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1.
J Org Chem ; 89(12): 8357-8362, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38819110

ABSTRACT

Oxidation contributes as a secondary driver of the prevailing carbon emission in the chemical industries. To address this issue, photocatalytic aerobic oxidation has emerged as a promising alternative. However, the challenge of achieving satisfactory chemoselectivity and effective use of solar light has hindered progress in this area. In this context, the present study introduces a novel homogeneous photocatalyst, [Sm6O(OH)8(H2O)24]I8(H2O)8 cluster (Sm-OC), via a unique auxiliary ligand-free oxidative hydrolysis. Using Sm-OC as catalyst, a solar photocatalyzed aerobic oxidation of thiols has been developed for the synthesis of valuable disulfides. Remarkably, this catalyst manifested a significant turnover number ≥2000 under tested conditions. Sm-OC-catalyzed aerobic oxidation showcased remarkable chemoselectivity. In thiol oxidations, despite the vulnerability of disulfides toward overoxidation, overoxidized byproducts or oxidation of nontarget functional groups was not detected across all 28 tested substrates. This investigation presents the first application of a lanthanide-oxo/hydroxy cluster in photocatalysis.

2.
Heliyon ; 10(1): e23945, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38205297

ABSTRACT

Status epilepticus (SE) is a life-threatening disorder that can result in death or severe brain damage, and there is a substantial body of evidence suggesting a strong association between pyroptosis and SE. Sterol regulatory element binding protein 1 (SREBP1) is a significant transcription factor participating in both lipid homeostasis and glucose metabolism. However, the function of SREBP1 in pyroptosis during SE remains unknown. In this study, we established a SE rat model by intraperitoneal injection of lithium chloride and pilocarpine in vivo. Additionally, we treated HT22 hippocampal cells with glutamate to create neuronal injury models in vitro. Our results demonstrated a significant induction of SREBP1, inflammasomes, and pyroptosis in the hippocampus of SE rats and glutamate-treated HT22 cells. Moreover, we found that SREBP1 is regulated by the mTOR signaling pathway, and inhibiting mTOR signaling contributed to the amelioration of SE-induced hippocampal neuron pyroptosis, accompanied by a reduction in SREBP1 expression. Furthermore, we conducted siRNA-mediated knockdown of SREBP1 in HT22 cells and observed a significant reversal of glutamate-induced cell death, activation of inflammasomes, and pyroptosis. Importantly, our confocal immunofluorescence analysis revealed the co-localization of SREBP1 and NLRP1. In conclusion, our findings suggest that deficiency of SREBP1 attenuates glutamate-induced HT22 cell injury and hippocampal neuronal pyroptosis in rats following SE. Targeting SREBP1 may hold promise as a therapeutic strategy for SE.

3.
J Glob Antimicrob Resist ; 35: 307-313, 2023 12.
Article in English | MEDLINE | ID: mdl-37879457

ABSTRACT

OBJECTIVES: To characterize a carbapenem-resistant Pseudomonas aeruginosa (CRPA) with an IncP-2 plasmid containing a novel transposon, Tn6485h, which carries both blaIMP-45 and blaAFM-1. METHODS: Antimicrobial susceptibility testing and filter mating experiment were performed on PA942. The stability of the plasmid carrying both blaIMP-45 and blaAFM-1 was carried out. We determined the growth rate of the transconjugant to investigate fitness cost. Additionally, whole-genome sequencing and genomic analysis were performed on PA942. RESULTS: PA942 strain was resistant to most antibiotics except for ciprofloxacin and colistin. Bioinformatics analysis confirmed that PA942 contains an IncP-2 plasmid with a novel transposon Tn6485h carrying both blaIMP-45 and blaAFM-1. The plasmid pPA942-IMP45 can be transferred into recipient bacteria PAO1Rif with an efficiency of 2.2 × 10-7 and the transconjugant PAO1Rif/ pPA942-IMP45 can be stably inherited for 10 generations in the absence of antibiotics. CONCLUSION: We report a carbapenem-resistant P. aeruginosa strain with an IncP-2 plasmid containing a novel transposon, Tn6485h, which carries both blaIMP-45 and blaAFM-1. The IncP-2 plasmid and transposon Tn6485h may contribute to the spread of MBL genes. Therefore, effective measures to prevent the spread of these plasmids should be taken.


