TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Effect of electroacupuncture on urodynamics and Raf/MEK/ERK signaling pathway in spinal cord tissue of rats with detrusor hyperreflexia after suprasacral spinal cord injury. / ç”µé’ˆå¯¹éª¶ä¸Šè„Šé«“æŸä¼¤åŽé€¼å°¿è‚Œåå°„äº¢è¿›åž‹å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè„Šé«“Raf/MEK/ERK信号通路的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on urodynamics and Raf/MEK/ERK signaling pathway in spine cord tissue of rats after suprasacral spinal cord injury (SSCI), so as to explore its possible mechanism in improving bladder function in rats with detrusor hyperreflexia after SSCI. METHODS: Female SD rats were randomly divided into blank, sham operation, model, EA and EA+PD98059 groups, with 12 rats in each group. Thorax (T) 10 spinal cord transection was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3), "Sanyinjiao" (SP6) and "Dazhui" (GV14) once daily for 7 d. Rats of the EA+PD98059 group received intraperitoneal injection of PD98059 (5 mg/kg) 2 h before EA intervention. The urodyna-mics was used to measure the base pressure, leak point pressure, maximum pressure, maximum capacity and comp-liance of bladder, and the morphology of bladder detrusor tissue was observed with HE staining. The TUNEL staining was used to detect the cell apoptosis of the spinal cord tissue. The expression levels of exchange protein directly activated by cAMP 2 (Epac2), Rap, phosphorylated rapidly accelerated fibrosarcoma (p-Raf), phosphorylated mitogen-activated extracellular signal-regulated kinase (p-MEK), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) were determined by Western blot. RESULTS: Compared with the sham operation group, the base pressure, leak point pressure and maximum pressure of bladder were significantly increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), the cell apoptosis rate of spinal cord tissue was increased (P<0.01), and the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were decreased (P<0.01), while the expression level of Bax protein was increased (P<0.01) in the model group. After the treatment and compared with the model group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate of spinal cord tissue, the expression level of Bax protein were decreased (P<0.05) in the EA group, while the maximum bladder capacity and bladder compliance, the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were all increased (P<0.05, P<0.01). In comparison with the EA group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate, the expression level of Bax protein were significantly increased (P<0.05), whereas the maximum bladder capacity, bladder compliance, and the expression levels of p-MEK, p-ERK1/2, and Bcl-2 protein were decreased (P<0.05) in the EA+PD98059 group. Results of HE staining showed disordered transitional epithelial cells and destroyed lamina propria in bladder detrusor tissue, with the infiltration of monocytes in the model group, which was obviously milder in both EA and EA+PD98059 groups, especially in the EA group. CONCLUSIONS: EA can improve the bladder function in detrusor hyperreflexia rats after SSCI, which may be related to its effect in up-regulating Epac2 and Rap, activating the Raf-MEK-ERK pathway, and reducing the cell apoptosis of spinal cord tissue.

Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown. PURPOSE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI. METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF. RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-ß1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice. CONCLUSION: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

[Effects of moxibustion of "biaoben acupoint combination" on heart rate variability, atrial natriuretic peptide in the model rats of IBS-D complicated with anxiety].

OBJECTIVE: To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination". METHODS: Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence. RESULTS: Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group. CONCLUSION: Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.

[Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo].

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

[Research progress on chemical constituents and pharmacological effects of Ajania plants].

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

Monolithic integration of embedded III-V lasers on SOI.

