Pharmacological upregulation of macrophage-derived itaconic acid by pubescenoside C attenuated myocardial ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion injury (MIRI) remains a prevalent clinical challenge globally, lacking an ideal therapeutic strategy. Macrophages play a pivotal role in MIRI pathophysiology, exhibiting dynamic inflammatory and resolutive functions. Macrophage polarization and metabolism are intricately linked to MIRI, presenting potential therapeutic targets. Pubescenoside C (PBC) from Ilex pubescens showed significantly anti-inflammatory effects, however, the effect of PBC on MIRI is unknown. OBJECTIVES: This study aimed to assess the cardioprotective effects of PBC against MIRI and elucidate the underlying mechanisms. METHODS: Sprague-Dawley rats, H9c2 and RAW264.7 macrophages were used to establish the in vitro and in vivo models of MIRI. TTC/Evans blue staining, immunohistochemical staining, metabonomics analysis, chemical probe, surface plasmon resonance (SPR), co-immunoprecipitation (CO-IP) assays were used for pharmacodynamic and mechanism study. RESULTS: PBC administration effectively reduced myocardial infarct size, decreased ST-segment elevation, and lowered CK-MB levels, concurrently promoting macrophage M2 polarization in MIRI. Furthermore, PBC-treated macrophages and their conditioned culture medium attenuated the apoptosis of H9c2 cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Metabonomics analysis revealed that PBC increased the production of itaconic acid (ITA) and malic acid (MA) in macrophages, which conferred protection against OGD/R injury in H9c2 cells. Mechanistic investigations indicated that ITA exerted its effects by covalently modifying pyruvate kinase M2 (PKM2) at Cys474, Cys424, and Lys151, thereby facilitating PKM2's mitochondrial translocation and enhancing the PKM2/Bcl2 interaction, subsequently leading to decreased degradation of Bcl2. SPR assays further revealed that PBC bound to HSP90, facilitating the interaction between HSP90 and GSK3ß and resulting in the inactivation of GSK3ß activity and upregulation of key metabolic enzymes for ITA and MA production (Acod1 and Mdh2). CONCLUSION: PBC alleviates MIRI-induced cardiomyocyte apoptosis by modulating the HSP90/ITA/PKM2 axis. Furthermore, pharmacological upregulation of ITA emerges as a promising therapeutic approach for MIRI, hinting at PBC's potential as a candidate drug for MIRI therapy.

Analyzing HPV Vaccination Service Preferences among Female University Students in China: A Discrete Choice Experiment.

OBJECTIVE: Despite being primary beneficiaries of human papillomavirus (HPV) vaccines, female university students in China exhibit low vaccination rates. This study aimed to assess their preferences for HPV vaccination services and evaluate the relative importance of various factors to inform vaccination strategy development. METHODS: Through a literature review and expert consultations, we identified five key attributes for study: effectiveness, protection duration, waiting time, distance, and out-of-pocket (OOP) payment. A D-efficient design was used to create a discrete choice experiment (DCE) questionnaire. We collected data via face-to-face interviews and online surveys from female students across seven universities in China, employing mixed logit and latent class logit models to analyze the data. The predicted uptake and compensating variation (CV) were used to compare different vaccination service scenarios. RESULTS: From 1178 valid questionnaires, with an effective response rate of 92.9%, we found that effectiveness was the most significant factor influencing vaccination preference, followed by protection duration, OOP payment and waiting time, with less concern for distance. The preferred services included a 90% effective vaccine, lifetime protection, a waiting time of less than three months, a travel time of more than 60 min, and low OOP payment. Significant variability in preferences across different vaccination service scenarios was observed, affecting potential market shares. The CV analysis showed female students were willing to spend approximately CNY 5612.79 to include a hypothetical 'Service 5' (a vaccine with higher valency than the nine-valent HPV vaccine) in their prevention options. CONCLUSIONS: The findings underscore the need for personalized, need-based HPV vaccination services that cater specifically to the preferences of female university students to increase vaccination uptake and protect their health.

