Publications by authors named "Jiani Chen"

80 Publications

Inpatient Dignity Scale: Mandarin translation and psychometric characteristics evaluation.

Nurs Open 2021 Oct 6. Epub 2021 Oct 6.

School of Health Sciences, Caritas Institute of Higher Education, Hong Kong SAR, China.

Aim: The aim of this paper was to translate the English version of the Inpatient Dignity Scale into Mandarin and to test the psychometric properties of the Mandarin version of the Inpatient Dignity Scale.

Design: This research is a cross-sectional survey, using convenience sampling.

Methods: The English version of the Inpatient Dignity Scale was translated into Mandarin Chinese. From June-August 2020, 736 inpatients from 50 tertiary hospitals in Guangzhou were recruited to assess the psychometric attributes of the Inpatient Dignity Scale.

Results: The Mandarin version of the Inpatient Dignity Scale consists of expectation and satisfaction subscales. It differs from the English language version, as the expectation subscale includes three dimensions and the satisfaction subscale includes two dimensions. The total Cronbach alpha coefficient of the expectation subscale and the satisfaction subscale were .820 and .965, respectively, and the split-half reliability of the expectation subscale and the satisfaction subscale were 0.740 and 0.928, respectively, indicating good internal consistency and effectiveness. Known-groups validity was established, as 70% of the hypotheses were supported.
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http://dx.doi.org/10.1002/nop2.1088DOI Listing
October 2021

Spermine-Related DNA Hypermethylation and Elevated Expression of Genes for Collagen Formation are Susceptible Factors for Chemotherapy-Induced Hand-Foot Syndrome in Chinese Colorectal Cancer Patients.

Front Pharmacol 2021 1;12:746910. Epub 2021 Sep 1.

Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.
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http://dx.doi.org/10.3389/fphar.2021.746910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440935PMC
September 2021

Neofunctionalization of an ancient domain allows parasites to avoid intraspecific competition by manipulating host behaviour.

Nat Commun 2021 09 16;12(1):5489. Epub 2021 Sep 16.

Institute of Insect Sciences, Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insect Pests, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite's manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system.
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http://dx.doi.org/10.1038/s41467-021-25727-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446075PMC
September 2021

Mass Spectrometry-Based Targeted Serum Monomethylated Ribonucleosides Profiling for Early Detection of Breast Cancer.

Front Mol Biosci 2021 26;8:741603. Epub 2021 Aug 26.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

RNA methylation plays a significant regulatory role in various of physiological activities and it has gradually become a hotspot of epigenetics in the past decade. 2'-O-methyladenosine (Am), 2'-O-methylguanosine (Gm), 2'-O-methylcytidine (Cm), 2'-O-methyluridine (Um), -methyladenosine (mA), -methylguanosine (mG), 5-methylcytidine (mC), and 5-methyluridine (mU) are representative 2'-O-methylation and base-methylation modified epigenetic marks of RNA. Abnormal levels of these ribonucleosides were found to be related to various diseases including cancer. Serum is an important source of biofluid for the discovery of biomarkers, and novel tumor biomarkers can be explored by measuring these ribonucleoside modifications in human serum. Herein, we developed and applied a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method to determine the content of monomethylated ribonucleosides in human serum. The developed method enabled sensitive and accurate determination of these monomethylated ribonucleosides. By applying this robust method, we demonstrated the presence of Gm and Um in human serum for the first time, and we successfully quantified mA, Gm, mG, Cm, Um and mU in serum samples collected from 61 patients with breast cancer and 69 healthy controls. We discovered that the levels of Gm, mG, Cm, Um and mU in serum were all significantly decreased in breast cancer patients whereas mA was increased. We performed receiver operating characteristic (ROC) curve analysis, and obtained highest area under curve (AUC) value when combining these six monomethylated ribonucleosides together. These results suggest that mA, Gm, mG, Cm, Um and mU might have great potential to be novel biomarkers for detection of breast cancer in the early stage. In addition, this study may stimulate future investigations about the regulatory roles of monomethylated ribonucleosides on the initiation and development of breast cancer.
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http://dx.doi.org/10.3389/fmolb.2021.741603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427278PMC
August 2021

DNA methyltransferase CHROMOMETHYLASE3 prevents ONSEN transposon silencing under heat stress.

PLoS Genet 2021 Aug 19;17(8):e1009710. Epub 2021 Aug 19.

Wisconsin Institute for Discovery & Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

DNA methylation plays crucial roles in transposon silencing and genome integrity. CHROMOMETHYLASE3 (CMT3) is a plant-specific DNA methyltransferase responsible for catalyzing DNA methylation at the CHG (H = A, T, C) context. Here, we identified a positive role of CMT3 in heat-induced activation of retrotransposon ONSEN. We found that the full transcription of ONSEN under heat stress requires CMT3. Interestingly, loss-of-function CMT3 mutation led to increased CHH methylation at ONSEN. The CHH methylation is mediated by CMT2, as evidenced by greatly reduced CHH methylation in cmt2 and cmt2 cmt3 mutants coupled with increased ONSEN transcription. Furthermore, we found more CMT2 binding at ONSEN chromatin in cmt3 compared to wild-type accompanied with an ectopic accumulation of H3K9me2 under heat stress, suggesting a collaborative role of H3K9me2 and CHH methylation in preventing heat-induced ONSEN activation. In summary, this study identifies a non-canonical role of CMT3 in preventing transposon silencing and provides new insights into how DNA methyltransferases regulate transcription under stress conditions.
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http://dx.doi.org/10.1371/journal.pgen.1009710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376061PMC
August 2021

Genomic methylation variations predict the susceptibility of six chemotherapy related adverse effects and cancer development for Chinese colorectal cancer patients.

