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Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii . Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B ( 16 ) and trioxacarcin G ( 20 ), together with known gutingimycin ( 12 ), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.

Two new lignans ( 1 - 2 ), along with five known compounds ( 3 - 7 ) with different structures were isolated from leaves and twigs of Cleistanthus concinnus Croizat. The new lignans were elucidated as (7'R,8'S)-3,3',5'-trimethoxy-4,4'-dihydroxy-7-en-7',9- epoxy-8,8'-lignan ( 1 ) and (7'R,8'S)-3,3'-dimethoxy-4,4'-dihydroxy-7-en-7',9-epoxy-8, 8'-lignan ( 2 ) by comprehensive spectroscopic analysis including 1D and 2D NMR as well as HREIMS and comparing their NMR data with known compounds in the literature. Among these isolated compounds, compound 1 , 2 , 3 , and 6 were tested for anti- inflammatory effects by inhibiting NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Compound 1 , 2 , and 6 exhibit NO inhibitory activity.[Formula: see text].

Background: Guanxin V (GXV), a traditional Chinese medicine (TCM), has been widely used to treat coronary artery disease (CAD) in clinical practice in China. However, research on the active components and underlying mechanisms of GXV in CAD is still scarce., Methods: A virtual screening and network pharmacological approach was utilized for predicting the pharmacological mechanisms of GXV in CAD. The active compounds of GXV based on various TCM-related databases were selected and then the potential targets of these compounds were identified. Then, after the CAD targets were built through nine databases, a PPI network was constructed based on the matching GXV and CAD potential targets, and the hub targets were screened by MCODE. Moreover, Metascape was applied to GO and KEGG functional enrichment. Finally, HPLC fingerprints of GXV were established., Results: A total of 119 active components and 121 potential targets shared between CAD and GXV were obtained. The results of functional enrichment indicated that several GO biological processes and KEGG pathways of GXV mostly participated in the therapeutic mechanisms. Furthermore, 7 hub MCODEs of GXV were collected as potential targets, implying the complex effects of GXV-mediated protection against CAD. Six specific chemicals were identified., Conclusion: GXV could be employed for CAD through molecular mechanisms, involving complex interactions between multiple compounds and targets, as predicted by virtual screening and network pharmacology. Our study provides a new TCM for the treatment of CAD and deepens the understanding of the molecular mechanisms of GXV against CAD.

One new lignan derivative 2,3-dimethyl-4-(4'-hydroxy-3',5'-dimethoxyphenyl)-6-hydroxy-7-methoxy-naphthalene ( 1 ), together with four known analogues ( 2-5 ), were isolated from acetone extract of the fruiting bodies of Ganoderma lipsiense collected in the Hainan Province, China. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Compound 1 showed insecticidal activity against newly hatched karvae of Helicoverpa armigera Hubner . Compounds 1 - 5 showed moderate antibacterial activity against Staphylococcus aureus with the same MIC value of 1.25 μg/mL.