Silicon photonic integration has gained great success in many application fields owing to the excellent optical device properties and complementary metal-oxide semiconductor (CMOS) compatibility. Realizing monolithic integration of III-V lasers and silicon photonic components on single silicon wafer is recognized as a long-standing obstacle for ultra-dense photonic integration, which can provide considerable economical, energy-efficient and foundry-scalable on-chip light sources, that has not been reported yet. Here, we demonstrate embedded InAs/GaAs quantum dot (QD) lasers directly grown on trenched silicon-on-insulator (SOI) substrate, enabling monolithic integration with butt-coupled silicon waveguides. By utilizing the patterned grating structures inside pre-defined SOI trenches and unique epitaxial method via hybrid molecular beam epitaxy (MBE), high-performance embedded InAs QD lasers with monolithically out-coupled silicon waveguide are achieved on such template. By resolving the epitaxy and fabrication challenges in such monolithic integrated architecture, embedded III-V lasers on SOI with continuous-wave lasing up to 85 °C are obtained. The maximum output power of 6.8 mW can be measured from the end tip of the butt-coupled silicon waveguides, with estimated coupling efficiency of approximately -6.7 dB. The results presented here provide a scalable and low-cost epitaxial method for the realization of on-chip light sources directly coupling to the silicon photonic components for future high-density photonic integration.

[Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology].

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Radix Glycyrrhizae extract and licochalcone a exert an anti-inflammatory action by direct suppression of toll like receptor 4.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Glycyrrhizae (GL), a herbal medicine that is widely available, has shown advantages for a variety of inflammatory diseases. Toll like receptor 4 (TLR4) pathway has been shown to play a key role in the progression of inflammation. AIM OF THE STUDY: The purpose of this study was to investigate the involvement of TLR4 in the anti-inflammatory mechanism of GL extract and its active constituent on acute lung injury (ALI). MATERIALS AND METHODS: A model of inflammation produced by lipopolysaccharide (LPS) was established in C57BL/6 mice and macrophages derived from THP-1. To screen the active components of GL, molecular docking was used. Molecular dynamics and surface plasmon resonance imaging (SPRi) were used to study the interaction of a specific drug with the TLR4-MD2 complex. TLR4 was overexpressed by adenovirus to confirm TLR4 involvement in the anti-inflammatory activities of GL and the chosen chemical. RESULTS: We observed that GL extract significantly reduced both LPS-induced ALI and the production of pro-inflammatory factors including TNF-α, IL-6 and IL-1ß. Additionally, GL inhibited the binding of Alexa 488-labeled LPS (LPS-488) to the membrane of THP-1 derived macrophages. GL drastically reduce on the expression of TLR4 and the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB). Furthermore, molecular docking revealed that Licochalcone A (LicoA) docked into the LPS binding site of TLR4-MD2 complex. MD2-LicoA binding conformation was found to be stable using molecular dynamic simulations. SPRi indicated that LicoA bound to TLR4-MD2 recombinant protein with a KD of 3.87 × 10-7 M. LicoA dose-dependently reduced LPS-488 binding to the cell membrane. LicoA was found to significantly inhibit LPS-induced lung damage and inflammation. Furthermore, LicoA inhibited TLR4 expression, MAPK and NF-κB activation in a dose-dependent manner. The inhibitory effects of GL and LicoA on LPS-induced inflammation and TLR4 signaling activation were partly eliminated by TLR4 overexpression. CONCLUSION: Our findings imply that GL and LicoA exert inhibitory effects on inflammation by targeting the TLR4 directly.

Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2.

Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress-induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress-induced apoptosis in NCMs. Molecular docking revealed that the ALDH2-Calycosin complex had a binding energy of -9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2-Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD  = 1.9 × 10-4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 µM. Pre-incubation with ALDH2 inhibitor (CVT-10216 or disulfiram) reduced the cardio-protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress-induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

Integrative transcriptional characterization of cell cycle checkpoint genes promotes clinical management and precision medicine in bladder carcinoma.