Spatiotemporal changes of urban heat island effect relative to land surface temperature: a case study of Jinan City, China.

The urban heat island (UHI) effect has become increasingly prevalent and significant with the accelerated pace of urbanization, posing challenges for urban planners and policymakers. To reveal the spatiotemporal variations of the urban heat island effect in Jinan City, this study utilized Landsat satellite images from 2009, 2014, and 2019, employing the classic Mono-Window algorithm to extract land surface temperature (LST). Additionally, Geodetector was introduced to conduct a detailed analysis of the relationship between LST in Jinan City and land cover types (vegetation, water bodies, and buildings). The results indicate a significant increase in the severity of the urban heat island effect in Jinan from 2009 to 2019, with the central urban area consistently exhibiting a high-intensity core heat island. Suburban areas of Jinan show a clear trend of merging their heat island effects with the central urban area. The combined area of strong cool island effect zones and cool island effect zones within water bodies reaches 89.7%, while the combined proportion of heat island and strong heat island effect zones in building areas is 62.2%. Vegetation cover (FVC) exerts the greatest influence among all factors on the intensity level of the urban heat island effect. These findings provide a reliable basis for decision-making related to urban planning and construction in Jinan City.

Updating local and global probabilities during maze navigation.

We examined the human ability to encode and utilize local and global uncertainty information during a navigational task. Participants were tasked with navigating a virtual maze in which wall locations were obscured. Local cues and a global direction provided guidance. The validities of the global and local cues were separately and jointly varied across the two experiments. The results demonstrated that participants effectively utilized both global and local cues for navigation with a stronger reliance on local cues and a heightened precision in estimating their reliability. Our findings suggest that the representation of uncertainty for proximate events can be dissociated from that of distal events. Furthermore, humans effectively integrate both forms of information when making decisions during navigation tasks. This research advances our understanding of uncertainty processing and its implications for decision making in complex environments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.

Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (ß = - 0.037, 95% CI = - 0.070, - 0.005), while CRP was associated with telomere length in males only (ß = - 0.019, 95% CI = - 0.035, - 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role.

Review of tracer kinetic models in evaluation of gliomas using dynamic contrast-enhanced imaging.

Glioma is the most common type of primary malignant tumor of the central nervous system (CNS), and is characterized by high malignancy, high recurrence rate and poor survival. Conventional imaging techniques only provide information regarding the anatomical location, morphological characteristics, and enhancement patterns. In contrast, advanced imaging techniques such as dynamic contrast-enhanced (DCE) MRI or DCE CT can reflect tissue microcirculation, including tumor vascular hyperplasia and vessel permeability. Although several studies have used DCE imaging to evaluate gliomas, the results of data analysis using conventional tracer kinetic models (TKMs) such as Tofts or extended-Tofts model (ETM) have been ambiguous. More advanced models such as Brix's conventional two-compartment model (Brix), tissue homogeneity model (TH) and distributed parameter (DP) model have been developed, but their application in clinical trials has been limited. This review attempts to appraise issues on glioma studies using conventional TKMs, such as Tofts or ETM model, highlight advancement of DCE imaging techniques and provides insights on the clinical value of glioma management using more advanced TKMs.

Plasmon AgNPs/MoS2/ZnO nanorods array ternary heterojunctions enabling high-efficiency solar-light energy utilization for photocatalysis and recyclable SERS detection.

