Guanxinning tablets improve myocardial hypertrophy by inhibiting the activation of MEK-ERK1/2 signaling pathway.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma.

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.

Phosphorus limitation induced by nitrogen addition changed soil microbial community structure in a subtropical Pinus taiwanensis forest.

Soil microorganisms play an important role in the biogeochemical cycles of terrestrial ecosystems. How-ever, it is still unclear how the amount and duration of nitrogen (N) addition affect soil microbial community structure and whether there is a correlation between the changes in microbial community structure and their nutrient limi-tation status. In this study, we conducted an N addition experiment in a subtropical Pinus taiwanensis forest to simulate N deposition with three treatments: control (CK, 0 kg N·hm-2·a-1), low N (LN, 40 kg N·hm-2·a-1), and high N (HN, 80 kg N·hm-2·a-1). Basic soil physicochemical properties, phospholipid fatty acids content, and carbon (C), N and phosphorus (P) acquisition enzyme activities were measured after one and three years of N addition. The relative nutrient limitation status of soil microorganisms was analyzed using ecological enzyme stoichiometry. The results showed that one-year N addition did not affect soil microbial community structure. Three-year LN treatment significantly increased the contents of Gram-positive bacteria (G+), Gram-negative bacteria (G-), actinomycetes (ACT), and total phospholipid fatty acids (TPLFA), whereas three-year HN treatment did not significantly affect soil microbial community, indicating that bacteria and ACT might be more sensitive to N addition. Nitrogen addition exacerbated soil C and P limitation. Phosphorus limitation was the optimal explanatory factor for the changes in soil microbial community structure. It suggested that P limitation induced by N addition might be more beneficial for the growth of certain oligotrophic bacteria (e.g. G+) and the microorganisms participating in the P cycling (e.g. ACT), with consequences on soil microbial community structure of subtropical Pinus taiwanensis forest.

[Responses of soil microbial carbon use efficiency to short-term nitrogen addition in Castanopsis fabri forest]. / ç½—æµ®æ ²æž—åœŸå£¤å¾®ç”Ÿç‰©ç¢³åˆ©ç”¨æ•ˆçŽ‡å¯¹çŸ­æœŸæ°®æ·»åŠ çš„å“åº”.

As an important parameter regulating soil carbon mineralization, microbial carbon use efficiency (CUE) is essential for the understanding of carbon (C) cycle in terrestrial ecosystems. Three nitrogen supplemental levels, including control (0 kg N·hm-2·a-1), low nitrogen (40 kg N·hm-2·a-1), and high nitrogen (80 kg N·hm-2·a-1), were set up in a Castanopsis fabri forest in the Daiyun Mountain. The basic physical and chemical properties, organic carbon fractions, microbial biomass, and enzyme activities of the soil surface layer (0-10 cm) were measured. To examine the effects of increasing N deposition on microbial CUE and its influencing factors, soil microbial CUE was measured by the 18O-labelled-water approach. The results showed that short-term N addition significantly reduced microbial respiration rate and the activities of C and N acquisition enzymes, but significantly increased soil microbial CUE. ß-N-acetyl amino acid glucosidase (NAG)/microbial biomass carbon (MBC), microbial respiration rate, ß-glucosidase (BG)/MBC, cellulose hydrolase (CBH)/MBC, and soil organic carbon content were the main factors affecting CUE. Moreover, CUE significantly and negatively correlated with NAG/MBC, microbial respiration rate, BG/MBC, and CBH/MBC, but significantly and positively correlated with soil organic carbon. In summary, short-term N addition reduced the cost of soil microbial acquisition of C and N and microbial respiration, and thus increased soil microbial CUE, which would increase soil carbon sequestration potential of the C. fabri forest.

Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

[Effects of nitrogen addition on the kinetic parameters of soil acid phosphomonoesterase in a Moso bamboo forest]. / æ°®æ·»åŠ å¯¹æ¯›ç«¹æž—åœŸå£¤é ¸æ€§ç£·é ¸å•é ¯é ¶åŠ¨åŠ›å­¦å‚æ•°çš„å½±å“.

