[Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice].

Objective: Curcumin was used as photosensitizers in photodynamic therapy on cervical cancer xenografts in nude mice.Analysis the expression changes of Notch and downstream gene as NF-κB and VEGF before and after DAPT inhibition of Notch signaling pathway in vivo experiments.Our aim was to investigate the possible mechanism of Notch signaling pathway in the treatment of cervical cancer with PDT. Methods: A cervical cancer model of nude mice was established by subcutaneous inoculation of human cervical cancer Me180 cells 200 µl.After the success of the model, the experimental animals were divided into 4 groups (model group, curcumin PDT group, simple DAPT group, curcumin-PDT+ DAPT group), each group was 12.Tumor volume changes were analyzed and HE staining was observed in each group.MRNA and protein expression of Notch1 and its downstream NF-κB, VEGF were detected by RT-PCR, immunohistochemistry and Western blot before and after inhibition of Notch signaling pathway by DAPT. Results: Except the control group, the tumor volume of the other three groups remained unchanged or slightly reduced after 1-7 days of treatment.The difference was significant (P<0.05). HE staining showed the most obvious necrosis of curcumin-PDT group with DAPT.Both DAPT and curcumin-PDT could reduce the expression level of Notch1 in mRNA.The inhibition rates were 42.17% and 40.54%, respectively.And the inhibitory effect of curcumin-PDT with DAPT on Notch-1 was the strongest (79.22%) (P<0.01), and two of them had synergistic effect after combination with curcumin-PDT.But the expression of Notch-2 has no obvious inhibitory effect (P>0.05). Both DAPT and curcumin-PDT can inhibit the protein expression of Notch1, NF-κB and VEGF, and two of them have synergistic effect after combined use. Conclusions: DAPT can effectively block the Notch signaling pathway and inhibit the proliferation of cervical cancer cell line Me180.The application of DAPT to inhibit Notch signaling pathway after photodynamic therapy can achieve synergistic effect, which is mainly related to the down-regulation of the expression of Notch1 and NF-κB.Notch signaling pathway may be one of the targets of curcumin-PDT photodynamic therapy.

[Outcomes of total deafness type of idiopathic suddendeafness in different ages].

Objective:This retrospective study was aimed to investigate the characteristics of hearing recovery in the complete deafness type of SSNHL(≥81 dBHL) in patients with different ages.Method:Clinical outcomes of 179 total deafness type of idiopathic sudden deafness were compared.Patients were divided into 5 groups according to age,they were,pediatric group(13 years or less),youthful group(14-44 years),middle-aged group(45-59 years),presenium group(60-74 years),senectitude group(75 years or higher).Patients were divided into 3 groups according to the initial degree of hearing loss: 81 dB group (81-89 dBHL),90 dB group(90- 99 dBHL),100 dB group(100 dBHL or higher).Routine comprehensive treatment including corticosteroids,the inner ear microcirculation improvement drugs,neurotrophic drugs,saturationoxygen and hyperbaric oxygen therapy,etc.was applied.Patients were treated in accordance with the age and body weight.Result:The percentage of youthful group(83/179,46.4%) was highest(P<0.05),middle-aged group(57/179,31.8%)followed(P<0.05),presenium group(26/179,14.5%)was lower(P<0.05),pediatric group(8/179,4.5%) and senectitude group(5/179,2.8%)were the lowest.No a complete recovery in either pediatric group or senectitude group.A complete recovery was rare in the other groups.Recovery rate of the different aged groups was similar(P>0.05).The percentage of 100 dB group(108/179,60.3%) was highest(P<0.05).The percentage of 81 dB group(39/179,21.8%)was similar to 90 dB group(32/179,17.9%)(P>0.05).Recovery rate was similar in 81 dB group(25/39,64.1%)and 90 dB group(18/32,56.2%)(P>0.05).Recovery rate of both 81 dB group and 90 dB group were greater than 100 dB group(24/108,22.2%)(P<0.05).The 100 dB group reduced the satisfactory recovery effects.There were no differences in the proportion of the patients with dizziness(95/179,53.1%)and without dizziness(84/179,46.9%)(P>0.05).Recovery rate of patients without dizziness(43/84,51.2%) was greater than with dizziness(24/95,25.3%)(P<0.05).The percentage of the patients without dizziness(31/39,79.5%)in 81 dB group was the highest(P<0.05),90 dB group(18/32,56.2%)followed(P<0.05).The percentage of the patients with dizziness in 100 dB group(73/108,67.6%)was highest(P<0.05).Recovery rate was similar in the patients without dizziness of 81 dB group(21/31,67.7%)and 90 dB group(11/18,61.1%)(P>0.05).Recovery rate of the above two groups was greater than that of 100 dB group(11/35,31.4%)(P<0.05).Conclusion:Recovery rate of the different aged groups was similar.The percentage of the patients with dizziness in 100 dB group was highest.Initial hearing threshold in excess of 100 dB reduced the satisfactory recovery in patients with total deafness type of SSNHL.Our results provided a good reference for other clinicians.

