Risk Factors of Hidden Blood Loss in Unilateral Biportal Endoscopic Surgery for Patients with Lumbar Spinal Stenosis.

OBJECTIVE: Unilateral biportal endoscopic (UBE) surgery has recently been used as a minimally invasive procedure for the treatment of lumbar spinal stenosis and is associated with less perioperative blood loss. However, perioperative hidden blood loss (HBL) may be neglected during UBE. This study aimed to examine the volume of HBL and discuss the influential risk factors for HBL during unilateral biportal endoscopic surgery. METHODS: From January 2022 to August 2022, 51 patients underwent percutaneous unilateral biportal endoscopic surgery for lumbar spinal stenosis at the Department of Spinal Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and were enrolled in this study. The data included general indicators (age, sex and body mass index [BMI]), underlying disease (hypertension and diabetes), laboratory test results (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [Fbg]), and preoperative and postoperative hematocrit and hemoglobin), related imaging parameters (severity of intervertebral disc [IVD] degeneration and soft tissue thickness of the interlaminar approach), number of operated vertebrae and operation time. Total blood loss (TBL) and HBL during surgical procedures were measured via the Gross formula. Influential factors were further analyzed by multivariate linear regression analysis and t-tests. RESULTS: The mean HBL was 257.89 ± 190.66 mL for single-operation patients and 296.58 ± 269.75 mL for two-operation patients. Patients with lower PT (p = 0.044), deeper tissue thickness (p = 0.047), and diabetes mellitus were determined to have more HBL during UBE. The operation time might also be an important factor (p = 0.047). However, sex (p = 0.265), age (p = 0.771/0.624), BMI (p = 0.655/0.664), APTT (p = 0.545/0.751), degree of degenerated IVD (p = 0.932/0.477), and hypertension (p = 0.356/0.896) were not related to HBL. CONCLUSION: This study determined the different influential factors of HBL during UBE. PT, tissue thickness, and diabetes mellitus are the independent risk factors that affect HBL incidence. Long PT may decrease the volume of HBL within a certain range. Tissue thickness and diabetes mellitus can lead to an increased volume of HBL.

Effect of omega-3 fatty acids supplementation on the prognosis of coronary artery disease: A meta-analysis of randomized controlled trials.

AIMS: To evaluate whether omega-3 fatty acids (É·-3 FAs) supplementation can improve cardiovascular outcomes in patients with established coronary artery disease (CAD). DATA SYNTHESIS: Five electronic databases were searched for randomized controlled trials that evaluated the effect of É·-3 FAs on cardiovascular outcomes in patients with CAD. The language was restricted to English. The risk ratio was pooled. Subgroup analyses were conducted to evaluate whether study-level variables might act as effect modifiers. A total of 12 studies involving 29913 patients were included. É·-3 FAs had no effects on major adverse cardiovascular events (MACEs) (RR, 0.93; 95 % CI: 0.85 to 1.01, P = 0.09). While É·-3 FAs reduced the incidences of all-cause death (RR, 0.90; 95 % CI: 0.83 to 0.97, P = 0.005), cardiovascular death (RR, 0.82; 95 % CI: 0.75 to 0.90, P < 0.0001), myocardial infarction (RR, 0.77; 95 % CI: 0.68 to 0.86, P < 0.0001), revascularization (RR, 0.80; 95 % CI: 0.69 to 0.93, P = 0.003), sudden cardiac death (RR, 0.67; 95 % CI: 0.52 to 0.86, P = 0.002) and hospitalization for heart failure or unstable angina pectoris (RR, 0.75; 95 % CI: 0.58 to 0.97, P = 0.03) in CAD. It did not statistically reduce the risk of stroke (RR, 0.96; 95 % CI: 0.77 to 1.21, P = 0.76). The favorable effects of É·-3 FAs on MACEs were significant in subgroups of intervention with EPA and baseline triglyceride ≥1.7 mmol/L. CONCLUSION: É·-3 FAs supplementation, especially EPA, appears to be an effective adjunct therapy for improving the prognosis of CAD. REGISTRATION NUMBER: PROSPERO CRD42022311237.

