Stimulating effects of Bacillus subtilis natto-fermented Radix astragali on hyaluronic acid production in human skin cells

Ethnopharmacological relevance

Radix astragali, a well-known Chinese herb, which has been traditionally used for skincare, and microbial fermentation is one of the conventional methods for processing Chinese herbs.

Aim of the study

This research studied the effects of non-fermented (HQNB) and fermented preparations (HQB) of Radix astragali on hyaluronic acid (HA) production in primary human skin cells.

Materials and methods

HQB and HQNB were prepared and added to the cultures of primary human skin cells. Hyaluronic acid content was determined using ELISA. Real-time RT-PCR was used to evaluate hyaluronan synthase gene expression. The bioactive compounds were analyzed by HPLC.

Results

The growth-stimulating effect of HQNB on both of keratinocytes and fibroblasts were significantly higher than that of HQB. Conversely, HQB, but not HQNB significantly stimulated HA production in both cultured primary human epidermal keratinocytes and human dermal fibroblasts in dose-dependent manners. In addition, HQB markedly and dose-dependently increased the expression of hyaluronan synthase 3 and hyaluronan synthase 2 mRNA in HaCaT cells and human fibroblasts, respectively. Therefore, HQB might be a promising candidate for preventing the age-dependent loss of HA content in aged human skin, and its effect on the enhancement of HA synthesis in skin cells is highly related to its effect on the expression of hyaluronan synthase genes. The three major active isoflavonoids in Radix astragali were identified as ononin, calycosin, and formononetin. After fermentation, all of these three compounds in HQB were significantly reduced. However, HQB still had significantly higher enhancement effect on the production of HA than HQNB. It appeared that isoflavonoid aglycones or other metabolites, converted from their primary isoflavones during fermentation, might be responsible for the skincare functions found in this study.

Conclusion

This study demonstrated the low toxicity and the stimulating effects of HQB on HA synthesis, and suggests that HQB may play a promising role in anti-aging cosmetic applications.     

Univariate and multivariate analysis of prognostic significance of betel quid chewing in squamous cell carcinoma of buccal mucosa in Taiwan

BACKGROUND AND OBJECTIVES: While betel quid (BQ) chewing is clearly the most avoidable risk factor of squamous cell carcinoma of buccal mucosa (BMSCC), little is known about the influence of this habit on the prognosis of BMSCC. METHODS: We surveyed 280 patients with BMSCC who were treated during an 8-year period in a cohort study to assess the independent predictive value of pretreatment BQ chewing habit on the prognosis by univariate and multivariate analysis. RESULTS: We found by univariate analysis that sex, age, clinical stage, smoking, and BQ chewing significantly affected the patients' prognosis and only age, clinical stage, and BQ chewing had significant influence on prognosis by multivariate analysis (P < 0.05). Further analysis revealed that the prognostic effect of BQ chewing changed in a dose- and time-dependent manner. The risk of death was 31.4-fold higher in heavy user (duration >30 years, daily consumption >30 quids, age of start <20 years old) when compared to those who chewed BQ to a milder degree (duration <10 years, daily consumption <15 quids, age of start > or =20 years old ) (P < 0.001). CONCLUSIONS: Pretreatment BQ chewing habit worsens the prognosis of BMSCC in Taiwan. BQ chewing is a prognostic indicator that can be used in conjunction with clinical staging to help plan the treatment for the patients.     

