Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used ...to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.
Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of ...neurotoxicity in Alzheimer's disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD.
Fungi represent a significant proportion of the gut microbiota. Aberrant immune responses to fungi are frequently observed in inflammatory bowel diseases (IBD) and colorectal cancer (CRC), and ...mutations in the fungal-sensing pathways are associated with the pathogenesis of IBD. Fungal recognition receptors trigger downstream signaling via the common adaptor protein CARD9 and the kinase SYK. Here we found that commensal gut fungi promoted inflammasome activation during AOM-DSS-induced colitis. Myeloid cell-specific deletion of Card9 or Syk reduced inflammasome activation and interleukin (IL)-18 maturation and increased susceptibility to colitis and CRC. IL-18 promoted epithelial barrier restitution and interferon-γ production by intestinal CD8+ T cells. Supplementation of IL-18 or transfer of wild-type myeloid cells reduced tumor burden in AOM-DSS-treated Card9−/− and Sykfl/flLysMCre/+ mice, whereas treatment with anti-fungal agents exacerbated colitis and CRC. CARD9 deletion changes the gut microbial landscape, suggesting that SYK-CARD9 signaling maintains a microbial ecology that promotes inflammasome activation and thereby restrains colitis and colon tumorigenesis.
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•Commensal gut fungi contribute to inflammasome activation during experimental colitis•Microbial landscape is altered in Card9−/− mice•Defective inflammasome activation, IL-18 maturation in myeloid cells lacking CARD9 or SYK•Metronidazole treatment protects Card9−/− and SykLysM mice from colon tumorigenesis
Fungi represent a significant proportion of the gut microbiota, but how anti-fungal immunity contributes to tumor-promoting inflammatory responses is unclear. Malik et al. find that recognition of commensal gut fungi, sensed via the Card9-Syk signaling axis, is protective in the context of inflammation-associated cancer. IL-18 maturation downstream of inflammasome activation promotes epithelial barrier restitution and IFN-γ production by intestinal CD8+ T cells.
Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial ...lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A "high" TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a "high" score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A "high" 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11-0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.
Negative pressure wound therapy (NPWT) decreases postoperative complications of various surgeries. However, the use of NPWT for oncological surgical wounds remains controversial. To evaluate the ...association of NPWT with oncologic recurrence in surgical wounds without residual malignancy, we analysed studies that compared NPWT with conventional non‐pressure dressings for cancer surgical wounds without residual tumour by August 12, 2020. We compared tumour recurrence rates and postoperative complications between the two procedures. The six studies included 118 patients who received NPWT, and 149 patients who received conventional non‐pressure wound care. The overall quality of the included studies was high based on the Newcastle–Ottawa scale score of 7.5. Tumour recurrence after NPWT was not significantly different compared with conventional non‐negative pressure wound care (9.3% versus 11.4%, P = 0.40). There was no significant heterogeneity between the studies (I2 = 3%). Although NTWT was associated with a lower complication rate compared with the control group, the result was non‐significant (P = 0.15). Application of NPWT in oncologic resection wounds without residual malignancy revealed no difference in local recurrence and may reduce the risk of postoperative complications compared with conventional non‐negative pressure dressings. NPWT can be considered an alternative method for reconstruction in challenging cases.
Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin‐binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical ...heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available D‐glucosamine, diacetone α‐D‐glucose, and penta‐O‐acetyl‐D‐glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one‐pot reactions that considerably reduce the synthetic effort and improve the yield.
Working against the clot: The synthetic anticoagulant fondaparinux, a pentasaccharide based on the antithrombin‐binding domain of heparin, was prepared in a concise and efficient manner in the shortest route reported to date. The application of one‐pot strategies, the use of common intermediates, and the efficient preparation of monosaccharide building blocks from commercial sources are key features of this approach.
This paper aims to develop a multisensor data fusion technology-based smart home system by integrating wearable intelligent technology, artificial intelligence, and sensor fusion technology. We have ...developed the following three systems to create an intelligent smart home environment: (1) a wearable motion sensing device to be placed on residents' wrists and its corresponding 3D gesture recognition algorithm to implement a convenient automated household appliance control system; (2) a wearable motion sensing device mounted on a resident's feet and its indoor positioning algorithm to realize an effective indoor pedestrian navigation system for smart energy management; (3) a multisensor circuit module and an intelligent fire detection and alarm algorithm to realize a home safety and fire detection system. In addition, an intelligent monitoring interface is developed to provide in real-time information about the smart home system, such as environmental temperatures, CO concentrations, communicative environmental alarms, household appliance status, human motion signals, and the results of gesture recognition and indoor positioning. Furthermore, an experimental testbed for validating the effectiveness and feasibility of the smart home system was built and verified experimentally. The results showed that the 3D gesture recognition algorithm could achieve recognition rates for automated household appliance control of 92.0%, 94.8%, 95.3%, and 87.7% by the 2-fold cross-validation, 5-fold cross-validation, 10-fold cross-validation, and leave-one-subject-out cross-validation strategies. For indoor positioning and smart energy management, the distance accuracy and positioning accuracy were around 0.22% and 3.36% of the total traveled distance in the indoor environment. For home safety and fire detection, the classification rate achieved 98.81% accuracy for determining the conditions of the indoor living environment.
