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Many G protein-coupled receptors (GPCRs) initiate a second phase of stimulatory heterotrimeric G protein (Gs)-coupled cAMP signaling after endocytosis. The prevailing current view is that the endosomal signal is inherently β-arrestin-dependent because β-arrestin is necessary for receptor internalization and, for some GPCRs, to prolong the endosomal signal. Here we revise this view by showing that the vasoactive intestinal peptide receptor 1 (VIPR1), a secretin-family polypeptide hormone receptor, does not require β-arrestin to internalize or to generate an endosomal signal. β-Arrestin instead resolves the plasma membrane and endosomal signaling phases into sequential cAMP peaks by desensitizing the plasma membrane phase without affecting the endosomal phase. This appears to occur through the formation of functionally distinct VIPR1-β-arrestin complexes at each location that differ in their phosphorylation dependence. We conclude that endosomal GPCR signaling can occur in the absence of β-arrestin and that β-arrestin sculpts the spatiotemporal profile of cellular GPCR-G protein signaling through location-specific remodeling of GPCR-β-arrestin complexes.

Pancreatic β-cells in the islets of Langerhans are key to maintaining glucose homeostasis by secreting the peptide hormone insulin. Insulin is packaged within vesicles named insulin secretory granules (ISGs), which recently have been considered to have intrinsic structures and proteins that regulate insulin granule maturation, trafficking, and secretion. Previously, studies have identified a handful of novel ISG-associated proteins, using different separation techniques. The present study combines an optimized ISG isolation technique and mass spectrometry–based proteomics, with an unbiased protein correlation profiling and targeted machine-learning approach to uncover 211 ISG-associated proteins with confidence. Four of these proteins, syntaxin-7, synaptophysin, synaptotagmin-13, and Scamp3 have not been previously associated with ISG. Through colocalization analysis of confocal imaging, we validate the association of these proteins to the ISG in MIN6 and human β-cells. We further validate the role for one (Scamp3) in regulating insulin content and secretion from β-cells for the first time. Scamp3 knockdown INS-1 cells have reduced insulin content and dysfunctional insulin secretion. These data provide the basis for future investigation of Scamp3 in β-cell biology and the regulation of insulin secretion. Article Highlights: This study optimizes insulin granule isolation techniques alongside enhanced proteomics analyses to establish the first murine insulin secretory granule proteome. We investigated what proteins are present on insulin granules from MIN6 cells to further our understanding of insulin granule biogenesis, trafficking, and secretion. We found 211 insulin granule–associated proteins and validated four novel proteins. Through further functional studies, we implicated Scamp3 as a novel protein that regulates insulin content and secretion in β-cells. [ABSTRACT FROM AUTHOR]

Adrenomedullin (ADM) is a multifaceted peptide hormone involved in numerous physiological processes, including vascular stability, vasodilation, angiogenesis, and anti-inflammatory responses. The processing of ADM results in several fragments, including midregional proadrenomedullin (MR-proADM), and glycine-extended ADM (ADM-Gly) and bioactive ADM (bio-ADM). MR-proADM, the stable ADM fragment, and bio-ADM, the active form of ADM with a short half-life, have been shown to be potent biomarkers in a variety of pathologies. ADM-Gly, the direct precursor of bio-ADM, is a predominant form in human plasma, but remains less understood and least investigated. This study presents the development of a specific immunoluminometric assay for the quantification of ADM-Gly and offers a robust one-step approach for large-scale sample screening. Applied to human and rodent plasma, it elucidates the release kinetics and plasma half-life of ADM-Gly. Our findings confirm the predominance of ADM-Gly in healthy individuals and its significant release under pathological conditions. Our immunoluminometric assay enables precise measurement of ADM-Gly, advancing research into ADM-related pathophysiology and supporting its use as a biomarker and therapeutic target in various diseases. [ABSTRACT FROM AUTHOR]

Background Aims and Methods Results Conclusions Dumping syndrome is a complex of gastrointestinal symptoms originally studied in peptic ulcer surgery patients. At present, it is most prevalent in patients who underwent bariatric, upper gastrointestinal cancer or anti‐reflux surgery. The symptom pattern comprises early and late dumping symptoms. Several management options have been reported including nutritional, pharmacological and surgical approaches.In this study, we aimed to review the current evidence on dumping syndrome definition, diagnosis and treatment, including preliminary data from newer pharmacological studies.Current pathophysiological concepts and analyses of provocative tests has led to a clear definition of dumping syndrome, including both early and late dumping symptoms. The term postbariatric hypoglycemia represents a limited focus on late dumping only. The diagnosis relies on recognition of symptoms and signs in a patient with appropriate surgical history; and can be confirmed by provocative testing or registration of spontaneous hypoglycemia. The initial treatment focuses on dietary intervention, to which meal viscosity enhancers and/or the glycosidase inhibitor acarbose can be added. The most effective therapy is the use of short‐ or long‐acting somatostatin analogues, which is however expensive and entails side effect issues. In case of refractory hypoglycemia, diazoxide or SGLT2 inhibitors can be considered, based on limited evidence. In refractory patients, continuous enteral feeding or (rarely) surgical reinterventions have been advocated, although not supported by solid evidence. Therapies under current evaluation include the broad‐spectrum somatostatin analogue pasireotide, GLP‐1 receptor antagonists, GLP‐1 receptor agonists and administration of stable forms of glucagon are currently under study.Dumping syndrome is a well‐defined but probably under‐diagnosed complication of upper gastrointestinal, especially bariatric, and surgeries. Diagnosis is confirmed by a provocative test and incremental therapies starting with diet, adding meal viscosity enhancers or glycosidase inhibitors and adding somatostatin analogues in refractory cases. A number of emerging therapies targeting intestinal propulsion, peptide hormone effects and hypoglycemic events are under evaluation. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression. Methods: Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry. Results: Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers. Conclusions: This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations. [ABSTRACT FROM AUTHOR]

The cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11. How a particular ligand affects the receptor's conformation or its ability to bind other ligands remains poorly understood. To address these questions, we purified a soluble form of the receptor from newborn calf serum, carried out glycoproteomics to define the N-glycans at its 19 potential glycosylation sites, probed its ability to bind lysosomal enzymes in the presence and absence of IGF2 using surface plasmon resonance, and assessed its conformation in the presence and absence of IGF2 by negative-staining electron microscopy and hydroxyl radical protein footprinting studies. Together, our findings support the hypothesis that IGF2 acts as an allosteric inhibitor of lysosomal enzyme binding by inducing global conformational changes of CI-MPR. [ABSTRACT FROM AUTHOR]

