Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Biocompatible N-carbazoleacetic acid decorated CuxO nanoparticles as self-cascading platforms for synergistic single near-infrared triggered phototherapy treating microbial infections.

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.

Gualou xiebai decoction ameliorates cardiorenal syndrome type II by regulation of PI3K/AKT/NF-κB signalling pathway.

BACKGROUND: Cardiorenal syndromes type II (CRS2) is a multi-organ ailment that manifests as a combination of cardiac and renal dysfunction, resulting in chronic kidney disease due to chronic cardiac insufficiency. It affects at least 26 million people worldwide, and its prevalence is increasing. Gualou Xiebai Decoction (GXD), a traditional Chinese medicine (TCM) with a rich history of application in the management of coronary artery disease, has been explored for its potential therapeutic benefits in CRS2. Nevertheless, the mechanism by which GXD alleviates CRS2 remains obscure, necessitating further investigation. PURPOSE: The aim of this study was to assess the effects of the ethanolic extract of GXD on CRS2 and to elucidate the underlying mechanism in a rat model of myocardial infarction, offering a potential target for clinical treatment for CRS2. STUDY DESIGN AND METHODS: A rat model of CRS2 was induced by surgical myocardial infarction and treated with GXD for 10 weeks. Cardiac function was assessed using echocardiography, while serum and urine biochemistry were analyzed to evaluate potential cardiac and renal damage. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active compounds, potential therapeutic targets, and interventional pathways through which GXD could potentially exert its effects on CRS2. Subsequently, these predictions were confirmed in vivo and vitro through various analyses. RESULTS: The current investigation employed echocardiography to exhibit the apparent cardiac remodeling following the induction of myocardial infarction. Damage to the heart and kidneys of CRS2 rats was effectively ameliorated by administration of GXD. The outcomes derived from the analyses of HE and Masson staining indicated that the pathological damage to the heart and kidney tissues of rats in the GXD groups was considerably alleviated. Using network pharmacology analysis, AKT1, IL-6, and TNF-α were identified as plausible therapeutic targets for the treatment of CRS with GXD. Subsequent functional and pathway enrichment analysis of the underlying targets disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the mechanism of GXD in the treatment of CRS2. Immunohistochemical, western blot, RT-PCR and immunofluorescence staining were employed to demonstrate that GXD can regulate the PI3K/AKT/NF-κB signaling pathway in the CRS2 rat model. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the effect of diosmetin, which was one of the potential active components of GXD analysed by compound-target-disease network, on p-PI3K and p-AKT in vitro. CONCLUSIONS: The findings of this study suggest that GXD improves cardiac and renal function in CRS2 rats and that the underlying mechanism involves inhibition of the PI3K/AKT/NF-κB pathway.

Insights into the metabolite profiles of Rubus chingii Hu at different developmental stages of fruit.

The fruits of Rubus chingii Hu have high medicinal and nutritional values. However, the metabolite profiles of R. chingii, especially the alterations during different development stages of fruit, have not been comprehensively analyzed, hindering the effective utilization of the unique species. In this study, we comprehensively analyzed the metabolites of R. chingii fruit at four developmental stages using systematic untargeted and targeted liquid chromatography-mass spectrometry metabolomics analysis and identified 682 metabolites. Significant changes were observed in metabolite accumulation and composition in fruits during the different developmental stages. The contents of the index components, kaempferol-3-O-rutinoside and ellagic acid, were the highest in immature fruit. The analysis identified 64 differentially expressed flavonoids and 39 differentially expressed phenolic acids; the accumulation of most of these differentially expressed metabolites decreased with the developmental stages of fruit from immaturity to maturity. These results confirmed that the developmental stages of fruit are a critical factor in determining its secondary metabolite compositions. This study elucidated the metabolic profile of R. chingii fruit at different stages of development to understand the dynamic changes in metabolites.

Cuprous oxide-demethyleneberberine nanospheres for single near-infrared light-triggered photoresponsive-enhanced enzymatic synergistic antibacterial therapy.