Poly-GLP-1, a novel long-lasting glucagon-like peptide-1 polymer, ameliorates hyperglycaemia by improving insulin sensitivity and increasing pancreatic beta-cell proliferation.

AIM: The clinical value of glucagon-like peptide-1 (GLP-1) is restricted because of its short half-life. To overcome this limitation, a new polymer of GLP-1 was developed by prodrug strategy, termed Poly-GLP-1, and its pharmacological properties were investigated. METHODS: The in vitro release kinetics of GLP-1 from Poly-GLP-1 was analysed by Western blot. Plasma GLP-1 levels following a single administration of Poly-GLP-1 were determined by enzyme-linked immunosorbent assay. The in vitro effects of Poly-GLP-1 were evaluated using isolated pancreatic islets. The acute effects on glycaemic control and food intake were investigated in C57BL/6J mice s.c. administered with Poly-GLP-1. The chronic effects of Poly-GLP-1 on glycaemic control were further assessed in C57BL/6J and db/db mice treated twice daily for 6 weeks. RESULTS: Pro-GLP-1 dose dependently increased insulin secretion and decreased glucose, but did not exhibit the insulinotropic action in isolated pancreatic islets without plasma. The glucose-lowering actions of Poly-GLP-1 (3 nmol/kg) remained no less than 12 h after a single injection. Poly-GLP-1 caused a durable restoration of glycaemic control, food intake and body weight gain in db/db mice following 6-week administration. The chronic treatment with Poly-GLP-1 improved glucose tolerance and insulin sensitivity and increased beta-cell mass and proliferation in db/db mice. There was little effect on normal mice treated in the same manner. CONCLUSIONS: Our results indicated that Poly-GLP-1, a novel GLP-1 polymer, has long-lasting and potent effects on glycaemic control in vivo, and these beneficial effects may be because of improvement of insulin sensitivity and promotion of islet growth and function.

Household CO and PM measured as part of a review of China's National Improved Stove Program.

UNLABELLED: In 2001-2003, a team of researchers from the United States and China performed an independent, multidisciplinary review of China's National Improved Stove Program carried out since the 1980s. As part of a 3500-household survey, a subsample of 396 rural households were monitored for particulate matter less than 4 microm (PM(4)) in kitchens and living rooms over 24 h, of which 159 were measured in both summer and winter. Carbon monoxide was measured in a 40% subsample. The results of this indoor air quality (IAQ) component indicate that for nearly all household stove or fuel groupings, PM(4) levels were higher than - and sometimes more than twice as high as - the national PM(10) standard for indoor air (150 microg PM(10)/m(3)). If these results are typical, then a large fraction of China's rural population is now chronically exposed to levels of pollution far higher than those determined by the Chinese government to harm human health. Further, we observed highly diverse fuel usage patterns in these regions in China, supporting the observations in the household survey of multiple stoves being present in many kitchens. Improved stoves resulted in reduced PM(4) from biomass fuel combinations, but still not at levels that meet standards, and little improvement was observed in indoor pollution levels when other unimproved stoves were present in the same kitchen. As many households change fuels according to daily and seasonal factors, resulting in different seasonal concentrations in living rooms and kitchens, assessing health implications from fuel use requires longitudinal evaluation of fuel use and IAQ levels, combined with accurate time-activity information. PRACTICAL IMPLICATIONS: Leaving aside the difficult issue of enforcement, it is uncertain whether Chinese household IAQ standards represent realistic objectives for current attainment given current patterns of energy consumption in rural China, which rely so heavily on unprocessed solid fuels. Even when used with chimneys, these fuels emit substantial pollution into the household environment. It is probable that low-emission technologies involving gaseous/liquid fuels or high combustion - efficiency biomass stoves need to be promoted in order to achieve these standards for the greater part of the population.

Effects of inoculum size and age on biomass growth and paclitaxel production of elicitor-treated Taxus yunnanensis cell cultures.

