[Tea polyphenols ameliorates acute lung injury in septic mice by inhibiting NLRP3 inflammasomes].

OBJECTIVE: To investigate the mechanism of tea polyphenols (TP) for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice. METHODS: Sixty C57BL/6 mice were randomly assigned into sham-operated, cecal ligation and puncture (CLP) and CLP +TP treatment groups, and survival of the mice was recorded after modeling in each group. The lung wet/dry weight ratio and myeloperoxidase (MPO) activity were determined, and lung injury of the mice was evaluated using HE staining and acute lung injury score. The expressions of IL-1ß, TNF-α, IL-6, NLRP3, caspase-1 p10, ASC, MPO, and caspase-8 in the lung tissue were detected using ELISA, Western blotting, or immunohistochemical staining. MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress. Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4. RESULTS: The postoperative mortality rate at 72 h, lung wet/dry weight ratio, MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group (P < 0.05). Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors (P < 0.05) and lowered MDA and H2O2 levels in the lung tissue of the septic mice (P < 0.05). Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group. CONCLUSION: TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

[Studies on newly recognized chronic sialadenitis].

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by 131I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

Clinical-grade Garcinia cambogia extract dissolves calcium oxalate crystals in Drosophila kidney stone models.

OBJECTIVE: Kidney stone formers have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication for treatment. Hydroxycitric acid (HCA), which is the major component of Garcinia cambogia extract, can dissolve calcium oxalate crystals in vitro, suggesting that Garcinia cambogia could be used to treat calcium oxalate kidney stone. In this study, we used the Drosophila kidney disease model to evaluate the effect of Garcinia cambogia on the prevention and removal of calcium oxalate stones in vivo. MATERIALS AND METHODS: Flies were reared in fly food containing different concentrations of GCE for one week. The effect of GCE on preventing the formation of calcium oxalate stone was examined. WT and v-ATPase gene RNAi knockdown flies were reared in fly food with 0.3% NaOx for one week, then fed different concentrations of GCE for one week. The effect of GCE on the removal of calcium oxalate stone was examined. RESULTS: Garcinia cambogia extract dissolves calcium oxalate crystals from Malpighian tubules in both genetic and non-genetic Drosophila kidney stone models compared to citric acid. Hydroxycitric acid also directly dissolves calcium oxalate crystals in Drosophila Malpighian tubules ex vivo. CONCLUSIONS: Garcinia cambogia extract removes calcium oxalate kidney stones from Drosophila Malpighian tubules via directly dissolving calcium oxalate stones by HCA. Our study strongly suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

Abnormal cortical activation in females with acute migraine: a magnetoencephalography study.

OBJECTIVE: The objective of this study was to investigate functional abnormalities of the brain in females with migraine using magnetoencephalography (MEG) and a finger-tapping task. METHODS: Twenty-nine female patients with migraine (aged 16-40years) and age- and gender-matched healthy controls were studied with an MEG system at a sampling rate of 6000Hz. MEG recordings were performed during an attack in migraineurs with and without aura. Neuromagnetic brain activation was elicited by a finger-tapping task. The latency and amplitude of neuromagnetic responses were analyzed with averaged waveforms in the frequency range of 5-100Hz. The Morlet wavelet and beamformers were used to analyze the spectral and spatial signatures of MEG data from subjects in two frequency ranges of 5-100 and 100-1000Hz. RESULTS: The latency of motor-evoked magnetic fields evoked by finger movement was significantly prolonged in migraineurs as compared with controls. Neuromagnetic spectral power in the motor cortex in migraineurs was significantly elevated. There were significantly higher odds of activation in 5-30, 100-300 and 500-700Hz frequency ranges in the ipsilateral primary motor cortices and the supplementary motor area in migraineurs as compared with controls. CONCLUSIONS: Neuromagnetic signal abnormalities in this study suggest cortical hyperexcitability in females with migraine during migraine attack, which could be measured and analyzed with MEG signal in a frequency range of 5-1000Hz. SIGNIFICANCE: These findings may help to identify neurophysiological biomarkers for studying mechanisms of migraine, and may facilitate to develop new therapeutic strategies for migraine by alterations in cortical excitability.

