Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 222
Filtrar
1.
Lancet Digit Health ; 4(1): e8-e17, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34952679

RESUMO

BACKGROUND: Accurate prediction of tumour response to neoadjuvant chemoradiotherapy enables personalised perioperative therapy for locally advanced rectal cancer. We aimed to develop and validate an artificial intelligence radiopathomics integrated model to predict pathological complete response in patients with locally advanced rectal cancer using pretreatment MRI and haematoxylin and eosin (H&E)-stained biopsy slides. METHODS: In this multicentre observational study, eligible participants who had undergone neoadjuvant chemoradiotherapy followed by radical surgery were recruited, with their pretreatment pelvic MRI (T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging) and whole slide images of H&E-stained biopsy sections collected for annotation and feature extraction. The RAdioPathomics Integrated preDiction System (RAPIDS) was constructed by machine learning on the basis of three feature sets associated with pathological complete response: radiomics MRI features, pathomics nucleus features, and pathomics microenvironment features from a retrospective training cohort. The accuracy of RAPIDS for the prediction of pathological complete response in locally advanced rectal cancer was verified in two retrospective external validation cohorts and further validated in a multicentre, prospective observational study (ClinicalTrials.gov, NCT04271657). Model performances were evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). FINDINGS: Between Sept 25, 2009, and Nov 3, 2017, 303 patients were retrospectively recruited in the training cohort, 480 in validation cohort 1, and 150 in validation cohort 2; 100 eligible patients were enrolled in the prospective study between Jan 10 and June 10, 2020. RAPIDS had favourable accuracy for the prediction of pathological complete response in the training cohort (AUC 0·868 [95% CI 0·825-0·912]), and in validation cohort 1 (0·860 [0·828-0·892]) and validation cohort 2 (0·872 [0·810-0·934]). In the prospective validation study, RAPIDS had an AUC of 0·812 (95% CI 0·717-0·907), sensitivity of 0·888 (0·728-0·999), specificity of 0·740 (0·593-0·886), NPV of 0·929 (0·862-0·995), and PPV of 0·512 (0·313-0·710). RAPIDS also significantly outperformed single-modality prediction models (AUC 0·630 [0·507-0·754] for the pathomics microenvironment model, 0·716 [0·580-0·852] for the radiomics MRI model, and 0·733 [0·620-0·845] for the pathomics nucleus model; all p<0·0001). INTERPRETATION: RAPIDS was able to predict pathological complete response to neoadjuvant chemoradiotherapy based on pretreatment radiopathomics images with high accuracy and robustness and could therefore provide a novel tool to assist in individualised management of locally advanced rectal cancer. FUNDING: National Natural Science Foundation of China; Youth Innovation Promotion Association of the Chinese Academy of Sciences.

2.
J Nanobiotechnology ; 19(1): 444, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34949180

RESUMO

BACKGROUND: Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer. RESULTS: HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis. CONCLUSIONS: To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer.

3.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 4066-4074, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34841806

RESUMO

Different fragments of SARS-CoV-2 nucleocapsid (N) protein were expressed and purified, and a fluorescence immunochromatography method for detection of SARS-CoV-2 total antibody was established. The effect of different protein fragments on the performance of the method was evaluated. The N protein sequence was analyzed by bioinformatics technology, expressed in prokaryotic cell and purified by metal ion affinity chromatography column. Different N protein fragments were prepared for comparison. EDC reaction was used to label fluorescence microsphere on the synthesized antigen to construct sandwich fluorescence chromatography antibody detection assay, and the performance was systemically evaluated. Among the 4 prepared N protein fragments, the full-length N protein (N419) was selected as the optimized coating antigen, N412 with 0.5 mol/L NaCl was used as the optimal combination; deleting 91-120 amino acids from the N-terminal of N412 reduced non-specific signal by 87.5%. the linear range of detection was 0.312-80 U/L, the limit of detection was 0.165 U/L, and the accuracy was more than 95%. A fluorescence immunochromatographic detection method for analysis of SARS-CoV-2 total antibody was established by pairing N protein fragments. The detection result achieved 98% concordance with the commercially available Guangzhou Wanfu test strip, which is expected to be used as a supplementary approach for detection of SARS-CoV-2. The assay could also provide experimental reference for improving the performance of COVID-19 antibody detection reagents.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Cromatografia de Afinidade , Imunofluorescência , Humanos , Microesferas , Sensibilidade e Especificidade
4.
Nat Commun ; 12(1): 6711, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795238

RESUMO

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

5.
Bioengineered ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719315

RESUMO

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus, which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund's Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1ß(IL-1ß), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1ßand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

