OBJECTIVE: To investigate the molecular mechanism by which a novel naphthalene allyl trifluoromethyl benzocyclopentanone XX0335 inhibits the proliferation and induces apoptosis of lung cancer A549 cells. METHODS: Lung cancer A549 cells were treated with 0.1% DMSO (control) or different concentrations (6.25, 12.5, and 25 μg/mL) of XX0335, and the changes in cell viability, cell cycle, proliferation and apoptosis were assessed with CCK-8 assay, EdU experiment, and flow cytometry. The effects of different concentrations of XX0335 on phosphorylation levels of proliferation-related proteins Akt, mTOR, Akt/mTOR and the expressions of cleaved PARP and cyclin D1 were determined using Western blotting. We also assessed the effect of XX0335 on tumor growth in a mouse model bearing A945 cell xenograft. RESULTS: Treatment with XX0335 reduced the viability of A549 cells in a dose-dependent manner (P < 0.01) and significantly inhibited cell proliferation (P < 0.001). Flow cytometry showed that XX0335 treatment promoted apoptosis of the cells (P < 0.01) and caused an obvious increase of the number of G1-phase cells. Compared with DMSO, XX0335 significantly inhibited the phosphorylation of Akt and mTOR, increased the expression of cleaved PARP, and lowered the protein expression of cyclin D1. In the tumor-bearing mouse models, injection of XX0335 significantly decreased the tumor volume (P < 0.01). CONCLUSION XX0335 inhibits the proliferation, cycle and induces apoptosis of lung cancer A549 cells possibly by inhibiting the Akt/mTOR signal pathway.
A549 Cells ; Animals ; Apoptosis ; Cell Proliferation ; Humans ; Lung Neoplasms/metabolism* ; Mice ; Naphthalenes/pharmacology*

A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).
Aldehydes ; isolation & purification ; pharmacology ; Antiviral Agents ; isolation & purification ; pharmacology ; Chromatography, High Pressure Liquid ; Gentianaceae ; chemistry ; Naphthalenes ; isolation & purification ; pharmacology ; Phytochemicals ; isolation & purification ; pharmacology ; Tobacco ; Tobacco Mosaic Virus ; drug effects

Suicide through naphthalene poisoning is rare. Prolonged hemolytic anemia and hemoglobinuria are typical symptoms of naphthalene poisoning. We report an unusual case of naphthalene poisoning. The decedent was an 87-year-old female who intentionally ingested over 5 g of naphthalene. After more than 5 hours, she was found in a drowsy state. During initial examination, hemoglobin level and urine test results were normal. Aspartate aminotransferase and alanine aminotransferase levels were elevated (854 and 1,197 U/L, respectively). Metabolic acidosis was found on arterial blood gas analysis. The patient was treated conservatively by administration of activated charcoal, calcium gluconate, insulin, and glucose. However, the patient died after 1 day of hospital admission. On autopsy, the liver showed toxic hepatitis with confluent necrosis. Naphthalene concentrations in the blood and gastric contents were 5.4 and 5.8 mg/L, respectively. In conclusion, the decedent ingested naphthalene and died due to liver failure without hemolysis.
Acidosis ; Aged, 80 and over ; Alanine Transaminase ; Anemia, Hemolytic ; Aspartate Aminotransferases ; Autopsy* ; Blood Gas Analysis ; Calcium Gluconate ; Charcoal ; Drug-Induced Liver Injury* ; Female ; Glucose ; Hemoglobinuria ; Hemolysis ; Humans ; Insulin ; Intention ; Liver ; Liver Failure ; Naphthalenes ; Necrosis ; Poisoning* ; Suicide

Simvastatin is one of the important prescription drugs for hypercholesterolemia. Monacolin J is a key intermediate during simvastatin synthesis, and also an intermediate of lovastatin biosynthesis. In this work, we construct a monacolin J producing strain via RNA interference to achieve one-step fermentation to obtain simvastatin. The lovF gene silencing plasmid pMHJ137 was constructed and transformed into Aspergillus terreus by Agrobacterium tumefaciens mediated transformation method. Precursor DMB-S-MMP was supplied during the fermentation to screen positive strains of transformants; which also further confirmed the simvastatin producing capability of MJ1-24 by one-step fermentation. Strain MJ1-24 produced monacolin J rather than lovastatin, and the feeding of DMB-S-MMP resulted in the generation of simvastatin. This study suggested that RNAi can efficiently silence the lovF gene of A. terreus and promote the simvastatin production by one-step fermentation.
3-Mercaptopropionic Acid ; analogs & derivatives ; Aspergillus ; chemistry ; genetics ; Fermentation ; Industrial Microbiology ; Naphthalenes ; chemistry ; RNA Interference ; Simvastatin ; chemistry

ObjectiveTo evaluate the effect and safety of Yimusake Tablets combined with dapoxetine hydrochloride and either of them used alone in the treatment of premature ejaculation (PE).

