Exploring the Mechanism of Si-miao-yong-an Decoction in the Treatment of Coronary Heart Disease based on Network Pharmacology and Experimental Verification.

BACKGROUND: To investigate the active ingredients and the mechanisms of Si-miaoyong- an Decoction (SMYA) in the treatment of coronary heart disease (CHD) by using network pharmacology, molecular docking technology, and in vitro validation. METHODS: Through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Uniprot database, GeneCards database, and DAVID database, we explored the core compounds, core targets and signal pathways of the effective compounds of SMYA in the treatment of CHD. Molecular docking technology was applied to evaluate the interactions between active compounds and key targets. The hypoxia-reoxygenation H9C2 cell model was applied to carry out in vitro verification experiments. A total of 109 active ingredients and 242 potential targets were screened from SMYA. A total of 1491 CHD-related targets were retrieved through the Gene- Cards database and 155 overlapping CHD-related SMYA targets were obtained. PPI network topology analysis indicated that the core targets of SMYA in the treatment of CHD include interleukin- 6 (IL-6), tumor suppressor gene (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), phosphorylated protein kinase (AKT1) and mitogen-activated protein kinase (MAPK). KEGG enrichment analysis demonstrated that SMYA could regulate Pathways in cancer, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxiainducible factor-1(HIF-1) signaling pathway, VEGF signaling pathway, etc. Results: Molecular docking showed that quercetin had a significant binding activity with VEGFA and AKT1. In vitro studies verified that quercetin, the major effective component of SMYA, has a protective effect on the cell injury model of cardiomyocytes, partially by up-regulating expressions of phosphorylated AKT1 and VEGFA. CONCLUSION: SMYA has multiple components and treats CHD by acting on multiple targets. Quercetin is one of its key ingredients and may protect against CHD by regulating AKT/VEGFA pathway.

Qishen granules regulate intestinal microecology to improve cardiac function in rats with heart failure.

Introduction: Qishen Granule (QSG), a clinically approved traditional Chinese medicine, has been researched for treating heart failure (HF) for many years. However, the effect of QSG on intestinal microecology remains unconfirmed. Therefore, this study aimed to elucidate the possible mechanism of QSG regulating HF in rats based on intestinal microecological changes. Methods: A rat model with HF induced by myocardial infarction was prepared by left coronary artery ligation. Cardiac functions were assessed by echocardiography, pathological changes in the heart and ileum by hematoxylin-eosin (HE) and Masson staining, mitochondrial ultrastructure by transmission electron microscope, and gut microbiota by 16S rRNA sequencing. Results: QSG administration improved cardiac function, tightened cardiomyocytes alignment, decreased fibrous tissue and collagen deposition, and reduced inflammatory cell infiltration. Electron microscopic observation of mitochondria revealed that QSG could arrange mitochondria neatly, reduce swelling, and improve the structural integrity of the crest. Firmicutes were the dominant component in the model group, and QSG could significantly increase the abundance of Bacteroidetes and Prevotellaceae_NK3B31_group. Furthermore, QSG significantly reduced plasma lipopolysaccharide (LPS), improved intestinal structure, and recovered barrier protection function in rats with HF. Conclusion: These results demonstrated that QSG was able to improve cardiac function by regulating intestinal microecology in rats with HF, suggesting promising therapeutic targets for HF.

Case Report: A case of COL1A1-PDGFB fusion uterine sarcoma at cervix and insights into the clinical management of rare uterine sarcoma.

COL1A1-PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor that was previously classified as an undifferentiated uterine sarcoma due to the lack of specific features of differentiation. Till now, only five cases have been reported, and here we presented another case recently diagnosed in a Chinese woman who had vaginal bleeding. She presented with a cervical mass at the anterior lip of the cervix invading the vagina and was treated with laparoscopic total hysterectomy plus bilateral salpingo-oophorectomy (TH+BSO) and partial vaginal wall resection with the final pathology of COL1A1-PDGFB fusion uterine sarcoma. Our aim is to emphasize the importance of differential diagnosis of this rare tumor, as early precise diagnosis may allow patients to benefit from the targeted therapy imatinib. This article also serves as further clinical evidence of this disease, serving to increase clinical awareness of this rare sarcoma to avoid misdiagnosis.