Background: The aberrant regulation of cell cycle is significantly correlated with cancer carcinogenesis and progression, in which cell cycle checkpoints control phase transitions, cell cycle entry, progression, and exit. However, the integrative role of cell cycle checkpoint-related genes (CRGs) in bladder carcinoma (BC) remains unknown. Methods: The transcriptomic data and clinical features of BC patients were downloaded from The Cancer Genome Atlas (TCGA), used to identify CRGs correlated with overall survival (OS) by univariate Cox regression analysis. Then, the multivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses further developed a prognostic CRG signature, which was validated in three external datasets retrieved from Gene Expression Omnibus (GEO). The receiver operating characteristic curve (ROC) analysis was conducted for evaluating the performance of the CRG signature in prognosis prediction. RNA sequencing (RNA-Seq) was performed to explore the expression difference in the identified CRGs between tumor and normal tissue samples from 11 BC patients in the local cohort. Ultimately, genomic profiles and tumor microenvironment (TME), and the Genomics of Drug Sensitivity in Cancer (GDSC) were investigated to guide precision treatment for BC patients with different CRG features. Results: The novel constructed 23-CRG prognostic signature could stratify BC patients into high-risk and low-risk groups with significantly different outcomes (median OS: 13.64 vs. 104.65 months). Notably, 19 CRGs were the first to be identified as being associated with BC progression. In three additional validation datasets (GSE13507, GSE31684, and GSE32548), higher CRG scores all indicated inferior survival, demonstrating the robust ability of the CRG signature in prognosis prediction. Moreover, the CRG signature as an independent prognostic factor had a robust and stable risk stratification for BC patients with different histological or clinical features. Then, a CRG signature-based nomogram with a better performance in prognostic prediction [concordance index (C-index): 0.76] was established. Functional enrichment analysis revealed that collagen-containing extracellular matrix (ECM), and ECM-related and MAPK signaling pathways were significantly associated with the signature. Further analysis showed that low-risk patients were characterized by particularly distinctive prevalence of FGFR3 (17.03% vs. 6.67%, p < 0.01) and POLE alterations (7.97% vs. 2.50%, p < 0.05), and enrichment of immune infiltrated cells (including CD8+ T cells, CD4+ naïve T cells, follicular helper T cells, Tregs, and myeloid dendritic cells). RNA-seq data in our local cohort supported the findings in the differentially expressed genes (DEGs) between tumor and normal tissue samples, and the difference in TME between high-risk and low-risk groups. Additionally, CRG signature score plus FGFR3 status divided BC patients into four molecular subtypes, with distinct prognosis, TME, and transcriptomic profiling of immune checkpoint genes. Of note, CRG signature score plus FGFR3 status could successfully distinguish BC patients who have a higher possibility of response to immunotherapy or chemotherapy drugs. Conclusions: The CRG signature is a potent prognostic model for BC patients, and in combination with FGFR3 alterations, it had more practical capacity in the prediction of chemotherapy and immunotherapy response, helping guide clinical decision-making.

The clinical effectiveness and safety of traditional Chinese medicine Jinfeng pill in adjuvant treatment of infertility with polycystic ovary syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the main cause of infertility in women, the essence of which is an endocrine disorder syndrome with abnormal sugar metabolism and reproductive dysfunction, and the incidence rate of about 6% of women. Traditional Chinese medicine (TCM) Jinfeng pill has achieved very good clinical results in the treatment of infertility with PCOS, but there is currently a lack of strong evidence-based medical evidence. This study uses meta-analysis method to analyze the clinical effectiveness and safety of TCM Jinfeng pill in the treatment of infertility with PCOS, hoping to provide help for the clinical treatment of infertility with PCOS. METHODS: Using the computer to retrieve SinoMed, CNKI, VIP, WANFANG Database, as well as Public, The Cochrane library, Medline (Ovid SP), Embase and other foreign language databases, while manually retrieving the relevant magazine supplements, special issues, professional materials, network information, and so on. The retrieval time is from the beginning of each database to June 2021. The selected literature is evaluated using the Cochrane System Rating Manual Bias Risk Tool. Statistical analysis and graphics of the inclusion literature are performed using Review Manager 5.3 statistical software. RESULTS: All the results of this study on the clinical effectiveness and safety of TCM Jinfeng pill in adjuvant treatment of infertility with PCOS will be published in a peer-reviewed academic journal of medicine. ETHICS AND DISSEMINATION: The type of study is systematic evaluation, the whole process of research does not involve human trials, the data used in the institute are obtained through published literature, so ethical review is not suitable for this study. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JEP2D. (https://osf.io/jep2d). CONCLUSION: Our research will provide evidence-based medical evidence on whether the TCM Jinfeng pill is effective and safe in the treatment of infertility with PCOS.

