Publications by authors named "Yuanyuan Lu"

185 Publications

Cell-autonomous role of EGFR in spontaneous duodenal tumors in LRIG1 null mice.

Cell Mol Gastroenterol Hepatol 2021 May 11. Epub 2021 May 11.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jcmgh.2021.05.004DOI Listing
May 2021

Selective enzymatic α-1,6- monoglucosylation of mogroside IIIE for the bio-creation of α-siamenoside I, a potential high-intensity sweetener.

Food Chem 2021 Apr 23;359:129938. Epub 2021 Apr 23.

Department of Biochemistry, College of Life Sciences and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, Jiangsu Province 211198, PR China. Electronic address:

A new compound, α-siamenoside I (α-SI), with a glucose unit selectively bound to the 6-hydroxyl group of the 24-O-β-glucosyl moiety of mogroside IIIE by α-1,6-glucosidic bond, was bio-created by two screened cyclodextrin glycosyltransferases with a maximum yield of 59.3%. Compared to mogroside IIIE, α-SI showed a significantly increased sweetness intensity (508 times sweeter than 5% sucrose), which is superior to siamenoside I (SI), the sweetest triterpenoid saponin isolated from Siraitia grosvenorii to date. Sensory evaluation showed that the taste quality of α-SI also was obviously better than mogroside IIIE. In addition to α-SI possessing a good stability similar to that of SI, it also did not cause a significant decrease in cell viability at a concentration of 200 μg/mL and had a negative influence on islets function at 1 μM. All of these preliminarily results pave the way for promoting α-SI as a potential low-calorie sweetener.
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http://dx.doi.org/10.1016/j.foodchem.2021.129938DOI Listing
April 2021

Krüppel-Like Factor 15 Modulates Signaling-Mediated Inflammatory Response Contributing to Angiotensin II-Induced Cardiac Remodeling.

Front Cell Dev Biol 2021 1;9:644954. Epub 2021 Apr 1.

Department of Cardiovascular Medicine, Ruijin Hospital and State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Inflammation is involved in cardiac remodeling. In response to pathological stimuli, activated cardiac fibroblasts (CFs) secreting inflammatory cytokines and chemokines play an important role in monocyte/macrophage recruitment. However, the precise mechanism of CF-mediated inflammatory response in hypertension-induced cardiac remodeling remains unclear. In the present study, we investigated the role of transcription factor Krüppel-like factor 15 (KLF15) in this process. We found that KLF15 expression decreased while chemokine and its receptor expression increased in the hearts of angiotensin II (Ang II)-infused mice. Compared to the wild-type mice, KLF15 knockout (KO) mice aggravated Ang II-induced cardiac hypertrophy and fibrosis. Deficiency of KLF15 promoted macrophage accumulation, increase of and expression, and mTOR, ERK1/2, NF-κB-p65 signaling activation in the hearts. Mechanistically, Ang II dose- dependently decreased KLF15 expression and increased secretion from cardiac fibroblasts but not cardiac myoblasts. Loss- or gain-of-function studies have shown that KLF15 negatively regulated expression through its transactivation domain (TAD). Intriguingly, the adenovirus-mediated full length of KLF15-but not KLF15 with TAD deletion overexpression-markedly prevented pathological change in Ang II-infused mice. Notably, the administration of inhibitor SB265610 reversed KLF15 knockout-mediated aggravation of cardiac dysfunction, remodeling, and inflammation induced by Ang II. In conclusion, our study identifies that KLF15 in cardiac fibroblasts negatively regulates axis-mediated inflammatory response and subsequent cardiac remodeling in hypertension.
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http://dx.doi.org/10.3389/fcell.2021.644954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047332PMC
April 2021

The FENDRR/FOXC2 Axis Contributes to Multidrug Resistance in Gastric Cancer and Correlates With Poor Prognosis.

Front Oncol 2021 22;11:634579. Epub 2021 Mar 22.

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

The dysregulation of long non-coding RNAs (lncRNAs) and transcription factors (TFs) is closely related to the development and progression of drug resistance in cancer chemotherapy. However, their regulatory interactions in the multidrug resistance (MDR) of gastric cancer (GC) has largely remained unknown. In this study, we report a novel oncogenic role of lncRNA FENDRR in conferring MDR in GC by coordinated regulation of FOXC2 expression at the transcriptional and posttranscriptional levels. and experiments demonstrated that downregulation of FENDRR expression remarkably decreased drug resistant ability of GC MDR cells while upregulation of FENDRR expression produced the opposite effect. FENDRR overexpression was observed in MDR GC cell lines, patient-derived xenografts, and clinical samples. And the high levels of FENDRR expression were correlated with poor prognosis in GC patients. Regarding the mechanism, FENDRR was revealed to increase proto-oncogene FOXC2 transcription by performing an enhancer-like role in the nucleus and by sponging miR-4700-3p in the cytoplasm. Both FOXC2 and miR-4700-3p were shown to be functionally involved in the FENDRR-induced chemoresistance. In addition, there is a positive correlation between FENDRR and FOXC2 expression in clinic and the overexpressed FOXC2 indicated a poor prognosis in GC patients. Collectively, our findings provide a new perspective for the lncRNA-TF regulatory interaction involved in MDR, suggesting that targeting the FENDRR/FOXC2 axis may be an effective approach to circumvent GC chemoresistance.
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http://dx.doi.org/10.3389/fonc.2021.634579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044876PMC
March 2021

BarH-like homeobox 1 induces the progression of cell malignant phenotype in endometrial carcinoma through the regulation of ERK/MEK signaling pathway.

