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1.
J Cell Mol Med ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793048

RESUMO

14-3-3 proteins are highly conserved in species ranging from yeast to mammals and regulate numerous signalling pathways via direct interactions with proteins carrying phosphorylated 14-3-3-binding motifs. Recent studies have shown that 14-3-3 proteins can also play a role in viral infections. This review summarizes the biological functions of 14-3-3 proteins in protein trafficking, cell-cycle control, apoptosis, autophagy and other cell signal transduction pathways, as well as the associated mechanisms. Recent findings regarding the role of 14-3-3 proteins in viral infection and innate immunity are also reviewed.

2.
Stem Cell Res Ther ; 12(1): 221, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789737

RESUMO

BACKGROUND: Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. METHODS: ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson's trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. RESULTS: The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. CONCLUSIONS: This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

3.
Nucleic Acids Res ; 49(6): 3322-3337, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33704464

RESUMO

RPA is a critical factor for DNA replication and replication stress response. Surprisingly, we found that chromatin RPA stability is tightly regulated. We report that the GDP/GTP exchange factor DOCK7 acts as a critical replication stress regulator to promote RPA stability on chromatin. DOCK7 is phosphorylated by ATR and then recruited by MDC1 to the chromatin and replication fork during replication stress. DOCK7-mediated Rac1/Cdc42 activation leads to the activation of PAK1, which subsequently phosphorylates RPA1 at S135 and T180 to stabilize chromatin-loaded RPA1 and ensure proper replication stress response. Moreover, DOCK7 is overexpressed in ovarian cancer and depleting DOCK7 sensitizes cancer cells to camptothecin. Taken together, our results highlight a novel role for DOCK7 in regulation of the replication stress response and highlight potential therapeutic targets to overcome chemoresistance in cancer.

4.
Cell Death Differ ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686256

RESUMO

Although ß-arrestins (ARRBs) regulate diverse physiological and pathophysiological processes, their functions and regulation in Parkinson's disease (PD) remain poorly defined. In this study, we show that the expression of ß-arrestin 1 (ARRB1) and ß-arrestin 2 (ARRB2) is reciprocally regulated in PD mouse models, particularly in microglia. ARRB1 ablation ameliorates, whereas ARRB2 knockout aggravates, the pathological features of PD, including dopaminergic neuron loss, neuroinflammation and microglia activation in vivo, and microglia-mediated neuron damage in vitro. We also demonstrate that ARRB1 and ARRB2 produce adverse effects on inflammation and activation of the inflammatory STAT1 and NF-κB pathways in primary cultures of microglia and macrophages and that two ARRBs competitively interact with the activated form of p65, a component of the NF-κB pathway. We further find that ARRB1 and ARRB2 differentially regulate the expression of nitrogen permease regulator-like 3 (Nprl3), a functionally poorly characterized protein, as revealed by RNA sequencing, and that in the gain- and loss-of-function studies, Nprl3 mediates the functions of both ARRBs in microglia inflammatory responses. Collectively, these data demonstrate that two closely related ARRBs exert opposite functions in microglia-mediated inflammation and the pathogenesis of PD which are mediated at least in part through Nprl3 and provide novel insights into the understanding of the functional divergence of ARRBs in PD.

5.
Medicine (Baltimore) ; 100(9): e24459, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655917

RESUMO

RATIOANLE: Interdigitating dendritic cell sarcoma (IDCS) is a rare sarcoma that originates from interdigitating dendritic cells in lymphoid tissue, the imaging characteristics of which are poorly defined. Pathological examination can identify the tumor, but reports on the imaging characteristics of IDCS are limited. PATIENT CONCERNS: Here, we report a case of IDCS in a 48-year-old female involving the retroperitoneal area. The patient had a lumbar mass on her right lower back for 4 years, and which started increasing in size 1 year before. DIAGNOSES: An irregular soft tissue mass (10.1cm × 8.5 cm in size) in the right lower back of retroperitoneum was detected by CT examination with unclear borders, uneven density, and necrosis. The solid components of the mass were significantly enhanced on postcontrast imaging. The soft tissue was irregular and uneven. Cystic solid masses were observed on MRI examination in the right retroperitoneum, lateral abdominal wall, waist, and back. Necrosis, hemorrhage, and cystic transformation were observed inside the lesion. The cyst wall, separation, and wall nodules were significantly enhanced on the postcontrast image. No distant metastasis was observed. Postoperative pathology confirmed the diagnosis of IDCS. INTERVENTIONS: The patient underwent surgical resection. The resected margin was positive, and the patient received adjuvant radiotherapy 2 months after the surgery. OUTCOMES: Twelve months after radiotherapy, the patient's chest CT showed multiple metastases in both lungs. The patient was started on combination chemotherapy of doxorubicin and ifosfamide, and the follow-up is still ongoing. LESSONS: Imaging provides a unique advantage to determine the extent of the IDCS, the invasion of adjacent tissues, and the presence or absence of distant metastases.


