Guowei Yang

Beijing Friendship Hospital

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Nicholas R. Waterfield

University of Warwick

Jian Yang

Chinese Academy of Medical Sciences & Peking Union Medical College

Lihong Chen

Fujian Medical University

Yun Wu

Zhejiang A & F University

Xu-Dong Qu

Zhongshan Hospital

Dongjie Zhang

Animal Science Research Institute

Richard H. ffrench‐Constant

University of Exeter

Qi Jin

Chinese Academy of Medical Sciences & Peking Union Medical College

Zhiping Yan

Qujing Normal University

Shaogang Li

China Agricultural University

Cooperative Institutions

Sun Yat-sen University

Fudan University

Chinese Academy of Sciences

Zhongshan Hospital

Chinese Academy of Medical Sciences & Peking Union Medical College

Capital Medical University

The First Affiliated Hospital, Sun Yat-sen University

Ministry of Agriculture and Rural Affairs

University of Bath

University of Chinese Academy of Sciences

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Percutaneous microwave ablation combined with simultaneous transarterial chemoembolization for the treatment of advanced intrahepatic cholangiocarcinoma

OncoTargets and Therapy (2015)

Guowei Yang Qing Zhao Sheng Qian Liang Zhu Xu-Dong Qu

To retrospectively evaluate the safety and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) combined with simultaneous transarterial chemoembolization (TACE) in the treatment of patients with advanced intrahepatic cholangiocarcinoma (ICC).All patients treated with ultrasound-guided percutaneous MWA combined with simultaneous TACE for advanced ICC at our institution were included. Posttreatment contrast-enhanced computed tomography and/or magnetic resonance imaging were retrieved and reviewed for tumor response to the treatment. Routine laboratory studies, including hematology and liver function tests were collected and analyzed. Procedure-related complications were reviewed and survival rates were analyzed.From January 2011 to December 2014, a total of 26 advanced ICC patients were treated at our single institute with ultrasound-guided percutaneous MWA combined with simultaneous TACE. There were 15 males and eleven females with an average age of 57.9±10.4 years (range, 43-75 years). Of 26 patients, 20 (76.9%) patients were newly diagnosed advanced ICC without any treatment, and six (23.1%) were recurrent and treated with surgical resection of the original tumor. The complete ablation rate was 92.3% (36/39 lesions) for advanced ICC. There were no major complications observed. There was no death directly from the treatment. Median progression-free survival and overall survival were 6.2 and 19.5 months, respectively. The 6-, 12-, and 24-month survival rates were 88.5%, 69.2%, and 61.5%, respectively.The study suggests that ultrasound-guided percutaneous MWA combined with simultaneous TACE therapy can be performed safely in all patients with advanced ICC. The complete ablation rate was high and there was no major complication. The overall 24-month survival was 61.5%.

Microwave ablation

Intrahepatic Cholangiocarcinoma

10.2147/ott.s84764

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Citations (36)

[Effects of light intensity on associated enzyme activity and gene expression during callus formation of Vitis vinifera].

PubMed (2015)

Rong Liu Guowei Yang Yueyan Wu Rao Huiyun Xuefu Li

We analyzed the best light intensity for callus induction and maintenance in Vitis vinifera and explored the mechanism of grape callus browning. Tender stem segments of grape cultivar "gold finger" were used to study the effects of different light intensities (0, 500, 1 000, 1 500, 2 000, 2 500, 3 000 and 4 000 Lx) on the induction rate, browning rate and associated enzyme activity and gene expression during Vitis vinifera callus formation. The callus induction rate under 0, 500, 1 000 and 1 500 Lx was more than 92%, significantly higher than in other treatments (P < 0.05). A lower browning rate and better callus growth were also observed during subculture under 1 000 and 1 500 Lx treatments. We found that chlorogenic acid, caffeic acid, p-hydroxybenzoic acid and coumaric acid contents were correlated with the browning rate of callus, among which chlorogenic acid content was positively correlated with the browning rate (P < 0.05). Peroxidase (POD) and polyphenol oxidase (PPO) activities were negatively correlated with the browning rate of callus (P < 0.01). The POD, PPO and phenylalanine ammonialyase (PAL) expression levels were positively correlated with the browning rate at P < 0.05 or P < 0.01. An appropriate light intensity for the tissue culture of Vitis vinifera was 1 000-1 500 Lx, higher or lower light intensities significantly impaired normal callus growth.