Toxicol Appl Pharmacol 2021 09 29;427:115657. Epub 2021 Jul 29.

Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Traditional Chinese Medicine Resource and Technology Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Colorectal cancer (CRC) remains a major concern with high morbidity and mortality worldwide. Despite the positive influence of chemotherapy on the decline in CRC mortality, the negative influence of chemotherapy-related adverse effects (CRAEs) caused by capecitabine (Cap) remains a challenging problem. DNA methylation alteration plays a pivotal role in gene expression regulation. Here, we aimed to screen reliable and novel biomarkers for CRC diagnosis and CRAE prediction using the advanced Illumina Infinium MethylationEPIC (850 K) BeadChip. Paired tumor and normal tissues from 21 Chinese CRC patients who received Cap-based adjuvant chemotherapy were analyzed. CRC-related methylation was characterized by hypermethylated promoter islands and hypomethylated intragenic openseas; CRAE-related methylation was characterized by hyper- (or hypo-) methylated intragenic (or intergenic) regions. Based on three types of methylation profiles (differentially methylated probes, differentially methylated regions, and gene-function-differentially methylated regions), pathway enrichment analyses revealed that CRC-related genes were significantly enriched in the neuronal system, metabolism of RNA, and extracellular matrix organization; CRAE-related genes were abundantly enriched in pathways controlling regeneration functions and immune response. Finally, based on genes within the mostly related pathways and LASSO logistic regression selection, the integrated-methylation-marker systems developed here demonstrated high discriminative accuracy in both CRC diagnosis (AUROC = 1) and CRAE prediction (AUROC = 0.817-1). In conclusion, we conducted a comprehensive DNA methylation analysis of CRC patients with chemotherapy, which provided new insights into the formation of CRC and CRAEs. Most importantly, our findings identified potentially CRAE-related metabolic pathways and markers, providing a valuable reference for personalized medicine promising better safety. Trail registration:ClinicalTrials.gov,NCT03030508, Registered 25 January 2017,https://www.clinicaltrials.gov/ct2/show/NCT03030508?term=NCT03030508&draw=2&rank=1.
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http://dx.doi.org/10.1016/j.taap.2021.115657DOI Listing
September 2021

Risk prediction models based on hematological/body parameters for chemotherapy-induced adverse effects in Chinese colorectal cancer patients.

Support Care Cancer 2021 Jul 2. Epub 2021 Jul 2.

Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.

Purpose: To determine risk factors and develop novel prediction models for chemotherapy-induced adverse effects (CIAEs) in Chinese colorectal cancer (CRC) patients receiving capecitabine.

Methods: A total of 233 Chinese CRC patients receiving post-operative chemotherapy with capecitabine were randomly divided into a training set (70%) and a validation set (30%). CIAE-related hematological/body parameters were screened by univariate logistic regression. Based on a set of factors selected from LASSO (least absolute shrinkage and selection operator) logistic regression, stepwise multivariate logistic regression was applied to develop prediction models. Area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow (HL) test were used to evaluate the discriminatory ability and the goodness of fit of each model.

Results: In total, 35 variables were identified to be associated with CIAEs in univariate analysis. Developed multivariable models had AUCs (area under curve) ranging from 0.625 to 0.888 and 0.428 to 0.760 in the training and validation set, respectively. The grade ≥ 1 anemia multivariable model achieved the best discriminatory ability with AUC of 0.760 (95%CI: 0.609-0.912) and good calibration with HL P value of 0.450. Then, a nomogram was constructed to predict grade ≥ 1 anemia, which included variables of age, pre-operative hemoglobin count, and pre-operative albumin count, with C-indexes of 0.775 and 0.806 in the training and validation set, respectively.

Conclusions: This study identified valuable hematological/body parameters related to CIAEs. A nomogram based on the multivariable model including three hematological/body predictors can accurately predict grade ≥ 1 anemia, facilitating clinicians to implement personalized medicine early for Chinese CRC patients receiving post-operative chemotherapy for better safety treatment. Trial registration This study was registered as a clinical trial at www.clinicaltrials.gov (NCT03030508).
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http://dx.doi.org/10.1007/s00520-021-06337-zDOI Listing
July 2021

Comparative transcriptome analysis reveals a potential mechanism for host nutritional manipulation after parasitization by Leptopilina boulardi.

Comp Biochem Physiol Part D Genomics Proteomics 2021 09 7;39:100862. Epub 2021 Jun 7.

Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insect Pests, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Zhejiang University, Hangzhou 310058, China. Electronic address:

Parasitoids have been extensively found to manipulate nutrient amounts of their hosts to benefit their own development and survival, but the underlying mechanisms are largely unknown. Leptopilina boulardi (Hymenoptera: Figitidae) is a larval-pupal endoparasitoid wasp of Drosophila melanogaster whose survival relies on the nutrients provided by its Drosophila host. Here, we used RNA-seq to compare the gene expression levels of the host midgut at 24 h and 48 h post L. boulardi parasitization. We obtained 95 and 191 differentially expressed genes (DEGs) in the parasitized host midgut at 24 h and 48 h post L. boulardi parasitization, respectively. A KEGG analysis revealed that several metabolic pathways were significantly enriched in the upregulated DEGs, and these pathways included "starch and sucrose metabolism" and "galactose metabolism". A functional annotation analysis showed that four classes of genes involved in carbohydrate digestion process had increased expression levels in the midgut post L.boulardi parasitization than nonparasitized groups: glucosidase, mannosidase, chitinase and amylase. Genes involved in protein digestion process were also found among the DEGs, and most of these genes, which belonged to the metallopeptidase and serine-type endopeptidase families, were found at higher expression levels in the parasitized host midgut comparing with nonparasitized hosts. Moreover, some immune genes, particularly those involved in the Toll and Imd pathways, also exhibited high expression levels after L.boulardi parasitization. Our study provides large-scale transcriptome data and identifies sets of DEGs between parasitized and nonparasitized host midgut tissues at 24 h and 48 h post L. boulardi parasitization. These resources help improve our understanding of how parasitoid infection affects the nutrient components in the hosts.
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http://dx.doi.org/10.1016/j.cbd.2021.100862DOI Listing
September 2021

Individual prediction of motor vehicle accidents for patients with epilepsy.

Epilepsy Behav 2021 08 7;121(Pt A):108046. Epub 2021 Jun 7.

Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, Sichuan 610041, People's Republic of China. Electronic address:

The objective of the study was to design a clinically useful tool to predict the risk of seizure-related motor vehicle accidents (MVAs) for people with epilepsy (PWE). Participants were patients who visited our epilepsy center in West China Hospital from October 2012 to October 2019 and were divided into a primary cohort and a validation cohort. Ultimately, we included 525 patients in the primary cohort and 86 patients in the validation cohort. Proportional hazard regression was performed to measure the prognostic factors of car accidents. The outcome was used to create a nomogram model. The final model had 7 factors, with a C-index of 0.85 (95% CI, 0.80-0.91), to predict the possibility of non-MVA for PWE. For the validation cohort, the C-index was 0.83 (95% CI, 0.72-0.95). This nomogram model can offer more individualized advice to PWE who are still driving by estimating the risk of car accidents.
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http://dx.doi.org/10.1016/j.yebeh.2021.108046DOI Listing
August 2021

Is There an Association Between Hypothyroidism and Sexual Dysfunction: A Systematic Review and Cumulative Analysis.

Sex Med 2021 Jun 1;9(3):100345. Epub 2021 Jun 1.

Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China. Electronic address:

Introduction: Many investigators have found a detrimental effect on sexual functioning developed by hypothyroidism in both sexes, but a cumulative analysis has not been conducted.

Aim: This study aims to summarize and quantify the association between overt or subclinical hypothyroidism and the risk of sexual dysfunction (SD) through a meta-analysis.

Methods: 4 electronic databases were systematically searched. The quality of evidence was rated by the GRADE approach. This meta-analysis was registered on the PROSPERO (ID: CRD42020186967).

Main Outcome Measure: The strength of the relationship between overt/subclinical hypothyroidism and SD was quantified by presenting the relative risk (RR) with its 95% confidence interval (CI).

Results: 7 studies involving 460 patients with hypothyroidism and 2,143 healthy controls were included in this meta-analysis. Among the 7 included studies, 2 studies were provided the data of both overt and subclinical hypothyroidism. Pooled results from 4 included studies investigating overt hypothyroidism indicated that overt hypothyroidism led to significant SD in both sexes (RR = 2.26, 95% CI: 1.42 to 3.62, P = 0.001), while synthetic RR of 5 eligible studies reporting subclinical hypothyroidism failed to find a positive association between subclinical hypothyroidism and SD (RR = 1.3, 95% CI: 0.85 to 1.99, P = 0.229), irrespective of gender (all P > 0.05). Subgroup analyses revealed that women with overt hypothyroidism rather than men with overt hypothyroidism were correlated with a significant higher risk of SD. The quality of evidence in the study of overt hypothyroidism and subclinical hypothyroidism was considered low and moderate, respectively.

Conclusion: SD is a devastating problem in female patients with clinical hypothyroidism but insusceptible in either women or men with subclinical hypothyroidism. Clinicians should be aware of these phenomena and manage the sufferers accordingly in clinical practice. More rigorous studies are still needed to validate this evidence. Shen M, Li X, Wu W, et al. Is There an Association Between Hypothyroidism and Sexual Dysfunction: A Systematic Review and Cumulative Analysis. Sex Med 2021;9:100345.
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http://dx.doi.org/10.1016/j.esxm.2021.100345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240328PMC
June 2021

Who is the main caregiver of the mother during the doing-the-month: is there an association with postpartum depression?

