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1.
Chin Med J (Engl) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32049747

RESUMO

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

2.
Bioresour Technol ; 302: 122742, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32007856

RESUMO

Recycling of biogas residues from corn stover anaerobic digestion is crucial for the development of biogas industry. Full-scale composting process is the feasible way to convert biogas residues to fertilizer. The aim of the study was to explore the feasibility of full-scale composting process to dispose biogas residue to fertilizer, and to evaluate the quality of the compost. The results showed the biogas residues could rapidly reach the thermophilic stage and last at least 20 days, NH4+-N, TOC and C/N decreased along with the composting process, while TP, TK and NO3--N showed an opposite trend. Germination index(GI) and seedling growth index showed that raw biogas residues was toxic for plant, but the GI and seedling growth index were increased during the composting process, except for the cooling stage sample. Anaerolineaceae and Limnochordaceae were the main bacteria involved in the composting process, and Chaetomium was the most important fungus.

3.
Orthop Surg ; 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064763

RESUMO

OBJECTIVE: To study the role of primary cilia formation disorder and osteoblasts autophagy in the pathogenesis of steroid-induced avascular necrosis of the femoral head (SANFH). METHODS: Osteoblasts were isolated from rabbit bones and treated with 1 µM Methylprednisolone for 0, 12, 24, 48, and 72 h. The Beclin1, MAP1LC3, Atg-5, Atg-12, IFT20 and OFD1 mRNAs and proteins were detected by PCR and Western blotting, and their correlation was statistically analyzed. The lengths of osteoblast cilia were measured under a laser confocal microscope, and the autophagy flux was tracked by transfecting the osteoblasts with GFP-RFP-LC3 lentivirus. RESULTS: Methylprednisolone significantly upregulated Beclin1, MAP1LC3, Atg-5, Atg-12 and OFD1 mRNAs and proteins in a time-dependent manner, and decreased that of IFT20 (P < 0.05). In addition, the autophagy flux in the osteoblasts also increased and the ciliary length decreased in a time-dependent manner after Methylprednisolone treatment. The length of the cilia were 5.46 ± 0.11 um at 0 h, 4.08 ± 0.09 um at 12 h, 3.07 ± 0.07 um at 24 h, 2.31 ± 0.10 um at 48 h, and finally 1.15 ± 0.04 um at 72 h. Methylprednisolone treatment also affects primary cilium numbers in cultures, for 0 to 72 h. The autophagy regulatory genes, Beclin1, MAP1LC3, Atg-5 and Atg-12, were found to be negatively correlated with IFT20, with an average correlation coefficient of -0.81. A negative correlation was also found between OFD1 and IFT20, with an average correlation coefficient of -0.53. CONCLUSION: Methylprednisolone inhibits primary cilia formation and promotes autophagy, which could be the pathological basis of SANFH. The exact regulatory mechanism needs to be further studied in vivo.

4.
Health Commun ; : 1-10, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036688

RESUMO

This study examined the key factors underlying parents' protective responses to avoid the threats of defective vaccines. We constructed a hypothetical model to explore this issue based on the protective action decision model and risk information perspective. A questionnaire survey involving 584 respondents was conducted in Anhui and Jiangsu provinces, China, after the 2018 vaccine scandal broke. The results indicate that perceived vaccine knowledge is a vital determinant of perceived negative publicity, information forwarding, risk perception, and systematic processing. Moreover, perceived negative publicity significantly predicts information forwarding and risk perception. Perceived negative publicity and information forwarding both positively influence systematic processing. Furthermore, parents' protective responses are motivated by risk perception but fail to be stimulated by systematic processing.