Subject(s)
Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/genetics , beta-Lactamases/genetics , Plasmids/genetics , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology
4.
Molecules ; 28(19)2023 Sep 24.
Article in English | MEDLINE | ID: mdl-37836632

ABSTRACT

Iodine is a well-known oxidant that is widely used in organic syntheses. Thiol oxidation by stoichiometric iodine is one of the most commonly employed strategies for the synthesis of valuable disulfides. While recent advancements in catalytic aerobic oxidation conditions have eliminated the need for stoichiometric oxidants, concerns persist regarding the use of toxic or expensive catalysts. In this study, we discovered that iodine can be used as a cheap, low-toxicity catalyst in the aerobic oxidation of thiols. In the catalytic cycle, iodine can be regenerated via HI oxidation by O2 at 70 °C in EtOAc. This protocol harnesses sustainable oxygen as the terminal oxidant, enabling the conversion of primary and secondary thiols with remarkable efficiency. Notably, all 26 tested thiols, encompassing various sensitive functional groups, were successfully converted into their corresponding disulfides with yields ranging from >66% to 98% at a catalyst loading of 5 mol%.

5.
Microbiol Spectr ; : e0102823, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37623430

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the bla NDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between bla NDM-1-carrying and bla NDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for bla NDM-1 and 11 were positive for bla NDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that bla NDM-1 and bla NDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the bla NDM-1-bearing plasmid were highly similar to those of the bla NDM-5-carrying plasmid, but the transferability of the bla NDM-1-positive plasmid was greater than that of the bla NDM-5-positive plasmid. In conclusion, the transmission of bla NDM-1 or bla NDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae. IMPORTANCE The emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of bla NDM-1 and bla NDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different bla NDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the bla NDM-1 and bla NDM-5 genes and demonstrate that the bla NDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

6.
Infect Drug Resist ; 16: 5149-5154, 2023.
Article in English | MEDLINE | ID: mdl-37581168

ABSTRACT

Purpose: Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Patients and Methods: A 53-year-old male was admitted to our emergency department with fever, thrombocytopenia, and abnormal liver function. Laboratory tests revealed significant bilirubin, AST, and ALT elevations, renal impairment, positive anti-HEV IgM and IgG antibody results, schistocytes on the blood smear, 0% ADAMTS-13 activity, and positive ADAMTS13 inhibitor results. He was diagnosed with acute hepatitis E, which induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Results: After receiving treatment with plasmapheresis, glucocorticoid medication, rituximab, and other supportive medicines, the patient's physiological circumstances and laboratory indicators improved, and a 4-month follow-up revealed no abnormalities. Conclusion: This is a unique case report of an acute hepatitis E-induced immune-mediated thrombotic thrombocytopenic purpura initial episode. This case report offers evidence that hepatitis E virus infection can cause thrombotic thrombocytopenic purpura. In patients with abnormal liver function and thrombocytopenia, we advise screening for hepatitis E or thrombotic thrombocytopenic purpura.