Cyst nematodes use a stylet to secrete CLE-like peptide effector mimics into selected root cells of their host plants to hijack endogenous plant CLE signaling pathways for feeding site (syncytium) formation. Here, we identified ATHB8, encoding a HD-ZIP III family transcription factor, as a downstream component of the CLE signaling pathway in syncytium formation. ATHB8 is expressed in the early stages of syncytium initiation, and then transitions to neighboring cells of the syncytium as it expands; an expression pattern coincident with auxin response at the infection site. Conversely, MIR165a, which expresses in endodermal cells and moves into the vasculature to suppress HD-ZIP III TFs, is down-regulated near the infection site. Knocking down HD-ZIP III TFs by inducible over-expression of MIR165a in Arabidopsis dramatically reduced female development of the sugar beet cyst nematode (Heterodera schachtii). HD-ZIP III TFs are known to function downstream of auxin to promote cellular quiescence and define stem cell organizer cells in vascular patterning. Taken together, our results suggest that HD-ZIP III TFs function together with a CLE and auxin signaling network to promote syncytium formation, possibly by inducing root cells into a quiescent status and priming them for initial syncytial cell establishment and/or subsequent cellular incorporation. Author summary: Plant-parasitic cyst nematodes are one of the most damaging pathogens impacting crop production. These nematodes establish a permanent feeding site called a syncytium to withdraw nutrients from plant roots, causing plant malnutrition and reduced crop yield. The syncytium is induced by nematode stylet-secreted effectors, many of which hijack innate plant developmental programs to convert a normal plant cell to a syncytial cell. One such group of effectors functions by mimicking plant CLE peptide hormones, which are important in plant cell fate determination, and play a crucial role in syncytium formation. In this study, we show that nematode secreted CLE-like effectors induce the expression of the ATHB8 gene, a member of the Class III HD-ZIP transcription factor family, at early stages of syncytium formation. Reducing the level of HD-ZIP III family genes compromised the nematode's ability to feed on plants, indicating that HD-ZIP III transcription factors are important for cyst nematode parasitism. [ABSTRACT FROM AUTHOR]

The theoretical foundations of understanding psychiatric disorders are undergoing changes. Explaining behaviour and neuroendocrine cell communication leaning towards immunology represents a different approach compared to previous models for understanding complex central nervous system processes. One such approach is the study of immunoglobulins or autoantibodies, and their effect on peptide hormones in the neuro-endocrine system. In the present review, we provide an overview of the literature on neuropeptide/transmitter and autoantibody modulation in psychiatric disorders featuring emotional problems and aggression, including associated illness behaviour. Finally, we discuss the role of psycho-immunology as a growing field in the understanding of psychiatric disorders, and that modulation and regulation by IgG autoAbs represent a relatively new subcategory in psycho-immunology, where studies are currently being conducted. [ABSTRACT FROM AUTHOR]

Peptide hormones regulate plant development, growth, and stress responses. Sulfated peptides represent a class of proteins that undergo posttranslational modification by tyrosylprotein sulfotransferase (TPST), followed by specific enzymatic cleavage to generate mature peptides. This process contributes to the formation of various bioactive peptides, including PSKs (PHYTOSULFOKINEs), PSYs (PLANT PEPTIDE CONTAINING SULFATED TYROSINE), CIFs (CASPARIAN STRIP INTEGRITY FACTOR), and RGFs (ROOT MERISTEM GROWTH FACTOR). In the past three decades, significant progress has been made in understanding the molecular mechanisms of sulfated peptides that regulate plant development, growth, and stress responses. In this review, we explore the sequence properties of precursors, posttranslational modifications, peptide receptors, and signal transduction pathways of the sulfated peptides, analyzing their functions in plants. The cross-talk between PSK/RGF peptides and other phytohormones, such as brassinosteroids, auxin, salicylic acid, abscisic acid, gibberellins, ethylene, and jasmonic acid, is also described. The significance of sulfated peptides in crops and their potential application for enhancing crop productivity are discussed, along with future research directions in the study of sulfated peptides. [ABSTRACT FROM AUTHOR]

α‐Melanocyte stimulating hormone (α‐MSH) is a peptide hormone released from the intermediate lobe of the pituitary which regulates body pigmentation. In addition to the pituitary, α‐MSH is also produced in the midbrain, and exerts both anorexigenic and an anxiogenic actions. Acyl ghrelin and cholecystokinin are peripheral hormones derived from the digestive tract which affect the brain to control food intake and feeding behavior in vertebrates. In the present study, hypothesizing that plasma α‐MSH may also stimulate the brain and exert central effects, we examined whether peripherally administered α‐MSH affects food intake and psychomotor activity using a goldfish model. Intraperitoneal (IP) administration of α‐MSH at 100 pmol g−1 body weight (BW) reduced food consumption and enhanced thigmotaxis. These α‐MSH‐induced actions were blocked by intracerebroventricular administration of HS024, an antagonist of the melanocortin 4 receptor (MC4R), at 50 pmol g−1 BW, whereas these actions were not attenuated by pretreatment with an IP‐injected excess amount of capsaicin, a neurotoxin that destroys primary sensory (vagal and splanchnic) afferents, at 160 nmol g−1 BW. Transcripts for the MC4R showed higher expression in the diencephalon in other regions of the brain. These results suggest that, in goldfish, IP administered α‐MSH is taken up by the brain, and also acts as anorexigenic and anxiogenic factor via the MC4R signaling pathway. [ABSTRACT FROM AUTHOR]

Background Growth differentiation factor 15 (GDF-15) holds promise as a novel marker for heart failure. However, current detection methods fall short of meeting essential clinical requirements. Objectives The aim of this investigation was to assess the clinical significance of serum GDF-15 detection through the chemiluminescence method and to enhance its clinical application for predicting and evaluating heart failure in patients. Methods A total of 122 patients were included in the study. Serum GDF-15 levels were assessed using the chemiluminescence method and compared with results for NT-proBNP, N-terminal pro-brain natriuretic peptide (NT-proBNP), growth stimulation expressed gene 2 (ST2), high-sensitivity C-reactive protein (hs-CRP), and left ventricular ejection fraction (LVEF). Additionally, we conducted an analysis to evaluate the correlation between these indicators and heart failure events. Results LVEF, ST2, NT-proBNP, and GDF-15 exhibited significant associations with heart failure. In the multivariate proportional hazard analysis, subsequent to adjusting for the effects of other markers, however, only LVEF and GDF-15 retained their associations with heart failure events. Notably, GDF-15 emerged as the exclusive marker suitable for diagnosing heart failure with preserved ejection fraction. Conclusion The chemiluminescence method proved efficient in the rapid and sensitive detection of GDF-15 in patients with heart failure. Additionally, GDF-15 combined with other markers created a robust multi-index model. This model is valuable for heart failure diagnosis, treatment, and monitoring, with broad clinical applicability. [ABSTRACT FROM AUTHOR]

