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1.
Jpn J Infect Dis ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31666495

RESUMO

Estimation of prevalence and genotypes distribution of High-risk Human Papillomavirus (HR-HPV) is important for formulating strategies for prevention and screening of cervical cancer. This study aimed to determine HR-HPV prevalence and genotypes distribution among Chinese women living in Sichuan province. A total of 3089 women were recruited from the Third people's,Hospital of Chengdu in Sichuan province. HR-HPV genotyping were assessed by real-time quantitative PCR. Up to 720 cases (23.3%) were HR-HPV positive. 81.1% (584/720) were detected for a single HR-HPV genotype and 18.9% (136/720) for multiple genotypes. The most frequently detected HPV genotype was HPV52, followed by HPV58, HPV16, and HPV51. Age subgroup analysis showed two peaks for the frequencies of HPV infections, one for the group of women under 29 years old, and the other group over 50 years old. Among the women for whom cytology results were available, HPV16 was the most common detected genotype among women affected by HSIL (32.5%) and SCC, followed by HPV58, HPV33 and HPV52.This is one of the largest studies to demonstrate HPV prevalence and genotypes distribution among Chinese women in Sichuan. The prevalence and genotype distribution of HR-HPV was unique with higher frequencies of HPV52 and HPV58.

2.
Radiat Oncol ; 14(1): 195, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699115

RESUMO

BACKGROUND: The optimal treatment for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains inconclusive. Previous studies have shown that stereotactic body radiotherapy (SBRT) provides encouraging local control though higher incidence of toxicity in elderly than younger populations. The objective of this study was to compare the outcomes of SBRT and surgical treatment in elderly patients with clinical stage I-II NSCLC. METHODS: This retrospective analysis included 205 patients aged ≥70 years with clinical stage I NSCLC who underwent SBRT or surgery at Zhejiang Cancer Hospital (Hangzhou, China) from January 2012 to December 2017. A propensity score matching analysis was performed between the two groups. In addition, we compared outcomes and related toxicity in both study arms. RESULTS: Each group included 35 patients who met the inclusion criteria. Median follow-up was 50.1 (0.8-74.4) months for surgery and 35.5 (11.5-71.4) months for SBRT. The rate of cancer-specific survival was similar between the two treatment arms (p = 0.958). In patients who underwent surgery, the corresponding 3- and 5-year cancer-specific survival rates were 85.3 and 81.7%, respectively. In those who received radiotherapy, these rates were 91.3 and 74.9%, respectively. Moreover, the 3- and 5-year locoregional control in patients who underwent surgery were 90.0 and 80.0%, respectively. In those who received radiotherapy, these rates were 91.1 and 84.1%, respectively. Notably, the observed differences in progression-free survival were not statistically significant (p = 0.934). In the surgery group, grade 1-2 complications were observed in eleven patients (31%). One patient died due to perioperative infection within 30 days following surgery. There was no grade 3-5 toxicity observed in the SBRT group. CONCLUSIONS: The outcomes of surgery and SBRT in elderly patients with early-stage NSCLC were similar.

3.
Nanotoxicology ; : 1-19, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

4.
Diagn Pathol ; 14(1): 121, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672150

RESUMO

BACKGROUND: Ischemia/reperfusion (I/R) injury of heart is one of the major causes of acute cardiac injury, which may result in worsening or even loss of heart function. With novel microRNAs being evolutionarily discovered, numbers of them remained functionally unknown. We aimed to discover novel microRNAs with therapeutic or diagnostic potential in the setting of early cardiac I/R injury. METHODS: Cardiac electrical activity, biochemical detection and histopathology analysis were performed to reveal early changes of cardiac I/R injury. A microRNA array was performed to screen differential microRNAs in the mouse model of cardiac I/R injury. The differentially expressed microRNAs were validated in cardiac tissues and in serum samples. RESULTS: The abnormality in electrocardiogram and increases in serum cTnI levels suggested the successful establishment of cardiac I/R injury in mice. A total of 1882 microRNAs were identified, of which 11 were significantly down-regulated and 41 were significantly up-regulated at 3 h post reperfusion. microRNA 223-3p and microRNA 3113-5p were among the mostly altered microRNAs and were validated to be up-regulated within the early hours of I/R injury in heart tissues. In the circulating system, cTnI, a sensitive marker of cardiac injury, or microRNA 223-3p only increased within the first 6 h post I/R injury. However, microRNA 3113-5p stably increased in the serum, keeping an increase of 2.5-fold throughout the 24 h. In the human serum samples, microRNA 3113-5p was detected to be significantly upregulated as soon as 3 h after I/R stimuli and kept significantly higher levels within the 48 h. CONCLUSION: This is the first study that reported the functional roles of microRNA 3113-5p in cardiovascular system. Our data suggested that cardiac microRNA 3113-5p might be a useful target for therapeutic purposes and circulating microRNA 3113-5p might serve as a stable marker for early diagnosis of cardiac I/R injury.