5.
Sci Rep ; 10(1): 2308, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047223

RESUMO

Cobalt (Co) is an essential component of several enzymes and coenzymes in living organisms. Excess Co is highly toxic to plants. The knowledge of molecular response mechanisms to cobalt stress in plants is still limited, especially in woody plants. The responses of weeping willow (Salix babylonica) seedlings to Co stress were studied using morphological and physiochemical measurements and RNA-seq analysis. The physiological and biochemical indexes such as growth rate, the content of chlorophyll and soluble sugar, photosynthesis and peroxidase activity were all changed in willow seedlings under Co stress. The metal ion concentrations in willow including Cu, Zn and Mg were disturbed due to excess Co. Of 2002 differentially expressed genes (DEGs), 1165 were root-specific DEGs and 837 were stem and leaf-specific DEGs. Further analysis of DEGs showed there were multiple complex cascades in the response network at the transcriptome level under Co stress. Detailed elucidation of responses to oxidative stress, phytohormone signaling-related genes and transcription factors (TFs), and detoxification of excess cellular Co ion indicated the various defense mechanisms in plants respond to cobalt stress. Our findings provide new and comprehensive insights into the plant tolerance to excess Co stress.

6.
Environ Pollut ; 260: 114049, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32014749

RESUMO

Acidification in variable charge soils is on the rise due to increased acid deposition and use of nitrogenous fertilizers. The associated low pH and cation exchange capacity make the soils prone to depleted base cations and increased levels of Al3+. Consequently, Al toxicity to plants and soil infertility decrease crop yield. This study was designed to investigate the effect of Pseudomonas fluorescens on the acidification of two Ultisols. The simulated acidification experiment demonstrated that the pH of bacteria-treated soil was higher than that of control under similar conditions, suggesting that the adhered bacteria inhibited soil acidification. This observation was attributed to the association of organic anions (RCOO- or RO-) on bacteria with H+ to form neutral molecules (RCOOH or ROH) and reducing the activity of H+ in solution. The bacteria also inhibited the increase in soil soluble Al and exchangeable Al during soil acidification. The adhesion of bacteria on the soils increased soil effective cation exchange capacity (ECEC) and exchangeable base cations at each pH compared to control. The release of exchangeable base cations from bacteria-treated soil, and the decrease in soil ECEC and exchangeable base cations with decreasing pH confirmed that protonation of organic anions on adhered bacteria was mainly responsible for the inhibition of soil acidification. The change of zeta potential of the bacteria with pH and the ART-FTIR analysis at various pH provided more evidence for this mechanism. Therefore, the bacteria in variable charge soils played an important role in retarding soil acidification.

7.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(5): 158639, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31988049

RESUMO

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with anti-inflammatory and anti-diabetic effects, having the potential to treat type 2 diabetes (T2D). In view of the important regulatory and therapeutic actions of FAHFAs on age-related diseases such as T2D, we hypothesized that they may also play crucial roles in the growth, development, and aging process. Here, we investigated the FAHFA footprint in the visceral adipose tissue (VAT) of mice across lifespan to attain potential clues for understanding the roles of FAHFAs in growth, development, and aging using chemical isotope labeling assisted liquid chromatography-mass spectrometry. VAT samples were harvested from 80 C57BL/6J male mice of nine different ages (1, 2, 3, 6, 9, 12, 15, 18, and 24 months). The results showed that a total of 51 FAHFA families, including 301 regioisomers, were detected in the VAT of mice of all ages, and the number of FAHFAs (both family and regioisomer) in VAT increased with age, from 35 families (186 ± 0 regioisomers) at 1-month-old mice to 46 families (278 ± 6 regioisomers) in 18-month-old mice. Furthermore, the content of 12 FAHFA families per 100 mg of VAT of mice was highly correlated with age, and was usually low in the middle-age (3-15 months). However, because the VAT mass was 4-5 fold higher in middle-aged mice compared to younger or older mice, the total amount of most of the FAHFA regioisomers in VAT was increased in middle-aged mice. To the best of our knowledge, this is the first study to show that the number of regioisomers from 51 FAHFA families and abundance of 15 FAHFA families are strongly dependent on age, which would be helpful for understanding the mechanisms underlying the effects of FAHFAs on growth, development, and aging.