Purpose: Soluble vascular adhesion protein-1 (sVAP-1) and adropin are 2 biomarkers of endothelial dysfunction. The main purpose of this study was to evaluate the levels of sVAP-1 in patients with moderate and severe obstructive sleep apnea (OSA) compared to healthy controls, and to further determine the relationship between sVAP-1 and adropin levels, as well as inflammatory biomarkers and sleep parameters. Methods: In this study, we included 50 male patients with OSA (25 moderate and 25 severe) and 20 age- and sex-matched control subjects. Patients with OSA underwent polysomnography. All subjects underwent fasting peripheral blood sampling for laboratory analysis. Results: Serum sVAP-1 and inflammatory biomarkers (IL-6, TNF-α, and hsCRP) levels were significantly higher in patients with severe OSA compared to those with moderate OSA and control groups, while plasma levels of adropin showed the opposite trend. Furthermore, sVAP-1 levels had a significant positive correlation with AHI, ODI, TNF-α, IL-6, and hsCRP levels and a significant negative correlation with adropin levels. The receiver operating characteristic analysis showed an Area Under Curve (AUC) of.876 (P <.001) for sVAP-1 levels predicting OSA. Serum sVAP-1 threshold of > 445.5 ng/mL had an 88% sensitivity and 80% specificity for detecting OSA status. Multivariate regression analysis demonstrated that sVAP-1 remained a significant positive predictor of OSA severity. Conclusions: Increased sVAP-1 levels in OSA patients are significantly correlated with indices of OSA severity, adropin levels, and inflammatory biomarkers, suggesting that sVAP-1 plays a vital role in the pathophysiology of OSA and may become a potential screening tool in the evaluation of OSA severity. [ABSTRACT FROM AUTHOR]

Background: For the initial treatment strategy for patients with cardiac resynchronization therapy (CRT) indications, whether to choose left bundle branch area pacing (LBBaP) or biventricular pacing (BVP) remains controversial. We aimed to investigate the cost‐effectiveness ratio (CER) of LBBaP and BVP in heart failure (HF) patients with left bundle branch block (LBBB). Methods: This observational study included HF patients with LBBB who underwent successful LBBaP or BVP. The primary outcomes were echocardiographic response (left ventricular ejection fraction [LVEF] increase ≥5%), LVEF improvement, hospitalization costs, and CER (CER = cost/echocardiographic response rate). Secondary outcomes included other echocardiographic parameters, New York Heart Association (NYHA), N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP), pacemaker parameters, complications, ventricular arrhythmia (VA) events, HF hospitalization (HFH), and all‐cause mortality. Results: A total of 130 patients (85 LBBaP and 45 BVP) were included (65.6 ± 10.0 years, 70.77% men). The median follow‐up period was 16(12,30), months. Compared with BVP, the LBBaP group showed a greater increase in LVEF (20.2% ± 11.8% vs. 10.5% ± 13.9%; p < 0.001), higher echocardiographic response rate (86.1% vs. 57.8%; p < 0.001), and lower hospitalization costs [$9707.7 (7751.2, 18,088.5) vs. $20,046.1 (18,840.1, 22,447.3); p < 0.0001]. The CER was 112.7 and 346.8 in LBBaP and BVP, respectively. The incremental cost‐effectiveness ratio (ICER = △cost/△echocardiographic response rate) was $−365.3/per 1% increase in effectiveness. LBBaP improved cardiac function more significantly than BVP. There were no significant differences in clinical outcomes. Conclusions: LBBaP‐CRT is more cost‐effective than BVP, offering greater LVEF improvement, higher echocardiographic response rates, lower hospitalization costs, and more significantly improved cardiac function. These findings need large randomized clinical trials for further confirmation. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin‐related arrhythmias and electrocardiographic alterations in hospitalized patients using real‐world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug‐induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156‐1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568‐9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800‐7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531‐3.690), and abnormally elevated level of amino‐terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640‐5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220‐0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin‐related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin‐administered population, offering significant clinical applications. [ABSTRACT FROM AUTHOR]

Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explored the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild-type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln modulates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation of ERα on serine 118 (S118), as well as by reducing the E2-dependent binding of ERα across the genome. These effects were associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of some genes and enhanced expression of others. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) diastolic dysfunction, atrial fibrillation (AF), and heart failure with preserved ejection fraction (HFpEF) share common risk factors and are closely related to one another and to adverse cardiovascular events. Exertional dyspnoea in patients with AF should trigger a comprehensive LV diastolic function evaluation since AF frequently precedes incident HFpEF. An echocardiographic assessment of LV diastolic function in patients with AF is challenging, mainly because of variability in cycle length, the absence of atrial contraction, and the frequent occurrence of left atrial enlargement regardless of LV filling pressures (LVFPs). The algorithm of the 2016 recommendations for the evaluation of LV diastolic function cannot be directly applied in this setting. This review discusses the modalities available for diastolic function assessment and HFpEF diagnosis in patients with AF. Based on currently available data, a reasonable clinical target of diastolic function evaluation in AF would be to reach a binary conclusion: LVFP elevated or not. Recently, a two-step algorithm that combined several echocardiographic parameters plus the inclusion of body mass index has been proposed to differentiate normal from elevated LVFP in patients with AF. The echocardiographic evaluation must be complemented by a thorough clinical evaluation along with natriuretic peptides and cardiac catheterization in selected cases. If a diagnosis of HFpEF cannot be ascertained, a close follow-up for timely identification of diastolic dysfunction markers, along with monitoring and correction of modifiable risk factors, is recommended. [ABSTRACT FROM AUTHOR]