6.
Opt Express ; 29(20): 32464-32473, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615316

RESUMO

A fundamental feature of micro objects is the wave-particle duality which is addressed by Bohr's complementarity principle. To observe the wave and particle behaviours, quantum delayed-choice experiments based on linear optics have been realized at the single-photon level. Since they were performed by using a single photon as the input, repeating measurements were required in order to obtain different experimental data and adjusting experimental parameters was necessary prior to each of measurements. Different from the previous works, we here realize a simulation of quantum delayed-choice experiment through a single shot, which employs a classical intense light beam as the input instead of a single photon. Experimentally, we demonstrate the trade-off between distinguishability and visibility of photons in a two-arm interferometer in an intuitive way by utilizing the finite beam profile of the light. We observe the morphing between wave and particle natures of photons via a single shot of a charged-coupled-device camera. Since the image is captured within the exposure time which is several milliseconds, the phase fluctuation is negligible, and therefore our experimental setup is robust against the noise. This work provides a simple and new route to inspect quantum duality, which does not require adjusting experimental parameters frequently and only needs performing measurement once.

7.
Plant Biotechnol J ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655511

RESUMO

Starch accounts for over 80% of the total dry weight in cereal endosperm and determines the kernel texture and nutritional quality. Amyloplasts, terminally differentiated plastids, are responsible for starch biosynthesis and storage. We screened a series of rice mutants with floury endosperm to clarify the mechanism underlying amyloplast development and starch synthesis. We identified the floury endosperm19 (flo19) mutant which shows opaque of the interior endosperm. Abnormal compound starch grains (SGs) were present in the endosperm cells of the mutant. Molecular cloning revealed that the FLO19 allele encodes a plastid-localized pyruvate dehydrogenase complex E1 component subunit α1 (ptPDC-E1-α1) that is expressed in all rice tissues. In vivo enzyme assays demonstrated that the flo19 mutant showed decreased activity of the plastidic pyruvate dehydrogenase complex. In addition, the amounts of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) were much lower in the developing flo19 mutant endosperm, suggesting that FLO19 participates in fatty acid supply for galactolipid biosynthesis in amyloplasts. FLO19 overexpression significantly increased seed size and weight, but did not affect other important agronomic traits, such as panicle length, tiller number and seed setting rate. An analysis of single nucleotide polymorphism data from a panel of rice accessions identified that the pFLO19L haplotype was positively associated with grain length, implying a potential application in rice breeding. In summary, our study demonstrates that FLO19 is involved in galactolipid biosynthesis which is essential for amyloplast development and starch biosynthesis in rice.

8.
Cell Death Dis ; 12(11): 970, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671012

RESUMO

Oncogenic c-Myc is a master regulator of G1/S transition. Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. Here, we found that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1-phase of cell cycle. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor cell growth in vitro and in vivo. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc expression, G1/S transition, and cell proliferation. The effect of SNHG17 in stimulating cell proliferation was attenuated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the level of ubiquitylated c-Myc and reduced the stability of c-Myc protein. Analysis of human hepatocellular carcinoma (HCC) tissues revealed that SNHG17, LRPPRC, and c-Myc were significantly upregulated in HCC, and they showed a positive correlation with each other. High level of SNHG17 or LRPPRC was associated with worse survival of HCC patients. These data suggest that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which may provide potential targets for cancer therapy.

9.
Natl Sci Rev ; 8(3): nwaa302, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34694298

RESUMO

[This corrects the article DOI: 10.1093/nsr/nwz188.].

10.
Clin Rheumatol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553293

RESUMO

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.

11.
Plant Physiol Biochem ; 167: 806-815, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34530325

RESUMO

The red light (R) to far-red light (FR) ratio (R:FR) regulates plant responses to salt stress, but the regulation mechanism is still unclear. In this study, tomato seedlings were grown under half-strength Hoagland solution with or without 150 mM NaCl at two different R:FR ratios (7.4 and 0.8). The photosynthetic capacity, antioxidant enzyme activities, and the phenotypes at chloroplast ultrastructure and whole plant levels were investigated. The results showed that low R:FR significantly alleviated the damage of tomato seedlings from salt stress. On day 4, 8, and 12 at low R:FR, the maximum photochemical quantum yields (Fv/Fm) of photosystem II (PSII) were increased by 4.53%, 3.89%, and 16.49%, respectively; the net photosynthetic rates (Pn) of leaves were increased by 16.21%, 90.81%, and 118.00%, respectively. Low R:FR enhanced the integrity and stability of the chloroplast structure of salinity-treated plants through maintaining the high activities of antioxidant enzymes and mitigated the degradation rate of photosynthetic pigments caused by reactive oxygen species (ROS) under salt stress. The photosynthesis, antioxidant enzyme-related gene expression, and transcriptome sequencing analysis of tomato seedlings under different treatments were also investigated. Low R:FR promoted the de novo synthesis of D1 protein via triggering psbA expression, and upregulated the transcripts of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) related genes. Meanwhile, the transcriptome analysis confirmed the positive function of low R:FR on enhancing tomato salinity stress tolerance from the regulation of photosynthesis and ROS scavenging systems.


