يعرض 1 - 10 نتائج من 23 نتيجة بحث عن '"Chunli Wu"', وقت الاستعلام: 0.74s تنقيح النتائج
  1. 1

    المصدر: Scientific reports. 12(1)

    الوصف: Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease that has an increasing death rate but no effective treatment to now. Although biological and immunological hallmarks of PDAC have been frequently reported recently, early detection and the particularly aggressive biological features are the major challenges remaining unclear. In the current study, we retrieved multiple scRNA-seq datasets and illustrated the genetic programs of PDAC development in genetically modified mouse models. Notably, the transcription levels of Id1 were elevated specifically along with the PDAC development. Pseudotime trajectory analysis revealed that Id1 was closely correlated with the malignancy of PDAC. The gene expression patterns of human PDAC cells were determined by the comparative analysis of the scRNA-seq data on human PDAC and normal pancreas tissues. ID1 levels in human PDAC cancer cells were dramatically increased compared to normal epithelial cells. ID1 deficiency in vitro significantly blunt the invasive tumor-formation related phenotypes. IPA analysis on the differentially expressed genes suggested that EIF2 signaling was the core pathway regulating the development of PDAC. Blocking EFI2 signaling remarkably decreased the expression of ID1 and attenuated the tumor-formation related phenotypes. These observations confirmed that ID1 was regulated by EIF2 signaling and was the critical determinator of PDAC development and progression. This study suggests that ID1 is a potential malignant biomarker of PDAC in both mouse models and human and detecting and targeting ID1 may be a promising strategy to treat or even rescue PDAC.

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    المصدر: Clinics, Volume: 77, Article number: 100119, Published: 02 DEC 2022

    الوصف: Objectives: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment. Method: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively. Results: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I. Conclusions: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.

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    المصدر: European journal of medicinal chemistry. 238

    الوصف: With the increasing incidence of antibiotic resistance, there is an urgent need to develop new antibiotics with excellent activity against drug-resistant bacteria. Three novel series of tylosin semisynthetic derivatives were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. Among these derivatives, compound C-2 demonstrated potent antibacterial activity against both gram-positive and gram negative bacteria, and non mutagenic. More importantly, compound C-2 displayed high antimicrobial potency against Gram-positive bacteria in a murine model, and was found to be more efficient than tildipirosin. Thus, compound C-2 had great potential as a promising lead compound for the treatment of bacterial infection.

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    المصدر: Nature metabolism. 4(5)

    الوصف: The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.

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    المصدر: Journal of Ethnopharmacology. 287:114940

    الوصف: Sanren decoction (SRD) is a well-known traditional Chinese medicine prescription containing eight kinds of materials. SRD has been used mainly in China for more than 200 years for the treatment of respiratory disorders that co-occur with a bad fever after midday.To evaluate the acute and 28-day subacute toxicity of an aqueous extract of SRD using in vivo methods.To determine acute toxicity, SRD was administered by gavage at a dosage of 58.5 g/kg/day to male and female mice for 7 days. To determine subacute toxicity, SRD was administered at 3.3, 6.5, or 13 g/kg/day to male and female rats for 28 days. The general behavior, body weight, biochemical and hematological parameters, organ coefficients and pathological morphology of the treated animals were analyzed.Neither acute nor subacute concentrations of SRD caused significant changes in the body weights, general behavior, hematology and biochemical parameters, organ weights, or histopathological appearances of the liver, kidney, spleen, brain, lung or heart in mice or rats.The administration of SRD can be considered safe within the conditions of this study.

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    المصدر: Virology. 523:35-40

    الوصف: Arboviruses have caused significant global health concerns during the past decade. In this regard, continuous viral surveillance is essential to timely identify emerging arboviruses and other novel viruses. Here, a novel isolate of Phasi Charoen-like virus (PCLV Zhanjiang01) was identified from field-captured Aedes aegypti mosquitoes in Zhanjiang by next generation sequencing. Phylogenetic analysis suggested that PCLV Zhanjiang01 belonged to the genus Phasivirus in the family Phenuiviridae. The presence of PCLV in three batches of Aedes aegypti confirmed its high prevalence in nature. Further detection of PCLV in progenies and adult males suggested vertical transmission in mosquitoes. In parallel, PCLV was detected from multiple organs indicating its broad tissue distribution in the infected mosquitoes. To the best of our knowledge, this is the first report of PCLV in China. Our results expanded the global biogeographic distribution of PCLV. Further investigations of PCLV on the arboviral transmission and control strategies are warranted.

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    المصدر: Organicbiomolecular chemistry. 19(4)

    الوصف: Hydrogen polysulfides (H2Sn, n > 1), which are important reactive sulfur species, play crucial roles in H2S-related bioactivities, including antioxidation, cytoprotection, activation of ion channels, transcription factor functions and tumour suppression. Monitoring H2Snin vivo is of significant interest for exploring the physiological roles of H2Sn and the exact mechanisms of H2Sn-related diseases. Herein, we conceive a novel near-infrared fluorescent probe, NIR-CPS, that is used to detect H2Sn in living cells and in vivo. With the advantages of high sensitivity, good selectivity and a remarkably large Stokes shift (100 nm), NIR-CPS was successfully applied in visualizing H2Sn in living cells and mice. More importantly, NIR-CPS monitored H2Sn stimulated by lipopolysaccharide in tumour-bearing mice. These results demonstrate that the NIR-CPS probe is a potentially powerful tool for the detection of H2Snin vivo, thus providing a valuable approach in H2Sn-related medical research.