Soil phosphatases are important in the mineralization of organophosphates and in the phosphorus (P) cycle. The kinetic mechanisms of phosphatases in response to nitrogen (N) deposition remain unclear. We carried out a field experiment with four different concentrations of N: 0 g N·hm-2·a-1(control), 20 g N·hm-2·a-1(low N), 40 g N·hm-2·a-1(medium N), and 80 g N·hm-2·a-1(high N) in a subtropical Moso bamboo forest. Soil samples were then collected from 0 to 15 cm depth, after 3, 5 and 7 years of N addition. We analyzed soil chemical properties and microbial biomass. Acid phosphatase (ACP) was investigated on the basis of maximum reaction velocity (Vm), Michaelis constant (Km), and catalytic efficiency (Ka). Results showed that N addition significantly decreased soil dissolved organic carbon (DOC), available phosphorus, and organophosphate content, but significantly increased soil ammonium, nitrate-N content, and Vm. There was a significant relationship between Vm and the concentrations of available phosphorus, organophosphate, and soil DOC. In general, N addition substantially increased Ka, but did not affect Km. The Km value in the high N treatment group was higher than that in the control group after five years of N addition. Km was significantly negatively associated with both available phosphorus and organophosphate. Medium and high N treatments had stronger effects on the kinetic parameters of ACP than low N treatment. Results of variation partition analysis showed that changes in soil chemical properties, rather than microbial biomass, dominated changes in Vm(47%) and Km(33%). In summary, N addition significantly affected substrate availability in Moso bamboo forest soil and modulated soil P cycle by regulating ACP kinetic parameters (especially Vm). The study would improve the understanding of the mechanisms underlying soil microorganisms-regulated soil P cycle under N enrichment. These mechanisms would identify the important parameters for improving soil P cycling models under global change scenarios.

[Soil enzyme stoichiometry revealed the changes of soil microbial carbon and phosphorus limitation along an elevational gradient in a Pinus taiwanensis forest of Wuyi Mountains, Southeast China]. / åœŸå£¤é ¶è®¡é‡æ­ç¤ºäº†æ­¦å¤·å±±é»„å±±æ¾æž—åœŸå£¤å¾®ç”Ÿç‰©æ²¿æµ·æ‹”æ¢¯åº¦çš„ç¢³ç£·é™åˆ¶å˜åŒ–.

Understanding changes in soil enzyme activities and ecoenzymatic stoichiometry is important for assessing soil nutrient availability and microbial nutrient limitation in mountain ecosystems. However, the variations of soil microbial nutrient limitation across elevational gradients and its driving factors in subtropical mountain forests are still unclear. In this study, we measured soil properties, microbial biomass, and enzyme activities related to carbon (C), nitrogen (N), and phosphorus (P) cycling in Pinus taiwanensis forests at different altitudes of Wuyi Mountains. By analyzing the enzyme stoichiometric ratio, vector length (VL), and vector angle (VA), the relative energy and nutrient limitation of soil microorganisms and its key regulatory factors were explored. The results showed that ß-glucosaminidase (BG) activities increased along the elevational gradient, while the activities of ß-N-acetyl glucosaminidase (NAG), leucine aminopeptidase (LAP), acid phosphatase (AcP) and (NAG+LAP)/microbial biomass carbon (MBC) and AcP/MBC showed the opposite trend. Enzyme C/N, enzyme C/P, enzyme N/P, and VL were enhanced with increasing elevation, while VA decreased, indicating a higher degree of microbial P limitation at low elevation and higher C limitation at high elevation. In addition, our results suggested that dissolved organic carbon and microbial biomass phosphorus are critical factors affecting the relative energy and nutrient limitation of soil microorganisms at different elevations. The results would provide a theoretical basis for the responses of soil carbon, nitrogen, and phosphorus availability as well as the relative limitation of microbial energy and nutrition to elevational gradients, and improve our understanding of soil biogeochemical cycle process in subtropical montane forest ecosystems.

