Apelin Receptor Research Articles

A Morphological and Behavioral Study of Demyelination and Remyelination in the Cuprizone Model: Insights into APLNR and NG2+ Cell Dynamics

Multiple sclerosis (MS) is a chronic neurodegenerative disorder involving demyelination. The cuprizone model is commonly used to study MS by inducing oligodendrocyte stress and demyelination. The subventricular zone (SVZ) plays a key role in neurogenesis, while the neuronal/glial antigen 2 (NG2) is a marker for immature glial cells, involved in oligodendrocyte differentiation. The apelin receptor (APLNR) is linked to neurogenesis and behavior modulation. This study explores the role of APLNR in NG2-positive cells during de- and remyelination phases in the experimental cuprizone mouse model. Thirty male C57BL/6 mice were divided into control (not treated), demyelination (5 weeks cuprizone administration), and remyelination (5 weeks cuprizone administration + 5 weeks recovery) groups. Histological examinations, immunohistochemistry, and immunofluorescence on serial coronal sections were conducted to evaluate corpus callosum (CC) morphology and APLNR and NG2 expression in the SVZ, in addition to behavioral assessments. The histological analysis showed a significant reduction in the CC’s thickness and area after five weeks of cuprizone exposure, followed by recovery five weeks post-exposure. During the demyelination phase, APLNR-expressing cells peaked while NG2-positive cells decreased. In the remyelination phase, APLNR-expressing cells declined, and NG2-positive cells increased. Confocal microscopy confirmed the co-localization of NG2 and APLNR markers. Statistically significant differences were observed across experimental groups. Correlation analyses highlighted associations between APLNR/NG2 cell counts and CC changes. Behavioral tests revealed impaired motor coordination and memory during demyelination, with gradual recovery during remyelination. Significant changes in the CC structure and the number of APLNR and NG2-positive cells were observed during de- and remyelination, suggesting that NG2-positive cells expressing APLNR may play a key role in remyelination.

Effect of SARS-CoV-2 Infection on Selected Parameters of the Apelinergic System in Repeat Blood Donors.

Background: SARS-CoV-2 enters cells primarily by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, thereby blocking its physiological functions, affecting the apelinergic system, and inhibiting the cleavage of its peptides. The appropriate concentration of peptides in the apelinergic system influences the maintenance of homeostasis and protects against cardiovascular diseases. In our research, we determined the level of selected parameters of the apelinergic system-apelin (AP), elabela (ELA), and the apelin receptor (APJ)-in repeat blood donors. Methods: We analyzed 120 serum samples obtained from 30 repeat donors (study group) within four time periods after a SARS-CoV-2 infection: <60 days, 61-90 days, 91-120 days, and >120 days. We compared the results from the study groups with those of the control group, which consisted of 30 serum samples collected from donors donating blood in the years 2018-2019. Results: We observed that the AP, ELA, and APJ concentrations in the control group are higher than in any period in the study group. In the study group, the concentrations of AP and ELA increased in subsequent study periods. AP and ELA concentrations were lower shortly after SARS-CoV-2 transfection and then slowly increased in subsequent periods. APJ concentrations, on the other hand, were lowest at 61-90 days after the infection, but the decrease, relative to their level in healthy subjects, was significant in every period studied. Conclusions: The results suggest that infection with SARS-CoV-2 causes changes in the parameters of the apelinergic system, both after a short period of time has passed since the onset of the SARS-CoV-2 infection, and even up to 4 months after the infection.

Divergent roles of DRY and NPxxY motifs in selective activation of downstream signalling by the apelin receptor.

G protein-coupled receptors (GPCRs) serve as critical communication hubs, translating a wide range of extracellular signals into intracellular responses that govern numerous physiological processes. In class-A GPCRs, conserved motifs mediate conformational changes of the active states of the receptor, and signal transduction is achieved by selectively binding to Gα proteins and/or adapter protein, arrestin. Apelin receptor (APJR) is a class-A GPCR that regulates a wide range of intracellular signalling cascades in response to apelin and elabela peptide ligands. Understanding how conserved motifs within APJR mediate activation and signal specificity remains unexplored. This study focuses on the functional roles of the DRY and NPxxY motifs within APJR by analyzing their impact on downstream signaling pathways across the receptor's conformational ensembles. Our findings provide compelling evidence that mutations within the conserved DRY and NPxxY motifs of APJR significantly alter its conformational preferences where modification of DRY motif leads to abrogation of G-protein coupling and mutation of NPxxY motif causing abolition of β-arrestin-2 recruitment. These observations shed light on the importance of these motifs in APJR activation and its potential for functional selectivity, highlighting the role of DRY/NPxxY as conformational switches of APJR signalling.

Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium.

IGF-1 and apelin are released in response to exercise training with beneficial effects. Previously we demonstrated that a swimming routine is effective to convert pathological into physiological cardiac hypertrophy, and that IGF-1 improves contractility and the redox state, in spontaneously hypertensive rats (SHR). Now, we hypothesize that the apelinergic pathway is involved in the cardioprotective effects of IGF-1 in the SHR. We assessed the redox state and mitochondrial effects of IGF-1 or apelin in the presence/absence of AG1024 or ML221 [pharmacological antagonists of IGF1 (IGF1R) and apelin (APJ) receptors, respectively] in SHR isolated cardiomyocytes or perfused hearts. Acute IGF-1 (10 nmol/L) significantly: -reduced H2O2 production (IGF-1:62 ± 6; control:100 ± 8.1, %), -increased the activity of superoxide dismutase (IGF-1:193 ± 17, control: 100 ± 13,%), -prevented H2O2-induced ΔΨm loss (TMREF10min/F0 min: IGF-1:0.93 ± 0.017, control: 0.72 ± 0.029), -reduced mitochondrial permeability transition pore (mPTP) opening estimated by the calcium retention capacity (nmol/mg protein, IGF-1:251 ± 34, control:112 ± 5), and -increased P-AMPK (IGF-1:129 ± 0.9, control: 100 ± 2%) and P-AKT (IGF-1:143 ± 17 control:100 ± 6, %). These effects were suppressed not only by the antagonism of IGF1R but also of APJ. Moreover, IGF-1 significantly increased APJ (IGF-1:198 ± 29 control:100 ± 15,%) and apelin mRNAs (IGF-1:251 ± 48, control:100 ± 6,%). On the other hand, an equipotent dose of exogenous apelin (50 nmol/L) emulated IGF-1 effects being cancelled by the antagonism of APJ however not by AG1024. IGF-1/IGF1R stimulates the apelinergic pathway, improving the redox balance and mitochondria status in the pathologically hypertrophied myocardium of the SHR.

Single-cell and spatial transcriptomics reveal apelin/APJ pathway's role in microvessel formation and tumour progression in hepatocellular carcinoma.

The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (p = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (p < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes.

Activation of Apelin Receptor Inhibits Cystogenesis in a Mouse Model of Polycystic Kidney Disease

Activation of Apelin Receptor Inhibits Cystogenesis in a Mouse Model of Polycystic Kidney Disease

Expression of the apelin system in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of apelin on LH and FSH secretion

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways.

Novel unimolecular peptides targeting GLP-1 and APJ receptors exert potent satiety inducing effects in mice

Novel unimolecular peptides targeting GLP-1 and APJ receptors exert potent satiety inducing effects in mice

Hybrid acylated and non-acylated GLP-1 and apelin receptor co-agonist peptides, show promising acute in vivo anti-hyperglycaemic actions in normal healthy and insulin resistant diet-induced obese mice

Hybrid acylated and non-acylated GLP-1 and apelin receptor co-agonist peptides, show promising acute <i>in vivo</i> anti-hyperglycaemic actions in normal healthy and insulin resistant diet-induced obese mice

Renal structural changes and apelin receptor expression in spontaneously hypertensive rats: implications for hypertension-induced kidney injury.

Arterial hypertension is a primary risk factor for kidney disease. Recent advances have implied a potential link between the apelin system and renal homeostasis. We used 6- and 12-month-old spontaneously hypertensive rats and age-matched normotensive controls to assess the changes in the renal expression of the apelin receptor by immunohistochemical method. The study also evaluated correlations between the renal apelin receptor's expression and renal injury indicators. The histological analysis showed elevated glomerular sclerosis and tubulointerstitial damage indices in both groups of hypertensive rats compared to age-matched controls. Older rats within each group exhibited higher scores than younger ones. The immunohistochemical analysis revealed varying apelin receptor expression patterns, with tubular expression intensifying both with hypertension severity and age. Glomerular expression was notably higher in older hypertensive rats compared to normotensive controls. We reported significant positive correlations between glomerular apelin receptor expression and glomerular sclerosis index in older hypertensive animals. Similarly, a positive correlation between tubular apelin receptor expression and tubulointerstitial damage index was discovered in hypertensive rats, suggesting hypertension-related changes in apelin receptor expression and renal damage. Our study found kidney changes and varying apelin receptor correlations in hypertensive rat kidneys, suggesting complex roles needing research.