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

羽叶三七叶中甙类成分的研究

从羽叶三七叶中分离到十三种甙类成分,经FAB-MS,¹³CNMR谱,双照射¹HN-MR谱,¹H-¹H COSY谱及与标准品直接对照,证明十一种为已知化合物,分别为人参皂甙F₁(Ⅰ),F₂(Ⅱ),F₃(Ⅲ),R_g2(Ⅳ),R_a(Ⅴ),R_d(Ⅵ),R_b1(Ⅷ),R_b3(Ⅷ),24(S)-假人参甙F₁₁(Ⅸ),人参黄酮(Ⅹ)和珠子参甙F₁(Ⅺ);另外两种为新的达玛烷型皂甙,命名为羽叶三七甙F₁(Ⅻ)和F₂(ⅫⅠ),并确定其化学结构。同时修正珠子参甙F₃的结构。进一步阐明人参黄酮甙结构中的两个糖的连接方式。     

Unique formosan mushroom Antrodia camphorata differentially inhibits androgen-responsive LNCaP and -independent PC-3 prostate cancer cells

Antrodia camphorata (AC), a precious and unique folkloric medicinal mushroom enriched in polyphenolics, isoflavonoids, triterpenoids, and polysaccharides, has been diversely used in Formosa (Taiwan) since the 18th century. In this study, prostate cancer (PCa) cell lines PC-3 (androgen independent) and LNCaP (androgen responsive) were treated with AC crude extract (ACCE) at 50-200 microg/mL, respectively, for 48 h. At the minimum effective dose 150 microg/mL, LNCaP showed a G1/S phase arrest with significant apoptosis. Such dose-dependent behavior of LNCaP cells in response to ACCE was confirmed to proceed as Akt-->p53-->p21-->CDK4/cyclin D1-->G1/S-phase arrest-->apoptosis, which involved inhibiting cyclin D1 activity and preventing pRb phosphorylation. In contrast, being without p53, PC-3 cells showed a G2/M-phase arrest mediated through pathway p21-->cyclin B1/Cdc2-->G2/M-phase arrest, however, with limited degree of apoptosis, implicating that ACCE is able to differentially inhibit the growth of different PCa cells by modulating different cell cycle signaling pathways. We conclude that this unique Formosan mushroom, A. camphorata, due to its nontoxicity, might be used as a good adjuvant anticancer therapy for prostate cancers despite its androgen-responsive behaviors, which has long been a serious drawback often encountered clinically in hormonal refractory cases treated by antihormonal therapies and chemotherapeutics.     

Outcomes and Costs of Risperidone versus Olanzapine in Patients with Chronic Schizophrenia or Schizoaffective Disorders: A Markov Model

OBJECTIVE: To compare expected outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders who are treated with risperidone versus olanzapine. METHODS: A Markov model was developed to examine outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders receiving risperidone or olanzapine. The time frame of interest was 1 year. The model focused particular attention on the likelihood of therapy switching and discontinuation as a result of treatment-emergent side effects, as the efficacy of these two agents is similar. Measures of interest included the incidence of relapse and selected side effects including extrapyramidal symptoms (EPS), prolactin-related disorders and diabetes, expected change in body weight, and the percentage of patients remaining on initial therapy at the end of 1 year. Costs of antipsychotic therapy and psychiatric and nonpsychiatric services also were examined. RESULTS: At 1 year, the rate of EPS was estimated to be slightly higher for risperidone, as was the incidence of symptomatic prolactin-related disorders. The expected incidence of diabetes mellitus, while low, was slightly higher for olanzapine. Approximately 25% and 4% of olanzapine and risperidone patients, respectively, were projected to experience an increase in body weight > or = 7%. The estimated percentage of patients remaining on initial therapy at the end of 1 year was higher for risperidone than olanzapine (76.9% vs. 45.6%, respectively). Expected mean total costs of care per month of therapy were $2163 for risperidone and $2316 for olanzapine. Results from sensitivity analyses suggest that the probability of therapy discontinuation following weight gain >5 kg would have to be lower than 0.1 for the number of patients remaining on therapy at the end of 1 year to be the same for risperidone and olanzapine. CONCLUSIONS: Compared with risperidone, treatment with olanzapine may result in greater increases in body weight, higher rates of therapy discontinuation, and higher costs of medical-care services.     

