Zhu M

References (22)

Title : Integrated transcriptomics and metabolomics analyses reveal the aerobic biodegradation and molecular mechanisms of 2,3',4,4',5-pentachlorodiphenyl (PCB 118) in Methylorubrum sp. ZY-1 - Wu_2024_Chemosphere__141921
Author(s) : Wu Y , Zhu M , Ouyang X , Qi X , Guo Z , Yuan Y , Dang Z , Yin H
Ref : Chemosphere , :141921 , 2024
Abstract : 2,3',4,4',5-pentachlorodiphenyl (PCB 118), a highly representative PCB congener, has been frequently detected in various environments, garnering much attention across the scientific community. The degradation of highly chlorinated PCBs by aerobic microorganisms is challenging due to their hydrophobicity and persistence. Herein, the biodegradation and adaptation mechanisms of Methylorubrum sp. ZY-1 to PCB 118 were comprehensively investigated using an integrative approach that combined degradation performance, product identification, metabolomic and transcriptomic analyses. The results indicated that the highest degradation efficiency of 0.5 mg L(-1) PCB 118 reached 75.66% after seven days of inoculation when the bacteria dosage was 1.0 g L(-1) at pH 7.0. A total of eleven products were identified during the degradation process, including low chlorinated PCBs, hydroxylated PCBs, and ring-opening products, suggesting that strain ZY-1 degraded PCB 118 through dechlorination, hydroxylation, and ring-opening pathways. Metabolomic analysis demonstrated that the energy supply and redox metabolism of strain ZY-1 was disturbed with exposure to PCB 118. To counteract this environmental stress, strain ZY-1 adjusted both the fatty acid synthesis and purine metabolism. The analysis of transcriptomics disclosed that multiple intracellular and extracellular oxidoreductases (e.g., monooxygenase, alpha/beta hydrolase and cytochrome P450) participated in the degradation of PCB 118. Besides, active efflux of PCB 118 and its degradation intermediates mediated by multiple transporters (e.g., MFS transporter and ABC transporter ATP-binding protein) might enhance bacterial resistance against these substances. These discoveries provided the inaugural insights into the biotransformation of strain ZY-1 to PCB 118 stress, illustrating its potential in the remediation of contaminated environments.
ESTHER : Wu_2024_Chemosphere__141921
PubMedSearch : Wu_2024_Chemosphere__141921
PubMedID: 38588902
Gene_locus related to this paper: meted-c7c8u4 , meted-c7cge7 , meted-c7ci36

Title : Computer-aided rational design strategy based on protein surface charge to improve the thermal stability of a novel esterase from Geobacillus jurassicus - Song_2024_Biotechnol.Lett__
Author(s) : Song R , Zhang J , Zhu M , Lin L , Wei W , Wei D
Ref : Biotechnol Lett , : , 2024
Abstract : OBJECTIVES: Although Geobacillus are significant thermophilic bacteria source, there are no reports of thermostable esterase gene in Geobacillus jurassicus or rational design strategies to increase the thermal stability of esterases. RESULTS: Gene gju768 showed a highest similarity of 15.20% to esterases from Geobacillus sp. with detail enzymatic properties. Using a combination of Gibbs Unfolding Free Energy (deltadeltaG) calculator and the distance from the mutation site to the catalytic site (Ds(Calpha-Calpha)) to screen suitable mutation sites with elimination of negative surface charge, the mutants (D24N, E221Q, and E253Q) displayed stable mutants with higher thermal stability than the wild-type (WT). Mutant E253Q exhibited the best thermal stability, with a half-life (T(1/2)) at 65 degreesC of 32.4 min, which was 1.8-fold of the WT (17.9 min). CONCLUSION: Cloning of gene gju768 and rational design based on surface charge engineering contributed to the identification of thermostable esterase from Geobacillus sp. and the exploration of evolutionary strategies for thermal stability.
ESTHER : Song_2024_Biotechnol.Lett__
PubMedSearch : Song_2024_Biotechnol.Lett__
PubMedID: 38523202