METHODSWe randomly assigned 180 PE patients to oral medication of Yimusake Tablets at 1.5 g per night (group A), dapoxetine hydrochloride at 30 mg at 1－3 hours before anticipated sexual activity (group B), the Yimusake Tablets plus dapoxetine hydrochloride simultaneously (group C), all for 8 weeks. After 4 and 8 weeks of medication, we recorded and compared the changes in the intravaginal ejaculation latency time (IELT), measures of the PE profile (PEP), and adverse events among the three groups of patients.

RESULTSThe treatment was accomplished and complete data obtained from 154 of the patients, 56 in group A, 52 in group B, and 46 in group C. After 4 and 8 weeks of medication, the mean IELT was dramatically prolonged in all the three groups as compared with the baseline (P<0.01), most significantly at 8 weeks in group C (［2.08±0.68］ min), followed by B (［1.76±0.52］ min) and A (［1.47±0.44］ min), with statistically significant differences among the three groups (P<0.01). The PEP measures were remarkably improved in group A at 8 weeks (P<0.05), and both in B and C at 4 and 8 weeks (P<0.05), most significantly at 8 weeks in group C (P<0.05), in which the patients scored 1.96±0.77 in perception of control over ejaculation, 2.62±0.98 in satisfaction with sexual intercourse, 3.04±0.62 in PE-related distress, and 3.57±0.80 in PE-induced difficult relationship with their partners, all markedly improved as compared with groups A and B (P<0.05). Adverse reactions were observed in 2 cases (3.6%) in group A, 6 cases (9.6%) in B, and 5 cases (10.9%) in C. No severe adverse events occurred in any of the patients during the study.

CONCLUSIONSCombined medication of Yimusake Tablets and dapoxetine hydrochloride, with its advantages of effectiveness and safety, deserves to be recommended for the treatment of PE.

Administration, Oral ; Adult ; Benzylamines ; therapeutic use ; Coitus ; psychology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Ejaculation ; Humans ; Male ; Naphthalenes ; therapeutic use ; Personal Satisfaction ; Premature Ejaculation ; drug therapy ; Sexual Behavior ; Tablets ; Time Factors ; Treatment Outcome

OBJECTIVETo evaluate the clinical effect and safety of dapoxetine in the treatment of premature ejaculation (PE).

METHODSWe randomly assigned 116 PE patients to receive dapoxetine on demand at 30 mg qd (dapoxetine group, n = 60, aged 23-49 years) or oral tamsulosin at 20 mg qd (control group, n = 56, aged 24-46 years). After 4 weeks of medication, we compared the clinical global impression of change (CGIC) , PE profile (PEP) scores, intravaginal ejaculation latency time (IELT) , and adverse reactions between the two groups of patients.

RESULTSCompared with the baseline, the IELT was remarkably prolonged after treatment both in the dapoxetine group ([0.86 ± 0.17] vs [4.32 ± 2.23] min, P < 0.05) and the control ([0.88 ± 0.15] vs [4.17 ± 2.26] min, P < 0.05), with no statistically significant difference between the two groups (P > 0. 05). The post-treatment rate of CGIC in the dapoxetine group had no statistically significant difference from that in the control (85.00% vs 82.14%, P > 0.05). In comparison with pre-treatment, the patients of both the dapoxetine and control groups showed dramatically improved scores after medication in perceived control over ejaculation (0.85 ± 0.23 vs 2.13 ± 0.97 and 0.88 ± 0.21 vs 2.06 ± 0.34, both P < 0.05), ejaculation-related personal distress (1.15 ± 0.64 vs 2.89 ± 0.26 and 1.19 ± 0.53 vs 2.82 ± 0.69, both P < 0.05), satisfaction with sexual intercourse (0.81 ± 0.33 vs 2.58 ± 0.37 and 0.79 ± 0.28 vs 2.45 ± 0.32, both P < 0.05), and ejaculation-related interpersonal difficulty (2.05 ± 0.61 vs 3.24 ± 0.35 and 2.03 ± 0.65 vs 3.18 ± 0.76, both P < 0.05), with no significant differences between the two groups (P > 0.05). The incidence of adverse reactions was significantly lower in the dapoxetine than in the control group (3.33% vs 30.36%, P < 0.05).