8.
BMC Nephrol ; 21(1): 12, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931722

RESUMO

BACKGROUND: Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy. METHODS: From 2017 to 2019, a total of 166 patients from Guangzhou Red Cross Hospital were recruited and divided into four groups with 17 cases in healthy control group, 47 cases in CKD non-dialysis group, 49 cases in HD group, and 53 cases in PD group. Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed. RESULTS: Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutes-dominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole- and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae, Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport. CONCLUSION: Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole- and p-cresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.

9.
Respir Res ; 21(1): 24, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937303

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. METHODS: This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. RESULTS: In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98-0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69-0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03-0.253, P <  0.001); this association was not significant for patients with UO/FI ratios > 0.5 (OR: 1.04, 95% CI: 0.96-1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96-0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. CONCLUSIONS: The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31983673

RESUMO

BACKGROUND: Hemorrhage is one of the most serious complications of endoscopic sphincterotomy (EST). The risk factors for delayed hemorrhage are not clear. This study aimed to explore the risk factors for post-EST delayed hemorrhage and suggest some precautionary measures. METHODS: This study analyzed 8477 patients who successfully underwent endoscopic retrograde cholangiopancreatography (ERCP) and EST between January 2007 and June 2015 in the First Affiliated Hospital of Nanchang University. Univariate and multivariate analyses were performed to find the risk factors for delayed hemorrhage after EST. RESULTS: Of the 8477 patients screened, 137 (1.62%) experienced delayed hemorrhage. Univariate analysis showed that male, the severity of jaundice, duodenal papillary adenoma and carcinoma, diabetes, intraoperative bleeding, moderate and large incisions, and directional deviation of incision are risk factors for post-EST delayed hemorrhage (P < 0.05). Multivariate analysis showed that intraoperative bleeding [odds ratio (OR) = 3.326; 95% CI: 1.785-6.196; P < 0.001] and directional deviation of incision (OR = 2.184; 95% CI: 1.266-3.767; P = 0.005) are independent risk factors for post-EST delayed hemorrhage. CONCLUSIONS: The incidence of post-EST delayed hemorrhage was 1.62% in our study. Intraoperative bleeding and directional deviation of incision are independent risk factors for post-EST delayed hemorrhage.

11.
Biomed Pharmacother ; 122: 109777, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918261

RESUMO

Sepsis is a critical illness that contributes a high mortality, while Xijiao Dihuang decoction (XJDHT) has been used in treatment against sepsis for many years by clinical doctors. Clinical studies confirmed a good efficacy of XJDHT against sepsis. The aim of this study is to observe the efficacy of XJDHT in sepsis model rats and macrophages activated by LPS, and to verify the underlying mechanisms. The key components of XJDHT and its targets against sepsis were analyzed and selected by network pharmacology. The potential mechanisms that XJDHT regulates the progress of sepsis were verified in sepsis rats and NR8383 cell lines. XJDHT at a dose of 25 mg/kg was administrated to rats which endured cecal ligation and perforation (CLP). After MTT assay, XJDHT at a dose of 4 mg/mL was selected to treat NR8383 cell lines activated by LPS. In vivo experiment, the survival of the rats was assessed. The content of cytokine in serum were assessed by Enzyme-linked immunosorbent assays (ELISA). Contents of cytokine and key molecules in relative signaling pathway were assessed by immunohistochemical method. The pathway protein expressions were detected by Western blotting. In vitro experiment, immunofluorescence was used to assess the content of cytokine and signaling pathway. A total of 42 targets of XJDHT against sepsis were identified by network pharmacology. After eliminating overlapping compounds and proteins, there were 8 compounds in XJDHT that associating with the 42 sepsis-related targets. NF-κB and HIF-1α signaling pathway were recognized to play important role for XJDHT against sepsis. XJDHT improved survival rate in the XJDHT group compared with the model group. The contents of IL-6 increased in the model group compared with the control group with ELISA and immunohistochemistry, while XJDHT reduced the content of IL-6. The expressions of p65 and HIF-1α reduced significantly in the XJDHT group compared with the model group. In vitro study, the content of IL-6 elevated significantly after LPS stimulation, while XJDHT reduced this increase. Furthermore, expressions of protein of p65 and HIF-1α decreased significantly compared with the LPS group. To conclude, our study demonstrated that XJDHT at a dose of 25 g/kg is capable of improving the survival of sepsis via regulating the NF-κB and HIF-1α signaling pathway.

