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1.
J Crohns Colitis ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030401

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a common chronic inflammatory bowel disease without curative treatment. METHODS: We conducted gene set enrichment analysis to explore potential therapeutic agents for UC. Human colon tissue samples were collected to test H3 acetylation in UC. Both in vivo and in vitro colitis models were constructed to verify the role and mechanism of H3 acetylation modification in UC. Intestine-specific vitamin D receptor (VDR)-/- mice and VD (vitamin D)-deficient diet-fed mice were used to explore downstream molecular mechanisms accordingly. RESULTS: According to the Connectivity Map database, MS-275 (class I histone deacetylase inhibitor) was the top-ranked agent, indicating the potential importance of histone acetylation in the pathogenesis of UC. We then found that histone H3 acetylation was significantly lower in the colon epithelium of UC patients and negatively associated with disease severity. MS-275 treatment inhibited histone H3 deacetylation, subsequently attenuating nuclear factor kappa B (NF-κB)-induced inflammation, reducing cellular apoptosis, maintaining epithelial barrier function, and thereby reducing colitis activity in a mouse model of colitis. We also identified VDR as be a downstream effector of MS-275. The curative effect of MS-275 on colitis was abolished in VDR-/- mice and in VD-deficient diet-fed mice and VDR directly targeted p65. In UC patients, histone H3 acetylation, VDR and zonulin-1 expression showed similar downregulation patterns and were negatively associated with disease severity. CONCLUSION: We demonstrate that MS-275 inhibits histone deacetylation and alleviates colitis by ameliorating inflammation, reducing apoptosis and maintaining intestinal epithelial barrier via VDR, providing new strategies for UC treatment.

2.
BMC Gastroenterol ; 20(1): 31, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028908

RESUMO

BACKGROUND: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients. METHODS: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. RESULTS: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage. CONCLUSIONS: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

3.
Sci Total Environ ; 715: 136871, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32014769

RESUMO

Sulfide production control in gravity sewer sediments is more complex and difficult due to the greater spatial complexity of biological processes as a result of the abundant microflora inside the sediments. In this study, a promising and cost-effective free nitrous acid (FNA)-based suppression strategy for sulfide production in sewer sediments was proposed. Novel in-situ measurement methods were implemented by incorporating the diffusive gradients in thin films (DGT) technique and high-resolution dialysis (HR-Peeper) with microbial characterization analysis along the vertical sediment profile to examine the effect mechanism of the FNA-based inhibition process on sulfide production in the sediments. The results revealed that the FNA-based exposure strategy could effectively suppress the sulfidogenic activity across the whole shallow active layer (approximately 0.5 cm below the surface) in the sediments. An initial high FNA concentration up to 2.5 mg HNO2-N/L was required to maintain a critical inhibition level (24-h average concentration > 0.2 mg HNO2-N/L) across the whole active sediment zone. The FNA concentration decreased sharply deeper than 0.5 cm with a significant pH increase, resulting in FNA inactivation only reducing the microbial live/total ratio and shifting the microbial community structure near the sediment surface. Maintaining a low pH is the critical factor for the FNA-based suppression strategy of the sulfidogenic activity in the shallow sediment zone.

4.
Eur Radiol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32006167

RESUMO

OBJECTIVE: To investigate the effect of image quality of coronary CT angiography (CCTA) on the diagnostic performance of a machine learning-based CT-derived fractional flow reserve (FFRCT). METHODS: This nationwide retrospective study enrolled participants from 10 individual centers across China. FFRCT analysis was performed in 570 vessels in 437 patients. Invasive FFR and FFRCT values ≤ 0.80 were considered ischemia-specific. Four-score subjective assessment based on image quality and objective measurement of vessel enhancement was performed on a per-vessel basis. The effects of body mass index (BMI), sex, heart rate, and coronary calcium score on the diagnostic performance of FFRCT were studied. RESULTS: Among 570 vessels, 216 were considered ischemia-specific by invasive FFR and 198 by FFRCT. Sensitivity and specificity of FFRCT for detecting lesion-specific ischemia were 0.82 and 0.93, respectively. Area under the curve (AUC) of high-quality images (0.93, n = 159) was found to be superior to low-quality images (0.80, n = 92, p = 0.02). Objective image quality and heart rate were also associated with diagnostic performance of FFRCT, whereas there was no statistical difference in diagnostic performance among different BMI, sex, and calcium score groups (all p > 0.05, Bonferroni correction). CONCLUSIONS: This retrospective multicenter study supported the FFRCT as a noninvasive test in evaluating lesion-specific ischemia. Subjective image quality, vessel enhancement, and heart rate affect the diagnostic performance of FFRCT. KEY POINTS: • FFRCTcan be used to evaluate lesion-specific ischemia. • Poor image quality negatively affects the diagnostic performance of FFRCT. • CCTA with ≥ score 3, intracoronary enhancement degree of 300-400 HU, and heart rate below 70 bpm at scanning could be of great benefit to more accurate FFRCTanalysis.