CONCLUSIONDapoxetine is effective for the treatment of PE, with its advantages of prolonging the intravaginal ejaculation latency time, improving the quality of sexual life, and low incidence of adverse reactions.

Adult ; Benzylamines ; administration & dosage ; therapeutic use ; Coitus ; Double-Blind Method ; Ejaculation ; Humans ; Male ; Middle Aged ; Naphthalenes ; administration & dosage ; therapeutic use ; Patient Satisfaction ; Premature Ejaculation ; drug therapy ; Serotonin Uptake Inhibitors ; administration & dosage ; therapeutic use ; Sexual Behavior ; Sulfonamides ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult

Premature ejaculation (PE) is a most common sexual dysfunction, for which dapoxetine, a novel selective serotonin (5-HT) re-uptake inhibitor (SSRI), is the only licensed oral medicine at present. With the advantages of fast absorption, rapid action, on-demand medication, and short half-life time, dapoxetine has been proved by clinical trials to be effective in prolonging the intravaginal ejaculation latency time (IELT) and improving the overall condition of PE patients in various areas and populations. Compared with the traditional SSRIs, dapoxetine has a better safety and tolerability. The most frequently reported dapoxetine-related adverse events include nausea, diarrhea, headache and dizziness, but with very few severe or serious cases.
Benzylamines ; therapeutic use ; Biomedical Research ; Ejaculation ; drug effects ; Humans ; Male ; Naphthalenes ; therapeutic use ; Premature Ejaculation ; drug therapy ; Reaction Time ; drug effects ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the efficacy and adverse effects of dapoxetine in the treatment of premature ejaculation.

METHODSWe randomly assigned outpatients with premature ejaculation in the proportion of 2:1 to receive 30 mg dapoxetine on demand (n =78) or 50 mg sertraline qd for one month (n = 39). Follow-up was accomplished in 95 cases, 63 in the dapoxetine group and 32 in the sertraline group. We recorded the intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, and adverse reactions of the patients and compared them between the two groups.

RESULTSIELT was significantly increased in both the dapoxetine (from [0.87 ± 0.31] to [2.84 ± 0.68] min, P < 0.05) and the sertraline group (from [0.84 ± 0.28] to [2.71 ± 0.92] min, P < 0.05) after medication. Based on the CGIC scores in premature ejaculation, the rate of excellence or effectiveness was 36.5% in the dapoxetine and 37. 5% in the sertraline group, and the rate of improvement was 63.5% in the former and 71.9% in the latter. The incidence rates of dizziness, nausea, headache, and diarrhea were slightly higher (P > 0.05) while those of fatigue, somnolence, and dry mouth significantly higher (P < 0.05) in the sertraline than in the dapoxetine group.

CONCLUSIONOn-demand oral medication of dapoxetine is effective and well-tolerated for the treatment of premature ejaculation.

Benzylamines ; adverse effects ; therapeutic use ; Double-Blind Method ; Ejaculation ; drug effects ; physiology ; Humans ; Male ; Naphthalenes ; adverse effects ; therapeutic use ; Outpatients ; Premature Ejaculation ; drug therapy ; Reaction Time ; drug effects ; physiology ; Serotonin Uptake Inhibitors ; adverse effects ; therapeutic use ; Sertraline ; administration & dosage ; adverse effects ; Time Factors ; Treatment Outcome

A new eremophilane derivative, (3aR,4R,5S,7S,7aS)-2-acetyl-7,7a-dihydroxy-3a,4-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-inden-5-yl acetate (1) and three known compounds, 10beta-hydroxy-eremophil-7 (11)-en-12,8alpha-olide(2), beta-sitosterol (3) and beta-daucosterol(4) have been isolated from Ligularia intermedia. The compounds were isolated by column chromatography on silica gel and Sephadex LH-20,and identified on the basis of spectral analyses (MS, 1H-NMR, 13C-NMR).
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Naphthalenes ; chemistry ; isolation & purification ; Sesquiterpenes

OBJECTIVETo examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate cancer in mice.

METHODSThirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice.

RESULTSAt 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P < 0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P < 0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P < 0.001).

CONCLUSIONEP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate cancer in mice.

Animals ; Bone Neoplasms ; prevention & control ; secondary ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Male ; Mice ; Mice, Nude ; Naphthalenes ; pharmacology ; Neoplasms, Experimental ; prevention & control ; Phenylbutyrates ; pharmacology ; Prostatic Neoplasms ; pathology