Enzyme stoichiometry evidence revealed that five years nitrogen addition exacerbated the carbon and phosphorus limitation of soil microorganisms in a Phyllostachys pubescens forest.

The activity and stoichiometry of soil extracellular enzyme can provide a good indication for changes in soil nutrient availability and microbial demands for nutrients. However, it remains unclear how would nitrogen (N) deposition affect nutrient limitation of microbes in subtropical forest soils. We conducted a 5 years N addition experiment in a subtropical Phyllostachys pubescens forest. The soil nutrients and enzyme activities associated with carbon (C), N, and phosphorus (P) cycles were measured. We also examined the nutrient distribution of microorganisms using enzyme stoichiometry and vector analysis. The results showed that N addition significantly decreased the contents of soil soluble organic C and available P and increased that of available N. Furthermore, N addition significantly decreased ß-N-acetyl-glucosaminidase (NAG) activity and NAG/ microbial biomass carbon (MBC), and increased acid phosphatase (ACP) and ACP/MBC. The low and moderate N addition levels significantly increased enzyme C/P, vector length, and vector angle, but significantly decreased enzyme N/P. Results of redundancy analysis showed that the change in soil enzyme activity and enzymatic stoichiometry were mainly driven by soil available P content under N addition. In summary, N addition altered the microbial nutrient acquisition strategy, which increased nutrient allocation to P-acquiring enzyme production but reduced that to N-acquiring enzyme production. Moreover, N addition exacerbated the C and P limitation of soil microorganisms. Appropriate amount of P fertilizer could be applied to improve soil fertility of subtropical P. pubescens forest in the future.

[Responses of soil phosphorus fractions and microorganisms to nitrogen application in a subtropical Phyllostachys pubescen forest]. / 亚热带毛竹林土壤磷组分和微生物对施氮的响应.

Phosphorus (P) is an important nutrient for plant and microbial growth. Soil P availabi-lity is poor in subtropical areas. Long-term heavy nitrogen (N) deposition might further reduce P availability. The experiment was performed in a Phyllostachys pubescens forest in Daiyun Mountain. The effects of N application on soil basic physical and chemical properties, soil P fractions, microbial biomass, and acid phosphomonoesterase activity were analyzed after three years of N application. The results showed that N application significantly increased NO3--N content and thus soil N availability, while it significantly reduced the percentage of decomposable organic P to total P, with the ratio of carbon (C) to organic P being over 200. The soil microbial biomass C, microbial biomass P, acid phosphomonoesterase, and the ratio of microbial biomass N to microbial biomass P and microbial biomass C to microbial biomass P were increased as the N application rate increased. There was a significant negative correlation between the percentage of decomposable organic P to total P and microbial biomass P. Consequently, N application enhanced soil P limitation and increased microbial P demand.

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3-9 homolog 1 and SET domain containing 1A histone methyltransferases.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA), which serves as a template for HBV RNA transcription, is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified silent mating type information regulation 2 homolog 3 (SIRT3) as a host factor restricting HBV transcription and replication by screening seven members of the sirtuin family, which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA, as well as replicative intermediate DNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. A mechanistic study found that nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9. Importantly, occupancy of SIRT3 on cccDNA could increase the recruitment of histone methyltransferase suppressor of variegation 3-9 homolog 1 to cccDNA and decrease recruitment of SET domain containing 1A, leading to a marked increase of trimethyl-histone H3 (Lys9) and a decrease of trimethyl-histone H3 (Lys4) on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor Yin Yang 1 to cccDNA. Finally, hepatitis B viral X protein could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. CONCLUSION: SIRT3 is a host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase; these data provide a rationale for the use of SIRT3 activators in the prevention or treatment of HBV infection. (Hepatology 2018).

[Brain gray matter abnormalities revealed by voxel-based morphometry in patients with chronic low back pain].

