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Article ; Online: Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis.

Yang, Ruwen / Jiang, Jiawei / Ouyang, Jun / Zhao, Yuanpei / Xi, Biao

Clinical nutrition ESPEN

2024 Volume 60, Page(s) 362–372

Abstract: Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting.: Aims: To conduct a ... ...

Abstract	Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting. Aims: To conduct a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety of probiotics for IBS patients. Methods: We searched relevant trials in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar from 2000 to June 2023. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes. A risk ratio (RR) and a 95% CI were calculated for dichotomous outcomes. Results: A total of 20 studies involving 3011 patients were obtained. The results demonstrated that probiotics are more effective than placebo in reducing global IBS symptoms improvement rate (RR = 1.401, 95% CI 1.182-1.662, P < 0.001) and quality of life scores (SMD = 0.286, 95% CI = 0.154-0.418, P < 0.001). Subgroup analyses showed that a shorter treatment time (less than eight weeks) could reduce distension scores (SMD = 0.197, 95% CI = 0.038-0.356, P = 0.015). High doses (daily dose of probiotics ≥ 10ˆ10) or multiple strains of probiotics exhibit beneficial effects on abdominal pain (SMD = 0.412, 95% CI = 0.112-0.711, P = 0.007; SMD = 0.590, 95% CI = 0.050-1.129, P = 0.032; respectively). However, there was no significant benefit on global symptom scores (SMD = 0.387, 95% CI 0.122 to 0.653, P = 0.004) with statistically high inter-study heterogeneity (I2 = 91.9%, P < 0.001). Furthermore, there was no significant inter-group difference in terms of adverse events frequency (RR = 0.997, 95% CI 0.845-1.177, P = 0.973). Conclusion: Probiotics are effective and safe for IBS patients. High doses or multiple probiotic strains seem preferable, but definite conclusions are challenging due to the high heterogeneity. Large-scale, well-designed, and rigorous trials are needed to confirm their effectiveness.
MeSH term(s)	Humans ; Irritable Bowel Syndrome/drug therapy ; Quality of Life ; Abdominal Pain/therapy ; Probiotics/adverse effects ; Odds Ratio
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ISSN	2405-4577
ISSN (online)	2405-4577
DOI	10.1016/j.clnesp.2024.02.025
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Article ; Online: Study on the Grading Model of Hepatic Steatosis Based on Improved DenseNet.

Yang, Ruwen / Zhou, Yaru / Liu, Weiwei / Shang, Hongtao

Journal of healthcare engineering

2022 Volume 2022, Page(s) 9601470

Abstract: To achieve intelligent grading of hepatic steatosis, a deep learning-based method for grading hepatic steatosis was proposed by introducing migration learning in the DenseNet model, and the effectiveness of the method was verified by applying it to the ... ...

Abstract	To achieve intelligent grading of hepatic steatosis, a deep learning-based method for grading hepatic steatosis was proposed by introducing migration learning in the DenseNet model, and the effectiveness of the method was verified by applying it to the practice of grading hepatic steatosis. The results show that the proposed method can significantly reduce the number of model iterations and improve the model convergence speed and prediction accuracy by introducing migration learning in the deep learning DenseNet model, with an accuracy of more than 85%, sensitivity of more than 94%, specificity of about 80%, and good prediction performance on the training and test sets. It can also detect hepatic steatosis grade 1 more accurately and reliably, and achieve automated and more accurate grading, which has some practical application value.
MeSH term(s)	Fatty Liver ; Humans
Language	English
Publishing date	2022-03-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2545054-2
ISSN	2040-2309 ; 2040-2295
ISSN (online)	2040-2309
ISSN	2040-2295
DOI	10.1155/2022/9601470
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Article: Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo

Liu, Weiwei / Shang, Jingyu / Deng, Yinxiang / Han, Xiuzhen / Chen, Yugen / Wang, Shuangshuang / Yang, Ruwen / Dong, Fan / Shang, Hongtao

Journal of ethnopharmacology. 2022 Sept. 15, v. 295

2022

Abstract: Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. We evaluated the effects and mechanisms of JPQGY and hepatic ... ...

