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6. rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels

Author

Kandel, Munal B., primary, Zhuang, Gerald Z., additional, Goins, William F., additional, Marzulli, Marco, additional, Zhang, Mingdi, additional, Glorioso, Joseph C., additional, Kang, Yuan, additional, Levitt, Alexandra E., additional, Kwok, Wai-Meng, additional, Levitt, Roy C., additional, and Sarantopoulos, Konstantinos D., additional

Published
2024
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8. Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.

Author

Zhuang, Gerald Z., Goins, William F., Kandel, Munal B., Marzulli, Marco, Zhang, Mingdi, Glorioso, Joseph C., Yuan Kang, Levitt, Alexandra E., Sarantopoulos, Konstantinos D., and Levitt, Roy C.

Abstract

Chronic pain is common in our population, and most of these patients are inadequately treated, making the development of safer analgesics a high priority. Knee osteoarthritis (OA) is a primary cause of chronic pain and disability worldwide, and lower extremity OA is a major contributor to loss of qualityadjusted life-years. In this study we tested the hypothesis that a novel JDNI8 replication-defective herpes simplex-1 viral vector (rdHSV) incorporating a modified carbonic anhydrase-8 transgene (CA8*) produces analgesia and treats monoiodoacetate-induced (MIA) chronic knee pain due to OA. We observed transduction of lumbar DRG sensory neurons with these viral constructs (vHCA8*) (~40% of advillin-positive cells and ~ 50% of TrkA-positive cells colocalized with V5-positive cells) using the intra-articular (IA) knee joint (KJ) route of administration. vHCA8* inhibited chronic mechanical OA knee pain induced by MIA was dose- and time-dependent. Mechanical thresholds returned to Baseline by D17 after IA KJ vHCA8* treatment, and exceeded Baseline (analgesia) through D65, whereas negative controls failed to reach Baseline responses. Weightbearing and automated voluntary wheel running were improved by vHCA8*, but not negative controls. Kv7 voltage-gated potassium channel-specific inhibitor XE-991 reversed vHCA8*-induced analgesia. Using IHC, IA KJ of vHCA8* activated DRG Kv7 channels via dephosphorylation, but negative controls failed to impact Kv7 channels. XE-991 stimulated Kv7.2-7.5 and Kv7.3 phosphorylation using western blotting of differentiated SH-SY5Y cells, which was inhibited by vHCA8* but not by negative controls. The observed prolonged dose-dependent therapeutic effects of IA KJ administration of vHCA8* on MIA-induced chronic KJ pain due to OA is consistent with the specific activation of Kv7 channels in small DRG sensory neurons. Together, these data demonstrate for the first-time local IA KJ administration of vHCA8* produces opioid-independent analgesia in this MIA-induced OA chronic pain model, supporting further therapeutic development. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Influence of the Parallel C-Layer Secondary Air on Flow, Combustion and Nox Generation Characteristics of a 600mwe FW Down-Fired Boiler Retrofitted with a Stable Combustion Organization Mode

Author

Du, He, Li, Zhengqi, Liu, Zheng, Zhang, Mingdi, Chen, Zhichao, Song, Jian, Fang, Fan, and Xiao, Ronghua

Subjects
Fuel Technology, General Chemical Engineering, General Physics and Astronomy, Energy Engineering and Power Technology, General Chemistry
Abstract

To improve the low-load stable combustion capacity of a low-grade coal-fired boiler, this study proposed to reform C-layer secondary air, which was then used to improve the ignition and combustion stability of coal/airflow of a 600 MWe Foster Wheeler down-fired boiler. Cold airflow experiments and industrial measurements were carried out to investigate the influence of the new C-layer secondary air on the aerodynamic and combustion characteristics at low load under different C-layer secondary air ratios and damper openings, respectively. The flow and mixing characteristics of the C-layer secondary air and coal/airflow, the flue gas temperature and NOx, O2, and CO concentration distributions in the furnace at low load were examined. With increase in the C-layer secondary air ratio, the flow range of coal/airflow gradually expanded. The mixing distance first increased and then decreased. At an air ratio of 25%, the mixing distance was the longest. Industrial measurements showed that compared with that at the C-layer secondary air damper opening of 0%, the coal/airflow ignited earlier at 40% (corresponding to the C-layer secondary air ratio of 23.73%), and the flue gas temperature in the furnace increased substantially. At C-layer secondary air damper opening of 0%, 20%, and 40%, carbon content in the fly ash was 4.62%, 5.32%, and 4.20%, respectively. The respective NOx emissions at the furnace exits were 450 mg/Nm3, 378 mg/Nm3, and 427 mg/Nm3, (O2 = 6%). In actual operation, 40% is recommended as the optimal C-layer secondary air damper opening.

Published
2022

15. Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models

Author

McCampbell, Alex, Cole, Tracy, Wegener, Amy J., Tomassy, Giulio S., Setnicka, Amy, Farley, Brandon J., Schoch, Kathleen M., Hoye, Mariah L., Shabsovich, Mark, Sun, Linhong, Luo, Yi, Zhang, Mingdi, Thankamony, Sai, Salzman, David W., Cudkowicz, Merit, Graham, Danielle L., Bennett, C. Frank, Kordasiewicz, Holly B., Swayze, Eric E., and Miller, Timothy M.

