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1.
Bioresour Technol ; 319: 124056, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-33038655

RESUMO

The related microbial metabolomics on biological recovery of manganese (Mn) from Electrolytic Manganese Slag (EMS) has not been studied. This study aimed at open the door to the metabolic characteristics of microorganisms in leaching Mn from EMS by using waste molasses (WM) as carbon source. Results show Microbacterium trichothecenolyticum Y1 (Y1) could effectively leach Mn from EMS in combination with using waste molasses as carbon and energy sources. For the first time, Y1 was identified to be capable of generating and then metabolizing several organic acids or other organic matter (e.g., fumaric acid, succinic acid, malic acid, glyoxylic acid, 3-hydroxybutyric acid, glutaric acid, L(+)-tartaric acid, citric acid, tetrahydrofolic acid, and L-methionine). The production of organic acids by Y1 bacteria was promoted by EMS with the carbon source. This study demonstrated for the first time that metabolic characteristics and carbon source metabolic pathways of Y1 in bioleaching of Mn from EMS.

2.
Nat Prod Res ; : 1-8, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054376

RESUMO

Two new cycloartane glycosides, cycloatriosides A and B (1-2), and a new oleanolic acid glycoside, thaliatrioside A (3), along with 7 known triterpenoids (4-10) were isolated from Thalictrum atriplex. The structures of the new compounds were established as 3-O-ß-D-galactopyranosyl (20S, 24 R)-3ß,16ß,25,29-tetrahydroxy-20,24-epoxycycloartane-29-O-ß-D-glucopyranoside (1), 3-O-ß-D-glucopyranosyl-(1→2)-α-arabinopyranosyl-3ß,22ξ,30-trihydroxycycloart-24-en-21-oic acid α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranoside (2) and 3-O-[α-L-rhamnopyranosyl-(1→3)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl]-oleanolic acid 28-O-ß-D-glucopyranosyl ester (3) on the basis of extensive NMR and HR-ESI-MS analyses, along with acid hydrolysis. Their cytotoxic activities against human lung cancer cells A549 and human breast cancer cells MDA-MB-231 were evaluated using MTT method. Compound 9 showed cytotoxicity against MDA-MB-231 cell line with the IC50 value of 72.53 ± 1.08 µM.

3.
Biomed Res Int ; 2020: 7658230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015179

RESUMO

Gastric cancer (GC) is one of the most common malignancies of the digestive system with few genetic markers for its early detection and prevention. In this study, differentially expressed genes (DEGs) were analyzed using GEO2R from GSE54129 and GSE13911 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING, and Cytoscape. Finally, we performed survival analysis of key genes through the Kaplan-Meier plotter. A total of 1034 DEGs were identified in GC. GO and KEGG results showed that DEGs mainly enriched in plasma membrane, cell adhesion, and PI3K-Akt signaling pathway. Subsequently, the PPI network with 44 nodes and 333 edges was constructed, and 18 candidate genes in the network were focused on by centrality analysis and module analysis. Furthermore, data showed that high expressions of fibronectin 1(FN1), the tissue inhibitor of metalloproteinases 1 (TIMP1), secreted phosphoprotein 1 (SPP1), apolipoprotein E (APOE), and versican (VCAN) were related to poor overall survivals in GC patients. In summary, this study suggests that FN1, TIMP1, SPP1, APOE, and VCAN may act as the key genes in GC.

5.
J Am Chem Soc ; 142(42): 17933-17937, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33043669

RESUMO

The coupling of material systems at different length scales enables new ways to take advantage of the unique properties of nano-/macroscale materials. Here, the self-organization of assembled metallacages generated ultralong nanowires, followed by the formation of nanowire-based soft films with diameters up to 6.5 cm. In contrast to previous reports that mainly focused on the preparation of metallacage assemblies with dimensions on the nano-/micrometer scale, the preparation of centimeter assemblies can serve as the bridge between nanostructures and the macroscopic world.