Abstract	Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice. Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting. JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model. The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease.
Keywords	blood serum ; body weight ; eosin ; fatty liver ; high fat diet ; histology ; lipid metabolism ; liver ; mice ; pharmacology ; protein synthesis ; quantitative polymerase chain reaction ; traditional medicine
Language	English
Dates of publication	2022-0915
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115382
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Article ; Online: Effects of probiotics on nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Yang, Ruwen / Shang, Jingyu / Zhou, Yaru / Liu, Weiwei / Tian, Yaozhou / Shang, Hongtao

Expert review of gastroenterology & hepatology

2021 Volume 15, Issue 12, Page(s) 1401–1409

Abstract: Objectives: Several studies have suggested that the gut-liver axis is closely related to nonalcoholic fatty liver disease (NAFLD). This study was designed to conduct a meta-analysis based on a randomized controlled trial (RCT) to systematically evaluate ...

Abstract	Objectives: Several studies have suggested that the gut-liver axis is closely related to nonalcoholic fatty liver disease (NAFLD). This study was designed to conduct a meta-analysis based on a randomized controlled trial (RCT) to systematically evaluate the efficacy of probiotics in the treatment of NAFLD. Methods: This study carried out a literature search of published scientific data (up to April 2021) on probiotic therapies of NAFLD. The quality of the included literature was evaluated, and the corresponding data were extracted using the RevMan5.4 software. Results: A total of 9 randomized clinical trials involving 352 patients with NAFLD were included in this study. Results of the meta-analysisstudy showed that probiotic therapy group have significant reduction in the levels of serum indices: alanine aminotransferase (ALT), aspartate transaminase (AST) and total cholesterol (TC) in comparison with the control group. Probiotic therapy was not associated with changes in body mass index (BMI) homeostasis model assessment of insulin resistance (HOMA-IR) and tumor necrosis factor (TNF) Subgroup analyses of BMI indicated that three or more composite probiotics or probiotic treatment for more than three months can significantly reduce the BMI level. Conclusion: This systematic review and meta-analysis demonstrated that modulating gut microbiota may be utilized as an effective method to improve liver function and reduce blood lipid levels in patients with NAFLD.
MeSH term(s)	Biomarkers/blood ; Body Mass Index ; Gastrointestinal Microbiome ; Humans ; Liver Function Tests ; Non-alcoholic Fatty Liver Disease/therapy ; Probiotics/therapeutic use ; Randomized Controlled Trials as Topic
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-12-08
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review ; Video-Audio Media
ZDB-ID	2481021-6
ISSN	1747-4132 ; 1747-4124
ISSN (online)	1747-4132
ISSN	1747-4124
DOI	10.1080/17474124.2022.2016391
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Article ; Online: Identification of chitin synthase activator in Aspergillus niger and its application in citric acid fermentation.

Jiang, Chunxu / Wang, Han / Liu, Menghan / Wang, Li / Yang, Ruwen / Wang, Peng / Lu, Zongmei / Zhou, Yong / Zheng, Zhiming / Zhao, Genhai

Applied microbiology and biotechnology

2022 Volume 106, Issue 21, Page(s) 6993–7011

Abstract: The biosynthesis of citric acid (CA) using Aspergillus niger as a carrier is influenced by mycelium morphology, which is determined by the expression level of morphology-related genes. As a key component of the fungal cell wall, chitin content has an ... ...