Title : Biosynthesis of diisooctyl 2,5-furandicarboxylate by Candida antarctica lipase B (CALB) immobilized on a macroporous epoxy resin - Mang_2023_Biotechnol.Appl.Biochem__
Author(s) : Mang R , Zhou Y , Du X , Zhou H , Zhu M
Ref : Biotechnol Appl Biochem , : , 2023
Abstract : Diisooctyl 2,5-furandicarboxylate (DEF), an ester derivative of 2,5-furandicarboxylic acid (FDCA, a bio-based platform chemical), resembles the physical and chemical properties of phthalates. Due to its excellent biodegradability, DEF is considered a safer alternative to the hazardous phthalate plasticizers. Although FDCA esters are currently mainly produced by chemical synthesis, the enzymatic synthesis of DEF is a green, promising alternative. The current study investigated the biosynthesis of DEF by Candida antarctica lipase B (CALB) immobilized on macroporous resins. Out of five macroporous resins (NKA-9, LX-1000EP, LX-1000HA, XAD-7HP, and XAD-8) evaluated, the LX-1000EP epoxy resin was identified as the best carrier for CALB, and the XAD-7HP weakly polar resin was identified as the second best. The optimal immobilization conditions were as follows: CALB (500 microL) and LX-1000EP (0.1 g) were incubated in phosphate butter (20 mM, pH 6.0) for 10 h at 35 degreesC. The resulting immobilized CALB (EP-CALB) showed an activity of 639 U/g in the hydrolysis of p-nitrophenyl acetate, with an immobilization efficiency of 87.8% and an activity recovery rate of 56.4%. Using 0.02 g EP-CALB as the catalyst in 10 mL toluene, and the molar ratio of 2,5-dimethyl furanediformate (1 mmol/mL) and isooctyl alcohol (4 mmol/mL) that was 1:4, a DEF conversion rate of 91.3% was achieved after a 24-h incubation at 50 degreesC. EP-CALB had similar thermal stability and organic solvent tolerance compared to Novozym 435, and both were superior to CALB immobilized on the XAD-7HP resin. EP-CALB also exhibited excellent operational stability, with a conversion rate of 52.6% after 10 repeated uses. EP-CALB could be a promising alternative to Novozym 435 in the biomanufacturing of green and safe plasticizers such as DEF.
ESTHER : Mang_2023_Biotechnol.Appl.Biochem__
PubMedSearch : Mang_2023_Biotechnol.Appl.Biochem__
PubMedID: 37264706

Title : AADAC promotes therapeutic activity of cisplatin and imatinib against ovarian cancer cells - Wang_2022_Histol.Histopathol__18460
Author(s) : Wang H , Wang D , Gu T , Zhu M , Cheng L , Dai W
Ref : Histol Histopathol , :18460 , 2022
Abstract : OBJECTIVE: To explore how AADAC functions in the malignant progression of ovarian cancer, and the effect of AADAC on drug therapeutic activity against ovarian cancer cells. METHODS: AADAC level in tumor and normal samples from TCGA-OV dataset and its survival significance were analyzed by bioinformatics methods. Signaling pathway enrichment analysis for the high- and low-AADAC patients was achieved by using GSEA software. AADAC expression in the cell lines with different treatments was evaluated via qRT-PCR. Cell proliferative ability was assessed via MTT assay Cell migratory and invasive abilities were evaluated via transwell assay. Angiogenesis assay was performed to examine the angiogenetic ability. RESULTS: AADAC was upregulated in ovarian cancer tissues, and patients with high expression of AADAC had favorable survival conditions compared to the low AADAC expression ones. Overexpression of AADAC inhibited the malignant progression of ovarian cancer cells. Both cisplatin and imatinib suppressed cancer cell malignant progression, while overexpressed AADAC synergistically enhanced such inhibition. CONCLUSIONS: The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.
ESTHER : Wang_2022_Histol.Histopathol__18460
PubMedSearch : Wang_2022_Histol.Histopathol__18460
PubMedID: 35451495