Suspension cultures of Taxus yunnanensis cells were inoculated with cells of different culture ages (12-24 days) at various densities [50-250 g fresh weight (fw)/l], and treated (on day 7) with a mixture of elicitors, including Ag(+), chitosan and methyl jasmonate. The biomass productivity (during the production stage) increased dramatically with inoculum size, but decreased with inoculum age over 16 days. The volumetric yield and productivity of taxol (paclitaxel) also increased with inoculum size, while the specific taxol yield (per cell) was mainly dependent on inoculum age, with an optimum of 20 days, during the early stationary phase. The highest taxol yield and productivity, 39.8 mg/l and 1.9 mg/l per day, respectively, were obtained with a 20-day-old inoculum at 200 g fw/l. Taxol excretion by the cells increased with inoculum age but decreased with inoculum size. The elicitor-induced activities of catalase (CAT) and phenylalanine ammonia-lyase (PAL) also depended mainly on inoculum age; higher PAL activity and lower CAT activity were obtained with an older inoculum, corresponding to a higher taxol yield. The results show that both inoculum size and age are important variables for taxol production, though the latter more profoundly influences elicitor-induced taxol biosynthesis of the cells. Inoculum size and age are also interrelated and should be optimized together in a two-stage culture process.

Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder.

AIM: To observe the effects of Qiwei Baizhu Powder (QWBZP) on rotaviral gastroenteritis in children and in animal models. METHODS: Enrolled patients were divided into two groups, and one group was treated with oral rehydration solution (ORS) and the other treated with oral liquid of QWBZP. Neonate mice were orally infected with 50 microL rotavirus suspension (4 X 10(8) PFU/mL) and treated with ORS or oral liquid of QWBZP, respectively. RESULTS: Eighty-three cases of rotaviral gastroenteritis treated with QWBZP revealed a better efficacy than that treated with ORS (X(2)=10.87, P < 0.05). The contents of sodium and glucose as well as number of patients with positive human rotavirus antigen in stool in QWBZP group were all less than that in ORS group. In animal models, QWBZP was found effective in treating rotavirus gastroenteritis in neonate NIH mice, as compared with control groups. In QWBZP group, the mortality of infected mice was decreased by 73.3%, the body weight of infected mice was increased, the contents of sodium and glucose as well as number of mice with positive rotavirus antigen in feces were significantly reduced, and the pathological changes such as damage of small intestinal mucosa and villi were also obviously alleviated. CONCLUSION: QWBZP has effects on improving the absorptive function of small intestine, shortening the duration of diarrhea and rotavirus shedding from stool and alleviating the pathological changes of small intestine induced by rotavirus.

[Studies on polysaccharide alkaloids and minerals from Dendrobium moniliforme (L.) Sw].

OBJECTIVE: To explore contents of active substances in different part of Dendrobium monilifrome and the quality influenced by different drying processes. METHOD: Contents of alkaloids and polysaccharides in upper, middle, lower-stem and root part of Dendrobium moniliforme were determined by uv-spectrophotometer method. Contents of essential trace elements were determined by ICP method. RESULT: Contents of polysaccharides and alkaloids were highest in the upper-stem of D. montiliforme. Contents of active substances in different part of D. moniliforme were unequal. Distributions of polysaccharides and alkaloids in different parts were greatly influenced by drying procedures. CONCLUSION: Dendrobium moniliforme has higher contents of active ingredients, such as essential tract elements, alkaloids and polysaccharides. The ideal drying process after harvesting is to be the way dried by fire at a high temperature and desiccated at a temperature of 60 degreeC.

[Determination of total flavonoids and dihydromyricetin in Ampelopsis grossedentala (Hand-Mazz) W. T. Wang].

OBJECTIVE: To establish a method for the assay of total flavonoids and dihydromyricetin in A. grossedentala. METHOD: The flavonoids were determined by spectrophotometry and dihydromyricetin by TCL-scanner. RESULT: The content of flavonoids was 43.4%-44.0%, RSD 1.56%-2.62% and the content of dihydromyricetin was 37.4%-38.5%, RSD 1.85%-2.65%. CONCLUSION: The method is rapid, simple, accurate and good for the determination of total flavonoids and dihydromyricetin in A. grossedentala.

Identification of two novel mutations in the hypoglycemic phenotype of very long chain acyl-CoA dehydrogenase deficiency.

