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1.
Curr Opin Biotechnol ; 73: 240-245, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536659

RESUMO

Engineering microbes to produce value-added chemicals from C6/C5 sugars sometimes requires long biosynthetic pathways, which causes carbon loss due to involving multiple metabolic branch nodes, leading to a lower product yield. Using C2 feedstocks derived from gaseous, cellulosic, and plastic wastes could establish shorter biosynthetic pathways to produce some target chemicals, for example, acetyl-CoA-derived natural products. Utilizing these waste-derived feedstocks would also contribute to reducing the carbon footprint of the chemical industry. In this review, we highlighted the promising waste-processing technologies that could provide C2 feedstocks that are compatible with microbial fermentation. We also analyzed the recent metabolic engineering works in which the microorganisms/fermentation processes were modified/optimized to utilize acetate, ethanol, or ethylene glycol more efficiently.

2.
BMC Med Imaging ; 21(1): 133, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530768

RESUMO

BACKGROUND: To compare the changes in quantitative parameters and the size and degree of 18F-fluorodeoxyglucose ([18F]FDG) uptake of malignant tumor lesions between Bayesian penalized-likelihood (BPL) and non-BPL reconstruction algorithms. METHODS: Positron emission tomography/computed tomography images of 86 malignant tumor lesions were reconstructed using the algorithms of ordered subset expectation maximization (OSEM), OSEM + time of flight (TOF), OSEM + TOF + point spread function (PSF), and BPL. [18F]FDG parameters of maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and signal-to-background ratio (SBR) of these lesions were measured. Quantitative parameters between the different reconstruction algorithms were compared, and correlations between parameter variation and lesion size or the degree of [18F]FDG uptake were analyzed. RESULTS: After BPL reconstruction, SUVmax, SUVmean, and SBR were significantly increased, MTV was significantly decreased. The difference values of %ΔSUVmax, %ΔSUVmean, %ΔSBR, and the absolute value of %ΔMTV between BPL and OSEM + TOF were 40.00%, 38.50%, 33.60%, and 33.20%, respectively, which were significantly higher than those between BPL and OSEM + TOF + PSF. Similar results were observed in the comparison of OSEM and OSEM + TOF + PSF with BPL. The %ΔSUVmax, %ΔSUVmean, and %ΔSBR were all significantly negatively correlated with the size and degree of [18F]FDG uptake in the lesions, whereas significant positive correlations were observed for %ΔMTV and %ΔTLG. CONCLUSION: The BPL reconstruction algorithm significantly increased SUVmax, SUVmean, and SBR and decreased MTV of tumor lesions, especially in small or relatively hypometabolic lesions.

3.
Lancet Digit Health ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34538736

RESUMO

BACKGROUND: Inadequate bowel preparation is associated with a decrease in adenoma detection rate (ADR). A deep learning-based bowel preparation assessment system based on the Boston bowel preparation scale (BBPS) has been previously established to calculate the automatic BBPS (e-BBPS) score (ranging 0-20). The aims of this study were to investigate whether there was a statistically inverse relationship between the e-BBPS score and the ADR, and to determine the threshold of e-BBPS score for adequate bowel preparation in colonoscopy screening. METHODS: In this prospective, observational study, we trained and internally validated the e-BBPS system using retrospective colonoscopy images and videos from the Endoscopy Center of Wuhan University, annotated by endoscopists. We externally validated the system using colonoscopy images and videos from the First People's Hospital of Yichang and the Third Hospital of Wuhan. To prospectively validate the system, we recruited consecutive patients at Renmin Hospital of Wuhan University aged between 18 and 75 years undergoing colonoscopy. The exclusion criteria included: contraindication to colonoscopy, family polyposis syndrome, inflammatory bowel disease, history of surgery for colorectal or colorectal cancer, known or suspected bowel obstruction or perforation, patients who were pregnant or lactating, inability to receive caecal intubation, and lumen obstruction. We did colonoscopy procedures and collected withdrawal videos, which were reviewed and the e-BBPS system was applied to all colon segments. The primary outcome of this study was ADR, defined as the proportion of patients with one or more conventional adenomas detected during colonoscopy. We calculated the ADR of each e-BBPS score and did a correlation analysis using Spearman analysis. FINDINGS: From May 11 to Aug 10, 2020, 616 patients underwent screening colonoscopies, which evaluated. There was a significant inverse correlation between the e-BBPS score and ADR (Spearman's rank -0·976, p<0·010). The ADR for the e-BBPS scores 1-8 was 28·57%, 28·68%, 26·79%, 19·19%, 17·57%, 17·07%, 14·81%, and 0%, respectively. According to the 25% ADR standard for screening colonoscopy, an e-BBPS score of 3 was set as a threshold to guarantee an ADR of more than 25%, and so high-quality endoscopy. Patients with scores of more than 3 had a significantly lower ADR than those with a score of 3 or less (ADR 15·93% vs 28·03%, p<0·001, 95% CI 0·28-0·66, odds ratio 0·43). INTERPRETATION: The e-BBPS system has potential to provide a more objective and refined threshold for the quantification of adequate bowel preparation. FUNDING: Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision and Hubei Province Major Science and Technology Innovation Project.