In this work, novel cuprous oxide-demethyleneberberine (Cu2O-DMB) nanomaterials are successfully synthesized for photoresponsive-enhanced enzymatic synergistic antibacterial therapy under near-infrared (NIR) irradiation (808 nm). Cu2O-DMB has a spherical morphology with a smaller nanosize and positive ζ potential, can trap bacteria through electrostatic interactions resulting in a targeting function. Cu2O-DMB nanospheres show both oxidase-like and peroxidase-like activities, and serve as a self-cascade platform, which can deplete high concentrations of GSH to produce O2˙- and H2O2, then H2O2 is transformed into ˙OH, without introducing exogenous H2O2. At the same time, Cu2O-DMB nanospheres become photoresponsive, producing 1O2 and having an efficient photothermal conversion effect upon NIR irradiation. The proposed mechanism is that the generated ROS (O2˙-, ˙OH and 1O2) and hyperthermia can have synergetic effects for killing bacteria. Moreover, hyperthermia is not only beneficial for destroying bacteria, but also effectively enhances the efficiency of ˙OH production and accelerates GSH oxidation. Upon NIR irradiation, Cu2O-DMB nanospheres exhibit excellent antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) with low cytotoxicity and bare bacterial resistance, destroy the bacterial membrane causing an efflux of proteins and disrupt the bacterial biofilm formation. Animal experiments show that the Cu2O-DMB + NIR group can efficiently treat MRSA infection and promote wound healing. These results suggest that Cu2O-DMB nanospheres are effective materials for combating bacterial infections highly efficiently and to aid the development of photoresponsive enzymatic synergistic antibacterial therapy.

Plasmonic Ag decorated AlOOH for highly sensitive SERS detection of affinity OH groups molecules enriched in hotspots.

Significant breakthroughs have been made in the development of surface-enhanced Raman scattering (SERS) substrates constructed by depositing plasmonic Ag onto nanostructured platforms. AlOOH is widely fabricated using hydrothermal, microwave, and microemulsion methods. Among these, the high catalytic activity of AlOOH prepared by the microemulsion method is derived from its high specific surface area, more active surface OH groups, and multi-active adsorption sites. And nanomaterials with such excellent properties have not yet been fabricated on a SERS-based platform to improve the Raman-enhanced properties of Ag achieving high-sensitivity detection of probe molecules especially with affinity for OH groups. The precious metal Ag has long been known to serve as traps to capture electrons and holes generated by plasmon resonance, reducing electron-hole recombination and exhibiting high activity in photocatalytic processes. In this work, to demonstrate the SERS substrate activity of the AlOOH@Ag complex, it has been successfully applied to identify congo red (CR) molecules with high sensitivity, methyl blue (MB) and methyl orange (MO), enabling trace-level detection with enhanced performance much stronger than Ag substrate.

[Spectrum-effect relationship of the blood-activating efficacy of Notoginseng Radix et Rhizoma].

This study aims to establish the high-performance liquid chromatography(HPLC) fingerprints of different batches of Notoginseng Radix et Rhizoma, determine their pharmacodynamic indexes of promoting blood circulation, and explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the efficacy of promoting blood circulation. Firstly, the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma were established. Then, the pharmacodynamic indexes were determined after the capillary coagulation experiment and the cerebral ischemia-reperfusion in rats, including capillary coagulation time, percentage of cerebral ischemic area, cerebral water loss rate, and brain-body index. Afterward, the partial least-squares method was used to explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the pharmacodynamic indexes. The results showed that this study successfully established the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma, found 23 common peaks, and identified 12 of them, all of which were saponins. The method was proved stable and reliable. Both the capillary coagulation experiment and the middle cerebral artery occlusion(MCAO)-induced cerebral ischemia-reperfusion experiment on rats revealed that there were obvious differences in the pharmacodynamic indexes of different batches of Notoginseng Radix et Rhizoma. The relationships between 23 common components of Notoginseng Radix et Rhizoma in different batches and the pharmacodynamic indexes were discussed by means of spectrum-effect correlation analysis, of which 17 components had positive effects while 6 components had negative effects on the pharmacodynamic indexes. This study provides a certain reference basis for the clinical rational use and quality control of Notoginseng Radix et Rhizoma.

Effects of massage and acupuncture on the range of motion and daily living ability of patients with frozen shoulder complicated with cervical spondylosis.