Dihydrotanshinone I inhibits the growth of hepatoma cells by direct inhibition of Src.

BACKGROUND: Liver cancer is one of the leading causes of cancer-related death worldwide. Dihydrotanshinone I (DHI) was shown to inhibit the growth of several types of cancer. However, research related to hepatoma treatment using DHI is limited. PURPOSE: Here, we explored the inhibitory effect of DHI on the growth of hepatoma cells, and investigated the underlying molecular mechanisms. METHODS: The proliferation of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells was evaluated using the MTS and Edu staining assay. Hepatoma cell death was analyzed with a LIVE/DEAD Cell Imaging Kit. The relative expression and phosphorylation of proto-oncogene tyrosine-protein kinase Src (Src) and signal transducer and activator of transcription-3 (STAT3) proteins in hepatoma cells, as well as the expression of other protein components, were measured by western blotting. The structural interaction of DHI with Src proteins was evaluated by molecular docking, molecular dynamics simulation, surface plasmon resonance imaging and Src kinase inhibition assay. Src overexpression was achieved by infection with an adenovirus vector encoding human Src. Subsequently, the effects of DHI on tumor growth inhibition were further validated using mouse xenograft models of hepatoma. RESULTS: In vitro studies showed that treatment with DHI inhibited the proliferation and promoted cell death of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells. We further identified and verified Src as a direct target of DHI by using molecular stimulation, surface plasmon resonance image and Src kinase inhibition assay. Treatment with DHI reduced the in vitro phosphorylation levels of Src and STAT3, a transcription factor regulated by Src. In the xenograft mouse models, DHI dose-dependently suppressed tumor growth and Src and STAT3 phosphorylation. Moreover, Src overexpression partly abrogated the inhibitory effects of DHI on the proliferation and cell death in hepatoma cells. CONCLUSION: Our results suggest that DHI inhibits the growth of hepatoma cells by direct inhibition of Src.

[Research progress on chemical constituents and pharmacological studies on root bark of Lycium barbarum].

Lycii Cortex, the dry root bark of Lycium barbarum(Solanaceae), is rich in chemical compositions with unique structures, such as organic acids, lipids, alkaloids, cyclopeptides and other components, and plays an important role in traditional Chinese medicine. It has the effect of cooling blood and removing steam, clearing lung and reducing fire. It is mainly used in the treatment of hot flashes due to Yin deficiency, hectic fever with night sweat, cough, hemoptysis and internal heat and diabetes. Modern pharmacological studies have shown that the crude extract or monomer of Lycii Cortex has a variety of pharmacological activities, such as hypoglycemic, hypotensive, hypolipidemic, antibacterial, and antiviral effects. In this paper, the chemical constituents and pharmacological effects of Cortex Lycii were reviewed in order to further clarify its effective substances, promote the development of medical undertakings, and ensure the "Healthy China" plan.

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

[A new 9,19-cycloartane glycoside from Asplenium ruprechtii].

Chemical constituents of water extracts of Asplenium ruprechtii were investigated. Five compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC, and their structures were identified by various spectral analyses as aspleniumside G(1), trans-p-coumaric acid(2), trans-p-coumaric acid 4-O-ß-D-glucoside(3), cis-p-coumaric acid 4-O-ß-D-glucoside(4), and(E)-ferulic acid-4-O-ß-D-glucoside(5). Among them, compound 1 is a new 9,19-cycloartane glycoside.

