Investigating the potential anti-inflammatory mechanism of benzophenone compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on network pharmacology and molecular docking strategies.

BACKGROUND: Aquilaria sinensis (Lour.) Gilg (ASG) has been used as traditional medicine for centuries. However, the active ingredients from leaves and their anti-inflammatory mechanism are rarely reported. The network pharmacology and molecular docking strategies were applied to explore the potential mechanisms of Benzophenone compounds from the leaves of ASG (BLASG) against inflammation. METHODS: BLASG-related targets were obtained from the SwissTargetPrediction and PharmMapper databases. Inflammation-associated targets were retrieved from GeneGards, DisGeNET, and CTD databases. Cytoscape software was used to draw a network diagram of BLASG and its corresponding targets. DAVID database was applied for enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify the hub targets of BLASG. Molecular docking analyses were performed by AutoDockTools 1.5.6. Moreover, we used ELISA and qRT-PCR assays to validate the anti-inflammatory effects of BLASG by cell experiments. RESULTS: Four BLASG were extracted from ASG, and corresponding 225 potential targets were identified. PPI network analysis indicated that SRC, PIK3R1, AKT1, and other targets were the core therapeutic targets. Enrichment analyses revealed that the effects of BLASG are regulated by targets associated with apoptosis and inflammation-related pathways. In addition, molecular docking revealed that BLASG combined well with PI3K and AKT1. Furthermore, BLASG significantly decreased the inflammatory cytokines levels and down-regulated PIK3R1 and AKT1 gene expression in RAW264.7 cells. CONCLUSION: Our study predicted the potential targets and pathways of BLASG against inflammation, which offered a promising strategy to reveal the therapeutic mechanism of natural active components in the treatment of diseases.

[ZHANG Wei-hua's clinical experience of Zhenjing Anshen method in treatment of insomnia].

The paper summarizes professor ZHANG Wei-hua's clinical experience in treatment of insomnia with Zhenjing Anshen (calming-down the spirit) method. It is believed that insomnia results from the unstable spirit in pathogenesis of TCM. The basic therapeutic principle is regulating the spirit, in which, stabilizing the primary spirit and tranquilizing the heart spirit are emphasized. Main acupoints are Baihui (GV 20), Sishencong (EX-HN 1) and Yintang (GV 24+) to stabilize the primary spirit, located on the head; and Shenmen (HT 7) located on the wrist to calm-down the heart spirit, as well as Sanyinjiao (SP 6) and Yongquan (KI 1) in the lower extremities to benefit yin and balance yang, and then to house the spirit eventually. The needles are inserted in different depths and to various directions. The external application of herbal plaster is combined at Yongquan (KI 1) and the supplementary acupoints are selected in terms of syndrome differentiation. This therapy is simple in acupoint selection and very effective in treatment of insomnia.

[Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation. METHODS: Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups. RESULTS: Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05). CONCLUSION: The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

[Professor ZHANG Wei-hua's clinical experience in chronic somatic pain treated with zhidong needling techniques].

The paper summarizes professor ZHANG Wei-hua's clinical experience for the treatment of chronic somatic pain with zhidong needling techniques. In terms of the characteristics of chronic somatic pain, professor ZHANG has integrated zhidong needling with acupuncture kinetic therapy. The satisfactory therapeutic effects are obtained by selecting the painful points and regions as the treatment sites and the specific techniques of zhidong needling depending on the size of affected area, the depth of illness, the size and shape of the cord-like muscle, etc. Five techniques of zhidong needling are used accordingly with twirling, pulling, lifting and thrusting, surrounding needling methods involved, as well as with the manipulation speed, direction and frequency considered.

Encapsulating Amidoximated Nanofibrous Aerogels within Wood Cell Tracheids for Efficient Cascading Adsorption of Uranium Ions.