Assuntos
Lycopersicon esculentum , Tolerância ao Sal , Antioxidantes , Fotossíntese , Folhas de Planta , Plântula
12.
J Periodontal Res ; 56(6): 1200-1212, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34492118

RESUMO

BACKGROUND AND OBJECTIVE: Cementum is a part of the periodontium and anchors periodontal ligaments to the alveolar bone. Cementoblasts are responsible for the cementum formation via matrix deposition and subsequently mineralization. Thus, exploring novel mechanisms underlying the function of cementoblast contributes to the treatment of cementum damage. Recently, circRNA Lrp6 (circLRP6) has been of interest due to its active role in cell differentiation, but its potential role in cementoblast differentiation remains unclear. Herein, we attempted to elucidate the role of circLRP6 in cementoblast differentiation and clarify any associated mechanisms. MATERIAL AND METHODS: The mRNA expressions of circLRP6, miR-145a-5p, zinc finger E-box binding homeobox 2 (Zeb2), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and bone sialoprotein (Bsp) were evaluated by qRT-PCR. The protein levels of Zeb2 were measured by Western blot. Bioinformatic analysis and dual-luciferase reporter assays were used to test the potential binding targets of miR-145a-5p. The differentiation potentials of the cementoblasts were assessed by Alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin red S (ARS) staining, and quantification. RESULTS: In this study, circLRP6 was significantly upregulated in cementoblast differentiation. Furthermore, circLRP6 knockdown inhibited ALP levels, reduced calcium nodule formation and the expression of Runx2, Opn, and Bsp. Mechanically, bioinformatic analysis and dual-luciferase reporter assays confirmed miR-145a-5p was a potential binding target of circLRP6. miR-145a-5p can negatively regulate cementoblast differentiation. Subsequently, bioinformatic analysis and dual-luciferase reporter assays confirmed Zeb2 was a potential miR-145a-5p target. miR-145a-5p overexpression resulted in a downregulation of Zeb2. Furthermore, Zeb2 inhibition partially reversed the effect of circLRP6 during cementoblast differentiation. CONCLUSION: Taken together, circLRP6 appears to modulate cementoblast differentiation by antagonizing the function of miR-145a-5p, thereby increasing Zeb2. This study serves as a stepping stone for the potential development of an approach to promote cementum formation.


Assuntos
Cemento Dentário , MicroRNAs , Diferenciação Celular , MicroRNAs/genética , Ligamento Periodontal , RNA Circular
13.
Heart Rhythm ; 18(12): 2148-2157, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34438043

RESUMO

BACKGROUND: Ventricular arrhythmias (VAs) ablated successfully at the right-left subvalvular interleaflet triangle (R-L ILT) between right and left coronary cusps have not been fully characterized. OBJECTIVE: The purpose of this study was to investigate the electrophysiological characteristics of these VAs and their relationships with the left ventricular (LV) summit. METHODS: Twenty-eight VAs ablated successfully at the R-L ILT were studied. RESULTS: Ninety-six percent of VAs had an early precordial electrocardiographic transition. R-wave amplitude in lead V1 was relatively high (RS morphology, R-wave amplitude 0.35 ± 0.09 mV; R/S ratio 0.35 ± 0.27), whereas the morphology of lead I was R-shaped in 71% and M-shaped in 50% of VAs. Earliest potential was recorded at the R-L ILT in 13 of 28 patients and the left pulmonary sinus cusp (LC) in 6 of 28 patients. Mapping the summit communicating vein (summit-CV) failed because of anatomic or instrumental limitations in these 19 patients. In the other 9 patients, earliest potential was successfully recorded at the summit-CV, while perfect pacemapping was achieved. Poor pace mapping was achieved at the R-L ILT or LC in most patients (27/28). Target site was located at the top of the R-L ILT in all cases. A presystolic potential was present at the target site in 18 of 28 patients. A U-curve via the retrograde method was conventionally used to reach the top of the R-L ILT. CONCLUSION: VAs ablated successfully at the R-L ILT have unique electrophysiological characteristics, and R-L ILT may be an endocardial anatomic ablation target for VAs originating from the base of the LV summit.