Chinese olive is served as a famous fruit and traditional herb in China. In this study, the anti-neuroinflammatory and antioxidant phytochemicals of Chinese olive fruits were investigated. Three new phenylpropanoids (2, 6, 19), together with sixteen known congeners, have been isolated and identified. A variety of bioactivities related to the traditional healthy benefits of Chinese olive, including anti-neuroinflammatory, antioxidant and antidiabetic, have been evaluated for the identified compounds. The phenylpropanoids could significantly inhibit the production of nitric oxide induced by lipopolysaccharide (LPS) in microglia cells (BV-2). Compounds 2, 6, and 19 could dose-dependently reduce the expression levels of pro-inflammatory mediator iNOS and COX-2 expressions induced by LPS in BV-2 cells. Meanwhile, some phenylpropanoids showed remarkable antioxidant and antidiabetic activities. This study suggested that Chinese olive could be served as a healthy product for neuroinflammatory related diseases, such as Alzheimer's disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An improved, reliable and comprehensive method for assessing the quality of the ethyl acetate extract from persimmon leaves (EAPL) and its commercial preparation, Naoxinqing (Brain and Heart Clear capsules), has been developed and validated. Based on HPLC-DAD-ESI-Q-TOF-MS analysis, myricetin-3-O-β-D-galactoside (1), myricetin-3-O-glucoside (2), quercetin-3-O-β-D-galactoside (3), quercetin-3-O-β-D-glucoside (4), quercetin-3-O-(2″-O-galloyl-β-D-galactoside) (5), quercetin-3-O-(2″-O-galloyl-β-D-glucoside) (6), kaempferol-3-O-β-D-galactoside (7), kaempferol-3-O-β-D-glucoside (8), kaempferol-3-O-(2″-O-galloyl-β-D-galactoside) (9), kaempferol-3-O-(2″-O-galloyl-β-D-glucoside) (10), quercetin (11) and kaempferol (12) were identified from 15 batch samples. A HPLC fingerprint analytical method was established. All compounds, with the exception of compound 2, were simultaneously quantified by the single standard to determine multi-components (SSDMC) method, using kaempferol-3-O-β-D-glucoside as the internal standard. The rate of analysis was found to be faster with the SSDMC method than with current acid hydrolysis method (Pharmacopoeia of the People's Republic of China 2015 edition) and the results were more intuitive and reliable. Three-dimensional principal component analysis revealed that there were similar characteristics in persimmon leaf from same district. Analysis of the myocardial cell protection activity of 11 monomeric compounds showed that compounds 12, 11 and 10 were the main active ingredients that produce pharmacologic functions in EAPL. Among these compounds, the bioactive constituent of myricetin-3-O-β-D-galactoside was determined for the first time in Diospyros khaki. Thus, we have established an effective assessment method that can be applied to the comprehensive quality evaluation of EAPL extract and Naoxinqing capsule.

Pheromones can be used as leafhopper attractants. However, commercial pheromone products, such as the Ingle lure, have certain limitations, including poor persistence in the field. In this study, ( E )-2-hexenal, ( Z )-3-hexen-1-ol, ( Z )-3-hexenyl acetate, ( E )-ocimene, linalool, and geraniol were selected and behaviorally tested as potential leafhopper attractants. Y-tube olfactometer tests showed that the C2 formulation was more effective than other formulations. In tea field trials, the number of leafhoppers caught by sticky board traps baited with C2 lures was greater than that caught by treatment. The number of leafhoppers attracted by the C2 lures was greater than that attracted by the commercial Ingle lures. Additionally, the total amount of active C2 components on lures was greater than that of the active components on the lure after 14 days. Thus, the results indicated that the C2 formulation may attract leafhoppers and have a greater persistence than other formulations in tea field.

Dicycloplatin (DCP) has better solubility and stability than both cisplatin and carboplatin. Pre-clinical and phase I studies demonstrated significant antitumor activity and fewer adverse events than carboplatin. Phase II clinical trials in advanced non-small cell lung cancer found efficacy and safety of DCP-plus-paclitaxel comparable to carboplatin-plus-paclitaxel but better tolerability. This article summarizes and reviews pre-clinical and clinical data for dicycloplatin from the Chinese medical literature. We also report on new mechanistic findings in our laboratory in West Virginia, USA. Patient blood samples were collected for DCP-prototype determination by liquid chromatography mass spectrometry (LC-MS/MS). Molecular studies of ovarian cancer cells treated with DCP or cisplatin were carried out for gene-signature profiling using immunoblotting. Pharmacokinetic mass-spectrometry showed different spectrum profiles of DCP and carboplatin in plasma. Plasma concentration of DCP prototype was 17.1 μg/ml 2h after administration, with a peak concentration of 26.9 μg/ml at 0.5 h. Immunoblotting showed DCP-induced activation of DNA damage pathways, including double-phosphorylated checkpoint kinase 2 (CHK2) and breast cancer 1 (BRCA1) and triple-phosphorylated p53, compared to controls. Cisplatin produced a similar profile, with increased p53 protein. DCP and cisplatin activate DNA-damage response through similar pathways. DCP may be more soluble and stable, and better-tolerated.