Title : Integrative Analysis of Transcriptome and Metabolome Reveals Molecular Responses in Eriocheir sinensis with Hepatopancreatic Necrosis Disease - Zhan_2022_Biology.(Basel)_11_
Author(s) : Zhan M , Wen L , Zhu M , Gong J , Xi C , Wen H , Xu G , Shen H
Ref : Biology (Basel) , 11 : , 2022
Abstract : Hepatopancreatic necrosis disease (HPND) is a highly lethal disease that first emerged in 2015 in Jiangsu Province, China. So far, most researchers believe that this disease is caused by abiotic factors. However, its true pathogenic mechanism remains unknown. In this study, the effects of HPND on the metabolism and other biological indicators of the Chinese mitten crab (Eriocheir sinensis) were evaluated by integrating transcriptomics and metabolomics. Our findings demonstrate that the innate immunity, antioxidant activity, detoxification ability, and nervous system of the diseased crabs were affected. Additionally, metabolic pathways such as lipid metabolism, nucleotide metabolism, and protein metabolism were dysregulated, and energy production was slightly increased. Moreover, the IL-17 signaling pathway was activated and high levels of autophagy and apoptosis occurred in diseased crabs, which may be related to hepatopancreas damage. The abnormal mitochondrial function and possible anaerobic metabolism observed in our study suggested that functional hypoxia may be involved in HPND progression. Furthermore, the activities of carboxylesterase and acetylcholinesterase were significantly inhibited, indicating that the diseased crabs were likely stressed by pesticides such as pyrethroids. Collectively, our findings provide new insights into the molecular mechanisms altered in diseased crabs, as well as the etiology and pathogenic mechanisms of HPND.
ESTHER : Zhan_2022_Biology.(Basel)_11_
PubMedSearch : Zhan_2022_Biology.(Basel)_11_
PubMedID: 36138745

Title : Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation - Jiang_2022_Brain.Behav__e2469
Author(s) : Jiang K , Zheng Y , Lin J , Wu X , Yu Y , Zhu M , Fang X , Zhou M , Li X , Hong D
Ref : Brain Behav , :e2469 , 2022
Abstract : INTRODUCTION: Mutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb-girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated. METHODS: In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. In addition, we summarized all GFPT1-related CMS patients with muscle biopsy in the literature. RESULTS: Pathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z-disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1-related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria-like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra-synaptic pathological changes might be associated with GFPT1-deficiency hypoglycosylation and altered function of muscle-specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy. CONCLUSIONS: Most patients with GFPT1-related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.
ESTHER : Jiang_2022_Brain.Behav__e2469
PubMedSearch : Jiang_2022_Brain.Behav__e2469
PubMedID: 34978387

Title : Employing Engineered Enolase Promoter for Efficient Expression of Thermomyces lanuginosus Lipase in Yarrowia lipolytica via a Self-Excisable Vector - Jiao_2022_Int.J.Mol.Sci_24_
Author(s) : Jiao L , Li W , Li Y , Zhou Q , Zhu M , Zhao G , Zhang H , Yan Y
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Yarrowia lipolytica is progressively being employed as a workhouse for recombinant protein expression. Here, we expanded the molecular toolbox by engineering the enolase promoter (pENO) and developed a new self-excisable vector, and based on this, a combined strategy was employed to enhance the expression of Thermomyces lanuginosus lipase (TLL) in Y. lipolytica. The strength of 11 truncated enolase promoters of different length was first identified using eGFP as a reporter. Seven of the truncated promoters were selected to examine their ability for driving TLL expression. Then, a series of enolase promoters with higher activities were developed by upstream fusing of different copies of UAS1B, and the recombinant strain Po1f/hp16e(100)-tll harboring the optimal promoter hp16e(100) obtained a TLL activity of 447 U/mL. Additionally, a new self-excisable vector was developed based on a Cre/loxP recombination system, which achieved efficient markerless integration in Y. lipolytica. Subsequently, strains harboring one to four copies of the tll gene were constructed using this tool, with the three-copy strain Po1f/3tll showing the highest activity of 579 U/mL. The activity of Po1f/3tll was then increased to 720 U/mL by optimizing the shaking flask fermentation parameters. Moreover, the folding-related proteins Hac1, Pdi, and Kar2 were employed to further enhance TLL expression, and the TLL activity of the optimal recombinant strain Po1f/3tll-hac1-pdi-kar2 reached 1197 U/mL. By using this combined strategy, TLL activity was enhanced by approximately 39.9-fold compared to the initial strain. Thus, the new vector and the combined strategy could be a useful tool to engineer Y. lipolytica for high-level expression of heterologous protein.
ESTHER : Jiao_2022_Int.J.Mol.Sci_24_
PubMedSearch : Jiao_2022_Int.J.Mol.Sci_24_
PubMedID: 36614159