OBJECTIVE: This study was designed to study the effects of massage and acupuncture on patients with frozen shoulder complicated with cervical spondylosis through range of motion (ROM) and daily living ability. METHODS: A total of 164 patients with frozen shoulder treated in our hospital from June 2016 to April 2019 were recruited and divided into a control group and an observation group. There were 100 cases in the observation group, all of whom were treated with massage combined with acupuncture. Another 64 cases were enrolled in the control group, all of whom were treated with acupuncture alone. The recovery of myodynamia, rating scale of the American Shoulder and Elbow Surgeons (ASES), score of American Spinal Injury Association (ASIA), ROM score, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), complication rate, total effective rate, and patient satisfaction were assessed. RESULTS: After treatment, patients in the observation group had better recovery of myodynamia than the control group. They also had lower VAS scores, higher life function score and total ASES scores, higher ASIA scores, higher ROM scores, lower VCAM-1 and ICAM-1 expression, lower complication rate, higher total effective rate, and higher patient satisfaction. CONCLUSION: Massage combined with acupuncture can better improve the ROM of joints and daily living ability of patients with frozen shoulder complicated with cervical spondylosis.

Discovery and proteomics analysis of effective compounds in Valeriana jatamansi jones for the treatment of anxiety.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhizhu Xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. However, there have been few investigations to clarify the compounds in ZZX for the treatment of anxiety. AIM OF THE STUDY: Our previous study has identified five anti-anxiety components, including hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C and chlorogenic acid, from extract of ZZX. In order to find the optimal combination and the underlying mechanism of these five components in the treatment of anxiety disorder, researches were designed based on uniform design method and proteomic technology. MATERIALS AND METHODS: The samples with different proportion and content of the five active components were arranged by uniform design method. Then a mathematical model was formulated using partial least square method and stepwise regression analysis. Moreover, the empty bottle stress-induced anxiety rat model was established, and the anti-anxiety effect was recorded by the unconditioned reflex elevated maze test and the open field test. In addition, the isobaric tags for relative and absolute quantitation (iTRAQ) technique, along with the multidimensional liquid chromatography and high-resolution mass spectrometry were applied in proteomic study. At last, the result of proteomic analysis was further confirmed by Western blot. RESULTS: The optimal combination of the components from the extract of ZZX was 1.153 mg/kg hesperidin, 2.197 mg/kg Isochlorogenic acid A, 0.699 mg/kg Isochlorogenic acid B and 1.249 mg/kg Chlorogenic acid. Total 6818 proteins were identified using proteomic analysis and 80 differentially expressed proteins were used for further bioinformatic analysis. These proteins were involved in the neuroactive ligand-receptor interaction, protein digestion and absorption, cholesterol metabolism, Chagas disease, and AGE/RAGE signaling pathway. CONCLUSIONS: The composition and proportion of anti-anxiety components in extract of ZZX was disclosed, and there was an anti-anxiety effect for the combined components of flavonoids and phenolic acids. Through proteomic analysis and Western blot, it was found that the effective components of extract of ZZX can exert synergistic anti-anxiety effects via the regulation of multi-signaling pathways. These findings could provide a preliminary research basis for the development of new low-toxic, efficient, stable and controllable anti-anxiety drugs.

Factor Xa inhibitor rivaroxaban suppresses experimental abdominal aortic aneurysm progression via attenuating aortic inflammation.

OBJECTIVE: Rivaroxaban is a specific factor Xa (FXa) inhibitor for venous thromboembolism treatment. Recently, increasing evidence have reported the beneficial effects of rivaroxaban on treating cardiovascular disorders such as coronary and peripheral artery disease. However, its potential influence on abdominal aortic aneurysm (AAA) remains unclear. This study aims to investigate whether rivaroxaban treatment could attenuate experimental AAA progression and its related mechanisms. APPROACHES AND RESULTS: In human aneurysmal aorta, FXa protein expression was significantly upregulated. Further investigations identified a positive correlation among plasma FXa level, AAA severity (the maximal aortic diameter), and intra-aneurysmal thrombus percentage. In Ang II (angiotensin II)-infused ApoE-/- mice, the administration of high dose rivaroxaban (15 mg/kg/d) for 14 days significantly reduced the maximal aortic diameter, while low dose rivaroxaban (5 mg/kg/d) did not display such a protective role. Although rivaroxaban treatments reduced the incidence of AAA and thrombus formation, these differences did not reach statistical significance. Immunohistochemistry revealed a pronounced aortic remodeling including increased collagen content and enhanced elastin degradation in Ang II-induced AAAs, which was inhibited by high dose rivaroxaban treatment. Further analysis demonstrated that rivaroxaban exerted its protective effects by decreasing leukocyte infiltration, inflammatory cytokines expression, and matrix metalloproteinases (MMPs) expression in the aortic wall. The inhibitory effect of rivaroxaban on aneurysm development was also observed in calcium chloride-induced AAA model. Mechanistically, in human aortic endothelial cells, FXa stimulation increased the expression of inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesive molecules, which were all reversed by the cotreatment of rivaroxaban. Subsequent monocyte-endothelial cell interaction was enhanced after FXa stimulation and was alleviated by rivaroxaban cotreatment. In addition, FXa induced a significantly heightened expression of MMP2 in human aortic endothelial cells, which was ameliorated by rivaroxaban coadministration. CONCLUSIONS: Rivaroxaban attenuated both angiotensin II- and calcium chloride-induced abdominal aortic aneurysm (AAA) progressions, through inhibiting aortic remodeling and inflammation. Rivaroxaban could be a promising therapeutic agent in attenuating AAA development by counteracting FXa-induced aortic wall inflammation.