4.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4103-4110, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467720

RESUMO

In this study, the colonization, diversity and relative abundance of arbuscular mycorrhizal fungi(AMF) in the roots of Panax quinquefolius in different habitats of Shandong province were analyzed by staining-microscopy and high-throughput sequencing. The data were analyzed by bioinformatics tools and statistical software. The results showed that the roots of P. quinquefolius in different habitats were colonized by AMF with different rates and intensities. The AMF in roots of P. quinquefolius belong to three genera, three families, three orders, one class and one phylum. At the level of order, the AMF mainly included Paraglomerales(52.48%), Glomerales(25.60%) and Archaeosporales(3.08%). At the level of family, the AMF were dominated by Paraglomeraceae(52.48%), Glomeraceae(18.94%) and Claroideoglomeraceae(3.05%). At the level of genus, Paraglomus(51.46%), Glomus(20.01%) and Claroideoglomus(3.52%) accounted for a large proportion, of which Paraglomus and Glomus were dominant. Cluster analysis showed that the AMF in roots of P. quinquefolius with close geographical locations could be clustered together. In this study, the diversity and dominant germplasm resources of AMF in roots of P. quinquefolius cultivated in the main producing areas were identified, which provi-ded basic data for revealing the quality formation mechanism of P. quinquefolius medicinal materials from the perspective of environment.


Assuntos
Glomeromycota , Micorrizas , Panax , Fungos , Humanos , Micorrizas/genética , Raízes de Plantas , Microbiologia do Solo
5.
Adv Food Nutr Res ; 98: 35-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507646

RESUMO

Polyphenols are a kind of complex secondary metabolites in nature, widely exist in the flowers, bark, roots, stems, leaves, and fruits of plants. Numerous studies have shown that plant-derived polyphenols have a variety of bioactivities due to their unique chemical structure, such as antioxidant, antimicrobial, and prevention of chronic diseases, cardiovascular disease, cancer, osteoporosis, and neurodegeneration. With the gradual rise of natural product development, plant polyphenols have gradually become one of the research hotspots in the field of food science due to their wide distribution in the plants, and the diversity of physiological functions. Owing to the extraordinary antioxidant and antibacterial activity of polyphenols, plant-derived polyphenols offer an alternative to chemical additives used in the food industry, such as oil, seafood, meat, beverages, and food package materials. Based on this, this chapter provides an overview of the potential antioxidant and antibacterial mechanisms of plant polyphenols and their application in food preservation, it would be providing a reference for the future development of polyphenols in the food industry.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34521298

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) is a major clinical challenge with no specific therapeutic drugs available. It is crucial to develop new agents to improve the clinical outcome of patients with DILI. In this study, we aimed to evaluate the efficacy and safety of Hugan tablets in patients with RUCAM based DILI using a nationwide database. RESEARCH DESIGN AND METHODS: We analyzed the clinical data of DILI patients from a nationwide DILI database (www.hepatox.org). Patients who received oral Hugan tablets for DILI were defined as the Hugan group, and those who received no treatment for DILI were defined as the control group. Propensity score matching was performed to compare the normalization of alanine aminotransferase (ALT) levels of the two groups. RESULTS: There were 111 cases in the Hugan group and 512 cases in the control group that met the inclusion criteria. One-to-one propensity score matching created 111 matched pairs. ALT normalization rate and aspartate aminotransferase (AST) normalization rate in the Hugan group were significantly higher than those in the control group (50.45% vs. 26.13%, p≤.0002 and 67.57% vs. 41.75%, p≤.0001). There were no differences in the incidence of renal function impairment or blood abnormality between the two groups. CONCLUSIONS: Hugan tablets are safe and effective in DILI treatment. Large-scale randomized controlled studies are needed to explore the effects of Hugan tablets on DILI induced by different offending drugs.