14.
Med Sci Monit ; 27: e931427, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34366426

RESUMO

BACKGROUND Acute chemical liver injury needs to be further explored. The present study aimed to compare the effects of intraperitoneal injection with carbon tetrachloride on acute liver toxicity after 24 h in male and female Kunming mice. MATERIAL AND METHODS In this study, female and male mice were simultaneously divided into 3 different groups. Each group was treated differently, and after 24 h, blood samples were collected to check for changes in the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were used to assess liver toxicity. Liver samples were used for hematoxylin-eosin staining, and periodic acid Schiff reagent staining was performed to detect the pathological changes of each group. The expression level of biomarker molecules in liver cells was also systematically analyzed. RESULTS Our results showed that, compared with male mice, female mice showed more serious damage: reduced glycogen and higher degree of necrosis, and the levels of heatshock protein 27 (HSP27), heat-shock protein 70 (HSP70), proliferating cell nuclear antigen (PCNA) and B cell lymphoma/lewkmia-2 (Bcl-2) were significantly lower than in the male group (P<0.05 or P<0.01), while the results of Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), and cytochrome P450 2E1 (CYP2E1) were the opposite (P<0.05 or P<0.01). CONCLUSIONS The findings from this study showed that, compared with male mice, at 24 h after CCl4 toxicity, female mice showed more severe changes of hepatocyte necrosis and PAS-positivity, with significantly reduced expression of HSP27, HSP70, PCNA, and Bcl-2, and significantly increased expression of Bax, caspase-3, and CYP2E1.

15.
Acta Odontol Scand ; : 1-7, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34392794

RESUMO

OBJECTIVE: Cementum which is a layer of thin and bone-like mineralised tissue covering tooth root surface is deposited and mineralised by cementoblasts. Recent studies suggested long noncoding RNA H19 (H19) promotes osteoblast differentiation and matrix mineralisation, however, the effect of H19 on cementoblasts remains unknown. This study aimed to clarify the regulatory effects of H19 on cementoblast differentiation, mineralisation, and proliferation. MATERIAL AND METHODS: An immortalised murine cementoblast cell line OCCM-30 was used in this study. H19 expression was examined by real-time quantitative polymerase chain reaction (RT-qPCR) during OCCM-30 cell differentiation. OCCM-30 cells were transfected with lentivirus or siRNA to up-regulate or down-regulate H19, then the levels of runt-related transcription factor 2 (Runx2), osterix (Sp7), alkaline phosphatase (Alpl), bone sialoprotein (Ibsp), osteocalcin (Bglap) were tested by RT-qPCR or western blot. Alizarin red staining, ALP activity assay and MTS assay were performed to determine the mineralisation and proliferation ability of OCCM-30 cells. RESULTS: H19 was dramatically increased during OCCM-30 cell differentiation. Overexpression of H19 increased the levels of Runx2, Sp7, Alpl, Ibsp, and Bglap and enhanced ALP activity and the formation of mineral nodules. While down-regulation of H19 suppressed the above cementoblast differentiation genes and inhibited ALP activity and mineral nodule formation. However, the proliferation of OCCM-30 cells was not affected. CONCLUSIONS: H19 promotes the differentiation and mineralisation of cementoblasts without affecting cell proliferation.

16.
Am J Cancer Res ; 11(6): 2838-2852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249431

RESUMO

Radioresistance is one of the main causes of cancer treatment failure, which leads to relapse and inferior survival outcome of cancer patients. Liquid-liquid phase separation (LLPS) of proteins is known to be involved in various biological processes, whereas its role in the regulation of radiosensitivity remains largely unknown. In this study, we characterized NONO, an RNA/DNA binding protein with LLPS capacity, as an essential regulator of tumor radioresistance. In vitro assay showed that NONO involved in DNA repair via non-homologous end joining (NHEJ) manner. NONO knockout significantly reduced DNA damage repair and sensitized tumor cells to irradiation in vitro and in vivo. NONO overexpression was correlated with an inferior survival outcome in cancer patients. Mechanically, NONO was associated with nuclear EGFR (nEGFR). Both irradiation and EGF treatment induced nEGFR accumulation, thereby increased the association between NONO and nEGFR. However, NONO was not a substrate of EGFR kinase. Furthermore, NONO promoted DNA damage-induced DNA-PK phosphorylation at T2609 by enhancing the interaction between EGFR and DNA-PK. Importantly, NONO protein formed high concentration LLPS droplets in vitro, and recruited EGFR and DNA-PK. Disruption of NONO droplets with LLPS inhibitor significantly reduced the interaction between EGFR and DNA-PK, and suppressed DNA damage-induced phosphorylation of T2609-DNA-PK. Taken together, LLPS of NONO recruits nuclear EGFR and DNA-PK and enhances their interaction, further increases DNA damage-activated pT2609-DNA-PK and promotes NHEJ-mediated DNA repair, finally leads to tumor radioresistance. NONO phase separation-mediated radioresistance may serve as a novel molecular target to sensitize tumor cell to radiotherapy.