OBJECTIVE: To explore the morphometric abnormalities of brain gray matter (GM) in patients with chronic low back pain (CLBP). METHODS: Thirty patients with CLBP and 30 healthy individuals were enrolled and examined with a 3.0 T magnetic resonance (MR) scanner. High-resolution T1 structural MR data were acquired and data analysis was performed using voxel-based morphometry (VBM) in FMRIB Software Library. The morphological differences were compared between the two groups. RESULTS: s Compared with the healthy control subjects, patients with CLBP showed decreased GM volumes in several brain cortical areas including the bilateral superior frontal gyrus, right frontal pole, left insular cortex, left middle and left inferior temporal gyrus (P<0.05, after TFCE correction). Increased GM volumes were found in the patients in the subcortical structures including the left thalamus, bilateral putamen, bilateral nucleus accumben and right caudate nucleus (P<0.05, after TFCE correction). CONCLUSION: Patients with CLBP have different patterns of GM abnormalities in different brain regions, characterized by reduced GM volume in cerebral cortical regions and increased GM volume in the subcortical nuclei. Such changes might be associated with the maladaptation of the brain in chronic pain state.

Brain gray matter abnormalities revealed by voxel-based morphometry in patients with chronic low back pain / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the morphometric abnormalities of brain gray matter (GM) in patients with chronic low back pain (CLBP).</p><p><b>METHODS</b>Thirty patients with CLBP and 30 healthy individuals were enrolled and examined with a 3.0 T magnetic resonance (MR) scanner. High-resolution T1 structural MR data were acquired and data analysis was performed using voxel-based morphometry (VBM) in FMRIB Software Library. The morphological differences were compared between the two groups.</p><p><b>RESULTS</b>s Compared with the healthy control subjects, patients with CLBP showed decreased GM volumes in several brain cortical areas including the bilateral superior frontal gyrus, right frontal pole, left insular cortex, left middle and left inferior temporal gyrus (P<0.05, after TFCE correction). Increased GM volumes were found in the patients in the subcortical structures including the left thalamus, bilateral putamen, bilateral nucleus accumben and right caudate nucleus (P<0.05, after TFCE correction).</p><p><b>CONCLUSION</b>Patients with CLBP have different patterns of GM abnormalities in different brain regions, characterized by reduced GM volume in cerebral cortical regions and increased GM volume in the subcortical nuclei. Such changes might be associated with the maladaptation of the brain in chronic pain state.</p>

Comparison of the effects of pretreatment with repeated electroacupuncture at GV20 and ST36 on fatigue in rats.

OBJECTIVE: To investigate and compare the effects of electroacupuncture (EA) pretreatment at GV20 and ST36 on fatigue in rats. METHODS: Rats were randomly allocated into 4 groups: control, fatigue, fatigue+GV20 and fatigue+ST36. The last two groups received EA pretreatment at GV20 or ST36 for 5 days before being maintained in cages filled with water to a height of 1.5 cm to establish an animal model of fatigue. We used the weight-loaded forced swimming test and open-field test and measured 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios and serum levels of blood urea nitrogen (BUN), lactic dehydrogenase (LDH) and testosterone as behavioural and biochemical markers of fatigue in the rats. RESULTS: Compared with controls, rats in the (untreated) fatigue group exhibited reduced weight-loaded swimming times and total movement/distance in the open-field test, plus higher BUN/LDH and lower testosterone levels. Both EA pretreatment at GV20 and ST36 increased swimming times, and reduced serum BUN/LDH. EA pretreatment at GV20 (but not ST36) increased serum testosterone. The 5-HIAA/5-HT ratios in four brain regions were decreased in the fatigue+GV20 group compared with the fatigue group (p<0.05). By contrast, 5-HIAA/5-HT ratios in striatum and hypothalamus (but not hippocampus or midbrain) were decreased in the fatigue+ST36 group compared with the fatigue group (p<0.05). Furthermore, only pretreatment at GV20 affected the results of the open-field test. CONCLUSIONS: These results suggest that EA pretreatment had a positive effect on the prevention of fatigue. Pretreatment at GV20 had a greater anti-fatigue effect than pretreatment at ST36.

Ophiobolins P-T, five new cytotoxic and antibacterial sesterterpenes from the endolichenic fungus Ulocladium sp.