Functional annotation of expressed sequence tags as a tool to understand the molecular mechanism controlling flower bud development in tree peony.

Tree peony (Paeonia suffruticosaAndrews) is an important medicinal and ornamental plant. In China, its root bark is an important ingredient for traditional Chinese medicine. It is valued as an ornamental plant because its flower shows a wide variation in shape and color. We used flower buds at different developmental stages to construct the first cDNA library for this organism. A total of 2241 raw expressed sequence tags (ESTs) were obtained after unidirectional sequencing. After processing and assembly, they resulted in a total of 1300 unigenes [363 contigs with an average size of 3.5 ESTs (ranging from 2 up to 36) and 937 singletons]. Gene Ontology categories were assigned and further summarized into 13 broad families with biological roles according to similar functional characteristics or cellular roles. A total of 185 single nucleotide polymorphisms were detected for all contigs. We were able to detect open reading frames in the consensus sequences of 1268 unigenes. 97.5% of the ESTs showed significant similarity to sequences present in public databases. One hundred and sixty-seven short sequence repeats were obtained in the whole data set. All the analysis and information will be valuable resources for a better understanding of this important plant and also can be used for functional study in Paeoniaceae.

Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis.

OBJECTIVE: To investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukin (IL-8) and monocyte chemoattractant protein (MCP-1). METHODS: The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group,and melatonin group (dose of 2.5, 5.0, and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interlukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. RESULTS: Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. CONCLUSION: Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory processes; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease.

Anti-hepatitis B virus activities of triterpenoid saponin compound from Potentilla anserine L.

The Tibetan herb Potentilla anserina L. has been widely used in China for many thousands of years to treat hepatitis-B. Bioassay-guided fractionation of the ethanol extract of the rhizomes led to the isolation of a triterpenoid saponin (TS) that was determined to be 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl ester. Using models of HBV infection, this compound was evaluated for its effect on HBV antigene expression in the 2.2.15 cell line in vitro and anti-hepatitis B virus (HBV) activities in Peking ducklings in vivo. Results showed that it could decrease the expression levels of HBsAg, HBeAg and HBVDNA in the 2.2.15 cell culture and the inhibitory effect was not due to the cytotoxity of the triterpenoid saponin. The antiviral study in vivo on Peking ducklings also demonstrated that this compound inhibits duck hepatitis B virus (DHBV) DNA replication.

Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS.

Nifedipine GITS has diuretic and natriuretic properties, which may enhance its antihypertensive efficacy. We assessed contributions of polymorphisms in the urea transporter-A gene (SLC14A2) to interindividual variations in blood pressure (BP) response to nifedipine treatment. 405 subjects from a single Chinese county received a single oral dose of 30 mg nifedipine GITS (gastrointestinal therapeutic system) daily for 16 days. We genotyped two SNPs in SLC14A2 and found significant associations for the Val227Ile (rs1123617) and Ala357Thr (rs3745009) polymorphisms with BP response to nifedipine treatment. After treatment, subjects with either Ala357/Thr357 or Thr357/Thr357 genotypes had significantly smaller mean changes in systolic BP (SBP) (beta +/- SE = -2.87 +/- 1.24 mmHg, p = 0.020) and diastolic BP (DBP) (beta +/- SE = -1.69 +/- 0.62 mmHg, p = 0.006) compared to those with the Ala357/Ala357 genotype. Subjects with either Val227/Ile227 or Ile227/Ile227 genotypes had significantly larger mean changes in SBP (beta +/- SE = 3.13 +/- 1.19, p = 0.009) and DBP (beta +/- SE = 1.50 +/- 0.60 mmHg, p = 0.013) compared with those with the Val227/Val227 genotype after treatment. Subjects carrying both the Ala357/Ala357 genotype in the Ala357Thr polymorphism and either Val227/Ile227 or Ile227/Ile227 genotypes in the Val227Ile polymorphism had the highest mean change in SBP and DBP. Our study supports the conclusion that polymorphisms in the SLC14A2 gene can predict the antihypertensive efficacy of nifedipine GITS.