Assuntos
Sarcoma de Células Dendríticas Interdigitantes/patologia , Neoplasias Retroperitoneais/patologia , Feminino , Humanos , Pessoa de Meia-Idade
6.
New Phytol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586184

RESUMO

The oomycete pathogen Hyaloperonospora arabidopsidis delivers diverse effector proteins into host plant cells to suppress the plant's innate immunity. In this study, we investigate the mechanism of action of a conserved RxLR effector, HaRxLL470, in suppressing plant immunity. Genomic, molecular and biochemical analyses were performed to investigate the function of HaRxLL470 and the mechanism of the interaction between HaRxLL470 and the target host protein during H. arabidopsidis infection. We report that HaRxLL470 enhances plant susceptibility to H. arabidopsidis isolate Noco2 by interacting with the host photomorphogenesis regulator protein HY5. Our results demonstrate that HY5 is not only an important component in the regulation of light signalling, but also positively regulates host plant immunity against H. arabidopsidis by transcriptional activation of defense-related genes. We show that the interaction between HaRxLL470 and HY5 compromises the function of HY5 as a transcription factor by attenuating its DNA-binding activity. The present study demonstrates that HY5 positively regulates host plant defense against H. arabidopsidis whereas HaRxLL470, a conserved RxLR effector across oomycete pathogens, enhances pathogenicity by interacting with HY5 and suppressing transcriptional activation of defense-related genes.

7.
Cell Metab ; 33(3): 666-675.e4, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33545051

RESUMO

The nervous system instructs the body's metabolism, including that in the liver. However, the neural anatomy of the liver under either normal or metabolically stressed conditions remains to be unequivocally assessed. Here, we examined neural distributions in the mouse, nonhuman primate, and human livers with advanced 3D imaging. We observed that neural innervations within the liver are predominantly sympathetic, but not parasympathetic, inputs. Moreover, we discovered the profound and reversible loss of such sympathetic innervations during metabolic challenges. This hepatic sympathetic neuropathy was caused by TNFα derived from CD11b+ F4/80+ immune cells under high-fat-diet (HFD) condition. We further demonstrated that the Sarm1 deletion mitigated the hepatic sympathetic neuropathy and improved metabolic parameters in HFD-challenged mice. Mechanistically, the sympathetic neurotransmitter norepinephrine attenuated the immune-cell inflammation that would otherwise trigger the insulin insensitivity of hepatocytes. These results together reveal the previously unrecognized neuropathic event in the liver with metabolic relevance.

8.
Mol Cancer ; 20(1): 36, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608029

RESUMO

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.