Title : Anti-dipeptidyl-peptidase-like protein 6 encephalitis with pure cerebellar ataxia: a case report - Lin_2022_BMC.Neurol_22_242
Author(s) : Lin J , Zhu M , Mao X , Jin Z , Zhou M , Hong D
Ref : BMC Neurol , 22 :242 , 2022
Abstract : BACKGROUND: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare autoimmune encephalitis. The clinical symptoms of anti-DPPX encephalitis are often severe, manifested as diarrhea/weight loss, central nervous system hyperexcitability and cognitive dysfunction. CASE PRESENTATION: An 18-year-old boy was admitted for 1-week-long cerebellar symptoms including dizziness, unsteady gait and frequent vomiting. Magnetic resonance imaging (MRI) displayed no abnormal findings. However, autoimmune encephalitis panel revealed anti-DPPX antibody was positive in the serum. This patient completely recovered after immunoglobulin and corticoids therapy. In addition, repeat serum antibody test for DPPX was negative within one month. CONCLUSION: In addition to the classic triad, anti-DPPX encephalitis may manifest as mild and rare symptoms due to lower antibody titers. Fast identification of rare symptoms can help to quickly diagnosis and effective treatment.
ESTHER : Lin_2022_BMC.Neurol_22_242
PubMedSearch : Lin_2022_BMC.Neurol_22_242
PubMedID: 35778696
Gene_locus related to this paper: human-DPP6

Title : Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes - Bi_2021_Cell_184_1377
Author(s) : Bi X , Wang K , Yang L , Pan H , Jiang H , Wei Q , Fang M , Yu H , Zhu C , Cai Y , He Y , Gan X , Zeng H , Yu D , Zhu Y , Qiu Q , Yang H , Zhang YE , Wang W , Zhu M , He S , Zhang G
Ref : Cell , 184 :1377 , 2021
Abstract : Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.
ESTHER : Bi_2021_Cell_184_1377
PubMedSearch : Bi_2021_Cell_184_1377
PubMedID: 33545088
Gene_locus related to this paper: atrsp-a0a8j7tiu5

Title : The facile formation of hierarchical mesoporous silica nanocarriers for tumor-selective multimodal theranostics - Guo_2021_Biomater.Sci__
Author(s) : Guo X , Zhu M , Yuan P , Liu T , Tian R , Bai Y , Zhang Y , Chen X
Ref : Biomater Sci , : , 2021
Abstract : The combination of therapeutic and diagnostic functions in a single platform has aroused great interest due to the more optimal synergistic effects that can be obtained as compared to any single theranostic approach alone. However, current nanotheranostics are normally formed via complicated construction steps involving the pre-synthesis of each component and further conjugation via chemical bonds, which may cause low integration efficiency and limit production and applications. Herein, a tumor-targeting and tumor-responsive all-in-one nanoplatform based on mesoporous silica nanocarriers (MSNs) was fabricated via a facile approach utilizing efficient and nondestructive physical interactions for long-wavelength fluorescence imaging-guided synergistic chemo-catalytic-photothermal tumor therapy. The MSNs were endowed with these multimodal theranostics via a simple hydrothermal method after coordinating with Fe2+ and glutathione (GSH) to introduce ferroferric oxide and carbon dots in situ. The former acts as a photothermal agent and catalytic agent to generate local heat under 808 nm irradiation and also when toxic hydroxyl radicals (OH) are in contact with abundant hydrogen peroxide in cancer cells, while the latter participates in fluorescence imaging. After loading with paclitaxel (PTX), polyester and folic-acid-conjugated cyclodextrin were employed to serve as an esterase-sensitive gatekeeper controlling PTX release from the MSN pores and as a tumor-targeting agent for accurate therapy, respectively. As expected, the nanoplatform was efficiently taken up by tumor cells over healthy cells, and then, synergetic chemo-catalytic-photothermal therapy was performed, resulting in 5-fold greater apoptosis of tumor cells as compared to healthy cells under 808 nm irradiation. Moreover, in vivo data from tumor-bearing mouse models showed that tumors were significantly inhibited, and the survival rates of these mice increased to greater than 80% after 5 weeks of treatment with our nanoplatform. These therapeutic processes could be directly tracked via fluorescence imaging enabled by carbon dots and, therefore, our nanoplatform provides a promising theranostics approach for tumor treatment.
ESTHER : Guo_2021_Biomater.Sci__
PubMedSearch : Guo_2021_Biomater.Sci__
PubMedID: 34223579