Studies indicated that lactate dehydrogenase C4 (LDH-C4) was a good target protein for development of contraceptive drugs. Virtual screening and in vitro enzyme assay using pika LDH-C4 as target protein revealed NSC61610, NSC215718, and NSC345647 with Ki of 7.8, 27, and 41 μM separately. This study might be helpful for development of pika contraceptive drugs.

Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes in the manufacturing process and vaccine formulation, to start directly with phase 1 clinical trials.

The oncolytic virus, being a promising new therapeutic strategy for cancer, has inspired a wave of recent clinical research and development in China. The first commercialized oncolytic virus, Oncorine, was approved by Chinese SFDA in November 2005 for nasopharyngeal carcinoma combined with chemotherapy. Since then, a number of oncolytic viruses have been moved into clinical trials. Among these are the armed oncolytic adenoviruses such as H103 (expressing the heat shock protein) currently has finished phase I trial, and KH901 (expressing GM-CSF) now launched in phase II trial In this review, we will discuss the current status of ongoing oncolytic virus projects being conducted at various clinical stages in China, including the preliminary market response for Oncorine after it was launched into the Chinese market in 2006.

Evaluation of the chemical composition and antihyperglycemic and antioxidant activity of five wild edible mushrooms (Clitocybe maxima, Catathelasma ventricosum, Stropharia rugoso-annulata, Craterellus cornucopioides and Laccaria amethystea) from Southwest China. The chemical composition assay includes proximate analysis (moisture, ash, crude protein, crude fat, total carbohydrates and total energy), bioactive compounds analysis (total phenolic, flavonoid, ascorbic acid, ergosterol, tocopherol), fatty acid analysis, amino acid analysis, phenolic compounds analysis and mineral analysis of these mushrooms. Furthermore, assays of α-glucosidase inhibitory and α-amylase inhibitory activity were used for evaluating antihyperglycemic activity of the mushrooms, and assays of reducing power, chelating effect on ferrous ions, scavenging effect on hydroxyl free radicals and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were used for evaluating antioxidant activity of the mushrooms. Based on the results, ethanolic and aqueous extract of these mushroom all showed antihyperglycemic and antioxidant potential. In particular, the aqueous extract of C. ventricosum revealed the highest α-glucosidase inhibitory activity (EC50 value 2.74 μg/mL), DPPH radical scavenging activity (EC50 value 2.86 mg/mL) and reducing power (EC50 value 0.96 mg/mL), while the aqueous extract of L. amethystea showed the highest α-amylase inhibitory activity (EC50 value 4.37 μg/mL) and metal chelating activity (EC50 value 2.13 mg/mL)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The traditional herbal medicinal formula Da-Cheng-Qi decoction (DCQD) has long been used to treat pancreatitis in China; however, the underlying mechanisms remain unclear., Aim: To investigate whether DCQD is beneficial to the patients with lung injury in severe acute pancreatitis (SAP); if it is, then to explore the lung protective effect of DCQD and the mechanism involved in rats., Methods: DCQD was enema administered to 70 patients for 7 days. Mortality, (multi)organ failure during admission were observed, blood samples for laboratory analysis were drawn on admission, on Days 3, 7, and 14 of the treatment. We also experimentally examined the function of two doses of DCQD in SAP rat models. IL-1β, IL-6, and IL-10 mRNA expression in rat lungs was measured quantitatively by the RT-PCR method and confirmed by morphometric studies of the lungs., Results: It was demonstrated that the administration of DCQD did shorten the average time that patients suffered acute respiratory distress syndrome (ARDS). Compared with untreated rats, the lungs of rats treated with DCQD showed significantly lower levels of proinflammatory cytokine IL-1β and IL-6 mRNA. Rats treated with DCQD had lower mean pathological lung lesion scores than those in SAP rats., Conclusion: DCQD has good prospects in the treatment for SAP because it did shorten the average time that patients suffered ARDS in the clinic. It exerts therapeutic effects on this disease through inhibiting the production of inflammatory mediators, decreasing the anti-inflammatory factors, and mitigating the pathological damage of the lung injury in SAP model.