Joint detection of multiple HPV-testing technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated cervical squamous cell carcinoma (CSCC) -an analysis of 3869 cases.

OBJECTIVES: This study aimed to investigate the frequency and clinicopathological characteristics of HPV-independent cervical squamous cell carcinoma (CSCC). METHODS: A total of 3869 patients with CSCC from 2017 to 2021 were searched. p16INK4a immunochemistry (IHC), two HPV-DNA(L1) polymerase chain reactions and HPV mRNA in situ hybridization were performed. Viral copies were detected using the 21 HPV quantitative test. RESULTS: Six cases showed negative results in all four assays (group 1, 0.16%). Twenty-seven cases showed discordant results (group 2), and 3836 cases presented all-positive results (group 3). p16INK4a IHC showed similar sensitivity, specificity, and positive predictive value compared to the other three direct HPV assays. 21 HPV genotyping showed 100% of negative predictive value. HPV copies were extremely lower in Group 2 than in Group 3 (P < 0.01), but were not significantly different from those in Group 1. Older age, advanced FIGO stage (III-IV) and abnormal p53 (p53abn) IHC were independent predictors of HPV-negative status in univariate and multivariate logistic regression. Group 2 had similar proportions of age >60 years and p53abn IHC with Group 1, but had fewer cases with advanced FIGO stage (P < 0.05) and TILs (P < 0.05). Groups 1 and 2 had worse disease-free survival (DFS) and disease-specific survival (DSS) than Group 3 (P < 0.01), while no significant difference was found between these two groups. HPV-negative status was a risk factor for both DFS (P < 0.05) and DSS (P < 0.01) in univariate but not multivariate Cox regression. CONCLUSIONS: Joint detection of multiple technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated CSCC cases that present similar prognoses. Additional attention should be paid to these low-copy HPV-associated cases in clinical practice.

Evaluation of the transverse aortic constriction model in ICR and C57BL/6J mice.

Transverse aortic constriction (TAC) is a frequently used model to investigate pressure overload-induced progressive heart failure (HF); however, there is considerable phenotypic variation among different mouse strains and even sub-strains. Moreover, less is known about the TAC model in ICR mice. Therefore, to determine the suitability of the ICR strain for TAC-induced HF research, we compared the effects of TAC on ICR and C57BL/6J mice at one, two and four weeks post-TAC via echocardiography, organ index, morphology, and histology. At the end of the study, behavior and gene expression patterns were assessed, and overall survival was monitored. Compared to the sham-operated mice, ICR and C57BL/6J mice displayed hypertrophic phenotypes with a significant increase in ventricle wall thickness, heart weight and ratio, and cross-sectional area of cardiomyocytes after a 2-week TAC exposure. In addition, ICR mice developed reduced systolic function and severe lung congestion 4 weeks post-TAC, whereas C57BL/6J did not. Besides, ICR mice demonstrated comparable survival, similar gene expression alteration but severer fibrotic remodeling and poor behavioral performance compared to the C57BL/6J mice. Our data demonstrated that ICR was quite sensitive to TAC-induced heart failure and can be an ideal research tool to investigate mechanisms and drug intervention for pressure overload-induced HF.

Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT-IKK/STAT3 Axis.