BMC Psychiatry 2021 05 25;21(1):270. Epub 2021 May 25.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.

Background: To examine the relationship between the main caregiver during the "doing-the-month" (a traditional Chinese practice which a mother is confined at home for 1 month after giving birth) and the risk of postpartum depression (PPD) in postnatal women.

Methods: Participants were postnatal women stayed in hospital and women who attended the hospital for postpartum examination, at 14-60 days after delivery from November 1, 2013 to December 30, 2013. Postpartum depression status was assessed using the Edinburgh Postnatal Depression Scale. Univariate and multivariable logistic regressions were used to identify the associations between the main caregiver during "doing-the-month" and the risk of PPD in postnatal women.

Results: One thousand three hundred twenty-five postnatal women with a mean (SD) age of 28 (4.58) years were included in the analyses. The median score (IQR) of PPD was 6.0 (2, 10) and the prevalence of PPD was 27%. Of these postnatal women, 44.5% were cared by their mother-in-law in the first month after delivery, 36.3% cared by own mother, 11.1% by "yuesao" or "maternity matron" and 8.1% by other relatives. No association was found between the main caregivers and the risk of PPD after multiple adjustments.

Conclusions: Although no association between the main caregivers and the risk of PPD during doing-the-month was identified, considering the increasing prevalence of PPD in Chinese women, and the contradictions between traditional culture and latest scientific evidence for some of the doing-the-month practices, public health interventions aim to increase the awareness of PPD among caregivers and family members are warranted.
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http://dx.doi.org/10.1186/s12888-021-03203-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147344PMC
May 2021

Incidence and risk factors associated with the development of epilepsy in patients with intracranial alveolar echinococcosis.

Epilepsy Res 2021 Aug 27;174:106643. Epub 2021 Apr 27.

Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, Sichuan, 610041, People's Republic of China. Electronic address:

Parasitic infection remains a critical health problem in Ganzi Tibetan Autonomous Prefecture of China. The association of epilepsy and intracranial alveolar echinococcosis (IAE) is still largely unclear. This study primarily aimed to assess both the incidence and possible risk factors of epilepsy in patients with IAE. According to the occurrence of seizures, patients were separated into two different groups consisting of patients with epilepsy and those without epilepsy. Univariate and multivariate logistic regression analysis was used to identify the potential risk factors associated with the development of epilepsy in patients with IAE. A total of 97 patients (42 women, 55 men; age 19-76 years) were enrolled. Epilepsy was observed in almost 20 % of patients with IAE. The use of anti-seizure medications was not standardized, as 83.3 % of female patients of childbearing age used sodium valproate. It was observed that cortical lesions (hazard ratio (HR) = 29.740, P = 0.006) were significantly associated with development of epilepsy. In addition, epilepsy had no significant effect on the overall survival rate of patients with IAE.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106643DOI Listing
August 2021

[Corrigendum] Cyclophilin D modulates cell death transition from early apoptosis to programmed necrosis induced by honokiol.

Int J Oncol 2021 Jun 6;58(6). Epub 2021 May 6.

Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine,Zhejiang University, Hangzhou 310009, P.R. China.

Subsequently to the publication of the above article, the authors have realized that the printed version of Fig. 6 on p. 1661 contained some mistakes. Potential anomalies regarding this figure concerning the duplication of data both within Fig. 6 and comparing data between Figs. 5 and 6 were also drawn to our attention by an interested reader. Specifically, the authors realized that the bands of BCL‑xl were erroneously selected from the GAPDH dataset during the process of compiling this figure. The authors subsequently found that the original photographs of these western blot bands had been lost during the time period that had elapsed since these experiments were completed. In order to corroborate the results, the authors repeated the contentious experiments shown in Fig. 6 and obtained similar results, thereby corroborating the results and conclusions reported in this study. A revised version of Fig. 6, containing the newly obtained data, is shown below. The errors made with the assembly of Fig. 6 originally did not have an adverse bearing on the overall conclusions reported in this study. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum, and all of the authors agree to the publication of this Corrigendum. The authors sincerely apologize for their errors, and apologize to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 42: 1654‑1663, 2013; DOI: 10.3892/ijo.2013.1863].
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http://dx.doi.org/10.3892/ijo.2021.5212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104921PMC
June 2021

RSV genomic diversity and the development of a globally effective RSV intervention.

Vaccine 2021 05 22;39(21):2811-2820. Epub 2021 Apr 22.