Gentiana rhodantha Franch. ex Hemsl. (Gentianaceae), an annual herb widely distributed in the southwest of China, has been medicinally used for the treatment of inflammation, cholecystitis, and tuberculosis by the local people of its growing areas. Chemical investigation on the whole plants led to the identification of eight new phenolic compounds, rhodanthenones A-D (1-4, resp.), apigenin 7-O-glucopyranosyl-(1→3)-glucopyranosyl-(1→3)-glucopyranoside (5), 1,2-dihydroxy-4-methoxybenzene 1-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (6), 1,2-dihydroxy-4,6-dimethoxybenzene 1-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (7), and methyl 2-O-β-D-glucopyranosyl-2,4,6-trihydroxybenzoate (8), together with eleven known compounds, 9-19. Their structures were determined on the basis of detailed spectroscopic analyses and chemical methods. Acetylcholinesterase (AChE) inhibition and cytotoxicity tests against five human cancer cell lines showed that only rhodanthenone D (4) and mangiferin (12) exhibited 18.4 and 13.4% of AChE inhibitory effects at a concentration of 10(-4) M, respectively, while compounds 1-5 and the known xanthones lancerin (11), mangiferin (12), and neomangiferin (13) displayed no cytotoxicity at a concentration of 40 μM., (Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.)

The aim of this study was to determine the most effective hypoglycemic component of polysaccharides from Opuntia dillenii Haw. by preliminary screening and to specifically study the antidiabetic effects of O. dillenii polysaccharide (ODP)-Ia in mice with streptozotocin (STZ)-induced diabetes. Three kinds of ODPs - ODP-Ia, ODP-Ib, and ODP-II' - were isolated by using an ultrasonic extraction method and diethylaminoethyl (DEAE)-Sepharose fast-flow column chromatography. The mice were administered ODPs for 3 weeks. Gavage administration of ODP-Ia significantly decreased (P<0.05) their intake of food and water; the fasting levels of blood glucose (BG), total cholesterol (TC), triglycerides (TGs), plasma urea nitrogen (PUN), and malondialdehyde (MDA); and the activity of glucose-6-phosphatase (G-6-Pase). In contrast, it significantly increased (P<0.05) the body weights, hepatic glycogen (HG) levels, high-density lipoprotein cholesterol (HDL-C) levels, and the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in diabetic mice. However, ODP-Ia did not significantly increase insulin levels in the mice with STZ-induced diabetes. We propose that ODP-Ia exerts its antihyperglycemic effect by protecting the liver from peroxidation damage and by maintaining tissue function, thereby improving the sensitivity and response of target cells in diabetic mice to insulin., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Cornu Rhinoceri Asiatici (rhinoceros horn, RH), Cornu Bubali (water buffalo horn, WBH), and Cornu Bovis grunniens (yak horn, YH) are traditional Chinese medicine (TCM), and have been used in China for thousands of years. In this study, ethnopharmacological experiments were used to evaluate and verify the traditional efficacies of horns. Area under curve (AUC) was used to quantify the pharmacological efficacy strength of three horns. Two-dimensional electrophoresis (2-DE) was used to analyze the protein components in horns, as a result, 14 common protein spots in rhinoceros horn, water buffalo horn, and yak horn electrophoresis gels were found by image analysis. Then linear regression analysis was used to establish the correlation between pharmacological efficacies and components in the horns, and five potential active components were selected from the 14 common protein spots. Finally, two protein spots from five were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). In this study, a simple method to construct correlation between components and efficacy strength was explored by linear regression analysis, which could be applied to screen potential active components of animal horns., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the effect of general glycosides from Cynanchun auriculatum of Jiangsu on liver fibrosis of rats., Method: Seventy-two Wistar rats were randomly divided into normal group, model group, BSW three doses treated group and hydrocortisone treated group. CCl4 (50%, 2 mL x kg(-1)) was orally administraeated twice a week for 8 weeks. The liver and spleen indices were observed. The level of serum GPT, GOT, and HA, PCIII and the level of SOD, HyP, MDA in liver homogenates was also measured. The histopathologic change in hepatic of rats was examined., Result: The elevation of serum GPT, GOT, HA, PCIll, MDA and HyP and the content of liver homogenates were attanuated remarkably by BSW treatment. BSW groups also increased the level of SOD of liver homogenates, and make the fibrotic liver better., Conclusion: The general glycosides in C. auriculatum of jiangsu province have an anti-hepatic fibrosis ettect on CCl4-induced fibrosis rats, the mechanisms might be associated with its anti-oxidative action.

