Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague–Dawley rats

Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.     

心尖锚的力学分析

设计了一种六齿镍钛合金锚钩用于封堵器等二尖瓣、三尖瓣返流修复系统的心尖固定,并对其力学特性进行研究.通过分析心脏结构及解剖数据,确定锚钩形状和可控尺寸设计变量,利用Solidworks建立锚钩3D模型,运用Abaqus软件对23个不同尺寸锚钩模型的入鞘过程进行有限元计算,分析锚钩入鞘过程中的最大入鞘力、最大冯米塞斯应变和入鞘轨迹的影响因素.制作了一种规格锚钩实物,与计算结果进行对比分析.结果表明:鞘部长度、鞘部角度及齿宽对应力、应变的影响最大,可以通过减小鞘部长度、鞘部角度及齿宽,有效降低最大应力、应变值;厚度、曲率半径及齿宽对入鞘力起到决定性作用,而根长和角度对入鞘力的影响很小;轴向刺入深度主要通过控制鞘部长度及鞘部角度来定义,径向刺入深度则由曲率半径的大小所决定.研究可为需心尖固定的心脏介入产品设计提供一定的借鉴意义.     

Functional polymorphism among members of abscisic acid receptor family(ZmPYL) in maize

Pyrabactin resistance 1-like proteins(PYLs) are direct receptors of abscisic acid(ABA). For the redundant and polymorphic functions, some members of the PYL family interact with components of other signaling pathways. Here, 253 positive colonies from a maize cDNA library were screened as interacting proteins with the members of ZmPYL family. After sequencing and function annotation, 17 of 28 interaction combinations were verified by yeast two-hybrid(Y2 H). The germination potential, taproot length and proline content of a quartet mutant of Arabidopsis PYL genes were significantly deceased comparing to the wild type(WT) under alkaline stress(pH 8.5) and 100 μmol L–1 methyl jasmonate(MeJA) induction. The malondialdehyde(MDA) content was significantly increased. After germinating in darkness, the characteristics of dark morphogenesis of the quartet mutant seedlings were more obvious than those of the WT. The differential expression of the related genes of photomorphogenesis in the mutant was much more than that in the WT. Three light and two JA responsive cis-affecting elements were identified during the promoter sequences of the AtPYL1 and AtPYL2 genes. These results suggested that functional polymorphism has evolved among the members of ZmPYL family. In response to developmental and environmental stimuli, they not only function as direct ABA receptors but also interact with components of other signaling pathways mediated JA, brassinosteroid(BR), auxin, etc., and even directly regulate downstream stress-related proteins. These signaling pathways can interact at various crosstalk points and different levels of gene expression within a sophisticated network.     

灌水对强筋小麦籽粒产量及营养品质的影响

为明确水地强筋冬小麦高产、优质、高效的灌溉技术,试验设3个灌水时期8个灌溉处理［越冬期灌1水（W₁）,拔节期灌1水（W₂）,孕穗期灌1水（W₃）,越冬期和拔节期灌2水（W₁₂）,越冬期和孕穗期灌2水（W₁₃）,拔节期和孕穗期灌2水（W₂₃）,越冬期、拔节期和孕穗期灌3水（W₁₂3）,全生育期不灌水处理（CK）］,于小麦成熟期测定籽粒产量、总蛋白及其组分含量和淀粉含量。结果表明,与不灌水的CK比较,所有灌水处理的籽粒产量、有效穗数、穗粒数、千粒重、蛋白质产量以及籽粒淀粉含量均显著增加,但籽粒的总蛋白及其组分含量均呈不同程度降低（W₁处理除外）。越冬期灌水对有效穗数、籽粒产量、总蛋白及其组分含量、淀粉含量的提升作用较大;拔节期灌水对穗粒数的提升作用较大,但对淀粉含量的提升作用较小,对总蛋白及其组分含量的降低作用较大;孕穗期灌水对千粒重的提升作用较大,对蛋白质产量的提升作用较小。随着灌水次数增加,小麦籽粒产量显著提高,淀粉含量先显著提高后基本不变,而籽粒总蛋白及其组分含量降低。W₁₂3处理籽粒产量最高,其次是W₁₃处理;W₁处理籽粒蛋白质及其组分含量最高,其次是W₁₂及W₁₃处理;W₂₃处理淀粉含量最高,其次是W₁₂或W₁₃处理。综合各项指标,最好的灌水组合是越冬期和孕穗期灌2水（W₁₃）。     