Fogarty International Center, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract illness in infants and children and causes significant disease in the elderly and immunocompromised. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics. However, the effects of RSV genomic variability on the implementation of vaccines and therapeutics remain poorly understood. To address this knowledge gap, the National Institute of Allergy and Infectious Diseases and the Fogarty International Center held a workshop to summarize what is known about the global burden and transmission of RSV disease, the phylogeographic dynamics and genomics of the virus, and the networks that exist to improve the understanding of RSV disease. Discussion at the workshop focused on the implications of viral evolution and genomic variability for vaccine and therapeutics development in the context of various immunization strategies. This paper summarizes the meeting, highlights research gaps and future priorities, and outlines what has been achieved since the meeting took place. It concludes with an examination of what the RSV community can learn from our understanding of SARS-CoV-2 genomics and what insights over sixty years of RSV research can offer the rapidly evolving field of COVID-19 vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.096DOI Listing
May 2021

Characterization and discrimination of human colorectal cancer cells using terahertz spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 17;256:119713. Epub 2021 Mar 17.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Terahertz technology has been widely used in biomedical research. Herein, terahertz time-domain attenuated total reflection (THz TD-ATR) spectroscopy was employed to characterize and discriminate human cancer cell lines (DLD-1 and HT-29). Terahertz responses of the cell lines were measured and Savitzky-Golay algorithm was applied to smooth the spectra of refractive index, absorption coefficient and dielectric loss tangent in terahertz regime. Principal component analysis (PCA) was then adopted for feature extraction and cell characterization. Based on the processed data, cancer cell lines were discriminated by applying random forests (RF) method to analyze three characteristic parameters separately and the results from them were compared. Results indicate that absorption coefficient was the most sensitive parameter for cancer cell discrimination. Our study suggests great potential for human cancer cell recognition and provides experimental basis for liquid biopsy.
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http://dx.doi.org/10.1016/j.saa.2021.119713DOI Listing
July 2021

HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/β-catenin axis in right-sided colon cancer.

Cell Death Dis 2021 04 1;12(4):337. Epub 2021 Apr 1.

Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Patients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.
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http://dx.doi.org/10.1038/s41419-021-03630-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016886PMC
April 2021

Hypermutated tumours across 11 cancer types show three distinct immune subtypes.

Eur J Cancer 2021 05 19;148:230-238. Epub 2021 Mar 19.

Key Laboratory of Reproductive and Genetics, Ministry of Education, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China. Electronic address:

Background: Complete remission is observed in less than half of hypermutated (HM) tumours after immune checkpoint blockade therapy, indicating that HM tumours are very heterogeneous. Thus, there is an urgent requirement to decipher the unknown intrinsic HM tumour subtypes.

Methods: Statistical analysis was performed on somatic mutation data from 5519 tumours across 11 cancer types obtained from The Cancer Genome Atlas and 338 colorectal cancer (CRC) samples obtained from an Asian cohort. Samples with a tumour mutation burden >10 mut/Mb were classified as HM. A total of 1040 HM samples harbouring corresponding transcriptomes were used for non-negative matrix factorisation clustering. Tumour mutational burden, neoantigens, T cell receptor (TCR) diversity, stromal score and immune score were compared between the subtypes.

Results: HM tumours fell into three distinct immune subtypes: HM1, HM2 and HM3. HM3 tumours were correlated with increased CD8 T cell infiltration, high TCR diversity, a high immune score and prolonged survival. HM2 tumours were correlated with an abundant stromal component, epithelial-mesenchymal transition, TGFβ, angiogenesis hallmarks and poor outcomes. The infiltration of more CD8 T cells and increased chemokine expression in HM3 were validated in CRC by immunofluorescence.

Conclusions: These findings will facilitate the development of a subtype-oriented therapy strategy to enhance the treatment effect in the near future.
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http://dx.doi.org/10.1016/j.ejca.2021.01.044DOI Listing
May 2021

Symbiotic bracovirus of a parasite manipulates host lipid metabolism via tachykinin signaling.

PLoS Pathog 2021 03 1;17(3):e1009365. Epub 2021 Mar 1.

Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

Parasites alter host energy homeostasis for their own development, but the mechanisms underlying this phenomenon remain largely unknown. Here, we show that Cotesia vestalis, an endoparasitic wasp of Plutella xylostella larvae, stimulates a reduction of host lipid levels. This process requires excess secretion of P. xylostella tachykinin (PxTK) peptides from enteroendocrine cells (EEs) in the midgut of the parasitized host larvae. We found that parasitization upregulates PxTK signaling to suppress lipogenesis in midgut enterocytes (ECs) in a non-cell-autonomous manner, and the reduced host lipid level benefits the development of wasp offspring and their subsequent parasitic ability. We further found that a C. vestalis bracovirus (CvBV) gene, CvBV 9-2, is responsible for PxTK induction, which in turn reduces the systemic lipid level of the host. Taken together, these findings illustrate a novel mechanism for parasite manipulation of host energy homeostasis by a symbiotic bracovirus gene to promote the development and increase the parasitic efficiency of an agriculturally important wasp species.
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http://dx.doi.org/10.1371/journal.ppat.1009365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951984PMC
March 2021

Biological role and mechanism of chromatin readers in plants.

Curr Opin Plant Biol 2021 06 10;61:102008. Epub 2021 Feb 10.

Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

Epigenetic modifications are important gene regulatory mechanisms conserved in plants, animals, and fungi. Chromatin reader domains are protein-protein/DNA interaction modules acting within the chromatin-modifying complex to function as molecular interpreters of the epigenetic code. Understanding how reader proteins recognize specific epigenetic modifications and mediate downstream chromatin and transcriptional events is fundamental to many biological processes. Recent studies have uncovered a number of novel reader proteins with diverse functions and mechanisms in plants. Here, we provide an overview of the recent progress on reader-mark recognition modes, the mechanisms by which reader proteins influence chromatin dynamics, and how reader-chromatin interactions regulate biological function. Because of space limitations, this review focuses on reader domains in plants that specifically bind histone methylation, histone acetylation, and DNA methylation.
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http://dx.doi.org/10.1016/j.pbi.2021.102008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222062PMC
June 2021

Biological role and mechanism of chromatin readers in plants.