Self-Report Amphiphilic Polymer-Based Drug Delivery System with ROS-Triggered Drug Release for Osteoarthritis Therapy.

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 µg mL-1 CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.

Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy.

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.

Exploration of the effect and mechanism of Scutellaria barbata D. Don in the treatment of ovarian cancer based on network pharmacology and in vitro experimental verification.

The mortality rate of ovarian cancer is the highest among gynecological cancers, posing a serious threat to women health and life. Scutellaria barbata D. Don (SBD) can effectively treat ovarian cancer. However, its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of SBD in the treatment of ovarian cancer using network pharmacology, and to verify the experimental results using human ovarian cancer SKOV3 cells. The Herb and Disease Gene databases were searched to identify common targets of SBD and ovarian cancer. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind SBD. Finally, the molecular docking and main possible pathways were verified by experimental studies. Cell proliferation, the mRNA expression level of key genes and signaling pathway were all investigated and evaluated in vitro. A total of 29 bioactive ingredients and 137 common targets in SBD were found to inhibit ovarian cancer development. The active ingredients identified include quercetin, luteolin, and wogonin. Analysis of the PPI network showed that AKT1, VEGFA, JUN, TNF, and Caspase-3 shared centrality among all target genes. The results of the KEGG pathway analysis indicated that the cancer pathway, PI3K-Akt signaling pathway, and MAPK signaling pathways mediated the effects of SBD against ovarian cancer progression. Cell experiments showed that quercetin, luteolin, and wogonin inhibited the proliferation and clone formation of SKOV3 cells and regulated mRNA expression of 5 key genes by inhibiting PI3K/Akt signaling pathway. Our results demonstrate that SBD exerted anti-ovarian cancer effects through its key components quercetin, luteolin and wogonin. Mechanistically, its anti-cancer effects were mediated by inhibition of the PI3K/Akt signaling pathways. Therefore, SBD might be a candidate drug for ovarian cancer treatment.

Efficacy and safety of Qixue Tongzhi Granule in improving the exercise capacity of stable coronary artery disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Background: Despite optimal medical therapy, patients with stable coronary artery disease (SCAD) still have a high risk of recurrent cardiovascular events. Exercise capacity measured by cardiopulmonary exercise testing (CPET) is a good surrogate marker for the long-term prognosis of SCAD. Qixue Tongzhi Granule (QTG) is created by academician Chen Keji and has the function of tonifying qi, promoting blood circulation, and regulating qi-flowing. This trial aims to investigate the efficacy and safety of QTG in improving exercise tolerance, alleviating angina pectoris and anxiety/depression symptoms, promoting health-related quality of life, and reducing the risk of adverse cardiovascular events in subjects with SCAD. Methods: This is a randomized, double-blind, placebo-controlled trial. 150 SCAD patients with qi deficiency, blood stasis, and liver qi stagnation syndrome are enrolled. Patients will be randomly allocated to the QTG or placebo groups at a 1:1 ratio. QTG and placebo will be added to the modern guideline-directed medical therapy for 12 weeks and patients will be followed up for another 24 weeks. The primary outcome is the improvement of metabolic equivalents measured by CPET. The secondary outcomes are cumulative incidence of composite endpoint events, other indicators in CPET, changes in the Seattle Angina Questionnaire, traditional Chinese medicine syndrome scale, 12 items of Short Form Health Survey Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, changes of ST-T segment in the electrocardiogram, improvement of left ventricular ejection fraction and left ventricular end-diastolic diameter in echocardiography. In addition, metabolomics analysis will be performed based on blood samples. Adverse events and safety evaluations will also be documented. A full analysis set, per protocol set, and safety analysis set will be conducted. Discussion: This clinical trial can enrich treatment options for CHD patients with low cardiorespiratory fitness and psychological imbalance, and it may also create a new situation for promoting the application of traditional Chinese medicine in cardiac rehabilitation.Clinical Trial Registration: [http://www.chictr.org.cn], identifier: [ChiCTR2200058988].

