Publications by authors named "X J David Lu"

18,951 Publications

Pharmacological inhibition of KDM5A for cancer treatment.

Eur J Med Chem 2021 Sep 15;226:113855. Epub 2021 Sep 15.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, 315211, Zhejiang, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, 315211, China; Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, 315211, China. Electronic address:

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.
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http://dx.doi.org/10.1016/j.ejmech.2021.113855DOI Listing
September 2021

An efficient and user-friendly method for cytohistological analysis of organoids.

J Tissue Eng Regen Med 2021 Sep 23. Epub 2021 Sep 23.

Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.

Organoid culture is a recently developed in-vitro three-dimensional (3D) cell culture technology. It has wide applications in tissue engineering studies. However, histological analysis of organoid is quite complex and tedious for researchers. This study proposes a user-friendly, affordable and efficient method for making formalin-fixed paraffin embedded (FFPE) organoid blocks and Optimal Cutting Temperature compound (OCT) embedded frozen organoid blocks. This method implements a key pre-embedding step for preparing paraffin embedded organoid blocks, which could concentrate organoid togethor without damaging or loss of samples. This method could be used to process even a small number of organoids with high efficiency. In addition, with minor modifications, the method is readily applied for OCT embedded organoid blocks. The slides generated were ready for H&E staining, immunohistochemistry staining and immunofluorescent staining. The method described in this study can be easily used for routine histological analysis of organoid, and could be performed in general pathology labs and requires no dedicated equipment and reagent. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/term.3248DOI Listing
September 2021

Triboelectric Nanogenerator for Ocean Wave Graded Energy Harvesting and Condition Monitoring.

ACS Nano 2021 Sep 23. Epub 2021 Sep 23.

Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China.

Using triboelectric nanogenerators (TENGs) to harvest blue energy in the ocean is advanced technology at present. In wave environments, the wave magnitude is constantly changing, so designing a TENG that can adjust the energy harvesting ability is necessary. Herein, a graded energy harvesting triboelectric nanogenerator (GEH-TENG) is fabricated, in which double generation units can operate in different transmission states to adapt to wave changes. Under small waves, the GEH-TENG is in the primary transmission state. Once waves are large enough, it enters the secondary transmission state, realizing graded energy harvesting to enhance power generation performance. Experiments show that when the input frequency is 1.0 Hz and the amplitude is 120 mm, the GEH-TENG can generate 0.7 mJ of energy in a single operation cycle, which is 2.3 times of it without grading. Moreover, it can be placed on the shore to monitor ocean wave conditions. An idea of graded energy harvesting is proposed in this study, and the proposal provides useful guidance for practical applications of TENGs in ocean wave condition monitoring.
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http://dx.doi.org/10.1021/acsnano.1c05685DOI Listing
September 2021

Biallelic Mutations in Cause a Disruption in Lipid Homeostasis That Is Associated With Global Developmental Delay, Microcephaly, and Dysmorphic Facial Features.

Front Cell Dev Biol 2021 6;9:618492. Epub 2021 Sep 6.

The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.

Objective: We proposed that the deficit of ACC1 is the cause of patient symptoms including global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. We evaluated the possible disease-causing role of the gene in developmental delay and investigated the pathogenesis of ACC1 deficiency.

Methods: A patient who presented with global developmental delay with unknown cause was recruited. Detailed medical records were collected and reviewed. Whole exome sequencing found two variants of with unknown significance. ACC1 mRNA expression level, protein expression level, and enzyme activity level were detected in patient-derived cells. Lipidomic analysis, and functional studies including cell proliferation, apoptosis, and the migratory ability of patient-derived cells were evaluated to investigate the possible pathogenic mechanism of ACC1 deficiency. RNAi-induced ACC1 deficiency fibroblasts were established to assess the causative role of ACC1 deficit in cell migratory disability in patient-derived cells. Palmitate supplementation assays were performed to assess the effect of palmitic acid on ACC1 deficiency-induced cell motility deficit.

Results: The patient presented with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. A decreased level of ACC1 and ACC1 enzyme activity were detected in patient-derived lymphocytes. Lipidomic profiles revealed a disruption in the lipid homeostasis of the patient-derived cell lines. functional studies revealed a deficit of cell motility in patient-derived cells and the phenotype was further recapitulated in ACC1-knockdown (KD) fibroblasts. The cell motility deficit in both patient-derived cells and ACC1-KD were attenuated by palmitate.

Conclusion: We report an individual with biallelic mutations in , presenting global development delay. studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.
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http://dx.doi.org/10.3389/fcell.2021.618492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450402PMC
September 2021

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

Front Endocrinol (Lausanne) 2021 6;12:721198. Epub 2021 Sep 6.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.
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http://dx.doi.org/10.3389/fendo.2021.721198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450670PMC
September 2021
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