Title : Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss - Liu_2021_Front.Cell.Dev.Biol_9_640867
Author(s) : Liu H , Zhou C , Qi D , Gao Y , Zhu M , Tao T , Sun X , Xiao J
Ref : Front Cell Developmental Biology , 9 :640867 , 2021
Abstract : Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) pathways was inhibited by JZL184 and deletion of MAGL. Our in vivo study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
ESTHER : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedSearch : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedID: 33777947

Title : miR-4454 up-regulated by HPV16 E6\/E7 promotes invasion and migration by targeting ABHD2\/NUDT21 in cervical cancer - Wang_2020_Biosci.Rep_40_
Author(s) : Wang H , Hu H , Luo Z , Liu S , Wu W , Zhu M , Wang J , Liu Y , Lu Z
Ref : Bioscience Reports , 40 : , 2020
Abstract : The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.
ESTHER : Wang_2020_Biosci.Rep_40_
PubMedSearch : Wang_2020_Biosci.Rep_40_
PubMedID: 32816024

Title : Donepezil down-regulates propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation in the brain of bilateral common carotid artery occlusion-induced vascular dementia rats - Wang_2020_Clin.Exp.Pharmacol.Physiol__
Author(s) : Wang H , Lu J , Gao WC , Ma X , Li N , Ding Z , Wu C , Zhu M , Qiao G , Xiao C , Zhang C , Chen C , Weng Z , Yang W , Zheng CB
Ref : Clinical & Experimental Pharmacology & Physiology , : , 2020
Abstract : Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris Water Maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Abeta1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Posttranslational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlightes the importance of PTMs in neurodegenerative diseases. In this study, we used Western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.
ESTHER : Wang_2020_Clin.Exp.Pharmacol.Physiol__
PubMedSearch : Wang_2020_Clin.Exp.Pharmacol.Physiol__
PubMedID: 32424975

Title : 14,15-Epoxyeicosatrienoic Acid Alleviates Pathology in a Mouse Model of Alzheimer's Disease - Chen_2020_J.Neurosci_40_8188
Author(s) : Chen W , Wang M , Zhu M , Xiong W , Qin X , Zhu X
Ref : Journal of Neuroscience , 40 :8188 , 2020
Abstract : Alzheimer's disease (AD) is the leading cause of late-onset dementia, and there exists an unmet medical need for effective treatments for AD. The accumulation of neurotoxic amyloid-beta (Abeta) plaques contributes to the pathophysiology of AD. EPHX2 encoding soluble epoxide hydrolase (sEH)-a key enzyme for epoxyeicosatrienoic acid (EET) signaling that is mainly expressed in lysosomes of astrocytes in the adult brain-is cosited at a locus associated with AD, but it is unclear whether and how it contributes to the pathophysiology of AD. In this report, we show that the pharmacologic inhibition of sEH with 1-trifluoromethoxyphenyl- 3-(1-propionylpiperidin-4-yl) urea (TPPU) or the genetic deletion of Ephx2 reduces Abeta deposition in the brains of both male and female familial Alzheimer's disease (5xFAD) model mice. The inhibition of sEH with TPPU or the genetic deletion of Ephx2 alleviated cognitive deficits and prevented astrocyte reactivation in the brains of 6-month-old male 5xFAD mice. 14,15-EET levels in the brains of these mice were also increased by sEH inhibition. In cultured adult astrocytes treated with TPPU or 14,15-EET, astrocyte Abeta clearance was increased through enhanced lysosomal biogenesis. Infusion of 14,15-EET into the hippocampus of 5xFAD mice prevented the aggregation of Abeta. Notably, a higher concentration of 14,15-EET (200 ng/ml) infusion into the hippocampus reversed Abeta deposition in the brains of 6-month-old male 5xFAD mice. These results indicate that EET signaling, especially 14,15-EET, plays a key role in the pathophysiology of AD, and that targeting this pathway is a potential therapeutic strategy for the treatment of AD.SIGNIFICANCE STATEMENT There are limited treatment options for Alzheimer's disease (AD). EPHX2 encoding soluble epoxide hydrolase (sEH) is located at a locus that is linked to late-onset AD, but its contribution to the pathophysiology of AD is unclear. Here, we demonstrate that sEH inhibition or Ephx2 deletion alleviates pathology in familial Alzheimer's disease (5xFAD) mice. Inhibiting sEH or increasing 14,15-epoxyeicosatrienoic acid (EET) enhanced lysosomal biogenesis and amyloid-beta (Abeta) clearance in cultured adult astrocytes. Moreover, the infusion of 14,15-EET into the hippocampus of 5xFAD mice not only prevented the aggregation of Abeta, but also reversed the deposition of Abeta. Thus, 14,15-EET plays a key role in the pathophysiology of AD and therapeutic strategies that target this pathway may be an effective treatment.
ESTHER : Chen_2020_J.Neurosci_40_8188
PubMedSearch : Chen_2020_J.Neurosci_40_8188
PubMedID: 32973044