[Analysis of internal exposure levels of manganese, cobalt, selenium and molybdenum in blood and urine among general population in parts of Shaanxi Province].

OBJECTIVE: To investigate the internal exposure levels of manganese(Mn), cobalt(Co), selenium(Se) and molybdenum(Mo) in blood and urine among the general population in parts of Shaanxi Province, and thereby to analyze their population distribution characteristics. METHODS: In 2017, a total of 720 subjects of general people aged 3-79 years were recruited from 5 counties in Shaanxi Province, by stratified random sampling method, blood and urine samples were collected, and the contents of Mn, Co, Se and Mo in blood and urine samples were detected by inductively coupled plasma mass spectrometry(ICP-MS). The test result were statistically analyzed according to different genders, regions and age groups. RESULTS: Among general people in Shaanxi Province, the median of Mn in blood and urine were separately 8. 43 and 0. 60 µg/L. The median of Mn in blood among males and females were 7. 99 and 8. 81 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mn between urban and rural areas was statistically significant(P<0. 05). The median of Co in blood and urine were separately 0. 13 and 0. 17 µg/L, the median of Co in blood among males and females were 0. 12 and 0. 15 µg/L, the median of Co in urine among males and females were 0. 16 and 0. 20 µg/L, the differences were statistically significant(P<0. 05), the differences of blood Co and urine Co in urban and rural areas were statistically significant(P<0. 05). The median of Se concentration in blood and urine were separately 73. 20 and 13. 30 µg/L, the median of Se in urine among males and females were 14. 40 and 12. 40 µg/L, the difference were statistically significant(P<0. 05), the differences of blood Se and urine Se in urban and rural areas were statistically significant(P<0. 05). The median of Mo concentration in blood and urine were separately 0. 60 and 50. 40 µg/L, the median of Mo in urine among males and females were 56. 60 and 43. 00 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mo between urban and rural areas was statistically significant(P<0. 05). Within the same gender, all indexes in whole blood(except female blood Se) were statistically significant among age groups(P<0. 05). The differences of male urine Co, urine Se, urine Mo and female urine Co among age groups were statistically significant(P<0. 05). CONCLUSION: Among general population in Shaanxi Province, the Mn, Co, Se and Mo levels in blood and urine are varied by gender age and area, the blood Se level is relatively low.

Anxiolytic Effect of Alcohol-Water Extracted Suanzaoren-Wuweizi Herb-Pair by Regulating ECS-BDNF-ERK Signaling Pathway Expression in Acute Restraint Stress Male Rats.

Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)-brain-derived neurotrophic factor (BDNF)-extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs.

Effect of sulfur-fumigation process on ginseng: Metabolism and absorption evidences.

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.

[Effects of total C-21 steroidal glucosides from Cynanchum auriculatum on oxidative stress pathway in mice with liver injury].