Phytohormones are organic compounds produced in trace amounts within plants that regulate their physiological processes. Their physiological effects are highly complex and diverse. They influence processes ranging from cell division, elongation, and differentiation to plant germination and rooting. Therefore, phytohormones play a crucial regulatory role in plant growth and development. Recently, various studies have highlighted the role of PHs, such as auxin, cytokinin (CK), and abscisic acid (ABA), and newer classes of PHs, such as brassinosteroid (BR) and peptide hormone, in the plant responses toward environmental stresses. These hormones not only have distinct roles at different stages of plant growth but also interact to promote or inhibit each other, thus effectively regulating plant development. Roots are the primary organs for water and mineral absorption in plants. During seed germination, the radicle breaks through the seed coat and grows downward to form the primary root. This occurs because the root needs to quickly penetrate the soil to absorb water and nutrients, providing essential support for the plant's subsequent growth. Root development is a highly complex and precisely regulated process influenced by various signals. Changes in root architecture can affect the plant's ability to absorb nutrients and water, which in turn impacts crop yield. Thus, studying the regulation of root development is of great significance. Numerous studies have reported on the role of phytohormones, particularly auxins, in root regulation. This paper reviews recent studies on the regulation of root development by various phytohormones, both individually and in combination, providing a reference for researchers in this field and offering perspectives on future research directions for improving crop yields. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Sensing dietary components in the gut is important to ensure an appropriate hormonal response and metabolic regulation after food intake. The fall webworm, Hyphantria cunea, is a major invasive pest in China and has led to significant economic losses and ecosystem disruption. The larvae's broad host range and voracious appetite for leaves make H. cunea a primary cause of serious damage to both forests and crops. To date, however, the gustatory receptors (Grs) of H. cunea and their regulatory function remain largely unknown. RESULTS: We identified the fall webworm gustatory receptor HcGr76 as a fructose and chlorogenic acid receptor using Ca2+ imaging and determination of intracellular Ca2+ concentration by a microplate reader. Moreover, reverse transcription–quantitative polymerase chain reaction (RT–qPCR) analysis revealed that HcGr76 is highly expressed in the anterior and middle midgut. Knockdown of HcGr76 caused a significant reduction in the expression of neuropeptide F 1 (NPF1) and CCHamide‐2, and led to a decrease in carbohydrate and lipid levels in the hemolymph. CONCLUSION: Our studies provide circumstantial evidence that HcGr76 expressed in the midgut is involved in sensing dietary components, and regulates the expression of relevant peptide hormones to alter metabolism in H. cunea larvae, thus providing a promising molecular target for the development of new insect‐specific control products. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging. [ABSTRACT FROM AUTHOR]

Background: Ketamine has emerged as a prominent substance of misuse. Leptin, an adipocyte-derived polypeptide hormone, has been implicated in the development of addiction. Sex-specific changes in leptin levels have been demonstrated following acute ketamine administration; the persistence of long-term ketamine use on leptin levels is uncertain.Objectives: To assess the sex-difference of leptin levels, and their persistence, in individuals with ketamine use disorder (KUD) compared to healthy controls.Methods: Plasma leptin levels were measured in 62 healthy controls (37 males, 25 females) and 68 participants with KUD (50 males, 18 females) on the first day (baseline) and after 1 and 2 weeks of abstinence. As leptin levels are affected by body mass index (BMI), BMI-adjusted leptin (leptin/BMI ratio) was also examined. Mixed model for repeated measures was used to examine changes after ketamine abstinence.Results: Compared to same-sex controls, female, but not male, participants with KUD demonstrated lower leptin levels and leptin/BMI ratio at baseline, week 1, and week 2 (leptin levels: p = .001, 0.006 and 0.032, respectively; leptin/BMI ratio: p = .004, 0.022, and 0.09, respectively). Repeated measures showed that leptin levels and the leptin/BMI ratio increased after 2 weeks of abstinence in male participants with KUD (p = .002 and 0.011, respectively), but females did not show such an increase (p > .05).Conclusions: Sex-specific differences were observed in leptin levels and the leptin/BMI ratio in individuals with KUD compared to controls. Lower leptin levels in females with KUD persisted after 2 weeks of abstinence. [ABSTRACT FROM AUTHOR]

Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologs within the endodermallyderived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem. [ABSTRACT FROM AUTHOR]

Simple Summary: Many patients diagnosed with gastroenteropancreatic neuroendocrine tumors present with metastatic disease at the time of diagnosis. As many as 20% of patients with this diagnosis will present with metastasis to the peritoneal cavity which portends a significantly worse prognosis than solid organ metastasis alone. There is little to no evidence to guide treatment algorithms given the rarity of this disease. Surgical cytoreduction has been found to improve symptoms related to disease burden, though an understanding of the optimal cytoreductive strategies to offer the greatest benefit to most patients is lacking. While the current body of literature pertaining to the systemic treatment of the solid organ metastasis of this disease is more robust, it largely excludes patients with peritoneal metastasis. We provide a review of the current literature which is used to guide these management strategies and offer insight into the knowledge gaps that exist. Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival—particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed. [ABSTRACT FROM AUTHOR]

Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting. [ABSTRACT FROM AUTHOR]

Endothelin type B receptor (ETBR) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ETBR activation by the endogenous peptide hormones endothelin (ET)−1–3 stimulates several signaling pathways, including Gs, Gi/o, Gq/11, G12/13, and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ETBR possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ETBR–Gi complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ETBR activation and the essential roles of the diverse NPxxL motif in stabilizing the active conformation of ETBR and organizing the assembly of the binding pocket for the α5 helix of Gi protein. These findings enhance our understanding of the interactions between GPCRs and G proteins, thereby advancing the development of therapeutic strategies. Tani et al. present the cryo-EM structure of the endothelin type B receptor (ETBR) in complex with the Gi protein, emphasizing the movements of transmembrane helix 7 during ETBR activation. The study underscores the crucial role of the NPxxL motif in stabilizing the receptor's active state and organizing the Gi protein binding site, enhancing our understanding of GPCR activation and aiding therapeutic development. [ABSTRACT FROM AUTHOR]

In cardiogenic shock, biomarkers should ideally help make the diagnosis, choose the right therapeutic options and monitor the patient in addition to clinical and echocardiographic indices. Among "old" biomarkers that have been used for decades, lactate detects, quantifies, and follows anaerobic metabolism, despite its lack of specificity. Renal and liver biomarkers are indispensable for detecting the effect of shock on organ function and are highly predictive of poor outcomes. Direct biomarkers of cardiac damage such as cardiac troponins, B-type natriuretic and N-terminal pro-B-type natriuretic peptides have a good prognostic value, but they lack specificity to detect a cardiogenic cause of shock, as many factors influence their plasma concentrations in critically ill patients. Among the biomarkers that have been more recently described, dipeptidyl peptidase-3 is one of the most interesting. In addition to its prognostic value, it could represent a therapeutic target in cardiogenic shock in the future as a specific antibody inhibits its activity. Adrenomedullin is a small peptide hormone secreted by various tissues, including vascular smooth muscle cells and endothelium, particularly under pathological conditions. It has a vasodilator effect and has prognostic value during cardiogenic shock. An antibody inhibits its activity and so adrenomedullin could represent a therapeutic target in cardiogenic shock. An increasing number of inflammatory biomarkers are also of proven prognostic value in cardiogenic shock, reflecting the inflammatory reaction associated with the syndrome. Some of them are combined to form prognostic proteomic scores. Alongside clinical variables, biomarkers can be used to establish biological "signatures" characteristic of the pathophysiological pathways involved in cardiogenic shock. This helps describe patient subphenotypes, which could in the future be used in clinical trials to define patient populations responding specifically to a treatment. [ABSTRACT FROM AUTHOR]