Callus

Browning

Chlorogenic Acid

Light intensity

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Citations (1)

Photorhabdus: Genomics of a Pathogen and Symbiont

ASM Press eBooks (2014)

Richard H. ffrench‐Constant Andrea J. Dowling Michelle C. Hares Guowei Yang Nicholas R. Waterfield

This chapter addresses questions related to the genomics of Photorhabdus, compares the Photorhabdus genome with Escherichia coli to identify putative pathogenicity islands, and compares different Photorhabdus species in order to identify islands that are putatively specific to different species with different life cycles. At present, we have full genome sequences from both an exclusive insect pathogen, P. luminescens TT01, and an insect pathogen that has also been recovered from human wounds, P. asymbiotica. Comparisons between these two very different species should therefore also shed light on the evolution of vertebrate pathogenicity in the Photorhabdus genus. Comparison of Photorhabdus virulence cassette (PVC) loci of different Photorhabdusstrains shows that different strains possess different complements of units. In order to clarify the relationship between the Photorhabdus insect-related (PIR) AB toxins and the protein labeled as a JHE in the Colorado potato beetle, we cloned plu4093 and plu4092 from TT01 and tested them for injectable activity against Galleria. Similarly, comparisons of the tca loci of different Photorhabdus species show that three different deletions have led to the three independent losses of tca components in P. temperata, P. asymbiotica, and P. luminescens TT01. DNA-based microarrays have been used in the comparative genomics of different Photorhabdus species and strains in order to attempt to identify regions involved in the specificity of the Photorhabdus nematode interaction. The authors have compared the genome of the insect pathogen with that of the human pathogen in an attempt to understand what makes Photorhabdus asymbiotica so pathogenic.

Photorhabdus

Photorhabdus luminescens

Comparative Genomics

Human pathogen

Consilience

10.1128/9781555815530.ch16

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Citations (3)

Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion

PLoS Pathogens (2012)

Guowei Yang Carmen Sara Hernández‐Rodríguez Michael L. Beeton Paul A. Wilkinson Richard H. ffrench‐Constant

The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4∶1∶1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in Gram negative pathogens.

Photorhabdus

Photorhabdus luminescens

Xenorhabdus

Virulence factor

Heterologous

Heterologous expression

10.1371/journal.ppat.1002692

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Citations (20)

Hypoxia blocks ferroptosis of hepatocellular carcinoma via suppression of METTL14 triggered YTHDF2‐dependent silencing of SLC7A11

Journal of Cellular and Molecular Medicine (2021)

Zhuoyang Fan Guowei Yang Wei Zhang Qian Liu Guangqin Liu

Residue hepatocellular carcinoma (HCC) cells enduring hypoxic environment triggered by interventional embolization obtain more malignant potential with little clarified mechanism. The N6 -methyladenosine (m6 A) biological activity plays essential roles in diverse physiological processes. However, its role under hypoxic condition remains largely unexplored. RT-qPCR and Western blot were used to evaluate METTL14 expression in hypoxic HCC cells. MDA assay and electronic microscopy photography were used to evaluate ferroptosis. The correlation between SLC7A11 and METTL14 was conducted by bioinformatical analysis. Flow cytometry was used to verify the effect of SLC7A11 on ROS production. Cell counting kit-8 assay was performed to detect cells proliferation ability. Hypoxia triggered suppression of METTL14 in a HIF-1α-dependent manner potently abrogated ferroptosis of HCC cells. Mechanistic investigation identified SLC7A11 was a direct target of METTL14. Both in vitro and in vivo assay demonstrated that METTL14 induced m6 A modification at 5'UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14-induced tumour-suppressive effect in hypoxic HCC. Our investigations lay the emphasis on the hypoxia-regulated ferroptosis in HCC cells and identify the HIF-1α /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.

Hypoxia

10.1111/jcmm.16957

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Citations (115)

Predicting Synthetic Lethal Genetic Interactions in Breast Cancer using Decision Tree

Zibo Yin Bowen Qian Guowei Yang Li Guo

Recently, a type of genetic interaction, termed synthetic lethality, is emerging as a potential promising anticancer strategy. Synthetic lethality indicates that simultaneous silencing of two complementary signaling pathways can cause cell death, while deficiency of any single gene will not show phenotype. In this study, we aimed to analyze and predict synthetic lethal genetic interactions based on decision tree in breast cancer using TCGA data. First, candidate gene pairs were collected using mutation data based on Misl algorithm, and involved genes were found in more than 2.5% total samples. Based on this method, we obtained 51,040 candidate gene pairs containing 320 genes. Second, 281 experimentally validated gene pairs were used to classify and optimize two features of mutation coverage and copy number variations (CNV) gain/loss, and the final integrated scores were used to predict synthetic lethal genetic interactions based on decision tree. Finally, candidate gene pairs were performed multi-level integrative analysis to search potential interactions, and 11,758 pairs were primarily identified. Some key gene pairs could be further screened based on drug responses and amplification features for experimentally identification, and we finally screened 5 gene pairs to perform further analysis. These results may contribute to screening and identifying synthetic lethal genetic interactions to uncover potential therapeutic target.

Synthetic Lethality

Candidate gene

Gene interaction

Identification

Tree (set theory)

10.1145/3375923.3375933

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Citations (2)

Additional file 2 of Establish an allele-specific real-time PCR for Leishmania species identification

Figshare (2022)

Yun Wu Mengyuan Jiang Shaogang Li Nicholas R. Waterfield Guowei Yang

Additional file 2: Table S2. Leishmania interspecies polymorphism in 21 genes.