Continuous filtering adsorption has drawn growing interest in the exploration of uranium resources in seawater and reduction in the environmental risks of uraniferous wastewater from nuclear industries. For most filtering adsorbents, repeated filtration, high membrane thickness, and high pressure are normally essential to achieve both a high rejection ratio and high filtration flux. Herein cellulose fibrils were preferentially exfoliated from the lignin-poor layer of secondary cell walls of balsa wood during an in situ amidoximation process. By maintaining honeycomb-like cellular microstructures and cellulose aerogel stuffing in their cell tracheids, the resultant nanowoods showed superior mechanical properties (e.g., compressive strength ∼1.3 MPa in transverse direction) with large surface areas (∼80 m2 g-1). When their cell tracheids were aligned perpendicular to the flow and the edges sealed with a thermoset polymer, they could serve as efficient and high-pressure filtration membranes to capture aquatic uranium ions. In analogy to a typical cascading filtration system, the filtrate passed successively the layered-organized cell tracheids through abundant micropores on their cell walls, enabling a high rejection ratio of >99% and flux of ∼920 L m-2 h-1 under pressure up to 6 bar (membrane thickness of 2 mm). Thus, this study not only provides an in situ approach to producing robust woods with functional nanocellulose encapsulated into their cell tracheids but also offers a sustainable route for high-efficiency extraction of aqueous uranium.

[ZHANG Wei-hua's experience in clinical treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture].

The clinical experience in treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture of professor ZHANG Wei-hua was summarized. Professor ZHANG integrates the theories of the cutaneous region of meridian, biaoben, "taking tender point as acupoint" and local holography as a whole in treatment of somatalgia. The "point-stimulation technique" of acupuncture (subcutaneous needling technique) is adopted for the painful site less than 3 cm in diameter, the "zone-stimulation technique" (surrounding needling technique) is for the site larger than 3 cm in diameter and the "strip-stimulation technique" (cubit-tibia needling technique) is for various acute and chronic somatalgia. These three needling techniques are applicable singly or in combination in clinical practice.

Establishment of a Lung Cancer Discriminative Model Based on an Optimized Support Vector Machine Algorithm and Study of Key Targets of Wogonin in Lung Cancer.

An optimized support vector machine model was used to construct a lung cancer diagnosis model based on serological indicators, and a molecular regulation model of Wogonin, a component of Scutellaria baicalensis, was established. Serological indexes of patients were collected, the grid search method was used to identify the optimal penalty coefficient C and parameter g of the support vector machine model, and the benign and malignant auxiliary diagnosis model of isolated pulmonary nodules based on serological indicators was established. The regulatory network and key targets of Wogonin in lung cancer were analyzed by network pharmacology, and key targets were detected by western blot. The relationship between serological susceptibility genes and key targets of Wogonin was established, and the signaling pathway of Wogonin regulating lung cancer was constructed. After support vector machine parameter optimization (C = 90.597, g = 32), the accuracy of the model was 90.8333%, with nine false positives and two false negative cases. Ontology functional analysis of 67 common genes between Wogonin targets and lung cancer-related genes showed that the targets were associated with biological processes involved in peptidye-serine modification and regulation of protein kinase B signaling; cell components in the membrane raft and chromosomal region; and molecular function in protein serine/threonine kinase activity and heme binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that the regulation pathways involved the PI3K-Akt signaling pathway, ERBB signaling pathway, and EGFR tyrosine kinase inhibitor resistance. In vitro analyses using lung cancer cells showed that Wogonin led to significantly increased levels of cleaved caspase-3 and Bad and significantly decreased Bcl-2 expression in a concentration-dependent manner. ErbB4 expression also significantly decreased in lung cancer cells after treatment with Wogonin. A regulatory network of Wogonin regulating lung cancer cell apoptosis was constructed, including the participation of serological susceptibility genes. There is a certain regulatory effect between the serological indexes that can be used in the diagnosis of lung cancer and the key targets of Chinese herbal medicine treatment of lung cancer, which provides a new idea for the diagnosis, treatment and prognosis of clinical lung cancer.

Efficacy and safety of astragalus injection combined with Western medicine in the treatment of early diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes. Its clinical manifestation is proteinuria, and it is a common cause of renal failure. At present, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists are often used to treat early DN, and they have good curative effect. On this basis, the treatment of early DN with the combination of astragalus injection is becoming more and more widespread. Therefore, the purpose of this study is to prove the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN, and to provide reference value for clinical practice in the future. METHODS: English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructur, Wanfang, VP Information Chinese Journal Service Platform, China Biology Medicine disc) will be searched by computer. From the establishment of the database to February 2021, a randomized controlled trial of astragalus injection combined with Western medicine in the treatment of early DN will be conducted. Two researchers independently evaluate the quality of the included study and extract the data. Included literature is analyzed by Meta with RevMan5.3 software. RESULTS: In this study, the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN are evaluated by serological indexes such as Urinary albumin excretion rates (UAER), serum creatinine and blood urea nitrogen, as well as the adverse reactions of drugs. CONCLUSION: This study will provide reliable evidence-based evidence for astragalus injection combined with Western medicine for the treatment of early DN. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/A9JGP.