5.
Glia ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721324

RESUMO

Schwann cell, the major glial cell in the peripheral nervous system, plays an essential role in peripheral nerve regeneration. However, the regulation of Schwann cell behavior following nerve injury is insufficiently explored. According to the development of high-throughput techniques, long noncoding RNAs (lncRNAs) have been recognized. Accumulating evidence shows that lncRNAs take part in diverse biological processes and diseases. Here, by microarray analysis, we identified an upregulated lncRNA profile following sciatic nerve injury and focused on BC088259 for further investigation. Silencing or overexpression of BC088259 could affect Schwann cell migration. Mechanistically, BC088259 might exert this regulatory role by directly binding with Vimentin. Collectively, our study not only revealed a set of upregulated lncRNAs following nerve injury but also identified a new functional lncRNA, BC088259, which was important for Schwann cell migration, providing a therapeutic avenue toward peripheral nerve injury.

6.
Int J Gynecol Pathol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569185

RESUMO

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus that has been described as the second most common malignant uterine mesenchymal tumor. The Primary extrauterine ESS (EESS) is an extremely uncommon occurrence. We hereby report a new bona fide case of low-grade EESS in a 74-yr-old woman arising in the vagina, presenting as a polypoid mass associated with irregular vaginal bleeding. On examination, a 6×2×2 cm polypoid mass was found in the left vaginal wall. Consequently, the patient underwent partial vaginectomy and repair. No ESS or endometriotic lesion was found in the endometrium and bilateral adnexa. The diagnosis of ESS performed by typical pathologic and immunohistochemical evaluation was as follows: beta-catenin (+++), estrogen receptor (+++), progesterone receptor (++), vimentin (++), and uniformly negative for CD10, EMA, CD31, CD34, CD117,CD99, SMA, desmin, h-caldesmon, S-100, MelanA, and HMB45. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 46 mo. Although CD10 is the most useful immunohistochemical marker for the diagnosis of this tumor, negative CD10 staining can be encountered with underfixation. Therefore, it is important to use a panel of immunostains that includes CD10, beta-catenin, and smooth muscle markers. The present study describes the clinical and pathologic features of low-grade EESS through a case report and literature review. To the best of our knowledge, this is the eighth report of EESS arising from the vagina.

7.
Aging (Albany NY) ; 11(19): 8542-8555, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590160

RESUMO

Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.

8.
Biochem Biophys Res Commun ; 520(3): 538-543, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31615653

RESUMO

The BioH carboxylesterase which is a typical α/ß-hydrolase enzyme involved in biotin synthetic pathway in most bacteria. BioH acts as a gatekeeper and blocks the further elongation of its substrate. In the pathogen Klebsiella pneumoniae, BioH plays a critical role in the biosynthesis of biotin. To better understand the molecular function of BioH, we determined the crystal structure of BioH from K. pneumoniae at 2.26 Šresolution using X-ray crystallography. The structure of KpBioH consists of an α-ß-α sandwich domain and a cap domain. B-factor analysis revealed that the α-ß-α sandwich domain is a rigid structure, while the loops in the cap domain shows the structural flexibility. The active site of KpBioH contains the catalytic triad (Ser82-Asp207-His235) on the interface of the α-ß-α sandwich domain, which is surrounded by the cap domain. Size exclusion chromatography shows that KpBioH prefers the monomeric state in solution, whereas two-fold symmetric dimeric formation of KpBioH was observed in the asymmetric unit, the conserved Cys31-based disulfide bonds can maintain the irreversible dimeric formation of KpBioH. Our study provides important structural insight for understanding the molecular mechanisms of KpBioH and its homologous proteins.