7.
Infect Drug Resist ; 16: 4857-4865, 2023.
Article in English | MEDLINE | ID: mdl-37520453

ABSTRACT

Purpose: Time-consuming culture methods and wet-mount microscopy (WMM) with low sensitivity have difficulties in diagnosing Vulvovaginal candidiasis (VVC). Rapid and highly sensitive polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) for the diagnosis of VVC has not been reported to date. This study was the first to evaluate the performance of PCR-QDFA for diagnosis of Candida strains in the leukorrhea samples from patients with suspected VVC. Patients and Methods: Leukorrhea samples from all visited patients were taken from the vagina using vaginal swabs by clinicians. We evaluated patients admitted with suspected VVC who completed WMM for diagnosis and reported the diagnostic effectiveness of PCR-QDFA and Candida culture (gold standard) when testing leucorrhea samples. Results: A total of 720 leukorrhea samples from 387 VVC-positive patients and 333 VVC-negative patients were included in this study. Of the 387 leukorrhea samples from the VVC-positive patients, 391 Candida strains were identified by culture. 99.23% (388/391) Candida strains were included in the PCR-QDFA list. The 388 Candida strains belonged to four different species of Candida, including C. albicans (n = 273, 70.36%), C. glabrata (n = 85, 21.91%), C. tropicalis (n = 16, 4.12%), and C. krusei (n = 14, 3.61%). PCR-QDFA diagnosed Candida strains in 340/384 (88.54%) of the leucorrhea samples with Candida strains infection. The sensitivity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis, and C. krusei was 89.01%, 85.88%, 81.25% and 92.86%, respectively. The specificity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis and C. krusei was 93.69%, 99.37%, 99.71%, and 99.57%, respectively. Conclusion: The highly sensitive and specific PCR-QDFA technique can be exploited as a rapid (approximately 4 h) diagnostic tool for common Candida strains of leucorrhea samples from patients with suspected VVC.

8.
Food Chem ; 426: 136534, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37302307

ABSTRACT

A highly sensitive and selective HPLC method for the determination of vitamin K vitamers including phylloquinone (PK) and menaquinones (MK-4) in infant formulas is described. The K vitamers were quantified with a fluorescence detector after online post-column electrochemical reduction occurring in a laboratory-made electrochemical reactor (ECR) equipped with platinum plated porous titanium (Pt/Ti) electrodes. The morphology of the electrode showed that the grain size of Pt was homogeneous and well plated on the porous Ti substrate, resulting in largely improved electrochemical reduction efficiency due to the large specific surface area. In addition, the operation parameters such as mobile phase/supporting electrolyte and working potential were optimized. The detection limits of PK and MK-4 were 0.81 and 0.78 ng g-1. Infant formula varying in stages were detected, showing PK ranged from 26.4 to 71.2 µg/100 g, while MK-4 was not detected.


Subject(s)
Infant Formula , Vitamin K , Humans , Infant , Titanium , Porosity , Vitamin K 1/analysis , Chromatography, Liquid , Chromatography, High Pressure Liquid/methods , Electrodes
9.
PeerJ ; 11: e15315, 2023.
Article in English | MEDLINE | ID: mdl-37220525

ABSTRACT

Background: Cardiotoxicity is a side effect of the anthracycline broad-spectrum anti-tumor agent, doxorubicin (DOX). Hyperoside, a flavonoid glycoside extracted from many herbs, has anti-apoptotic and anticancer properties. However, its impact on the alleviation of DOX-induced apoptosis in cardiomyocytes remains elusive. Methods: The HL-1 cell line was treated with 100 µ M hyperoside for 1 h prior to treatment with 100 µ M hyperoside and 1 µ M DOX for 24 h. The cell counting kit-8 (CCK-8) assay was used to detect cell viability; DCFH-DA fluorescent probe was used to detect (reactive oxygen species) ROS; biochemical methods were used to detect the activity of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA); the degree of apoptosis following DOX insult was assessed using immunofluorescence staining and terminal deoxynucleotidyl transferase mediated deoxy uridine triphosphate nick end labeling (TUNEL) assay; the change in protein expression of apoptosis signal-regulating kinase 1 (ASK1), p38, and apoptosis markers was determined using western blot. Results: Hyperoside ameliorated DOX-induced oxidative stress in HL-1 cells, up-regulated GSH, SOD and CAT activity, reduced ROS production and inhibited MDA overproduction. Moreover, in addition to promoting HL-1 cell apoptosis, DOX administration also increased B-cell lymphoma (Bcl)-2-associated X-protein and cleaved caspase-3 protein levels and decreased Bcl-2 protein level. Hyperoside therapy, however, significantly reversed the impact of DOX on the cardiomyocytes. Mechanically, DOX treatment increased the phosphorylation of the ASK1/p38 axis whereas hyperoside treatment attenuated those changes. In a further step, hyperoside synergizes with DOX to kill MDA-MB-231 cells. Conclusions: Hyperoside protects HL-1 cells from DOX-induced cardiotoxicity by inhibiting the ASK1/p38 signaling pathway. Meanwhile, hyperoside maintained the cytotoxicity of DOX in MDA-MB-231 cells.