BACKGROUND: Surface-enhanced Raman scattering (SERS) has gained widespread use in molecule-level detection benefiting from its high sensitivity, nondestructive data acquisition, and capacity for providing molecular fingerprint information. However, the strong adhesion of target molecules to the substrate (known as the "memory effect") inherently hinders the reusability of SERS substrates. Research has shown that self-cleaning SERS substrates based on versatile semiconductor materials with SERS enhancement capabilities and solar photocatalytic properties offer an effective platform for the sensitive detection and degradation of harmful molecules. RESULTS: In this research, a resuable SERS-active substrate was facilely fabricated by anchoring silver nanoparticles (AgNPs) to the edges of MoS2 nanosheet decorated on ZnO nanorod arrays (NRAs). This innovative design exhibited a remarkable SERS enhancement factor (EF) of 4.6 × 107 and demonstrated significant solar photocatalytic efficiency. Such superior characteristics of ternary plasma heterojunction were ascribable to the synergistic effect of the "Schottky barrier" and "hot spots" between MoS2 and AgNPs, the inherent chemical enhancement proficiency of the MoS2/ZnO NRAs heterojunction, as well as the ultrafast electron transfer within the ternary heterojunction. SIGNIFICANCE: The developed ternary heterojunction substrate enabled highly sensitive SERS detection of trace amounts of organic molecules. Moreover, this SERS substrate exhibited self-cleaning and recyclability via solar-light-driven photocatalysis. This bifunctional recyclable SERS substrate proved capable of meeting various requirements for routine monitoring of environmental organic pollutants and provided a robust avenue for advancing energy utilization materials that serve as high-performance SERS sensors and catalysts.

Strain Engineering of Unconventional Crystal-Phase Noble Metal Nanocatalysts.

The crystal phase, alongside the composition, morphology, architecture, facet, size, and dimensionality, has been recognized as a critical factor influencing the properties of noble metal nanomaterials in various applications. In particular, unconventional crystal phases can potentially enable fascinating properties in noble metal nanomaterials. Recent years have witnessed notable advances in the phase engineering of nanomaterials (PEN). Within the accessible strategies for phase engineering, the effect of strain cannot be ignored because strain can act not only as the driving force of phase transition but also as the origin of the diverse physicochemical properties of the unconventional crystal phase. In this review, we highlight the development of unconventional crystal-phase noble metal nanomaterials within strain engineering. We begin with a short introduction of the unconventional crystal phase and strain effect in noble metal nanomaterials. Next, the correlations of the structure and performance of strain-engineered unconventional crystal-phase noble metal nanomaterials in electrocatalysis are highlighted, as well as the phase transitions of noble metal nanomaterials induced by the strain effect. Lastly, the challenges and opportunities within this rapidly developing field (i.e., the strain engineering of unconventional crystal-phase noble metal nanocatalysts) are discussed.

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas.

RATIONALE AND OBJECTIVES: Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. MATERIALS AND METHODS: Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, Kep, Ve, Vp, and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. RESULTS: Multivariate analysis for all patients demonstrated that age (OR=1.103, p = 0.002) and Ktrans (OR=1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR=1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR=1.111, p = 0.002) and Ktrans (OR=1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. CONCLUSION: Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

Calcitonin Inhibits Phenotypic Switching of Aortic Smooth Muscle Cells and Neointimal Hyperplasia through the AMP-Activated Protein Kinase/Mechanistic Target of Rapamycin Pathway.

Calcitonin (CT) is a peptide hormone secreted by the parafollicular C cells of the thyroid gland, salmon calcitonin was originally extracted from the hind cheek of salmon. Neointimal hyperplasia refers to the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, a rat model of restenosis was employed to explore the impact of calcitonin on neointima proliferation. Calcitonin was administered via continuous injections for a duration of 14 days postsurgery, and the expression of proteins associated with proliferation, migration, and phenotypic switching was assessed using the vascular smooth muscle cells. Additionally, metabolomic analyses were conducted to shed light on the mechanisms that underlie the role of calcitonin in the development of cardiovascular disease. In our study, we found that calcitonin possesses the capability to dispute the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet-derived growth factor-BB (PDGF-BB) and 15% fetal bovine serum in vitro. Calcitonin has demonstrated a favorable impact on smooth muscle cells, both in vitro and in vivo. More specifically, it has been observed to mitigate phenotypic switching, proliferation, and migration of these cells. Moreover, calcitonin has been identified as a protective factor against phenotypic switching and the formation of neointima, operating through the AMP-activated protein kinase/mechanistic target of rapamycin (mTOR) pathway.

Suramin inhibits phenotypic transformation of vascular smooth muscle cells and neointima hyperplasia by suppressing transforming growth factor beta receptor 1 /Smad2/3 pathway activation.