Aim of the Study: Since ancient times, practicians of traditional Chinese medicine have discovered that Artemisia sphaerocephala Krasch. (Asteraceae) seed powder was useful for the treatment of diabetes. Artemisia sphaerocephala Krasch. gum (ASK gum), which is extracted from seed powder of the plant, is a novel food additive favored by the food industry in China. The objective of this study was to determine the antidiabetic function of ASK gum on type 2 diabetes., Materials and Methods: Type 2 diabetic rat model was induced with high fat diet and low dose of streptozotocin (STZ). The effects of ASK gum on hyperglycemia, hyperlipemia, insulin resistance, and liver fat accumulation in type 2 diabetic rats were evaluated. The results were compared to those of normal rats and diabetic rats treated with metformin., Results: The addition of ASK gum to the rats' food supply significantly lowered fasting blood glucose, glycated serum protein, serum cholesterol, and serum triglyceride in type 2 diabetic rats, and significantly elevated liver glucokinase, liver glycogen, and serum high density protein cholesterol in the diabetic rats. ASK gum significantly reduced insulin resistance and liver fat accumulation of type 2 diabetes., Conclusion: Artemisia sphaerocephala Krasch. gum can alleviate hyperglycemia, hyperlipemia and insulin resistance of type 2 diabetes.

Objective: To evaluate the safety and epidemiological effect of the Freeze-dried Live attenuated varicella vaccine., Methods: A random, double-blind control clinical trial was adopted., Results: In the observation period, the incidence of varicella was 0.8 per thousand in the experimental group and 8.7 per thousand in control group. There was a significant difference (B.P=0.000017). Vaccine effectiveness (VE(%)) was 90.8%, the lower limit of 95%CI was 88.7%., Conclusion: The varicella vaccine produced by Changchun keygen biological products co., Ltd. was safe and effective.

Background: There is increasing evidence to suggest an immunomodulation function both within the intestines and systemically upon consuming probiotic species. We recently isolated a novel LAB, Lactobacillus caseiZhang (LcZhang) from koumiss. LcZhang exhibited favorable probiotic properties, such as acid resistance, bile resistance, gastrointestinal (GI) colonization ability, etc. In order to examine the immunomodulatory qualities of LcZhang, we administered LcZhang to healthy mice with varying doses of either live or heat-killed LcZhang and measured various parameters of the host immune response., Results: The study was performed in four separate experiments via oral administration of live and heat-killed LcZhang to BALB/c mice for several consecutive days. We investigated the immunomodulating capacity of LcZhang in vivo by analyzing the profile of cytokines, T cell subpopulations, and immunoglobulin concentrations induced in blood serum and intestinal fluid in BALB/c mice. Only live bacteria elicited a wide range of immune responses, which include the increased production of interferon-gamma (IFN-gamma), and depression of tumor necrosis factor-alpha (TNF-alpha) levels. In addition, interleukin-2 (IL-2) and IL-2 receptor gene transcription increased significantly, but the proportion of T cell subsets appeared to be unaffected. We also observed that LcZhang was capable of inducing gut mucosal responses by enhancing the production of secretory Immunoglobulin A (sIgA) as well influencing the systemic immunity via the cytokines released to the circulating blood., Conclusion: The present work shows that the dose-dependent administration of LcZhang is capable of influencing immune responses, implying that it may be a valuable strain for probiotic use in humans.