Identification

10.6084/m9.figshare.19976656

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Application of Quantitative PCR in the Diagnosis and Evaluating Treatment Efficacy of Leishmaniasis

Frontiers in Cellular and Infection Microbiology (2020)

Yun Wu Xiao‐Jun Tian Nan Song Minjun Huang Zhaoyong Wu

Leishmaniasis is still a serious neglected tropical disease that may cause death in infected individuals. At present, the clinical diagnosis and treatment monitoring still rely on parasitological culture and microscopy that needs experienced technicians. The low sensitivity and inconvenience of microscopic examination could cause misdiagnosis and relapse of leishmaniasis. There is an urgent need for developing a sensitive and easily operated diagnostic method for the diagnosis and disease management of leishmaniasis. Thus, a quantitative real-time PCR (qPCR) based on the conversed regions of kinetoplast minicircle DNA (mkDNA) of Leishmania spp. was developed to detect different species of Leishmania. The designed mkDNA-based qPCR was able to detect as low as one copy of Leishmania mkDNA or DNA from single parasite. It also detected Pan-Leishmania protozoa including L. donovani, L. infantum and L. major without cross-reaction with other pathogen DNAs available in our lab. This method was clinically applied to quantitatively detect skin lesion samples from 20 cutaneous leishmaniasis (CL) and bone marrow and/or PBMC samples from 30 current and cured visceral leishmaniasis (VL) patients, and blood samples from 11 patients with other infections and 5 normal donors as well. Total 20 skin lesion samples from current CL patients and 20 bone marrow and/or PBMC samples from current VL patients were all detected as positive with qPCR without cross-reaction with samples from patients with malaria, brucellosis and dengue or normal donors. Two VL patients with parasite converted to microscopically negative after treatment were detected positive with qPCR. The patients with bigger skin lesion in CL and higher level of immunoglobulin or splenomegaly in VL, had the higher parasite load detected by qPCR. The parasite load was significantly reduced after treatment. In conclusion, the mkDNA-based qPCR assay that we developed in this study can be used not only for diagnosis of both cutaneous and visceral leishmaniasis with high sensitivity and specificity, but also for evaluating the severity and treatment efficacy of this disease, presenting a rapid and accurate tool for clinical surveillance, treatment monitoring and the end point determination of leishmaniasis.

Kinetoplast

Parasite load

Kinetoplastida

10.3389/fcimb.2020.581639

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Citations (22)

KDM5c Promotes Colon Cancer Cell Proliferation Through the FBXW7-c-Jun Regulatory Axis

Frontiers in Oncology (2020)

Haishan Lin Nina Ma Lei Zhao Guowei Yang Bangwei Cao

KDM5c is a histone demethylase that specifically demethylates trimethylated and dimethylated H3 Lys-4 to play a central role in transcriptional repression. C-Jun is a proto-oncogene and promotes cell proliferation when ectopically accumulated, but can be ubiquitinated by SCF (FBXW7), leading to its degradation. FBXW7 is an E3 ubiquitin ligase of c-Jun, and exhibits carcinostasis in colon cancer. Here, we report that overexpression of KDM5c in human colon cancer cells results in attenuated FBXW7 transcription and accumulated c-Jun protein, leading to increased proliferation of colon cancer cells. We show that overexpression of KDM5c can result in increased c-Jun protein levels and decreased ubiquitin levels, with no significant change in mRNA levels of c-Jun. KDM5c overexpression blocks the ubiquitin-proteasome proteolytic pathway of c-Jun by down-regulating the expression of FBXW7. KDM5c down-regulation of FBXW7 occurs by demethylation of H3K4me3 at TSS and downstream of the FBXW7 gene. And interaction of KDM5c with H3K4me3 downstream of FBXW7 gene may be followed by recruitment of DNMT3b to methylate the spatially close CpG island located near the FBXW7 TSS. This methylation represses FBXW7 gene expression, which can reduce c-Jun degradation via the ubiquitin-proteasome pathway. TCGA database analysis revealed high expression of KDM5c in colon cancer tissues. KDM5c expression in colon cancer was correlated with poor overall survival of patients in the first 7 years. Data from TCGA showed that high expression of KDM5c was correlated with high DNA methylation of the FBXW7 gene, but was not positively correlated with methylation of the Jun gene. These results suggest that KDM5c regulation of colon cell proliferation is mainly mediated by the KDM5c-FBXW7-c-Jun axis.

Demethylase

H3K4me3

10.3389/fonc.2020.535449

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Citations (23)

Research on expression expression and cold induced of Min pig PGD and LDHA

Dongbei Nongye Daxue xuebao (2011)

Guowei Yang

6-phosphogluconate dehydrogenase is a key enzyme in the pentose pathway.Lactate dehydrogenase A is one of the key enzymes in glycolysis.The objective of this study was to investigate PGD and LDHA genes were whether exercise the biological function during Min pig against cold weather.RT-PCR and Real-time PCR method were used;analyses of PGD and LDHA gene in Min pig's large intestines,leg muscle,lung,fat,heart,spleen and liver as well as the expression of cold induced changes in the leg muscle were done.The results showed that PGD gene in the seven tissues was highly expressed,and the expression of cold induced had a significant increase(P0.05).LDHA gene in the seven tissues were all expressed,and the level of cold-induced expression decreased significantly(P0.05).

Lactate dehydrogenase A

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