Five ophiobolane sesterterpenes, ophiobolins P-T, and three known compounds, 6-epi-21,21-O-dihydroophiobolin G, 6-epi-ophiobolin G and 6-epi-ophiobolin K, were isolated from the acetone extract of the endolichenic fungus Ulocladium sp. by using OSMAC method. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configuration of the 18,19-diol moieties in ophiobolin Q was assigned using the Frelek's method. The cytotoxic effects on KB and HepG2 cell lines, antibacterial activity against Bacillus subtilis, methicillin-resistant Staphylococcus aureus, and Bacille Calmette-Guerin were evaluated for all isolated compounds. Ophiobolin T and 6-epi-ophiobolin G exhibited the most potent cytotoxic activity against HepG2 with IC50 of 0.24 and 0.37 µM, respectively. In antibacterial assay, ophiobolins P and T showed moderate antibacterial activity against B. subtilis and meticillin-resistant S. aureus. Ophiobolin T also displayed moderate antibacterial activity against the Bacille Calmette-Guerin strain.

Tricycloalternarenes F-H: three new mixed terpenoids produced by an endolichenic fungus Ulocladium sp. using OSMAC method.

Three new mixed terpenoids, tricycloalternarenes (TCAs) F-H (1-3), together with ten known tricycloalternarenes (4-13), were isolated from the Czapek's culture of an endophytic fungus Ulocladium sp. Their structures were identified by extensive spectroscopic experiments (NMR and MS) and comparison with literature data. TCA 1b (5) showed weak activity against the Bacille Calmette-Guerin strain with the MIC of 125µg/mL. TCA 9b (10) exhibited strong cytotoxic activity against Hela cell line with IC50 of 8.58µM.

[Clinical research on facial neuritis treated with Chen's needling therapy].

OBJECTIVE: To evaluate the effect of Chen's needling therapy on facial neuritis. METHODS: Eighty-four patients of facial neuritis were randomized into a Chen's needling therapy group and a conventional needling group, 42 cases in each one. In the Chen's needling therapy group, the few acupoints were selected (5 acupoints). Chen's flying insertion of needle and the reinforcing and reducing techniques were applied. In the conventional needling group, the acupoint selection and needling method were used routinely. The treatment of 1 month was 1 session in the two groups. According to the symptom and physical sign quantification scale, the effect was assessed at multiple time points respectively (in 2 weeks of treatment, 1 session of treatment and 1 month after 1 session of treatment). Simultaneously, House-Brackmann scale and EMG were adopted to determine the function of facial nerve. RESULTS: After treatment, the results of symptoms and physical sign quantification scale and facial nerve EMG were different significantly as compared with those before treatment in the patients of the two groups (all P < 0.05). But the differences were not significant between the two groups (all P > 0.05). CONCLUSION: Chen's needling therapy achieves the same effect on facial neuritis as compared with the conventional acupuncture therapy, and additionally it is specialized at flying insertion of needle technique and selection of few acupoints.

Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp.

Two new polyketides, 7-hydroxy-3, 5-dimethyl-isochromen-1-one (1) and 6-hydroxy-8-methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (2), along with eleven known compounds, 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (3), 7-hydroxy-3-(2-hydroxy-propyl)-5-methyl-isochromen-1-one (4), rubralactone (5), isoaltenuene (6), altenuene (7), dihydroaltenuenes A (8), altenusin (9), alterlactone (10), 6-O-methylnorlichexanthone (11), norlichexanthone (12), and griseoxanthone C (13) were isolated from the culture of the endolichenic fungus Ulocladium sp. Compound 2 was obtained as a racemate with an unprecedented chemical skeleton. The NMR data assignments for 3 and 4 were achieved for the first time. Compounds 1-13 were screened for their antimicrobial and radical scavenging activities. Compound 1 showed some antifungal activity against Candida albicans SC 5314 with IC(50) of 97.93 ± 1.12 µM. Compounds 11-13 showed strong activity against Bacillus subtilis with IC(50) in the range of 1-5 µM. Compound 12 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus with IC(50) of 20.95 ± 1.56 µM. Compounds 9 and 10 showed strong radical scavenging activity in comparison with vitamin C. The plausible biosynthetic pathways for compounds 1, 2, and 4-8 were discussed.