Quiescence is an essential property of meristematic cells, which restrains the cell cycle while retaining the capacity to divide. This crucial process not only facilitates life-long tissue homeostasis and regenerative capacity but also provides protection against adverse environmental conditions, enabling cells to conserve the proliferative potency while minimizing DNA damage. As a survival attribute, quiescence is inherently regulated by the products of aerobic life, in particular reactive oxygen species (ROS) and the redox (reduction/oxidation) mechanisms that plant have evolved to channel these into pervasive signals. Adaptive responses allow quiescent cells to compensate for reduced oxygen tension (hypoxia) in a reversible manner, while the regulated production of the superoxide anion (O2·−) facilitates cell division and the maintenance of stem cells. Here we discuss the role of ROS and redox reactions in the control of the quiescent state in plant meristems, and how this process is integrated with cellular energy and hormone biochemistry. We consider the pathways that sense and transmit redox signals with a focus on the central significance of redox regulation in the mitochondria and nucleus, which is a major regulator of quiescence in meristems. We discuss recent studies that suggest that ROS are a critical component of the feedback loops that control stem cell identity and fate, and suggest that the ROS/hypoxia interface is an important 'outside/in' positional cue for plant cells, particularly in meristems. [ABSTRACT FROM AUTHOR]

Background: Different responses in human coronary arteries (HCA) and human middle meningeal arteries (HMMA) were observed for some of the novel CGRP receptor antagonists, the gepants, for inhibiting CGRP-induced relaxation. These differences could be explained by the presence of different receptor populations in the two vascular beds. Here, we aim to elucidate which receptors are involved in the relaxation to calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2) in HCA and HMMA. Methods: RNA was isolated from homogenized human arteries (23 HCAs; 12 F, 11 M, age 50 ± 3 years and 26 HMMAs; 14 F, 12 M, age 51 ± 3 years) and qPCR was performed for different receptor subunits. Additionally, relaxation responses to CGRP, AM or AM2 of the human arteries were quantified using a Mulvany myograph system, in the presence or absence of the adrenomedullin 1 receptor antagonist AM22-52 and/or olcegepant. Results: Calcitonin-like receptor (CLR) mRNA was expressed equally in both vascular beds, while calcitonin receptor (CTR) and receptor activity-modifying protein 3 (RAMP3) expression was low and could not be detected in all samples. RAMP1 expression was similar in HCA and HMMA, while RAMP2 expression was higher in HMMA. Moreover, receptor component protein (RCP) expression was higher in HMMA than in HCA. Functional experiments showed that olcegepant inhibits relaxation to all three agonists in both vascular beds. In HCA, antagonist AM22-52 did not inhibit relaxation to any of the agonists, while a trend for blocking relaxation to AM and AM2 could be observed in HMMA. Conclusion: Based on the combined results from receptor subunit mRNA expression and the functional responses in both vascular tissues, relaxation of HCA is mainly mediated via the canonical CGRP receptor (CLR-RAMP1), while relaxation of HMMA can be mediated via both the canonical CGRP receptor and the adrenomedullin 1 receptor (CLR-RAMP2). Future research should investigate whether RAMP2 predominance over RAMP1 in the meningeal vasculature results in altered migraine susceptibility or in a different response to anti-migraine medication in these patients. Moreover, the exact role of RCP in CGRP receptor signalling should be elucidated in future research. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are plant steroid hormones that control growth and stress responses. In the context of development, BRs play diverse roles in controlling cell differentiation and tissue patterning. The vascular system, which is essential for transporting water and nutrients throughout the plant body, initially establishes a tissue pattern during primary development and then dramatically increases the number of vascular cells during secondary development. This complex developmental process is properly regulated by a network consisting of various hormonal signaling pathways. Genetic studies have revealed that mutants that are defective in BR biosynthesis or the BR signaling cascade exhibit a multifaceted vascular development phenotype. Furthermore, BR crosstalk with other plant hormones, including peptide hormones, coordinately regulates vascular development. Recently, the involvement of BR in vascular development, especially in xylem differentiation, has also been suggested in plant species other than the model plant Arabidopsis thaliana. In this review, we briefly summarize the recent findings on the roles of BR in primary and secondary vascular development in Arabidopsis and other species. [ABSTRACT FROM AUTHOR]

Introduction: The effects of breaking up sitting on gut hormone responses and free-living energy compensatory behaviors are still unclear in people of Asian ethnicity. Methods: Twenty-six Asians including 13 lean individuals (Lean) and 13 individuals with centrally overweight/obesity (OW), aged between 20 and 45 yr, completed a randomized crossover study with either 5.5-h uninterrupted sitting (SIT) or 5.5-h sitting with 2-min walking at 6.4 km·h−1 every 20 min (ACTIVE) in the laboratory. Blood samples were collected at regular time points to examine postprandial glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) concentrations. Free-living physical activity and energy intake were recorded using wearable devices and weighed food diaries outside the laboratory until midnight. Paired t-tests were conducted to compare responses between trials. Results: Postprandial GLP-1 and PYY incremental area under the curve values were higher in the ACTIVE trial versus SIT in both Lean and OW groups (all, P < 0.05), but there was no difference in GIP in either group (both, P > 0.05). There were no differences in free-living physical activity (volume and intensity) or energy intake (total and macronutrients) between trials in either group (all, P > 0.05), resulting in greater total physical activity over the 24-h monitoring period in ACTIVE trial versus SIT trial (both, P < 0.05). Conclusions: Breaking up sitting increases postprandial GLP-1 and PYY concentrations in Asians, but does not induce subsequent behavioral compensation, resulting in greater 24-h physical activity levels and lower relative energy intake, in inactive individuals irrespective of bodyweight status. [ABSTRACT FROM AUTHOR]