Vascular smooth muscle cells (VSMCs) contribute to neointimal hyperplasia (NIH) after vascular injury, a common feature of vascular remodelling disorders. Suramin is known to exert antitumour effects by inhibiting the proliferation of various tumour cells; however, its effects and mechanism on VSMCs remain unclear. This study investigated the effects of suramin on human aortic smooth muscle cells (HASMCs), rat aortic smooth muscle cells (RASMCs) and NIH to examine its suitability for the prevention of vascular remodelling disorders. In vitro, suramin administration reduced platelet-derived growth factor type BB (PDGF-BB)-stimulated proliferation, migration, and dedifferentiation of VSMCs through a transforming growth factor beta receptor 1 (TGFBR1)/Smad2/3-dependent pathway. Suramin dramatically inhibited NIH ligation in the left common carotid artery (LCCA) vivo. Therefore, our results indicate that suramin protects against the development of pathological vascular remodelling by attenuating VSMCs proliferation, migration, and phenotypic transformation and may be used as a potential medicine for the treatment of NIH.

Fluorescent and Colorimetric Dual-Mode Strategy Based on Rhodamine 6G Hydrazide for Qualitative and Quantitative Detection of Hg2+ in Seafoods.

In this study, a rapid fluorescent and colorimetric dual-mode detection strategy for Hg2+ in seafoods was developed based on the cyclic binding of the organic fluorescent dye rhodamine 6G hydrazide (R6GH) to Hg2+. The luminescence properties of the fluorescent R6GH probe in different systems were investigated in detail. Based on the UV and fluorescence spectra, it was determined that the R6GH has good fluorescence intensity in acetonitrile and good selective recognition of Hg2+. Under optimal conditions, the R6GH fluorescent probe showed a good linear response to Hg2+ (R2 = 0.9888) in the range of 0-5 µM with a low detection limit of 2.5 × 10-2 µM (S/N = 3). A paper-based sensing strategy based on fluorescence and colorimetric analysis was developed for the visualization and semiquantitative analysis of Hg2+ in seafoods. The LAB values of the paper-based sensor impregnated with the R6GH probe solution showed good linearity (R2 = 0.9875) with Hg2+ concentration in the range of 0-50 µM, which means that the sensing paper can be combined with smart devices to provide reliable and efficient Hg2+ detection.

Analysis of Hospitalization Costs in Patients Suffering from Cerebral Infarction along with Varied Comorbidities.

OBJECTIVE: This study aimed to study the influence of comorbidities on hospitalization costs for inpatients with cerebral infarction. METHODS: The data from the medical records pertaining to 76,563 inpatients diagnosed with cerebral infarction were collected from public hospital records for the period between 1 January 2020 and 30 December 2020 in Gansu Province. EpiData 3.1 software was used for data collation, and SPSS 25.0 was used for data analysis. Numbers and percentages were calculated for categorical variables, the chi-squared test was used to compare differences between groups, and multiple independent-sample tests (Kruskal-Wallis H test, test level α = 0.05) and multiple linear regression were used to analyze the influence of different types of comorbidity on hospitalization costs. RESULTS: Among the 76,563 cerebral infarction inpatients, 41,400 were male (54.07%); the average age of the inpatients was 67.68 ± 10.75 years (the 60~80-year-old group accounted for 65.69%). Regarding the incidence of varied chronic disease comorbidities concomitant with cerebral infarction, hypertension was reported as the most frequent, followed by heart disease and chronic pulmonary disease. The average hospitalization cost of cerebral infarction inpatients is US $1219.66; the hospitalization cost increases according to the number of comorbidities with which a patient suffers (H = 404.506, p < 0.001); Regarding the types of comorbidities, the hospitalization cost of cancer was the highest, at US $1934.02, followed by chronic pulmonary disease (US $1533.02). Regarding the cost of hospitalization for combinations of comorbidities, cerebral infarction + chronic pulmonary disease was the most costly (US $1718.90), followed by cerebral infarction + hypertension + chronic pulmonary disease (US $1530.60). In the results of multiple linear regression analysis, cerebral infarction with chronic pulmonary disease had significant effects on hospitalization costs (ß = 0.181, p < 0.001), drug costs (ß = 0.144, p < 0.001) and diagnosis costs (ß = 0.171, p < 0.001). CONCLUSIONS: Comorbidities are significantly associated with high hospitalization costs for cerebral infarction patients. Furthermore, relevant health departments should build preventative and control systems to reduce the risk of comorbidities, as well as to improve hospital clinical pathway management and to strengthen and refine the cost-control management of cerebral infarction from the perspective of comorbidities.