Subject(s)
Cardiotoxicity , MAP Kinase Kinase Kinase 5 , Humans , Reactive Oxygen Species , Doxorubicin , Apoptosis
10.
Infect Drug Resist ; 16: 2271-2279, 2023.
Article in English | MEDLINE | ID: mdl-37090037

ABSTRACT

Objective: Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, with a broad-spectrum antimicrobial activity, including against carbapenem-resistant gram-negative bacteria (CRGNB). However, the in vitro activity of eravacycline against CRGNB has not been well known in China. In this study, we analysed the antibacterial activity of eravacycline against CRGNB isolates in order to provide a theoretical basis for the clinical treatment. Methods: A total of 346 isolates of CRGNB were collected from two different tertiary care hospitals in Zhejiang, China. Carbapenem resistance genes of all isolates were detected by polymerase chain reaction. And we analysed the in vitro activity of eravacycline against CRGNB by antimicrobial susceptibility tests. In addition, the time-kill curves were generated to evaluate the antibacterial effect of tigecycline and eravacycline. Results: Four different types of carbapenem-resistant isolates were collected, including 50 Escherichia coli isolates, 160 Klebsiella pneumoniae isolates, 42 Enterobacter cloacae complex isolates, and 94 Acinetobacter baumannii isolates. The carbapenem resistance genes were identified in 346 isolates, including bla KPC-2 (48.0%), bla OXA-23 (27.2%), bla NDM-1 (23.1%), and bla NDM-16 (0.3%). The antimicrobial susceptibility testing results showed that the minimum inhibitory concentration (MIC) values of 346 isolates were within the sensitivity range (≤0.0625~16 mg/L) and that the MIC50 or MIC90 of eravacycline was generally approximately 2-fold lower than tigecycline. In addition, the time-kill curves showed that the bactericidal effect of eravacycline was stronger than that of tigecycline against four different types of isolates. Conclusion: Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future.

11.
J Infect Public Health ; 15(12): 1363-1369, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36334462

ABSTRACT

BACKGROUND: Co-harbouring of carbapenem and colistin resistance genes in multidrug-resistant Enterobacterales strains poses a serious public health problem. In this study, an MCR-1.1 and NDM-5 coproducing Escherichia coli strain named EC6563 was isolated and characterized. OBJECTIVES: This study aimed to characterize a clinical carbapenem-resistant E. coli isolate which co-harbours mcr-1.1 and blaNDM-5 on separate plasmids, and explored the phenotypic and genotypic characteristics of the mcr-1.1- and blaNDM-5-harbouring plasmids. METHODS: E. coli isolate EC6563 was subjected to antimicrobial susceptibility testing, conjugation assay, stability of the plasmid and growth rate determination. In addition, the whole genome sequence of this strain was obtained and the genetic characteristics of the mcr-1.1- and blaNDM-5-harbouring plasmids were analyzed. RESULTS: Carbapenem-resistant E. coli isolate EC6563 was resistant to all the tested antibiotics except tigecycline. Bioinformatic analysis confirmed that the IncHI2 plasmid carrying mcr-1.1 was highly similar to the previously reported mcr-1.1-harbouring plasmid pGDP37-4, and carried multiple drug resistance genes and the IncI1-I plasmid carrying blaNDM-5 had low similarity to the published blaNDM-5-carrying IncI1-I plasmid pEC-16-10-NDM-5. The pEC6563-NDM5 plasmid was capable of conjugation with an efficiency of 1.34 × 10-2 in a filter mating experiment. The transconjugant J53/pEC6563-NDM5 was able to be stably inherited after 12 days of passage. CONCLUSIONS: To the best of our knowledge, this is the first time that an IncHI2 plasmid carrying mcr-1.1 and an IncI1-I plasmid carrying blaNDM-5 is found to coexist in an E. coli isolate. Our research expands the known diversity of plasmids in NDM-5-producing Enterobacterales strains. Meanwhile, effective measures should be taken to prevent the spread of these plasmids.


Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Humans , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , beta-Lactamases/pharmacology , Carbapenems/pharmacology , China , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli/genetics , Escherichia coli Proteins/genetics , Microbial Sensitivity Tests , Plasmids/genetics
12.
Front Aging Neurosci ; 14: 905115, 2022.
Article in English | MEDLINE | ID: mdl-35860670

ABSTRACT

Background: Spinal cord injury (SCI) is a severe traumatic disorder of the central nervous system (CNS) that causes irreversible damage to the nervous tissue. The consequent hemorrhage contributed by trauma induces neuronal ferroptosis post SCI, which is an important death mode to mediate neuronal loss. Growth differentiation factor 15 (GDF15) is a cytokine that regulates cell proliferation, differentiation, and death. However, the specific role of GDF15 in neuronal ferroptosis post SCI remains unknown. Materials and Methods: Neuronal ferroptosis in vitro was measured by detection of lipid peroxidation, glutathione, iron content, and reactive oxidative stress. In vivo, western blotting and immunofluorescence (IF) staining was utilized to measure ferroptosis post SCI. IF staining, TUNEL staining, hematoxylin-eosin staining, and Nissl staining were used to measure neurological damage. Finally, locomotor function recovery was analyzed using the Basso Mouse Scale and Louisville Swim Scale. Results: GDF15 was significantly increased in neuronal ferroptosis and silencing GDF15 aggravated ferroptosis both in vitro and in vivo. Besides, GDF15-mediated inhibition of neuronal ferroptosis is through p62-dependent Keap1-Nrf2 pathway. In SCI mice, knockdown of GDF15 significantly exacerbated neuronal death, interfered with axon regeneration and remyelination, aggravated ferroptosis-mediated neuroinflammation, and restrained locomotor recovery. Conclusion: GDF15 effectively alleviated neuronal ferroptosis post SCI via the p62-Keap1-Nrf2 signaling pathway and promoted locomotor recovery of SCI mice, which is suggested as a potential target on SCI pathogenesis and treatment.

13.
Eur J Pharmacol ; 927: 175068, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35644423

ABSTRACT

Whether colchicine reduces the levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) remains uncertain. Therefore, this systematic review and meta-analysis were conducted to evaluate the overall effect of colchicine treatment on hs-CRP and IL-6 levels in patients with coronary artery disease (CAD). PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published before October 2021. Clinical trials in patients with CAD with reports of hs-CRP and IL-6 level changes before and after colchicine intervention were included. In total, 11 trials on hs-CRP and two trials on IL-6 were included in this meta-analysis. Compared with that in the control group, colchicine treatment was significantly associated with decreased hs-CRP levels (weighted mean differences [WMDs], -0.81 mg/L; 95% confidence interval [CI], -1.34 to -0.28 mg/L; P = 0.003) in patients with CAD. Besides, the levels of IL-6 were significantly reduced in colchicine users compared to that of placebo (WMD, -1.28 pg/mL; 95% CI, -2.35 to -0.21 pg/mL; P = 0.02). In a subgroup analysis, colchicine led to a significant reduction in hs-CRP levels in studies with duration of intervention >7 days (WMD, -0.65 mg/L; 95% CI, -1.08 to -0.21 mg/L; P = 0.004) and studies with baseline hs-CRP levels ≥3.0 mg/L (WMD, -0.99 mg/L; 95% CI, -1.92 to -0.06 mg/L; P = 0.04). Colchicine intervention was associated with a reduction in hs-CRP and IL-6 levels in patients with CAD. Future investigations are required to verify the effect of colchicine on inflammatory markers and clarify the potential mechanisms of the cross talk between colchicine, inflammation, and cardiovascular outcomes.