Systemin, the first peptide hormone identified in plants, was initially isolated from tomato (Solanum lycopersicum) leaves. Systemin mediates local and systemic wound‐induced defense responses in plants, conferring resistance to necrotrophic fungi and herbivorous insects. Systemin is recognized by the leucine‐rich‐repeat receptor‐like kinase (LRR‐RLK) receptor SYSTEMIN RECEPTOR1 (SYR1), but how the systemin recognition signal is transduced to intracellular signaling pathways to trigger defense responses is poorly understood. Here, we demonstrate that SERK family LRR‐RLKs function as co‐receptors for SYR1 to mediate systemin signal transduction in tomato. By using chemical genetic approaches coupled with engineered receptors, we revealed that the association of the cytoplasmic kinase domains of SYR1 with SERKs leads to their mutual trans‐phosphorylation and the activation of SYR1, which in turn induces a wide range of defense responses. Systemin stimulates the association between SYR1 and all tomato SERKs (SlSERK1, SlSERK3A, and SlSERK3B). The resulting SYR1‐SlSERK heteromeric complexes trigger the phosphorylation of TOMATO PROTEIN KINASE 1B (TPK1b), a receptor‐like cytoplasmic kinase that positively regulates systemin responses. Additionally, upon association with SYR1, SlSERKs are cleaved by the Pseudomonas syringae effector HopB1, further supporting the finding that SlSERKs are activated by systemin‐bound SYR1. Finally, genetic analysis using Slserk mutants showed that SlSERKs are essential for systemin‐mediated defense responses. Collectively, these findings demonstrate that the systemin‐mediated association of SYR1 and SlSERKs activates defense responses against herbivorous insects. [ABSTRACT FROM AUTHOR]

Background: B-type natriuretic peptides (BNP) and cardiac enzymes are both recognized biomarkers of heart health. Many studies have reported that using these indicators can assess cardiac condition and predict prognosis of patients undergoing surgery. Currently little is known on the effect of increased cardiac input after venous recanalization on cardiac physiology in patients with chronic venous obstruction (CVO). Objectives: The aim of this study was to explore the effect of iliocaval recanalization and stenting on cardiac biomarkers in patients with CVO. Methods: This was a prospective study involving 60 patients in a single unit. Blood tests were collected 1 day before and 1 day after venous intervention. Three groups as group 1: patients with iliofemoral post-thrombotic syndrome (PTS) but without involvement of inferior vena cava (IVC) (n = 33); group 2: patients with iliofemoral PTS and involvement of IVC (n = 19) and group 3: patients with non-thrombotic vein lesion (NIVL) (n = 8) were compared based on cardiac biomarker levels. Results: Median concentration of post-operative BNP (259.60 pg/mL) was greater than preoperative levels (49.80 pg/mL) [interquartile range (IQR), 147.15/414.68 versus 29.85/82.88; p < 0.001]. The levels of CK-MB [preop: 3 U/l (IQR, 1.40/11.00) versus postop: 14 U/l (IQR, 12/17), p < 0.001] and troponin T [preop: 3.00 pg/mL (IQR, 3.00/5.25) versus postop: level of 6 pg/mL (IQR, 3.00/9.50), p < 0.001]. Post-procedure increases in cardiac enzymes showed significant differences in BNP (p = 0.023) and troponin T (p = 0.007) across the three groups, while CK-MB levels were not significantly different (p > 0.05). Intergroup comparisons of postoperative BNP: group 1 versus group 2 (p = 0.013), group 2 versus group 3 (p = 0.029), group 1 versus group 3 (p = 0.834); and postoperative troponin T: group 1 versus group 2 (p = 0.018), group 2 versus group 3 (p = 0.002), group 1 versus group 3 (p = 0.282). According to multiple linear regression analysis, length of stenting and level of preoperative BNP were independent determinants of postoperative BNP levels (p < 0.05), and preoperative troponin T affected postoperative troponin T independently (p < 0.05). Conclusions: Troponin T, CK-MB and BNP seem to increase after venous recanalization and stent implantation, the elevation being more prominent for longer lesions. [ABSTRACT FROM AUTHOR]

The peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis in mouse models by signaling via the kisspeptin 1 receptor (KISS1R). However, whether kisspeptin impacts fibrogenesis in the human liver is not known. We investigated the impact of a potent kisspeptin analog (KPA) on fibrogenesis using human precision-cut liver slices (hPCLS) from fibrotic livers from male patients, in human hepatic stellate cells (HSCs), LX-2, and in primary mouse HSCs. In hPCLS, 48 h and 72 h of KPA (3 nM, 100 nM) treatment decreased collagen secretion and lowered the expression of fibrogenic and inflammatory markers. Immunohistochemical studies revealed that KISS1R is expressed and localized to HSCs in MASH/fibrotic livers. In HSCs, KPA treatment reduced transforming growth factor b (TGFβ)-the induced expression of fibrogenic and inflammatory markers, in addition to decreasing TGFβ-induced collagen secretion, cell migration, proliferation, and colony formation. Mechanistically, KISS1R signaling downregulated TGFβ signaling by decreasing SMAD2/3 phosphorylation via the activation of protein phosphatases, PP2A, which dephosphorylates SMAD 2/3. This study revealed for the first time that kisspeptin reverses human hepatic fibrogenesis, thus identifying it as a new therapeutic target to treat hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin's role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease. [ABSTRACT FROM AUTHOR]

The extracellular matrix plays an integrative role in cellular responses in plants, but its contribution to the signalling of extracellular ligands largely remains to be explored. Rapid alkalinisation factors (RALFs) are extracellular peptide hormones that play pivotal roles in various physiological processes. Here, we address a crucial connection between the de- methylesterification machinery of the cell wall component pectin and RALF1 activity. Pectin is a polysaccharide, contributing to the structural integrity of the cell wall. Our data illustrate that the pharmacological and genetic interference with pectin methyl esterases (PMEs) abolishes RALF1-induced root growth repression. Our data suggest that positively charged RALF1 peptides bind negatively charged, de-methylesterified pectin with high avidity. We illustrate that the RALF1 association with de-methylesterified pectin is required for its FERONIA- dependent perception, contributing to the control of the extracellular matrix and the regulation of plasma membrane dynamics. Notably, this mode of action is independent of the FER-dependent extracellular matrix sensing mechanism provided by FER interaction with the leucine-rich repeat extensin (LRX) proteins. We propose that the methylation status of pectin acts as a contextualizing signalling scaffold for RALF peptides, linking extracellular matrix dynamics to peptide hormone-mediated responses. [ABSTRACT FROM AUTHOR]

The purpose of this study is to analyze the early clinical features of coronary artery lesion (CAL) in Kawasaki disease (KD), evaluate systemic inflammation indicators, and enhance early recognition of CAL in the acute phase of KD. A total of 314 children with KD were divided into those with CAL (CAL group) and without CAL (NCAL group) using echocardiographic results, and their clinical data were retrospectively analyzed. For KD patients, male, children aged 3 to 9 years, and those with fever longer than 6 days before intravenous immunoglobulin (IVIG) use were more likely to have CAL. There were significant differences in sex, age, and fever time (P <.05). Moreover, some laboratory indicator test results revealed there was a significant difference between N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and interleukin-6 (IL-6), and the CAL (P <.05). This study has certain guiding significance for early clinical evaluation. [ABSTRACT FROM AUTHOR]

The article focuses on an 11-year-old boy presenting with slurred speech and involuntary movements, later diagnosed with a neurological disorder. Topics include his clinical symptoms such as dysarthria and abnormal involuntary movements, his physical exam findings including hyperreflexia and abnormal gait, and the absence of significant prior medical or family history.

