Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC₅₀ and CC₅₀ of compound 3 against HBV were 4.5 μmol·L^-1 and 92.3 μmol·L^-1, respectively. This is the first report of the antiviral activity of compound 3.

In order to find highly active antidiabetic lead compound, sixteen 4-aminobenzoic acid derivatives were designed and synthesized directly through Mannich reaction in the solution of ethanol at 15-35 degrees C with facile method, mild reaction condition and high yield (45%-90%). Fifteen of them are new compounds. Their structures were confirmed by 1H NMR, 13C NMR, IR, ESI-MS and HR-MS. Alpha-glucosidase inhibitory activity of these compounds indicated that most of these compounds possess the activity with the order: 2c > 2b > 2h > 1a > 1f. The structure-activity relationship of these 4-aminobenzoic acid derivatives was also discussed.
4-Aminobenzoic Acid ; chemical synthesis ; pharmacology ; Drug Design ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Mannich Bases ; chemistry ; Molecular Structure ; Structure-Activity Relationship ; alpha-Glucosidases ; metabolism ; para-Aminobenzoates

Objective To investigate the therapeutic effect of dense-packing auto hair grafting technique on the restoration of seborrheic alopecia. Methods With local anesthesia, a scalp strip was harvested from the back of the head. Under operating microscope (Various graft was created from the scalp strip, including micro-grafts with 1-2 hairs, mini-grafts with 3-4 hairs and sliver graft with 5-6 hairs. In the alopecia recipient area, micro slots were made with a small triangle-edged needle for the micro-grafts,mini slits were made with mini blade for the mini-grafts and foramen ovale were made with a slot punch. The grafts were then implanted into these holes. Results 32 cases of seborrheice alopecia were treated with the above mentioned technique from March 2007 to July 2009. Postoperative following up for 12-24 month showed that the grafted hairs were growing well with average 90 % survival of the hair. 81 % of the patients obtained satisfactory results with only one stage operation. Six patients needed the second operation to improve the appearance. All of the patients were satisfied with the appearance. Conclusions The dense-packing hair grafting technique with various grafts not only saves time of operation, but also obtains dense grafted hair and well appearance. The results are satisfactory to most patients with only one stage operation.

The discovery of high performance leading antidiabetic compounds containing sulfonamide and 4-aminophenylacetic acid moieties is reported. This was achieved by the synthesis of 6 intermediates and subsequently 20 target molecules using 4-aminophenylacetic acid as the starting materials, and through a few synthetic routes aided by multi-step reactions including sulfonylation of amino group, deacylation of amides and esterification of carboxyl group, as well as acylation of amino group. The chemical structures of the twenty-four new compounds were determined using 1H NMR, 13C NMR and HR-MS techniques. Screening in vitro of their peroxisome proliferator-activated receptor (PPAR) activation activities showed weak relative PPAR activation activities to most of the target molecules. However, 4 target molecules exhibit PPAR over 58%, and as high as 81.79% for TM2-i, presenting itself as potent leading compound for antidiabetic drugs. This research also confirms that it is probable to achieve esterification of carboxyl group and deacylation of fatty acid N-phenyl amides concurrently in SOCl2/alcohol solvent system. This provides new synthetic method for the selective reaction within molecules containing both carboxyl and N-aryl amido groups of fatty acids.
Aniline Compounds ; chemistry ; Fatty Acids ; chemistry ; Hep G2 Cells ; metabolism ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Phenylacetates ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Sulfonamides ; chemistry

Twenty five new beta-aminoalcohols containing nabumetone moiety were prepared via the reduction of potassium borohydride with a convenient and efficient procedure, starting from beta-aminoketones that have been synthesized by our group. Their chemical structures were determined by IR, MS, 1H NMR, 13C NMR, HR-MS and antidiabetic activities were screened in vitro. Preliminary results revealed that the antidiabetic activity of most beta-aminoalcohols were better than that of the corresponding beta-aminoketones. Although most compounds showed weak antidiabetic activity, the alpha-glucosidase inhibitory activity of compounds 5hd(1) and 5id(2) reached 74.37% and 90.15%, respectively, which were superior to the positive control. The relative peroxisome proliferator-activated receptor response element (PPRE) activity of five compounds were more than 60%, among them compound 5ca possessed the highest activity (112.59%). As lead molecules of antidiabetic agents, compounds 5hd(1), 5id(2) and 5ca deserve further study.
Amino Alcohols ; chemical synthesis ; chemistry ; pharmacology ; Butanones ; chemical synthesis ; chemistry ; pharmacology ; Cyclooxygenase 2 Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Peroxisome Proliferator-Activated Receptors ; agonists ; metabolism ; Response Elements ; alpha-Glucosidases ; metabolism

BACKGROUNDGene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell (Hep-2) tumor-bearing mice were used.

METHODSA xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR.

RESULTSGene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin.

CONCLUSIONSThe combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.

Animals ; Azacitidine ; analogs & derivatives ; therapeutic use ; Cadherins ; analysis ; DNA Modification Methylases ; antagonists & inhibitors ; Epigenesis, Genetic ; Genes, p53 ; Genetic Therapy ; Humans ; Laryngeal Neoplasms ; genetics ; pathology ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Tumor Suppressor Protein p53 ; analysis ; Xenograft Model Antitumor Assays

BACKGROUNDThe application of pulmonary valved conduit to reconstruct the continuity between right ventricles and pulmonary artery is one of the major surgeries. This study aimed to establish an in vivo model of in situ implantation using pulmonary valved conduit in large animals under off-pump condition to validate the long-term effects of artificial pulmonary valved conduit.