7.
Chemosphere ; 287(Pt 1): 132074, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34474384

RESUMO

Refractory organic pollutant effluent has led to severe water pollution. In this study, magnetic Co-N-doped carbon hybrid catalysts (Co-NC-x) were fabricated using a facile cation exchange combined pyrolysis and self-reduction technique to activate peroxymonosulfate (PMS) for rehabilitation of the water environment. Factors affecting the catalytic activity of the Co-NC-850 were comprehensively examined. 100% of RhB degradation efficiency within 20 min was achieved in the Co-NC-850/PMS system at the optimum conditions (C0 = 80 mg L-1, catalyst loading 0.025 g L-1, PMS concentration 0.8 mM, native pH and 25 °C). The electron paramagnetic resonance measurements and competitive quenching tests demonstrated that a sulfate radical (SO4•-) and singlet oxygen (1O2) account for RhB degradation in the Co-NC-850/PMS system, and 1O2 contributed ~86.2% to RhB removal. The synergistic effect of Co0 nanoparticles (NPs) and NC on Co-NC-850 might induce a predominant non-radical route to trigger PMS activation for RhB degradation. Direct oxidation of O2•- by a hydroxyl radical (•OH) might be the crucial process for forming 1O2. Magnetic response and successive cycles verified that Co-NC-850 has superior separable performance and reusability. This innovative magnetic Co-NC-850 hybrid catalyst for PMS activation delivered vast potential for disintegration of refractory organic contaminants.

8.
Neural Plast ; 2021: 9960304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484327

RESUMO

Background: Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer's disease (AD). Amyloid-ß (Aß) is the key factor that triggers the course of AD, and reducing the deposition of Aß in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aß clearance. Objective: The purpose of this study was to explore whether EA modifies the accumulation of Aß through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods: Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aß accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results: This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aß accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion: EA treatment might reduce Aß accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

9.
Nature ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488225

RESUMO

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine effectiveness against B.1.617.2 relative to non- B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

10.
Chemosphere ; 287(Pt 1): 132082, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34523456

RESUMO

Knowledge is insufficient on feasible remediation techniques to agricultural soils contaminated by multiple heavy metal(loid)s with elevated concentrations and extreme acidy from acid mine drainages (AMD). We aimed to elucidate the effect of integrated biochar (BC) and soil replacement on improving the mining soil properties and then alleviating the phytotoxicity of As, Pb, Cd, Cu, and Zn on radish (Raphanus sativus L.)-soya bean (Glycine max Merr.) -amaranth (Amaranthus tricolor L.) rotation and the potential risk of crops to human health. Biochar and soil replacement showed outstanding effects on improving soil properties by increasing soil pH values, reducing available metal(loid)s, and enhancing the activity of catalase, urease and acid phosphatase. Also, the integrated technique regulated the physiological disorders of crops caused by metal(loid)s, specifically increasing chlorophyll content and reducing malondialdehyde (MDA) in the three crops, and reducing the content of metal(loid)s in edible parts of plants. The combination of biochar and soil replacement exhibited better remediation effect than the single application of biochar or soil replacement, which played different roles in remediating mining farmland. Biochar exhibited efficacy in soil pH amelioration, metal stabilization and soil enzyme activity enhancement, while soil replacement alleviated metal(loid)s stress through the dilution effect. Among the 8 treatments, only biochar combined with 35% (S35BC) and 50% (S50BC) of replaced soil could achieve the safe production of the three crops under the three-season crop rotation.

11.
Int J Med Sci ; 18(15): 3516-3525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522178

RESUMO

PLK1 inhibitors were shown, in vitro and in vivo, to possess inhibitory activities against non-small cell lung cancer (NSCLC), and such inhibition has been proven by clinical trials. However, it remains unclear whether and how the immune microenvironment is associated with the action. In this study, we found that inhibiting PLK1 could alter the tumor immune microenvironment by increasing DC maturation, and enriching T cells infiltration. PLK1 inhibitors, serving as immunogenic cell death (ICD) inducers, indirectly activated DCs, instead of directly acting on DC cells, through the surface expression of costimulatory molecules on and enhanced phagocytosis by DCs. Furthermore, upon targeting PLK1, tumor cells that had undergone ICD were converted into an endogenous vaccine, which triggered the immune memory responses and protected the mice from tumor challenge. Collectively, these results suggested that the PLK1 inhibitor might function as an immune modulator in antitumor treatment.