Silencing APLNR enhances the radiosensitivity of prostate cancer by modulating the PI3K/AKT/mTOR signaling pathway.

Aberrant expression of apelin receptor (APLNR) has been found to be involved in various cancers' development, however, its function in prostate cancer (PCa) remains unclear. The research aimed to investigate the role and potential mechanism of APLNR in PCa. The mRNA expression of APLNR was detected via qRT-PCR assay. PCa cell proliferation and apoptosis were determined through plate cloning and flow cytometry. In addition, the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) was evaluated using western blot. DNA damage marker (γ-H2AX) was analyzed by immunofluorescence and western blot. GSEA analysis was performed for seeking enrichment pathways of APLNR in PCa, and the protein levels of PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR were tested using western blot. APLNR expression was up-regulated in PCa tissues and cells. Silencing APLNR enhanced the sensitivity of PCa cells to radiotherapy, which was manifested by inhibiting cell proliferation, promoting cell apoptosis, and promoting DNA damage. Next, silencing APLNR inhibited the PI3K/AKT/mTOR pathway. Specifically, 740Y-P (the PI3K/AKT/mTOR pathway activator) reversed the effects of silencing APLNR on PCa cell proliferation, apoptosis and DNA damage. Silencing APLNR inhibited cell proliferation, promoted cell apoptosis, and enhanced the radiosensitivity of PCa cells, which was involved in the PI3K/AKT/mTOR signaling pathway. This study is conducive to the deeper understanding of PCa and further provides a new perspective for the treatment of PCa.

Apelin-13 alleviates intrauterine adhesion by inhibiting epithelial-mesenchymal transition of endometrial epithelial cells and promoting angiogenesis.

Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-β1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-β1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-β1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-β1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-β1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA.

Apelin-13 administration allows for norepinephrine sparing in a rat model of cecal ligation and puncture-induced septic shock

BackgroundInfusion of exogenous catecholamines (i.e., norepinephrine [NE] and dobutamine) is a recommended treatment for septic shock with myocardial dysfunction. However, sustained catecholamine infusion is linked to cardiac toxicity and impaired responsiveness. Several pre-clinical and clinical studies have investigated the use of alternative vasopressors in the treatment of septic shock, with limited benefits and generally no effect on mortality. Apelin-13 (APL-13) is an endogenous positive inotrope and vasoactive peptide and has been demonstrated cardioprotective with vasomodulator and sparing life effects in animal models of septic shock. A primary objective of this study was to evaluate the NE-sparing effect of APL-13 infusion in an experimental sepsis-induced hypotension.MethodsFor this goal, sepsis was induced by cecal ligation and puncture (CLP) in male rats and the arterial blood pressure (BP) monitored continuously via a carotid catheter. Monitoring, fluid resuscitation and experimental treatments were performed on conscious animals. Based on pilot assays, normal saline fluid resuscitation (2.5 mL/Kg/h) was initiated 3 h post-CLP and maintained up to the endpoint. Thus, titrated doses of NE, with or without fixed-doses of APL-13 or the apelin receptor antagonist F13A co-infusion were started when 20% decrease of systolic BP (SBP) from baseline was achieved, to restore SBP values ≥ 115 ± 1.5 mmHg (baseline average ± SEM).ResultsA reduction in mean NE dose was observed with APL-13 but not F13A co-infusion at pre-determined treatment time of 4.5 ± 0.5 h (17.37 ± 1.74 µg/Kg/h [APL-13] vs. 25.64 ± 2.61 µg/Kg/h [Control NE] vs. 28.60 ± 4.79 µg/Kg/min [F13A], P = 0.0491). A 60% decrease in NE infusion rate over time was observed with APL-13 co-infusion, (p = 0.008 vs NE alone), while F13A co-infusion increased the NE infusion rate over time by 218% (p = 0.003 vs NE + APL-13). Associated improvements in cardiac function are likely mediated by (i) enhanced left ventricular end-diastolic volume (0.18 ± 0.02 mL [Control NE] vs. 0.30 ± 0.03 mL [APL-13], P = 0.0051), stroke volume (0.11 ± 0.01 mL [Control NE] vs. 0.21 ± 0.01 mL [APL-13], P < 0.001) and cardiac output (67.57 ± 8.63 mL/min [Control NE] vs. 112.20 ± 8.53 mL/min [APL-13], P = 0.0036), and (ii) a reduced effective arterial elastance (920.6 ± 81.4 mmHg/mL/min [Control NE] vs. 497.633.44 mmHg/mL/min. [APL-13], P = 0.0002). APL-13 administration was also associated with a decrease in lactate levels compared to animals only receiving NE (7.08 ± 0.40 [Control NE] vs. 4.78 ± 0.60 [APL-13], P < 0.01).ConclusionAPL-13 exhibits NE-sparing benefits in the treatment of sepsis-induced shock, potentially reducing deleterious effects of prolonged exogenous catecholamine administration.

Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in Vascular Dementia.

Vascular dementia (VD), a progressive vascular cognitive impairment, is characterised by the presence of cerebral hypoperfusion, increased blood-brain barrier permeability, and white matter lesions. Although current treatment strategies primarily focus on risk factors such as hypertension, diabetes, and heart disease, efficient and targeted therapies are lacking and the underlying mechanisms of VD remain unclear. We previously discovered that Apelin receptors (APJ), which are G protein-coupled receptors (GPCRs), can homodimerize and generate signals that are distinct from those of APJ monomers in VD rats. Apelin-13 reduces the level of APJ homodimers and leads to the proliferation of endogenous neural stem cells in the hippocampal dentate gyrus area, suggesting that it has a neuroprotective role. In this study, we established a rat and cellular oxygen-glucose deprivation/reoxygenation VD model to investigate the impact of APJ homodimerisation on autophagy. We found that APJ homodimers protect against VD by inhibiting autophagy through the Gαq and PI3K/Akt/mTOR pathways upon Gαi signalling, both in vivo and in vitro. This discovery provides a promising therapeutic target for chronic cerebral ischaemia-reperfusion diseases and an experimental foundation for the development of drugs that target APJ homodimers.

Hyperandrogenemia elevates expression of apelin and apelin receptor protein in the mice pituitary.

Hyperandrogenemia is associated with polycystic ovarian syndrome (PCOS) and imbalances in the pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Apelin and its receptor, APJ (class A, rhodopsin-like G- protein-coupled receptor), belongs to adipokines, and its expression has been shown in the pituitary. It is also well known that, hyperandrogenism and PCOS have deregulation of different adipokines. Whether hyperandrogenism also deregulates the apelin system in the pituitary has yet to be investigated. Thus, we have investigated the expression and localization of apelin and its receptor, APJ, in the letrozole-induced hyperandrogenised pituitary of female mice. Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice. Recently, a direct role of apelin has also been reported in the female pituitary, where apelin inhibits LH secretion. Thus, apelin could be one of the factors for deregulated gonadotropin secretion in hyperandrogenised conditions. However, more research is needed to fully understand the complex interactions between apelin and androgen regarding gonadotropin secretion in hyperandrogenised conditions.

Hormonal dependent expression of apelin and apelin receptor in the ovary and uterus of mice

Apelin and APJ have been shown to regulate female reproductive functions. However, its uterine expression during the oestrous cycle and its regulation by ovarian steroids, along with gonadotropin regulation in the ovary, has not been investigated. This study aimed to analyze the steroid-dependent uterine expression of apelin/APJ in the uterus along with the oestrous cycle. Furthermore, it also aimed to investigate gonadotropin-dependent ovarian expression of apelin and APJ. To investigate the uterine expression of apelin and APJ during estrous cycle in mice, uterus at different estrous stage were collected. To explore the ovarian steroids dependent expression of apelin system in the uterus, ovariectomized mice were treated with only estrogen at dose of 30 ng/g, only progesterone at dose of 150 μg/g and combined doses. To study the effect of gonadotropin on ovarian expression of apelin system, immature mice were injected with 2.5 IU of pregnant mare serum gonadotropin (PMSG) alone and both PMSG plus 2.5 IU of chorionic gonadotropin (hCG). Apelin and APJ protein expression are modulated by estrous phases in the uterus. The uterine apelin and APJ expression are up-regulated by estrogen and down-regulated by progesterone. The expression and localization of APJ showed increased abundance in the follicles of PMSG treated mice, however, the PMSG plus HCG treatment showed formation of corpus luteum with increased abundance of APJ and progesterone secretion. The expression of apelin and APJ are regulated by pituitary gonadotropin in the ovary and uterine apelin system by ovarian steroid hormone.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

118-OR: The Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to That of Lean Controls

118-OR: The Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to That of Lean Controls

Neoadjuvant toripalimab combined with axitinib in patients with locally advanced clear cell renal cell carcinoma: a single-arm, phase II trial

BackgroundA combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy,...