6.
Parasit Vectors ; 13(1): 514, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054862

RESUMO

BACKGROUND: Culex pipiens pallens poses a serious threat to human health because of its widespread distribution, high carrier capacity for several arboviruses, frequent human-biting, and growth in urban environments. Pyrethroid insecticides have been mainly used to control adult Cx. pipiens pallens during outbreaks of mosquito-borne diseases. Unfortunately, mosquitoes have developed resistance, rendering the insecticides ineffective. Cuticular resistance is the primary mechanism of pyrethroid resistance. Previously, we revealed that cuticular protein of low complexity CPLCG5 is a major cuticular protein associated with deltamethrin resistance in Cx. pipiens pallens, which is enriched in the cuticle of mosquitoes' legs and participates in pyrethroid resistance by forming a rigid matrix. However, the regulatory mechanisms of its transcription remain unknown. RESULTS: First, qRT-PCR analysis revealed that the expression of FTZ-F1 (encoding Fushi tarazu-Factor 1) was ~ 1.8-fold higher in the deltamethrin-resistant (DR) than deltamethrin-susceptible (DS) strains at 24 h post-eclosion (PE) and ~ 2.2-fold higher in the DR strain than in the DS strain at 48 h PE. CPLCG5 and FTZ-F1 were co-expressed in the legs, indicating that they might play an essential role in the legs. Dual luciferase reporter assays and EMSA (electrophoretic mobility shift experiments) revealed that FTZ-F1 regulates the transcription of CPLCG5 by binding to the FTZ-F1 response element (- 870/- 864). Lastly, knockdown of FTZ-F1 not only affected CPLCG5 expression but also altered the cuticle thickness and structure of the legs, increasing the susceptibility of the mosquitoes to deltamethrin in vivo. CONCLUSIONS: The results revealed that FTZ-F1 regulates the expression of CPLCG5 by binding to the CPLCG5 promoter region, altering cuticle thickness and structure, and increasing the susceptibility of mosquitoes to deltamethrin in vivo. This study revealed part of the mechanism of cuticular resistance, providing a deeper understanding of insecticide resistance.

7.
Medicine (Baltimore) ; 99(42): e22804, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080755

RESUMO

BACKGROUND: Octamer binding transcription factor 4 (Oct4) is critically important in the development and progression of cancer, and is considered a potential biomarker for tumor prognosis. However, the prognostic value of Oct4 in patients with solid tumors remains elusive. Herein, we conducted a meta-analysis to assess the prognostic value of Oct4 in patients with solid tumors. METHODS: We conducted a literature search on PubMed, Embase, and Web of Science databases to retrieve comprehensive and eligible studies published until December 2019. The study was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS)/progress-free survival (PFS) were used to evaluate the prognostic value of Oct4 in patients with solid tumors via either random or fixed-effects models. RESULTS: In total, 36 studies with 5198 patients were included in the meta-analysis. Notably, elevated Oct4 expression was associated with worse OS (pooled HR: 2.02, 95% CI: 1.55-2.62, P < .001) and DFS/RFS/PFS (pooled HR: 2.34, 95% CI: 1.88-2.92, P < .001). CONCLUSION: This work demonstrated that patients with solid tumors show high expression of Oct4 which is linked to worse prognosis in patients with solid tumors including hepatocellular carcinoma (OS, DFS/RFS/PFS), esophageal squamous cell carcinoma (OS), gastric cancer (OS), cervical cancer (OS, DFS/RFS/PFS), and colorectal cancer (OS, DFS/RFS/PFS), this implicated Oct4 as a potential biomarker to predict the prognosis of tumors.

8.
DNA Cell Biol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33085515

RESUMO

N6-Methyladenosine (m6A) refers to the methylation modification occurring at the nitrogen-6 position of adenosine. Many human physiological processes such as modulation of spermatogenesis are caused by m6A RNA modifications. However, the relationship between m6A RNA methylation regulators and kidney renal clear cell carcinoma (KIRC) remains rarely investigated. This work aimed to explore the influence of m6A RNA methylation regulators in KIRC. We examined abnormally expressed m6A RNA methylation regulators among different clinicopathological features of KIRC. We recognized three subgroups (KIRC1, KIRC2, and KIRC3) with significant differences in overall survival through consensus clustering of m6A RNA methylation regulators. Surprisingly, KIRC2 displayed elevated immune activity, but high proportions of immune-inhibitory cells (Tregs and myeloid-derived suppressor cell) based on single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT analysis. Moreover, the KIRC2 subgroup had the lowest tumor mutation burden levels and the highest expression levels of 80% (12/15) of co-inhibitory molecules. Next, correlation analysis indicated that RBM15B expression was negatively correlated with multiple immune signatures, which was verified by ssGSEA and CIBERSORT analyses. Multiple immune-related and cancer-related pathways were enriched in the group with high RBM15B expression. Furthermore, a four-m6A RNA methylation regulator-based risk signature was constructed based on an ArrayExpress (E-MTAB-3267) dataset and confirmed in the The Cancer Genome Atlas (TCGA) testing cohort. In conclusion, our study successfully classified TCGA samples into three subgroups with different immune signatures, and suggested that the worse prognosis of KIRC2 is probably mediated by immune evasion. These findings will facilitate personalized immunotherapy in patients with KIRC. In addition, the risk score system was revealed as an independent prognostic marker that can predict survival in KIRC patients.