Further molecular characterisation of potyviruses infecting aroid plants for medicinal use in China.

Degenerate primers were used to detect and amplify 3'-terminal genome fragments of potyviruses from medicinal aroid plants growing at 16 sites in China. Virus was detected in 7 samples of which six, all of Pinellia ternata, contained a strain of soybean mosaic virus (SMV) similar to that previously reported from this host in China. The complete sequence of one isolate and the P1 protein coding region of the other isolates were also sequenced. In all cases, the P1 proteins resembled isolates of Dasheen mosaic virus (DsMV) more closely than SMV, confirming earlier suggestions of recombination in this region. In a phylogenetic analysis of SMV, DsMV and related sequences, the aroid sequences of SMV formed a distinct group which also included a sequence published as Zantedeschia symptomless virus (AF469171). One of the P. ternata samples was also infected with a second potyvirus, the 3'-terminal sequence of which was similar to DsMV and to some sequences published as Vanilla mosaic virus. The seventh infected sample was Typhonium flagelliforme and the virus from it was identified from its sequence as zantedeschia mosaic virus (ZaMV), providing the first report of this virus from mainland China.

Nitric oxide in vPAG mediates the depressor response to acupuncture in stress-induced hypertensive rats.

The hypertensive rat model was made by chronic stress of electric foot-shocks and noises. On such hypertensive rats, when anesthetized with urethane and chloralose, the electroacupuncture (EA) to bilateral "Zusanli (st.36)" acupoints for 20 min, could result in a depressor (including both systolic and diastolic pressure) and bradycardiac response as well as an attenuation in the maximum of left ventricular pressure, end diastolic pressure and +/-dp/dt. In power spectrum analysis of heart rate variability aspect, EA could increase all total variance, very low frequency component, low frequency component and the ratio of low frequency component and high frequency component. When EA with microinjection of N(omega) - Nitro- L-Arginine , a blocker of the formation of nitric oxide, into the ventral periaqueductal gray matter (vPAG), the above effects of EA were abolished or reduced significantly. The results suggest that the depressor effect of EA on stress-induced hypertensive rats might be mediated by nitric oxide in the vPAG due to activation of sympathetic inhibitory system and by attenuated cardiac activities.

Chemical constituents of two Chinese Magnoliaceae plants, Tsoongiodendron odorum and Manglietiastrum sinicum, and their inhibition of platelet aggregation.

Phytochemical investigations of Tsoongiodendron odorum and Manglietiastrum sinicum, both Magnoliaceae, led to the isolation of twenty compounds in total. Among them, one was a new sesquiterpene, 11-O-oleoyl-beta-eudesmol (2), and another, 1-(3,4-dimethoxypheny)-4-(3,4-methylenedioxyphenyl)-2,3-dimethy lbutane (12) was isolated as a natural product for the first time. Moreover, 13C-NMR spectral data of isoguaiacin (16) are reported here for the first time. Structure elucidations for compounds reported here were mainly based on their spectral data. The ethanolic extracts of T. odorum and M. sinicum, and six pure compounds, 4(15)-eudesmen-11-ol (beta-eudesmol) (1), 1 beta-hydroxy-4(15),11(13)-eudesmadien-12,6 alpha-olide (reynosin) (3), 3,11(13)-eudesmadien-12,6 alpha-olide (alpha-cyclocostunolide) (5), erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3- dimethylbutane (11), nectandrin-B (18), and syringaresinol (19), displayed considerable inhibition against platelet aggregation induced by AA, by ADP, or by PAF.

Structural revision of four spiramine diterpenoid alkaloids from the roots of Spiraea japonica.

On the basis of detailed 1H-NMR 13C-NMR spectral analysis, especially by 2D NMR experiments (1H-1H COSY, HMQC, HMBC, and NOESY) as well as by chemical transformations. four isoatisine type diterpenoid alkaloids, spiramines P and Q, and U and T, have been reassigned as the 6beta hydroxyl and 6beta acetoxyl substituents, respectively, rather than the previously assigned 15alpha counterparts in our further studies on chemical constituents of the roots of Spiraea japonica var. acuta.

Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia.

We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.

Treatment of chloroquine-resistant malaria using pyrimethamine in combination with berberine, tetracycline or cotrimoxazole.

Two hundred and fifteen patients with chloroquine-resistant malaria were randomised into three groups. The first group of 82 patients were given pyrimethamine and berberine (berberine group), the second group of 64 patients, pyrimethamine and tetracycline (tetracycline group) and the third group of 69 patients were given pyrimethamine and cotrimoxazole (cotrimoxazole group). In the berberine group, the clearance, rate of asexual parasitaemia was 74.4% after treatment, while in the tetracycline group it was 67.2% and in the cotrimoxazole group 47.8%. These results indicate that berberine is more effective in clearing the parasite than both tetracycline and cotrimoxazole, and that the combination of pyrimethamine and berberine gives the best results for chloroquine resistant malaria.

Clinical research on acute hemoptysis treated with kexue ning.

The efficacy of Kexue Ning (stopping hemoptysis) in the treatment of acute hemoptysis, and its comparison with that of the control group (treated with western medicine) are reported in this paper. The results showed that both the time for cessation of hemoptysis and the cure rate were better in the therapeutic group than in the control group. In addition, marked improvement in blood rheology after treatment was also found in the therapeutic group, but not in the control group.

[A comparative study on amino acids of guang horn, buffalo horn and cattle horn].

The results show that the total amino acids of three species of horns are different to a certain degree, but the composition and content distribution of these acids are similar. The composition and content of different parts of two species of ox horns are similar too.

[A comparative study on inorganic elements of guangjiao, buffalo horn and cattle horn].

Determination and comparison were made on the contents of Ca, Mg, Fe, Zn, Cu, Mn, Co and Pb in Guangjiao, buffalo horn and cattle horn. The results show that among the three species of horns there exist differences as well as similarities.

[Comparison of lipoperoxidative damage in plasma and platelet with the ratio of thromboxane A2 and prostaglandin I2 in blood stasis syndrome with coronary heart disease].

In order to study the biochemical and pathophysiological mechanism of the Blood Stasis Syndrome (BSS) or Non-BSS of coronary heart disease (CHD) patients, the activities of SOD, Selenium-glutathione peroxidase, the content of LPO in plasma and platelets and the contents of TXB2 and 6-keto-PGF1 alpha in plasma were determined in 109 BSS and Non-BSS of CHD patients compared with 98 healthy controls. It was discovered that the contents of TXB2, LPO, PL-LPO, and the ratio of TXB2/6-keto-PGF1 alpha were significantly increased in BSS-CHD patients compared with controls and Non-BSS-CHD patients. It was also discovered that the SOD activities and the contents of 6-keto-PGF1 alpha decreased significantly in Non-BSS-CHD patients. The results suggested that the injury of platelets by oxygen free radicals might be one of the primary injury factors in BSS-CHD patients. Our conclusion is that PGI2, SOD belong to the category of Heart-Qi, while TXA2, LPO to the Blood category. Therefore TXB2, 6-keto-PGF1 alpha, SOD, LPO should serve as some of the objective indexes for BSS patients of CHD.

[Efficacy of xiaoxingzhang guttae ophthalmic eye drops in the treatment of experimental herpes simplex keratitis].

The new guttae ophthalmic Xiaoxingzhang (XXZ) was extracted from Radix Actinidiae, a traditional Chinese herbal drug. The 50% inhibition concentration (IC50) of XXZ on type I Herpes Simplex Virus (HSV-1) in virus cell cultures is 165.48-174.73 micrograms/ml. However, XXZ concentrations greater than 400 micrograms/ml did not cause any microscopically visible disruption of vero cells. The efficacy of XXZ in the treatment of experimental Herpes Simplex Keratitis (HSK) in rabbits is higher than that of idoxuridine. The effective doses of XXZ are not toxic to corneal epithelium. The results suggest that XXZ as a new anti-HSV preparation is potentialy useful in the treatment of patients with HSK.