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1.
J Colloid Interface Sci ; 581(Pt A): 31-43, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768733

RESUMO

The use of nanoscale metal-organic frameworks (MOFs) as drug delivery vehicles has attracted considerable attention in tumor therapy. In this study, novel biocompatible MOF-based nanocarriers were used as part of a facile and reproducible strategy for precision cancer theranostics. Both diagnostic (Mn2+) and therapeutic compounds (doxorubicin, DOX) were incorporated into the multifunctional MOF-based nanocarriers, which exhibited high colloidal stability and promoted T1-weighted proton relaxivity and low-pH-activated drug release. The obtained MOF-based nanocarriers exhibited significantly high cellular uptake and efficient intracellular drug delivery into cancer cells, which resulted in high apoptosis and cytotoxicity, in addition to effectively inhibiting the migration of 4T1 breast cancer cells. Moreover, the MOF-based nanocarriers could intensively deliver diagnostic and therapeutic agents to tumors to enable precise visualization of the nanocarrier accumulation and accurate tumor positioning, diagnosis, and imaging-guided therapy using magnetic resonance imaging (MRI). In addition, the functional MOF-based nanocarriers exhibited effective ablation of the primary breast cancer, as well as significant inhibition of lung metastasis with a high survival rate. Therefore, the developed nanocarriers represent a viable platform for cancer theranostics.

2.
Eur Radiol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180166

RESUMO

OBJECTIVE: To determine whether a radiomics signature (rad-score) outperforms ADC in TSR estimation by developing a radiomics biomarker for preoperative TSR diagnosis in rectal cancer. METHODS: This study included 149 patients (119 and 30 in the training and validation cohorts, respectively). All patients underwent T2-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. A rad-score was generated using the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate logistic regression. Meanwhile, the mean ADCs were calculated from ADC maps. For both the mean ADC and rad-score, binary logistic regression and Spearman correlation coefficients were used to determine associations with the TSR, and the area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance. The reliability of the rad-score was quantified by comparing the imaging-estimated TSR with the actual TSR of each patient. RESULTS: Both the mean ADC and rad-score were positively correlated with the TSR in the training cohort (mean ADC: p < 0.001, r = 0.566; rad-score: p < 0.001, r = 0.559) and validation cohort (mean ADC: p < 0.001, r = 0.671; rad-score: p = 0.002, r = 0.536). The rad-score, with AUCs of 0.917 (95% CI 0.869-0.965) and 0.787 (95% CI 0.602-0.972) in the training and validation cohorts, respectively, outperformed the mean ADC (training cohort: AUC = 0.776, 95% CI 0.693-0.859; validation cohort: AUC = 0.764, 95% CI 0.592-0.936) in TSR estimation. CONCLUSION: The ADC possesses potential diagnostic value for TSR estimation in rectal cancer, and the rad-score shows increased diagnostic value over the ADC and may be a promising supplemental tool for patient stratification and informing decision-making. KEY POINTS: • Tumor-stroma ratio has been verified as an independent prognostic factor for various solid tumors including rectal cancer. • The ADC and multiparametric MRI-based radiomics features were significantly and positively correlated with the tumor-stroma ratio in rectal cancer. • The radiomics signature outperformed the ADC in discriminating TSR in rectal cancer.

