Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease.

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract.

Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway.

PURPOSE: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. METHODS: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. RESULTS: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1ß (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN. AntagomiR-1297 increased PTEN expression and suppressed PI3K and AKT phosphorylation (all p < 0.001). CONCLUSIONS: AntagomiR-1297 can mitigate renal fibrosis, renal inflammation, apoptosis, and oxidative stress levels through the PTEN/PI3K/AKT pathway.

CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions.

Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug-drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially in special populations, remain inadequately investigated. While some clinical trials have explored DDIs between therapeutic drugs like antiepileptic drugs and CBD/THC, more potential interactions remain to be examined. This review summarizes the published studies on CBD and THC-drug interactions, outlines the mechanisms involved, discusses the physiological considerations in pharmacokinetics (PK) and DDI studies in special populations (including pregnant and lactating women, pediatrics, older adults, patients with hepatic or renal impairments, and others), and presents modeling approaches that can describe the DDIs associated with CBD and THC in special populations. The PK of CBD and THC in special populations remain poorly characterized, with limited studies investigating DDIs involving CBD/THC in these populations. Therefore, it is critical to evaluate potential DDIs between CBD/THC and medications that are commonly used in special populations. Modeling approaches can aid in understanding these interactions.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway

Abstract Purpose: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. Methods: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. Results: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1β (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN... (AU)

Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity.

Cannabidiol (CBD) is a pharmacologically active metabolite of cannabis that is FDA-approved to treat seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in children aged one year and older. During clinical trials, CBD caused dose-dependent hepatocellular toxicity at therapeutic doses. The risk for toxicity was increased in patients taking valproate (VPA), another hepatotoxic antiepileptic drug, through an unknown mechanism. With the growing popularity of CBD in the consumer market, an improved understanding of the safety risks associated with CBD is needed to ensure public health. This review details current efforts to describe CBD pharmacokinetics and mechanisms of hepatotoxicity using both pharmacokinetic models and in vitro models of the liver. In addition, current evidence and knowledge gaps related to intracellular mechanisms of CBD-induced hepatotoxicity are described. The authors propose future directions that combine systems-based models with markers of CBD-induced hepatotoxicity to understand how CBD pharmacokinetics may influence the adverse effect profile and risk of liver injury for those taking CBD. Significance Statement This review describes current pharmacokinetic modeling approaches to capture the metabolic clearance and safety profile of cannabidiol (CBD). CBD is an increasingly popular natural product and FDA-approved antiepileptic drug known to cause clinically significant enzyme-mediated drug interactions and hepatotoxicity at therapeutic doses. CBD metabolism, pharmacokinetics, and putative mechanisms of CBD-induced liver injury are summarized from available preclinical data to inform future modeling efforts for understanding CBD toxicity.

Structural and functional investigation on stem and peel polysaccharides from different varieties of pitaya.

Varieties of plant species may affect the composition and structures of the polysaccharides, thus have an impact on their chemical properties and biological activities. Herein, the present study comparatively evaluated the differences in the chemical composition, morphological structures, antioxidant activity, and anti-inflammatory activity of the stem and peel polysaccharides from different varieties of pitaya. The FT-IR and NMR spectra indicated that the six polysaccharides had similar structural features, whereas the physicochemical characterization showed that they differed significantly in terms of the monosaccharide composition, molecular weight, and surface morphology. In addition, different varieties of pitaya polysaccharides exhibited different antioxidant activities and similar anti-inflammatory activities. These data suggested that varietal differences resulted in pitaya stem and peel polysaccharides with different monosaccharide compositions and molecular weights, thus led to different antioxidant activities and protection against oxidative damage, while similar structural features were closely related to their similar anti-inflammatory activities. Therefore, the study of the stem and peel polysaccharides from different varieties of pitaya can help us to better understand the relationship between their composition and structure and their biological activities. In addition, pitaya stem and peel polysaccharides have the potential to act as antioxidants or to treat inflammatory damage.

Changes of FGF23 and hearing in chronic renal failure and their correlation analysis.