Prevention of Diabetes in Overweight/Obese Adults through Traditional Chinese Patent Medicine: Study Protocol for a Prospective Cohort Study.

Background. Early intervention in prediabetes can prevent or delay the incidence of type 2 diabetes mellitus (T2DM). Traditional Chinese patent medicine (TCPM) is widely used in China to prevent T2DM. This study aims to evaluate the efficacy and safety of TCPMs for preventing T2DM. Method/Design. This study is a multicenter, cohort study with two arms. A total of 600 participants will be recruited. The participants will be divided into either intervention or control groups according to their own desire, and the exposure factor is the application of TCPMs. All participants will be encouraged to lead a healthy lifestyle, and the intervention group also used TCPMs based on syndrome differentiation. Incident diabetes and normalization of blood glucose are indexes of end point. Safety assessments and adverse event monitoring will also be conducted. The treatment duration is set for 24 weeks, and we will follow-up for another 2 years. Discussion. This trial may provide initial evidence regarding the efficacy and safety of TCPMs plus lifestyle intervention (LI) compared to LI alone for preventing T2DM and provide a comprehensive intervention plans that choose suitable TCPMs for diabetes prevention according to syndrome differentiation. Trial Registration Number. Chinese Clinical Trial Registry ID: ChiCTR1900023541, registered on 1 Jun 2019. The version identifier is 2018121702.

Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFß3-Smad2/3-Nedd9 Signaling Pathway.

Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-ß3 (TGFß3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGFß3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGFß3-SMAD2/3-NEDD9 pathway.

Facilitating Granule Cell Survival and Maturation in Dentate Gyrus With Baicalin for Antidepressant Therapeutics.

Baicalin isolated from Scutellaria baicalensis possesses antidepressant abilities through its relation to hippocampal neurogenesis. Current research has found that baicalin can promote the proliferation of hippocampal granule cells, however, the detailed mechanism of baicalin on the survival and maturation of hippocampal granule cells has yet to be sufficiently explored. The purpose of this study was to evaluate whether baicalin could facilitate the survival and maturation of hippocampal granule cells, and to explore its potential mechanism. The chronic corticosterone (CORT)-induced mouse model of depression was used to assess antidepressant-like effects of baicalin and to illuminate possible molecular mechanisms by which baicalin affects hippocampal neurogenesis. The survival and maturation of granule cells were measured by immunohistochemistry, immunofluorescence and Golgi staining. The expression of Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK3ß)/ß-catenin pathway related proteins were measured by western blot analysis. PI3K inhibitor LY292002 and AKT inhibitor Perifosine were administered to HT-22 cells to explore the relationship between the PI3K/AKT/GSK3ß/ß-catenin pathway and baicalin. The results of the study illustrated that baicalin significantly decreased chronic CORT-induced depressive-like behaviors and reduced serum corticosterone levels. In addition, baicalin (administered at 60 mg/kg) reversed chronic CORT-induced lesions on hippocampal granule cells. Moreover, baicalin significantly increased the phosphorylation rate of PI3K, AKT, GSK3ß, and total ß-catenin. The study found that administration of LY292002/Perifosine counteracted the effects of baicalin in HT-22 cells. These results demonstrate that baicalin can alleviate chronic CORT-induced depressive-like behaviors through promoting survival and maturation of adult-born hippocampal granule cells and exhibiting protective effect on hippocampal neuron morphology. We propose the underlying mechanisms involve the activation of the PI3K/AKT/GSK3ß/ß-catenin pathway.

Inhibition of UDP-glucuronosyltransferases by different furoquinoline alkaloids.