Reprod Biol 2021 Mar 27;21(2):100502. Epub 2021 Mar 27.

Reproductive Medicine Center of Zibo Maternity and Child Health Hospital, Zibo, 255000, PR China. Electronic address:

The aim of this article was to assess whether and how BARX1 affects the progression of malignant phenotype of endometrial carcinoma (EC) cells. BARX1 levels and its prognostic value were evaluated using the EC-related RNA sequence dataset from The Cancer Genome Atlas (TCGA) database. Functional experiments were performed to evaluate the biological roles of BARX1 in EC HEC-1-A and KLE cells by silencing BARX1. BARX1 was upregulated in EC tissues according to the public database and in EC cells. High expression of BARX1 led to a poor prognosis and significantly related to clinical stage, pathological grade, death, histological subtypes, and menopause status in patients with EC. Silencing BARX1 notably suppressed the aggressive phenotypes of EC cells, as evidenced by inhibiting cells viability, growth, invasion and migration. Furthermore, depletion of BARX1 decreased the phosphorylation (p) levels of ERK and MEK, also reinforced the suppressive effects of ERK/MEK pathway blocker PD98059 on the p-ERK and p-MEK levels. Together, our results demonstrated that BARX1 functions as a carcinogen by regulating the cell viability, invasion, and migration at least partly through the ERK/MEK pathway.
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http://dx.doi.org/10.1016/j.repbio.2021.100502DOI Listing
March 2021

Airapus rakovici (Coleoptera: Scarabaeidae: Aphodiinae: Eupariini), a new species from Fujian, China.

Zootaxa 2021 Jan 27;4920(1):zootaxa.4920.1.8. Epub 2021 Jan 27.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 10010, People's Republic of China. Department of Zoology, Faculty of Science, Charles University, Viničná 7, CZ-128 43 Praha 2, Czech Republic..

The genus Airapus Stebnicka Howden, 1996 currently comprises 26 extant species distributed in the Australian and Oriental zoogeographical regions (Stebnicka Howden 1996; Stebnicka 1998, 2009; Rakovič et al. 2019; Král et al. 2019; Minkina 2020) and one fossil species from the Eocene Baltic amber (Tamutis et al. 2017). Of the continental Southeast Asia, only three species have been known so far: Airapus cechovskyi Král, Mencl Rakovič, 2019 (mainland Malaysia: Kelantan), A. tyri Král, Mencl Rakovič, 2019 (Central Thailand: Phetchaburi Province) and A. sicardi ( Paulian, 1945) (Laos: "Cochinchine: Long Xuyen" and South Vietnam: "Annam: Tanh Hoa") (Paulian 1945; Balthasar 1964; Král et al. 2019). Examination of the material housed in the collections of the Institute of Zoology, Chinese Academy of Sciences, Beijing, China, revealed Airapus material belonging to an undescribed species. Its formal description is presented in this paper. This new species is another, fourth species occurring in mainland Southeast Asia. It is also the first country record from China. The geographical distribution of the genus is now known to the north as far as Fujian Province.
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http://dx.doi.org/10.11646/zootaxa.4920.1.8DOI Listing
January 2021

New immunosuppressive secondary metabolites from the endophytic fungus Aspergillus sp.

Fitoterapia 2021 Mar 19;151:104882. Epub 2021 Mar 19.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address:

Six new metabolites, including two diphenolic derivatives (1 and 2), one pseurotin (3), one butenolide derivative (4), one benzopyran (5) and one isochromane lactone (6), together with ten known compounds (7-16) were isolated from an endophytic fungus Aspergillus sp. Their planar structures and absolute configurations were established based on techniques of MS, NMR, IR, UV, [Rh2(OCOCF3)4] complex-induced ECD, quantum chemical electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Structurally, compound 2 represents the first example of diphenolic derivative possessing an unusual 1-oxaspiro[2.4]heptane core bearing a 5/3 bicyclic skeleton; compound 3 represents the first example of pseurotin type natural products that only one hydroxy group is substituted at side chain. In bioassay, compounds 3, 7 and 8 exhibited potential inhibitory effect on the proliferation of anti-CD3/anti-CD28 monoclonal antibodies (mAbs) induced murine T cells, with IC50 values of (7.81 ± 0.71), (8.25 ± 0.78) and (8.84 ± 0.81) μM, respectively.
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http://dx.doi.org/10.1016/j.fitote.2021.104882DOI Listing
March 2021

Design, synthesis and biological evaluations of diverse Michael acceptor-based phenazine hybrid molecules as TrxR1 inhibitors.

Bioorg Chem 2021 Apr 19;109:104736. Epub 2021 Feb 19.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; School of Engineering, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

A series of novel phenazine derivatives (1~27) containing the Michael acceptor scaffolds were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against Bel-7402 cancer cell line in vitro, in which compound 26 were found to have the best antiproliferative activity. Meanwhile, compound 26 showed no obvious cell toxicity against human normal liver epithelial L02 cells, which means this compound possessed a better safety potential. In the following research, compound 26 was verified to inhibit TrxR1 enzyme activity, ultimately resulting in cellular molecular mechanism events of apoptosis including growth of intracellular ROS level, depletion of reduced Trx1, liberation of ASK1 and up-regulation of p38, respectively. Together, all these evidences implicated that compound 26 acted as the TrxR1 inhibitor against Bel-7402 cells, and could activate apoptosis through the ROS-Trx-ASK1-p38 pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.104736DOI Listing
April 2021

Furin inhibits epithelial cell injury and alleviates experimental colitis by activating the Nrf2-Gpx4 signaling pathway.