9.
Cell Death Dis ; 10(11): 787, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624232

RESUMO

Accumulating evidence suggests that circular RNAs (circRNAs) are abundant and play critical roles in the nervous system. However, their functions in axon regeneration after neuronal injury are unclear. Due to its robust regeneration capacity, peripheral nervous system is ideal for seeking the regulatory circRNAs in axon regeneration. In the present work, we obtained an expression profile of circRNAs in dorsal root ganglions (DRGs) after rat sciatic nerve crush injury by RNA sequencing (RNA-Seq) and found the expression level of circ-Spidr was obviously increased using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, circ-Spidr was proved to be a circular RNA enriched in the cytoplasm of DRG neurons. Through in vitro and in vivo experiments, we determined that down-regulation of circ-Spidr could suppress axon regeneration of DRG neurons after sciatic nerve injury partially through modulating PI3K-Akt signaling pathway. Together, our results reveal a crucial role for circRNAs in regulating axon regeneration after neuronal injury which may further serve as a potential therapeutic avenue for neuronal injury repair.

10.
Arch Toxicol ; 93(11): 3305-3320, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612242

RESUMO

Aflatoxin B1 (AFB1), a food contaminant derived from Aspergillus fungi, has been reported to cause hepatic immunotoxicity via inflammatory infiltration and cytokines release. As a pro-inflammatory factor, cyclooxygenase-2 (COX-2) is widely involved in liver inflammation induced by xenobiotics. However, the mechanism by which AFB1-induced COX-2 regulates liver inflammatory injury via hepatocytes-Kupffer cells (KCs) crosstalk remains unclear and requires further elucidation. Here, we established a COX-2 upregulated model with AFB1 treatment in vivo (C57BL/6 mice, 1 mg/kg body weight, i.g, 4 weeks) and in vitro (human liver HepaRG cells, 1 µM for 24 h). In vivo, AFB1-treated mice exhibited NLRP3 inflammasome activation, inflammatory infiltration, and increased recruitment of KCs. In vitro, dephosphorylated COX-2 by protein phosphatase 2A (PP2A)-B55δ promoted NLRP3 inflammasome activation, including mitochondrial translocation of NLRP3, caspase 1 cleavage, and IL-1ß release. Moreover, phosphorylated COX-2 at serine 601 (p-COX-2Ser601) underwent endoplasmic reticulum (ER) retention for proteasome degradation. Furthermore, pyroptosis and inflammatory response induced by AFB1 were relieved with COX-2 genetic (siPTGS2) intervention or pharmaceutic (celecoxib, 30 mg/kg body weight, i.g, 4 weeks) inhibition of COX-2 via NLRP3 inflammasome suppression in vivo and in vitro. Ex vivo, in a co-culture system with murine primary hepatocytes and KCs, activated KCs induced by damaged signals from pyroptotic hepatocytes, formed a feedback loop to amplify NLRP3-dependent pyroptosis of hepatocytes via pro-inflammatory signaling, leading to liver inflammatory injury. Taken together, our data suggest a novel mechanism that protein quality control of COX-2 determines the intracellular distribution and activation of NLRP3 inflammasome, which promotes liver inflammatory injury via hepatocytes-KCs crosstalk.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1568-1573, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607313

RESUMO

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose decitabine (DAC) alone for treatment of myelodysplastic syndrome (MDS) Methods: Fifty-one patients with meddle- and high-risk MDS were selected, and were randomly divided into A, B and C groups according to the drug regimens: the therapeutic regimen in A group consisted of low dose DAC 10 mg/(m2·d)×7 d; the therapeutic regimen in B group: normal dose DAC 20 mg/(m2·d) ×5 d; the therapeutic regimen in C group: low dose DAC+CAG DAC 10 mg/(m2·d) d 1-5,cytarabine 10 mg/(m2·d) q12h d 1-7, aclaromycin 10 mg/d d 1-4,G-CSF 200 µg/(m2·d), d 1-7. All patients in 3 groups were treated for 4 circles. The efficacy and response were compared among 3 groups. RESULTS: The complete remission rates (CR%) in A, B and C groups were 18.75%, 22.22% and 23.53% respectively, and the overall response rate (ORR%) in A, B and C groups were 56.25%, 61.11% and 58.82% respectively, without statistical difference among 3 groups (P>0.05).After 1 year of follow-up, the survival rate was not significantly different among 3 groups, the blood cell accounts were higher than the basic value. After 1 course of treatment, the inhibition rate of III-IV grade myelosuppression was statistically significantly different among the 3 groups (P<0.05), and the infection rate among 3 groups also was statistically different, The incidence of myelosuppression and infection in A group was significantly lower than that in B and C groups. The per capita blood transfusion during the four-month treatment was not statistically different among 3 groups. however, that in the A group was lesser than B and C groups. CONCLUSION: The therapeutic efficacy of low dose decitabine alone for treatment of MDS is equal to routine dose decitabine and decitabine plus CAG, but the low dose group shows less myelosuppressive and more safe effects.