Herbs are often administered in combination with therapeutic drugs, raising the possibility for herb-drug interactions (HDIs). Furoquinoline alkaloids are found in Rutaceae plants, which are structurally similar and have many medicinal properties. This study aims to investigate the inhibition of four furoquinoline alkaloids on the activity of UDP-glucuronosyltransferases (UGTs).The recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition type and parameters were determined, and in silico docking was employed to elucidate the inhibition difference of furoquinoline alkaloids towards UGTs.Dictamine, haplopine, γ-fagarine and skimmianine strongly inhibited UGT1A3, UGT1A7, UGT1A9 and UGT2B4, respectively. Among them, dictamnine inhibited more than 70% of the four UGTs. Inhibition kinetics determination showed that they all exerted competitive inhibition, and the inhibition kinetic constant (Ki) was determined to be 8.3, 7.2, 3.7 and 33.9 µM, respectively. In vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the inhibition possibility for four alkaloids. Skimmianine was proved to be more suitable for clinical application. In silico docking study indicated that the hydrophobic interactions played a key role in the inhibition of furoquinoline alkaloids towards three of the four UGTs. In conclusion, monitoring the interactions between furoquinoline alkaloids and drugs mainly undergoing UGTs-catalyzed metabolism is necessary.

A systematic review and meta-analysis on the efficacy and safety of traditional Chinese patent medicine Jinqi Jiangtang Tablet in the treatment of type 2 diabetes.

INTRODUCTION: At present, a large number of people in the world are suffering from type 2 diabetes (T2DM), so it is urgent to develop effective treatment measures of T2DM. In China, many clinical studies have shown that Jinqi Jiangtang Tablet (JQJTT), a traditional Chinese patent medicine (TCPM), has a good effect in the treatment of T2DM. This systematic review and meta-analysis is intended to assess the efficacy and safety of JQJTT plus conventional therapy in the treatment of T2DM. METHODS: Seven electronic databases were searched to include in eligible studies published from inception to May 24, 2018. Randomized controlled trials (RCTs) of JQJTT in combination with the conventional therapy versus conventional therapy alone or combined with placebo were included. The two reviewers independently conducted data extraction and quality assessment. For different variable types, the outcome measures were expressed as risk ratios (RRs) or mean differences (MDs). According to the value of I2, a fixed or random effect model was used for statistical analysis. RESULTS: Seventeen studies conducted in China were identified in this systematic review, which included 1,425 participants. The meta-analysis on the effective rate of the comparison groups showed a significant difference in favor of the JQJTT group (RR 1.34; 95%CI [1.02, 1.75]; p = 0.04). In addition, the results showed a statistically significant reduction in FBG (MD -0.85; 95%CI [-1.03, -0.68]; p < 0.00001), 2hPG (MD -1.95; 95%CI [-2.33, -1.56]; p < 0.00001), HbA1c (MD -0.76; 95%CI [-1.03, -0.49]; p < 0.00001), FINS (MD -3.05; 95%CI [-3.69, -2.42]; p < 0.00001), PINS (MD -10.22; 95%CI [-13.93, -6.50]; p < 0.00001), HOMA-IR (MD -1.11; 95%CI [-1.55, -0.68]; p < 0.00001), LDL-C (MD -0.37; 95%CI [-0.63, -0.11]; p = 0.006), TC (MD -0.46; 95%CI [-0.85, -0.08]; p = 0.02), TG (MD -0.34; 95%CI [-0.47, -0.20]; p < 0.00001) with JQJTT plus conventional therapy versus conventional therapy alone. There was no statistical difference between the two comparison groups in HDL-C, total incidence of adverse events and incidence of hypoglycemia. CONCLUSION: The available evidence indicates that JQJTT combined with conventional therapy for treating T2DM has a good performance in regulating glycolipid metabolism and improving insulin resistance. However, due to the limitations of this systematic review, the results should be interpreted with caution.

Effect of a modified Banxia Xiexin decoction plus chemotherapy on stage â ¢ colon cancer.

OBJECTIVE: To investigate the effect of a modified Banxia Xiexin decoction (MBXD) plus chemotherapy on postoperative adverse reaction in patients with stage Ⅲ colon cancer in patients whose symptoms were identified as cold-heat complicated pattern in terms of the theory of Traditional Chinese Medicine (TCM). METHODS: A prospective non-randomized control study of patients with stage Ⅲ colon cancer in Beijing Shijitan Hospital and Guang'anmen Hospital between January 2012 and December 2013. A total of 80 patients were divided into experimental group (MBXD + chemotherapy) and control group (chemotherapy). The adverse reactions, life quality and disease-free survival (DFS) were compared between the two groups. RESULTS: The cold-heat complex pattern was released in 94.3% of patients in experimental group whereas 62.2% in control group (P < 0.05). Life quality was improved in 24 vs 14 cases, stabilized in 9 vs 14 cases whereas decreased in 2 vs 15 cases in experimental group and control group, respectively (P < 0.05). The average DFS was 22.371 months in experimental group, while 13.932 months in control group (P < 0.05). CONCLUSION: MBXD combined with chemotherapy may significantly relieve clinical symptoms, reduce chemotherapy associated adverse effects, improve life quality, and prolong DFS of patients with stage Ⅲ colon cancer (cold-heat complicated pattern).