Although certain inhibitors of histone deacetylases have been shown to induce cytotoxicity alone or in combination with chemotherapeutic agents in cancer cells, the molecular mechanism is not clear. ...The goal of the present study was to determine whether the antiseizure drug valproic acid (2‐propylpentanoic acid; VPA), which is also able to inhibit histone deacetylase, exhibits synergistic cytotoxicity with cisplatin, and the possible pathways for this. Our results clearly show that VPA not only exhibits synergistic cytotoxicity with cisplatin in all of the ovarian carcinoma cells tested, but also can resensitize the cells that have acquired resistance to cisplatin. Consistent with the increased cytotoxicity, cotreatment with VPA was shown to upregulate the cisplatin‐mediated DNA damage revealed by phosphorylation of ataxia telangiectasia mutation and histone H2AX. Reactive oxygen species accumulation and tumor suppressor phosphatase and tensin homolog (PTEN) overexpression, which could contribute to the enhanced cytotoxicity, were also observed to be upregulated by VPA. Because PTEN knockdown by small interference RNA or antioxidant treatment can reduce cisplatin‐mediated cytotoxicity, it is suggested that upregulation of PTEN and reactive oxygen species by VPA contributes to the enhancement of cisplatin‐mediated cytotoxicity. These results with resensitization of cisplatin‐resistant cells particularly may provide benefits in the treatment of ovarian cancer patients. (Cancer Sci 2008; 99: 1218–1226)
A White Random Laser Chang, Shu-Wei; Liao, Wei-Cheng; Liao, Yu-Ming ...
Scientific reports,
02/2018, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Random laser with intrinsically uncomplicated fabrication processes, high spectral radiance, angle-free emission, and conformal onto freeform surfaces is in principle ideal for a variety of ...applications, ranging from lighting to identification systems. In this work, a white random laser (White-RL) with high-purity and high-stability is designed, fabricated, and demonstrated via the cost-effective materials (e.g., organic laser dyes) and simple methods (e.g., all-solution process and self-assembled structures). Notably, the wavelength, linewidth, and intensity of White-RL are nearly isotropic, nevertheless hard to be achieved in any conventional laser systems. Dynamically fine-tuning colour over a broad visible range is also feasible by on-chip integration of three free-standing monochromatic laser films with selective pumping scheme and appropriate colour balance. With these schematics, White-RL shows great potential and high application values in high-brightness illumination, full-field imaging, full-colour displays, visible-colour communications, and medical biosensing.
p21, an inhibitor of cyclin-dependent kinase, functions as an oncogene or tumor suppressor depending on the context of a variety of extracellular and intracellular signals. The expression of p21 ...could be regulated at the transcriptional and/or post-translational levels. The p21 gene is well-known to be regulated in both p53-dependent and -independent manners. However, the detailed regulatory mechanisms of p21 messenger RNA and protein expression via statins remain unknown, and the possible application of statins as anticancer reagents remains to be controversial. Our data showed that the statins-fluvastatin and lovastatin-induced p21 expression as general histone deacetylase inhibitors in a p53-independent manner, which is mediated through various pathways, such as apoptosis, autophagy, cell cycle progression, and DNA damage, to be involved in the function of p21 in HeLa cells. The curative effect repositioning of digoxin, a cardiovascular medication, was combined with fluvastatin and lovastatin, and the results further implied that p21 induction is involved in a p53-dependent and p53-independent manner. Digoxin modified the effects of statins on ATF3, p21, p53, and cyclin D1 expression, while fluvastatin boosted its DNA damage effect and lovastatin impeded its DNA damage effect. Fluvastatin and lovastatin combined with digoxin further support the localization specificity of their interactivity with our subcellular localization data. This study will not only clarify the regulatory mechanisms of p21 induction by statins but will also shed light on the repurposing of widely cardiovascular medications for the treatment of cervical cancer.
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