Dig Liver Dis 2021 Feb 24. Epub 2021 Feb 24.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province 430071, China; Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Wuhan City, Hubei Province 430071, China. Electronic address:

Background And Aim: Furin is a proprotein convertase reported to have protective effects in several autoimmune diseases. However, the role of furin in ulcerative colitis (UC) remains unclear. We aimed to clarify this role.

Methods: Furin expression was measured in UC and dextran sulfate sodium (DSS)-induced colitis. Gain- and loss-of-function experiments were conducted to evaluate the effect of furin in UC using DSS-treated NCM460 cells. Several ferroptotic parameters, including cell viability, cell death rate, lipid reactive oxygen species level, mitochondrial membrane damage and glutathione peroxidase 4 (Gpx4) expression, were measured. Exogenous furin was used to treat the DSS-induced colitis in mice to confirm the results in vivo. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism.

Results: Furin expression was aberrant in UC. Furin overexpression attenuated DSS-induced ferroptosis-like injury and upregulated Gpx4 in NCM460 cells, whereas silencing furin had the opposite effects. Exogenous furin treatment alleviated DSS-induced colitis in mice by upregulating Gpx4. Mechanistic experiments revealed that furin activated Nrf2 both in vitro and in vivo.

Conclusions: Furin protects epithelial cells from DSS-induced ferroptosis-like cell injury and alleviates experimental colitis by activating the Nrf2-Gpx4 signaling pathway.
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http://dx.doi.org/10.1016/j.dld.2021.02.011DOI Listing
February 2021

Cerebrovascular segmentation from TOF-MRA based on multiple-U-net with focal loss function.

Comput Methods Programs Biomed 2021 Apr 11;202:105998. Epub 2021 Feb 11.

School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Background And Objective: Accurate cerebrovascular segmentation plays an important role in the diagnosis of cerebrovascular diseases. Considering the complexity and uncertainty of doctors' manual segmentation of cerebral vessels, this paper proposed an automatic segmentation algorithm based on Multiple-U-net (M-U-net) to segment cerebral vessel structures from the Time-of-flight Magnetic Resonance Angiography (TOF-MRA) data.

Methods: First, the TOF-MRA data was normalized by volume and then divided into three groups through slices of axial, coronal and sagittal directions respectively. Three single U-nets were trained by divided dataset. To solve the problem of uneven distribution of positive and negative samples, the focal loss function was adopted in training. After obtaining the prediction results of three single U-nets, the voting feature fusion and the post-processing process based on connected domain analysis would be performed. 95 volumes of TOF-MRA provided by the MIDAS platform were applied to the experiment, among which 20 volumes were treated as the training dataset, 5 volumes were used as the validation dataset and the remaining 70 volumes were divided into 10 groups to test the trained model respectively.

Results: Experiments showed that the proposed M-U-net based algorithm achieved 88.60% and 87.93% Dice Similarity Coefficient (DSC) on the verification dataset and testing dataset, which performed better than any single U-net.

Conclusions: Compared with other existing algorithms, our algorithm reached the state of the art level. The feature fusion of three single U-nets could effectively complement the segmentation results.
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http://dx.doi.org/10.1016/j.cmpb.2021.105998DOI Listing
April 2021

Five new secondary metabolites from the fungus Phomopsis asparagi.

Fitoterapia 2021 Jan 31;150:104840. Epub 2021 Jan 31.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address:

Five new compounds, including a pair of diphenylcyclopentenone enantiomers (±)-phomopsisin A (1), a sesquiterpenoid 15-hydroxylithocarin A (2), a new diketopiperazine alkaloid prenylcyclotryprostatin A (3) and 7-hydroxy-cis-L(-)-3,6-dibenzyl-2,5-dioxopiperazine (6), along with five known compounds were isolated from the fungus Phomopsis asparagi. Their structures were elucidated on the basis of spectroscopic analyses (1D and 2D NMR), theoretical electronic circular dichroism (ECD) calculation, modified Mosher's method, and X-ray crystallography. The racemates of (±)-phomopsisin A showed inhibition on α-glucosidase with IC of 30.07 ± 0.75 μM (positive control acarbose, 121 ± 2.7 μM).
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http://dx.doi.org/10.1016/j.fitote.2021.104840DOI Listing
January 2021

Real-world drug survival and reasons for treatment discontinuation of biologics and apremilast in patients with psoriasis in an academic center.

Dermatol Ther 2021 Mar 12;34(2):e14826. Epub 2021 Feb 12.

Department of Dermatology and Cutaneous Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.

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http://dx.doi.org/10.1111/dth.14826DOI Listing
March 2021

New secondary metabolites from the endophytic fungus sp. from .

Nat Prod Res 2021 Jan 15:1-10. Epub 2021 Jan 15.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

One new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (), one prenylated tryptophan derivative (), together with ten known compounds (-) were isolated from the endophytic fungus sp. from . Their structures and absolute configurations were determined by NMR spectroscopic data, HRESIMS data, UV and IR data as well as electronic circular dichroism (ECD) calculation. In structure, compound was a rare example of DMOA-based meroterpenoid with a -fused C/D ring system, and compound possessed an unusual ()-oxime group. In bioactivity, the lovastatin analogues , , and showed potential immunosuppressive activity against anti-CD3/anti-CD28 monoclonal antibodies (mAbs)-irritated murine splenocytes proliferation, with IC values ranging from (5.30 ± 0.51) M to (16.51 ± 1.62) M.
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http://dx.doi.org/10.1080/14786419.2020.1868464DOI Listing
January 2021

Infiltrating Immune Cells in Gastric Cancer: A Novel Predicting Model for Prognosis.