Versatile self-assembled electrospun micropyramid arrays for high-performance on-skin devices with minimal sensory interference.

On-skin devices that show both high performance and imperceptibility are desired for physiological information detection, individual protection, and bioenergy conversion with minimal sensory interference. Herein, versatile electrospun micropyramid arrays (EMPAs) combined with ultrathin, ultralight, gas-permeable structures are developed through a self-assembly technology based on wet heterostructured electrified jets to endow various on-skin devices with both superior performance and imperceptibility. The designable self-assembly allows structural and material optimization of EMPAs for on-skin devices applied in daytime radiative cooling, pressure sensing, and bioenergy harvesting. A temperature drop of ~4 °C is obtained via an EMPA-based radiative cooling fabric under a solar intensity of 1 kW m-2. Moreover, detection of an ultraweak fingertip pulse for health diagnosis during monitoring of natural finger manipulation over a wide frequency range is realized by an EMPA piezocapacitive-triboelectric hybrid sensor, which has high sensitivity (19 kPa-1), ultralow detection limit (0.05 Pa), and ultrafast response (≤0.8 ms). Additionally, EMPA nanogenerators with high triboelectric and piezoelectric outputs achieve reliable biomechanical energy harvesting. The flexible self-assembly of EMPAs exhibits immense potential in superb individual healthcare and excellent human-machine interaction in an interference-free and comfortable manner.

Cathepsin B/HSP70 complex induced by Ilexsaponin I suppresses NLRP3 inflammasome activation in myocardial ischemia/reperfusion injury.

BACKGROUND: Myocardial ischemia/reperfusion injury (MI/RI) is a clinical issue in MI therapy that requires effective intervention. Cathepsin B (CTSB) plays an essential role in regulating cell death, inflammatory response and angiogenesis. Ilexsaponin I (ISI), a triterpenoid saponin obtained from Ilex pubescens Hook. et Arn, has anti-inflammatory and cardioprotective effects. However, the effect of ISI on MI/RI is unclear. PURPOSE: The study aims to disclose the mechanism of ISI as a potent therapeutic agent for MI/RI. METHODS: Left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) were used to establish MI/RI model in vivo and in vitro. ELISA, western blot and immunofluorescence were carried out to detect CTSB activity and NLRP3 inflammasome activation. Coimmunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis were used to detect the interaction of CTSB/HSP70 complex. Infarct area determination, echocardiography and hematoxylin and eosin (HE) staining were performed to assess the cardioprotection of ISI in vivo. RESULTS: Plasma CTSB was elevated in patients after percutaneous coronary intervention (PCI), and was positively correlated with the level of cTnI in plasma, which was also found in MI/RI rat model. ISI significantly suppressed the overexpression and activity of CTSB after MI/RI or OGD/R. ISI remarkably suppressed CTSB triggered-NLRP3 inflammasome activation and reduced the maturation of IL-1ß and IL-18. Importantly, we firstly found that ISI promoted CTSB/HSP70 complex formation to disrupt CTSB/NLRP3 complex, leading to NLRP3 inflammasome inactivation. ISI could also limit infarct size, improve cardiac function and reduce inflammatory infiltrates in vivo and protected H9c2 cells against OGD/R insult in vitro. Interrupting the HSP70 and CTSB interaction with HSP70 siRNA blocked the effect of ISI on CTSB, NLRP3 inflammasome activation and the cardioprotective effect. CONCLUSION: ISI probably exerts cardioprotective effect against MI/RI by modulating HSP70 competitively bind to CTSB to suppress the activation of the NLRP3 inflammasome.