BACKGROUND: To explore the association between fibroblast growth factor 23 (FGF23) and hearing in chronic renal failure (CRF). METHODS: Pure tone audiometry was used to detect the hearing of patients with CRF; the level of serum FGF23, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), and mean binaural hearing threshold were compared to the control group (people without kidney disease). The rat model of renal failure was established by 5/6 nephrectomy, and the auditory brainstem response (ABR) of rats after modeling was detected by the Tucker Davis Technologies (TDT) system; the expression level of FGF23 in the peripheral blood, renal and cochlear tissue was also detected. RESULTS: The incidence of hearing loss (HL) and serum FGF23 were higher in CRF patients than the control group; the sFGF23 was positively correlated with the mean binaural hearing threshold. Animal studies showed that the ABR threshold, creatinine, FGF23, BUN, and PTH increased after modeling; although, an increase in FGF23 was observed earlier than other indicators. The HL of rats with renal failure was significantly correlated with BUN, phosphate, PTH, sFGF23, kFGF23/ß-actin, eFGF23/ß-actin, weight, and modeling cycle. CONCLUSIONS: Both CRF patients and rat models showed high-frequency HL. FGF23 was highly expressed in the serum of HL renal failure patients and rats, as well as in the renal tissue and cochlea of renal failure rats. Therefore, FGF23 may be involved in the occurrence and development of HL caused by CRF.

Predictive value of serum d-serine level for hearing impairment in uremic patients.

OBJECTIVE: To investigate the predictive value of serum d-serine level for hearing impairment (HI) in uremic patients. METHODS: In this study, 30 uremic patients with HI and 30 with normal hearing were selected. The basic conditions, biochemical indicators, and serum serine levels of the two groups were compared to analyze the influencing factors of HI. RESULTS: The age and d-serine levels were higher in the HI group, while the l-serine level was lower than uremia in the normal hearing group. Logistic regression analysis showed that d-serine level ≥10 µM and older age increased the risk of HI. The area of the receiver operating characteristic (ROC) curve drawn by the prediction probability of HI was 0.838, indicating that age, d-serine, and l-serine had predictive diagnostic values for HI (p < .001). Among these, the ROC curve area of d-serine in predicting HI in uremic patients was 0.822 (p < .001). CONCLUSIONS: Increased d-serine and age are two risk factors for HI, while l-serine is a protective factor. d-Serine level has a predictive value for HI in uremic patients. Uremic patients are recommended hearing assessment, estimation of d-serine levels, and early intervention.

An Approach of Vibration Compensation for Atomic Gravimeter under Complex Vibration Environment.

Atomic gravimeter has been more frequently applied under complex and dynamic environments, but its measurement accuracy is seriously hampered by vibration-induced noise. In this case, vibration compensation provides a way to enhance the accuracy of gravity measurements by correcting the phase noise that resulted from the vibration of a Raman reflector, and improving the fitting of an interference fringe. An accurate estimation of the transfer function of vibration between the Raman reflector and the sensor plays a significant role in optimizing the effect of vibration compensation. For this reason, a vibration compensation approach was explored based on EO (equilibrium optimizer) for estimating the transfer function simplified model of a Raman reflector, and it was used to correct the interference fringe of an atomic gravimeter. The test results revealed that this approach greatly restored the actual vibration of the Raman reflector in a complex vibration environment. With a vibration compensation algorithm, it achieved the correction and fitting of the original interference fringe. In general, it dramatically reduced the RMSE (root mean square error) at the time of fitting and significantly improved the residual error in the gravity measurement. Compared with other conventional algorithms, such as GA (genetic algorithm) and PSO (particle swarm optimization), this approach realized a faster convergence and better optimization, so as to ensure more accurate gravity measurements. The study of this vibration compensation approach could provide a reference for the application of an atomic gravimeter in a wider and more complex environment.

A gene signature driven by abnormally methylated DEGs was developed for TP53 wild-type ovarian cancer samples by integrative omics analysis of DNA methylation and gene expression data.