Assuntos
Decitabina/uso terapêutico , Síndromes Mielodisplásicas , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Resultado do Tratamento
12.
Dermatology ; : 1-10, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553991

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic, recurrent skin condition with recently increased incidence in younger children. AD development has been correlated with the skin microbiome, and Staphylococcus aureus enrichment causes significant increases in skin lesions. OBJECTIVE: Our objectives were to compare the microbial diversity of the cheek skin of children with or without AD aged 0-1 years in China, and to determine whether 4 types of skin-isolated bacteria could inhibit S. aureus in vitro. METHODS: The skin microbial samples of cheek skin of children were sequenced by 16S rRNA V1-V2 region. Four skin isolated bacterial fermentation supernatants were tested for effects on S. aureus growth, membrane formation, and induction of cytokine secretion from HaCaT cells. RESULTS: Bacterial diversity decreased significantly in skin with severe AD compared to healthy skin (p < 0.01). Seven phyla had content >1%, 4 of which differed in AD (p < 0.05). 38 genera had content >1%, 15 differed (p < 0.05). Differences in 8 species were observed (p < 0.05). In vitro antibacterial and cellular experiments showed that S. aureus growth, biofilm formation, and induction of interleukin (IL)-1α and IL-6 secretion from HaCaT cells were significantly inhibited by Klebsiella oxytoca, Kocuria rhizophila, and Staphylococcus epidermidis culture supernatants (p < 0.05). CONCLUSION: Skin microbiome changes in children varied with age and with AD. There were complex interactions between skin isolated bacteria and S. aureus which could inhibit S. aureus growth and biofilm formation in vitro, suggesting that these microorganisms could be used in AD treatment.

13.
Exp Dermatol ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472099

RESUMO

BACKGROUND: The microbiological basis of diaper dermatitis has not been clearly elucidated; however, a better understanding of microbial colonization may be vital for developing appropriate therapies. METHODS: Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities obtained from the buttock skin sites of children with diaper dermatitis and from healthy controls. Bacterial diversity in the buttock lesion area and subsequent recovery after emollient treatment have been discussed herein. RESULTS: In buttock skin of children with or without diaper dermatitis, Staphylococcus and Anaerococcus were predominant in the total skin microbiome. Compared with the healthy group, the overall skin bacterial richness and diversity were higher in children with diaper dermatitis, with the abundance of Proteobacteria being significantly higher. In the diaper dermatitis group, the richness of Enterococcus, Erwinia and Pseudomonas was significantly higher, and the levels of Clostridium and Actinomyces were significantly lower than those in healthy children. Richness of Staphylococcus aureus was significantly higher in the diaper dermatitis group, whereas that of Staphylococcus epidermidis and Bifidobacterium longum was lower. Staphylococcus epidermidis and Staphylococcus haemolyticus, the dominant species found in buttock skin, were observed to recover earlier after the disease had improved through emollient treatment. CONCLUSION: Staphylococcus epidermidis, as skin probiotic bacterium, and B longum, Clostridium butyricum and Lactobacillus ruminis, which are intestinal probiotic bacteria, are significantly decreased in diaper dermatitis lesions. These changes in the buttock skin microflora indicate an imbalance in the microflora and suggest that the intestinal microflora may be undergoing dynamic changes. The results of this study suggest that probiotic bacterial supplementation may be useful in the treatment and prevention of diaper dermatitis.