Chemical constituents from endophytic fungus Fusarium oxysporum.

A new oxysporidinone analogue (1) and a new 3-hydroxyl-2-piperidinone derivative (2), along with the known compounds (-)-4,6'-anhydrooxysporidinone (3), (+)-fusarinolic acid (4), gibepyrone D (5), beauvercin (6),cerevisterol (7), fusaruside (8), and (2S,2'R,3R,3'E,4E,8E)-1-O-D-glucopyranosyl-2-N-(2'-hydroxy-3'-octadecenoyl)-3-hydroxy-9-methyl-4,8-sphingadienine (9) were isolated from Fusarium oxysporum. Compounds 1-9 were evaluated for cytotoxicity using the MTT method against cancer cell lines, PC-3, PANC-1, and A549. Beauvericin showed cytotoxicity against PC-3, PANC-1, and A549 with IC(50) value of 49.5 ± 3.8, 47.2 ± 2.9, and 10.4 ± 1.6µM, respectively. Beauvericin also exhibited anti-bacterial activity towards methicillin-resistant Staphylococcus aureus (MIC=3.125 µg/mL) and Bacillus subtilis (MIC=3.125 µg/mL).

[Therapy for replenishing qi, nourishing yin and promoting blood circulation in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a randomized controlled trial].

BACKGROUND: No-reflow phenomenon after reperfusion treatment of acute myocardial infarction (AMI) is becoming more recognized today. The effective treatment for no-reflow has not been reported. OBJECTIVE: To observe the effects of traditional Chinese medicine (TCM) therapy for replenishing qi, nourishing yin, and promoting blood circulation on AMI patients undergoing percutaneous coronary intervention (PCI). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted from January 2005 to March 2006 using a double-blinded, randomized method. Thirty-five AMI patients (Killip I-II) were first diagnosed as ST segment elevation AMI and obtained primary PCI. They were recruited from People's Hospital, Peking University. All patients' symptoms accorded with qi-yin deficiency syndrome and blood stasis syndrome. They were randomly and double blindly divided into control group (18 cases) and treatment group (17 cases). The patients in the control group received Western medicine treatment, and the patients in the treatment group were treated with Western medicine plus American ginseng and Salviae miltiorrhizae preparations. They were all treated for 3 months. MAIN OUTCOME MEASURES: Before and after 3-month treatment, the TCM symptoms were observed and scored. At the state of baseline and dobutamine stress, left ventricular ejection fraction (LVEF), wall motion score (WMS), WMS index and normal cardiac muscle percentage (NCMP), and the myocardial contrast echocardiography index k, which reflects myocardium microcirculation perfusion, were detected. RESULTS: After 3-month treatment, the TCM symptoms in the treatment group were improved as compared with the control group (X(2)=4.118, P=0.042). At the state of dobutamine stress, LVEF in the treatment group after treatment was higher than those in the control group (t=2.130, P=0.041) and before treatment (t=2.345, P=0.032). Although the number of the segments with increased k value was more than that in the control group, there was no significant difference. CONCLUSION: TCM therapy for replenishing qi, nourishing yin and promoting blood circulation can improve the clinical symptoms and quality of life of the AMI patients undergoing PCI, and is beneficial to myocardium microcirculation. Thus, it may be an alternative cardioprotective treatment strategy for successful myocardial microcirculation in AMI patients after reperfusion.

[Effects of indole-3-carbinol on the outcome of tumor and the changes of anti-oxidative system in null mice grafted with nasopharyngeal carcinoma].

