When the production of reactive oxygen species (ROS) is overloaded surpassing the capacity of the reductive rheostat, mammalian cells undergo a series of oxidative damage termed oxidative stress ...(OS). This phenomenon is ubiquitously detected in many human pathological conditions. Wound healing program implicates continuous neovascularization, cell proliferation, and wound remodeling. Increasing evidence indicates that reactive oxygen species (ROS) have profound impacts on the wound healing process through regulating a series of the physiological and pathological program including inflammatory response, cell proliferation, angiogenesis, granulation as well as extracellular matrix formation. In most pathological wound healing processes, excessive ROS exerts a negative role on the wound healing process. Interestingly, the moderate increase of ROS levels is beneficial in killing bacteria at the wound site, which creates a sterile niche for revascularization. In this review, we discussed the physiological rhythms of wound healing and the role of ROS in this progress, aim to explore the potential manipulation of OS as a promising therapeutic avenue.
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•ROS regulates the wound healing process by affecting inflammation, cell proliferation, angiogenesis, granulation formation, and extracellular matrix formation.•Excess ROS negatively affects the healing process in most pathological wounds.•Moderate elevation of ROS facilitates the re-establishment of a sterile ecological niche at the wound site.•Targeting oxidative stress therapy prompts clinical wound healing treatment.
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The exploration of carbon dots (CDs) with high quantum yield, facile synthesis path and satisfying output for their multiple applications remains a challenge. Thus, a silicon-doped ...orange-emitting carbon dots (O-CDs) is synthesized via a one-step hydrothermal method o-phenylenediamine and ethyl orthosilicate as raw materials. The O-CDs exhibits a bright and non-excitation-dependent emission peaking at 580 nm, and the corresponding quantum yield could be greatly boosted from 39.2 % to 64.1 % by silicon doping. The obtained O-CDs possess good biocompatibility and promising luminescence stability with varying solvents, ionic concentrations and temperatures. Its bio-imaging ability is performed by incubating zebrafish embryos with O-CDs aqueous solution, and clear in-vivo fluorescent images are obtained. Furthermore, due to its high-efficient and specific pH-sensitive emission with excellent dispersibility, the O-CDs can be used as a fluorescent ink for dual-model data encry/decryption in both hand-writing and stamp printing. Therefore, the as-prepared O-CDs show the potential as promising candidate for biomedical diagnosis, data encryption, and anti-counterfeiting.
Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the ...premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression.
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•V dopant and its induced O vacancies tune the electron structure of Ni/V-MoO2/NF.•Regular nanorod morphology obtained by V doping enlarge the ECSA of Ni/V-MoO2/NF.•Highly efficient ...HER performance with an overpotential of 13.1 mV at 10 mA cm−2.
The development of efficient and non-precious electrocatalysts to produce hydrogen by electrolysis of water is critical to meeting the world's growing energy demand and overcoming the challenges of global warming. In this work, we have successfully synthesized a new heterostructured material in form of Ni nanoparticles modified V doped MoO2 supported by Ni foam (Ni/V-MoO2/NF) and applied it as an excellent HER electrocatalyst under alkaline conditions. The introduction of V can tune the morphology of material to be further regular, which is conducive to the exposure of active sites and mass transport. Meanwhile, the V doping and its resulting abundant oxygen vacancies can modulate the electronic structure and boost the conductivity, which benefits the improvement of electrocatalytic HER performance. Thus, compared with the non-V-doped contrast sample, the as-prepared Ni/V-MoO2/ NF has shown excellent and stable HER activity with a low overpotential of 13.1 mV at the current density of 10 mA cm−2 and Tafel slope of 34.8 mV dec−1. This work may provide positive suggestion for the design of high-performanced V-doped heterostructured electrocatalysts for various sustainable energy applications.
Cancer stem cells (CSC) play critical roles in cancer initiation, progression, and therapeutic refractoriness. Although many studies have focused on the genes and pathways involved in stemness, ...characterization of the factors in the tumor microenvironment that regulate CSCs is lacking. In this study, we investigated the effects of stromal fibroblasts on breast cancer stem cells. We found that compared with normal fibroblasts, primary cancer-associated fibroblasts (CAF) and fibroblasts activated by cocultured breast cancer cells produce higher levels of chemokine (C-C motif) ligand 2 (CCL2), which stimulates the stem cell-specific, sphere-forming phenotype in breast cancer cells and CSC self-renewal. Increased CCL2 expression in activated fibroblasts required STAT3 activation by diverse breast cancer-secreted cytokines, and in turn, induced NOTCH1 expression and the CSC features in breast cancer cells, constituting a cancer-stroma-cancer signaling circuit. In a xenograft model of paired fibroblasts and breast cancer tumor cells, loss of CCL2 significantly inhibited tumorigenesis and NOTCH1 expression. In addition, upregulation of both NOTCH1 and CCL2 was associated with poor differentiation in primary breast cancers, further supporting the observation that NOTCH1 is regulated by CCL2. Our findings therefore suggest that CCL2 represents a potential therapeutic target that can block the cancer-host communication that prompts CSC-mediated disease progression.