Subjects
Antisense drugs -- Research -- Health aspects -- Dosage and administration, Amyotrophic lateral sclerosis -- Genetic aspects -- Research -- Care and treatment, Gene mutation -- Research, Health care industry
Abstract

Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% of familial ALS. Given the gain of toxic function in this dominantly inherited disease, lowering SOD1 mRNA and protein is predicted to provide therapeutic benefit. An early generation antisense oligonucleotide (ASO) targeting SOD1 was identified and tested in a phase I human clinical trial, based on modest protection in animal models of SOD1 ALS. Although the clinical trial provided encouraging safety data, the drug was not advanced because there was progress in designing other, more potent ASOs for CNS application. We have developed next- generation SOD1 ASOs that more potently reduce SOD1 mRNA and protein and extend survival by more than 50 days in [SOD1.sup.G93A] rats and by almost 40 days in [SOD1.sup.G93A] mice. We demonstrated that the initial loss of compound muscle action potential in [SOD1.sup.G93A] mice is reversed after a single dose of SOD1 ASO. Furthermore, increases in serum phospho-neurofilament heavy chain levels, a promising biomarker for ALS, are stopped by SOD1 ASO therapy. These results define a highly potent, new SOD1 ASO ready for human clinical trial and suggest that at least some components of muscle response can be reversed by therapy., Introduction Amyotrophic lateral sclerosis (ALS) is caused by the loss and dysfunction of neurons in motor pathways and leads to severe weakness, stiffness, and ultimately death in 3-5 years. Approximately [...]

Published
2018
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19. Changes in the Density and Composition of Rhizosphere Pathogenic Fusarium and Beneficial Trichoderma Contributing to Reduced Root Rot of Intercropped Soybean

Author

Xu, Huiting, primary, Yan, Li, additional, Zhang, Mingdi, additional, Chang, Xiaoli, additional, Zhu, Dan, additional, Wei, Dengqin, additional, Naeem, Muhammd, additional, Song, Chun, additional, Wu, Xiaoling, additional, Liu, Taiguo, additional, Chen, Wanquan, additional, and Yang, Wenyu, additional

Published
2022
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24. Varicella-zoster virus early infection but not complete replication is required for the induction of chronic hypersensitivity in rat models of postherpetic neuralgia

Author

Warner, Benjamin E., primary, Yee, Michael B., additional, Zhang, Mingdi, additional, Hornung, Rebecca S., additional, Kaufer, Benedikt B., additional, Visalli, Robert J., additional, Kramer, Phillip R., additional, Goins, William F., additional, and Kinchington, Paul R., additional

Published
2021
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26. HOTAIR Facilitates Endocrine Resistance in Breast Cancer Through ESR1/miR-130b-3p Axis: Comprehensive Analysis of mRNA-miRNA-lncRNA Network

Author

Zhang,Mingdi, Wu,Kejin, Zhang,Peng, Qiu,Yiran, Bai,Fang, Chen,Hongliang, Zhang,Mingdi, Wu,Kejin, Zhang,Peng, Qiu,Yiran, Bai,Fang, and Chen,Hongliang

Abstract

Mingdi Zhang, Kejin Wu, Peng Zhang, Yiran Qiu, Fang Bai, Hongliang Chen Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongliang ChenDepartment of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, People’s Republic of ChinaTel/Fax +86-21-33189900Email 13671852284@163.comBackground: To summarize the regulatory role of mRNA-miRNA-lncRNA network associated with endocrine therapy resistance (ETR) in breast cancer.Methods: We analyzed the differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) in long-term estrogen-deprived (LTED) estrogen receptor (ER)-positive breast cancer cells (LTED MCF7) (modeling relapse on endocrine therapy) and MCF7 cells in the presence of estrogen (E2) (modeling a patient at primary diagnosis) by mining GSE120929 and GSE120930 datasets. The mRNA-miRNA-lncRNA network was constructed by multiple bioinformatic tools. The prognosis of genes from the network was validated in breast cancer patients with following systemic treatment (endocrine therapy) by GEPIA, Kaplan–Meier plotter and UALCAN database.Results: Totally, 769 DEGs, 33 DEMs, and 10 DELs were selected. The mRNA-miRNA-lncRNA network was established including 60 mRNA nodes, 6 miRNA nodes and 3 lncRNA nodes. A significant module containing 3 nodes and 3 edges was calculated based on the mRNA-miRNA-lncRNA network. The hub genes in the network are ABCG2, ESR1 and GJA1. ESR1/miR-130b-3p/HOTAIR are significantly correlated with the prognosis of breast cancer patients with endocrine therapy.Conclusion: This study provides a novel ETR-related mRNA-miRNA-lncRNA network. Further, we suggest that ESR1/miR-130b-3p/HOTAIR may be promising targets for clinical treatment of endocrine therapy-resistant breast cancer.Keywords: endocrine therapy resistance, breast cancer, bioinformatic an