J Cancer 2021 1;12(4):965-975. Epub 2021 Jan 1.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

: Immune cells infiltrating has been proved to be associated with prognosis in gastric cancer (GC) by studies. This study aims to explore the prognosis value of infiltrating immune cells in gastric cancer. In our study, the CIBERSORT algorithm was used to calculate the fraction of 22 tumor-infiltrating immune cells (TIIC) in 100 normal and 300 tumor samples from the GEO cohort and 30 normal and 344 tumor samples from the TCGA cohort. Univariate and multivariate Cox regression were used to construct an immune risk score model. Multivariate cox regression was also used to validate whether our risk score model could predict prognosis in GC independently. Furthermore, the model was validated in different patient subgroups to test its independence. 0.05 was considered statistically significant. The results showed that the fraction of 3 immune cells increased in tumor tissues compared with normal tissues in both the GEO and TCGA cohort. Univariate cox regression analysis showed four cells significantly correlated with survival rate in GC (0.05). The immune risk score model was constructed based on the four cells through multivariate cox regression and further validated. The KM survival curve suggested that patients with high risk had poor prognosis than patients with low risk (0.05). ROC curve indicated the model was reliable (AUC= 0.67 in the GEO cohort, AUC = 0.65 in the TCGA cohort). Furthermore, multivariate Cox regression showed the model was an independent factor for overall survival predicting in GC (hazard ratio (HR) = 2.35, 95% confidence interval (CI) = 1.63~3.40 in the GEO cohort, HR = 2.87, 95% CI = 1.94~4.25 in the TCGA cohort). Finally, we validated the model in patient subgroups by the KM survival curve. In summary, tumor-infiltrating immune cells play an essential role in GC progression and affect the outcome of GC patients. The immune risk score can predict overall survival for GC independently, and high immune risk score is associated with poor prognosis.
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http://dx.doi.org/10.7150/jca.51079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797666PMC
January 2021

Clinical and Endoscopic Characteristics of Chinese Cronkhite-Canada Syndrome Patients: A Retrospective Study of 103 cases.

Dig Dis 2021 Jan 13. Epub 2021 Jan 13.

Introduction: Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by extensive gastrointestinal (GI) polyposis and ectodermal dysplasia. So far, most of CCS related literatures are published as single case report or reviewed with limited case numbers. Our study was to update the clinical and endoscopic characteristics of Chinese CCS patients.

Methods: This retrospective study was conducted in 103 Chinese CCS patients (102 cases from literatures and 1 case from our department). Their clinical and endoscopic data were collected, and statistical analyses were performed.

Results: 1) In Chinese population, people aged 50-70 years (62.62%) had a high incidence of CCS, and the ratio of male-to-female was 2.68:1. 2) The diverse range of GI manifestations were observed in all the patients, and almost all the patients had at least one symptom of ectodermal dysplasias. 3) All CCS patients presented multiple polyps in the GI tract except esophagus, and the size and appearance of polyps were diverse. Congestion, edema and erosion were very common on the surface of polyps (96.83%) and the surrounding mucosa (85.71%) . 4) The common pathological features of polyps were hyperplastic polyps (49.25%) and tubular adenomatous polyps (44.78%). There is 5.97% cancer reported.

Conclusions: middle-aged and elderly people are the high-risk group; various GI symptoms are observed in Chinese patients; the typical endoscopic finding is multiple small sessile polyps; these GI polyps has a chance of malignant potential. Long-term endoscopic surveillance and follow-up are recommended for the Chinese CCS patients. Key words: Cronkhite-Canada syndrome, Clinical characteristics, Endoscopy.
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http://dx.doi.org/10.1159/000514354DOI Listing
January 2021

An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells.

Cell Death Dis 2020 12 14;11(12):1067. Epub 2020 Dec 14.

College of Life Sciences, Sichuan University, Chengdu, Sichuan, P.R. China.

MircoRNA-21 (miR-21) was found to be highly expressed in various solid tumors, and its oncogenic properties have been extensively studied in recent years. However, the reason why miR-21 is highly expressed in various tumors remains elusive. Here, we found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA (saRNA) or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116. Considering the overlapping location of VMP1 and miR-21 gene in genome, the result suggested that the transcription of miR-21 was inhibited by the endogenous transcriptional activation of VMP1. Furthermore, we identified that miR-21 inhibited the activation and nuclear translocation of transcription factor EB (TFEB) through reducing the inhibitory of PTEN on AKT phosphorylation, which can directly activate the transcription of VMP1. Loss of miR-21 significantly increased VMP1 expression, which could be blocked by PTEN inhibitor (VO-Ohpic) or TFEB siRNA. These results showed that miR-21 negatively regulated VMP1 transcription through the PTEN/AKT/TFEB pathway, and TFEB-induced transcriptional activation of VMP1 could inhibit miR-21 expression, thus forming a feedback regulatory loop of miR-21/VMP1. We further found that disrupting the miR-21/VMP1 feedback loop will decrease the expression of miR-21, reduce the malignancy, and increase their sensitivity to 5-fluorouracil in colorectal cancer cells. Taken together, our results revealed a novel regulatory mechanism of miR-21 expression, and targeting the miR-21/VMP1 feedback loop may provide a new approach to inhibit miR-21 expression in colorectal cancer cells.
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http://dx.doi.org/10.1038/s41419-020-03265-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736343PMC
December 2020

Clinical features and genotypes of Laing distal myopathy in a group of Chinese patients, with in-frame deletions of MYH7 as common mutations.