Application of Real-Time Cell Electronic Analysis System in Modern Pharmaceutical Evaluation and Analysis.

Objective: We summarized the progress of the xCELLigence real-time cell analysis (RTCA) technology application in recent years for the sake of enriching and developing the application of RTCA in the field of Chinese medicine. Background: The RTCA system is an established electronic cellular biosensor. This system uses micro-electronic biosensor technology that is confirmed for real-time, label-free, dynamic and non-offensive monitoring of cell viability, migration, growth, spreading, and proliferation. Methods: We summarized the relevant experiments and literature of RTCA technology from the principles, characteristics, applications, especially from the latest application progress. Results and conclusion: RTCA is attracting more and more attention. Now it plays an important role in drug screening, toxicology, Chinese herbal medicine and so on. It has wide application prospects in the area of modern pharmaceutical evaluation and analysis.

[Electroacupuncture Intervention Reduces Mammary Gland Hyperplasia by Regulating Serum Estradiol and Progesterone Levels and Their Mammary Receptor Expression in Female Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on hyperplastic mammary glands, serum estradiol (E2) and progesterone (P) contents, estrogen receptor alpha (ERα) and progesterone receptor (PR) expression of breast tissues in mammary gland hyperplasia (MGH) rats, so as to reveal its mechanisms underlying improvement of MGH. METHODS: Sixty female SD rats were randomly divided into control, model, EA, EA＋ovariectomy(OVX) and EA＋sham-OVX groups (n＝12 in each). The MGH model was established by injection of Estradiol Benzoate injection (0.5 mg/kg, once daily for 25 d) and P injection (0.5 mg/kg, once daily for 5 d after estradiol injection) into the medial hind-leg muscle. After model establishment, bilateral OVX was performed for rats of the EA＋OVX group, and sham OVX (only exposure of ovaries) was performed for rats of the EA＋sham OVX group. EA (2 Hz, 2 mA) was applied to bilateral "Tianzong"(SI 11), "Ganshu"(BL 18), "Zusanli" (ST 36) for point group A, and "Wuyi"(ST 15), "Hegu"(LI 4), "Danzhong" (CV 17) for point group B for 20 min, once daily, 5 days a week for 4 weeks. The two acupoint groups were used alternately. The height of the rats' nipples (the 2nd pairs) were measured. Serum E2 and P levels were assayed by ELISA. The expression of ERα and PR in mammary tissues was detected by immunofluorescence staining and Western blot, separately. RESULTS: The height of nipples, serum E2content, and mammary ERα protein expression level were significantly higher in the model group than in the control group (P<0.01), while serum P content and PR expression were remarkably lower in the model group than in the control group (P<0.01). Following EA intervention, the height of nipples, serum E2content and mammary ERα protein expression level in both EA and EA＋sham OVX groups, and ERα expression in the EA＋OVX group were considerably lower in comparison with those of the model group(P<0.01), and serum P content and PR expression in the 3 EA groups were significantly higher than those in the model group (P<0.01，P<0.05). But there were no significant changes in the nipple height and serum E2 levels in the EA＋OVX group relevant to the model group (P>0.05), suggesting an important role of the ovary in producing EA's effect. CONCLUSION: EA intervention can improve hyperplastic mammary glands by down-regulating serum E2content and mammary ERα protein expression, and up-regulating serum P content and PR expression in MGH rats, which has a close relation with the intact ovaries.

Development and evaluation of in murine model, of an improved live-vaccine candidate against brucellosis from to Brucella melitensis vjbR deletion mutant.