12.
J Microbiol Biotechnol ; 31(1)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34528912

RESUMO

Hsa_circ_0001947 is associated with multiple cancers, but its function in non-small cell lung cancer (NSCLC) is ambiguous and needs further research. The targeting relationship among circ_0001947, miR-661, and downstream of tyrosine kinase 7 (DOK7) was predicted by database and further verified by dual-luciferase reporter assay, while their expressions in cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, cell biological behaviors and expressions of miRNAs, miR-661 and DOK7 were determined by cell function experiments and qRT-PCR, respectively. Circ_0001947 was low-expressed in NSCLC tissues and cells. Circ_0001947 knockdown intensified cell viability and proliferation, induced cell cycle arrest at S phase, suppressed apoptosis and evidently enhanced miR-510, miR-587, miR-661 and miR-942 levels, while circ_0001947 overexpression did the opposite. MiR-661 was a target gene of circ_0001947 that participated in the regulation of circ_0001947 on cell biological behaviors. Furthermore, DOK7, the target gene of miR-661, partly participated in the regulation of miR-661 on cell viability. Hsa_circ_0001947 acts as a sponge of miR-661 to repress NSCLC development by elevating the expression of DOK7.

13.
Cell Cycle ; : 1-14, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494933

RESUMO

Intervertebral disc degeneration (IDD) is one of the main causes of lower back pain (LBP). It results from an imbalance between the degradation and synthesis of extracellular matrix (ECM) components in nucleus pulposus (NP) cells. Atorvastatin, an HMG-CoA reductase inhibitor, plays a vital role in many diseases, such as cardiovascular disease and osteoarthritis. However, the effect of atorvastatin on IDD is unclear. Herein, we demonstrated that atorvastatin affects matrix degradation induced by TNF-α and demonstrated the mechanism by which TNF-α modulates matrix metabolism in rat NP cells. Real-time PCR, western blotting and immunofluorescence staining were performed to detect the mRNA and protein expression of related genes. mRFP-GFP-LC3 adenovirus plasmid transfection and transmission electron microscopy (TEM) were used to detect cell autophagy. NLRP3 inhibitor and lentiviral vectors containing shRNA-NLRP3 were used to show the effect of NLRP3 on autophagic flux and the NF-κB signaling pathway. The results revealed that atorvastatin might suppress matrix degradation induced by TNF-α by suppressing NLRP3 inflammasome activity and inducing autophagic flux. Moreover, atorvastatin suppressed NF-κB signaling induced by TNF-α. NF-κB signaling inhibition suppressed NLRP3 inflammasome activity, and NLRP3 inhibition suppressed NF-κB signaling activation induced by TNF-α. NLRP3 inhibition or NLRP3 knockdown induced autophagic flux in the presence of TNF-α. Overall, the present study demonstrated that atorvastatin might suppress matrix degradation induced by TNF-α and further revealed the crosstalk among NLRP3 inflammasome activity, autophagy and NF-κB signaling.

14.
IEEE Trans Image Process ; 30: 7663-7676, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473625

RESUMO

In this paper, we propose an attention pyramid method for person re-identification. Unlike conventional attention-based methods which only learn a global attention map, our attention pyramid exploits the attention regions in a multi-scale manner because human attention varies with different scales. Our attention pyramid imitates the process of human visual perception which tends to notice the foreground person over the cluttered background, and further focus on the specific color of the shirt with close observation. Specifically, we describe our attention pyramid by a "split-attend-merge-stack" principle. We first split the features into multiple local parts and learn the corresponding attentions. Then, we merge local attentions and stack these merged attentions with the residual connection as an attention pyramid. The proposed attention pyramid is a lightweight plug-and-play module that can be applied to off-the-shelf models. We implement our attention pyramid method in two different attention mechanisms including: channel-wise attention and spatial attention. We evaluate our method on four large-scale person re-identification benchmarks including Market-1501, DukeMTMC, CUHK03, and MSMT17. Experimental results demonstrate the superiority of our method, which outperforms the state-of-the-art methods by a large margin with limited computationa cost. Code is available at https://github.com/CHENGY12/APNet.