Orphanet J Rare Dis 2020 12 9;15(1):344. Epub 2020 Dec 9.

Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Beijing, 100034, China.

Background: Laing distal myopathy is a rare autosomal dominant inherited distal myopathy caused by mutations of the MYH7 gene affecting mainly the rod region. We described the clinical features, muscle MRI and pathological changes as well as genetic mutations in a group of Chinese patients with Laing distal myopathy.

Results: Six patients with the confirmed diagnoses of Laing distal myopathy were recruited. Ankle dorsiflexion and finger extension weakness, as well as neck flexion weakness were common in our patients. Myopathic as well as neurogenic lesions were suggested by electromyography in different patients. Respiratory abnormality of sleep apnea was detected in two of our patients stressing the necessity of close respiratory monitoring in this disease. Muscle MRIs showed similar features of concentric fatty infiltration of anterior thigh muscles together with early involvement of tibialis anterior and extensor hallucis longus. However, muscle pathological presentations were varied depending on the biopsied muscles and the severity of the disease. In-frame deletions of the MYH7 gene made up 3/4 of mutations in our patients, suggesting that these are common mutations of Laing distal myopathy.

Conclusions: Our study further expanded the phenotypes and genotypes of Laing distal myopathy. In-frame deletions of the MYH7 gene are common causes of Laing distal myopathy.
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http://dx.doi.org/10.1186/s13023-020-01626-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727133PMC
December 2020

Pathological lung segmentation in chest CT images based on improved random walker.

Comput Methods Programs Biomed 2021 Mar 25;200:105864. Epub 2020 Nov 25.

School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

Background And Objective: Pathological lung segmentation as a pretreatment step in the diagnosis of lung diseases has been widely explored. Because of the complexity of pathological lung structures and gray blur of the border, accurate lung segmentation in clinical 3D computed tomography images is a challenging task. In view of the current situation, the work proposes a fast and accurate pathological lung segmentation method. The following contributions have been made: First, the edge weights introduce spatial information and clustering information, so that walkers can use more image information during walking. Second, a Gaussian Distribution of seed point set is established to further expand the possibility of selection between fake seed points and real seed points. Finally, the pre-parameter is calculated using original seed points, and the final results are fitted with new seed points.

Methods: This study proposes a segmentation method based on an improved random walker algorithm. The proposed method consists of the following steps: First, a gray value is used as the sample distribution. Gaussian mixture model is used to obtain the clustering probability of an image. Thus, the spatial distance and clustering result are added as new weights, and the new edge weights are used to construct a random walker map. Second, a large number of marked points are automatically selected, and the intermediate results are obtained from the newly constructed map and retained only as pre-parameters. When new seed points are introduced, the probability value of the walker is quickly calculated from the new parameters and pre-parameters, and the final segmentation result can be obtained.

Results: The proposed method was tested on 65 sets of CT cases. Quantitative evaluation with different methods confirms the high accuracy on our dataset (98.55%) and LOLA11 dataset (97.41%). Similarly, the average segmentation time (10.5s) is faster than random walker (1,332.5s).

Conclusions: The comparison of the experimental results show that the proposed method can accurately and quickly obtain pathological lung processing results. Therefore, it has potential clinical applications.
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http://dx.doi.org/10.1016/j.cmpb.2020.105864DOI Listing
March 2021

Erenumab and OnabotulinumtoxinA Combination Therapy for the Prevention of Intractable Chronic Migraine without Aura: A Retrospective Analysis.

J Pain Palliat Care Pharmacother 2021 Mar 30;35(1):1-6. Epub 2020 Oct 30.

Erenumab is a monoclonal antibody that mediates calcitonin-gene-related peptide (CGRP), a pro-inflammatory polypeptide implicated in migraine pathology, by targeting its receptor. To date, no clinical trial has evaluated combination therapy with both erenumab and onabotulinumtoxinA therapy for the treatment of chronic migraine. We conducted a retrospective chart review of 78 patients to investigate if the addition of erenumab to patients with chronic migraines receiving onabotulinumtoxinA had a decrease in their total monthly headache days (MHDs) and monthly migraine days (MMD). At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 ± 8.7 and mean MMDs were 15.8 ± 8.3, and 65 patients (83.3%) failed at least three preventative therapies. Our results demonstrated a significant reduction in MHDs and MMDs at 30- (-6.8 MHDs; p < 0.001, -7.0 MMDs; p < 0.001), 60- (-7.2 MHDs; p < 0.001, -6.7 MMDs; p < 0.001), and 90 days (-8.1 MHDs; p < 0.001, -7.4 MMDs; p < 0.001). Thus, the results of this study suggest favorable outcomes with the addition of erenumab to patients who were still suffering while receiving onabotulinumtoxinA therapy. Additional investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers.
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http://dx.doi.org/10.1080/15360288.2020.1829249DOI Listing
March 2021

AHNAK2 Is Associated with Poor Prognosis and Cell Migration in Lung Adenocarcinoma.

Biomed Res Int 2020 20;2020:8571932. Epub 2020 Aug 20.

Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Background: Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown.

Methods: We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan-Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration.

Results: The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD.

Conclusion: In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.
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http://dx.doi.org/10.1155/2020/8571932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456490PMC
May 2021

An immune landscape based prognostic signature predicts the immune status and immunotherapeutic responses of patients with colorectal cancer.

Life Sci 2020 Nov 1;261:118368. Epub 2020 Sep 1.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China. Electronic address:

Aims: Colorectal cancer (CRC) is one of the most common cancers with poor prognosis worldwide. The advent of immunotherapy has greatly improved survival in refractory patients of CRC. In this study, we aimed to identify reliable immune classification and biomarkers that predict immunotherapeutic responses in CRC patients.