Very long chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial step of long chain fatty acid oxidation in the mitochondria. Patients with VLCAD deficiency have recently been observed with two clinical phenotypes. The cardiac form presents with an early onset cardiomyopathy and a high incidence of infant death, while the hypoglycemic form resembles medium chain acyl-CoA dehydrogenase (MCAD) manifesting with hypoketotic hypoglycemia. In our investigation on the molecular basis for these phenotypes, we identified two novel mutations in one VLCAD patient with the hypoglycemic form, a C953T (Pro318Leu) mutation in exon 10 resulting in a substitution of proline 318 by leucine on one allele, and a C1194A (Tyr398Stop) mutation in exon 12 which created a premature stop codon TAA on another allele. The Tyr398Stop mutation may result in a truncated protein or instable messenger RNA.

Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.

OBJECTIVES: We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time. METHODS: Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine. RESULTS: After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes. CONCLUSIONS: Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.

[Comparative study on therapeutic effects of gandou tablet I and dimercaptosuccinate acid in treating Wilson disease].

OBJECTIVE: To compare the effects of Gandou I (GD, a Chinese herbal preparation) and dimercaptosuccinate acid (DMSA) in treating Wilson disease (WD). METHODS: Ninety-four patients with WD were divided into 2 groups, 32 cases in the GD group and 62 in the DMSA group, they were treated with GD and DMSA respectively. The therapeutic course was 4 weeks for both groups. Modified Goldstein's Degree was adopted to evaluate the clinical effect. RESULTS: The total effective rate of the GD group was 71.9%, which was similar to that of the DMSA group (77.4%, P > 0.05). But the adverse reaction occurred in the latter group was more than that in the former. CONCLUSION: GD is a low toxic and highly effective drug for long-term treatment of WD.

[Protection of naoyi-an granule in ischemic brain injury secondary to intracerebral hemorrhage in rats].

AIM: To explore the protective effect and its mechanism of the traditional Chinese medicine complex, naoyi-an granule(NYAG), on intracerebral hemorrhage(ICH) in rats. METHODS: Collagenase-induced ICH rats were used. Inducible nitric oxide synthase(iNOS) activity of ischemic cerebral cortex surrounding the intracerebral hematoma was assayed by monitoring the conversion of L-3H-arginine to L-3H-citrulline. Pathologic changes in the same area were observed with transmission electron microscope on the 2nd day, the 4th day and the 7th day after ICH. RESULTS: The iNOS activities of NYA-treated group decreased remarkably(P < 0.01) compared with those of the saline-treated group. Ultrastructural observation also indicated that NYAG ameliorated the brain edema, cell degeneration and necrosis. CONCLUSIONS: The inhibitory effect of NYAG on iNOS activity may be related to its protection against ischemic brain injury secondary to ICH.

[Chemical changes of compatibility for shaoyao decoction].

OBJECTIVE: To probe the regular patterns of interactions among chemical components in Chinese medicinal complex prescriptions. METHOD: The active components of Rhubarb, Coptis root and Baikal skullcap root in different patterns of compatibility were determined by TLC-scanner. RESULT: The berberine content in Coptis root can be decreased obviously by Rhubarb, Baikai skullcap root and Licorice root, especially by Rhubarb. Coptis root can also decrease the contents of acid components. CONCLUSION: The acid components can affect each other, thus reducing the contents of effective components.

[Pharmacological actions of different species form genus Pyrola].

This paper reporst the pharmacological actions and toxicities of the water extracts from Pyrola calliantha, Pyrola decorta and P. forrestiana. The results show that the actions of P. forrestiana on antiventricular fibrillation, strengthening cardiac musicular contraction and antihypoxia abitity are more stronger, but on antiinflammation and antipyretic, effects of P. decorta and P. calliantha are significantly better than that of P. forrestiana. The effects of the three species on immunization and antisepsis are similar.

[Extraction and sequencing of trace DNA from cornu Cervi pantotrichum].

The trace DNA extraction method was used to extract DNA from the blood, hair, Cornu cervi pantotrichum, hairy antler of the sika deer, Cervus nippon, and penis of Bulbalus bublis and Asinus vulgaris. A 307 bp fragment of mitochondrial DNA cytochrome b gene was amplified with primers L14841 and H15149 for these extractions. The purified PCR products were sequenced by the dideoxy method. DNA sequence obtained from the Cornu cervi pantotrichum is the same as that obtained from the fresh blood and hair of the sika deer, but the sequence of the so-called hairy antler is quite different, implying that it is not from the sika deer. In addition, the phylogenetic relationships among different species are congruent with the traditional known phylogeny.

280 cases of hyperplasia of mammary gland treated by ru he chong ji.