15.
J Hazard Mater ; 423(Pt B): 127167, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34536843

RESUMO

Although there is growing evidence that micropollutants can be microbially converted in rapid sand filters of drinking water treatment plants (DWTPs), little is known about the biotransformation pathways and associated microbial strains in this process. Here, we constructed sand filter columns filled with manganese or quartz sand obtained from full-scale DWTPs to explore the biotransformation of eight micropollutants. Under seven different empty bed contact times (EBCTs), the column experiments showed that caffeine and atenolol were easily removed (up to 92.1% and 97.6%, respectively) with adsorption and microbial biotransformation of the filters. In contrast, the removal of other six micropollutants (i.e., naproxen, carbamazepine, atrazine, trimethoprim, sulfamethoxazole, and sulfadiazine) in the filters were less than 27.1% at shorter EBCTs, but significantly increased at EBCT = 4 h, indicating the dominant role of microbial biotransformation in these micropollutants removal. Integrated analysis of metagenomic reads and transformation products of micropollutants showed a shift in caffeine oxidation and demethylation pathways at different EBCTs, simultaneous occurrence of atrazine hydrolysis and oxidation pathways, and sulfadiazine and sulfamethoxazole oxidation in the filters. Furthermore, using genome-centric analysis, we observed previously unidentified degrading strains, e.g., Piscinibacter, Hydrogenophaga, and Rubrivivax for caffeine transformation, and Methylophilus and Methyloversatilis for atenolol transformation.

16.
Ecotoxicol Environ Saf ; 225: 112719, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478976

RESUMO

Dissipation of imidacloprid (IMI) and its metabolites (urea, olefin, 5-hydroxy, guanidine, 6-chloronicotinic acid) in Chinese prickly ash (CPA) was investigated using QuEChERS combined with UPLC-MS/MS. Good linearity (r2 ≥0.9963), accuracy (recoveries of 71.8-104.3%), precision (relative standard deviations of 0.9-9.4%), and sensitivity (limit of quantification ≤0.05 mg kg-1) were obtained. After application of IMI at dosage of 467 mg a.i. L-1 for three times with interval of 7 d, the dissipation dynamics of IMI in CPA followed first-order kinetics, with half-life of 6.48-7.29 d. IMI was the main compound in CPA, followed by urea and guanidine with small amounts of olefin, 5-hydroxy, and 6-chloronicotinic acid. The terminal residues of total IMI and its metabolites at PHI of 14-21 d were 0.16-7.80 mg kg-1 in fresh CPA and 0.41-10.44 mg kg-1 in dried CPA, with the median processing factor of 3.62. Risk assessment showed the acute (RQa) and chronic dietary risk quotients (RQc) of IMI in CPA were 0.020-0.083% and 0.052-0.334%, respectively. Based on the dietary structures of different genders and ages of Chinese people, the whole dietary risk assessment indicated that RQc was less than 100% for the general population except for 2- to 7-year-old children (RQc of 109.9%), implying the long-term risks of IMI were acceptable to common consumers except for children.

17.
Blood ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482400

RESUMO

Post-transcriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among post-transcriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site (PAS) usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in acute myeloid leukemia (AML) patients by performing 3' Region Extraction And Deep Sequencing (3'READS) on a subset of AML patient samples along with healthy hematopoietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3' untranslated region (UTR) shortening and coding sequence (CDS) lengthening due to differences in PAS usage. Among APA regulators, expression of FIP1L1, one of the core cleavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS dataset. Targeting global APA by FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mTORC1 signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block of AML patients.

18.
Biomed Phys Eng Express ; 7(6)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34500439

RESUMO

Melanoma is one of the most aggressive skin cancers. However, there remain many limitations in the current clinical treatments of it. Zinc oxide nanoparticles (ZnO NPs) have been considered to be a promising antitumor drug due to their excellent biocompatibility, biodegradability and biofunctionality. In this study, we prepared spherical ZnO NPs with an average diameter of less than 10 nm by a simple chemical method. According to thein vitrocytotoxicity assay, ZnO NPs in a certain concentration range (20-35µg ml-1) showed significant cytotoxicity to B16F10 melanoma cells, while having little effect on the viability of 3T3L1 fibroblasts. When cultured with B16F10 melanoma cells, ZnO NPs induced the generation of reactive oxygen and mitochondrial superoxide through the release of Zn2+, leading to oxidative stress in the cells, further reducing the mitochondrial membrane potential and decreasing the number of mitochondrial cristae. Furthermore, damaged mitochondria induced the release of apoptosis factors to promote cell apoptosis. FITC-Annexin V/propidium iodide double staining assay was used to analyze different apoptosis stages of B16F10 cells induced by ZnO NPs. A polymer hydrogel (Gel-F127-ZnO NPs) with Pluronic F127 as the carrier of ZnO NPs was fabricated for evaluating the antitumor effect of ZnO NPsin vivo. Thein vivoexperiment indicated that the tumor recurrence was significantly inhibited in tumor-bearing mice after treated with Gel-F127-ZnO NPs. Conclusively, ZnO NPs showed a strong antitumor effect bothin vitroandin vivo.