12.
Biochim Biophys Acta Mol Cell Res ; 1867(4): 118647, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31926942

RESUMO

Cisplatin-based chemotherapies have long been considered as a standard chemotherapy in ovarian cancer. However, cisplatin resistance restricts beneficial therapy for patients with ovarian cancer. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the post-translational modification of diverse proteins. In this work, we found that ISG15 was downregulated in cisplatin resistant tissues and cell lines of ovarian cancer. Functional studies demonstrated that overexpression of wild type (WT) ISG15, but not nonISGylatable (Mut) ISG15 increased cell responses to cisplatin in resistant ovarian cancer cells. Furthermore, we found that WT ISG15 decreased ABCC2 expression at the protein level. Importantly, overexpression of ABCC2 blocked sensitizing effect of ISG15 on cisplatin. In addition, we identified that hnRNPA2B1 was recruited to 5'UTR of ABCC2 mRNA and promoted its translation, which was blocked by ISG15. We further demonstrated that hnRNPA2B1 could be ISGylated, and ISGylation blocked its recruitment to ABCC2 mRNA, thereby suppressed translation of ABCC2. Altogether, our data support targeting ISG15 might be a potential therapeutic strategy for patients with cisplatin-resistant ovarian cancer.

13.
Acta Biomater ; 104: 210-220, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31927113

RESUMO

Multi-modality imaging agents are desirable for tumor diagnosis because they can provide more alternative and reliable information for accurate detection and therapy of diseases than single imaging technique. However, most reported conventional imaging agents have not been found to successfully overcome the disadvantages of traditional diagnoses such as sensitivity, spatial resolution, short half-decay time and complexity. Therefore, exploring a multifunctional nanocomposite with the combination of their individual modality characteristics has great impact on preoperative imaging and intraoperative diagnosis of cancer. In our study, mesoporous silica gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) specifically for preoperative and intraoperative imaging are designed and their imaging capability and biosafety are examined. They exhibit strong attenuation property for computed X-ray tomography (CT) imaging, high T1 relaxivity for magnetic resonance (MR) imaging capability and surface-enhanced Raman spectroscopy (SERS) signal with good dispersity and stability, which presents CT/MR/SERS multi-mode imaging performance of the tumor of mice within a given time. Furthermore, in vivo biodistribution and long-term toxicity studies reveal that the Gd-GERTs have good biocompatibility and bio-safety. Therefore, Gd-GERTs are of great potential as a multifunctional nanoplatform for accurate preoperative CT/MRI diagnosis and intraoperative Raman imaging-guide resection of cancers. STATEMENT OF SIGNIFICANCE: Recent advances in molecular imaging technology have provided a myriad of opportunities to prepare various nanomaterials for accurate diagnosis and response evaluation of cancer via different imaging modalities. However, single bioimaging modality is still challenging to overcome the issues such as sensitivity, spatial resolution, imaging speed and complexity for clinicians. In this work, we designed a kind of unique multifunctional nanoprobes with computed X-ray tomography/magnetic resonance/surface-enhanced Raman spectroscopy (CT/MR/SERS) triple-modal imaging capabilities. Multifunctional nanotags offer the capabilities of preoperative noninvasive CT/MR imaging for identification of tumors as well as intraoperative real-time SERS imaging for guidance of complete resection of tumors. These multifunctional nanoprobes show critical clinical significance on the improvement of tumor diagnosis and therapy.