OBJECTIVE: To observe the effects of indole-3-carbinol (I3C) on the outcome of the tumor as well as the changes of the anti-oxidative system in null mice grafted with nasopharyngeal carcinoma. METHODS: 48 BALB/c null mice were divided by means of random number table into control group (0.5% sodium carboxyl methyl cellulose), low dosage (0.02 g/kg), middle dosage (0.1 g/kg) and high dosage (0.5 g/kg) of I3C. The mice were administered with different solutions by gavage for 10 days before CNE1 cells were inoculated subcutaneously into the back (near the armpit) of the nude mice, then the solutions were continually administered by gavage. The tumor volume was measured and the tumor inhibitory rate was calculated. The level of malondialdehyde (MDA), the activity of superoxide dismutases (SOD), the activity of glutathione peroxidase (GSHPx) and the expression of cleaved caspase-3 were determined on the 31th day of the study. RESULTS: I3C could reduce the tumor volume [the tumor volumes of the control group, the middle dosage group and the high dosage group were (4.13 +/- 0.53) x 10(-6) m(3), (3.14 +/- 0.71) x 10(-6) m(3), (2.72 +/- 0.29) x 10(-6) m(3)], as compared with the control, the shrinkage of tumor volume of the middle dosage group and the high dosage group were significant (the t valued at 0.990 and 1.510, P < 0.01). The tumor inhibitory rates of 3 groups were 3.8%, 20.5% and 34.9%, respectively. The contents of MDA in the tumor tissue tended to decrease [the values of control group, the low dosage group, the middle dosage group and the high dosage group were (31.29 +/- 2.51) x 10(-6) mol/L, (30.12 +/- 2.37) x 10(-6) mol/L, (23.32 +/- 1.93) x 10(-6) mol/L, (16.45 +/- 1.43) x 10(-6) mol/L] (F = 98.752, P < 0.01), and that of the high and the middle dosage group could obviously be reduced (t = 8.970, 14.840, P < 0.01) as compared with the control. The activity of SOD seemed to be elevated according to the increase of I3C dosage [the values were (387.24 +/- 23.16) x 10(3) U/L, (399.37 +/- 34.45) x 10(3) U/L, (431.63 +/- 31.24) x 10(3) U/L, (476.45 +/- 44.67) x 10(3) U/L] (F = 53.444, P < 0.01). When compared with the control, the SOD activity of the middle and the high dosage group be obviously increased (t = 44.390, 89.210, P < 0.01). I3C could also elevate the GSHPx activity [the GSHPx values of the four groups were (226.98 +/- 18.35) x 10(3) U/L, (234.65 +/- 15.59) x 10(3) U/L, (247.72 +/- 22.73) x 10(3) U/L, (300.37 +/- 26.02) x 10(3) U/L] (F = 25.916, P < 0.01). The GSHPx of the high dosage group was enhanced remarkable (t = 73.390, P < 0.01) as compared with the control. The expression of cleaved caspase-3 (relative molecular weight = 19 000 000) seemed to be elevated according to the increase of I3C dosage and the relative expression levels of which were 0.87 +/- 0.01, 0.97 +/- 0.01, 1.02 +/- 0.06 and 1.14 +/- 0.02 (F = 39.864, P < 0.01). When compared with the control, the elevation of this kind of cleaved caspase-3 was considered statistical significant (the t values were 0.100, 0.086 and 0.303, respectively, P < 0.05). When I3C dosage increased, the expression of cleaved caspase-3 (relative molecular weight = 17 000 000) seemed to increased too [the relative expression levels of which were 0.00 +/- 0.00, 0.05 +/- 0.02, 0.11 +/- 0.02, 0.20 +/- 0.02 (F = 56.629, P < 0.01)], and the increase of this kind of cleaved caspase-3 was esteemed significantly as compared with those of the control (the t valued at 0.046, 0.103 and 0.193, respectively, P < 0.05). Linear correlate analysis showed that the correlation coefficients between the shrinkage of tumor volume and the expression of the two kinds of cleaved caspase-3 protein was -0.732 (t = 3.404, P < 0.01) and -0.901 (t = 6.642, P < 0.01). CONCLUSION: I3C could reduce the growth of tumor, the mechanism underlie it could be related to the decrease of the content of MDA as well as the elevated levels of SOD, GSHPx, and perhaps could be related to the apoptosis transduced by cleaved caspase-3.