Abstract	The biosynthesis of citric acid (CA) using Aspergillus niger as a carrier is influenced by mycelium morphology, which is determined by the expression level of morphology-related genes. As a key component of the fungal cell wall, chitin content has an important effect on morphogenesis, and to investigate the effects of this on fermentation performance, we used RNA interference to knockdown chitin synthase C (CHSC) and chitin synthase activator (CHS3) to obtain the single-gene mutant strains A. niger chs3 and chsC and the double mutant A. niger chs3C. We found that the CA fermentation performance of the two single mutants was significantly better than that of the double mutant. The mutant A. niger chs3-4 exhibited CA production potential compared to that of the parent strain in scale-up fermentation; we determined certain characteristics of CA high-yielding strain fermentation pellets. In addition, when chsC alone was silenced, there was very little change in chs3 mRNA levels, whereas those of chsC were significantly reduced when only chs3 was silenced. As this may be because of a synergistic effect between chsC and chs3, and we speculated that the latent activation target of CHS3 is CHSC, our results confirmed this hypothesis. This study is the first application of a separation and combination silence strategy of chitin synthase and chitin synthase activator in the morphology of A. niger CA fermentation. Furthermore, it provides new insights into the method for the morphological study of A. niger fermentation and the interaction of homologous genes. KEY POINTS: • The function of chitin synthase C (chsC) and chitin synthase activator (chs3) is tightly interrelated. • Mycelial morphology was optimized by knockdown of CHS3, resulting in the overproduction of citric acid. • The separation and combination silence strategies are promising tools for the interaction of homologous housekeeping genes.
MeSH term(s)	Chitin Synthase/genetics ; Aspergillus niger/genetics ; Aspergillus niger/metabolism ; Citric Acid ; Fermentation ; Chitin/metabolism ; RNA, Messenger/metabolism
Chemical Substances	Chitin Synthase (EC 2.4.1.16) ; Citric Acid (2968PHW8QP) ; Chitin (1398-61-4) ; RNA, Messenger
Language	English
Publishing date	2022-09-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-022-12174-9
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Article ; Online: Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo.

Liu, Weiwei / Shang, Jingyu / Deng, Yinxiang / Han, Xiuzhen / Chen, Yugen / Wang, Shuangshuang / Yang, Ruwen / Dong, Fan / Shang, Hongtao

Journal of ethnopharmacology

2022 Volume 295, Page(s) 115382

Abstract: Ethnopharmacological relevance: Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear.: Aim of the study: We ... ...

Abstract	Ethnopharmacological relevance: Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. Aim of the study: We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice. Materials and methods: Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting. Results: JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model. Conclusions: The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Animals ; Diet, High-Fat ; Inflammation/pathology ; Lipid Metabolism ; Liver ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Network Pharmacology ; Non-alcoholic Fatty Liver Disease/metabolism ; PPAR alpha/genetics ; PPAR alpha/metabolism
Chemical Substances	NF-kappa B ; PPAR alpha ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2022-05-14
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115382
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Article ; Online: Identification of chitin synthase activator in Aspergillus niger and its application in citric acid fermentation

Jiang, Chunxu / Wang, Han / Liu, Menghan / Wang, Li / Yang, Ruwen / Wang, Peng / Lu, Zongmei / Zhou, Yong / Zheng, Zhiming / Zhao, Genhai

Appl Microbiol Biotechnol. 2022 Nov., v. 106, no. 21 p.6993-7011

2022

Abstract	The biosynthesis of citric acid (CA) using Aspergillus niger as a carrier is influenced by mycelium morphology, which is determined by the expression level of morphology-related genes. As a key component of the fungal cell wall, chitin content has an important effect on morphogenesis, and to investigate the effects of this on fermentation performance, we used RNA interference to knockdown chitin synthase C (CHSC) and chitin synthase activator (CHS3) to obtain the single-gene mutant strains A. niger chs3 and chsC and the double mutant A. niger chs3C. We found that the CA fermentation performance of the two single mutants was significantly better than that of the double mutant. The mutant A. niger chs3-4 exhibited CA production potential compared to that of the parent strain in scale-up fermentation; we determined certain characteristics of CA high-yielding strain fermentation pellets. In addition, when chsC alone was silenced, there was very little change in chs3 mRNA levels, whereas those of chsC were significantly reduced when only chs3 was silenced. As this may be because of a synergistic effect between chsC and chs3, and we speculated that the latent activation target of CHS3 is CHSC, our results confirmed this hypothesis. This study is the first application of a separation and combination silence strategy of chitin synthase and chitin synthase activator in the morphology of A. niger CA fermentation. Furthermore, it provides new insights into the method for the morphological study of A. niger fermentation and the interaction of homologous genes. KEY POINTS: • The function of chitin synthase C (chsC) and chitin synthase activator (chs3) is tightly interrelated. • Mycelial morphology was optimized by knockdown of CHS3, resulting in the overproduction of citric acid. • The separation and combination silence strategies are promising tools for the interaction of homologous housekeeping genes.
Keywords	Aspergillus niger ; RNA interference ; biosynthesis ; cell walls ; chitin ; chitin synthase ; citric acid ; fermentation ; fungi ; morphogenesis ; mutants ; mycelium ; synergism
Language	English
Dates of publication	2022-11
Size	p. 6993-7011.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-022-12174-9
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Article: Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice.