Predicting MGMT Promoter Methylation in Diffuse Gliomas Using Deep Learning with Radiomics.

This study aimed to investigate the feasibility of predicting oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in diffuse gliomas by developing a deep learning approach using MRI radiomics. A total of 111 patients with diffuse gliomas participated in the retrospective study (56 patients with MGMT promoter methylation and 55 patients with MGMT promoter unmethylation). The radiomics features of the two regions of interest (ROI) (the whole tumor area and the tumor core area) for four sequences, including T1 weighted image (T1WI), T2 weighted image (T2WI), apparent diffusion coefficient (ADC) maps, and T1 contrast-enhanced (T1CE) MR images were extracted and jointly fed into the residual network. Then the deep learning method was developed and evaluated with a five-fold cross-validation, where in each fold, the dataset was randomly divided into training (80%) and validation (20%) cohorts. We compared the performance of all models using area under the curve (AUC) and average accuracy of validation cohorts and calculated the 10 most important features of the best model via a class activation map. Based on the ROI of the whole tumor, the predictive capacity of the T1CE and ADC model achieved the highest AUC value of 0.85. Based on the ROI of the tumor core, the T1CE and ADC model achieved the highest AUC value of 0.90. After comparison, the T1CE combined with the ADC model based on the ROI of the tumor core exhibited the best performance, with the highest average accuracy (0.91) and AUC (0.90) among all models. The deep learning method using MRI radiomics has excellent diagnostic performance with a high accuracy in predicting MGMT promoter methylation in diffuse gliomas.

The anticardiac fibrosis of total alkaloids of Plumula nelumbinis by regulating circulating lipidomic profile: In vivo study.

Plumula nelumbinis has great medicinal potential as a herbal tea and traditional drug in China. This study was aimed to evaluate the anticardiac fibrosis of the total alkaloids of P. nelumbinis (TAP). TAP at 50 mg/kg/day significantly ameliorated isoproterenol-induced cardiac fibrosis in mice (p < .05). The circulating lipidomics study revealed that TAP improved the lipid metabolism dysfunction in cardiac fibrosis. Meanwhile, TAP suppressed the lipid accumulation, decreased MDA level (p < .01) in heart, and increased FFA level (p < .01). Furthermore, integrating lipidomics, chemical profiles and pharmacology network analysis found that AMPK and PI3K/Akt signaling pathways were the potential targeted pathway by TAP to regulate lipid metabolism dysfunction including glycerophospholipid metabolism. Above all, TAP provided a potential anticardiac fibrosis effect partly through regulation of lipid profiles. PRACTICAL APPLICATIONS: The total alkaloids of Plumula nelumbinis (TAP) suppressed ISO-induced cardiac fibrosis in mice. Network pharmacology analysis and experiments revealed that TAP-regulated AMPK and PI3K/Akt signaling pathway to improve lipid metabolism disorder in cardiac fibrosis. This study provides evidence to the therapeutic potential of TAP in the treatment of ISO-induced cardiac fibrosis and could be a drug candidate for prevention and treatment of cardiac fibrosis.

Integrated chemical profiling, network pharmacology and pharmacological evaluation to explore the potential mechanism of Xinbao pill against myocardial ischaemia-reperfusion injury.

CONTEXT: Xinbao pill (XBW), a traditional Chinese herbal formula, is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischaemia-reperfusion injury (MI/RI) is unclear. OBJECTIVE: This study evaluates the cardioprotective effect and molecular mechanism of XBW against MI/RI. MATERIALS AND METHODS: A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was used to identify chemicals. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database, etc. Sprague-Dawley (SD) rats under anterior descending artery ligation model were divided into Sham, MI/RI and XBW (180 mg/kg, intragastric administration). After 30 min ischaemia and 24 h reperfusion, heart tissues were collected for measurement of myocardial infarct size. After oxygen glucose deprivation for 6 h, H9c2 cells were treated with XBW (60, 240 and 720 µg/mL) and diazoxide (100 µM) for 18 h of reperfusion. RESULTS: Thirty-seven chemicals were identified in XBW; 50 MI/RI-related targets of XBW were predicted using indicated databases. XBW significantly reduced infarct size and creatine kinase MB (CK-MB) level after MI/RI; XBW protected H9c2 cells against OGD/R injury. Gene ontology (GO) and KEGG pathway enrichment analyses by String database showed that the cardioprotective effect of XBW was associated with autophagy and apoptosis signalling pathways. Experimental investigation also verified that XBW suppressed apoptosis, autophagy and endoplasmic reticulum (ER) stress. CONCLUSIONS: XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.