METHODSDomesticate juvenile male sheep and tissue-engineered porcine pulmonary valved conduit were used for the experiment: 30 sheep, weighing (15 ± 3) kg (range 13 to 17 kg) were randomly divided into two groups which were all operated under general anesthesia by off-pump surgery (group 1) and left thoracotomy (group 2). Two different off-pump surgical methods were used to perform cannulation in sheep pulmonary artery to replace part of sheep pulmonary artery with pulmonary valved conduit which will work together with sheep pulmonary artery and valves. During the experiments, animal survival, complication rates, operating time and blood loss were recorded to compare the results between groups and to establish a surgical method with minimal invasion, simplicity, safety, and high success rates.

RESULTSIn group 1, a total of 15 cases of surgeries were performed, in which two sheep died; the operative mortality was 13.3% (2/15). In group 2, a total of 15 cases of surgeries were performed, and the surgical mortality rate was 0 (0/15). The operation time and blood loss in group 2 was significantly better than that in group 1. The postoperative echocardiograms showed that, after the surgeries by these two methods, the blood flows were normal, and the valves can open and close freely. Autopsy after 6 months showed that the inner wall and the valves of pulmonary valved conduit were smooth with no thrombus formation.

CONCLUSIONThese two off-pump methods are feasible and safe with fewer traumas; but the second method is better and particularly suitable for the establishment of a juvenile animal model.

Animals ; Heart Valve Prosthesis ; Male ; Pulmonary Valve ; Sheep ; Swine ; Tissue Engineering

OBJECTIVEPatient with myocardial bridging (MB) usually has a benign prognosis, but some MB patients might experience myocardial ischemia, infarction and sudden cardiac death, especially during active physical activities. The purpose of the study was to study the stress-induced blood flow changes of the mural coronary artery in MB patients determined by intracoronary Doppler.

METHODSIn 8 patients with MB, the basic average peak velocity (bAPV), hyperemic average peak velocity (hAPV) of blood flow, coronary flow reverse (CFR) proximal and distal to the mural coronary artery were measured before and during intravenously dobutamine (10 microg kg-1 min-1, then add 10 microg kg-1 min-1 at 3 min interval till 40 microg kg-1 min-1) by intracoronary Doppler.

RESULTSThe baseline mural coronary diameter reduction was (51.7+/-21.4)% and significantly increased to (90.0+/-12.7)% (P<0.01) during dobutamine infusion. bAPV on the segments proximal and distal to the mural coronary artery significantly increased from (19.83+/-5.84) cm/s and (20.75+/-4.91) cm/s to (31.52+/-10.93) cm/s and (30.46+/-9.01) cm/s (all P<0.05 vs. baseline) respectively post dobutamine infusion. CFR measured at proximal and distal to myocardial bridging also significantly decreased from (2.91+/-0.62) and (2.46+/-0.82) to (2.17+/-0.66) and (1.83+/-0.51) (all P<0.01).

CONCLUSIONStress can significantly increase the compression of intramural coronary artery and reduce CFR on coronary segments both proximal and distal to the MB. Thus, active exercise might induce myocardial ischemia in patients with myocardial bridging.

Blood Flow Velocity ; Cardiotonic Agents ; pharmacology ; Coronary Circulation ; drug effects ; Coronary Vessel Anomalies ; physiopathology ; Coronary Vessels ; drug effects ; Dobutamine ; pharmacology ; Female ; Humans ; Male ; Middle Aged

Searching for new antidiabetic lead compound, 4-(1-aryl-3-oxo-5-phenylpentylamino) benzenesulfonamides were designed and synthesized directly by three component one-pot condensation of 4-phenyl-2-butanone and sulfanilamide with some aromatic aldehydes at an yield of 23%-97%. The chemical structures of the twelve new Mannich bases were confirmed by 1H NMR, 13C NMR, FTIR, ESI-MS and HR-MS. The screening results of antidiabetic activity indicated that most of these title compounds possess alpha-glucosidase inhibitory activity, among which compound le is the strongest one. And compound 11 possesses good peroxisome proliferator-activated receptor response element (PPRE) agonist activity. The structure-activity relationship of these new beta-amino ketones containing benzenesulfonamide unit was also discussed preliminarily.
Drug Design ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Peroxisome Proliferator-Activated Receptors ; agonists ; Structure-Activity Relationship ; Sulfanilamides ; chemistry ; Sulfonamides ; chemical synthesis ; chemistry ; pharmacology ; alpha-Glucosidases ; metabolism

OBJECTIVEExplore a good method for treating various hypospadias.

METHODSOral mucosa graft combined with a local turn-over flap was used for urethral reconstruction in 39 cases of hypospadias.

RESULTSAll the 39 cases were cured successfully in one stage, and satisfactory penile configuration obtained.

CONCLUSIONThis operation solved the problem of tissue scarcity in urethral reconstruction. It made use of the merits of different materials and avoided the disadvantage of a single tissue. It is good for treating various hypospadias and worthy of popularization.

Humans ; Hypospadias ; complications ; surgery ; Male ; Mouth Mucosa ; transplantation ; Penis ; surgery ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; Urethra ; surgery