The evaluation of structure-activity relationships associated with the modification of the R115777 quinolinone ring moiety displaying potent in vitro inhibiting activity is described. 相似文献
Endomorphin (Endo) 1 and 2, two tetrapeptides isolated from the bovine and human brain, have been proposed to be the endogenous ligand for the mu-opiate receptor. A multi-disciplinary study was undertaken to address the issues of localization, release and biological action of Endo with respect to the rat dorsal horn. First, immunohistochemical studies showed that Endo-1- or Endo-2-like immunoreactivity (Endo-1- or Endo-2-LI) is selectively expressed in fiber-like elements occupying the superficial layers of the rat dorsal horn, which also exhibit a high level of mu-opiate receptor immunoreactivity. Second, release of immunoreactive Endo-2-like substances (irEndo) from the in vitro rat spinal cords upon electrical stimulation of dorsal root afferent fibers was detected by the immobilized antibody microprobe technique. The site of release corresponded to laminae I and II where the highest density of Endo-2-LI fibers was localized. Lastly, whole-cell patch clamp recordings from substantia gelatinosa (SG) neurons of rat lumbar spinal cord slices revealed two distinct actions of exogenous Endo-1 and Endo-2: (1) depression of excitatory and/or inhibitory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (2) hyperpolarization of SG neurons. These two effects were prevented by the selective mu-opiate receptor antagonist beta-funaltrexamine. The localization of endomorphin-positive fibers in superficial layers of the dorsal horn and the release of irEndo upon stimulation of dorsal root afferents together with the observation that Endo inhibits the activity of SG neurons by interacting with mu-opiate receptors provide additional support of a role of Endo as the endogenous ligand for the mu-opiate receptor in the rat dorsal horn. 相似文献
We report a protocol for the amplified detection of target DNA by using a chronocoulometric DNA sensor (CDS). Electrochemistry is known to be rapid, sensitive and cost-effective; it thus offers a promising approach for DNA detection. Our CDS protocol is based on a 'sandwich' detection strategy, involving a capture probe DNA immobilized on a gold electrode and a reporter probe DNA loaded on gold nanoparticles (AuNPs). Each probe flanks one of two fragments of the target sequence. A single DNA hybridization event brings AuNPs, along with hundreds of reporter probes, in the proximity of the electrode. We then employ chronocoulometry to interrogate [Ru(NH3)6]3+ electrostatically bound to the captured DNA strands. This AuNP-amplified DNA sensor can selectively detect as low as femtomolar (zeptomoles) concentrations of DNA targets and conveniently analyze a breast cancer-associated BRCA-1 mutant DNA. The time range for the entire protocol is approximately 3 d, whereas the DNA sensing takes less than 2 h to complete. 相似文献
Terpene trilactones (TTLs) are one of the main active ingredients of Ginkgo biloba. Owing to TTL’s unique chemical structure, it is difficult to increase TTL content through chemical and biological methods. Studying its regulatory mechanism is important in the G. biloba industry.
Results
The effect of exogenous methyl jasmonate (MeJA) on the physiological and molecular mechanism of TTL biosynthesis was studied. These results showed that MeJA treatment could improve the TTL contents, soluble sugar, starch, soluble protein, endogenous hormones (ZT, GA3, IAA, and ABA), antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), and the efficiency of photosynthesis in G. biloba leaves. A total of 100 differentially expressed genes (DEGs) were identified between the control group and MeJA treatment through RNA-seq analysis. The results indicated that exogenous MeJA treatment upregulated the expression levels of the following genes: BMY (beta-amylase) in the starch and sucrose metabolic pathway; PEX7 (peroxin-7) in the peroxisome pathway; psbA (photosystem II reaction center D1 protein), psbC (photosystem II CP43 chlorophyll apoprotein), psaA (photosystem I P700 chlorophyll a apoprotein A1), and petF (photosynthetic electron transport ferredoxin) in the photosynthesis pathway; and CYP450 (Gb-16765) (cytochromeP450).
Conclusions
Exogenous MeJA treatment can promote physiological indexes (photosynthetic efficiency, starch, sucrose, antioxidant enzyme activities, etc.) and then regulating differential genes, thus controlling the synthesis of TTLs.
Chemoresistance is a common occurrence during advanced or recurrent cervical cancer therapy when treated by conventional treatment, platinum‐based chemotherapy. This study aimed to investigate the effect and underlying mechanism of tanshinone I on attenuating proliferation and chemoresistance of cervical cancer cells. In cervical cancer cells, cell proliferation was examined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), cell count, and soft‐agar colony‐formation assay. rVista analysis and luciferase reporter assay were used to explore the upstream regulator of KRAS, and the expression levels of key genes were also detected. Western blot analysis showed that tanshinone I significantly suppressed KRAS expression and inhibited AKT phosphorylation. rVista analysis and luciferase reporter assay demonstrated that ELK1 can binds directly to KRAS promoter and positively regulates KRAS expression. MTT assay showed that KRAS or ELK1 overexpression significantly attenuated the suppressive effects of tanshinone I on HeLa cells proliferation. In addition, tanshinone I recovered the cisplatin sensitivity of HeLa CR cells, whereas KRAS or ELK1 overexpression significantly inhibited this phenomenon. Our results suggested that tanshinone I had anticancer effects on cervical cancer cells via inhibiting ELK1 and downregulating KRAS‐AKT axis, which subsequently suppressed the proliferation and cisplatin resistance of cervical cancer cells. 相似文献
Asian corn borer, Ostrinia furnacalis (Guenée), is a key corn pest in the Asian‐Western Pacific countries. It overwinters as full‐grown larvae in plant stalks or in a spun‐silk covering located in the plant debris in the temperate regions of China. Supercooling point (SCP) and survival rate after low sub‐zero temperature treatment were assessed for field‐collected populations in the laboratory using a cool bath with a 1°C/min cooling rate until ?40°C. Mean SCPs were varied among geographical populations, with a significant decline from ?22.7°C of Haikou, the multivoltine tropical population in the south, to ?28.5°C of Gongzhuling, the univoltine temperate population in the northeast of China. In addition, there was more than 1°C difference in SCP between Gongzhuling univoltine and bivoltine populations that were from the same geographic origin. Mean SCPs of the Guangzhou population fluctuated over the year, with significantly lower SCPs in winter than in other seasons, which correlated with a significantly higher proportion of diapausing larvae in winter than in other seasons. Over 41% of overwintering larvae from the northeast population could withstand to be supercooled for a few minutes to the low sub‐zero temperature of ?40°C, but only 6.7% of their southern counterparts did so. The findings from this study suggest that O. furnacalis mostly takes advantage of freeze avoidance as diapausing larvae for overwintering in the southern region, whereas it exhibits freeze tolerance in diapause in the northeastern region. 相似文献
IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.
Methods and Results
Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apo)E deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC) natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.
Conclusions
The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses. 相似文献