Published
2021

32. GBM-Targeted oHSV Armed with Matrix Metalloproteinase 9 Enhances Anti-tumor Activity and Animal Survival

Author

Sette, Paola, primary, Amankulor, Nduka, additional, Li, Aofei, additional, Marzulli, Marco, additional, Leronni, Daniela, additional, Zhang, Mingdi, additional, Goins, William F., additional, Kaur, Balveen, additional, Bolyard, Chelsea, additional, Cripe, Timothy P., additional, Yu, Jianhua, additional, Chiocca, E. Antonio, additional, Glorioso, Joseph C., additional, and Grandi, Paola, additional

Published
2019
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34. Development of Structure-Switching Aptamers for Kanamycin Detection Based on Fluorescence Resonance Energy Transfer

Author

Ruifang Su, Hongjing Sun, Xinyue Ma, Zhang Mingdi, Chunyan Sun, and Shangna Qiao

Subjects
kanamycin, Fluorophore, Aptamer, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Helix structure, lcsh:Chemistry, chemistry.chemical_compound, medicine, structure-switching, Original Research, Detection limit, Chemistry, aptamer, Kanamycin, General Chemistry, 021001 nanoscience & nanotechnology, Combinatorial chemistry, Fluorescence, 0104 chemical sciences, Förster resonance energy transfer, Linear range, lcsh:QD1-999, FRET, fluorescence, 0210 nano-technology, medicine.drug
Abstract

The structure-switching aptamers are designed for the simple and rapid detection of kanamycin based on the signal transduction principle of fluorescence resonance energy transfer (FRET). The structure switch is composed of kanamycin-binding aptamers and the complementary strands, respectively labeled with fluorophore and quencher, denoted as FDNA and QDNA. In the absence of kanamycin, FDNA and QDNA form the double helix structure through the complementary pairing of bases. The fluorophore and the quencher are brought into close proximity, which results in the fluorescence quenching because of the FRET mechanism. In the presence of kanamycin, the FDNA specifically bind to the target due to the high affinity of aptamers, and the QDNA are dissociated. The specific recognition between aptamers and kanamycin will obstruct the formation of structure switch and reduce the efficiency of FRET between FDNA and QDNA, thus leading to the fluorescence enhancement. Therefore, based on the structure-switching aptamers, a simple fluorescent assay for rapid detection of kanamycin was developed. Under optimal conditions, there was a good linear relationship between kanamycin concentration and the fluorescence signal recovery. The linear range of this method in milk samples was 100-600 nM with the detection limit of 13.52 nM (3σ), which is well below the maximum residue limit (MRL) of kanamycin in milk. This method shows excellent selectivity for kanamycin over the other common antibiotics. The structure-switching aptamers have been successfully applied to the detection of kanamycin spiked in milk samples with the satisfying recoveries between 101.3 and 109.1%, which is well-consistent with the results from LC-MS/MS. Due to the outstanding advantages of facile operation, rapid detection, high sensitivity, excellent specificity, and low cost, the application and extension of this strategy for rapid determination of antibiotics in food samples may greatly improve the efficiency in food safety and quality supervision.

Published
2019

48. Targeting gallbladder cancer: hyaluronan sensitizes cancer cells to chemo-therapeutics

Author

Ma, Mingzhe, Weng, Mingzhe, Zhang, Mingdi, Qin, Yiyu, Gong, Wei, and Quan, Zhiwei

Subjects
Time Factors, Dose-Response Relationship, Drug, Paclitaxel, Cell Survival, Mice, Nude, Antineoplastic Agents, Xenograft Model Antitumor Assays, Tumor Burden, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, Animals, Humans, Original Article, Female, Gallbladder Neoplasms, Hyaluronic Acid
Abstract

Gallbladder cancer is the most common biliary tract malignancy and the fifth most common gastrointestinal malignancy. Chemo-resistance is the most remarkable characteristic of gallbladder cancer. The relatively dense extracellular space in tumor is the main barrier to nanotherapeutics' anticancer efficacy. Hyaluronan (HA) was shown in our previous study to significantly improve the myxoma virus distribution via promoting the MMP-9 production, which degrades collagen IV. We demonstrated that HA increased the chemo-sensitivity of gallbladder cancer cells both in vitro and in vivo. The in vivo chemo-sensitization effect of HA could partially be due to the penetration-promoting effect of HA via degrading collagen IV.

Published
2015

49. The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer

Author

Zhang, Mingdi, primary, Gong, Wei, additional, Zuo, Bin, additional, Chu, Bingfeng, additional, Tang, Zhaohui, additional, Zhang, Yong, additional, Yang, Yong, additional, Zhou, Di, additional, Weng, Mingzhe, additional, Qin, Yiyu, additional, Ma, Mingzhe, additional, Jiang, Alex, additional, Ma, Fei, additional, and Quan, Zhiwei, additional

Published
2016
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