5.
Acta Crystallogr D Struct Biol ; 76(Pt 1): 41-50, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31909742

RESUMO

Three-dimensional structure models refined using low-resolution data from crystallographic or electron cryo-microscopy experiments can benefit from high-quality restraints derived from quantum-chemical methods. However, nonperiodic atom-centered quantum-chemistry codes do not inherently account for nearest-neighbor interactions of crystallographic symmetry-related copies in a satisfactory way. Here, these nearest-neighbor effects have been included in the model by expanding to a super-cell and then truncating the super-cell to only include residues from neighboring cells that are interacting with the asymmetric unit. In this way, the fragmentation approach can adequately and efficiently include nearest-neighbor effects. It has previously been shown that a moderately sized X-ray structure can be treated using quantum methods if a fragmentation approach is applied. In this study, a target protein (PDB entry 4gif) was partitioned into a number of large fragments. The use of large fragments (typically hundreds of atoms) is tractable when a GPU-based package such as TeraChem is employed or cheaper (semi-empirical) methods are used. The QM calculations were run at the HF-D3/6-31G level. The models refined using a recently developed semi-empirical method (GFN2-xTB) were compared and contrasted. To validate the refinement procedure for a non-P1 structure, a standard set of crystallographic metrics were used. The robustness of the implementation is shown by refining 13 additional protein models across multiple space groups and a summary of the refinement metrics is presented.

6.
Curr Microbiol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919671

RESUMO

Muscovy duck reovirus (MDRV) is highly pathogenic to young Muscovy ducklings. Although MDRV infection results in ducklings' acute watery diarrhea, the effect of MDRV infection on the composition of host's intestinal microbiota remains poorly understood. This study was conducted to investigate the impacts of MDRV on the composition of Muscovy ducklings' intestinal bacterial community. Three-day-old Muscovy ducklings were inoculated with either the virulent MDRV strain MW9710 or sterile Hank's solution, respectively. The cecal microbiota was analyzed between control and mock MDRV-infected ducklings using Illumina MiSeq sequencing at 6 dpi and 17 dpi, respectively. The results indicated that MDRV infection damaged the intestinal mucosa. In addition, MDRV infection caused severe perturbations of gut microbiota by decreasing microbial richness, altering the abundance of certain genera of the gut microbiota at 6 dpi. Specifically, the relative abundance of short chain fatty acids-producing bacteria (including Shuttleworthia, Streptococcus, and Ruminococcus) was reduced in MDRV-infected ducklings than those of control group, whereas, with an enrichment of Enterobacteriaceae (including Plesiomonas, Escherichia_Shigella and Proteus). Furthermore, microbiota analysis showed that the gut microbiota dysbiosis caused by MDRV infection was basically recovered at 17 dpi. Collectively, this study demonstrated that the gut microbiota of Muscovy ducklings were altered due to MDRV infection, mainly featuring as a net loss of beneficial bacteria and a compensatory proliferation of pathogenic bacteria, which may lead to severe pathology to the intestinal mucosa, and ultimately acute diarrhea. These results will provide insights into the pathology of MDRV infection.