Potential Anti-Aging Substances Derived from Seaweeds

Aging is a major risk factor for many chronic diseases, such as cancer, cardiovascular disease, and diabetes. The exact mechanisms underlying the aging process are not fully elucidated. However, a growing body of evidence suggests that several pathways, such as sirtuin, AMP-activated protein kinase, insulin-like growth factor, autophagy, and nuclear factor erythroid 2-related factor 2 play critical roles in regulating aging. Furthermore, genetic or dietary interventions of these pathways can extend lifespan by delaying the aging process. Seaweeds are a food source rich in many nutrients, including fibers, polyunsaturated fatty acids, vitamins, minerals, and other bioactive compounds. The health benefits of seaweeds include, but are not limited to, antioxidant, anti-inflammatory, and anti-obese activities. Interestingly, a body of studies shows that some seaweed-derived extracts or isolated compounds, can modulate these aging-regulating pathways or even extend lifespans of various animal models. However, few such studies have been conducted on higher animals or even humans. In this review, we focused on potential anti-aging bioactive substances in seaweeds that have been studied in cells and animals mainly based on their anti-aging cellular and molecular mechanisms.     

Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro

Phenolic compounds and carotenoids are potential inhibitors of cytochrome P450s. Sixteen known compounds, phenolic compounds and carotenoids from seaweed were examined for potential inhibitory capacity against CYP1A2 and CYP3A4 in silico and in vitro. Morin, quercetin, and fucoxanthin inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose-dependent manner. The IC₅₀ values of morin, quercetin, and fucoxanthin were 41.8, 22.5, and 30.3 μM for CYP1A2 and 86.6, 16.1, and 24.4 μM for CYP3A4, respectively. Siphonaxanthin and hesperidin did not show any significant effect on CYP1A2, but they slightly inhibited CYP3A4 activity at high concentrations. In silico modeling of CYP’s binding site revealed that the potential inhibitors bound in the cavity located above the distal surface of the heme prosthetic group through the 2a or 2f channel of CYPs. This study presents an approach for quickly predicting CYP inhibitory activity and shows the potential interactions of compounds and CYPs through in silico modeling.     

Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD₅₀ of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD₅₀ of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.     

Sargassum horneri as a Functional Food Ameliorated IgE/BSA-Induced Mast Cell Activation and Passive Cutaneous Anaphylaxis in Mice

Sargassum horneri (S. horneri), an edible brown alga, has been proposed as a functional food with an improvement effect on abnormal skin immune responses. The present study investigates the anti-allergic effect of an ethanol extract from S. horneri (SHE) on immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation in bone marrow-derived cultured-mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) reaction in mice. SHE markedly and dose-dependently suppressed the degranulation of BMCMCs by reducing the β-hexosaminidase and histamine release without cytotoxicity. In addition, SHE significantly decreased the FcεRI expression on the surface of BMCMCs and its IgE binding. Moreover, SHE reduced the mRNA expression and the production of allergic cytokines; interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-10, IL-13; interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α; and a chemokine, thymus and activation-regulated chemokine (TARC), by suppressing the activation of Src-family kinases and nuclear factor (NF)-κB signaling. In further study, the application of SHE reduced the PCA reaction in an IgE/BSA-induced type I allergic mice model. Taken together, we suggest that SHE has an anti-allergic effect in type I allergic responses.