9.
Ir J Med Sci ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635447

RESUMO

BACKGROUND: High-mobility group box 2 (HMGB2) is considered as oncogene in non-small cell lung cancer (NSCLC), while its clinical implication is still unknown. This study aimed to explore the correlation of HMGB2 with clinicopathological characteristics and prognosis in NSCLC patients. METHODS: A total of 133 NSCLC patients who received radical excision were enrolled. HMGB2 expression in the tumor specimens and paired adjacent tissue specimens was determined by immunohistochemical assay (for protein expression) and reverse transcription quantitative polymerase chain reaction assay (for gene expression), respectively. RESULTS: HMGB2 protein expression was higher in tumor tissue compared with adjacent tissue, and it could distinguish tumor tissue from adjacent tissue (area under the curve (AUC): 0.775, 95%confidence interval (95%CI): 0.720-0.830). Meanwhile, tumor HMGB2 protein high expression correlated with lymph node (LYN) metastasis and advanced TNM stage. Additionally, tumor HMGB2 protein high expression associated with worse disease-free survival (DFS), while HMGB2 protein expression did not correlate with overall survival (OS). Besides, HMGB2 mRNA expression was raised in tumor tissue compared with adjacent tissue, and it had a good value in differentiating tumor tissue from adjacent tissue (AUC: 0.875, 95% CI: 0.834-0.915). Furthermore, tumor HMGB2 mRNA high expression correlated with higher Eastern Cooperative Oncology Group performance status score, LYN metastasis, and advanced TNM stage. Meanwhile, tumor HMGB2 mRNA high expression associated with shorter DFS and OS. CONCLUSION: HMGB2 could be a biomarker that reflects disease features and prognosis of NSCLC, which is beneficial to improve clinical efficacy in NSCLC patients.

10.
Sci Adv ; 7(9)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33627425

RESUMO

Mechanical stimuli on cells and mechanotransduction are essential in many biological and pathological processes. Glucocorticoid is an important hormone, roles, and mechanisms of which in cellular mechanotransduction remain unknown. Here, we report that glucocorticoid counteracted cellular mechanoresponses dependently on a novel long noncoding RNA (lncRNA), LINC01569 Further, LINC01569 mediated glucocorticoid effects on mechanotransduction by destabilizing messenger RNA (mRNA) of mechanosensors including early growth response protein 1 (EGR1), Cbp/P300-interacting transactivator 2 (CITED2), and bone morphogenic protein 7 (BMP7) in glucocorticoid receptor-mediated mRNA decay (GMD) manner. Mechanistically, LINC01569 directly bound to the GMD factor Y-box-binding protein 1 (YBX1). Then, the LINC01569-YBX1 complex was guided to the mRNAs of EGR1, CITED2, and BMP7 through specific LINC01569-mRNA interaction, thereby contributing to the successful assembly of GMD complex and triggering GMD. Our results uncovered roles of glucocorticoid in cellular mechanotransduction and novel lncRNA-dependent GMD machinery and provided potential strategy for early intervention in mechanical disorder-associated diseases.

11.
J Gynecol Oncol ; 32(2): e17, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33470062

RESUMO

OBJECTIVE: To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. METHODS: We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type. RESULTS: LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58-1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65-2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). CONCLUSIONS: Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors. TRIAL REGISTRATION: International Clinical Trials Registry Platform Identifier: CHiCTR180017778.

12.
J Biotechnol ; 327: 106-116, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33421510

RESUMO

Soil salinity is one of the major environmental factors, influencing agricultural productivity of crops. As a non-edible and ideal oilseed crop, castor (Ricinus communis L.) has great industrial value in biofuel, but molecular mechanisms of salt stress regulation are still unknown. In this study, the differentially expressed genes (DEGs) for differential salt tolerance in two castor cultivar (wild castor : Y, cultivated castor 'Tongbi 5': Z) were identified. 12 libraries were sampled for Illumina high-throughput sequencing to consider 132,426 nonredundant unigenes and 31,221 gene loci. Multiple phytohormones and transcription factors (TFs) were correlated with salt-tolerance and differently enriched in these two genotypes. The type 2C protein phosphatases (PP2C) homologs were all upregulated under salt stress. Importantly, IAA (1), DELLA (1) and Jasmonate zim domain (JAZ) (1) were also identified and found to be differentially expressed. Based on the co-expressed module by regulatory networks and heatmap analysis, ERF/AP2, WRKY and bHLH families were prominently participate in high salt stress response of wild and cultivated castor. Finally, these results highlight that the hub DEGs and families were more accumulated in cultivated castor than those in wild castor, providing novel insights into the salinity adaptive mechanisms and genetic improvement in castor.

13.
J Nanobiotechnology ; 19(1): 22, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436002

RESUMO

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. EXPERIMENTAL DESIGN: Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. RESULTS: We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. CONCLUSIONS: We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.

14.
J Hematol Oncol ; 14(1): 18, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461583

RESUMO

Accurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls. Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers. Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2-5 and 15-23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.