7.
Mar Biotechnol (NY) ; 22(1): 31-40, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897745

RESUMO

The yellow catfish (Pelteobagrus fulvidraco) is a very important aquaculture species distributed in freshwater area of China. All-male yellow catfish is very popular in aquaculture because of their significant sex dimorphism phenomena. The males grow much faster than females in full-sibling family. However, the sex dimorphism mechanism is still unclear in yellow catfish. In order to better understand the genetic basis of yellow catfish sexual dimorphism, it is vital to map the sex-related traits and localize the candidate genes across yellow catfish whole genome. Here, we constructed a high-density linkage map of yellow catfish using genotyping-by-sequencing (GBS) strategy. A total of 5705 single-nucleotide polymorphism (SNP) markers were mapped to 26 different linkage groups (LGs) using 184 F1 offspring. The total genetic map length was 3071.59 cM, with an average interlocus distance of 0.54 cM. Eleven significant sex-related QTLs in yellow catfish were identified. Six sex-related genes were identified from the region of reference genome near these QTLs including amh, gnrhr, vasa, lnnr1, foxl2, and bmp15. The high-density genetic linkage map provides valuable resources for yellow catfish molecular assistant breeding and elucidating sex differentiation process. Moreover, the comparative genomic study was analyzed among yellow catfish, channel catfish, and zebrafish. It revealed highly conserved chromosomal distribution between yellow catfish and channel catfish.

8.
Med Sci Monit ; 26: e920371, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910201

RESUMO

BACKGROUND Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. MATERIAL AND METHODS Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment). RESULTS Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. CONCLUSIONS We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.

9.
Am J Reprod Immunol ; : e13220, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31925865

RESUMO

PROBLEM: For women of reproductive age, achieving a successful pregnancy requires both the normal functioning of reproductive endocrine and the health of the reproductive tract environment. We aimed to study how these fertility factors, such as female age, baseline sexual hormone levels, tubal patency, and vaginal pH, affect the composition of vaginal microbiome. METHOD OF STUDY: The 16S rRNA sequencing was carried on vaginal microbiome samples from 85 women of reproductive age without vaginal infections or reproductive endocrine diseases. The detailed correlations between fertility factors and vaginal microbiome were quantified by Spearman's rank tests. A linear discriminant analysis was carried out to explore the effects of fertility factors on the relative abundances of vaginal bacterial species. RESULTS: The vaginal pH, levels of basal E2, LH, and FSH all had significant effects on the distribution of vaginal microbiome. The relative abundances of vaginal bacterial species, including Escherichia coli, Streptococcus agalactiae, and Prevotella intermedia, were significantly different due to the host's state of reproductive endocrine and tubal patency. It was worth noting that women with tubal obstruction, or prolonged menstrual cycle, or antral follicle count >15, or vaginal pH > 4.5 all had a higher abundance of Escherichia coli in vagina. CONCLUSION: The fertility factors associated with the reproductive endocrine and the genital tract environment affected vaginal microbiome in women of reproductive age. The species Escherichia coli, Streptococcus agalactiae, Prevotella intermedia, etc could be used as biomarkers to reflect the pathological state of reproductive endocrine and genital tract.

10.
Histol Histopathol ; : 18203, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31970720

RESUMO

AIMS: The prognostic application of YES1 in epithelial ovarian cancer (EOC) is currently unclear. We aimed to investigate the expression of YES1 and its correlation with survival outcome in patients with EOC. METHODS: A retrospective study of patients diagnosed with EOC at the Cancer Center, Sun Yat-Sen University, Guangzhou, China between 2002 and 2013 was conducted. The immunohistochemical expression of YES1 was assessed using tissue microarray. Survival rates were analyzed by the Kaplan-Meier method and were compared between groups using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: A total of 132 patients with EOC were enrolled. Patients in the YES1-high group exhibited significantly better OS and PFS, compared with those in the YES1-low group (P=0.02 and P=0.03, respectively). Further univariate and multivariate regression analyses indicated YES1 as an independent prognostic factor for the OS of patients with EOC. Notably, within the high YES1 expression group, 40 cases (74.1%) were of the platinum-sensitive group while 14 (25.9%) overlapped were of the platinum-resistant group. Conversely, in the low YES1 expression group, 11 cases (47.8%) were platinum-sensitive, and 12 (52.2%) platinum-resistant. Overall, patients within the high YES1 expression group were deemed significantly more sensitive to platinum-based chemotherapy than the low YES1 expression group (P=0.03), and YES1 levels were consistently and significantly higher in the platinum-sensitive group. CONCLUSIONS: High YES1 cytoplasmic expression in EOC patient tissue is significantly correlated with favorable prognosis. Patients with high YES1 expression tend to be sensitive to platinum-based chemotherapy.

