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.

Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies.

This study aims to explore biomarkers associated with vitiligo and analyze the pathological role of immune cell infiltration in the disease. We used the robust rank aggregation (RRA) method to integrate three vitiligo data sets downloaded from gene expression omnibus database, identify the differentially expressed genes (DEGs) and analyze the functional correlation. Then, the comprehensive strategy of combined weighted gene coexpression network analysis (WGCNA) and logical regression of the selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) machine learning algorithm are employed to screen and biomarkers associated with vitiligo. Finally, the immune cell infiltration of vitiligo was evaluated by CIBERSORT, and the correlation between biomarkers and infiltrating immune cells was analyzed. Herein, we identified 131 robust DEGs, and enrichment analysis results showed that robust DEGs and melanogenesis were closely associated with vitiligo development and progression. TYR, TYRP1, DCT and LARP7 were identified as vitiligo-related biomarkers. Immune infiltration analysis demonstrated that CD4 T Cell, CD8 T Cell, Tregs, NK cells, dendritic cells, and macrophages were involved in vitiligo's pathogenesis. In summary, we adopted a comprehensive strategy to screen biomarkers related to vitiligo and explore the critical role of immune cell infiltration in vitiligo.Abbreviations: TYR, Tyrosinase; TYRP1, Tyrosinase-related protein-1; DCT, dopachrome tautomerase; LARP7, La ribonucleoprotein domain family, member-7; RRA, robust rank aggregation; DEGs, differentially expressed genes; WGCNA, weighted gene coexpression network analysis; LASSO, logical regression of the selection operator; SVM-RFE, support vector machine recursive feature elimination; RF, random forest; GWAS, Genome-wide association study; FasL, Fas-Fas ligand; Tregs, T-regulatory cells; NK, natural killer; GEPCs, gene expression profiling chips; GO, gene ontology; GSEA, gene set enrichment analysis; FDR, false discovery rate; AUC, area under the curve; ROC, receiver-operating characteristic; BP, biological process; CC, cellular component; MF, molecular function.

Epigenetics-based therapeutics for myocardial fibrosis.

Myocardial fibrosis (MF) is a reactive remodeling process in response to myocardial injury. It is mainly manifested by the proliferation of cardiac muscle fibroblasts and secreting extracellular matrix (ECM) proteins to replace damaged tissue. However, the excessive production and deposition of extracellular matrix, and the rising proportion of type I and type III collagen lead to pathological fibrotic remodeling, thereby facilitating the development of cardiac dysfunction and eventually causing heart failure with heightened mortality. Currently, the molecular mechanisms of MF are still not fully understood. With the development of epigenetics, it is found that epigenetics controls the transcription of pro-fibrotic genes in MF by DNA methylation, histone modification and noncoding RNAs. In this review, we summarize and discuss the research progress of the mechanisms underlying MF from the perspective of epigenetics, including the newest m6A modification and crosstalk between different epigenetics in MF. We also offer a succinct overview of promising molecules targeting epigenetic regulators, which may provide novel therapeutic strategies against MF.

Mechanism and therapeutic strategies of depression after myocardial infarction.

Depression resulted as an important factor associated with the myocardial infarction (MI) prognosis. Patients with MI also have a higher risk for developing depression. Although the issue of depression after MI has become a matter of clinical concern, the molecular mechanism underlying depression after MI remains unclear, whereby several strategies suggested have not got ideal effects, such as selective serotonin reuptake inhibitors. In this review, we summarized and discussed the occurrence mechanism of depression after MI, such as 5-hydroxytryptamine (5-HT) dysfunction, altered hypothalamus-pituitary-adrenal (HPA) axis function, gut microbiota imbalance, exosomal signal transduction, and inflammation. In addition, we offered a succinct overview of treatment, as well as some promising molecules especially from natural products for the treatment of depression after MI.

Covalent modification of Keap1 at Cys77 and Cys434 by pubescenoside a suppresses oxidative stress-induced NLRP3 inflammasome activation in myocardial ischemia-reperfusion injury.