Aim: Inflammation and fibrosis have been shown to be critical factors in heart failure (HF) progression. Calycosin (Cal) is the major active component of Astragalus mongholicus Bunge and has been reported to have therapeutic effects on the cardiac dysfunction after myocardial infarction. However, whether Cal could ameliorate myocardial infarction (MI)-induced inflammation and fibrosis and precise mechanisms remain uncertain. The aim of this study is to explore the role of Cal in HF and to clarify the underlying mechanisms. Methods: For in vivo experiments, rats underwent left anterior descending artery ligation for heart failure model, and the cardioprotective effects of Cal were measured by echocardiographic assessment and histological examination. RNA-seq approach was applied to explore potential differential genes and pathways. For further mechanistic study, proinflammatory-conditioned media (conditioned media)-induced H9C2 cell injury model and TGFß-stimulated cardiac fibroblast model were applied to determine the regulatory mechanisms of Cal. Results: In the in vivo experiments, echocardiography results showed that Cal significantly improved heart function. GO and reactome enrichment revealed that inflammation and fibrosis pathways are involved in the Cal-treated group. KEGG enrichment indicated that the PI3K-AKT pathway is enriched in the Cal-treated group. Further experiments proved that Cal alleviated cardiomyocyte inflammatory responses evidenced by downregulating the expressions of phosphorylated IκB kinase α/ß (p-IKKα/ß), phosphorylated nuclear factor kapa B (p-NFκB), and tumor necrosis factor α (TNFα). Besides, Cal effectively attenuated cardiac fibrosis through the inhibitions of expressions and depositions of collagen I and collagen III. In the in vitro experiments, the phosphatidylinositol three kinase (PI3K) inhibitor LY294002 could abrogate the anti-inflammation and antifibrosis therapeutic effects of Cal, demonstrating that the cardioprotective effects of Cal were mediated through upregulations of PI3K and serine/threonine kinase (AKT). Conclusion: Cal inhibited inflammation and fibrosis via activation of the PI3K-AKT pathway in H9C2 cells, fibroblasts, and heart failure in postacute myocardial infarction rats.

The roles of the mitophagy inducer Danqi pill in heart failure: A new therapeutic target to preserve energy metabolism.

BACKGROUND: Mitophagy can regulate mitochondrial homeostasis, preserve energy metabolism and cardiomyocytes survival effectively to restrain the development of heart failure (HF). Danqi Pill (DQP), composed of the dry roots of Salvia miltiorrhiza Bunge and Panax notoginseng, is included in the 2015 national pharmacopeia and effective in the clinical treatment of coronary heart diseases. Our previous studies have approved that DQP exerted remarkable cardioprotective effects on HF. However, the effect and mechanism of DQP on mitophagy have not been proved yet. HYPOTHESIS/PURPOSE: We aim to explore whether DQP regulates mitophagy to protect against HF and to elucidate the in-depth mechanism. STUDY DESIGN: The HF rat model for evaluating DQP's efficacy was established with left anterior descending coronary artery ligation. The oxygen-glucose deprivation-reperfusion-induced cardiomyocyte model was conducted to clarify the potential mechanism of DQP. METHODS: The mitochondria-targeted fluorescent protein Keima (mt-Keima) was applied for detecting mitophagy flux. Co-immunofluorescence and co-immunoprecipitation were performed to detect protein co-localization. Flow cytometry for JC-1 and Annexin-FITC/PI staining was utilized for assessing mitochondrial activity and function. RESULTS: In vivo, medium dose of DQP (1.5 g/kg) notably improved cardiac function and inhibited cardiac apoptosis in HF rats. Co-immunofluorescent staining of LC3B and TOM20 showed that DQP restored mitophagy. Further co-immunoprecipitation demonstrated that DQP increased the co-localization of FUNDC1 with either ULK1 or PGAM5. In vitro, DQP markedly protected mitochondrial membrane potential damage, reduced cardiomyocytes apoptosis, decreased the level of mitochondrial ROS, and increased the ATP level. Parallel with the in vitro results, DQP increased the interaction of FUNDC1 and LC3B, while knockdown of FUNDC1 diminished the interaction. Besides, Mt-Keima signaling detection further confirmed that DQP significantly promoted mitophagy. Intriguingly, knockdown of ULK1 or PGAM5 separately weakened rather than eliminated these effects of DQP on FUNDC1-mediated mitophagy, mitochondrial homeostasis and energy metabolism. CONCLUSION: Our results demonstrated that DQP protected against HF by improving FUNDC1-mediated mitophagy to perverse energy metabolism through the coordinated regulation of ULK1 and PGAM5.

Mechanistic Insights of Qingre Jiedu Recipe Based on Network Pharmacology Approach against Heart Failure.