Background: Integrated omics analysis based on transcriptome and DNA methylation data combined with machine learning methods is very promising for the diagnosis, prognosis, and classification of cancer. In this study, the DNA methylation and gene expression data of ovarian cancer (OC) were analyzed to identify abnormally methylated differentially expressed genes (DEGs), screen potential therapeutic agents for OC, and construct a risk model based on the abnormally methylated DEGs to predict patient prognosis. Methods: The gene expression and DNA methylation data of primary OC samples with tumor protein 53 (TP53) wild-type and normal samples were obtained from The Cancer Genome Atlas (TCGA) database. DEGs with aberrant methylation were analyzed by screening the intersection between DEGs and differentially methylated genes (DMGs). We attempted to search for potential drugs targeting DEGs with aberrant methylation by employing a network medicine framework. A gene signature based on the DEGs with aberrant methylation was constructed by regularized least absolute shrinkage and selection operator (LASSO) regression analysis. Results: A total of 440 aberrant methylated DEGs were screened. Based on their gene expression profiles and methylation data from different regions, the results of both discriminative pattern recognition analysis and principal component analysis (PCA) showed a significant separation between tumor tissue and healthy ovarian tissue. In total, 126 potential therapeutic drugs were identified for OC by network-based proximity analysis. Five genes were identified in 440 aberrant methylated DEGs, which formed an aberrant methylated DEGs-driven gene signature. This signature could significantly distinguish the different overall survivals (OS) of OC patients and showed better predictive performance in both the training and validation sets. Conclusions: In this study, the DNA methylation and gene expression data of OC were analyzed to identify abnormally methylated DEGs and potential therapeutic drugs, and a gene signature based on five aberrant methylation DEGs was constructed, which could better predict the risk of death in patients.

Diversity in Clinical Pharmacology: A Call to Action.

Prioritization of diversity, equity, and inclusion in all facets of our work is long overdue for the clinical pharmacology community. Increasing diversity in clinical research will deepen our understanding of nuanced patient populations and help improve all patient outcomes. Fostering an inclusive and diverse workforce will lead to broader perspectives that can better inform critical decisions and create work environments where everyone can thrive. In this call to action, we invite you to join us.

Conductive Cellulose-Derived Carbon Nanofibrous Membranes with Superior Softness for High-Resolution Pressure Sensing and Electrophysiology Monitoring.

Here, a strategy to overcome the stiff and brittle nature of cellulose-derived carbon nanofibrils (CCNFs) is proposed through a facile, low-cost, and scalable approach. Flexible and conformal CCNFs with a low bending rigidity below 55.4 mN and tunable conductivities of 0.14-45.5 S m-1 are developed by introducing silanol as a multieffect additive in the electrospun hybrid nanofibrous network and subsequent carbonization at a relatively high temperature (900 °C) and chemical vapor deposition of polypyrrole (PPy) on the hybrid carbon nanofibril surface. Silica acts as a lubricant in each rigid carbon fiber to improve flexibility of the CCNF structure as well as a template during cellulose carbonization to prevent the melting of carbon nanofibrils. Meanwhile, the uniform coating of PPy leads to an improvement in electrical conductivity while conserving the porous structure and compressibility of the CCNF nets. These conductive hybrid CCNF films are evaluated as mechanoreceptors and physiological sensors, which are demonstrated to be applied in intelligent electronics including electronic skin, human-machine interfaces, and epidermic electrodes. The design or working principles of the hybrid CCNFs for achieving optimum applicable effects when applied in different scenarios are revealed.

Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines.

Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein. Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein. Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1-1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h. Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.

Analysis of Energy and Density in Treating Hypertrophic Scar After Burn in Children with CO2 Dot Matrix Laser.

Objective: To analyze and compare the effect of the combination of energy and density parameters of CO2 dot matrix laser in the hyperplastic stage of pediatric burn. Materials and Methods: A total of 160 pediatric patients with hypertrophic scar after limb burn from 2017 to 2020 were randomly divided into four parameter groups (n = 40). The patients were treated with ablative fraction carbon dioxide laser, once every 10 weeks. During the interval of laser treatment, Compound Heparin Sodium and Allantoin Gel (Contractubex) was applied externally, tid, and elastic cover or elastic bandage is attached to the affected limb. Scoring based on the Vancouver Scar Scale is performed before each laser treatment, The score before the first treatment was the initial score, which was scored by two people separately, and the average score was calculated. Subsequently, the patients were treated four times and scored. The differences between each treatment and the first score of each parameter group were compared. Under the same energy and different treatment density, the scores after each treatment were compared. Under the same density and different energy, the scores after each treatment were compared. The bleeding and pigmentation of each parameter group were compared. Results: The increase of density can show the therapeutic effect earlier than the increase of energy, and 25mj energy and 10% density have better intervention effect. With the course of disease and the progress of treatment, the correlation between intervention effect and parameters tends to weaken. Comparing the number of cases with different scores between each treatment and the first time, the score in the 5% density group was lower than that in the 10% density group, but there was no significant difference between the 25mj and 17.5mj energy levels in the same density group. The intervention effect of the increase of density on scar was better than that of energy, and the increase of energy and density could aggravate the pain. Conclusion: In pediatric burn hypertrophic scars treated by CO2 dot matrix laser in exfoliation mode, the intervention effect of increasing density is better than that of energy. When setting laser treatment parameters, we should give priority to increasing density and adjust energy according to the effect of treatment and the condition of pain, bleeding and color precipitation. In this study, the best combination of parameters is 17.5mj/10%.