Title : Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD(+) in axon regeneration - Kim_2018_Elife_7_
Author(s) : Kim KW , Tang NH , Piggott CA , Andrusiak MG , Park S , Zhu M , Kurup N , Cherra SJ, 3rd , Wu Z , Chisholm AD , Jin Y
Ref : Elife , 7 : , 2018
Abstract : The mechanisms underlying axon regeneration in mature neurons are relevant to the understanding of normal nervous system maintenance and for developing therapeutic strategies for injury. Here, we report novel pathways in axon regeneration, identified by extending our previous function-based screen using the C. elegans mechanosensory neuron axotomy model. We identify an unexpected role of the nicotinamide adenine dinucleotide (NAD(+)) synthesizing enzyme, NMAT-2/NMNAT, in axon regeneration. NMAT-2 inhibits axon regrowth via cell-autonomous and non-autonomous mechanisms. NMAT-2 enzymatic activity is required to repress regrowth. Further, we find differential requirements for proteins in membrane contact site, components and regulators of the extracellular matrix, membrane trafficking, microtubule and actin cytoskeleton, the conserved Kelch-domain protein IVNS-1, and the orphan transporter MFSD-6 in axon regrowth. Identification of these new pathways expands our understanding of the molecular basis of axonal injury response and regeneration.
ESTHER : Kim_2018_Elife_7_
PubMedSearch : Kim_2018_Elife_7_
PubMedID: 30461420

Title : Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle - Gao_2017_J.Physiol_595_6231
Author(s) : Gao N , Tsai MH , Chang AN , He W , Chen CP , Zhu M , Kamm KE , Stull JT
Ref : Journal de Physiologie , 595 :6231 , 2017
Abstract : KEY POINTS: Smooth muscle myosin regulatory light chain (RLC) is phosphorylated by Ca(2+) /calmodulin-dependent myosin light chain kinase and dephosphorylated by myosin light chain phosphatase (MLCP). Tracheal smooth muscle contains significant amounts of myosin binding subunit 85 (MBS85), another myosin phosphatase targeting subunit (MYPT) family member, in addition to MLCP regulatory subunit MYPT1. Concentration/temporal responses to carbachol demonstrated similar sensitivities for bovine tracheal force development and phosphorylation of RLC, MYPT1, MBS85 and paxillin. Electrical field stimulation releases ACh from nerves to increase RLC phosphorylation but not MYPT1 or MBS85 phosphorylation. Thus, nerve-mediated muscarinic responses in signalling modules acting on RLC phosphorylation are different from pharmacological responses with bath added agonist. The conditional knockout of MYPT1 or the knock-in mutation T853A in mice had no effect on muscarinic force responses in isolated tracheal tissues. MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction. ABSTRACT: Ca(2+) /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cdelta) subunits. RLC phosphorylation-dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment vs. neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle. Concentration/temporal responses to carbachol demonstrated tight coupling between force development and RLC phosphorylation but sensitivity differences in MLCK, MYPT1 T853, MYPT1 T696, myosin binding subunit 85 (MBS85), paxillin and CPI-17 (PKC-potentiated protein phosphatase 1 inhibitor protein of 17 kDa) phosphorylations. EFS increased force and phosphorylation of RLC, CPI-17 and MLCK. In the presence of the cholinesterase inhibitor neostigmine, EFS led to an additional increase in phosphorylation of MYPT1 T853, MYPT1 T696, MBS85 and paxillin. Thus, there were distinct pharmacological vs. physiological responses in signalling modules acting on RLC phosphorylation and force responses, probably related to degenerate G protein signalling networks. Studies with genetically modified mice were performed. Expression of another MYPT1 family member, MBS85, was enriched in mouse, as well as bovine tracheal smooth muscle. Carbachol concentration/temporal-force responses were similar in trachea from MYPT1(SM+/+) , MYPT1(SM-/-) and the knock-in mutant mice containing nonphosphorylatable MYPT1 T853A with no differences in RLC phosphorylation. Thus, MYPT1 T853 phosphorylation was not necessary for regulation of RLC phosphorylation in tonic airway smooth muscle. Furthermore, MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction.
ESTHER : Gao_2017_J.Physiol_595_6231
PubMedSearch : Gao_2017_J.Physiol_595_6231
PubMedID: 28749013