14.
Clin Chim Acta ; 499: 54-63, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476302

RESUMO

Chronic kidney disease (CKD), characterized as renal dysfunction, is recognized as a major public health problem with high morbidity and mortality worldwide. Unfortunately, there are no obvious clinical symptoms in early stage disease until severe damage has occurred. Further complicating early diagnosis and treatment is the lack of sensitive and specific biomarkers. As such, novel biomarkers are urgently needed. Metabolomics has shown an increasing potential for identifying underlying disease mechanisms, facilitating clinical diagnosis and developing pharmaceutical treatments for CKD. Recent advances in metabolomics revealed that CKD was closely associated with the dysregulation of numerous metabolites, such as amino acids, lipids, nucleotides and glycoses, that might be exploited as potential biomarkers. In this review, we summarize recent metabolomic applications based on animal model studies and in patients with CKD and highlight several biomarkers that may play important roles in diagnosis, intervention and development of new therapeutic strategies.

15.
J Am Heart Assoc ; 8(18): e011948, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31480879

RESUMO

Background Few reports have addressed the mechanism by which microRNA miR-10b-5p regulates post-myocardial infarction (post-MI) cardiomyocyte apoptosis under hypoxic conditions. Methods and Results C57BL/6 mice underwent surgical ligation of the left anterior descending artery to create an MI or ischemia/reperfusion animal model. The expression of miR-10b-5p, PTEN (phosphatase and tensin homolog), and HIF-1α (hypoxia-inducible factor 1α) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR-10b-5p, overexpression lentiviruses were made in the areas surrounding the MI sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR-10b-5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and PTEN expression. Meanwhile, PTEN as a target of miR-10b-5p was verified via luciferase reporter gene assays. Cotransfection of miR-10b-5 and PTEN verified the relationship between miR-10b-5 and PTEN. Under hypoxic stress, the expression of HIF-1α and miR-10b-5p was examined. The results showed that miR-10b-5p expression was markedly reduced in the infarct border zone. Overexpression of miR-10b-5p in the murine model of MI significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR-10b-5p in vitro antagonized hypoxia-induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis-related gene PTEN, but overexpression of PTEN weakened these effects. We also found that hypoxia-induced accumulation of HIF-1α resulted in decreased expression of miR-10b-5p. Interfering with the activation of the HIF-1α signaling pathway promoted Pri-miR-10b and miR-10b-5p expression and inhibited PTEN expression. Conclusions MicroRNA miR-10b-5p antagonizes hypoxia-induced cardiomyocyte apoptosis, indicating that miR-10b-5p may serve as a potential future clinical target for the treatment of MI.

16.
Biochem Biophys Res Commun ; 519(2): 274-279, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493870

RESUMO

Lipases are widely present in various plants, animals and microorganisms, constituting a large category of enzymes. They have the ability to catalyze the cleavage of ester bonds. The lipase CinB from Enterobacter asburiae (E. asburiae) is an acetyl esterase. The primary amino acid sequence suggests that the EaCinB protein belongs to the α/ß-hydrolase (ABH) superfamily of the esterase/lipase superfamily. However, its molecular functions have not yet been determined. Here, we report the crystal structure of E. asburiae CinB at a 1.45 Šresolution. EaCinB contains a signal peptide, cap domain and catalytic domain. The active site of EaCinB contains the catalytic triad (Ser180-His307-Asp277) on the catalytic domain. The oxyanion hole is composed of Gly106 and Gly107 within the conserved sequence motif HGGG (amino acid residues 106-109). The substrate is accessible between the α1 and α2 helices or the α1 helix and catalytic domain. Narrow substrate pockets are formed by the α2 helix of the cap domain. Site-directed mutagenesis showed that EaCinB-W208H exhibits a higher catalytic ability than EaCinB-WT by approximately nine times. Our results provide insight into the molecular function of EaCinB.

17.
Biochem Biophys Res Commun ; 519(2): 280-286, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495495

RESUMO

The emergence of drug-resistant strains of Klebsiella pneumoniae, has exacerbated the treatment and control of the disease caused by this bacterium. Cytidine deaminases (CDA) are zinc-dependent enzymes involved in the pyrimidine salvage pathway and catalyze the formation of uridine and deoxyuridine from cytidine and deoxycytidine, respectively. To illustrate the structural basis of CDA for a deeper knowledge of the molecular mechanisms underlying the salvage pathway, we reported here the biochemical and structural analysis of CDA from pathogenic K. pneumonia. KpCDA showed deaminase activity against cytidine as well as its analog cytarabine. The deaminase activity of KpCDA on cytarabine was 1.8 times higher than that on cytidine. KpCDA is composed of an N-terminal catalytic domain and a C-terminal noncatalytic domain. Zinc, which is involved in the activity of the catalytic domain, is coordinated by His102, Cys129, and Cys132, and two 1,4-dioxane molecules were present at the active sites. KpCDA exists as a dimer and shows distinct dimeric interface compared with other CDAs. Our results provide the structural features of KpCDA, and KpCDA might be a potential antibacterial target for the disease caused by K. pneumoniae.