9.
J Am Chem Soc ; 142(41): 17340-17345, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33016703

RESUMO

Chiral metal-organic complexes hold great promise as new functional materials that exhibit unique stereochemical and optical properties. Here, we report the formation of optically pure pillar[5]arene-based platinum chiral metallacycles. By coordination with 60° and 90° Pt(II) acceptors, planar chiral platinum triangles were self-assembled efficiently and characterized by multiple spectroscopic techniques. Optical studies indicated that these metallacycles had chiral properties: pS enantiomers showed a negative Cotton effect, and pR enantiomers exhibited a positive Cotton effect. In addition, these metallacycles also exhibited circularly polarized luminescence.

10.
Carbohydr Polym ; 250: 116892, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049829

RESUMO

The development of science and technology brings forward higher and higher requirements for the properties of materials. Nanocellulose, with many fascinating properties including large specific surface area, template structure, good modifiability, biodegradability, and etc., has wide application prospects. The surface properties and interfacial compatibility of nanocellulose are the keys to its application performance. This review mainly summarizes the colloid and surface chemistry of nanocellulose and their effects on the dispersity in various solvents and polymer matrices, and especially focuses on the impact of surface hydrophilicity/hydrophobicity, charge repulsion and steric hindrance on the dispersion properties. Various surface modification methods to improve the dispersion performance of nanocellulose, such as oxidation, etherification, esterification, amidation, graft polymerization, and etc., are summarized. In addition, the application of nanocellulose as the dispersant for Pickering emulsion, carbon nanomaterials, metal nanoparticles and etc. is also introduced. The development trend and potential application of nanocellulose are finally prospected.

11.
Small ; 16(43): e2002804, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33006250

RESUMO

The fibrillization and deposition of ß-amyloid protein (Aß) are recognized to be the pathological hallmarks of Alzheimer's disease (AD), which signify the need for the effective detection and inhibition of Aß accumulation. Development of multifunctional agents that can inhibit Aß aggregation, rapidly disaggregate fibrils, and image aggregates is one of the effective strategies to treat and diagnose AD. Herein, the multifunctionality of nitrogen-doped carbonized polymer dots (CPDs) targeting Aß aggregation is reported. CPDs inhibit the fibrillization of Aß monomers and rapidly disintegrate Aß fibrils by electrostatic interactions, hydrogen-bonding and hydrophobic interactions with Aß in a time scale of seconds to minutes. Moreover, the interactions make CPDs label Aß fibrils and emit enhanced red fluorescence by the binding, so CPDs can be used for in vivo imaging of the amyloids in transgenic Caenorhabditis elegans CL2006 as an AD model. Importantly, CPDs are demonstrated to scavenge the in vivo amyloid plaques and to promote the lifespan extension of CL2006 strain by alleviating the Aß-triggered toxicity. Taken together, the multifunctional CPDs show an exciting prospect for further investigations in Aß-targeted AD treatment and diagnosis, and this study provides new insight into the development of carbon materials in AD theranostics.

12.
Echocardiography ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070402

RESUMO

Shone's syndrome is a rare congenital heart disease that includes 4 cardiovascular anomalies: supravalvular mitral ring, parachute mitral valve, subaortic stenosis, and coarctation of the aorta. Early diagnosis and treatment result in better outcomes. Echocardiography plays an important role in the diagnosis and is the optimal examination for detecting this disease. Pressure gradients are often unreliable and inaccurate; thus, careful anatomical observation of the left ventricular inflow and outflow tracts, particularly the mitral valve, is vital for accurate diagnosis and planning appropriate management. Herein, we describe 9 cases of Shone's syndrome, diagnosed with echocardiography and treated surgically.

13.
Int Arch Allergy Immunol ; : 1-12, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080611

RESUMO

As an ancient Gram-negative bacterium, Helicobacter pylori has settled in human stomach. Eradicating H. pylori increases the morbidities of asthma and other allergic diseases. Therefore, H. pylori might play a protective role against asthma. The "disappearing microbiota" hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in our early life, contributing to the development of some diseases. And the Hygiene Hypothesis links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent immune-mediated diseases. H. pylori can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. H. pylori can also target dendritic cells to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. The remote regulation of lung immune function by H. pylori is consistent with the gut-lung axis theory. Perhaps, H. pylori also protects against asthma by altering levels of stomach hormones, affecting the autonomic nervous system and lowering the expression of heat shock protein 70. Therapeutic products from H. pylori may be used to prevent and treat asthma. This paper reviews the possible protective influence of H. pylori on allergic asthma and the possible application of H. pylori in treating asthma.