Subject(s)
Coronary Artery Disease , Biomarkers , C-Reactive Protein/metabolism , Colchicine/pharmacology , Colchicine/therapeutic use , Coronary Artery Disease/drug therapy , Humans , Interleukin-6
14.
Int J Public Health ; 67: 1604329, 2022.
Article in English | MEDLINE | ID: mdl-35250431

ABSTRACT

Objective: The aim of our case-control study was to find the influence of lifestyle and comorbidities on COVID-19 susceptibility, identify risk factors and protective factors, and identify ways to encourage people to adopt a healthy lifestyle. Methods: Patients with COVID-19 were matched with non-COVID-19 participants in a ratio of 1:2. Univariate analysis was performed using the chi-square test, and multivariate analysis was performed using conditional logistic regression. Results: Multivariate analysis using conditional logistic regression found that alcohol consumption (AC) and a bland diet increased the risk of COVID-19, while college degrees and above, smoking, drinking tea, and exercise, especially walking, significantly reduced the risk of COVID-19. Conclusion: After removing the effects of demographic factors, the study demonstrated that AC significantly reduced the ability of the body to resist COVID-19 infection. Moreover, following a bland diet increased the susceptibility to COVID-19. Notably, people who drank tea and performed regular exercises, especially walking, were significantly less likely to be infected with COVID-19. College degree or above relative illiteracy is COVID-19 protective factors of infection.


Subject(s)
COVID-19 , Adult , Alcohol Drinking , Areca/adverse effects , COVID-19/epidemiology , Case-Control Studies , Humans , Life Style , Risk Factors , SARS-CoV-2
15.
Cell Mol Life Sci ; 78(24): 8261-8281, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34773477

ABSTRACT

Colorectal cancer (CRC) is the leading cause of cancer-related mortality worldwide, which makes it urgent to identify novel therapeutic targets for CRC treatment. In this study, DHX9 was filtered out as the prominent proliferation promoters of CRC by siRNA screening. Moreover, DHX9 was overexpressed in CRC cell lines, clinical CRC tissues and colitis-associated colorectal cancer (CAC) mouse model. The upregulation of DHX9 was positively correlated with poor prognosis in patients with CRC. Through gain- and loss-of function experiments, we found that DHX9 promoted CRC cell proliferation, colony formation, apoptosis resistance, migration and invasion in vitro. Furthermore, a xenograft mouse model and a hepatic metastasis mouse model were utilized to confirm that forced overexpression of DHX9 enhanced CRC outgrowth and metastasis in vivo, while DHX9 ablation produced the opposite effect. Mechanistically, from one aspect, DHX9 enhances p65 phosphorylation, promotes p65 nuclear translocation to facilitate NF-κB-mediated transcriptional activity. From another aspect, DHX9 interacts with p65 and RNA polymerase II (RNA Pol II) to enhance the downstream targets of NF-κB (e.g., Survivin, Snail) expression to potentiate the malignant phenotypes of CRC. Together, our results suggest that DHX9 may be a potential therapeutic target for prevention and treatment of CRC patients.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology , DEAD-box RNA Helicases/metabolism , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Liver Neoplasms/secondary , NF-kappa B/metabolism , Neoplasm Proteins/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , DEAD-box RNA Helicases/antagonists & inhibitors , DEAD-box RNA Helicases/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/genetics , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Prognosis , RNA, Small Interfering/genetics , Signal Transduction , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
16.
Nanomaterials (Basel) ; 10(4)2020 Apr 23.
Article in English | MEDLINE | ID: mdl-32340312