Qingre Jiedu (QJ) recipe exerted significant cardioprotective efficacy against heart failure (HF), which is a growing health concern that continues to endanger patients' lives. To investigate the protective properties and mechanism of the QJ recipe, we established hydrogen peroxide (H2O2)-induced H9C2 cells and HF rats. The predicted targets and significant pathways of QJ against HF were collected and screened based on network pharmacology from key ingredients and validated by in vivo and in vitro experiments. The decoction of QJ (0.823 g/kg/day) was intragastrically administered for four weeks. QJ (400 µg/mL) was cultured with H2O2 stimulated in the H9C2 cells. A total of 31 effective active compounds were screened in QJ and covered 277 targets, of which 85 were shared with HF-related targets. In vivo, the QJ recipe remarkably protected heart function and reduced serum IL-1, IL-6, PIIINP, and CIV levels. Furthermore, QJ downregulated the key proteins mediating inflammatory responses (p-IKKα/ß, p-NFκB, and IL-6) and cardiac fibrosis (STAT3 and MMP-9). In vitro, QJ protected the cardiomyocytes against H2O2-stimulated reactive oxygen species (ROS) production and upregulated PI3K and AKT expressions. Further experiments demonstrate that PI3K inhibitor LY294002 remarkably compromised the effects of QJ. In conclusion, our findings indicate that QJ could exert a cardioprotective effect and inhibit fibrosis and inflammation in HF rats via the PI3K-AKT signaling pathway.

Visible-light-promoted trifluoromethylselenolation of ortho-hydroxyarylenaminones.

Development of an efficient process that employs easy to handle and shelf-stable reagents for the synthesis of trifluoromethylselenylated heterocyclics remains a daunting challenge in organic synthesis. Herein, we report a green and practical protocol using trifluoromethyl tolueneselenosulfonate and ortho-hydroxyarylenaminones to access a wide range of chromone derivatives under photocatalyst and oxidant free conditions. This reaction proceeded smoothly under photoirradiation conditions and various functional groups were tolerant of the reaction conditions.

Ginsenoside Rb3 upregulates sarcoplasmic reticulum Ca2+-ATPase expression and improves the contractility of cardiomyocytes by inhibiting the NF-κB pathway.

A causal relationship between ginsenoside Rb3 (G-Rb3) and improved inflammation and cardiac function has not been established. To determine which specific signaling pathways were involved in G-Rb3 improvement of inflammation and myocardial function. In vivo, we found that G-Rb3 decreased the levels of both nuclear factor κB (NF-κB p65) and CD45, an inflammatory marker. G-Rb3 also enhanced key proteins of the contraction unit (cardiac troponin protein I (cTnI) and α-actinin) to improve cardiac function. G-Rb3 inhibited NF-κB p65 nuclear translocation in vitro, as verified by western blot and IF. When NF-κB p65 was overexpressed, a decrease in cyclic nucleotide phosphodiesterase 3B (PDE3B) and SERCA2a expression, while no statistical significance was observed in the expressions of cAMP, PKA, and calcium/calmodulin-dependent protein kinase type II (CaMKⅡ) in each group. The NF-κB p65 plasmid blocked the SERCA2a promoter, as verified by the luciferase reporter system, and G-Rb3 truncated the NF-κB p65 block on the SERCA2a promoter. qPCR was also used to confirm that G-Rb3 increased the mRNA of SERCA2a. In conclusion, we confirmed that the mechanisms of G-Rb3 on ventricular systolic dysfunction causing inflammation are not via the cAMP/PKA pathway, but via suppressing the blockage of NF-κB p65 on the SERCA2a promoter and increasing the SERCA2a expression.

Selective difunctionalization of electron-deficient alkynes: access to (E)-2-iodo-3-(methylthio)acrylate.

A convenient and efficient approach to (E)-2-iodo-3-(methylthio)acrylate has been developed through direct iodothiomethylation of alkynes with aqueous HI and DMSO under mild conditions. This novel protocol has demonstrated a unique difunctionalization of electron-deficient alkynes with a broad substrate scope and excellent functional-group tolerance. Preliminary mechanistic studies indicated that prior diiodination of alkynes, followed by nucleophilic substitution with in situ generated DMS led to the formation of (E)-2-iodo-3-(methylthio)acrylate.

Identification of Potential Bioactive Ingredients and Mechanisms of the Guanxin Suhe Pill on Angina Pectoris by Integrating Network Pharmacology and Molecular Docking.