280 patients with hyperplasia of mammary gland were treated by Ru He Chong Ji, a breast nodule granular dissolvable agent. Thirty-one were cured, 117 markedly improved, 119 improved, and 13 showed no change. The rate of cure and marked effectiveness was 52.86%, with a total effective rate of 95.36%. The agent is also effective for treatment of depression of liver-energy and menoxenia.

A eukaryotic transcriptional repressor with carboxypeptidase activity.

Adipocyte differentiation involves the transcriptional activation of several genes in triglyceride metabolism, including the adipose P2 (aP2 or 422) gene that encodes the adipocyte lipid-binding protein ALBP. Within the mouse aP2 promoter region, the AE-1 sequence functions as either a positive or a negative element in the regulation of aP2 gene expression. The AE-1 sequence is the binding site for the positive murine (3T3) adipocyte factor C/EBP-alpha, several human preadipocyte factors, and a 3T3 preadipocyte factor(s) that has been implicated as a repressor of aP2 gene expression. Here we report the cloning of new complementary DNAs that encode the 3T3 preadipocyte factor (termed AEBP1) and demonstrate that AEBP1 expression is abolished during adipocyte differentiation. Furthermore, we show that an activity of a carboxypeptidase associated with AEBP1 is important in the transcriptional repression function of AEBP1. Thus AEBP1 might represent a new type of transcription factor that regulates transcription by cleavage of factors involved in transcription.

[Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus].

The experimental results indicate that the decoction of Chinese drugs Carthamus tinctorius, Angelica sinensis and Leonurus sibiricus has stimulating action on the uterus of mouse in vitro. The stimulating action of Carthamus tinctorius and Leomurus sibiricus has been found related to stimulating H1-receptor and alpha-adrenergic receptor of uterus, but the action of Angelica sinensis to stimulating H1-receptor of uterus only.

[Effects of lyophilized royal jelly on experimental hyperlipidemia and thrombosis].

Rat models with experimental hyperlipidemia were fed with lyophilized royal jelly 700 mg/kg body weight daily for six weeks. Results showed lyophilized royal jelly can reduce serum cholesterol level (P < 0.01) and increase high-density lipoprotein-cholesterol level (P < 0.05). Lyophilized royal jelly can also increase the red cell deformability (RCD) and decrease plasma fibrinogen level. Thrombus was formed less in trial animals than in controls with a statistical significance. It suggested lyophilized royal jelly can be used in preventing and treatment of hyperlipidemia, and improving highly-coagulant status of blood.

Middle and proximal sections of the human internal mammary artery are not "passive conduits".

Recent studies have shown that blood flow through the internal mammary artery graft is inadequate for maximal exercise and that hypoperfusion may be worsened by high-dose vasopressor therapy that could further reduce arterial graft flow. Histologic studies have suggested that the human internal mammary artery is an elastic "passive conduit" along the majority of its length. However, although the pharmacologic reactivity at the distal section of the internal mammary artery has been extensively studied, this evaluation has never been done at the middle and proximal sections. It is extremely important to understand the contractility at the midsection of the internal mammary artery because, in a critical situation, any contraction may further reduce the internal mammary artery flow. The present study was designed to investigate the following: (1) Is it true that the pharmacologic reactivity of the human internal mammary artery is different among various sections? and (2) Is the human internal mammary artery a nonreactive "passive conduit" at its most important area used as the graft--the middle and the proximal sections? One hundred six human internal mammary artery ring segments taken from patients who underwent internal mammary artery grafting procedures (29 from the proximal, 38 from the middle, and 39 from the distal sections) were studied in the organ bath under a physiologic pressure. Concentration-response curves were established for norepinephrine, endothelin-1, U46619, potassium, and glyceryl trinitrate (precontracted with 10 nmol/L U46619). Contraction forces were standardized (in grams per millimeter circumference) at a pressure of 100 mm Hg. The contraction force was greater in the distal section than in other sections for norepinephrine (p = 0.002) and endothelin-1 (p = 0.04). No differences were seen for potassium, U46619, or glyceryl trinitrate, whereas the effective concentration inducing 50% of maximal response for U46619 was 100-fold lower in the distal than in the middle section (9.06 +/- 0.34 versus 7.06 +/- 0.48 -log M; p = 0.01) indicating higher sensitivity in the distal section. This study for the first time shows various reactivity along the full length of the human internal mammary artery and shows that the distal section is the most reactive part of the graft. However, although the middle and the proximal sections are less reactive to some vasoconstrictors (norepinephrine and endothelin-1), it is not a "passive conduit" and it contracts with all four vasoconstrictors tested.(ABSTRACT TRUNCATED AT 400 WORDS)