15.
Genome Res ; 31(3): 497-511, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33408157

RESUMO

Emu and other ratites are more informative than any other birds in reconstructing the evolution of the ancestral avian or vertebrate karyotype because of their much slower rate of genome evolution. Here, we generated a new chromosome-level genome assembly of a female emu, and estimated the tempo of chromosome evolution across major avian phylogenetic branches, by comparing it to chromosome-level genome assemblies of 11 other bird and one turtle species. We found ratites exhibited the lowest numbers of intra- and inter-chromosomal changes among birds since their divergence with turtles. The small-sized and gene-rich emu microchromosomes have frequent inter-chromosomal contacts that are associated with housekeeping genes, which appears to be driven by clustering their centromeres in the nuclear interior, away from the macrochromosomes in the nuclear periphery. Unlike nonratite birds, only less than one-third of the emu W Chromosome regions have lost homologous recombination and diverged between the sexes. The emu W is demarcated into a highly heterochromatic region (WS0) and another recently evolved region (WS1) with only moderate sequence divergence with the Z Chromosome. WS1 has expanded its inactive chromatin compartment, increased chromatin contacts within the region, and decreased contacts with the nearby regions, possibly influenced by the spreading of heterochromatin from WS0. These patterns suggest that alteration of chromatin conformation comprises an important early step of sex chromosome evolution. Overall, our results provide novel insights into the evolution of avian genome structure and sex chromosomes in three-dimensional space.

16.
Chemosphere ; 263: 127954, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32854008

RESUMO

Chlorine disinfection is required to inactivate pathogens in drinking water, but it inevitably generates potentially toxic halogenated disinfection byproducts (halo-DBPs). A previous study has reported that the addition of ascorbate to tap water before boiling could significantly decrease the concentration of overall halo-DBPs in the boiled water. Since the fruit lemon is rich in vitamin C (i.e., ascorbic acid), adding it to tap water followed by heating and boiling in an effort to decrease levels of halo-DBPs was investigated in this study. We examined three approaches that produce lemon water: (i) adding lemon to tap water at room temperature, termed "Lemon"; (ii) adding lemon to boiled tap water (at 100 °C) and then cooling to room temperature, termed "Boiling + Lemon"; and (iii) adding lemon to tap water then boiling and cooling to room temperature, termed "Lemon + Boiling". The concentrations of total and individual halo-DBPs in the resultant water samples were quantified with high-performance liquid chromatography-tandem mass spectrometry and the cytotoxicity of DBP mixtures extracted from the water samples was evaluated using human epithelial colorectal adenocarcinoma Caco-2 cells and hepatoma HepG2 cells. Our results show that the "Lemon + Boiling" approach substantially decreased the concentrations of halo-DBPs and the cytotoxicity of tap water. This strategy could be applied to control halo-DBPs, as well as to lower the adverse health effects of halo-DBPs on humans through tap water ingestion.


Assuntos
Ácido Ascórbico/química , Desinfecção/métodos , Ácido Ascórbico/análise , Células CACO-2 , Cloro/análise , Desinfetantes/química , Água Potável/química , Halogenação , Humanos , Poluentes Químicos da Água/análise , Purificação da Água/métodos
17.
Cell Signal ; 79: 109878, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309838

RESUMO

Circular RNAs (circRNAs) are implicated in the initiation and advancement of diverse tumors. CircRNA hsa_circ_0069094 (circ_0069094) has been reported to be upregulated in BC, but the biological role of circ_0069094 in BC is indistinct. Hence, we aimed to survey the biological role of circ_0069094 in BC. In the present study, we verified that circ_0069094 was upregulated in BC tissues and cells. BC patients with high circ_0069094 expression had a poor prognosis. Functional analysis revealed that circ_0069094 silencing induced apoptosis, curbed proliferation, and reduced glycolysis in BC cells in vitro, but circ_0069094 overexpression had an opposing influence. Also, circ_0069094 knockdown reduced BC growth in vivo. Mechanically, circ_0069094 was validated as a decoy for miR-591, which targeted HK2. Importantly, circ_0069094 sponged miR-591 to regulate HK2 expression. Both miR-591 silencing and HK2 overexpression counteracted circ_0069094 inhibition-mediated influence on cell proliferation, apoptosis, and glycolysis in BC cells. In conclusion, these results indicated that circ_0069094 facilitated cell malignancy and glycolysis by upregulating HK2 through adsorbing miR-591, suggesting that circ_0069094 might be a prognostic biomarker and therapeutic target for BC.