The Guanxin Suhe pill (GSP), a traditional Chinese medicine, has been widely used to treat angina pectoris (AP) in Chinese clinical practice. However, research on the bioactive ingredients and underlying mechanisms of GSP in AP remains scarce. In this study, a system pharmacology approach integrating gastrointestinal absorption (GA) evaluation, drug-likeness (DL) evaluation, target exploration, protein-protein-interaction analysis, Gene Ontology (GO) enrichment analysis, network construction, and molecular docking was adopted to explore its potential mechanisms. A total of 481 ingredients from five herbs were collected, and 242 were qualified based on GA and DL evaluation. Target exploration identified 107 shared targets between GSP and AP. Protein-protein interaction identified VEGFA (vascular endothelial growth factor A), TNF (tumor necrosis factor), CCL2 (C-C motif chemokine ligand 2), FN1 (fibronectin 1), MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), IL10 (interleukin 10), CXCL8 (C-X-C motif chemokine ligand 8), IL6 (interleukin 6), and INS (insulin) as hub targets for GSP, which were involved in the inflammatory process, ECM proteolysis, glucose metabolism, and lipid metabolism. GO enrichment identified top pathways in the biological processes, molecular functions, and cell components, explaining GSP's potential AP treatment mechanism. Positive regulation of the nitric oxide biosynthetic process and the response to hypoxia ranked highest of the biological processes; core targets that GSP can regulate in these two pathways were PTGS2 and NOS2, respectively. Molecular docking verified the interactions between the core genes in the pathway and the active ingredients. The study lays a foundation for further experimental research and clinical application.

ß-elemene blocks lipid-induced inflammatory pathways via PPARß activation in heart failure.

This study aims to investigate the effects of ß-elemene on a mouse model of heart failure (HF) and to elucidate the underlying mechanisms in vitro approaches. In this study, left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were leveraged to assess the therapeutic effects of ß-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of ß-elemene in lipid-induced inflammation. Results showed that ß-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, ß-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, ß-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-ß (PPARß). In vitro, treatment of ß-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor κB (NF-κB) and the degradation of inhibitory κBα (IκBα) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNFα) in ß-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between ß-elemene and PPARß protein. Furthermore, ß-elemene increased the expression of PPARß, which was validated by antagonist of PPARß and siRNA for PPARß.

TFEB Overexpression, Not mTOR Inhibition, Ameliorates RagCS75Y Cardiomyopathy.

A de novo missense variant in Rag GTPase protein C (RagCS75Y) was recently identified in a syndromic dilated cardiomyopathy (DCM) patient. However, its pathogenicity and the related therapeutic strategy remain unclear. We generated a zebrafish RragcS56Y (corresponding to human RagCS75Y) knock-in (KI) line via TALEN technology. The KI fish manifested cardiomyopathy-like phenotypes and poor survival. Overexpression of RagCS75Y via adenovirus infection also led to increased cell size and fetal gene reprogramming in neonatal rat ventricle cardiomyocytes (NRVCMs), indicating a conserved mechanism. Further characterization identified aberrant mammalian target of rapamycin complex 1 (mTORC1) and transcription factor EB (TFEB) signaling, as well as metabolic abnormalities including dysregulated autophagy. However, mTOR inhibition failed to ameliorate cardiac phenotypes in the RagCS75Y cardiomyopathy models, concomitant with a failure to promote TFEB nuclear translocation. This observation was at least partially explained by increased and mTOR-independent physical interaction between RagCS75Y and TFEB in the cytosol. Importantly, TFEB overexpression resulted in more nuclear TFEB and rescued cardiomyopathy phenotypes. These findings suggest that S75Y is a pathogenic gain-of-function mutation in RagC that leads to cardiomyopathy. A primary pathological step of RagCS75Y cardiomyopathy is defective mTOR-TFEB signaling, which can be corrected by TFEB overexpression, but not mTOR inhibition.

Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3ß-mPTP Pathway In Vitro.