Enfuvirtide (T20) is the first and only HIV-1 fusion inhibitor approved for clinical use, but it can easily induce drug resistance limiting its practical application. A novel anti-HIV peptide, termed sifuvirtide, was designed based on the three-dimensional structure of the HIV-1 gp41 fusogenic core conformation. Here we report its in vitro anti-HIV potency, its mechanism of action, as well as the results from Phase Ia clinical studies. We demonstrated that sifuvirtide inhibited HIV-1-mediated cell-cell fusion in a dose-dependent manner and exhibited high potency against infections by a wide range of primary and laboratory-adapted HIV-1 isolates from multiple genotypes with R5 or X4 phenotypes. Notably, sifuvirtide was also highly effective against T20-resistant strains. Unlike T20, sifuvirtide could efficiently block six-helix bundle formation in a dominant negative fashion. These results suggest that sifuvirtide has a different mechanism of action from that of T20. Phase Ia clinical studies of sifuvirtide (FS0101) in 60 healthy individuals demonstrated good safety, tolerability, and pharmacokinetic profiles. A single dose regimen (5, 10, 20, 30, and 40 mg) by subcutaneous injection once daily at abdominal sites was well tolerated without serious adverse events. Pharmacokinetic studies of single and multiple administration of sifuvirtide showed that its decay half-lives were 20.0 +/- 8.6 h and 26.0 +/- 7.9 h, respectively. In summary, sifuvirtide has potential to become an ideal fusion inhibitor for treatment of HIV/AIDS patients, including those with HIV-1 strains resistant to T20.

The antifungal susceptibility of isolates from Chinese dermatomycosis patients to amorolfine was investigated following National Committee for Clinical Laboratory Standards (NCCLS) protocols. In total, 383 isolates were tested, including 132 strains from tinea pedis, 148 strains from tinea corporis/cruris, and 103 strains from onychomycosis. The minimum inhibitory concentration (MIC) of amorolfine against dermatophytes ranged from 0.01 to 0.08 microg ml(-1). The MIC(50) and MIC(90) of amorolfine for Trichophyton rubrum were both equal to 0.04 micro ml(-1); for T. mentagrophytes these MICs were 0.04 microg ml(-1) and 0.08 microg ml(-1) respectively; and for Epidermophyton floccosum they were 0.02 microg ml(-1) and 0.04 microg ml(-1) respectively. The MIC range of amorolfine against Candida parapsilosis was 0.5-16 microg ml(-1). MIC(50) and MIC(90) for C. parapsilosis were 0.5 and 2 microg ml(-1). MIC ranges of amorolfine against Scopulariopsis spp. and Acremonium spp. were 0.5-4 and 2-8 microg ml(-1), respectively. Candida albicans, Fusarium solani and Aspergillus flavus required relatively higher concentrations of amorolfine to inhibit their growth (MIC 0.125-64 microg ml(-1), MIC(50) and MIC(90) were 4 and 64 microg ml(-1)). The results demonstrated that amorolfine is the only topical agent that has such a potent antifungal activity and a broad spectrum against a wide range of pathogenic fungi.

An increasing portion of patients with HIV infection and/or AIDS cannot use currently FDA-approved anti-HIV drugs, including the reverse transcriptase and protease inhibitors, due to the adverse effects and the emergence of drug resistance. Thus, it is essential to develop new anti-HIV agents with a target different from the HIV reverse transcriptase and protease. Using a conformation-specific monoclonal antibody NC-1, we previously established a high throughput screening assay for identification of small molecular organic compounds that disrupt the HIV-1 gp41 six-helix bundle formation, a critical step of membrane fusion between the HIV and the target cell. In the present study, we used this assay to screen for inhibitors of the gp41 six-helix bundle formation from aqueous extracts of nine Chinese medicinal herbs with antiviral activity. We found that the extracts of two herbs, Prunella vulgaris and Rhizoma cibotte, showed potent inhibitory activity. The inhibitory activity of these two herb extracts significantly decreased after they were passed through polyamide resin mini-columns, which are able to bind polyphenols including tannin, an HIV-1 inhibitor with multiple mechanisms of action. The bound polyphenols were eluted from the polyamide columns and also showed potent inhibitory activity on the gp41 six-helix bundle formation. Tannin purchased from different commercial sources inhibited the gp41 six-helix bundle formation in a manner similar to the polyphenols isolated from the herb extracts. These results suggest that tannin may be one of major inhibitors of the HIV-1 gp41 six-helix bundle formation in the herb extracts and that tannin may inhibit HIV-1 entry by disrupting the gp41 six-helix bundle formation.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.