Brucellosis is an infectious disease that brings enormous economic burdens for developing countries. The Brucella melitensis (B. melitensis) M5-90 vaccine strain (M5-90) has been used on a large scale in China, but may cause abortions if given to pregnant goats or sheep subcutaneously during the late stages of gestation. Moreover, the vaccine M5-90 cannot differentiate natural from vaccinated infection. Therefore, a safer and more potent M5-90 vaccine is required. In this study, a vjbR mutant of M5-90 (M5-90ΔvjbR) was constructed and overcame these drawbacks. M5-90ΔvjbR strain showed reduced survival capability in murine macrophages (RAW 264.7) and BALB/c mice and induced high protective immunity in mice. In addition, M5-90ΔvjbR induced an anti-Brucella-specific immunoglobulin G (IgG) response and stimulated the expression of gamma interferon (INF-γ) and interleukin-4 (IL-4) in vaccinated mice. Furthermore, M5-90ΔvjbR induced IgG response and stimulated the secretion of IFN-γ and IL-4 in immunized sheep. Moreover, the VjbR antigen allowed serological differentiation between infected and vaccinated animals. These results suggest that M5-90ΔvjbR is an ideal live attenuated and efficacious live vaccine candidate against B. melitensis 16 M infection.

Design, synthesis and antifungal activity evaluation of coumarin-3-carboxamide derivatives.

A series of coumarin-3-carboxamides/hydrazides have been designed and synthesized, all the target compounds were evaluated in vitro for their antifungal activity against Botrytis cinerea, Alternaria solani, Gibberella zeae, Rhizoctorzia solani, Cucumber anthrax and Alternaria leaf spot, some of the designed compounds 4a-4g exhibited potential activity in the primary assays, this highlighted by the compounds 4a, 4d, 4e and 4f, EC50 values of which against Rhizoctorzia solani were as low as 1.80 µg/mL, 2.50 µg/mL, 2.25 µg/mL and 2.10 µg/mL, respectively, exhibiting more effective control with that of the positive control than Boscalid. Furthermore, compounds 4a and 4e represented equivalent antifungal activity with Boscalid against Botrytis cinerea.

Chelant-enhanced washing of CCA-contaminated soil: Coupled with selective dissolution or soil stabilization.

Remediation of CCA-contaminated soil (Cr, Cu, and As) by biodegradable chelant-enhanced washing (EDDS, S,S-ethylene-diamine-disuccinic-acid) needs further enhancement. This study investigated the effectiveness of coupling with pre-treatment by selective dissolution and post-treatment by soil amendments, respectively. Three groups of reagents (reductants, alkaline solvents, and organic ligands) were adopted in the pre-treatment to dissolve the oxide minerals before EDDS extraction. In the post-treatment, soil amendments (coal fly ash (CFA), acid mine drainage sludge (AMDS), green waste compost (GWC)), and their mixtures) were used for a 2-month stabilization after 2-h EDDS washing. Multi-endpoint evaluation was performed by assessing the chemical state, leachability, mobility, bioaccessibility, and plant-availability of residual metal(loid)s as well as the cytotoxicity, enzyme activities, and available nutrients of the treated soils. Pre-treatment by dithionite-citrate-bicarbonate significantly enhanced extraction efficiency, but also increased the leachability of As and Cr and bioaccessibility of Cr in the treated soils. While sodium hydroxide removed the majority of As without increasing its leachability and bioaccessibility, it increased the cytotoxicity and inhibited the acid phosphatase activity. Post-treatment with AMDS and CFA effectively controlled the mobility and leachability of residual As and Cr after EDDS washing. However, destabilized Cu was only marginally immobilized by GWC due to strong Cu-EDDS complexation. The bioaccessibility and phytoavailability of Cu was primarily reduced by EDDS washing, while those of As and Cr could be attenuated by AMDS and CFA. This study indicates that coupling chemical extraction with subsequent soil amendment plays complementary roles in mitigating effects of residual metal(loid)s and improving environmental quality.

An efficient synthesis and antifungal evaluation of natural product streptochlorin and its analogues.

Streptochlorin, a small indole alkaloid isolated from marine Streptomyces sp., exhibits a wide range of potent biological activities. An efficient and economic synthetic protocol for streptochlorin has been developed and validated, 4 steps from indole in a total yield of 45%, and further applied for the synthesis of its analogues. Biological testing showed that most of the target compounds exhibited potential antifungal activity in the primary assays, especially compounds 6, 7 and 9c were the most active ones, representing effective activity against the phytopathogenic fungi screened in preliminary test and might be explored for the study of mode of action in the future.