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

The miR-33a-5p/CROT axis mediates ovarian cancer cell behaviors and chemoresistance via the regulation of the TGF-ß signal pathway.

Due to the lack of symptoms and detection biomarkers at the early stage, most patients with ovarian cancer (OC) are diagnosed at an advanced stage and often face chemoresistance and relapse. Hence, defining detection biomarkers and mechanisms of chemoresistance is imperative. A previous report of a cDNA microarray analysis shows a potential association of carnitine O-octanoyltransferase (CROT) with taxane resistance but the biological function of CROT in OC remains unknown. The current study explored the function and regulatory mechanism of CROT on cellular behavior and paclitaxel (PTX)-resistance in OC. We found that CROT was downregulated in OC tissues and PTX-resistant cells. Furthermore, CROT expression was negatively correlated with the prognosis of OC patients. Overexpression of CROT inhibited the OC cell proliferation, migration, invasion, and colony formation, arrested the cell cycle at the G2/M phase, and promoted cell apoptosis. In addition, miR-33a-5p bound directly to the 3'UTR of CROT to negatively regulate the expression of CROT and promoted OC cell growth. Finally, overexpression of CROT decreased the phosphorylation of Smad2, whereas knockdown of CROT increased the nuclear translocation of Smad2 and Smad4, two transducer proteins of TGF-ß signaling, indicating that CROT is a tumor suppressor which mediates OC cell behaviors through the TGF-ß signaling pathway. Thus, targeting the miR-33a-5p/CROT axis may have clinical potential for the treatment of patients with OC.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model.

OBJECTIVE: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish. METHODS: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 µmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio. RESULTS: According to the Chinese Pharmacopoeia (2015), ß-ecdysone (ß-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of ß-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 µmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 µmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and ß-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1. CONCLUSION: RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Astaxanthin alleviates inflammatory pain by regulating the p38 mitogen-activated protein kinase and nuclear factor-erythroid factor 2-related factor/heme oxygenase-1 pathways in mice.

Inflammatory pain is a complex process that has a substantial negative impact on post-injury quality of life. Astaxanthin (AST), which is a lipid-soluble red-orange carotenoid that is found in lobsters, inhibits the development and maintenance of inflammation in mice via its antioxidant and anti-inflammatory activities. However, the specific mechanisms underlying these effects remain unclear. In this study, we aimed to elucidate the mechanism by which astaxanthin alleviated inflammation using a mouse model with Complete Freund's adjuvant (CFA)-induced inflammatory pain. Mechanical allodynia and thermal hyperalgesia were observed on days 1-14 post CFA injection. Expression of p38 mitogen-activated protein kinase (MAPK) in the left paw and L4-6 dorsal root ganglia (DRG) were upregulated in the CFA-induced mice. Expression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were also increased. Astaxanthin relieved mechanical allodynia and thermal hyperalgesia induced by CFA and inhibited the inflammatory response (e.g., infiltration of inflammatory cells and production of inflammatory factors) in the ipsilateral paw and DRG. Additionally, AST  inhibited p38 MAPK and enhanced Nrf2/HO-1 contents in the left paw and DRG, and reversed the pain induced by p38 MAPK agonist and Nrf2 inhibitors. These findings suggest that AST exerts anti-inflammatory effects and regulates p38 MAPK and Nrf2/HO-1 to alleviate inflammatory pain. AST may be a potential therapeutic agent for relieving inflammation.

Effects of Reducing the South and Reinforcing the North Method on Inflammatory Injury Induced by Hyperlipidemia.

