The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal ...breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown. In this study, we demonstrate that in the estrogen receptor (ERα)-positive LBC cells Twist1 silences Foxa1 expression, which has an essential role in relieving Foxa1-arrested migration, invasion and metastasis of breast cancer cells. Mechanistically, Twist1 binds to Foxa1 proximal promoter and recruits the NuRD transcriptional repressor complex to de-acetylate H3K9 and repress RNA polymerase II recruitment. Twist1 also silences Foxa1 promoter by inhibiting AP-1 recruitment. Twist1 expression in MCF7 cells silenced Foxa1 expression, which was concurrent with the induction of EMT, migration, invasion and metastasis of these cells. Importantly, restored Foxa1 expression in these cells largely inhibited Twist1-promoted migration, invasion and metastasis. Restored Foxa1 expression did not change the Twist1-induced mesenchymal cellular morphology and the expression of Twist1-regulated E-cadherin, β-catenin, vimentin and Slug, but it partially rescued Twist1-silenced ERα and cytokeratin 8 expression and reduced Twist1-induced integrin α5, integrin β1 and MMP9 expression. In a xenografted mouse model, restored Foxa1 also increased Twist1-repressed LBC markers and decreased Twist1-induced BLBC markers. Furthermore, Twist1 expression is negatively correlated with Foxa1 in the human breast tumors. The tumors with high Twist1 and low Foxa1 expressions are associated with poor distant metastasis-free survival. These results demonstrate that Twist1's silencing effect on Foxa1 expression is largely responsible for Twist1-induced migration, invasion and metastasis, but less responsible for Twist1-induced mesenchymal morphogenesis and expression of certain EMT markers.
To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors.
H. pylori strains were collected from ...patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method.
H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China.
The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.
Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) ...rats.
Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno-associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA).
The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous Vegf expression level decreased over time in RCS rats. The treatment of AAV2-VEGF showed comparable therapeutic effects as hADSCs but siRNA knockdown of VEGF in hADSCs essentially abolished the therapeutic effects.
Subretinal transplantation of hADSCs in RCS rats effectively delayed the retinal degeneration, enhanced the retinal cell survival and improved the visual function. Mechanistically this was mainly due to hADSC dependent anti-apoptotic and neuroprotective effects through its secretion of growth and neurotrophic factors including VEGF. Clinical application of hADSCs merits further investigation.
Summary
Clonostachys rosea is a promising saprophytic filamentous fungus that belongs to phylum Ascomycota. Clonostachys rosea is widespread around the world and exists in many kinds of habitats, ...with the highest frequency in soil. As an excellent mycoparasite, C. rosea exhibits strong biological control ability against numerous fungal plant pathogens, nematodes and insects. These behaviours are based on the activation of multiple mechanisms such as secreted cell‐wall‐degrading enzymes, production of antifungal secondary metabolites and induction of plant defence systems. Besides having significant biocontrol activity, C. rosea also functions in the biodegradation of plastic waste, biotransformation of bioactive compounds, as a bioenergy sources and in fermentation. This mini review summarizes information about the biology and various applications of C. rosea and expands on its possible uses.
Gastric cancer (GC) is among the most common malignancy in the world with poor prognosis and limited treatment options. It has been established that gastric carcinogenesis is caused by a complex ...interaction between host and environmental factors. Copy number variation (CNV) refers to a form of genomic structural variation that results in abnormal gene copy numbers, including gene amplification, gain, loss and deletion. DNA CNV is an important influential factor for the expression of both protein-coding and non-coding genes, affecting the activity of various signaling pathways. CNV arises as a result of preferential selection that favors cancer development, and thus, targeting the amplified 'driver genes' in GC may provide novel opportunities for personalized therapy. The detection of CNVs in chromosomal or mitochondrial DNA from tissue or blood samples may assist the diagnosis, prognosis and targeted therapy of GC. In this review, we discuss the recent CNV discoveries that shed light on the molecular pathogenesis of GC, with a specific emphasis on CNVs that display diagnostic, prognostic or therapeutic significances in GC.
Corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome by many clinicians because of their perceived anti-inflammatory effects. However, for patients with ...severe viral pneumonia, the corticosteroid treatment is highly controversial.
The purpose of this review is to systematically evaluate the effect and potential mechanism of corticosteroid administration in pandemic viral pneumonia.
We comprehensively searched all manuscripts on corticosteroid therapy for influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and SARS coronavirus 2 (SARS-CoV-2) viral pneumonia from the PubMed, EMBASE, Web of Science and Cochrane Library databases.
We systematically summarized the effects of corticosteroid therapy for pandemic viral pneumonia and the potential mechanism of action for corticosteroids in coronavirus disease 2019 (COVID-19).
Observational studies showed that corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delayed virus clearance for SARS-CoV and MERS-CoV. Limited data on corticosteroid therapy for COVID-19 were reported. Corticosteroids were used in about a fifth of patients (670/2995, 22.4%). Although clinical observational studies reported the improvement in symptoms and oxygenation for individuals with severe COVID-19 who received corticosteroid therapy, case fatality rate in the corticosteroid group was significantly higher than that in the non-corticosteroid group (69/443, 15.6% versus 56/1310, 4.3%). Compared individuals with non-severe disease, those with severe disease were more likely to receive corticosteroid therapy (201/382, 52.6% versus 201/1310, 15.3%). Although there is no evidence that corticosteroid therapy reduces mortality in people with COVID-19, some improvements in clinical symptoms and oxygenation were reported in some clinical observational studies. Excessive inflammatory response and lymphopenia might be critical factors associated with severity of and mortality from COVID-19. Sufficiently powered randomized controlled trials with rigorous inclusion/exclusion criteria and standardized dose and duration of corticosteroids are needed to verify the effectiveness and safety of corticosteroid therapy.
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