Schifflers, Christoph / Zottnick, Samantha / Förster, Jonas D / Kruse, Sebastian / Yang, Ruwen / Wiethoff, Hendrik / Bozza, Matthias / Hoppe-Seyler, Karin / Heikenwälder, Mathias / Harbottle, Richard P / Michiels, Carine / Riemer, Angelika B

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 2

Abstract: Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological ... ...

Abstract	Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities.
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12020188
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Article ; Online: Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children's Medical Center.

Tao, Yue / Yan, Hui / Liu, Yujie / Zhang, Fang / Luo, Lijuan / Zhou, Yajuan / An, Kang / Yang, Ruwen / Yang, Bin / Xu, Teng / Xie, Li / Ren, Hong / Xu, Zhuoming / Cao, Qing / Mo, Xi

Clinical chemistry

2022 Volume 68, Issue 8, Page(s) 1031–1041

Abstract: Background: Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of ... ...

Abstract	Background: Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. Methods: From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. Results: According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). Conclusions: For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.
MeSH term(s)	Child ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/methods ; Retrospective Studies ; Sensitivity and Specificity
Language	English
Publishing date	2022-06-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvac067
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Article ; Online: Folate Repletion after Deficiency Induces Irreversible Genomic and Transcriptional Changes in Human Papillomavirus Type 16 (HPV16)-Immortalized Human Keratinocytes.

Savini, Claudia / Yang, Ruwen / Savelyeva, Larisa / Göckel-Krzikalla, Elke / Hotz-Wagenblatt, Agnes / Westermann, Frank / Rösl, Frank

International journal of molecular sciences

2019 Volume 20, Issue 5

Abstract: Supplementation of micronutrients like folate is a double-edged sword in terms of their ambivalent role in cell metabolism. Although several epidemiological studies support a protective role of folate in carcinogenesis, there are also data arguing for an ...

Abstract	Supplementation of micronutrients like folate is a double-edged sword in terms of their ambivalent role in cell metabolism. Although several epidemiological studies support a protective role of folate in carcinogenesis, there are also data arguing for an opposite effect. To address this issue in the context of human papillomavirus (HPV)-induced transformation, the molecular events of different folate availability on human keratinocytes immortalized by HPV16 E6 and E7 oncoproteins were examined. Several sublines were established: Control (4.5 µM folate), folate deficient (0.002 µM folate), and repleted cells (4.5 µM folate). Cells were analyzed in terms of oncogene expression, DNA damage and repair, karyotype changes, whole-genome sequencing, and transcriptomics. Here we show that folate depletion irreversibly induces DNA damage, impairment of DNA repair fidelity, and unique chromosomal alterations. Repleted cells additionally underwent growth advantage and enhanced clonogenicity, while the above mentioned impaired molecular properties became even more pronounced. Overall, it appears that a period of folate deficiency followed by repletion can shape immortalized cells toward an anomalous phenotype, thereby potentially contributing to carcinogenesis. These observations should elicit questions and inquiries for broader additional studies regarding folate fortification programs, especially in developing countries with micronutrient deficiencies and high HPV prevalence.
MeSH term(s)	Carcinogenesis/genetics ; DNA Damage/ethics ; DNA Repair/genetics ; Folic Acid/genetics ; Folic Acid Deficiency/genetics ; Folic Acid Deficiency/pathology ; Folic Acid Deficiency/virology ; Genomics ; Human papillomavirus 16/genetics ; Human papillomavirus 16/pathogenicity ; Humans ; Keratinocytes/virology ; Oncogene Proteins, Viral/genetics ; Papillomavirus E7 Proteins/genetics ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; Repressor Proteins/genetics ; Transcription, Genetic
Chemical Substances	E6 protein, Human papillomavirus type 16 ; Oncogene Proteins, Viral ; Papillomavirus E7 Proteins ; Repressor Proteins ; oncogene protein E7, Human papillomavirus type 16 ; Folic Acid (935E97BOY8)
Language	English
Publishing date	2019-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20051100
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