Background and Purpose: Kelch ECH-associating protein 1 (Keap1) is a crucial chaperonin for E3 ubiquitin ligases. Modification of the key reactive cysteine residues in Keap1 affects the interaction between Keap1 and its substrate nuclear factor erythroid 2-related factor 2 (Nrf2), subsequently regulating oxidative stress and NLPR3 inflammasome activation, which are important factors for myocardial ischemia-reperfusion injury (MI/RI). Pubescenoside A (PBA), an active compound from Ilex pubescens, has antithrombotic and anti-inflammatory effects. However, the effect of PBA on MI/RI is still unknown. In the present study, we aimed to determine whether PBA can protect the heart against MI/RI and clarify the direct target and the underlying mechanism of PBA. Methods: The left anterior descending artery (LAD) ligation-induced MI/RI mice model or oxygen and glucose deprivation/reperfusion (OGD/R) were used to evaluate the cardioprotective effect of PBA. Pull-down assays, co-immunoprecipitation (Co-IP) assays, LC/MS/MS, isothermal calorimetry (ITC) experiments and covalent docking were used to identify the target of PBA. Results: PBA protected cardiomyocytes against OGD/R in vitro and LAD-induced MI/RI in vivo. PBA suppressed NLRP3 inflammation activation and induced the Nrf2 signaling pathway. Interestingly, PBA targeted Keap1 by selectively covalently binding to conserved cysteine residues, cysteine 77 (Cys77) in the BTB domain and cysteine 434 (Cys434) in the Kelch domain of Keap1, subsequently inhibiting ubiquitination of Nrf2 and activating antioxidant enzymes. Additionally, the cysteines of Keap1 has different degree of activation by PBA as follows: Cys77 > Cys434 > Cys23 > Cys38 > Cys226 > Cys273, which further elucidates the cysteine sensitivity of Keap1. Conclusions: Our results indicated that PBA might be a new Nrf2 activator that covalently binds to two critical domains of Keap1, and shows cardioprotective activities against ischemia-reperfusion injury.

Plumula Nelumbinis: A review of traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety. METHODS: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis. RESULTS: Plumula Nelumbinis is used to treat hypertension, arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects, such as protective effects against cardiovascular diseases, neurological diseases, lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in cardiovascular and neurological diseases and perspectives on Plumula Nelumbinis research were discussed. CONCLUSION: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of cardiovascular and neurological diseases, have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary.

Therapeutic perspectives of heat shock proteins and their protein-protein interactions in myocardial infarction.

Myocardial infarction (MI) is one of major causes of human death around the world. Heat shock proteins (HSPs) are a large family of conserved proteins, which can promote correct protein folding, maintain protein stability, and regulate cell metabolism, cellular homeostasis and other biological processes as molecular chaperones. Notable, HSPs are involved in MI-related pathophysiology, such as apoptosis, inflammatory response and oxidative stress. Here, we review recent studies and systematically summarize the role of HSPs in MI and myocardial ischemia/reperfusion injury (MIRI) and discuss the role of direct and indirect protein-protein interactions (PPI) of HSP complexes in the pathophysiology and therapeutic strategies of myocardial infarction. A comprehensive understanding of the cardioprotective role of PPIs of HSP complexes in myocardial infarction can provide new insights for MI or MIRI therapy.

NB-UVB irradiation attenuates inflammatory response in psoriasis.

Psoriasis is a chronic inflammatory disease characterized by immunological imbalance and vasodilation. Many triggering factors for psoriasis initiate inflammation via the activation of NF-κB. Narrow-band ultraviolet B (NB-UVB) irradiation can be used as a general treatment for psoriasis, although the molecular mechanism has not yet been determined. The aim of this study was to elucidate the potential molecular mechanism of NB-UVB irradiation therapy on psoriasis. We collected serum samples from patients with psoriasis and healthy control, and detected the expression of inflammatory factors by ELISA. In addition, we established mouse model of psoriasis. After different doses of NB-UVB irradiation, the proportion of CD4+ , CD8+ , and CD11c+ cells in mouse spleen was detected by flow cytometry. Meanwhile, the expression of inflammatory factors in the damaged skin of mice was detected by RT-PCR and Western blot analysis, and mouse serum levels of inflammatory factors were detected by ELISA. Our results showed that NB-UVB irradiation regulated the expression of inflammatory factors in psoriasis patients. In mice, high-dose NB-UVB irradiation effectively eliminated IMQ-induced psoriasis-like dermatitis and inhibited the expression of pro-inflammatory factors. In conclusion, our results indicate that NB-UVB irradiation could regulate the expression of inflammatory factors and attenuate psoriasis plaques.