Dormancy is an essential ecological characteristic for the survival of organisms that experience harsh environments. Although factors that initiate dormancy vary, suppression or cessation of feeding activities are common among taxa. To distinguish between extrinsic and intrinsic causes of metabolic reduction, we focused on estivation, which occurs in summer when the feeding activity is generally enhanced. Sand lances (genus Ammodytes) are a unique marine fish with a long estivation period from early summer to late autumn. In the present study, we aimed to elucidate the control mechanisms of estivation in western sand lance (A. japonicus), and firstly examined behavioral changes in 8 months including a transition between active and dormant phases. We found that swimming/feeding behavior gradually decreased from June, and completely disappeared by late August, indicating all individuals had entered estivation. Next, we focused on leptin, known as a feeding suppression hormone in various organisms, and examined leptin‐A gene (AjLepA) expression in the brain that may regulate the seasonal behavioral pattern. AjLepA expression decreased after 7 days of fasting, suggesting that leptin has a function to regulate feeding in this species. The monthly expression dynamics of AjLepA during the feeding (active) and non‐feeding (estivation) periods showed that the levels gradually increased with the onset of estivation and reached its peak when all the experimental fish had estivated. The present study suggests that the suppression of feeding activity by leptin causes shift in the physiological modes of A. japonicus before estivation. Research highlights: Sand lance spends in sand for more than half a year without feeding, a unique dormancy among teleosts called estivationLeptin, a peptide hormone, was found to be involved in appetite suppression in brain and work to exert the onset of estivation [ABSTRACT FROM AUTHOR]

Stanniocalcin (STC) 1 and 2 serve as antihyperglycemic polypeptide hormones with critical roles in regulating calcium and phosphate homeostasis. They additionally function as paracrine and/or autocrine factors involved in numerous physiological processes, including female reproduction. STC1 and STC2 contribute to the pathophysiology of several diseases, including female infertility- and pregnancy-associated conditions, and even tumorigenesis of reproductive organs. This comprehensive review highlights the dynamic expression patterns and potential dysregulation of STC1 and STC2, restricted to female fertility, and infertility- and pregnancy-associated diseases and conditions, such as endometriosis, polycystic ovary syndrome (PCOS), abnormal uterine bleeding, uterine polyps, and pregnancy complications, like impaired decidualization, preeclampsia, and preterm labor. Furthermore, the review elucidates the role of dysregulated STC in the progression of cancers of the reproductive system, including endometrial, cervical, and ovarian cancers. Additionally, the review evaluates the expression patterns and prognostic significance of STC in gynecological cancers by utilizing existing public datasets from The Cancer Genome Atlas to help decipher the multifaceted roles of these pleiotropic hormones in disease progression. Understanding the intricate mechanisms by which STC proteins influence all these reviewed conditions could lead to the development of targeted diagnostic and therapeutic strategies in the context of female reproductive health and oncology. [ABSTRACT FROM AUTHOR]

Iron delivery to the plasma is closely coupled to erythropoiesis, the production of red blood cells, as this process consumes most of the circulating plasma iron. In response to hemorrhage and other erythropoietic stresses, increased erythropoietin stimulates the production of the hormone erythroferrone (ERFE) by erythrocyte precursors (erythroblasts) developing in erythropoietic tissues. ERFE acts on the liver to inhibit bone morphogenetic protein (BMP) signaling and thereby decrease hepcidin production. Decreased circulating hepcidin concentrations then allow the release of iron from stores and increase iron absorption from the diet. Guided by evolutionary analysis and Alphafold2 protein complex modeling, we used targeted ERFE mutations, deletions, and synthetic ERFE segments together with cell-based bioassays and surface plasmon resonance to probe the structural features required for bioactivity and BMP binding. We define the ERFE active domain and multiple structural features that act together to entrap BMP ligands. In particular, the hydrophobic helical segment 81 to 86 and specifically the highly conserved tryptophan W82 in the N-terminal region are essential for ERFE bioactivity and Alphafold2 modeling places W82 between two tryptophans in its ligands BMP2, BMP6, and the BMP2/6 heterodimer, an interaction similar to those that bind BMPs to their cognate receptors. Finally, we identify the cationic region 96-107 and the globular TNFα-like domain 186-354 as structural determinants of ERFE multimerization that increase the avidity of ERFE for BMP ligands. Collectively, our results provide further insight into the ERFE-mediated inhibition of BMP signaling in response to erythropoietic stress.

Introduction: Albumin plays a vital role in improving osmotic pressure and hemodynamics. A lower serum albumin level may cause pulmonary congestion and edema and contribute to myocardial dysfunction, diuresis resistance, and fluid retention in acute heart failure. Hypothesis: We hypothesized that AHF patients with normal serum albumin have shorter hospital stays. Methods: Using Electronic Medical Records, patients admitted from May 2020 through May 2021 aged >18, ICD-10, and positive Framingham Heart Failure Diagnostic Criteria were included. We excluded patients without albumin records and eGFRs less than 30 mL/min/1.73 m2. Prolonged hospitalization was defined as >8 days of hospitalization. Results: During index emergency department visits, patients were symptomatic (New York Heart Association), aged median of 70 years (Interquartile range (IQR) 18), 59% (n = 103) were male, predominantly White (73%, n = 128), and had a high Charleston Comorbidity index score [5, IQR (4–7)]. Nearly one-fourth (23%, n = 41) of the patients had <3.5 g/dL albumin levels. The median length of hospital stay was eight days (IQR of 11). Comparing differences between lengths of hospital stays (< 8 vs. >8 days), there was different serum albumin (3.9 + 0.48 vs. 3.6 + 0.53, p <.001) and left ventricular ejection fraction (45% (range 26–63) versus 30% (range 24–48), p =.004). An increased serum albumin decreased prolonged hospitalization (odds ratio (OR), 0.28; 95% confidence interval (CI), 0.14–0.55, p = <0.001). Patients in the lower albumin group had higher NT-proBNP (median: 8521 (range 2025–9134) versus 5147 (range 2966–14,795) pg/ml, p =.007) and delay in administering intravenous diuretics (391 (167–964) minutes versus 271 (range 157–533) minutes, p =.02). Conclusion: Hypoalbuminemia is strongly associated with prolonged hospitalization. Timely and effective diuretic therapy may reduce hospital stay durations, particularly with albumin supplementation. [ABSTRACT FROM AUTHOR]