Evaluation of Klotho gene expression and NGAL levels following acute kidney injury during pregnancy hypertensive disorders.

BACKGROUND: This study examined the relationship between hypertensive disorders and acute kidney injury (AKI) during pregnancy by evaluating Klotho (KL) gene expression and Neutrophil gelatinase-associated lipocalin (NGAL) levels in pregnant women. MATERIAL AND METHODS: Pregnant women were divided into 3 groups: (1) Pregnancy related hypertensive disorders with AKI (PR-AKI) (9 cases), (2) hypertensive disorders pregnancy (HDP) (40 cases), and (3) normal pregnancy (30 cases). For each group, Klotho gene transcription levels in the blood, Klotho and NGAL proteins levels, Malondialdehyde (MDA) and superoxide dismutase (SOD) activity levels were measured in serum. Statistical comparisons were made among the three groups. RESULTS: Klotho/ß-actin transcript levels and serum KL protein concentrations were significantly decreased in hypertensive disorder pregnancies with AKI complications. Serum NGAL protein levels were significantly increased in the hypertensive disorder pregnancies with AKI complications. Total serum Klotho protein was negatively correlated with creatinine, while serum NGAL was positively correlated with serum creatinine, urea nitrogen, uric acid, systolic blood pressure, diastolic blood pressure and 24 h urine protein levels. Serum levels of MDA and SOD were significantly increased in the hypertensive disorder pregnancy with AKI and the overall MDA concentration was negatively correlated with Klotho protein concentration. Klotho protein was found to have a direct effect on creatinine, and a mediating effect of MDA was found. CONCLUSION: Decreased expression of Klotho protein in correlation with increased levels of oxidative stress are found during of AKI complications in pregnancy hypertensive disorders.

Application of Angiotensin Receptor-Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus.

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin-angiotensin-aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin-angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

Chromosome-level genome of Entada phaseoloides provides insights into genome evolution and biosynthesis of triterpenoid saponins.

As a medicinal herbal plant, Entada phaseoloides has high levels of secondary metabolites, particularly triterpenoid saponins, which are important resources for scientific research and medical applications. However, the lack of a reference genome for this genus has limited research on its evolution and utilization of its medicinal potential. In this study, we report a chromosome-scale genome assembly for E. phaseoloides using Illumina, Nanopore long reads and high-throughput chromosome conformation capture technology. The assembled reference genome is 456.18 Mb (scaffold N50 = 30.9 Mb; contig N50 = 6.34 Mb) with 95.71% of the sequences anchored onto 14 pseudochromosomes. E. phaseoloides was estimated to have diverged from the Leguminosae lineage at ~72.0 million years ago. With the integration of transcriptomic and metabolomic data, gene expression patterns and metabolite profiling of E. phaseoloides were determined in different tissues. The pattern of gene expression and metabolic profile of the kernel were distinct from those of other tissues. Furthermore, the evolution of certain gene families involved in the biosynthesis of triterpenoid saponins and terpenes was analysed and offers new insights into the formation of these two metabolites. Four CYP genes, one UGT gene and related transcription factors were identified as candidate genes contributing to regulation of triterpenoid saponin biosynthesis. As the first high-quality assembled reference genome in the genus Entada, it will not only provide new information for the evolutionary study of this genus and conservation biology of E. phaseoloides but also lay a foundation for the formation and utilization of secondary metabolites in medicinal plants.