15.
Chin Med J (Engl) ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021767

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms. METHODS: Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance. RESULTS: BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 µg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB). CONCLUSIONS: BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

16.
Ren Fail ; 42(1): 958-965, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32924720

RESUMO

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the mutation of the GLA gene, encoding the α-galactosidase, which is responsible for the catabolism of neutral glycosphingolipids. Microalbuminuria or low-grade proteinuria, and continuously progressive renal failure are common manifestations in FD males. However, sudden onset of nephrotic syndrome in FD, is rarely reported. CASE REPORT: A 32-year-old Chinese man was admitted to our hospital because of sudden onset of generalized edema due to nephrotic syndrome. He denied hypohidrosis, nocturia, and any history of episodic hand or foot pain. A few scattered angiokeratoma can be found on the low back skin on examination. Except for the similar locating pattern of angiokeratoma, no evident abnormality was found in the laboratory work up and physical examination of his younger brother. The patient was diagnosed with FD companying with minimal change disease by renal biopsy. Genetic analysis on our patient and his sibling revealed a nonsense GLA gene variant (c.707G > A, p.Trp236*), which has been previously reported in FD. Immunotherapy alone (steroids and tacrolimus), but without enzyme replacement therapy, much improved the massive proteinuria. Follow up to date, his 24-h urine protein is stable at about 0.5 g, and renal function keeps normal. CONCLUSION: Sudden onset of nephrotic syndrome, although rare, may occur in FD, even as the primary renal manifestation, but this usually suggests additional renal disease. Immunosuppressive treatment should be considered in such FD patient companying with nephrotic syndrome.

17.
Sci Rep ; 10(1): 15337, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948823

RESUMO

The aim of this study was to develop a model that could be used to forecast the bleeding risk of ITP based on proinflammatory and anti-inflammatory factors. One hundred ITP patients were recruited to build a new predictive nomogram, another eighty-eight ITP patients were enrolled as validation cohort, and data were collected from January 2016 to January 2019. Four demographic characteristics and fifteen clinical characteristics were taken into account. Eleven cytokines (IFN-γ, IL-1, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-22, IL-23, TNF-α and TGF-ß) were used to study and the levels of them were detected by using a cytometric bead array (CBA) human inflammation kit. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariate logistic regression analysis was applied to build a new predictive nomogram based on the results of the least absolute shrinkage and selection operator regress ion model. The application of C-index, ROC curve, calibration plot, and decision curve analyses were used to assess the discrimination, calibration, and clinical practicability of the predictive model. Bootstrapping validation was used for testing and verifying the predictive model. After feature selection, cytokines IL-1, IL-6, IL-8, IL-23 and TGF-ß were excluded, cytokines IFN-γ, IL-4, IL-10, IL-17A, IL-22, TGF-ß, the count of PLT and the length of time of ITP were used as predictive factors in the predictive nomogram. The model showed good discrimination with a C-index of 0.82 (95% confidence interval 0.73376-0.90 624) in training cohortn and 0.89 (95% CI 0.868, 0.902) in validation cohort, an AUC of 0.795 in training cohort, 0.94 in validation cohort and good calibration. A high C-index value of 0.66 was reached in the interval validation assessment. Decision curve analysis showed that the bleeding risk nomogram was clinically useful when intervention was decided at the possibility threshold of 16-84%. The bleeding risk model based on IFN-γ, IL-4, IL-10, IL-17A, IL-22, TGF-ß, the count of PLT and the length of time of ITP could be conveniently used to predict the bleeding risk of ITP.