3.
Sci Total Environ ; : 143233, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33158535

RESUMO

The marine ecosystems of the marginal seas of the Western Pacific region are frequently disturbed by terrigenous materials. It is of great significance to investigate the ecological functioning of these marine areas, which can be well understood by exploring the microbial communities of sediments. However, the geographical distribution, composition, and genetic functions of sedimentary bacterial communities of the Yellow Sea and East China Sea (YEC Seas) are poorly understood. In this work, sediment samples were collected from YEC Sea areas to investigate bacterial communities by high-throughput sequencing. A total of 1960 genera were determined, with Proteobacteria being the dominant phylum (45.03%), followed by Planctomycetes, Bacteroidetes, Acidobacteria, and Chloroflexi. Correlation analysis indicates that the bacterial composition is influenced by environmental factors, including pressure, depth, seawater density, salinity, organic matter content, nutrient, and heavy metal. Approximately 178 metabolism pathways annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were detected in the bacterial communities, including ones for nutrient metabolism (C, 3.04%; S, 0.70%; N, 0.52%; and P, 0.22%) and exogenous pollutant metabolism (e.g., polycyclic aromatic hydrocarbons (PAHs), chlorobenzene, and benzoate; up to 4.97%). The results demonstrate that the abundant bacterial communities in the sediments of the YEC Seas are important for maintaining marine ecological functioning, especially for elemental biogeochemical cycling and exogenous pollutant transformation.

4.
Biomed Res Int ; 2020: 4031015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204694

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in-house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.

5.
J Mol Med (Berl) ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206213

RESUMO

There was an error in Fig. 6A during the proofing stage which has since been corrected. The corrected figure is presented in this paper.

6.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33231560

RESUMO

Inhalation anesthetics have been demonstrated to have protective effects against myocardial ischemia reperfusion injury (MIRI). O-linked GlcNAcylation (O-GlcNAc) modifications have been shown to protect against MIRI. This study aimed to investigate whether O-GlcNAcylation and necroptosis signaling were important for sevoflurane postconditioning (SPC) induced cardioprotective effects. Apart from rats in the SHAM and sevoflurane (SEVO) group, rats underwent 30 min ischemia followed by 2 h reperfusion. Cardiac hemodynamics and function were determined. In addition, myocardial infarction size, cardiac function parameters, myocardial lactic dehydrogenase (LDH) content, myocardium histopathological changes, necrotic myocardium, O-GlcNAcylation, and protein expression levels of necroptosis biomarkers were measured, together with co-immunoprecipitation experiments using proteins associated with the necroptosis pathway and O-GlcNAcylation. SPC reduced myocardial infarction size, ameliorated cardiac function, restored hemodynamic performance, improved histopathological changes, and reduced receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like (MLKL) mediated necroptosis. In addition, SPC up-regulated O-GlcNAc transferase (OGT) mediated O-GlcNAcylation, increased O-GlcNAcylated RIPK3, and inhibited the association of RIPK3 and MLKL. However, OSMI-1, an OGT inhibitor, abolished SPC mediated cardioprotective effects and inhibited OGT mediated up-regulation of O-GlcNAcylation and down-regulation of RIPK3 and MLKL proteins induced by SPC. Our study demonstrated that SPC restrained MIRI induced necroptosis via regulating OGT mediated O-GlcNAcylation of RIPK3 and lessening the formulation of RIPK3/MLKL complex.

7.
J Hazard Mater ; : 124312, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33144003

RESUMO

Microplastics have attracted extensive attention regarding their role in the cycling of organic pollutants in aquatic environments. However, the influence of microplastics on the sorption of organic pollutants in soil is unclear. Herein, we investigated the sorption of polar diazepam and nonpolar phenanthrene to two soils (Inceptisol and Oxisol). Batch sorption experiments were used to evaluate the effect of polyethylene (PE), polypropylene (PP), and polystyrene (PS) microplastics at addition rates of 0.1%, 1%, and 10% (w/w). The addition of microplastics significantly decreased the overall sorption of diazepam at 10%, and increased the sorption of phenanthrene at 1%, while the effects were negligible at other addition rates. Decreased sorption of diazepam was attributed to its lower sorption affinity to microplastics than to soil. Microplastics, even at 0.1%, substantially decreased the relative distribution of phenanthrene in soil, particularly for PE in the Oxisol with lower foc. The sorption affinity of phenanthrene followed the order PE > soil organic carbon (SOC) > PP > PS, suggesting that PE can be a significant sink of phenanthrene in contaminated soils. Overall, microplastics can change the sorption of diazepam and phenanthrene to soil and therefore affect their mobility and environmental risk in soil ecosystems.