[Suitable planting area of Poria cocos in Jinzhai county of Dabie Mountains region].

Dabie Mountain in Anhui province is a genuine producing area of Poria cocos, commonly known as Anling. Jinzhai county in Anhui province is a traditional producing area of P. cocos, and it is also a key county for poverty alleviation in Dabie Mountains. Poverty alleviation of traditional Chinese medicine producing area is an important measure to implement the major strategic deployment of the central government. The planting of P. cocos is helpful to promote the development of traditional Chinese medicine industry in Dabie Mountains and help poverty alleviation. P. cocos is a saprophytic fungus with special demands on soil and ecological environment, and its planting appears a scattered and irregular distribution. Traditional investigation methods are time-consuming and laborious, and the results are greatly influenced by subjective factors. In order to obtain the suitable planting area of P. cocos in Jinzhai county, according to the field survey, the research team has explored the regional, biological characteristics and cultivation methods of P. cocos in the county, and obtained the altitude distribution area suitable for the growth of P. cocos. Then, the MaxEnt niche model was used to analyze the relationship between ecological factors and distribution areas, and the potential distribution zoning of P. cocos in Jinzhai county was studied. Combined with the characteristics of P. cocos planting pattern, taking ZY-3 remote sensing image as the data source, the maximum likelihood method was used to extract the area that could be used for P. cocos cultivation in Jinzhai county, and the reason why artificial planting P. cocos was mainly distributed in the west of Jinzhai county was analyzed. The suitable regional classification of P. cocos in Jinzhai county was obtained by superposition of suitable altitude distribution area, MaxEnt analysis and area extracted from remote sensing image, which provided data support for the planting planning of P. cocos in Jinzhai county.

HPLC coupled with quadrupole time of flight tandem mass spectrometry for analysis of glycosylated components from the fresh flowers of two congeneric species: Robinia hispida L. and Robinia pseudoacacia L.

Developing methods for the systematic and rapid identification of the chemical compositions of fresh plant tissues has long attracted the attention of phytochemists and pharmacologists. In the present study, based on highly efficient sample pretreatment and high-throughput analysis of high-performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry data using molecular networks, a method was developed for systematically analyzing the chemical constituents of the fresh flowers of Robinia hispida L. and Robina pseudoacacia L., two congeneric ornamental species that lack prior consideration. A total of 44 glycosylated structures were characterized. And on the basis of establishing of the fragmentation pathways of 11 known flavonoid glycosides, together with the molecular networking analysis, 18 other ions of flavonoid glycosides in five classes were clustered. Moreover, 15 soyasaponins/triterpenoid glycosides were tentatively identified by comparison of their tandem mass spectrometry characteristic ions with those reported in the literature or the online Global Natural Product Social Molecular Networking database. The water extracts were separated by flash chromatography, which resulted in the discovery of one new compound, named rohispidascopolin, along with five known entities. The pharmacological targets were predicted by SwissTargetPrediction.

Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways / 药学学报

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.

Research progress on chemical constituents and pharmacological studies on root bark of Lycium barbarum / 中国中药杂志

Lycii Cortex, the dry root bark of Lycium barbarum(Solanaceae), is rich in chemical compositions with unique structures, such as organic acids, lipids, alkaloids, cyclopeptides and other components, and plays an important role in traditional Chinese medicine. It has the effect of cooling blood and removing steam, clearing lung and reducing fire. It is mainly used in the treatment of hot flashes due to Yin deficiency, hectic fever with night sweat, cough, hemoptysis and internal heat and diabetes. Modern pharmacological studies have shown that the crude extract or monomer of Lycii Cortex has a variety of pharmacological activities, such as hypoglycemic, hypotensive, hypolipidemic, antibacterial, and antiviral effects. In this paper, the chemical constituents and pharmacological effects of Cortex Lycii were reviewed in order to further clarify its effective substances, promote the development of medical undertakings, and ensure the "Healthy China" plan.