11.
Int J Oncol ; 56(2): 606-617, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894296

RESUMO

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem­like cells (GSCs), by culturing patient­derived primary GSCs as well as a GSC cell line in glucose­restricted, ß­hydroxybutyrate­containing medium (BHB­Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB­Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self­renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB­Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB­Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia­inducible factor 1 and B­cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB­Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.

12.
J Exp Clin Cancer Res ; 39(1): 4, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898515

RESUMO

BACKGROUND: MiR-199a-3p (miR-199a) can enhance the chemosensitivity of hepatocellular carcinoma (HCC). Because of the easy degradation of miRNA by direct infusion, effective vehicle-mediated delivery of miR-199a may represent a new strategy for improving HCC chemotherapy. Considering mesenchymal stem cell (MSC)-derived exosomes as promising natural nanovectors for drug and molecule delivery, we aimed to determine whether exosomes from adipose tissue-derived MSCs (AMSCs) could be used to deliver miR-199a and improve HCC chemosensitivity. METHODS: MiR-199a-modified AMSCs (AMSC-199a) were constructed by miR-199a lentivirus infection and puromycin selection. MiR-199-modified exosomes (AMSC-Exo-199a) were isolated from the supernatant of AMSC-199a and were assessed by transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry analysis. The expression levels of miR-199a in HCC samples, AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The effects of AMSC-Exo-199a on HCC chemosensitivity were determined by cell proliferation and apoptosis assays and by i.v. injection into orthotopic HCC mouse models with doxorubicin treatment. MTOR, p-4EBP1 and p-70S6K levels in HCC cells and tissues were quantified by Western blot. RESULTS: AMSC-Exo-199a had the classic characteristics of exosomes and could effectively mediate miR-199a delivery to HCC cells. Additionally, AMSC-Exo-199a significantly sensitized HCC cells to doxorubicin by targeting mTOR and subsequently inhibiting the mTOR pathway. Moreover, i.v.-injected AMSC-Exo-199a could distribute to tumor tissue and markedly increased the effect of Dox against HCC in vivo. CONCLUSIONS: AMSC-Exo-199a can be an effective vehicle for miR-199a delivery, and they effectively sensitized HCC to chemotherapeutic agents by targeting mTOR pathway. AMSC-Exo-199a administration may provide a new strategy for improving HCC chemosensitivity.

13.
J Virol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915277

RESUMO

Under different circumstances, alteration of several viral genes could give an evolutionary advantage to the virus to maintain its prevalence in nature. In this study, a 70-nucleotide deletion in the Small-fragment (S-fragment) of viral 5'-untranslated region (5'-UTR) together with one amino acid insertion in the leader protein (Lpro) was identified that naturally occurred in several serotype O foot-and-mouth disease virus (FMDV) strains in China. The properties of two field serotype O FMDV strains, with or without the 70-nucleotide deletion in S-fragment and the amino acid insertion in Lpro, were compared in vitro and in vivo Clinical manifestations of FMD were clearly observed in the cattle and pigs infected by the virus without the mutations. However, the virus with the mentioned mutations only caused FMD outcomes in pigs but not in cattle. To determine the role of the 70-nucleotide deletion in S-fragment and the single amino acid insertion in Lpro for the pathogenicity and host range of FMDV, four recombinant viruses, with complete genome, a 70-nucleotide deletion in the S-fragment or one single amino acid insertion in Lpro, or containing both the two mutations, were constructed and rescued. It showed that deletion of the 70-nucleotide in S-fragment or insertion of one amino acid (leucine) at the 10 site of Lpro partly decreased the viral pathogenicity of Mya-98 lineage virus in cattle and pigs. However, the virus with dual mutations only caused clinical disease in pigs but not in cattle. This suggested that the S-fragment and the Lpro are significantly associated with the virulence and host specificity of FMDV. The naturally occurred dual mutation in the S-fragment and Lpro is a novel determinant of viral pathogenicity and host range for serotype O FMDV.IMPORTANCE FMD is probably the most important livestock disease in the world due to the severe economic consequences caused. Alteration of several viral genes could give virus selective advantage to maintain its prevalence in nature. Here, we identified that the 70 nucleotides deletion in the S-fragment combined with one single leucine insertion in the Lpro is a novel determinant of restricted growth on bovine cells, which significantly contributes to the altered virulence of serotype O FMDV to cattle. A synergistic and additive effect of the 70 nucleotides deletion in the S-fragment and the single leucine insertion in the Lpro on the virulence and host specificity of the virus was determined. These results will benefit the efforts to understand the vial pathogenicity mechanism and molecular characteristics of FMDV.