17.
Chemphyschem ; 22(18): 1900-1906, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34216092

RESUMO

The present study proposes a new approach for direct CO2 conversion using primary radicals from water irradiation. In order to ensure reduction of CO2 into CO2 -. by all the primary radiation-induced water radicals, we use formate ions to scavenge simultaneously the parent oxidizing radicals H. and OH. producing the same transient CO2 -. radicals. Conditions are optimized to obtain the highest conversion yield of CO2 . The goal is achieved under mild conditions of room temperature, neutral pH and 1 atm of CO2 pressure. All the available radicals are exploited for selectively converting CO2 into oxalate that is accompanied by H2 evolution. The mechanism presented accounts for the results and also sheds light on the data in the literature. The radiolytic approach is a mild and scalable route of direct CO2 capture at the source in industry and the products, oxalate salt and H2 , can be easily separated.

18.
J Biomed Nanotechnol ; 17(6): 1007-1019, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34167616

RESUMO

In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles with dual response of endogenous peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe2O3 nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe2O3 nanoparticles could simulate the activity of catalase and decompose hydrogen peroxide into H2O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe2O3 nanoparticles could simulate the activity of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe2O3 nanoparticles and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe2O3 nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic nanozymes for the treatment of lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Nanopartículas , Células A549 , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Compostos Férricos , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Microambiente Tumoral
19.
Am J Cancer Res ; 11(5): 2291-2302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094685

RESUMO

Siglec15 is a recently characterized immunosuppressive transmembrane protein, which expresses in various types of solid tumors and promotes cancer development. Several studies reported that Siglec15 is a prognostic biomarker of cancer patients, and targeting Siglec15 may be a promising strategy for cancer therapy. However, the regulation of Siglec15 function remains unclear. Here we show that the immunosuppression activity of Siglec15 is largely modulated by N-glycosylation. Through mass spectrum and site mutation analysis, we identified that Siglec15 was extensively glycosylated at N172 (N173 for mouse) in cancer cells. Meanwhile, Siglec15 N172Q had a similar molecular weight with PNGase-F-treated Siglec15, suggesting N172 as the only one glycosylation residue. In xenograft model, glycosylation deficiency of Siglec15 reduced tumor growth in C57BL/6 mice, but had no impact in nude mice, indicating the requirement of N-glycosylation for immunosuppressive function of Siglec15. Furthermore, colorectal cancer patients with high Siglec15 expression had a poor response to neoadjuvant chemo-radiotherapy and short survival time. Interestingly, removal of N-glycosylation enhances the detection of Siglec15, which may be employed in the prediction of immunotherapy response. Together, our results disclose a pivotal role of glycosylated Siglec15 in tumor immune escape, which may be a therapeutic target for cancer immunotherapy.

20.
IEEE J Biomed Health Inform ; 25(7): 2487-2496, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34129511

RESUMO

Estimating and surveillance volumes of patients are of great importance for public health and resource allocation. In many situations, the change of these volumes is correlated with many factors, e.g., seasonal environmental variables, medicine sales, and patient medical claims. It is often of interest to predict patient volumes and to that end, discovering causalities can improve the prediction accuracy. Correlations do not imply causations and they can be spurious, which in turn may entail deterioration of prediction performance if the prediction is based on them. By contrast, in this paper, we propose an approach for prediction based on causalities discovered by Gaussian processes. Our interest is in estimating volumes of patients that suffer from allergy and where the model and the results are highly interpretable. In selecting features, instead of only using correlation, we take causal information into account. Specifically, we adopt the Gaussian processes-based convergent cross mapping framework for causal discovery which is proven to be more reliable than the Granger causality when time series are coupled. Moreover, we introduce a novel method for selecting the history or look-back length of features from the perspective of a dynamical system in a principled manner. The quasi-periodicities that commonly exist in observations of volumes of patients and environment variables can readily be accommodated. Further, the proposed method performs well even in cases when the data are scarce. Also, the approach can be modified without much difficulty to forecast other types of patient volumes. We validate the method with synthetic and real-world datasets.


Assuntos
Distribuição Normal , Causalidade , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...