8.
Cancer Sci ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058325

RESUMO

Although anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has achieved great success in some cancers, most colorectal cancer (CRC) patients remain unresponsive. Therefore, further clarification of the underlying mechanisms is needed to improve the therapy. In this study, we explored the distinct functions of different PD-L1 alternative splicing isoforms in CRC. We investigated the biological functions in PD-L1 knocked down/knockout cells, which were verified through overexpression of PD-L1 isoforms a, b, and c. The roles of PD-L1 isoforms in immune surveillance resistance was also analyzed. Meanwhile, we performed RNA-seq to screen the downstream molecules regulated by PD-L1 isoforms. Finally, we detected PD-L1 and PD-L1 isoforms levels in a cohort of serum samples, two cohorts of CRC tissue samples, and analyzed the correlation of PD-L1 isoforms with PD-1 blockade therapy response in two clinical CRC cases. The results indicated that PD-L1 knockout inhibited proliferation, migration, and invasion, and isoform b exerted a more significant inhibitory effect on T cells than the other two isoforms. Moreover, isoform c could promote CRC progression through regulating epithelial-mesenchymal transition. Clinical data showed that CRC patients with positive PD-L1 expression were associated with poorer overall survival. High serum PD-L1 level was associated with poor prognosis. The level of isoform b or c was negatively associated with prognosis, and a higher level of isoform b was associated with a good response to anti-PD-1 therapy. In conclusion, isoform b should be considered as a biomarker for clinical responsiveness to anti-PD-1/PD-L1 immunotherapy; isoform c had a prometastatic role and is a new potential target for CRC therapy.

9.
Insect Sci ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089948

RESUMO

In insects, 20-hydroxyecdysone (20E) limits systemic growth by triggering developmental transitions. Previous studies have shown that 20E-induced let-7 exhibits crosstalk with the cell cycle. Here, we examined the underlying molecular mechanisms and physiological functions of 20E-induced let-7 in the fat body, an organ for energy storage and nutrient mobilization which plays a critical role in the larval growth. First, the overexpression of let-7 decreased the body size and led to the reduction of both nucleolus and cell sizes in the larval fat body. In contrast, the overexpression of let-7-Sponge increased the nucleolus and cell sizes. Moreover, we found that cdc7, encoding a conserved protein kinase that controls the endocycle, is a target of let-7. Notably, the mutation of cdc7 in the fat body resulted in growth defects. Overall, our findings revealed a novel role of let-7 in the control of endoreduplication-related growth during larval-prepupal transition in Drosophila.

10.
Ann Rheum Dis ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998865

RESUMO

OBJECTIVES: Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA. METHODS: For a proof-of-concept study, four citrullinated peptide epitopes derived from citrullinated autoantigens, namely, citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen and tenascin-C, and a cyclocitrulline peptide-1 were selected as ligands for targeting autoreactive B cells; Engineered T cells expressing a fixed anti-FITC CAR were constructed and applied as a universal CAR-T cell system to specifically eliminate these protein-specific autoreactive B cells via recognition of the aforementioned FITC-labelled autoantigenic peptide epitopes. RESULTS: We demonstrated that anti-FITC CAR-T cells could be specifically redirected and kill hybridoma cells generated by immunisation with antigenic peptides, and autoreactive B cell subsets from RA patients via recognition of corresponding FITC-labelled citrullinated peptide epitopes. Additionally, the cytotoxicity of the CAR-T cells was dependent on the presence of the peptides and occurred in a dose-dependent manner. CONCLUSIONS: The approach described here provides a direction for precise, customised approaches to treat RA and can likely be applied to other systemic autoimmune diseases.