Gut microbiota diversity is a result of co-evolution between microorganisms and their hosts. However, there are few studies on the evolution of the gut microbiota of wild boars and domestic pigs. ...Therefore, this study aimed to analyze the composition and function of the gut microbiota of wild boars and domestic pigs using 16S rRNA gene V3-V4 region sequencing, 16S rRNA gene full-length sequencing, and metagenomic sequencing. This study showed that after a long evolution, as compared to wild boars, the domestic pigs exhibited significantly increased relative abundances of Lactobacillus, Lactobacillus reuteri, Lactobacillus johnsonii, Lactobacillus sp.DJF_WC5, and Lactobacillus; s_uncultured bacterium, while the relative abundances of Bifidobacterium and Methanococcaceae decreased significantly. In addition, the relative abundances of “carbohydrate metabolism”, “starch and sucrose metabolism”, “valine, leucine, and isoleucine biosynthesis”, “lysine biosynthesis”, and starch-degrading CAZymes were significantly increased in the domestic pigs, while the relative abundances of “environmental adaptation”, “immune system”, “fatty acid degradation and synthesis”, and cellulose-hemicellulose-degrading CAZymes were significantly increased in the wild boars. Finally, the diversity of ARGs and the “antimicrobial resistance genes” in domestic pigs also increased significantly. This study illustrates that the gut microbiota composition and function of wild boars and domestic pigs changed during the long evolution process. These findings provide a basic research theory for the evolution of gut microbiota and the treatment of health and disease.
Background Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and ...a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. Methods Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. Results GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/beta-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/beta-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. Conclusions Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target. Keywords: HER2+ , Breast cancer, GRB7, TCF12, EMT
MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been ...reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.
The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.
More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.
Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
The lung is one of the most frequent distant metastasis sites in colorectal cancer (CRC) patients; however, lung metastasis risk and prognostic factors have not been comprehensively elucidated. This ...study aimed to identify the homogeneous and heterogeneous lung metastasis risk and prognostic factors in CRC patients using the Surveillance, Epidemiology, and End Results (SEER) database.
CRC patients registered in the SEER database between 2010 and 2016 were included to analyse risk factors for developing lung metastasis by using univariable and multivariable logistic regression. Patients diagnosed between 2010 and 2015 were selected to investigate prognostic factors for lung metastasis by conducting Cox regression. Kaplan-Meier analysis was used to estimate overall survival outcomes.
A total of 10,598 (5.2%) patients with synchronous lung metastasis were diagnosed among 203,138 patients with CRC. The median survival time of patients with lung metastasis was 10.0 months (95% CI 9.6-10.5 months). Older age, unmarried status, uninsured status, poor histological differentiation, more lymphatic metastasis, CEA positivity, liver metastasis, bone metastasis and brain metastasis were lung metastasis risk and prognostic factors. Black patients and those with left colon, rectum, and stage T4 disease were more likely to develop lung metastasis, while patients with right colon cancer and no surgical treatment of the primary tumour had poor survival outcomes.
The incidence of lung metastasis in CRC patients was 5.2%. CRC patients with lung metastasis exhibited homogeneous and heterogeneous risk and prognostic factors. These results are helpful for clinical evaluation and individual treatment decision making.
Dual-emitting alkaline silicate phosphors Na2Mg2Si6O15: Eu2+, Mn2+ have been synthesized to realize blue and red emissions to boost photosynthesis process. At UV excitation, Na2Mg2Si6O15: Eu2+, Mn2+ ...phosphors exhibit efficient blue and red emissions due to Eu2+ 4f-5d transition and Mn2+ 3d-3d transition, which matches well with the absorption of plant chlorophylls, and also could be excited by near ultraviolet LED chip. The emitting color could be readily tuned from blue through pink to red due to effective Eu2+-Mn2+ energy transfer by changing Eu2+/Mn2+ ratio. And the corresponding energy transfer mechanism is found to be dipole-dipole interaction. The thermal stability of Na2Mg2Si6O15: Eu2+, Mn2+ is significantly higher than that of most reported Eu2+, Mn2+ co-activated dual-emitting phosphors, due to thermally activated defect-Eu2+-Mn2+ energy transfer process. Thus, it indicates that Na2Mg2Si6O15: Eu2+, Mn2+ is of great potential as converted phosphors for plant growth application.
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•Novel Na2Mg2Si6O15: Eu2+, Mn2+ phosphors with controllable emission was synthesized.•Phosphor shows efficient blue (400–500 nm) and red (600–700 nm) double-band light under NUV excitation.•The energy transfer efficiency and the energy transfer mechanism were investigated.•Efficient and stable blue-red emission in Na2Mg2Si6O15: Eu2+, Mn2+ promote application in plant growth LED.
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