19.
Cell Immunol ; 368: 104419, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34371260

RESUMO

Rheumatoid arthritis (RA) is a complicated rheumatic autoimmune disease. Lectin, galactoside-binding soluble, 2 (LGALS2), LGALS3 and LGALS9, three members of the galectin family, play potential roles in autoimmune diseases, including RA. However, association of genetic polymorphisms of LGALS2, LGALS3 and LGALS9 with RA risk in a Southern Chinese Han population has not been elucidated. A case-control study was conducted herein, including 500 RA patients and 650 healthy individuals of Southern Chinese Han origin. Twelve single nucleotide polymorphisms (SNPs), including rs7291467 for the LGALS2 gene, rs4644, rs4652, rs1009977, rs2274273 and rs17128183 for the LGALS3 gene, and rs4795835, rs3763959, rs4239242, rs3751093, rs732222 and rs4794976 for the LGALS9 gene, were genotyped. Polymorphisms were genotyped using the KASP method. Frequencies of rs1009977 genotype TG and rs3751093 genotype GA of LGALS3 gene were significantly different between RA patients and healthy controls (P = 0.049, P = 0.033). Allele T and genotypes TT and TT + TG of rs4794976 for LGALS9 gene were significantly correlated with RA risk (P = 0.017, P = 0.012, P = 0.041). Subgroup analysis revealed that rs1009977, rs2274273 and rs17128183 polymorphisms of LGALS3 gene and rs4795835 polymorphism of LGALS9 gene were correlated with several RA clinical manifestations (all P < 0.05). In addition, haplotype GCGTT showed an increased risk for RA (OR = 1.216, 95% CI: 1.028-1.438, P = 0.023), whereas haplotype GCGTG showed a reduced risk for RA susceptibility (OR = 0.779, 95% CI: 0.625-0.971, P = 0.026). In conclusion, LGALS3 and LGALS9 gene polymorphisms may associate with RA predisposition in a Southern Chinese Han population.

20.
Nutr Metab Cardiovasc Dis ; 31(10): 2756-2765, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34348878

RESUMO

AIM: Increasing evidence supports the hypothesis that high serum uric acid (SUA) levels are related to atrial fibrillation (AF). However, the incidence of AF in patients with hyperuricemia and SUA levels in different types of AF is not entirely clear. This meta-analysis was designed to evaluate the relationship between SUA and incidence of AF, and the variation in SUA levels in different types of AF. DATA SYNTHESIS: Relevant reports were searched for in Embase, PubMed and the Cochrane Library. A fixed-effects model combining relative risk (RR) and the corresponding 95% confidence interval (95% CI) was used to evaluate the correlation between SUA and AF. The standardized mean differences (SMDs) of SUA values were calculated using a random-effects model to evaluate the differences in SUA levels among different types of AF. A total of 31 studies with 504,958 participants were included in this research. The results from 8 cohort studies showed that high SUA levels significantly increased the incidence of AF [RR (95% CI): 1.92 (1.68-2.20); P < 0.01]. The results from 29 studies revealed that SUA levels elevated in patients with AF [SMD (95% CI): 0.55 (0.43-0.66); P < 0.001]. Meanwhile, SUA levels in new-onset AF [SMD (95%CI): 0.24 (0.10-0.38); P = 0.001], paroxysmal AF [SMD (95%CI): 0.52 (0.33-0.72); P < 0.001] and persistent AF [SMD (95%CI): 1.23 (0.98-1.48); P < 0.001] were significantly higher than that in patients without AF. CONCLUSIONS: High SUA levels had an obvious correlation with the occurrence rate of AF. In addition, SUA levels were significantly different among patients with new-onset, paroxysmal and persistent AF.

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