11.
Biol Trace Elem Res ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015744

RESUMO

The article High-Dose Aluminum Exposure Further Alerts Immune Phenotype in Aplastic Anemia Patients, written by Yao Zuo, Xiang Lu, Xiaochao Wang, Suren R. Sooranna, Liju Tao, Shiqiang Chen, Hongwen Li, Dan Huang, Guanye Nai, Hong Chen, Chunfeng Pan, Caihong Huang and Yanmin Pang.

12.
BMJ Open ; 10(10): e032833, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046460

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60-72 months. DESIGN: Cross-sectional. PARTICIPANTS: 1342 children with complete data on the questionnaire, stereoacuity and refraction were included. RESULTS: The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis. CONCLUSION: Later-borns had poorer stereoacuity than first-borns.

13.
Int J Biol Sci ; 16(15): 2868-2882, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061802

RESUMO

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.

14.
J Clin Invest ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108353

RESUMO

Small extracellular vesicles (SEVs) are functional messengers of certain cellular niches to permit non-contact cell communications. Whether niche-specific SEVs fulfill this role in cancer is unclear. Here, we used seven cell-type specific mouse Cre lines to conditionally knockout Vps33b in Cdh5+ or Tie2+ endothelial cells (ECs), Lepr+ bone marrow perivascular cells, Osx+ osteo-progenitor cells (OPCs), Pf4+ megakaryocytes and Tcf21+ spleen stromal cells. We then examined the effects of reduced SEV secretion on progression of MLL-AF9 induced acute myeloid leukemia (AML) as well as normal hematopoiesis. Blocking SEV secretion from ECs, but not perivascular cells, megakaryocytes or spleen stromal cells, markedly delayed the leukemia progression. Notably, reducing SEV production from ECs had no effect on normal hematopoiesis. Protein analysis showed that EC-derived SEVs contained a high level of ANGPTL2, which accelerated leukemia progression via binding to LILRB2 receptor. Moreover, ANGPTL2-SEVs released from ECs were governed by VPS33B. Importantly, ANGPTL2-SEVs were also required for primary human AML cell maintenance. These findings demonstrate a role of niche-specific SEVs in cancer development and suggest that targeting ANGPTL2-SEVs from ECs might be a potential strategy to interfere certain types of AML.

15.
Immunol Rev ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037700

RESUMO

Unique Vγ2Vδ2 (Vγ9Vδ2) T cells existing only in human and non-human primates, account for the majority of circulating γδ T cells in human adults. Vγ2Vδ2 T cells are the sole γδ T-cell subpopulation capable of recognizing the microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by selected pathogens during infections. Recent seminal studies in non-human primate models have demonstrated that the unique HMBPP-specific Vγ2Vδ2 T cells are fast-acting, multi-functional, and protective during infections. This article reviews the recent seminal observations of Vγ2Vδ2 T cells in protective mechanisms against tuberculosis and other infections.

16.
Brain Behav ; 10(11): e01818, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869541

RESUMO

OBJECTIVE: As a result of the pandemic of COVID-19, the public have been experiencing psychological distress. However, the prevalence of psychological distress during the COVID-19 pandemic remains unknown. Our objective was to evaluate the prevalence of psychological distress during COVID-19 outbreak and their risk factors, especially their internal paths and causality. METHODS: A nationwide cross-sectional survey of the prevalence of mental disorders was conducted. We used Hospital Anxiety and Depression Scale (HADS) to estimate the prevalence of anxiety and depression. The internal paths and the causality of the psychological health were analyzed using a structural equation modeling (SEM) approach. RESULTS: A total of 24,789 respondents completed the survey. We found that the overall prevalence of anxiety, depression, combination of anxiety, and depression were 51.6% (95% CI: 51.0-52.2), 47.5% (95% CI: 46.9-48.1), and 24.5% (95% CI: 24.0-25.0), respectively. The risk of psychological disorders in men was higher than that in women. The status of psychological health was different across different age groups, education levels, occupations, and income levels. The SEM analysis revealed that inadequate material supplies, low income, low education, lack of knowledge or confidence of the epidemic, and lack of exercise are major risk factors for psychological distress. CONCLUSIONS: The evidence from this survey poses serious challenges related to the high prevalence of psychological distress, but also offers strategies to deal with the mental health problems caused by the COVID-19 pandemic.