Curr Opin Plant Biol 2021 06 10;61:102008. Epub 2021 Feb 10.

Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

Epigenetic modifications are important gene regulatory mechanisms conserved in plants, animals, and fungi. Chromatin reader domains are protein-protein/DNA interaction modules acting within the chromatin-modifying complex to function as molecular interpreters of the epigenetic code. Understanding how reader proteins recognize specific epigenetic modifications and mediate downstream chromatin and transcriptional events is fundamental to many biological processes. Recent studies have uncovered a number of novel reader proteins with diverse functions and mechanisms in plants. Here, we provide an overview of the recent progress on reader-mark recognition modes, the mechanisms by which reader proteins influence chromatin dynamics, and how reader-chromatin interactions regulate biological function. Because of space limitations, this review focuses on reader domains in plants that specifically bind histone methylation, histone acetylation, and DNA methylation.
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http://dx.doi.org/10.1016/j.pbi.2021.102008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222062PMC
June 2021

Clinical Features, Radiological Characteristics, and Outcomes of Patients With Intracranial Alveolar Echinococcosis: A Case Series From Tibetan Areas of Sichuan Province, China.

Front Neurol 2020 15;11:537565. Epub 2021 Jan 15.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

Intracranial alveolar echinococcosis (IAE), a zoonotic disease, is a critical health problem in the Tibetan region. We aimed to describe the clinical and radiological characteristics and outcomes among patients with IAE. We screened patients diagnosed with IAE between March 2015 and May 2019 at the Ganzi Tibetan Autonomous Prefecture People's Hospital. Detailed demographics, clinical characteristics, neuroimaging features, and outcomes were recorded. A total of 21 patients with an average age of 44.1 ± 12.7 years were included. Thirteen (61.9%) patients were male. The most common chief neurological complaint was headache ( = 17, 81.0%), followed by dizziness, seizure, visual disturbances, hemiparesis, disturbed consciousness, and dysphasia. All the patients had coexisting liver localizations. The typical neuroimaging features of IAE on cerebral magnetic resonance imaging scans showed obvious low-signal shadow with multiple small vesicles inside the lesions on T2-weighted images and FLAIR images. The pathological HE staining demonstrates vesicular lesions with several internal sacs. For hepatic alveolar echinococcosis (AE), the hepatic portal was invaded in six (28.6%) patients, and the portal vein ( = 5, 23.8%) was the mostly commonly involved vessel. As for treatment, 11 patients (52.4%) had poor compliance with albendazole. The duration of patients taken albendazole ranged from 2 months to 3 years. Cerebral AE surgery was performed in 11 patients, five of them underwent partial resection of AE lesions, and six patients received total resection. One patient with primary IAE underwent radical surgery. Ten patients (47.6%) died during the follow-up for a mean of 21.7 ± 11.9 (3-46) months. In total, 28.9% of the patients died within 5 years, and 71.6% died within 10 years. The median interval between the date of diagnosis as AE and death was 84 (19-144) months. Despite substantial advances in diagnostic and therapeutic methods, the treatment of IAE remains difficult and results in unsatisfactory outcomes. The major critical issue is surgical treatment of IAE although the disease is disseminated. Besides, lifelong albendazole would be indicated, but most patients had poor medication compliance. It is important to educate patients about the necessity of medical treatment.
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http://dx.doi.org/10.3389/fneur.2020.537565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843382PMC
January 2021

The complete mitochondrial genome of (Hymenoptera: Figitidae).

Mitochondrial DNA B Resour 2021 Jan 6;6(1):17-18. Epub 2021 Jan 6.

Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

(Hymenoptera: Figitidae) is a newly recorded species of parasitic wasp, and it attacks the larval stage of Drosophilidae, mainly the species. Few works have been done in the basic study of , including the data of mitochondrial genome. In this study, the complete mitochondrial genome of (GeneBank accession number: MT649407) was sequenced using Illumina HiSeq X Ten system. The mitochondrial genome is 15,882bp long and comprises 13 protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. Meanwhile, 26 genes are in majority strand, and the remaining 11 genes are in minority strand. The overall base composition is 41.7% for A, 6.0% for G, 13.6% for C, and 38.7% for T, with an A + T content of 80.4%, respectively. We also performed a phylogenetic analysis with other known mitochondrial genomes of some parasitic wasps. The results show that is closely related to , which is another parasitoid.
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http://dx.doi.org/10.1080/23802359.2020.1845106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801089PMC
January 2021

The complete mitochondrial genome of (Hymenoptera: Diapriidae).

Mitochondrial DNA B Resour 2020 Jun 8;5(3):2391-2393. Epub 2020 Jun 8.

Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.