18.
Thyroid ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32907517

RESUMO

Background: Although studies have reported an increased risk for cognitive disorders in Hashimoto's thyroiditis (HT) patients, even in the euthyroid state, the mechanisms involved remain unclear. The hippocampus is a classic brain region associated with cognitive function, among which the formation of long-term potentiation (LTP) in the Schaffer collateral-CA1 pathway plays an important role in the process of learning and memory. Therefore, this study established a euthyroid HT model in mice and investigated whether and how HT itself has the ability to trigger LTP alterations accompanied by learning and memory abnormality. Methods: An experimental euthyroid HT model was established in NOD mice through immunization with porcine thyroglobulin (Tg). Morris water maze was measured to determine mice spatial learning and memory. We investigated the effect of HT on synaptic transmission and high-frequency stimulation-induced LTP in the Schaffer collateral-CA1 synapse of mice hippocampus in vivo. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with the induction of LTP. Results: HT mice showed intrathyroidal lymphocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function. The HT mice had poorer performance in Morris water maze than controls. These alterations were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. The integrity of the synaptic structure is the premise for the production of LTP. As detected by transmission electron microscopy, the ultrastructure of synapse and astrocyte in the hippocampus were impaired in euthyroid HT mice. Additionally, Western blot and real-time polymerase chain reaction analyses confirmed that in HT mice, GS, GLAST, and GLT-1, key elements in glutamate-glutamine circulation located in astrocyte, were downregulated, accompanied by elevated levels of glutamate in the hippocampus, which impaired the material basis for LTP induction. NMDR2B expression in the hippocampus was also downregulated. Conclusion: HT can induce damage of LTP in the hippocampal Schaffer collateral-CA1 pathway in the euthyroid state, and this can be attributed, at least partly, to astrocytes impairment, which may underlie the deleterious effects of HT itself on hippocampal-dependent learning and memory function.

19.
Cell Prolif ; : e12911, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985730

RESUMO

OBJECTIVES: Fibrotic cataract, including posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC), renders millions of people visually impaired worldwide. However, the underlying mechanism remains poorly understood. Here, we report a miRNA-based regulatory pathway that controls pathological fibrosis of lens epithelium. MATERIALS AND METHODS: Expression of miR-22-3p and histone deacetylase 6 (HDAC6) in normal and PCO patient samples were measured by qPCR. Human lens epithelial explants were treated with TGF-ß2 in the presence or absence of miR-22-3p mimics or inhibitor. Cell proliferation was determined by MTS assay, and migration was tested by transwell assay. Expression of HDAC6 and EMT-related molecules were analysed by Western blot, qPCR and immunocytochemical experiments. RESULTS: We identify miR-22-3p as a downregulated miRNA targeting HDAC6 in LECs during lens fibrosis and TGF-ß2 treatment. Mechanistically, gain- and loss-of-function experiments in human LECs and lens epithelial explants reveal that miR-22-3p prevents proliferation, migration and TGF-ß2 induced EMT of LECs via targeting HDAC6 and thereby promoting α-tubulin acetylation. Moreover, pharmacological targeting of HDAC6 deacetylase with Tubacin prevents fibrotic opaque formation through increasing α-tubulin acetylation under TGF-ß2 stimulated conditions in both human lens epithelial explants and the whole rat lenses. CONCLUSIONS: These findings suggest that miR-22-3p prevents lens fibrotic progression by targeting HDAC6 thereby promoting α-tubulin acetylation. The 'miR-22-HDAC6-α-tubulin (de)acetylation' signalling axis may be therapeutic targets for the treatment of fibrotic cataract.

20.
Bioengineered ; 11(1): 1027-1033, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32951505

RESUMO

Currently, there are no relevant findings on the diagnostic and prognostic roles of adenomatous polyposis coli 2 (APC2) in colorectal cancer (CRC). This study investigated the clinical value of APC2 dysregulation in the prognosis of CRC. Immunohistochemical scores obtained from tissue microarrays were used to quantify the expression of APC2 protein in 201 CRC tissues and 139 adjacent normal tissues. A chi-squared test was performed to analyze the association between APC2 expression and various clinical characteristics. Differences in 5-year survival between groups were analyzed. A receiver operating characteristic (ROC) curve was generated to investigate the potential association between APC2 and CRC diagnosis. Compared with adjacent normal tissues, APC2 was downregulated in CRC tissues (P = 0.0004). Survival analyses revealed that CRC patients with high APC2 expression (96.74%) obtained better 5-year survival rates than those with low APC2 expression (88.07%). CRC patients with low APC2 expression exhibited obvious lymphovascular invasion (P = 0.010), lymph node metastasis (P = 0.007), and high tumor node metastasis (TNM) stage (P = 0.007). Furthermore, ROC curves confirmed that APC2 was associated with lymphovascular invasion (P = 0.004), lymph node metastasis (P = 0.002), and TNM staging (P = 0.002). In summary, low APC2 expression in CRC tissues was associated with poor prognosis and may be a useful biomarker for the prognosis and clinical classification of CRC.

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