14.
Biomed Res Int ; 2020: 7380172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998797

RESUMO

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.

15.
Cancer Med ; 9(2): 711-723, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31769216

RESUMO

BACKGROUND: CCL22 played critical roles in Tregs recruitment. The upstream regulators modulating CCL22 in hepatocellular carcinoma (HCC) were not clearly understood. METHODS: MiR-23a, p-p65, p65, CCL22, and Foxp3 levels were monitored by RT-qPCR and western blotting. Immunofluorescence assay was used to perform the costaining of Foxp3 and CD4 on liver tissues. Transwell assay was applied to evaluate the migration ability of Tregs. Dual-luciferase assay was performed to determine relationship of miR-23a/CCL22 and p65/miR-23a. Chromatin immunoprecipitation (ChIP) was applied to detect the direct binding of p65 to miR-23a promoter. Xenograft tumor models were developed to investigate the functions of p65 and miR-23a in vivo. RESULTS: HBV infection was associated with reduced survival and increased Tregs recruitment in HCC patients. MiR-23a was decreased, whereas p65, CCL22, and Foxp3 were increased in HBV+ tumors. MiR-23a was inversely correlated with CCL22 and Foxp3 expression in HCC. MiR-23a directly targeted CCL22 3'UTR, leading to CCL22 reduction and attenuated Tregs recruitment. Meanwhile, p65 functioned as a transcription repressor of miR-23a by directly binding to its promoter. Inhibition of p65 induced miR-23 expression, leading to less CCL22 expression and Tregs recruitment in vitro. CCL22 was the indispensable effector underlying p65/miR-23a axis and Tregs recruitment. MiR-23a inhibitor promoted xenografted tumor growth accompanying with upregulation of CCL22, whereas p65 inhibition exerted opposite effects. CONCLUSION: Blockage of p65 disinhibited miR-23a expression, leading to CCL22 reduction and repress Tregs recruitment. Targeting p65/miR-23a/CCL22 axis was a novel approach for HBV+ HCC treatment.

16.
Eur J Pharmacol ; 867: 172797, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31747547

RESUMO

Endothelial dysfunction plays important roles in vascular dysfunction under diabetic conditions. The generation of advanced glycation end products (AGEs), which can induce inflammation and oxidative stress, is pivotal in endothelial dysfunction. Salidroside, a major active compound in Rhodiola rosea, exerts protective effects against vascular diseases. To study the effects and mechanism of salidroside in diabetes-induced vascular endothelial dysfunction, an in vitro model was established with AGEs-induced human umbilical vein endothelial cells (HUVECs). Then, cell viability, cell apoptosis, pro-inflammatory cytokines and oxidative biomarkers were tested to determine the effects of salidroside at 10, 50 and 100 µM doses on AGEs induced HUVECs. Additionally, RNA-Seq and bioinformatics analyses were used to search for the underlying mechanism of salidroside. The results showed that salidroside promoted cell viability and significantly alleviated cell apoptosis in AGEs-induced HUVECs. Furthermore, salidroside remarkably decreased the levels of the pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 and impeded the expression of VCAM-1 and ICAM-1 induced by AGEs. Additionally, salidroside promoted superoxide dismutase (SOD) activity and increased catalase (CAT) and glutathione peroxidase (GSH-Px) levels while inhibiting the intracellular generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in AGEs-induced HUVECs. Importantly, salidroside alleviated endothelial inflammation and oxidative stress by activating AMPK phosphorylation and inhibiting NF-ĸB p65 and NLRP3 inflammasome activation. Therefore, we used compound C, an accepted AMPK inhibitor, to further demonstrate the mechanism. Interestingly, the phenomenon produced by salidroside was abolished. Our findings suggest that salidroside ameliorates AGEs-induced endothelial inflammation and oxidative stress, partially via the AMPK/NF-κB/NLRP3 signaling pathway.