Materials And Methods: Based on transcriptome profiles of two publicly available CRC datasets, we performed single-sample gene set enrichment analysis (ssGSEA) to calculate the relative abundance of 29 immune-related items of each sample. Unsupervised clustering was used to classify CRC patients. Furthermore, an immune prognostic signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.

Key Findings: The CRC patients were clustered into high, medium, low immune infiltration subtypes based on the immune landscape. There was significant heterogeneity among the three subtypes. The high immune infiltration group showed higher expression of programmed cell death-ligand 1 and better prognosis than the median and low immune infiltration groups. Furthermore, we constructed a 7-immune-related prognostic gene signature and found that the signature had high predictive value and was superior to other clinicopathological parameters. Finally, the correlation analysis of the signature with immune cell infiltration and immune checkpoint molecules suggested that the signature had the potential to assess the immunotherapeutic responses of CRC patients.

Significance: The immune landscape and prognostic signature of CRC contribute to a deeper understanding of the tumor microenvironment and guide accurate immunotherapy.
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http://dx.doi.org/10.1016/j.lfs.2020.118368DOI Listing
November 2020

Terreuspyridine: An Unexpected Pyridine-Fused Meroterpenoid Alkaloid with a Tetracyclic 6/6/6/6 Skeleton from .

Org Lett 2020 09 25;22(17):7041-7046. Epub 2020 Aug 25.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Terreuspyridine (), the first 3,5-demethylorsellinic acid (DMOA) derived meroterpenoid alkaloid, was isolated from the fungus , which represents a new type of meroterpenoid possessing an unexpected tetracyclic 6/6/6/6 architecture. The structure of with absolute configuration was determined by X-ray diffraction analysis. Biogenetically, it was proposed to be derived from the fusion of a DMOA-meroterpenoid and a glutamate. Terreuspyridine () exhibited moderate inhibitory activity against the BChE with an IC value of 16.4 μM.
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http://dx.doi.org/10.1021/acs.orglett.0c02641DOI Listing
September 2020

Comparison of Supervised and Telehealth Delivery of Worksite Exercise for Prevention of Low Back Pain in Firefighters: A Cluster Randomized Trial.

J Occup Environ Med 2020 10;62(10):e586-e592

US Spine & Sport Foundation, San Diego, California (Dr Mayer, Ms Lane, Dr Johnson), Tampa, Florida (Dr Brady), University of South Florida, Tampa, Florida (Dr Chen, Ms Lu), Spine Research LLC, Winchester, Massachusetts (Dr Dagenais).

Objective: This study assessed worksite exercise delivered by on-site supervision (supervised) or telehealth to reduce lost work time (LWT) related to low back pain (LBP) in firefighters.

Methods: A cluster randomized controlled trial assigned 264 career firefighters to supervised (n = 86) or telehealth (n = 95) back and core exercises 2×/week for 12 months, or control (n = 83).

Results: 58.0% (153/264) of participants reported LBP and 7.6% (20/264) reported LWT related to LBP (control n = 10, supervised n = 5, telehealth n = 5). Participants in the control group experienced 1.15 times as many hours of LWT as the supervised group, and 5.51 times as many hours of LWT as the telehealth group.

Conclusions: Worksite exercise, delivered by on-site supervision or telehealth, can reduce LWT related to LBP in career firefighters.
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http://dx.doi.org/10.1097/JOM.0000000000001993DOI Listing
October 2020

Gene mutations associated with early onset familial Alzheimer's disease in China: An overview and current status.

Mol Genet Genomic Med 2020 10 6;8(10):e1443. Epub 2020 Aug 6.

Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Mutations of three causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies worldwide but remains unclear in China. The patients with these known mutations always show considerable clinical phenotypic variability. However, to date, there have been no detailed descriptions of the clinical phenotypes associated with these Chinese EOFAD mutations. Thus, the aim of this study was to describe all of the known mutations in three EOFAD causative genes and genotype-phenotype correlations in Chinese patients with EOFAD.

Method: We systematically searched the PubMed, MEDLINE, CNKI, VIP, and WAN-FANG databases to find Chinese EOFAD mutations in reports from inception through May 2020.

Result: We identified 31 studies reporting mutations of three causative genes in China. 10 mutations in APP gene, 27 mutations in PSEN1 gene and six mutations in PSEN2 were discovered in Chinese EOFAD. This review summarized all these probably pathogenic mutations as well as its clinical features. To the best of our knowledge, this is the first systemic review of causative gene mutations in patients with EOFAD in China.

Conclusion: The analysis of the genetic and clinical phenotype correlations in this review supports the idea that the clinical phenotype might be influenced by specific genetic defects. It also suggests genetic testing and genotype-phenotype correlations are important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.
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http://dx.doi.org/10.1002/mgg3.1443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549583PMC
October 2020

Complex I mutations synergize to worsen the phenotypic expression of Leber's hereditary optic neuropathy.

J Biol Chem 2020 09 28;295(38):13224-13238. Epub 2020 Jul 28.