The study aimed to investigate the mechanism of hepatoprotective effect of C-21 steroidal glucosides from Cynanchum auriculatum( Baishouwu) on oxidative stress in mice with liver injury. Mice were randomly divided into normal group,model group,positive control group,Baishouwu high group and Baishouwu low group. The liver injury model was induced by intraperitoneal injection of CCl4 peanut oil solution. All mice were sacrificed to collect blood and liver specimens. The activities of serum levels of ALT and AST were detected. The content of MDA and the activity of SOD in liver homogenate were examined by colorimetry method. Tissues were stained with hematoxylin-eosin for histological examination. The hepatic protein expressions of NF-κB p65,p-IκBα,i NOS and COX-2 were detected by Western blot. The mRNA expressions of TNF-α and IL-6 were determined by RT-PCR. It was found that treatment with C-21 steroidal glucosides from Baishouwu successfully attenuated liver injury induced by CCl4,as shown by decreased levels of serum biochemical indicators( AST,ALT)( P<0. 01). Administration of total C-21 steroidal glucosides enhanced the activity of SOD( P<0. 01) and decreased the content of MDA( P<0. 01) in liver homogenate. Microscopic features suggested that treatment with C-21 steroidal glucosides from Baishouwu was effective in inhibiting CCl4-induced hepatocyte edema and degeneration. Further studies showed that NF-κB p65 overexpression induced by CCl4 was decreased by C-21 steroidal glucosides,leading to the markedly down-regulated protein expression levels of p-IκBα,i NOS and COX-2,as well as the depression of TNF-α and IL-6 mRNA expressions. In conclusion,total C-21 steroidal glucosides from Baishouwu exhibited potent effect on oxidative stress pathway in mice with liver injury induced by CCl4,with enhanced activity of SOD,decreased content of MDA,and down-regulated levels of NF-κB p65,p-IκBα,i NOS and COX-2.

PHMH, a diarylheptanoid from Alpinia officinarum attenuates VEGF-induced angiogenesis via inhibition of the VEGFR-2 signaling pathway.

The rhizome of Alpinia officinarum Hance, a popular spice used as a condiment in China and Europe, has various reported bioactivities, including anticancer, anti-inflammatory and antioxidant effects. However, its anti-angiogenic activity has not previously been reported. In this study, a diarylheptanoid was isolated from Alpinia officinarum and identified as 1-phenyl-7-(4-hydroxy-3-methoxyphenyl)-4E-en-3-heptanone (PHMH). We demonstrated that PHMH exerts anti-angiogenic activity both in vitro and in vivo. PHMH inhibited vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro, and also suppressed VEGF-induced sprout formation of rat aorta ex vivo. Furthermore, PHMH was found to block VEGF-induced vessel formation in mice and suppress angiogenesis in both zebrafish and chorioallantoic membrane models. Mechanistic studies indicated that PHMH inhibited VEGF-induced VEGF receptor-2 (VEGFR-2) auto-phosphorylation and resulted in the blockage of VEGFR-2-mediated signaling cascades in HUVECs, including the Akt/mTOR, ERK1/2, and FAK pathways. Our findings provide new insights into the potential application of PHMH as a therapeutic agent for anti-angiogenesis.

[Transurethral holmium laser enucleation of the prostate combined with Jisheng Shenqi Decoction for benign prostatic hyperplasia].

OBJECTIVE: To assess the clinical effects of transurethral holmium laser enucleation of the prostate (HoLEP) combined with Jisheng Shenqi Decoction (HoLEP + JSSD) on BPH. METHODS: This study included 110 BPH patients treated in our hospital from August 2017 to April 2018, who were randomly assigned to receive HoLEP (n = 55) or HoLEP + JSSD (n = 55). We compared the pre- and post-operative IPSS, quality of life (QOL) score, prostate volume, postvoid residual urine volume (PVR), maximum urinary flow rate (Qmax), average urinary flow rate (Qavg) and levels of serum T, E2 and T/E2 as well as postoperative complications between the two groups of patients. RESULTS: After treatment, both IPSS and QOL score were significantly lower in the HoLEP + JSSD than in the HoLEP group (P < 0.05), and so were the prostate volume and PVR (P < 0.05). The Qmax, Qavg and serum T level were significantly higher (P < 0.05) while T/E2 markedly lower in the former than in the latter group (P < 0.05). There were no statistically significant differences between the HoLEP + JSSD and HoLEP groups in the E2 level (P > 0.05) or the total incidence rate of complications postoperatively (21.82% vs 29.09%, P > 0.05). CONCLUSIONS: HoLEP + JSSD can significantly alleviate the lower urinary tract symptoms as well as improve the QOL and bladder and urinary tract functions of BPH patients.

Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety in Rat by Fingerprint-Efficacy Study.

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.

[Effects of total C-21 steroidal glycosides from Baishouwu on proliferation invasion and apoptosis of human hepatic cancer HepG2 cells].

This study aimed to investigate the inhibitory effect of total C-21 steroidal glycoside (TCSG) from Baishouwu on the proliferation, invasion and apoptosis of human hepatoma HepG2 cells in vitro and the relevant molecular mechanism. The experiment was divded into control group, TCSG groups (25, 60, 150 mg·L⁻¹) and positive control cisplatin group (1.33 mg·L⁻¹). Human hepatocyte L-02 cells and hepatoma HepG2 cells were treated with different concentrations of TCSG. Then, the inhibitory effect of TCSG on the proliferation of HepG2 cells was detected by CCK-8 method. Cell cycle, cell apoptosis and mitochondrial membrane potential were detected by flow cytometry. The apoptotic morphology was observed by Hoechst 33258 staining. Cell migration and invasion abilities were analyzed by Transwell chamber model. The protein expressions of Bcl-2, Bax, caspase 3, cleaved caspase 3 and Cyt C (cytosolchondrial) were detected by Western blot. Compared with the control group, the proliferation of HepG2 cells was significantly inhibited after treatment with different concentrations of TCSG for 48 h in a dose-dependent manner(P<0.01), but no obvious effect was observed on the proliferation of L-02 cells. After treatment with TCSG for 48 h, apoptotic morphology such as nuclear shrinkage, fragmentation and semilunar or circular was observed; migration and invasion abilities of cells were significantly decreased, cell cycle was blocked in the G0/G1 phase(P<0.01), mitochondrial membrane potential was remarkably decreased(P<0.01), and so did the ratio of apoptosis(P<0.01).Western blot results showed that the protein expressions of Bax, caspase 3, cleaved caspase 3, and Cyt C were significantly up-regulated(P<0.05, P<0.01), while the Bcl-2 protein was significantly down-regulated(P<0.05, P<0.01). Furthermore, the ratio of Bax/Bcl-2 was increased (P<0.01). The results suggested that TCSG could inhibit the proliferation and invasion of HepG2 cells, and induce the apoptosis of HepG2 cells. The potential mechanism may be related to the blocking of cell cycle and the regulation of the expressions of apoptosis-related proteins by activating mitochondrial pathway.

SDG721 and SDG705 are required for rice growth.

H3K4me3 plays important roles in development, transcription, and environmental responses. Here, we report that SDG721 (SET-domain group protein 721) and SDG705 are involved in regulating rice development. SDG721 and SDG705 encode TRITHORAX-like proteins, which appear to modulate H3K4 methylation levels. Loss of SDG721 and SDG705 function resulted in GA-deficient phenotypes, including semi-dwarfism, reduced cell length, and reduced panicle branching. The transcripts levels and H3K4me3 levels of GA biosynthesis genes and GA signaling pathway genes were downregulated in the sdg721 sdg705 plants. Together, these results suggest that SDG721 and SDG705 regulate H3K4 methylation, which is crucial for plant development in rice.

Antitumor evaluation and multiple analysis on different extracted fractions of the root of Cynanchum auriculatum Royle ex Wight.

The root of Cynanchum auriculatum (C. auriculatum) Royle ex Wight has been shown to possess various pharmacological effects and has recently attracted much attention with respect to its potential role in antitumor activity. The C-21 steroidal glycosides are commonly accepted as the major active ingredients of C. auriculatum. In this study, the antitumor abilities of different extracted fractions of the root bark and the root tuber of C. auriculatum were investigated by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human cancer cell lines HepG2 and SMMC-7721. The results showed that the chloroform and ethyl acetate fractions of the root tuber suppressed tumor cell growth strongly. To identify and characterize the chemical constituents of different active fractions, an ultra high performance liquid chromatography with triple-quadrupole tandem mass spectrometry method was developed for the simultaneous quantitation of eight C-21 steroidal glycosides. The analysis revealed that the C-21 steroidal glycosides were concentrated in the chloroform and ethyl acetate fractions, and the total contents of different fractions in the root tuber were significantly higher than those of corresponding ones in the root bark. Furthermore, the C-21 steroidal glycosides based on different types of aglucones were prone in different medicinal parts of C. auriculatum.