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    المصدر: Biomedicine & Pharmacotherapy. 102:86-93

    الوصف: Purpose To investigate the protective effects of miR-320 on cerebral ischemia/reperfusion (I/R) injury in mice and PC12 cells. Methods miR-320 normal control (NC), inhibitor fragment and overexpression fragments were injected into mice lateral ventricles. Thereafter, the middle cerebral artery occlusion (MCAO) for left cerebrum method was employed in order to establish a cerebral I/R injury mice model. Apoptosis in the peripheral region of cerebral infarction and the volume of cerebral infarction and brain edema were tested as well. For simulating MCAO in vitro, the PC12 cells were subjected to oxygen-glucose deprivation. The lentivirus transfection technique was used to overexpress or inhibit miR-320. Furthermore, the effects of miR-320 on the survival and apoptosis of PC12 were monitored by MTT and TUNEL detection. Results A cerebral I/R injury mice model was successfully established. MiR-320 enhanced cell apoptosis of the injury side cortical infarcted peripheral zone and increased brain infarction volume and edema volume in MCAO/R mice. In addition, Insulin growth factor-1 (IGF-1) mRNA and protein expressions in MCAO/R mice were inhibited by miR-320 as well. Moreover, the results of cell studies were consist with the animal studies. Conclusions miR-320 may be involved in the regulation of cerebral I/R for brain parenchyma injury by inhibition of IGF-1 pathway.

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    المصدر: Journal of ethnopharmacology. 248

    الوصف: Ethnopharmacological relevance Bei Qi Wu Jia (BQWJ), a modern preparation of a traditional Chinese medicinal formula, is a combination of Radix Astragali and Acanthopanacis Senticosi. Although BQWJ has been used to treat insomnia, fatigue, and loss of appetite, toxicological safety studies are rare in the literature. Aim of the study: To evaluate the acute and subacute toxicity of BQWJ extract after oral administration in mice and rats, respectively. Materials and methods In the acute toxicity study, mice underwent oral administration of 67.5 g extract/kg/day. In the subacute toxicity study, rats underwent a single oral administration of 1.25, 2.5, 5.0, or 10.0 g/kg/day of BQWJ extract for 28 days. The animals’ general behavior, body weight, food intake, biochemical and hematologic parameters, organ coefficients, and pathological morphology were analyzed. Results No evidence of toxicity was observed in the mice after acute exposure to BQWJ extract. The subacute results included no deaths and no changes in general behavior. Although BQWJ extract resulted in some significant changes in other parameters, these alterations cannot be considered treatment-related because they remained within normal ranges throughout the 28 days. Conclusions In conclusion, the oral administration of BQWJ extract at doses of less than 67.5 g/kg/day for 1 day or 10.0 g/kg/day for 28 consecutive days can be considered safe and showed no distinct toxicity or side effects in this study.

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    المصدر: Virology Journal
    Virology Journal, Vol 15, Iss 1, Pp 1-10 (2018)

    الوصف: Background Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus within the family Togaviridae, which has attracted global attention due to its recent re-emergence. In one of our previous studies, we successfully isolated two CHIKV virus strains, SZ1050 and SZ1239, from the serum samples of two imported patients in 2010 and 2012, respectively. However, the differences in their genome characters and cell tropisms remain undefined. Methods We extracted the RNA of two CHIKV isolates and performed PCR to determine the sequence of the whole viral genomes. The genotypes were classified by phylogenetic analysis using the Mega 6.0 software. Furthermore, the cell tropisms of the two CHIKV isolates were evaluated in 13 cell lines. Results The lengths of the whole genomes for SZ1050 and SZ1239 were 11,844 nt and 12,000 nt, respectively. Phylogenetic analysis indicated that SZ1050 belonged to the Indian Ocean lineage (IOL), while SZ1239 was of the Asian lineage. Comparing to the prototype strain S27, a gap of 7 aa in the nsP3 gene and missing of one repeated sequence element (RSE) in the 3’ UTR were observed in SZ1239. The E1-A226V mutation was not detected in both strains. SZ1050 and SZ1239 could infect most of the evaluated mammalian epithelial cells. The K562 cells were permissive for both SZ1050 and SZ1239 while the U937 cells were refractory to both viruses. For Aedes cell lines C6/36 and Aag-2, both SZ1050 and SZ1239 were able to infect and replicate efficiently. Conclusions Compared to the prototype S27 virus, some deletions and mutations were found in the genomes of SZ1050 and SZ1239. Both viruses were susceptible to most evaluated epithelia or fibroblast cells and Aedes cell lines including C6/36 and Aag-2 in spite of marginal difference. Electronic supplementary material The online version of this article (10.1186/s12985-018-1024-5) contains supplementary material, which is available to authorized users.