17.
Int J Biol Macromol ; 142: 1-10, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805321

RESUMO

Corbicula fluminea (Asian clam), a freshwater bivalve mollusk, has been consumed in China for centuries as a health food and traditional Chinese medicine for treating liver diseases and alcoholism. This study aimed to evaluate the hepato-protective effects and potential mechanisms of a proteoglycan (PSP) from C. fluminea on alcohol-induced liver injury in mice. Results showed that PSP pretreatment significantly antagonized the increases in serum alanine aminotransferase, aspartate aminotransferase, triacylglycerides, and hepatic malondialdehyde levels; elevated the antioxidant enzyme activities and hepatic glutathione levels; and suppressed the levels of hepatic inflammatory cytokines in alcohol-induced liver injury in mice (P < 0.05). Histopathological observation further revealed the potential hepato-protective effect of PSP against alcohol damage. Particularly, PSP pretreatment resulted in significantly decreased expression of cytochrome P450 2e1 (CYP2E1) while significantly upregulating the expression of hemeoxygenase-1 (HO-1) (P < 0.05). These results suggested that PSP could protect the liver from hepatocyte injury induced by alcohol possibly by alleviating hepatic lipid metabolism, elevating antioxidant-enzyme activity, suppressing the immune inflammatory response, and reversing the expression levels of CYP2E1 and HO-1. Therefore, PSP may be developed as a food supplement that can be used to prevent liver diseases.

18.
J Cell Mol Med ; 24(1): 562-572, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657880

RESUMO

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.

19.
Oncogene ; 39(3): 546-559, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31501523

RESUMO

TRIM family proteins are defined as E3 ubiquitin ligases because of their RING-finger domains. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the posttranslational modification of diverse proteins. Both TRIM29 and ISG15 play both pro-tumoral and anti-tumoral functions in cancer cells derived from different histology. In the current study, we demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas (PDACs). The current study demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3 (CAPN3). Importantly, the current study found that TRIM29 knockdown suppressed cancer stem cell-like features of PDACs, which can be rescued by ISG15 independent of its conjugation function. In addition, the current study demonstrated that extracellular free ISG15 played an important role in maintenance of cancer stem cell-like features of PDACs. Thereby, the current study displayed a novel mechanism by which TRIM29 modulates ISG15 stability via CAPN3-mediated processing, and subsequently extracellular ISG15 maintains the cancer stem cell-like features of PDAC via autocrine mode of action.

20.
Cancer Lett ; 469: 78-88, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31629931

RESUMO

Selective estrogen receptor modulators (SERMs) are a class of structurally diverse compounds, which have been extensively used to treat hormone-responsive cancers due to their unique partially agonistic and antagonistic properties toward estrogen receptors. Our previous studies have identified a three-dimensional SERM, oxabicycloheptene sulfonate (OBHS), as an estrogen receptor α (ERα) ligand, which is effective for the prevention and treatment of estrogen-dependent endometriosis in vivo. Here, using genome-wide ChIP-seq and RNA-seq analysis, we report that OBHS rapidly induces genome-wide ERα occupancy and acts as a partial agonist and antagonist for ERα. Interestingly, OBHS downregulates the homologous recombination and repair (HRR) modules, resulting in increased DNA damage, apoptosis and cell cycle arrest, inducing synthetic lethality with poly (ADP-ribose) polymerase (PARP) inhibitor olaparib through ERα antagonism. Mechanistically, OBHS impairs the RNA polymerase II (Pol II) loading at the promoters of estrogen-responsive HRR genes. Furthermore, combination therapy of OBHS with olaparib significantly reduces the tumour burden and delays the progression of breast cancer in vivo. Together, our studies not only characterise a novel SERM which uniquely targets the homologous recombination and repair programmes through ERα antagonism but also propose a synthetic lethal strategy by combining OBHS with PARP inhibitor olaparib for ERα-responsive cancers.

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