Inflammation is the pathophysiological basis of hyperlipidemia-related disease (HRD). Reducing the south and reinforcing the north method (RSRN) has a positive effect on HRD. However, the pharmacological mechanisms of RSRN are still unclear in the treatment of HRD. We obtained RSRN compounds from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and identified potential targets of these compounds through target fishing based on the TCMSP databases. Next, we identified the HRD targets by using multiple databases. Then, the overlapping genes between the RSRN potential targets and the HRD targets were used to establish a protein-protein interaction (PPI) network, and we further analyzed their interactions and identified the major hub genes in this network. Subsequently, the Metascape database was utilized to conduct the enrichment of Gene Ontology biological processes (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. A total of 187 potential active components and 106 related core targets were obtained and identified overall. Then after the Metascape enrichment analysis, a total of 148 KEGG pathways were screened, which were mainly associated with AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Furthermore, 34 hub genes, such as AKT1, NF-κBp65(RELA), IκBα(CHUK), MAPK8, and MAPK14, CCND1, were considered potential therapeutic targets. Furthermore, evaluations of protein levels of NF-κBp65, IκBα, TNF-α, IL-1 ß, and IL-6 were performed for experimental validation. RSRN can reduce the expression of NF-κBp65 protein, increase the level of IκBα protein, and reduce the protein levels of TNF-α, IL-1ß, and IL-6 in ovariectomized rats. The results indicate that the mechanism of RSRN against inflammation may be related to AKT1, NF-κBp65, IκBα, MAPK8, and MAPK14, as well as TNF, NF-kappa B, PI3K-Akt signaling pathways.

Application Progress and Prospect of Herbal and Western Medicine Combined with Antiplatelet Therapy for Cardiovascular Events.

Antiplatelet therapy is the key point in the treatment of cardiovascular and cerebrovascular diseases. Effective and safe antiplatelet therapy can avoid the risk of thrombosis or bleeding again. Herbal and Western medicine combined with antiplatelet therapy for ischemic cardiovascular events is a common phenomenon in clinical application, and more and more animal experiments, in vitro cell experiments, and randomized controlled clinical studies have also clarified the efficacy and interaction mechanism of the combination and safety. Herbal and Western medicine combined with antiplatelet therapy has made some progress in improving aspirin resistance and clopidogrel resistance, enhancing antiplatelet and antithrombotic effect, and reducing gastrointestinal adverse reactions caused by antiplatelet drugs. Both of them play the role of antiplatelet and antithrombotic by reducing platelet adhesion, inhibiting platelet activation and aggregation, and inhibiting platelet release, and the combination of drugs is safe. This article elaborates and analyzes the application progress and prospect of Chinese and Western medicine combined with antiplatelet therapy, in order to provide more theoretical support for future research.

Comparative Analysis of Compatibility Influence on Invigorating Blood Circulation for Combined Use of Panax Notoginseng Saponins and Aspirin Using Metabolomics Approach.

The combined use of Panax notoginseng saponins (PNS)-based drugs and aspirin (ASA) to combat vascular diseases has achieved good clinical results. In this study, the superior efficacy was observed via the combined use of PNS and ASA on acute blood stasis rats, and untargeted metabolomics was performed to holistically investigate the therapeutic effects of coupling application and its regulatory mechanisms. The combined use of PNS and ASA exhibited better improvement effects when reducing the evaluated hemorheological indicators (whole blood viscosity, plasma viscosity, platelet aggregation, and fibrinogen content) in the blood stasis rats vs. single use of PNS or ASA at the same dose. The combined use of both drugs was the most effective application method, as shown by the relative distance in partial least-squares discriminant analysis score plots. Twelve metabolites associated with blood stasis were screened as potential biomarkers and were mainly involved in amino acid metabolism, lipid metabolism, and energy metabolism. After coherently treated with PNS and ASA, the altered metabolites could be partially adjusted to be closer to normal levels than single use. The collective results revealed that PNS could cooperate with ASA to treat blood stasis and provided a scientific explanation for the superior efficacy of their combined use.

Acupuncture Treatment for Cough-Variant Asthma: A Meta-Analysis.