Uncovering the molecular mechanisms of Ilex pubescens against myocardial ischemia-reperfusion injury using network pharmacology analysis and experimental pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex pubescens (I. pubescens), has been widely used to treat cardiovascular disease (CVD) in South China. Several studies have revealed aspect of its phytochemistry and pharmacological activities in cardiovascular diseases, but its active compounds and mechanisms of action are still unclear. The aim of this study was to search for the active compounds and the pharmacological mechanisms of I. pubescens for myocardial ischemia-reperfusion injury (MI/RI) by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main targets of compounds in I. pubescens were predicted using the TargetNet webserver (http://targetnet.scbdd.com). The network between compounds and predicted targets related to MI/RI and compounds was constructed. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate I. pubescens targets acting on MI/RI, which were further validated by in vitro and in vivo experiments. RESULTS: A total of 191 targets were predicted for 64 chemical compounds in I. pubescens. Following Venn's analysis, we found that 38 candidate targets of I. pubescens were associated with protective effects against MI/RI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these targets were related to estrogen signaling pathway. Importantly, the cardioprotective effects of I. pubescens and its active compounds were evaluated and the regulatory effects on key targets of heat shock protein 90 alpha family class A member 1 (HSP90AA1) and Estrogen receptor 1 (ESRα) in estrogen signaling pathway were validated in vitro and in vivo. CONCLUSION: Our discoveries revealed that I. pubescens ameliorated MI/RI by regulating HSP90AA1 and ESRα in estrogen signaling pathway.

MR-Based Radiomics for Differential Diagnosis between Cystic Pituitary Adenoma and Rathke Cleft Cyst.

BACKGROUND: It is often tricky to differentiate cystic pituitary adenoma from Rathke cleft cyst with visual inspection because of similar MRI presentations between them. We aimed to design an MR-based radiomics model for improving differential diagnosis between them. METHODS: Conventional diagnostic MRI data (T1-,T2-, and postcontrast T1-weighted MR images) were obtained from 215 pathologically confirmed patients (105 cases with cystic pituitary adenoma and the other 110 cases with Rathke cleft cyst) and were divided into training (n = 172) and test sets (n = 43). MRI radiomics features were extracted from the imaging data, and semantic imaging features (n = 15) were visually estimated by two radiologists. Four classifiers were used to construct radiomics models through 5-fold crossvalidation after feature selection with least absolute shrinkage and selection operator. An integrated model by combining radiomics and semantic features was further constructed. The diagnostic performance was validated in the test set. Receiver operating characteristic curve was used to evaluate and compare the performance of the models at the background of diagnostic performance by radiologist. RESULTS: In test set, the combined radiomics and semantic model using ANN classifier obtained the best classification performance with an AUC of 0.848 (95% CI: 0.750-0.946), accuracy of 76.7% (95% CI: 64.1-89.4%), sensitivity of 73.9% (95% CI: 56.0-91.9%), and specificity of 80.0% (95% CI: 62.5-97.5%) and performed better than multiparametric model (AUC = 0.792, 95% CI: 0.674-0.910) or semantic model (AUC = 0.823, 95% CI: 0.705-0.941). The two radiologists had an accuracy of 69.8% and 74.4%, respectively, sensitivity of 69.6% and 73.9%, and specificity of 70.0% and 75.0%. CONCLUSIONS: The MR-based radiomics model had technical feasibility and good diagnostic performance in the differential diagnosis between cystic pituitary adenoma and Rathke cleft cyst.