18.
Water Sci Technol ; 80(2): 308-316, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31537767

RESUMO

In this study, a novel composite of modified diatomite supported nanoscale zero-valent iron (mD-NZVI) was synthesized and characterized. The effects of four factors (mD-NZVI dose, temperature, contact time and initial pH) on the removal of Cr(VI) by mD-NZVI were studied by experimental work and analyzed by response surface methodology (RSM). A second-order polynomial equation fitted by Box-Behnken design was used as a statistical model and proved to be precise in describing the significance of four factors. The analysis results show that the effects of four factors on the removal efficiency of Cr(VI) were significant (F value is 19.83), initial pH was found to be the key factor. In addition, the effect of initial pH was further studied and the maximum removal efficiency of 89.34% was obtained at pH of 3, the decrease in removal efficiency with the increase in pH is a synergistic effect of Cr(VI) species, surface charge of mD-NZVI and OH- amount at different pH.


Assuntos
Cromo/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Cromo/análise , Terra de Diatomáceas , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/análise
19.
Emerg Microbes Infect ; 8(1): 1361-1369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522608

RESUMO

Rapid and simple-to-use diagnostic methods for tuberculosis are urgently needed. Recent development has unveiled the diagnostic power of the CRISPR system in the detection of viral infections. However, its potential use in detecting the Mycobacterium tuberculosis complex (MTB) remained unexplored. We developed a rapid CRISPR-based assay for TB detection and conducted a retrospective cohort study of 179 patients to evaluate the CRISPR-MTB test for identifying MTB in various forms of direct clinical samples. Its diagnostic performance was compared, in parallel with culture and the GeneXpert MTB/RIF assay (Xpert). The CRISPR-MTB test is highly sensitive with a near single-copy sensitivity, demands less sample input and offers shorter turnaround time than Xpert. When evaluated in the clinical cohort of both pulmonary and extra-pulmonary tuberculosis, the CRISPR-MTB test exhibited an overall improved sensitivity over both culture (79% vs 33%) and Xpert (79% vs 66%), without comprise in specificity (62/63, 98%). The CRISPR-MTB test exhibits an improved overall diagnostic performance over culture and Xpert across a variety of sample types, and offers great potential as a new diagnostic technique for both pulmonary and extra-pulmonary tuberculosis.

20.
Mol Cell Biochem ; 462(1-2): 185-194, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31482388

RESUMO

Circular RNAs (circRNAs) are effector molecules that exert functions in cardiovascular diseases. Nevertheless, the effects of circRNAs on myocardial ischemia remain uninvestigated. This paper aimed to explore the functions of circ_0010729 in oxygen-glucose-deprivation (OGD)-caused injury of human cardiomyocytes (HCM). HCM were exposed to OGD environment for 4 h. Then the expression of circ_0010729 was evaluated by RT-qPCR. After transfection, cell viability, apoptosis, and migration were examined to evaluate the impact of overexpression and knockdown of circ_0010729 on OGD-induced cell injury. The regulation between circ_0010729 and microRNA-145-5p (miR-145-5p) was verified. After miR-145-5p inhibitor transfection, whether aberrant miR-145-5p expression affected the modulation of circ_0010729 in OGD-induced cell injury was measured. Western blot was utilized to analyze mTOR and MEK/ERK pathway-related proteins. OGD treatment enhanced circ_0010729 expression and evoked cell injury in HCM. Moreover, OGD-induced injury was aggrandized by circ_0010729 overexpression via suppressing cell growth and migration in HCM. Knockdown of circ_0010729 attenuated OGD-induced injury. In addition, circ_0010729 negatively regulated miR-145-5p expression. MiR-145-5p inhibition reversed the effects of silencing circ_0010729 on OGD-induced injury and mTOR and MEK/ERK pathways. We demonstrated that silencing circ_0010729 activated mTOR and MEK/ERK pathways by up-regulating miR-145-5p, thereby protecting HCM from OGD-induced injury.

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