ABSTRACT

Mn3O4 coated Ru nanoparticles (Ru@Mn3O4) were synthesized via a precipitation-reduction-gel method. The prepared catalysts were evaluated for partial hydrogenation of benzene towards cyclohexene generation by applying ZnSO4, MnSO4 and FeSO4 as reaction additives. The fresh and spent catalysts were thoroughly characterized by XRD, X ray fluorescence (XRF), XPS, TEM and N2-physicalsorption in order to understand the promotion effect of Mn3O4 as the modifier as well as ZnSO4, MnSO4 and FeSO4 as reaction additives. It was found that 72.0% of benzene conversion and 79.2% of cyclohexene selectivity was achieved after 25 min of reaction time over Ru@Mn3O4 with a molar ratio of Mn/Ru being 0.46. This can be rationalized in terms of the formed (Zn(OH)2)3(ZnSO4)(H2O)3 on the Ru surface from the reaction between Mn3O4 and the added ZnSO4. Furthermore, Fe2+ and Fe3+ compounds could be generated and adsorbed on the surface of Ru@Mn3O4 when FeSO4 is applied as a reaction additive. The most electrons were transferred from Ru to Fe, resulting in that lowest benzene conversion of 1.5% and the highest cyclohexene selectivity of 92.2% after 25 min of catalytic experiment. On the other hand, by utilizing MnSO4 as an additive, no electrons transfer was observed between Ru and Mn, which lead to the complete hydrogenation of benzene towards cyclohexane within 5 min. In comparison, moderate amount of electrons were transferred from Ru to Zn2+ in (Zn(OH)2)3(ZnSO4)(H2O)3 when ZnSO4 is used as a reaction additive, and the highest cyclohexene yield of 57.0% was obtained within 25 min of reaction time.

17.
J Cancer ; 11(4): 893-905, 2020.
Article in English | MEDLINE | ID: mdl-31949493

ABSTRACT

Background: DNA sensors are innate immune receptors that detect intracellular endogenous or exogenous DNA. They are critical to trigger immune response against DNA viral and intracellular bacterial infection, and are involved in inflammatory diseases and tumorigenesis. Recent accumulating evidences indicated that DNA sensors are also crucial for controlling the development of colorectal cancer (CRC). However, a systematic study on the expression profile of DNA sensors in CRC and their clinical significance are still lacking. Methods: We investigated the expression profile of DNA sensors in CRC and their clinical significance by taking advantage of clinical CRC samples, mouse AOM/DSS treatment model, and Oncomine ® bioinformatics platform. Results: Our study identified that the expression of DNA sensors, including AIM2, DAI, as well as inflammasome molecules ASC/IL-18, TLR9 and adaptor MyD88, and DDX60 decreased in human CRC, whereas the expression of DHX9, DHX36, and DDX41 significantly increased. Among them, the expression of AIM2/ASC/IL-18, MyD88, DAI, DHX36, and DDX60 were associated with cancer stages. In addition, we also performed correlation analysis between DNA sensors and their main signaling molecules to explore the possible mechanisms. The results showed that there were positive correlations between AIM2 and ASC/IL-18, DHX9 and MAVS, and TLR9 and MyD88 expression. In addition, the gene expression patterns of some DNA sensors were confirmed by Western-blot analysis. Conclusions: Our study revealed that the expression of multiple DNA sensors was deregulated in CRC and might be involved in tumor development. More importantly, the study identified that, among all these DNA sensors, AIM2, DAI, and DDX60 could be potentially critical for diagnosis, prognosis, and therapy of CRC and deserve further investigation.