Cardiotoxicity is one of the main side effects of doxorubicin (Dox) treatment. Dox could induce oxidative stress, leading to an opening of the mitochondrial permeability transition pore (mPTP) and apoptosis in cardiomyocytes. Previous studies have shown that Cryptotanshinone (Cts) has potential cardioprotective effects, but its role in Dox-induced cardiotoxicity (DIC) remains unknown. A Dox-stimulated H9C2 cell model was established. The effects of Cts on cell viability, reactive oxygen species (ROS), superoxide ion accumulation, apoptosis and mitochondrial membrane potential (MMP) were evaluated. Expressions of proteins in Akt-GSK-3ß pathway were detected by Western blot. An Akt inhibitor was applied to investigate the effects of Cts on the Akt-GSK-3ß pathway. The effects of Cts on the binding of p-GSK-3ß to ANT and the formation of the ANT-CypD complex were explored by immunoprecipitation assay. The results showed that Cts could increase cell viability, reduce ROS levels, inhibit apoptosis and protect mitochondrial membrane integrity. Cts increased phosphorylated levels of Akt and GSK-3ß. After cells were co-treated with an Akt inhibitor, the effects of Cts were abolished. An immunoprecipitation assay showed that Cts significantly increased GSK-3ß-ANT interaction and attenuated Dox-induced formation of the ANT-CypD complex, thereby inhibiting opening of the mPTP. In conclusion, Cts could ameliorate oxidative stress and apoptosis via the Akt-GSK-3ß-mPTP pathway.

The multi-faceted role of retinoid X receptor in cardiovascular diseases.

Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand.

Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models.

Anthracyclines are highly effective chemotherapeutics for antineoplastic treatment. However, cumulative cardiotoxicity is the main side effect with poor prognosis. No mechanism-based therapy is currently available to reverse chronic anthracycline-induced cardiotoxicity (AIC) after the deterioration of cardiac function. Calycosin (CA) is the main compound extracted from the traditional Chinese medicine Astragalus, and it has diverse beneficial effects, including autophagy modulation, anti-inflammatory and anti-tumor effects. Autophagy dysregulation is an important pathological event in AIC. Our study demonstrated a cardioprotective effect of CA in a zebrafish embryonic AIC model. To assess the effect of CA on late-onset chronic AIC, adult zebrafish were treated with CA 28 days after doxorubicin (DOX) injection, at which point heart function was obviously impaired. The results demonstrated that DOX blocked autophagic activity in adult zebrafish 8 weeks post-injection, and CA treatment improved heart function and restored autophagy. Further in vitro experiments demonstrated that atg7, which encodes an E1-like activating enzyme, may play an essential role in the CA regulation of autophagy. In conclusion, we used a rapid pharmacological screening system in embryo-adult zebrafish in vivo and elucidated the mechanism of gene targeting in vitro.

LINC00152 Promotes Tumor Progression and Predicts Poor Prognosis by Stabilizing BCL6 From Degradation in the Epithelial Ovarian Cancer.

Long non-coding RNA 00152 (LINC00152) is tumorigenic in multiple somatic malignancies. However, its prognostic significance and molecular mechanisms in the epithelial ovarian cancer (EOC) remain elusive. Here our study reveals that dysregulation of LINC00152 is a predictor of poor prognosis in patients with EOC and facilitates ovarian tumor growth and metastasis both in vitro and in vivo; the expression of LINC00152 positively correlates with the protein levels of BCL6 in EOC tissues and ovarian tumor cells; LINC00152 binds to Ser333 and Ser343 of BCL6 protein and stabilizes BCL6 from poly-ubiquitination thus facilitating the oncogenic functions in EOC. Moreover, overexpression of the mutant BCL6S333A/S343A fails to rescue the reduced proliferation and invasion caused by the knockdown of endogenous BCL6 in LINC00152-overexpressing cells. Our study might not only offer clues to the network of lncRNA-protein interactions but also provide potential therapeutic targets for the tumor pharmacology.

Recent advances of 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) in photocatalytic transformations.

1,2,3,5-Tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) is a typical donor-acceptor fluorophore, with carbazolyl as an electron donor and dicyanobenzene as an electron acceptor. It has emerged as a powerful organophotocatalyst since 2016. Excellent redox window, good chemical stability and broad applicability make 4CzIPN an attractive metal-free photocatalyst. In this review, the recent advances of the application of 4CzIPN as a photoredox catalyst in the past three years (2016-2018) for various organic reactions are summarized.

Metal-free difunctionalization of alkynes leading to alkenyl dithiocyanates and alkenyl diselenocyanates at room temperature.

A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.