ABSTRACT Posttranslational tyrosine sulfation of peptides and proteins is catalysed by tyrosylprotein sulfotransferases (TPSTs). In Arabidopsis, tyrosine sulfation is essential for the activities of peptide hormones, such as phytosulfokine (PSK) and root meristem growth factor (RGF). Here, we identified a TPST‐encoding gene, MtTPST, from model legume Medicago truncatula. MtTPST expression was detected in all organs, with the highest level in root nodules. A promoter:GUS assay revealed that MtTPST was highly expressed in the root apical meristem, nodule primordium and nodule apical meristem. The loss‐of‐function mutant mttpst exhibited a stunted phenotype with short roots and reduced nodule number and size. Application of both of the sulfated peptides PSK and RGF3 partially restored the defective root length of mttpst. The reduction in symbiotic nodulation in mttpst was partially recovered by treatment with sulfated PSK peptide. MtTPST‐PSK module functions downstream of the Nod factor signalling to promote nodule initiation via regulating accumulation and/or signalling of cytokinin and auxin. Additionally, the small‐nodule phenotype of mttpst, which resulted from decreased apical meristematic activity, was partially complemented by sulfated RGF3 treatment. Together, these results demonstrate that MtTPST, through its substrates PSK, RGF3 and other sulfated peptide(s), positively regulates nodule development and root growth. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). Methods: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. Results: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). Conclusion: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. Trial registration: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020. [ABSTRACT FROM AUTHOR]

Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity. [ABSTRACT FROM AUTHOR]

In humans, 15 genes encode the class B1 family of GPCRs, which are polypeptide hormone receptors characterized by having a large N-terminal extracellular domain (ECD) and receive signals from outside the cell to activate cellular response. For example, the insulinotropic polypeptide (GIP) stimulates the glucose-dependent insulinotropic polypeptide receptor (GIPR), while the glucagon receptor (GCGR) responds to glucagon by increasing blood glucose levels and promoting the breakdown of liver glycogen to induce the production of insulin. The glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) elicit a response from glucagon-like peptide receptor types 1 and 2 (GLP1R and GLP2R), respectively. Since these receptors are implicated in the pathogenesis of diabetes, studying their activation is crucial for the development of effective therapies for the condition. With more structural information being revealed by experimental methods such as X-ray crystallography, cryo-EM, and NMR, the activation mechanism of class B1 GPCRs becomes unraveled. The available crystal and cryo-EM structures reveal that class B1 GPCRs follow a two-step model for peptide binding and receptor activation. The regions close to the C-termini of hormones interact with the N-terminal ECD of the receptor while the regions close to the N-terminus of the peptide interact with the TM domain and transmit signals. This review highlights the structural details of class B1 GPCRs and their conformational changes following activation. The roles of MD simulation in characterizing those conformational changes are briefly discussed, providing insights into the potential structural exploration for future ligand designs. [ABSTRACT FROM AUTHOR]

GPRC6A, a member of the Family C G‐protein coupled receptors, regulates energy metabolism and sex hormone production and is activated by diverse ligands, including cations, L‐amino acids, the osteocalcin (Ocn) peptide and the steroid hormone testosterone. We sought a structural framework for the ability of multiple distinct classes of ligands to active GPRC6A. We created a structural model of GPRC6A using Alphafold2. Using this model we explored a putative orthosteric ligand binding site in the bilobed Venus fly trap (VFT) domain of GPRC6A and two positive allosteric modulator (PAM) sites, one in the VFT and the other in the 7 transmembrane (7TM) domain. We provide evidence that Ocn peptides act as a PAM for GPRC6A by binding to a site in the VFT that is distinct from the orthosteric site for calcium and L‐amino acids. In agreement with this prediction, alternatively spliced GPRC6A isoforms 2 and 3, which lack regions of the VFT, and mutations in the computationally predicted Ocn binding site, K352E and H355P, prevent Ocn activation of GPRC6A. These observations explain how dissimilar ligands activate GPRC6A and set the stage to develop novel molecules to activate and inhibit this previously poorly understood receptor. [ABSTRACT FROM AUTHOR]

Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock. Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects. Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel–Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I2 were used to examine heterogeneity, with I2 > 50% indicating marked heterogeneity. Results: A total of eight studies (n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68–1.02, I2 = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61–1.65, I2 = 0%; AF: RR = 1.27; 95% CI, 0.38–4.23, I2 = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = −9.60; 95% CI, −9.71, −9.49, I2 = 0%). Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension. [ABSTRACT FROM AUTHOR]

Using personification and the first person techniques, this article provides a brief introduction to the peptide hormone oxytocin in the form of a Blog, including its basic overview, research history, and functional effects. It also conducts analogical analysis with related substances, using vivid and interesting language to help people form a preliminary understanding of oxytocin. [ABSTRACT FROM AUTHOR]

Protein amyloid aggregation is linked with widespread and fatal neurodegenerative disorders as well as several amyloidoses. Insulin, a small polypeptide hormone, is associated with injection-site amyloidosis and is a popular model protein for in vitro studies of amyloid aggregation processes as well as in the search for potential anti-amyloid compounds. Despite hundreds of studies conducted with this specific protein, the procedures used have employed a vast array of different means of achieving fibril formation. These conditions include the use of different solution components, pH values, ionic strengths, and other additives. In turn, this variety of conditions results in the generation of fibrils with different structures, morphologies and stabilities, which severely limits the possibility of cross-study comparisons as well as result interpretations. In this work, we examine the condition–structure relationship of insulin amyloid aggregation under a range of commonly used pH and ionic strength conditions as well as solution components. We demonstrate the correlation between the reaction solution properties and the resulting aggregation kinetic parameters, aggregate secondary structures, morphologies, stabilities and dye-binding modes. [ABSTRACT FROM AUTHOR]