BACKGROUND: In recent years, there have been many clinical reports on acupuncture treatment of cough-variant asthma, but no researcher has objectively analysed and evaluated the efficacy and safety of acupuncture treatment of cough-variant asthma from the perspective of evidence-based medicine. OBJECTIVE: To systematically evaluate the clinical efficacy and safety of acupuncture in treating cough-variant asthma and to provide reference values for clinical decision-making. METHODS: The comprehensive computer retrieval Chinese journal full-text database (CNKI), Chinese science and technology periodical database (VIP), ten thousand data knowledge service platform (WanFang Data), PubMed, Embase, and the Cochrane Library were used to collect literature for relevant randomized controlled trials (RCT) of acupuncture treatment of cough-variant asthma, as well as to retrieve papers and add reference retrieval after literature review, in accordance with the standard of literature filtering, data extraction, and quality evaluation. The data were meta-analysed using ReviewManager5.3 software recommended by Cochrane. RESULTS: A total of 11 randomized controlled clinical studies were screened and included, comprising 929 patients. The results of the meta-analysis showed that, compared with the control group, acupuncture intervention on CVA could enhance the total clinical effectiveness rate, reduce the relapse rate of drug withdrawal, relieve symptoms of cough, phlegm, and diaphragmatic congestion, and improve lung function-related indicators and immune inflammation indicators. There were statistically significant differences in all efficacy evaluation criteria. CONCLUSION: The clinical curative effect of acupuncture treatment for cough-variant asthma is precise and has certain advantages in relieving symptoms and reducing the recurrence rate. However, the low quality of the evaluation in the RCT research literature is a problem, and more high-quality clinical randomized controlled trials are needed to further verify the comprehensive clinical efficacy and safety of this treatment. Registration number: PROSPERO (no. CRD42020155244) (https://www.crd.york.ac.uk/prospero/).

Panax quinquefolium saponin Optimizes Energy Homeostasis by Modulating AMPK-Activated Metabolic Pathways in Hypoxia-Reperfusion Induced Cardiomyocytes.

OBJECTIVE: To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS: The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS: PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION: PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.

Antidepressant-like effects of albiflorin involved the NO signaling pathway in rats model of chronic restraint stress.

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE) and dopamine (DA) in the hippocampus and increased the level of brain-derived neurotrophic factor (BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal (HPA) cascade, reduced the level of NO and cGMP in serum and inhibited the overexpression of 5-HT2AR mRNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors. These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.

Uncovering the pharmacological mechanism of motherwort (Leonurus japonicus Houtt.) for treating menstrual disorders: A systems pharmacology approach.

Leonurus japonicus (motherwort) is a traditional Chinese medicine that is widely used to treat menstrual disorders (MDs). However, the pharmacological mechanisms that underlie its clinical application remain unclear. In this study, a network pharmacology-based approach was used that integrated drug-likeness evaluation, oral bioavailability prediction, target exploration, network construction, bioinformatic annotation and molecular docking to investigate the mechanisms that underlie motherwort treatment for MDs. In total, 29 bioactive compounds were collected from 51 compounds in motherwort, which shared 17 common MDs-related targets. Network analysis indicated that motherwort played a therapeutic role in MDs treatment through multiple components that acted on multiple targets. Pathway enrichment analysis showed that the putative targets of motherwort were primarily involved in various pathways associated with the endocrine system, cancers, vascular system, and anti-inflammation process. Notably, five targets (i.e., AKT1, PTGS2, ESR1, AR and PPARG) were screened as hub genes based on a degree algorithm. Moreover, most of the bioactive components in motherwort had good binding ability with these genes, implying that motherwort could regulate their biological function. Collectively, this study elucidated the molecular mechanisms that underlay the efficiency of motherwort against MDs and demonstrated the potential of network pharmacology as an approach to uncover the action mechanism of herbal medicines.

TrMYB4 transcription factor regulates the rutin biosynthesis in hairy roots of F. cymosum.