Division of Medical Genetics and Genomics, Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Lab of Reproductive Genetics, Ministry of Education of PRC, Zhejiang University, Hangzhou, Zhejiang, China; Joint Institute of Genetics and Genomic Medicine between Zhejiang University and University of Toronto, Hangzhou, Zhejiang, China. Electronic address:

Leber's hereditary optic neuropathy (LHON) is a maternal inheritance of eye disease because of the mitochondrial DNA (mtDNA) mutations. We previously discovered a 3866T>C mutation within the gene for the ND1 subunit of complex I as possibly amplifying disease progression for patients bearing the disease-causing 11778G>A mutation within the gene for the ND4 subunit of complex I. However, whether and how the ND1 mutation exacerbates the ND4 mutation were unknown. In this report, we showed that four Chinese families bearing both m.3866T>C and m.11778G>A mutations exhibited higher penetrances of LHON than 6 Chinese pedigrees carrying only the m.3866T>C mutation or families harboring only the m.11778G>A mutation. The protein structure analysis revealed that the m.3866T>C (I187T) and m.11778G>A (R340H) mutations destabilized the specific interactions with other residues of ND1 and ND4, thereby altering the structure and function of complex I. Cellular data obtained using cybrids, constructed by transferring mitochondria from the Chinese families into mtDNA-less (ρ°) cells, demonstrated that the mutations perturbed the stability, assembly, and activity of complex I, leading to changes in mitochondrial ATP levels and membrane potential and increasing the production of reactive oxygen species. These mitochondrial dysfunctions promoted the apoptotic sensitivity of cells and decreased mitophagy. Cybrids bearing only the m.3866T>C mutation displayed mild mitochondrial dysfunctions, whereas those harboring both m.3866T>C and m.11778G>A mutations exhibited greater mitochondrial dysfunctions. These suggested that the m.3866T>C mutation acted in synergy with the m.11778G>A mutation, aggravating mitochondrial dysfunctions and contributing to higher penetrance of LHON in these families carrying both mtDNA mutations.
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http://dx.doi.org/10.1074/jbc.RA120.014603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504918PMC
September 2020

Performance of CuAl-LDH/Gr Nanocomposite-Based Electrochemical Sensor with Regard to Trace Glyphosate Detection in Water.

Sensors (Basel) 2020 Jul 25;20(15). Epub 2020 Jul 25.

College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.

Glyphosate, which has been widely reported to be a toxic pollutant, is often present at trace amounts in the environment. In this study, a novel copper-aluminum metal hydroxide doped graphene nanoprobe (labeled as CuAl-LDH/Gr NC) was first developed to construct a non-enzymatic electrochemical sensor for detection trace glyphosate. The characterization results showed that the synthesized CuAl-LDH had a high-crystallinity flowered structure, abundant metallic bands and an intercalated functional group. After mixed with Gr, the nanocomposites provided a larger surface area and better conductivity. The as-prepared CuAl-LDH/Gr NC dramatically improved the enrichment capability for glyphosate to realize the stripping voltammetry detection. The logarithmic linear detection range of the sensor was found to be 2.96 × 10-1.18 × 10 mol L with the detection limit of 1 × 10 mol L with excellent repeatability, good stability and anti-interference ability. Further, the sensor achieved satisfactory recovery rates in spiked surface water, ranging from 97.64% to 108.08%, demonstrating great accuracy and practicality.
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http://dx.doi.org/10.3390/s20154146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435834PMC
July 2020

The role of autophagy in human cytomegalovirus IE2 expression.

J Med Virol 2021 06 8;93(6):3795-3803. Epub 2020 Oct 8.

Department of Pediatrics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.

The purpose of this study was to determine whether autophagy regulates the expression of human cytomegalovirus (HCMV) immediately early two viral protein (IE2). Rapamycin and 3-methyladenine (3-MA) were used to stimulate or suppress autophagy during HCMV infection. UL122 recombinant plasmid was transfected to overexpress IE2 and small interference RNA against autophagy-related protein 3 (ATG3) was used to knockdown ATG3. Western blot was performed to measure the expression of viral proteins and autophagy levels. Immunofluorescence was used to detect the immediately early 1 viral protein (IE1) expression. In human embryonic lung fibroblasts, infection of HCMV promotes the lipidation of light chain 3 (LC3) at 6 and 24 hours post infection (hpi), which was accompanied by the increased expression of viral protein IE2. When only IE2 was overexpressed via UL122 recombinant plasmid transfection without HCMV infection, the autophagy hallmarks LC3II and ATG3 were upregulated. Furthermore, viral protein IE2 expression was reduced at 24 and 48 hpi either by the treatment of autophagy inducer rapamycin or by the inhibitor 3-MA before HCMV infection. At the same time, small interference ATG3 transient transfection, used to suppress autophagy, significantly inhibited IE2 expression. However, when 3-MA was used to regulate autophagy levels after HCMV infection, expression of IE2 and IE1 were both decreased, while autophagy inducer rapamycin treatment after HCMV infection increased IE2 expression slightly. IE2 was involved in autophagy induced by HCMV infection and blocking autophagy could inhibit the expression of HCMV viral protein IE2, which might be one way for autophagy to restrict HCMV replication.
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http://dx.doi.org/10.1002/jmv.26357DOI Listing
June 2021

KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling.

Theranostics 2020 5;10(16):7335-7350. Epub 2020 Jun 5.