17.
Gastroenterol Hepatol ; 43(9): 526-536, 2020 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32921478

RESUMO

OBJECTIVE: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. METHODS: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. RESULTS: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. CONCLUSIONS: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients.

18.
Med Ultrason ; 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32905565

RESUMO

The aim of this study is to investigate whether the use of contrast enhanced ultrasound (CEUS) can improve the differential diagnostic performance between hepatic inflammatory pseudotumor (HIPT) and other malignant tumors. MATERIAL AND METHODS: Forty-four patients with histological proven HIPTs were included in this retrospective study. The features of conventional ultrasound (US) and CEUS were evaluated. RESULTS: Three kinds of enhanced pattern can be seen in the 44 nodules including homogeneous (n=18, 41%), heterogeneous (n=16, 36%) and rim-like enhancement (n=10, 23%). All of the nodules showed hypo-enhancement during the portal and delayed phase. The dominant nodules (n=29, 66%) presented wash-out within 60 s after contrast injection. Quick wash-in and wash-out was seen in 18 nodules (41%). Eighteen nodules (41%) were correctly diagnosed as HIPT, whereas the remaining 26 cases were misdiagnosed as malignancies (n=20, 45%) or with an uncertain diagnosis (n=6, 14%). CONCLUSION: CEUS was not enough to differentiate HIPT from hepatic malignancies, especially intrahepatic cholangiocarcinoma and liver metastasis. However, some CEUS imaging characteristics may be helpful for HIPT diagnosis.

19.
Gastroenterology ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920015

RESUMO

BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. METHODS: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by ß-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. RESULTS: Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. ß-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and ß-galactosidase activity assay. ß-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional ß-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via ß-galactosidase. ß-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathways kinases, which partially mediated the anticancer effects of S thermophilus. CONCLUSION: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of ß-galactosidase.

20.
BMC Complement Med Ther ; 20(1): 276, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917204

RESUMO

BACKGROUND: In this study, Malus doumeri leaf flavonoids (MDLF) were used as the research object to observe their in vitro antioxidant stress ability. Hydrogen peroxide (H2O2) was used to induce oxidative stress in 293 T cells. METHODS: MTT, flow cytometry, and qPCR were used to verify the effect of MDLF. RESULTS: In vitro cell experiments showed that at a concentration of 0-160 µg/mL, MDLF did not affect the normal proliferation of human embryonic kidney 293 T cells (HEK 293 T cells), and MDLF had no cytotoxic effect in this concentration range. It was found that MDLF could maintain the survival of HEK 293 T cells (82.6%) at a high concentration (160 µg/mL). Morphological observation also found that MDLF can inhibit the cell structure imperfection caused by H2O2. It was also observed that MDLF could significantly increase the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and reduce the level of malondialdehyde (MDA). The results of quantitative polymerase chain reaction (qPCR) showed that MDLF could significantly up-regulate the mRNA expression levels of CAT, SOD, GSH, GSH-Px, B-cell lymphoma-2 (Bcl-2) and downregulate the expression levels of B-cell lymphoma-2 associated x protein (Bax), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) in oxidative stress-injured cells. The HPLC analysis showed that MDLF contained hyperin, isoquercetin, quercitrin, hesperidin, myricetin, baicalin and quercetin. CONCLUSION: From the experimental results, it was observed that MDLF has a strong anti-oxidation ability in vitro, and it can interfere with the oxidative stress damage caused by H2O2 in 293 T cells. Therefore, MDLF is a type of natural substance with good anti-oxidant effect, and it has the potential to interfere with many diseases.

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