Title : Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer - Yang_2016_Tumour.Biol_37_1183
Author(s) : Yang Y , Shao Y , Zhu M , Li Q , Yang F , Lu X , Xu C , Xiao B , Sun Y , Guo J
Ref : Tumour Biol , 37 :1183 , 2016
Abstract : Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.
ESTHER : Yang_2016_Tumour.Biol_37_1183
PubMedSearch : Yang_2016_Tumour.Biol_37_1183
PubMedID: 26280398
Gene_locus related to this paper: human-ABHD11

Title : Role of Rho kinase isoforms in murine allergic airway responses - Zhu_2011_Eur.Respir.J_38_841
Author(s) : Zhu M , Liu PY , Kasahara DI , Williams AS , Verbout NG , Halayko AJ , Fedulov A , Shoji T , Williams ES , Noma K , Shore SA , Liao JK
Ref : Eur Respir J , 38 :841 , 2011
Abstract : Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses. Wildtype (WT) mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1(+/-) and ROCK2(+/-), respectively) were sensitised and challenged with ovalbumin. ROCK expression and activation were assessed by western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment. Compared with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1(+/-) and ROCK2(+/-) mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1(+/-) and ROCK2(+/-) lungs. Airway responsiveness was comparable in WT, ROCK1(+/-), and ROCK2(+/-) mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1(+/-) or ROCK2(+/-) mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1(+/-) and ROCK2(+/-) versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses.
ESTHER : Zhu_2011_Eur.Respir.J_38_841
PubMedSearch : Zhu_2011_Eur.Respir.J_38_841
PubMedID: 21565918

Title : Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes - Zhang_2010_Neurochem.Int_57_119
Author(s) : Zhang L , Fu F , Zhang X , Zhu M , Wang T , Fan H
Ref : Neurochem Int , 57 :119 , 2010
Abstract : Considerable evidence has been accumulated demonstrating an important role for inflammation in ischemic brain injury and its contribution to greater cerebral damage after ischemia. Blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, demonstrates antiedematous and anti-inflammatory effects. Here we assessed neuroprotective effects of escin with a transient global cerebral ischemia model. Global cerebral ischemia was induced by occluding both common carotid arteries and withdrawing 0.3ml of blood from the tail vein in mice. Treatment with escin was initiated 0.5h after ischemia induction and given once a day for three consecutive days. Then animals were assessed using the Morris water-maze test and step-down passive avoidance test. Acetylcholinesterase (AChE) activity, histological pathology, and expression of inflammatory genes in the hippocampus were determined. The results showed escin significantly improved learning and memory recovery and reduced hippocampal damage in the cerebral ischemic mice. However, donepezil merely improved learning and memory recovery but did not ameliorate hippocampal damage in the cerebral ischemic mice. Furthermore, we found escin significantly downregulated certain inflammatory gene expression and upregulated expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was recently reported as a neuroprotective protein in the brain. Our results indicate that inhibition of inflammation and protection of hippocampal neurons by escin may be a potentially useful therapy for ischemic brain injury.
ESTHER : Zhang_2010_Neurochem.Int_57_119
PubMedSearch : Zhang_2010_Neurochem.Int_57_119
PubMedID: 20466027