14.
Virus Res ; 278: 197869, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31962065

RESUMO

Porcine deltacoronavirus (PDCoV) is the etiological agent of acute diarrhoea and vomiting in pigs, threatening the swine industry worldwide. Although several PDCoV studies have been conducted in China, more sequence information is needed to understand the molecular characterization of PDCoV. In this study, the partial ORF1a, spike protein (S) and nucleocapsid protein (N) were sequenced from Shandong Province between 2017 and 2018. The sequencing results for the S protein from 10 PDCoV strains showed 96.7 %-99.7 % nucleotide sequence identity with the China lineage strains, while sharing a lower level of nucleotide sequence identity, ranging from 95.7 to 96.8%, with the Vietnam/Laos/Thailand lineage strains. N protein sequencing analysis showed that these strains showed nucleotide homologies of 97.3%-99.3% with the reference strains. Phylogenetic analyses based on S protein sequences showed that these PDCoV strains were classified into the China lineage. The discontinuous 2 + 3 aa deletions at 400-401 and 758-760 were found in the Nsp2 and Nsp3 coding region in five strains, respectively, with similar deletions having been identified in Vietnam, Thailand, and Laos. Three novel patterns of deletion were observed for the first time in the Nsp2 and Nsp3 regions. Importantly, those findings suggest that PDCoV may have undergone a high degree of variation since PDCoV was first detected in China.

15.
Prenat Diagn ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990991

RESUMO

OBJECTIVES: Prenatal ventricular outpouchings (VOs), which include congenital ventricular aneurysms (CAs) and congenital ventricular diverticula (CD), are very rare. We describe the features and outcomes of prenatal VOs diagnosed over a 4-year period. METHODS: Retrospective cohort study of cases of prenatal diagnoses of CAs and CD at our center between June 2014 and January 2018. The prenatal and post-natal echocardiogram data were reviewed, telephone follow-up was conducted of liveborn cases. RESULTS: A total of 25 VOs were identified. Two were lost to follow-up, 15 chose termination of pregnancy, and 8 resulted in livebirths. Only 2 cases underwent autopsy: histopathology showed that the CA wall was substituted by collagen fibers. At follow-up, none of the 8 liveborn babies experienced adverse events, and three VOs near the tricuspid annulus almost disappeared, though one was extremely large. CONCLUSIONS: In our center, all liveborn babies with VO had good prognoses. We hypothesize that VOs located near the right ventricular annulus may be caused by prenatally unbalanced pressure, given their decrease in size after birth when the right heart pressure declines. This article is protected by copyright. All rights reserved.