Fagopyrum cymosum has been considered as a traditional medicinal plant that belongs to Fagopyrum, which has exhibited great pharmaceutical potential due to its abundant flavonoid accumulation. The hairy roots induced by Agrobacterium rhizogenes has been utilized to produce valuable specialized metabolites or reveals plant metabolic processes, whereas the underlying regulatory networks of flavonoid biosynthesis in hairy roots of F. cymosum remained unexplored. Here, the regulatory transcription factor TrMYB4 cloned from Trifolium repens with purple striped leaves was considered to investigate the mechanism of flavonoids biosynthesis in hairy roots of F. cymosum. Results showed that the expression of key genes involved in rutin biosynthesis pathway from TrMYB4 hairy roots were significantly up-regulated compared with non-transgenic hairy roots, while the content of total flavonoids and rutin in TrMYB4 hairy roots also increased consistently. It revealed the TrMYB4 transcription factor could regulate the rutin biosynthesis in F. cymosum. Meanwhile, our research provided a theoretical reference for the industrial production of rutin using F. cymosum hairy roots.

The efficacy of Chinese herbal medicines on acute coronary syndrome with renal insufficiency after percutaneous coronary intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Chuanxiong capsule consists of Angelica sinensis radix and Chuanxiong rhizome, which are used in the traditional Chinese medicine for the treatment of coronary artery disease, and Xinyue capsule is composed of panax quinquefolius saponin extracted from leaves and stems of Panax quinquefolium L, which has the functions of anti-myocardial ischemia, improving myocardial energy metabolism and inhibiting apoptosis of cardiomyocytes. OBJECTIVE: To observe the role of Chinese herbal medicines in the cardiovascular outcome among patients with acute coronary syndrome (ACS) and renal insufficiency after percutaneous coronary intervention (PCI). METHODS: The subjects came from the 5C trial (chictr.org number: chictr-trc-07000021), post-PCI patients suffered from ACS with mild-to-moderate renal insufficiency (30 mL•min-1•1.73 m-2 < estimated glomerular filtration rate≤89 mL•min-1•1.73 m-2) included. The study population consisted of 215 subjects in the control group who were treated with western medicine standard therapy, and 211 subjects in the treatment group who were treated with Chinese herbal medicines (Fufang Chuanxiong Capsule and Xinyue Capsule) for 6 months on the basis of western medicine standard therapy. All were followed for 1 year. The primary endpoint included the composite of cardiac death, nonfatal recurrent myocardial infarction, and ischemia-driven revascularization. Secondary endpoint included the composite of stroke, congestive heart failure, and readmission for ACS. The serum creatinine and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After 1 year follow-up of two groups, there were 16 cases of primary endpoint in the control group and 6 cases of primary endpoint in the treatment group [absolute risk reduction (ARR): 0.046, 95%CI: 0.004-0.088; relative risk (RR): 0.38, 95%CI: 0.15-0.96, P = 0.040]. There were 15 cases of secondary endpoint in the control group and 5 cases of secondary endpoint in the treatment (ARR: 0.041, 95%CI: 0.006-0.086; RR: 0.34, 95%CI: 0.13-0.92, P = 0.033). The eGFR in the treatment group was significantly higher than that in the control group (75.19 ±â€¯16.74 mL min-1·1.73 m-2 VS 72.03 ±â€¯14.96 mL min-1·1.73 m-2, P < 0.05). The eGFR in the treatment group was significantly higher after the intervention with Chinese herbal medicines than that before intervention (72.27 ±â€¯11.83 mL min-1·1.73 m-2 VS 75.19 ±â€¯16.74 mL min-1·1.73 m-2, P < 0.05). CONCLUSION: Chinese herbal medicines plus western medicine standard therapy improved clinical outcomes in patients with ACS and mild-to-moderate renal insufficiency. Additionally, this study also demonstrated Chinese herbal medicines were useful in deferring decline of renal function.