(Hymenoptera: Diapriidae) is an important pupal endoparasitoid of species, which has been found to be an ideal biocontrol agent to . In this study, the complete mitochondrial genome of (GeneBank accession number: MN966974) was sequenced using Illumina HiSeq X Ten system. The mitochondrial genome is 16,375 bp long and comprises 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. Among them, 24 genes are in majority strand, while the others are in minority strand. The nucleotide composition of A, G, C, T is 44.9%, 6.4%, 5.6%, 43.2% respectively. We also performed a phylogenetic analysis with other known mitochondrial genomes within four families that have been shown to parasitize drosophilid species. The result shows that is closely related to
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http://dx.doi.org/10.1080/23802359.2020.1775521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782102PMC
June 2020

Two novel venom proteins underlie divergent parasitic strategies between a generalist and a specialist parasite.

Nat Commun 2021 01 11;12(1):234. Epub 2021 Jan 11.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.

Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation.
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http://dx.doi.org/10.1038/s41467-020-20332-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801585PMC
January 2021

Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma.

Cancer Genet 2021 04 11;252-253:37-42. Epub 2020 Dec 11.

Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

ALK (Anaplastic lymphoma kinase) fusion proteins are oncogenic and have been seen in various tumors. PPP1CB-ALK fusions are rare but have been reported in a few patients with low- or high-grade gliomas. However, little is known regarding the mechanism of fusion formation and genomic break points of this fusion. We performed genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma. The PPP1CB-ALK consists of exons 1-5 of PPP1CB and exons 20-29 of ALK. The genomic translocation breakpoints were determined by real-time quantitative PCR (RT-qPCR) and Sanger sequencing of genomic DNA. Next generation sequencing, RT-qPCR and fluorescence in situ hybridization analyses demonstrated PPP1CB-ALK amplification. Copy number analyses of genes between PPP1CB and ALK using RT-qPCR suggest that the PPP1CB-ALK is likely the result of local chromothripsis followed by episomal amplification. Transcriptome sequencing demonstrated high-level SOX2 expression and predicted WNT/β-catenin pathway activation, suggesting possible therapeutic approaches.
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http://dx.doi.org/10.1016/j.cancergen.2020.12.005DOI Listing
April 2021

Hypoxia Correlates With Poor Survival and M2 Macrophage Infiltration in Colorectal Cancer.

Front Oncol 2020 20;10:566430. Epub 2020 Nov 20.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: It is widely accepted that the oxygen level in tumor tissue is significantly lower than the adjacent normal tissue, thus termed hypoxia. Intratumoral hypoxia represents a major driving force in cancer progression, recurrence, metastasis, and decreased survival. Though multiple gene signatures reflect the complex cellular response to hypoxia have been established in several cancer types such as head and neck, breast, and lung cancers, the hypoxic panorama in colorectal cancer (CRC) remains poorly understood.

Methods: A hypoxic signature constituted by a total of 356 genes, including canonical hypoxia-responsive ADM, ANGPTL4, CA9, and VEGFA, was established based on systemic literature search. A total of 1,730 CRC samples across four independent cohorts were used for Prognosis, molecular signatures, pathways, and tumor-infiltrating lymphocytes were compared between the subtypes.

Results: CRCs mainly fell into two subgroups, one indicated as hypoxia and the other one designated as normoxia. Hypoxia was correlated with poor outcomes in CRC and will increase the risk of a subset of stage II patients to the level of normoxic stage III. Additionally, hypoxia was closely associated with activation of RAS signaling pathway independent of mutation. More M2 macrophage infiltration was another hypoxic marker indicated that subsets of patients with high M2 macrophages may benefit from macrophage-targeting therapy.

Conclusions: These findings will facilitate the development of a hypoxia-oriented therapy strategy to enhance the treatment effect in the near future.
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http://dx.doi.org/10.3389/fonc.2020.566430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714992PMC
November 2020

F-box protein CFK1 interacts with and degrades de novo DNA methyltransferase in Arabidopsis.

New Phytol 2021 03 15;229(6):3303-3317. Epub 2020 Dec 15.

Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA.

DNA methylation plays crucial roles in cellular development and stress responses through gene regulation and genome stability control. Precise regulation of DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), the de novo Arabidopsis DNA methyltransferase, is crucial to maintain DNA methylation homeostasis to ensure genome integrity. Compared with the extensive studies on DRM2 targeting mechanisms, little information is known regarding the quality control of DRM2 itself. Here, we conducted yeast two-hybrid screen assay and identified an E3 ligase, COP9 INTERACTING F-BOX KELCH 1 (CFK1), as a novel DRM2-interacting partner and targets DRM2 for degradation via the ubiquitin-26S proteasome pathway in Arabidopsis thaliana. We also performed whole genome bisulfite sequencing (BS-seq) to determine the biological significance of CFK1-mediated DRM2 degradation. Loss-of-function CFK1 leads to increased DRM2 protein abundance and overexpression of CFK1 showed reduced DRM2 protein levels. Consistently, CFK1 overexpression induces genome-wide CHH hypomethylation and transcriptional de-repression at specific DRM2 target loci. This study uncovered a distinct mechanism regulating de novo DNA methyltransferase by CFK1 to control DNA methylation level.
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http://dx.doi.org/10.1111/nph.17103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902366PMC
March 2021

Qualitative and quantitative detection of liver injury with terahertz time-domain spectroscopy.