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. MicroRNAs (miRNAs) are usually dysregulated and play important regulatory roles in tumor progression. However, the KRAS mutation-responsive miRNA profile in CRC remains uninvestigated. miR-139-5p was identified and evaluated by small RNA sequencing, qRT-PCR and hybridization. The roles of miR-139-5p in CRC cells with and without KRAS mutation were determined by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays and by tumorigenesis and metastasis assays . Microarrays followed by bioinformatic analyses, luciferase reporter assays and Western blotting were applied for mechanistic studies. miR-139-5p was significantly downregulated in KRAS-mutated CRC cells and tissues compared with their wild-type counterparts. Low miR-139-5p expression was associated with aggressive phenotypes and poor prognosis in CRC patients. miR-139-5p overexpression inhibited CRC cell proliferation, migration and invasion , sensitized tumors to chemotherapy, and impaired tumor growth and metastasis . Transcriptomic profiling identified multiple modulators in the Ras (JUN and FOS) and Wnt (CTNNB1 and DVL1) signaling pathways and the epithelial-to-mesenchymal transition (EMT) process (ZEB1) as direct targets of miR-139-5p, and inverse correlations were confirmed in CRC clinical tissues. Aberrantly activated Wnt signaling in KRAS-mutant cells was demonstrated to transcriptionally repress miR-139-5p through TCF4, forming a miR-139-5p/Wnt signaling double-negative feedback loop. We identified miR-139-5p as a KRAS-responsive miRNA and demonstrated its involvement in CRC progression. KRAS mutation disrupted the miR-139-5p/Wnt signaling reciprocal negative feedback mechanism, which might cause miR-139-5p downregulation and derepression of oncogenic signaling pathways and EMT. These results reveal a transcriptional regulatory mode of KRAS-driven malignant transformation and highlight miR-139-5p as a novel regulator of crosstalk between the Ras and Wnt signaling pathways in CRC.
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http://dx.doi.org/10.7150/thno.45971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330859PMC
May 2021

Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice.

Genes Nutr 2020 Jun 26;15(1):12. Epub 2020 Jun 26.

Laboratory of Nutrition and Development, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: Adiponectin and resistin are typically secreted by the adipose tissue and are abnormally expressed in obesity. However, the underlying influential factors and mechanisms are to be elucidated. It is well known that the expression of genes is regulated by epigenetics while gut microbiota participates in epigenetic processes through its metabolites such as folate, biotin, and short-chain fatty acids (SCFAs). Therefore, we supposed that alteration of gut microbiota might affect the transcriptional expression of adiponectin and resistin through epigenetic regulation in obesity.

Methods: C57BL/6J mice were fed either a high-fat diet (34.9% fat by wt., 60% kcal) or a normal-fat diet (4.3% fat by wt., 10% kcal) for 16 weeks, with ampicillin and neomycin delivered via drinking water to interfere with gut microbiota development. Fecal microbiota was analyzed by 16S rRNA high-throughput sequencing. The mRNA expression levels of genes were measured by real-time quantitative RT-PCR. SCFA contents in feces were examined using gas chromatography.

Results: Alteration of the gut microbiota induced by antibiotic use, characterized by a dramatic reduction of the phylum Firmicutes and Actinobacteria and an increase of Proteobacteria with reductions of genera including Lactobacillus, norank_f_Bacteroidales_S24-7_group, Alistipes, Desulfovibrio, Helicobacter, etc., and increases in Bacteroides, Enterobacter, Klebsiella, inhibited the body weight gain in mice fed the high-fat diet instead of the normal-fat diet. The mRNA expression of adiponectin and resistin was upregulated by antibiotic use in mice fed the high-fat diet, accompanied by increased expression of fat oxidation and thermogenesis-related genes (PPAR-α, Pgc-1α, and Atgl) in the fat and/or liver, whereas no change in the expression of adiponectin and resistin was found in mice fed the normal-fat diet. Furthermore, antibiotic use reduced DNA methylation fractions of the adiponectin and resistin promoters and downregulated the expression of DNA methyltransferase 1 and 3a (DNMT1 and DNMT3a) with the high-fat diet feeding.

Conclusion: Alteration of gut microbiota induced by antibiotic use may affect the expression of adiponectin and resistin in mice fed the high-fat diet by modifying promoter DNA methylation, thus leading to increased fatty acid oxidation and less body weight gain.
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http://dx.doi.org/10.1186/s12263-020-00671-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318443PMC
June 2020

The key iron assimilation genes ClFTR1, ClNPS6 were crucial for virulence of Curvularia lunata via initiating its appressorium formation and virulence factors.

Environ Microbiol 2021 02 25;23(2):613-627. Epub 2020 Jun 25.

College of Plant Protection, Shenyang Agricultural University, Shenyang, 110161, China.

Iron is virtually an essential nutrient for all organisms, to understand how iron contributes to virulence of plant pathogenic fungi, we identified ClFTR1 and ClNPS6 in maize pathogen Curvularia lunata (Cochliobolus lunatus) in this study. Disruption of ClNPS6 significantly impaired siderophore biosynthesis. ClFTR1 and ClNPS6 did mediate oxidative stress but had no significant impact on vegetative growth, conidiation, cell wall integrity and sexual reproduction. Conidial germination delayed and appressoria formation reduced in ΔClftr1 comparing with wild type (WT) CX-3. Genes responsible for conidial germination, appressoria formation, non-host selective toxin biosynthesis and cell wall degrading enzymes were also downregulated in the transcriptome of ΔClftr1 and ΔClnps6 compared with WT. The conidial development, toxin biosynthesis and polygalacturonase activity were impaired in the mutant strains with ClFTR1 and ClNPS6 deletion during their infection to maize. ClFTR1 and ClNPS6 were upregulated expression at 12-24 and 48-120 hpi in WT respectively. ClFTR1 positively regulated conidial germination, appressoria formation in the biotrophy-specific phase. ClNPS6 positively regulates non-host selective toxin biosynthesis and cell wall degrading enzyme activity in the necrotrophy-specific phase. Our results indicated that ClFTR1 and ClNPS6 were key genes of pathogen known to conidia development and virulence factors.
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http://dx.doi.org/10.1111/1462-2920.15101DOI Listing
February 2021