18.
Front Physiol ; 11: 623498, 2020.
Article in English | MEDLINE | ID: mdl-33536941

ABSTRACT

The global outbreak of the coronavirus disease 2019 (COVID-19) pandemic occurred in late 2019 and early 2020. The factors that influence disease severity should be of clinical concern. Existing findings on the effects of smoking on COVID-19 are also controversial and need to be confirmed by further research. In addition, the effects of alcohol consumption and betel quid (BQ) chewing on COVID-19 are unclear. The aim of this study was to examine the demographic characteristics of COVID-19 patients and the effects of smoking, drinking, BQ chewing, and underlying diseases on the severity of COVID-19. A retrospective study was conducted on 91 patients with confirmed cases of COVID-19 hospitalized in Yueyang, Hunan Province, China from 21 January to 8 March, 2020. Patient demographic data, and information on smoking, drinking and BQ chewing, and underlying diseases were extracted from the patient electronic medical records (EMR) and telephone interviews. The chi-square test was used to conduct a univariate analysis of the factors influencing the severity of COVID-19, and ordinal logistic regression analysis was used to identify the factors related to the severity of COVID-19. The results showed that the rates of smoking, drinking and BQ chewing were 15.4, 26.4, and 7.1%, respectively, there was no significant relationship between these lifestyle factors and the severity of COVID-19 (P > 0.05). However, underlying diseases such as diabetes [odds ratio (OR) = 7.740, 95% confidence interval (CI):1.000-60.740, P = 0.050], source of infection (OR = 0.180, 95% CI: 0.030-0.980, P = 0.049), and employment status (retired/unemployed vs. employed: OR = 29.430, 95% CI, 1.050 - 822.330, P = 0.047) were significant independent predictors of severe COVID-19 infection. These individuals should be informed of methods to increase personal protection, and doctors should prevent these individuals from developing serious diseases. It is important to pay attention to the source of infection and timely medical treatment. This study showed that the clinical classification of COVID-19 was associated with patients with diabetes, source of infection, and retired/unemployed. Therefore in the clinical practice of COVID-19 should be more concern these factors. Although no statistical significance was found in smoking, drinking alcohol, BQ chewing, and severity of COVID-19 patients, more studies have confirmed that are harmful and risk factors for underlying diseases in the population. Health authorities should formulate policies to publicize the harmful effects of smoking, drinking, and betel nut chewing and promote a healthy lifestyle.

19.
Materials (Basel) ; 12(11)2019 Jun 05.
Article in English | MEDLINE | ID: mdl-31195604

ABSTRACT

A novel corrosion and scale inhibitor (TPP) containing tobacco stem extract (TSE), polyepoxysuccinic acid (PESA), and polyaspartic acid (PASP) was obtained by the optimal proportion of the orthogonal test. The anticorrosion effect of TPP for carbon steel was researched by static weight-loss method, on-line simulated dynamic test, electrochemical measurement, and scanning electron microscopy (SEM). The results showed that TPP could protect carbon steel efficiently with a maximal corrosion inhibition rate of 85.7% and it was a mixed-type corrosion inhibitor, mainly exhibiting cathode suppression capacity. Simultaneously, the results of calcium carbonate deposition experiment indicated that the scale inhibition rate of TPP was up to 100%.

20.
Cytotechnology ; 71(1): 107-116, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30603916

ABSTRACT

The intestinal epithelium has an average lifespan of 4-5 days. Normally, primary intestinal epithelial cells can be cultured for about 15 days in vitro. The aim of this study was to explore methods to isolate and immortalize intestinal epithelial cells (IECs) of tree shrews in order to establish a new resource of experimental material and to provide a cell model for drug development and infection mechanism research. Tissue from the small intestine of tree shrews was digested with collagenase XI, neutral protease I, and dithiothreitol. The human telomerase reverse transcriptase gene (hTERT) was transferred into tree shrew IECs using the pHBLV-CMVIE-ZsGreen-Puro vector. The level of hTERT mRNA was detected by quantitative reverse transcription polymerase chain reaction. Immunofluorescence and western blot assays were performed to detect biochemical markers of IECs. The micromorphology of cells was observed with electron microscopy. We then conducted experiments to assess proliferative activity and analyze the karyotype of isolated cells. The results showed the immortalized cell line that we established and screened, maintained the characteristics and biochemical markers of primary IECs. Our results showed that the cell line we established can be considered an alternative cell model for intestinal drug research and for studies on intestinal infection and cell signaling.

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