关于有尾类胚胎的表皮及非典型表皮的兴奋性

蝾螈胚胎表皮的兴奋性及传导能力在分期26出现,到分期37末结束,某些部位甚至更晚些消失。为了查明表皮细胞兴奋性的产生是否受到来自其它组织的影响,还是仅依赖于表皮细胞自身的分化状态,我们曾用非典型表皮进行过研究。当时曾报道,离体培养的表皮细胞,即使达到了产生兴奋性的分化状态,用电生理技术在刺激强度为1—2伏时,测试不到动作电位。然而,如果这样的非典型表皮被     

Characterization of Gastric and Neuronal Histaminergic Populations Using a Transgenic Mouse Model

Histamine is a potent biogenic amine that mediates numerous physiological processes throughout the body, including digestion, sleep, and immunity. It is synthesized by gastric enterochromaffin-like cells, a specific set of hypothalamic neurons, as well as a subset of white blood cells, including mast cells. Much remains to be learned about these varied histamine-producing cell populations. Here, we report the validation of a transgenic mouse line in which Cre recombinase expression has been targeted to cells expressing histidine decarboxylase (HDC), which catalyzes the rate-limiting step in the synthesis of histamine. This was achieved by crossing the HDC-Cre mouse line with Rosa26-tdTomato reporter mice, thus resulting in the expression of the fluorescent Tomato (Tmt) signal in cells containing Cre recombinase activity. As expected, the Tmt signal co-localized with HDC-immunoreactivity within the gastric mucosa and gastric submucosa and also within the tuberomamillary nucleus of the brain. HDC expression within Tmt-positive gastric cells was further confirmed by quantitative PCR analysis of mRNA isolated from highly purified populations of Tmt-positive cells obtained by fluorescent activated cell sorting (FACS). HDC expression within these FACS-separated cells was found to coincide with other markers of both ECL cells and mast cells. Gastrin expression was co-localized with HDC expression in a subset of histaminergic gastric mucosal cells. We suggest that these transgenic mice will facilitate future studies aimed at investigating the function of histamine-producing cells.     

Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models

Obesity-associated low-grade chronic inflammation plays an important role in the development of insulin resistance. The membrane lipid transporter ATP-binding cassette transporter A1 (ABCA1) promotes formation of nascent HDL particles. ABCA1 also dampens macrophage inflammation by reducing cellular membrane cholesterol and lipid raft content. We tested the hypothesis that myeloid-specific ABCA1 deletion may exacerbate insulin resistance by increasing the obesity-associated chronic low-grade inflammation. Myeloid cell-specific ABCA1 knockout (MSKO) and wild-type (WT) mice developed obesity, insulin resistance, mild hypercholesterolemia, and hepatic steatosis to a similar extent with a 45% high-fat (HF) diet feeding or after crossing into the ob/ob background. Resident peritoneal macrophages and stromal vascular cells from obese MSKO mice accumulated significantly more cholesterol. Relative to chow, HF diet markedly induced macrophage infiltration and inflammatory cytokine expression to a similar extent in adipose tissue of WT and MSKO mice. Among pro-inflammatory cytokines examined, only IL-6 was highly upregulated in MSKO-ob/ob versus ob/ob mouse peritoneal macrophages, indicating a nonsignificant effect of myeloid ABCA1 deficiency on obesity-associated chronic inflammation. In conclusion, myeloid-specific ABCA1 deficiency does not exacerbate obesity-associated low-grade chronic inflammation and has minimal impact on the pathogenesis of insulin resistance in both HF diet-induced and genetically obese mouse models.     

促白木香结香真菌的快速筛选

以海南省澄迈县海南科大林业公司所有的白木香人工林地为研究对象,采用前期已分离的菌株对白木香白木进行固体催化,利用GC-MS技术对具有催化效果(白木化学成分在催化前后变化显著)的菌株进行筛选,将筛选出的菌株接种至白木香树体中,6个月后对沉香物质挥发油以及化学成分进行测定。对白木固体催化产物的提取物分析,鉴定出其乙醚提取物共24种化学成分,其中共有成分5种、芳香族类化合物6种、其他类化合物18种。Trichoderma sp.、Neurospora sp.和Melanotus flavolivens这3种菌株使白木香白木的化学成分发生显著变化。对结香处理6个月后已结香木材的提取物分析,鉴定出其乙醚提取物共84种化学成分,其中共有成分30种,芳香族类化合物17种、倍半萜类化合物34种和其他类化合物33种。Trichoderma sp.、Neurospora sp.、Melanotus flavolivens和CK样品乙醚提取物得率分别为3.62%、4.04%、3.97%和1.94%。其中芳香族类成分相对含量之和分别为15.15%、17.29%、12.13%和7.95%。倍半萜类成分相对含量之和分别为10.61%、11.19%、11.4%和0%。在6个月内Trichoderma sp.、Neurospora sp.和Melanotus flavolivens这3种经过白木香白木固体催化筛选所得的菌株能够有效诱导白木香结香。     

PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non‐small cell lung cancer

BackgroundPappalysin 2 (PAPPA2) mutation, occurring most frequently in skin cutaneous melanoma (SKCM) and non‐small cell lung cancer (NSCLC), is found to be related to anti‐tumour immune response. However, the association between PAPPA2 and the efficacy of immune checkpoint inhibitors (ICIs) therapy remains unknown.MethodsTo analyse the performance of PAPPA2 mutation as an indicator stratifying beneficiaries of ICIs, seven public cohorts with whole‐exome sequencing (WES) data were divided into the NSCLC set (n = 165) and the SKCM set (n = 210). For further validation, 41 NSCLC patients receiving anti‐PD‐(L)1 treatment were enrolled in China cohort (n = 41). The mechanism was explored based on The Cancer Genome Atlas database (n = 1467).ResultsIn the NSCLC set, patients with PAPPA2 mutation (PAPPA2‐Mut) demonstrated a significantly superior progress free survival (PFS, hazard ratio [HR], 0.28 [95% CI, 0.14–0.53]; p < 0.001) and objective response rate (ORR, 77.8% vs. 23.2%; p < 0.001) compared to those with wide‐type PAPPA2 (PAPPA2‐WT), consistent in the SKCM set (overall survival, HR, 0.49 [95% CI: 0.31–0.78], p < 0.001; ORR, 34.1% vs. 16.9%, p = 0.039) and China cohort. Similar results were observed in multivariable models. Accordingly, PAPPA2 mutation exhibited superior performance in predicting ICIs efficacy compared with other published ICIs‐related gene mutations, such as EPHA family, MUC16, LRP1B and TTN, etc. In addition, combined utilization of PAPPA2 mutation and tumour mutational burden (TMB) could expand the identification of potential responders to ICIs therapy in both NSCLC set (HR, 0.36 [95% CI: 0.23–0.57], p < 0.001) and SKCM set (HR, 0.51 [95% CI: 0.34–0.76], p < 0.001). Moreover, PAPPA2 mutation was correlated with enhanced anti‐tumour immunity including higher activated CD4 memory T cells level, lower Treg cells level, and upregulated DNA damage repair pathways.ConclusionsOur findings indicated that PAPPA2 mutation could serve as a novel indicator to stratify beneficiaries from ICIs therapy in NSCLC and SKCM, warranting further prospective studies.

Flow diagram of the study. (A) Preliminary analysis. PAPPA2 mutated most frequently in skin cutaneous melanoma (SKCM) and non‐small cell lung cancer (NSCLC) in the The Cancer Genome Atlas (TCGA) database. PAPPA2 mutational rates in patients with objective response (CR + PR) versus without (SD + PD) were compared with other immune checkpoint inhibitors‐related gene mutations in the NSCLC and SKCM sets. (B) Biomarker development. Association between PAPPA2 mutation and clinical outcomes has been analysed in the NSCLC set, the SKCM set and China cohort. (C) Mechanism exploring. Based on the TCGA database, the correlation of PAPPA2 mutation with tumour mutation burden, infiltrating immune cells and DNA damage repair was explored for further immunogenicity and anti‐tumour activity mechanisms.     

7‐Epitaxol induces apoptosis in cisplatin‐resistant head and neck squamous cell carcinoma via suppression of AKT and MAPK signalling

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although cisplatin‐based chemotherapy is commonly used in HNSCC, frequent development of cisplatin resistance is a potential cause of poor HNSCC prognosis. In the present study, we investigated the anticancer efficacy of a major paclitaxel metabolite namely 7‐Epitaxol in cisplatin‐resistant HNSCC. The findings revealed that 7‐Epitaxol exerts cytotoxic effects in cisplatin‐resistant HNSCC cell lines by inducing cell cycle arrest and intrinsic and extrinsic apoptotic pathways. Specifically, 7‐Epitaxol increased Fas, TNF‐R1, DR5, DcR3 and DcR2 expressions, reduced Bcl‐2 and Bcl‐XL (anti‐apoptotic proteins) expressions, and increased Bid and Bim L/S (pre‐apoptotic proteins) expressions, leading to activation of caspase‐mediated cancer cell apoptosis. At the upstream cell signalling level, 7‐Epitaxol reduced the phosphorylation of AKT, ERK1/2 and p38 to trigger apoptosis. In vivo results showed that animals treated with 7‐Epitaxol show antitumor growth compared to control animals. Taken together, the study demonstrates the potential anticancer efficacy of 7‐Epitaxol in inducing apoptosis of cisplatin‐resistant HNSCC cells through the suppression of AKT and MAPK signalling pathways.     

Induktionsleistungen von frischen und gekochten Organteilen (Niere,Leber) nach ihrer Verpflanzung in Explantate und verschiedene Wirtsregionen von Tritonkeimen

Ohne ZusammenfassungD 19.