16.
Water Res ; 172: 115515, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31986403

RESUMO

In this study, the effects of free nitrous acid (FNA) pre-treatment on the rheological properties of digested sludge were investigated at a pilot-scale, along with the improvement in volatile solids (VS) destruction and biogas production. Two pilot-scale anaerobic sludge digesters were operated for one year, one receiving thickened waste activated sludge (TWAS) without pre-treatment (control) and one receiving TWAS pre-treated for 24 h at an FNA concentration of 4.9-6.1 mgN/L (nitrite = 250 mgN/L, pH = 5.0, T = 22-30 °C). The results confirmed the enhancing effect of FNA pre-treatment on methane production (37 ± 1%), consistent with previous laboratory studies. Equally importantly, FNA pre-treatment substantially reduced the shear viscosity of TWAS by 51 ± 8% at 100 s-1 and 49 ± 7% at 250 s-1, likely due to the solubilization of the TWAS (11.1 ± 0.8%). Similarly, FNA pre-treatment also reduced these viscosity parameters of the digested sludge by 80 ± 4% and 78 ± 4%, respectively, caused by both enhanced VS destruction and disintegration of the digested sludge. The dewaterability of digested sludge, assessed by dewatered solids content, capillary suction time and specific resistance to filtration, was not improved by FNA pre-treatment. The polymer requirement for dewatering was reduced by 24 ± 0.6% due to the lower solids concentration in the digested sludge achieved with FNA pre-treatment. The changes to sludge rheological properties revealed in this study further enhances the business case for the FNA pre-treatment technology.

17.
Life Sci ; 240: 117094, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760101

RESUMO

The liver serves as a central participant in immune system owing to its particular blood supply and large amounts of immune cells, in which macrophages play a significant role in liver homeostasis and disorders. Extracellular vesicles (EVs), membrane-defined nanometer-sized vesicles released by cells in a tightly controlled manner, have attracted intensive research attention as a critical vehicle for cell-cell communication in the pathophysiology of liver. Accumulating evidence has proved that extracellular vesicles are frequently involved in macrophage-mediated biological behaviors. Not only can macrophages produce and secrete EVs containing multifarious cargo themselves to exert immunomodulatory functions, but also macrophages may serve as target cells of EVs from other cells eliciting the alteration of their phenotype and function. Since both macrophage as well as EVs show pleiotropic and central effects in the progression of liver diseases, their roles in adjusting innate immunity of liver often present a crossover. In this review we are dedicated to deciphering the complex immunological network constituted by macrophages and EVs in several common liver diseases, including acute liver injury or failure and a set of chronic liver diseases such as viral hepatitis B and C, metabolic and alcoholic liver diseases, as well as hepatocellular carcinoma (HCC). From the aspect of immunology, we integrate the mechanism of EVs and hepatic macrophages in the setting of liver diseases and show a promising significance of utilizing this association into clinical immunotherapy.


Assuntos
Vesículas Extracelulares/imunologia , Hepatopatias/imunologia , Macrófagos/imunologia , Animais , Humanos , Imunomodulação
18.
J Cell Biochem ; 121(3): 2534-2542, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31692047

RESUMO

Lung cancer is the dominating cause of cancer-induced death and can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2-AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2-AS1 in LUAD tissues. Through quantitative real-time reverse transcription-polymerase chain reaction analysis, we observed an upregulation of ZFPM2-AS1 in LUAD cell lines. Conducting loss-of-function assays, we found that ZFPM2-AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial-mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2-AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2-AS1 functioned as a molecular sponge of miR-511-3p, which was a suppressor in LUAD. Moreover, ZFPM2-AS1 sponged miR-511-3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR-511-3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2-AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2-AS1 in LUAD.

19.
Bioconjug Chem ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31884783

RESUMO

A new type of fluorine-doped carbon dots (FCDs) with the nucleus-targeting capability was prepared and utilized as a promising candidate for drug and dye delivery. Doxorubicin (DOX) and boron dipyrromethene (BODIPY) was used as a model drug and dye, respectively, to construct FCD-DOX and FCD-BODIPY nanocomposites via coassembly with FCDs. The results demonstrate that FCDs can remarkably increase the cellular uptake and delivery of DOX and BODIPY. This work developed a convenient strategy to construct CDs-based nanohybrids for nucleus-targeted bioimaging and cancer treatment.

20.
Toxicol Lett ; 318: 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31585160

RESUMO

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.


Assuntos
Antineoplásicos/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Inseticidas/toxicidade , Piruvatos/toxicidade , Rotenona/toxicidade , Taquicardia Ventricular/induzido quimicamente , Fibrilação Ventricular/induzido quimicamente , Remodelação Ventricular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Conexina 43/genética , Conexina 43/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/ultraestrutura , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ratos Wistar , Período Refratário Eletrofisiológico/efeitos dos fármacos , Medição de Risco , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologia
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