific across all three organisms. Notably, the lungs of the mammalian species, and the central nervous system of the mollusk displayed the highest isomerase activity among the examined tissues. In vitro enzymatic conversion was observed for several endogenous peptides, such as the tetrapeptide GFFD in A. californica, and mammalian neuropeptide FF in R. norvegicus and B. taurus. To understand their mode of action, we explored the effects of several inhibitors on these enzymes, which suggest common active site residues. While further characterization of these enzymes is required, the investigations emphasize a widespread and overlooked enzyme activity related to the creation of bioactive peptides., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Four distinct types of sulfated peptides have been identified in Arabidopsis thaliana. These peptides play crucial roles in regulating plant development and stress adaptation. Recent studies have revealed that Xanthomonas and Meloidogyne can secrete plant-like sulfated peptides, exploiting the plant sulfated peptide signaling pathway to suppress plant immunity. Over the past three decades, receptors for these four types of sulfated peptides have been identified, all of which belong to the leucine-rich repeat receptor-like protein kinase subfamily. A number of regulatory proteins have been demonstrated to play important roles in their corresponding signal transduction pathways. In this review, we comprehensively summarize the discoveries of sulfated peptides and their receptors, mainly in Arabidopsis thaliana. We also discuss their known biological functions in plant development and stress adaptation. Finally, we put forward a number of questions for reference in future studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Oxytocin (OT) is a peptide hormone synthesized in the hypothalamus and released into systemic circulation or other areas of the brain. Its physiological roles include action as a hormone with stimulation of uterine contractions and that as a neuromodulator with involvement in social behaviors and regulation of mood. Its small size and low levels within biological matrices make it challenging to accurately measure. The goal of this study was to demonstrate the specificity of the antibody, sensitivity, and reproducibility of the Phoenix Pharmaceuticals (PP) OT radioimmunoassay (RIA) for use in human urine, serum, and saliva. Specificity of the antibody was assessed by high pressure liquid chromatography with ultraviolet (HPLC-UV) separation and assay of the fractions. Immunoreactivity was evaluated using the percent OT bound, and the fraction retention times were compared to the retention time of an intact OT standard to determine which fractions contained OT in the extracted samples. Reproducibility was assessed by running replicates of pools of each biomatrix over several assays. Sensitivity was assessed by repeated measurement of physiologically relevant low-concentration specimens. In all tested specimens the greatest reactivity in assay corresponded to the same fraction(s) as the OT standard. Only minimal reactivity was found in the other fractions, suggesting that in an unfractionated sample the antibody reacts mostly with intact OT. Reproducibility was acceptable for all specimens and the coefficient of variation (CV) ranged from 3.72 to 8.04% and 5.89-12.8%, for intra and inter-assay, respectively. The limits of quantitation (LOQ) were sufficient for measurement of normal values in urine (0.643 & 1.43 pg/mL), serum (1.90 pg/mL), and saliva pools (0.485 & 4.42 pg/mL). In conclusion, the PP OT RIA is specific and sensitive enough for reproducible measurement of intact OT in human peripheral biological matrices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Various secreted peptides, including peptide hormones, are present in the apoplast, but their biochemical characterization remains a challenge due to their low abundance, difficulty in extraction, and interference from numerous secondary metabolites. Here, we describe a simple and straightforward protocol for the extraction of apoplastic peptides with a high purity. This protocol takes advantage of the fact that apoplastic peptides diffuse and accumulate in the culture medium when Arabidopsis seedlings are subjected to whole-plant submerged culture. The peptides in the culture medium are efficiently recovered by o-chlorophenol extraction followed by acetone precipitation. The recovered peptides can be subjected to nano-liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) without any additional clean-up. This procedure enables the structural elucidation of mature peptide hormones in the apoplast with the use of Arabidopsis plants that overexpress peptide hormone genes., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Peptide therapeutics is gaining momentum. Advances in the field of peptidomics have enabled researchers to harvest vital information from various organisms and tissue types concerning peptide existence, expression and function. The development of mass spectrometry techniques for high-throughput peptide quantitation has paved the way for the identification and discovery of numerous known and novel peptides. Though much has been achieved, scientists are still facing difficulties when it comes to reducing the search space of the large mass spectrometry-generated peptidomics datasets and focusing on the subset of functionally relevant peptides. Moreover, there is currently no straightforward way to analytically compare the distributions of bioactive peptides in distinct biological samples, which may reveal much useful information when seeking to characterize tissue- or fluid-specific peptidomes. In this chapter, we demonstrate how to identify, rank, and compare predicted bioactive peptides and bioactivity distributions from extensive peptidomics datasets. To aid this task, we utilize MultiPep, a multi-label deep learning approach designed for classifying peptide bioactivities, to identify bioactive peptides. The predicted bioactivities are synergistically combined with protein information from the UniProt database, which assist in navigating through the jungle of putative therapeutic peptides and relevant peptide leads., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)