It is evident that intermittent iron supplementation is better than daily supplementation in two aspects: iron absorption is more efficient and has insignificant side effects in contrast to the daily dose. The significantly higher daily iron loss observed in the daily iron supplemented groups rats also suggests alterations in total body iron metabolism. Based on serum ferritin distribution patterns, intermittent iron supplementation avoids temporary iron overload with daily iron supplemented. We conclude that weekly iron supplementation scheme is safer and easier to administer. This feasible strategy for the control of iron deficient anemia in pregnant women and children would be an effective iron-supplementation program (Baily et al., 1993).

The results of research in China in recent years show that: 1) Different laboratory sensitivity of adult Anopheles minimus, An. sinensis and Culex pipiens quinquefasciatus to deltamethrin exist in Yunnan. Although the range and duration for the use of permethrin and deltamethrin was limited, resistance of An. minimus, An. sinensis and Cx. pipiens quinquefasciatus to different extent in some areas existed. 2) On walls built with cement and covered with a thin layer of lime on which deltamethrin at a dosage of 0.025 g/m2 was sprayed, 100% of the mosquitos were stricken down within 3 days, 80% at the 15th day, 50% at the 20th day. The residual effectiveness on the bamboo and wood walls was good and could last for over 40 days, but on the mud walls a mortality of only 40% on the spraying day was observed, indicating that deltamethrin was not suitable for this purpose. Deltamethrin spraying reduced total caught mosquitos within 30 days, but there was no difference between the effects of deltamethrin (0.025 g/m2) and DDT (2 g/m2) at the 60th day. Deltamethrin effect on reducing densities of endophilic An. vagus, An. culicifacies and exophilic An. philippinensis was better than that of DDT (lasting over 60 days), but its effect on semi-endophilic An. sinensis lasted only 15 days. Against An. mininus, it showed good effects within 20 days but did not last as long as DDT (60 days). Residual deltamethrin and DDT spraying could both control malaria vectors, reduce the infection of infants by malaria, and reduce malaria parasite carrier rates (within 50 days). 3) Laboratory experiments showed that deltamethrin-impregnated bednets at a dosage of 0.015 g/m2 had a positive effect on An. minimus. The residual effect of unwashed deltamethrin-impregnated bednets at a dosage of 0.015 mg/m2 against An. sinensis was apparent and could last for 13 months. When an impregnated bednet was washed for the first time at the 12th month, its mortality effect on An. sinensis was reduced quickly to lower than 50%. The residual effect could last for 2-3 months when washed at the 6th month, but was lost when washed for the second time at the 12th month. 4) The effects of the impregnated-bednets on An. sinensis were different, even opposite, between different investigations. However, the treated bednets caused the density of An. minimus in houses to fall by 67.94%, and the total density in houses and cattle shelters by 67.91%. Moreover, it could shorten the life span of An. minimus. It did not work on the outdoor density of An. minimus. It is necessary to integrate with other measures, for achieving the desired effect.

In order to investigate clonorchicidal activity in vivo, boiled water extracts of 32 species of clonorchicidal raw drugs in vitro were orally administered into rabbits infected with Clonorchis sinensis. The results of the observation of EPG variation were as follows: Suppression effects of egg-laying capacity from the rabbits administered Prunus mume and Inula helenium were greatest. Those from Dictamnus dasycarpus and Saussurea lappa were somewhat effective. Machilus thunbergii and Cassia obutusifolia, however, were less effective.

A review is presented which shows the vegetable kingdom as an almost inexhaustible reservoir of potential drugs. Some historical aspects about the use of plants and their constituents in medicine are dealth with. A number of problems connected with the search for new prototype drugs of biological origin is reported as well as modern methods used in this promising research. Some examples are given concerning recent results of investigations of plants used in traditional and modern medicine in China. Special attention is paid to the present role of natural products in therapy: as biologically active compounds as such, as starting materials for (semi)synthetic drugs and, last but not least, as source of inspiration or as models for the synthesis of new drugs with better therapeutic, chemical or physical properties than the original compounds.