Drug permeation across the skin: effect of penetrant hydrophilicity

The hydrophilicity of progesterone, a lipophilic steroid itself, was progressively increased by incorporating one or more hydroxy substituents at different positions on the steroidal skeleton. Effects of these hydrophilic substituents on the permeation of progesterone across the intact skin and stripped skin of the hairless mouse were studied using a hydrodynamically well-calibrated in vitro skin permeation system. The steady-state rate of permeation across the intact skin and stripped skin was found to be approximately proportional to the solubility of drugs in the stratum corneum or in the viable skin, respectively. Furthermore, the solubility of progesterone and its hydroxyl derivatives in the stratum corneum was noted to decrease gradually as the hydrophilicity of the penetrant increased. This finding was similar to that of a previously reported study of drug permeation across the lipophilic silicone membrane. However, the solubility of these progestins in the viable skin was observed to be dependent not only on the penetrant hydrophilicity but also on the position of the OH group on the penetrant molecule. The diffusivity of progesterone and its hydroxyl derivatives across the stratum corneum and viable skin was almost independent of the hydrophilicity of the drugs.     

Involvement of α2-Adrenoceptors in mechanism of intragastric nicotine protection against ethanol injury in rat stomach

To elucidate the role of - and -adrenoceptors in the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury, the following studies were performed. At 0.5-hr prior to the injury study, rats were pretreated with: subcutaneous control, prazosin (0.5 mg/kg) or yohimbine (5 mg/kg) to block ₁- or ₂-adrenoceptors; or intraperitoneal control, metoprolol (2 mg/kg) or butoxamine (4 mg/kg) to block ₁- or ₂-adrenoceptors, respectively. At 1-hr intervals, rats received intragastric vehicle or nicotine (4 mg/kg) and 40% ethanol (10 ml/kg). Total lengths of the linear gastric corpus mucosal lesions were measured by an unbiased observer using a caliper. In a separate study, 0.5-hr after subcutaneous control or yohimbine (5 mg/kg), rats were treated with intragastric vehicle or nicotine (4 mg/kg). One hour later, gastric mucus volume, gastric juice volume and pH, and titratable acid in the gastric juice were measured. In the rat stomach, the intragastric nicotine protection against 40% ethanol-induced mucosal injury was not blocked by selective ₁-(prazosin), ₁-(metoprolol), or ₂-(butoxamine) adrenoceptor antagonists. The protection was significantly reduced although not completely abolished by selective ₂-(yohimbine) adrenoceptor antagonist. Yohimbine also significantly reduced basal and nicotine-stimulated increase in gastric mucus volume. These data suggest that ₂-adrenoceptors are involved in the protective effect of intragastric nicotine against 40% ethanol-induced gastric mucosal injury possibly by a mucus-dependent mechanism.Supported by Veternas Administration Medical Research Funds, and in part by research grants (0162-01, 02, and 291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to F.W.L. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).     

Detection of high titres of Toxoplasma gondii antibodies in sera of patients with leprosy in Pakistan.

Untreated and treated leprosy patients and their household contacts were screened for antibody to Toxoplasma gondii using antigen-coated latex particles. A significantly high level of seroprevalence (29.6%) was observed in the untreated leprosy patients compared to endemic controls (P < 0.01) with a mean reciprocal antibody titre of 20,007 +/- 3580 (n = 98) in seropositive patients. In treated patients seroprevalence dropped to 13.5%. Seroprevalence in a group of household contacts of leprosy patients was similar to that of control subjects from an endemic area but not exposed to leprosy (7.8% and 6.1% respectively), indicating that the increased seroprevalence in leprosy patients was not merely due to increased exposure related to socioeconomic factors. Antigenic cross-reactivity between T. gondii and Mycobacterium leprae antigens was ruled out by cross inhibition experiments carried out with soluble antigens from each of the organisms. We believe these antibodies may be induced by an increase in T. gondii load in leprosy due to a transient reactivation of latent T. gondii infections, as the antibodies in these leprosy patients were not associated with any sign of eye or lymphatic pathology related to toxoplasmosis.