Title : Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors - Zhu_2010_Eur.J.Med.Chem_45_4953
Author(s) : Zhu Y , Xia S , Zhu M , Yi W , Cheng J , Song G , Li Z , Lu P
Ref : Eur Journal of Medicinal Chemistry , 45 :4953 , 2010
Abstract : A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC(50)=78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h.
ESTHER : Zhu_2010_Eur.J.Med.Chem_45_4953
PubMedSearch : Zhu_2010_Eur.J.Med.Chem_45_4953
PubMedID: 20800322

Title : Functions of the siderophore esterases IroD and IroE in iron-salmochelin utilization - Zhu_2005_Microbiology_151_2363
Author(s) : Zhu M , Valdebenito M , Winkelmann G , Hantke K
Ref : Microbiology , 151 :2363 , 2005
Abstract : The siderophore salmochelin is produced under iron-poor conditions by Salmonella and many uropathogenic Escherichia coli strains. The production of salmochelin, a C-glucosylated enterobactin, is dependent on the synthesis of enterobactin and the iroBCDEN gene cluster. An E. coli IroD protein with an N-terminal His-tag cleaved cyclic salmochelin S4 to the linear trimer salmochelin S2, the dimer salmochelin S1, and the monomers dihydroxybenzoylserine and C-glucosylated dihydroxybenzoylserine (salmochelin SX, pacifarinic acid). The periplasmic IroE protein was purified as a MalE-IroE fusion protein. This enzyme degraded salmochelin S4 and ferric-salmochelin S4 to salmochelin S2 and ferric-salmochelin S2, respectively. In E. coli, uptake of ferric-salmochelin S4 was dependent on the cleavage by IroE, and independent of the FepBDGC ABC transporter in the cytoplasmic membrane. IroC, which has similarities to ABC-multidrug-resistance proteins, was necessary for the uptake of salmochelin S2 from the periplasm into the cytoplasm. IroE did not function as a classical binding protein since salmochelin S2 was taken up in the absence of a functional IroE protein. IroC mediated the uptake of iron via enterobactin in a fepB mutant. IroE was also necessary in this case for the uptake of ferric-enterobactin, which indicated that only the linear degradation products of enterobactin were taken up via IroC. PfeE, the Pseudomonas aeruginosa IroE homologue, was cloned, and its enzymic activity was shown to be very similar to that of IroE. It is suggested that homologues in other bacteria are also periplasmic IroE-type esterases of siderophores.
ESTHER : Zhu_2005_Microbiology_151_2363
PubMedSearch : Zhu_2005_Microbiology_151_2363
PubMedID: 16000726

Title : Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic - Liu_2004_J.Biol.Chem_279_3787
Author(s) : Liu P , Ying Y , Zhao Y , Mundy DI , Zhu M , Anderson RG
Ref : Journal of Biological Chemistry , 279 :3787 , 2004
Abstract : The principal lipids in animal cell lipid droplets are cholesterol, cholesterol ester, and triglyceride, but the protein composition of this compartment is largely unknown. Here we report on the proteomic analysis of lipid droplets. Using a combination of mass spectrometry and immunoblotting, we identify nearly 40 specifically associated proteins in droplets isolated from Chinese hamster ovary K2 cells grown in normal medium. The proteins fall in to five groups: structural molecules of the droplet-like adipose differentiation-related protein; multiple enzymes involved in the synthesis, storage, utilization, and degradation of cholesterol esters and triglycerides; multiple, different Rab GTPases known to be involved in regulating membrane traffic; signaling molecules such as p50RhoGAP; and a group of proteins that do not fit any classification but include proteins often found in caveolae/rafts such as caveolin-1 and 2 and flotillin-1. The proteome of droplets isolated from cells grown in the presence of oleate is largely the same except for an increase in the amount of adipose differentiation-related protein, caveolin-1, and a protein thought to be involved in phospholipid recycling called CGI-58. Based on the protein profile, the lipid droplet appears to be a complex, metabolically active organelle that is directly involved in membrane traffic and possibly phospholipid recycling. We propose the name adiposome for this organelle.
ESTHER : Liu_2004_J.Biol.Chem_279_3787
PubMedSearch : Liu_2004_J.Biol.Chem_279_3787
PubMedID: 14597625