Biomed Opt Express 2020 Feb 21;11(2):982-993. Epub 2020 Jan 21.

State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Hangzhou, China.

Terahertz technology has been widely used as a nondestructive and effective detection method. Herein, terahertz time-domain spectroscopy was used to detect drug-induced liver injury in mice. Firstly, the boxplots were used to detect abnormal data. Then the maximal information coefficient method was used to search for the features strongly correlated with the degree of injury. After that, the liver injury model was built using the random forests method in machine learning. The results show that this method can effectively identify the degree of liver injury and thus provide an auxiliary diagnostic method for detecting minor liver injury.
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http://dx.doi.org/10.1364/BOE.381660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041463PMC
February 2020

Targeting the NAD salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/β-catenin signaling via increasing Axin level.

Cell Commun Signal 2020 01 31;18(1):16. Epub 2020 Jan 31.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, Hangzhou, China.

Background: The role and mechanism of the nicotinamide adenine dinucleotide (NAD) salvage pathway in cancer cell proliferation is poorly understood. Nicotinamide phosphoribosyltransferase (NAMPT), which converts nicotinamide into NAD, is the rate-limiting enzyme in the NAD salvage pathway. Here, we assessed the role of NAMPT in the proliferation of colorectal cancer.

Methods: Real-time PCR, immunohistochemistry, western blotting, and analyses of datasets from Oncomine and Gene Expression Omnibus were conducted to assess the expression of NAMPT at the mRNA and protein levels in colorectal cancer. The Kaplan Meier plotter online tool was used to evaluate the prognostic role of NAMPT. Knockdown of NAMPT was performed to assess the role of NAMPT in colorectal cancer cell proliferation and tumorigenesis both in vitro and in vivo. Overexpression of NAMPT was used to evaluate impact of NAMPT on colorectal cancer cell proliferation in vitro. NAD quantitation, immunofluorescence, dual luciferase assay and western blot were used to explore the mechanism of colorectal cancer proliferation. Transwell migration and invasion assays were conducted to assess the role of NAMPT in cell migration and invasion abilities of colorectal cancer cells.

Results: Our study indicated that the inhibition of NAMPT decreased proliferation capacity of colorectal cancer cells both in vitro and in vivo. Conversely, overexpression of NAMPT could promote cell proliferation in vitro. NAMPT inhibition induced β-catenin degradation by increasing Axin expression levels; this resulted in the inhibition of Wnt/β-catenin signaling and cell proliferation in colorectal cancer. The addition of nicotinamide mononucleotide, the enzymatic product of NAMPT, effectively reversed β-catenin protein degradation and inhibited growth. Similarly, the knockdown of Axin also decreased the cell death induced by the inhibition of NAMPT. In addition, we showed that colorectal cancer tissues harbored significantly higher levels of NAMPT than the levels harbored by paired normal tissues, especially in colorectal cancer stages I and II. And the overexpression of NAMPT was associated with unfavorable survival results.

Conclusions: Our findings reveal that NAMPT plays an important role in colorectal cancer proliferation via Wnt/β-catenin pathway, which could have vital implications for the diagnosis, prognosis and treatment of colorectal cancer.
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http://dx.doi.org/10.1186/s12964-020-0513-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995173PMC
January 2020

8-Hydroxyguanosine as a possible RNA oxidative modification marker in urine from colorectal cancer patients: Evaluation by ultra performance liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Jan 9;1136:121931. Epub 2019 Dec 9.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, Zhejiang 310009, China.

Oxidative RNA damage has been found to be associated with a variety of diseases, and 8-hydroxyguanosine (8-OHG) is a typical marker of oxidative modification of RNA. This guanosine modification is an emerging biomarker for disease detection and determination of 8-OHG in human urine is favored because it is noninvasive to patients. However, due to its poor ionization efficiency in mass spectrometry and trace amount in urine, accurate quantification of this modified nucleoside is still challenging. Herein, a rapid, accurate, sensitive and robust method using solid-phase extraction (SPE) combined with isotope dilution ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for detection of this oxidative RNA modification in human urine. The limit of detection can reach 1.5 fmol and the method exhibits good precision on intra-day (1.8-3.3%) and inter-day (0.6-1.2%) analyses. Satisfactory recovery (87.5-107.2%) at three spiked levels was achieved by using HLB cartridge for urine pretreatment. Using this method, we quantified 8-OHG in urine from 65 colorectal cancer (CRC) patients and 76 healthy volunteers. The measured level of urinary 8-OHG for CRC patients and healthy controls is 1.91 ± 0.63 nmol/mmol creatinine and 1.33 ± 0.35 nmol/mmol creatinine, respectively. We found the content of 8-OHG in urine was raised in CRC patients patients, implying this oxidative RNA modification marker could act as a potential noninvasive indicator for early screening of CRC. In addition, this study will make contributions to the investigations of the influences of oxidative stress on the formation and development of CRC.
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http://dx.doi.org/10.1016/j.jchromb.2019.121931DOI Listing
January 2020
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