18.
Chemosphere ; 263: 128035, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297053

RESUMO

Lead dioxide (PbO2(s)) is a corrosion product of lead-containing plumbing materials in water distribution pipelines. The presence of reductants in water could cause the release of soluble lead (mainly Pb(II)) from PbO2(s). Lead in drinking water is detrimental to public health. This paper presents the first application of ferrate (FeVIO42-, Fe(VI)) to decreasing the generation of soluble lead in water containing PbO2(s) and common reducing constituents (e.g., natural organic matter (NOM), iodide (I-), and bromide (Br-)) at different pH conditions (i.e., 6.0, 7.0, and 8.0). The released soluble lead from PbO2(s) was found to be dominantly controlled by NOM in water, via the redox dissolution of PbO2(s) and the reduction of PbO2(s) by reducing moieties of NOM. The feasibility of both processes increased when pH decreased. The I- and Br- in water played minor roles in generating soluble lead. Fe(VI) reacted with reducing functional groups of NOM, as determined by 13C nuclear magnetic resonance spectroscopy. Water pretreatment with Fe(VI) inhibited the reaction of NOM with PbO2(s) and therefore, caused lower soluble lead concentrations compared to water samples without Fe(VI) treatment. This study indicates that Fe(VI) pretreatment is a potential approach to controlling soluble lead in drinking water.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Brometos , Iodetos , Ferro , Chumbo , Oxirredução , Água
19.
Food Chem ; 335: 127522, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739804

RESUMO

Effect of twin-screw extrusion on soluble dietary fiber (SDF) from sweet potato residues (SPRs) were investigated using optimized conditions, at screw speed of 180 rpm, feed rate at 17 Hz, feed moisture at 40% and extrusion temperature at 150 °C. Extruded SDF, showed higher SDF levels (9.63%-29.25%), cholesterol and sodiumcholate adsorption capacity, radical scavenging capacity, and inhibition of digestive enzymes. Moreover, extrusion effectively reduced particle size and molecularweight of SDF, modulated monosaccharide ratios, and increased water retention capacity (WRC), oil retention capacity (ORC), swelling capacity (SC) and glucose absorption capacity (GAC). Additionally, scanning electron microscopy (SEM) demonstrated decomposition of macromolecules of SDF to smaller fractions and formation of a porous morphology following extrusion. Furthermore, the extruded SDF increased thermal stability as determined by differential scanning calorimetry (DSC). Overall, the SDF from SPRs with improved functional and physiochemical properties could be used as a functional additive in diverse food products.


Assuntos
Fibras na Dieta/análise , Ipomoea batatas/química , Peso Molecular , Monossacarídeos/análise , Solubilidade , Temperatura
20.
Emerg Microbes Infect ; : 1-22, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296295

RESUMO

Hepatitis B e antigen (HBeAg) is a widely-used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg. Among these mAbs, a novel mAb 16D9, which recognizes the SKLCLG (aa -10 to -5) motif on the N-terminal residues of HBeAg that is absent on HBcAg, exhibited excellent detection sensitivity and specificity in pairing with another 14A7 mAb targeting the HBeAg C-terminus (STLPETTVVRRRGR, aa141 to 154). Based on these two mAbs, we developed a novel chemiluminescent HBeAg immunoassay (NTR-HBeAg). By using HBV cell culture samples and sera from patients with chronic HBV infection, we demonstrated the new assay could detect HBeAg derived from various HBV genotypes. In contrast to widely-used commercial assays, the NTR-HBeAg completely eliminated the cross-reactivity with secreted HBcAg from precore mutant (G1896A) virus in either cell culture or patient sera. The improved specificity of the NTR-HBeAg assay enables its applicability in cccDNA-targeting drug screening in cell culture systems, and also provides an accurate tool for clinical HBeAg detection. Trial registration: Netherlands National Trial Register identifier: NTR-..

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