Article
Chemistry, Applied
Chen Jiang, Yingxue Li, Lingjuan Yan, Aiying Ye, Qiong He, Cheng Yao
Summary: The C3H probe can quickly respond to HOCl, with high sensitivity and low detection limit, as well as high selectivity and anti-interference properties. It can also monitor both exogenous and endogenous HOCl in mitochondria effectively. Additionally, in vivo imaging experiments on nude mice demonstrate the probe's ability to detect exogenous ClO-.
Article
Cell Biology
Zhou-rui Ma, Hong-Peng Li, Shi-zhong Cai, Sheng-Yang Du, Xia Chen, Jin Yao, Xu Cao, Yun-Fang Zhen, Qian Wang
Summary: The protein TIMM44 is essential for the integrity and function of mitochondria in endothelial cells, which play a crucial role in angiogenesis. Silencing or blocking TIMM44 disrupted mitochondrial functions and inhibited angiogenic activity in vitro and in vivo, while overexpression of TIMM44 enhanced angiogenesis. Therefore, TIMM44 could be a potential therapeutic target for diseases involving abnormal angiogenesis.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Amparo Olivares, Miguel Alcaraz-Saura, Daniel Gyingiri Achel, Juan de Dios Berna-Mestre, Miguel Alcaraz
Summary: The research investigated the modulation effect of rosmarinic acid on radiation-induced effects and found that it could reduce micronuclei frequency and increase cell survival rate, showing a certain radioprotective capacity.
Article
Pharmacology & Pharmacy
Kunfeng Zhang, Jingxin Fu, Xiaorui Liu, Yifei Guo, Meihua Han, Meifeng Liu, Xiangtao Wang
Summary: Mitochondria are involved in cancer cell diffusion and metastasis. The study developed a mitochondrial targeting anticancer medicine by conjugating hydroxycamptothecin (HCPT) with a mitochondrial targeting ligand 4-(carboxybutyl) triphenylphosphine bromide (TPP). The resulting conjugate self-assembled into nano-aggregates and could also co-assemble with mPEG(3000)-PLGA(5000) into nanoparticles. The nano-formulations showed enhanced cellular uptake, mitochondria-targetability and cytotoxicity against cancer cells, and displayed superior anti-tumor effects in vivo.
Article
Multidisciplinary Sciences
Ugne Zekonyte, Sandra R. Bacman, Jeff Smith, Wendy Shoop, Claudia Pereira, Ginger Tomberlin, James Stewart, Derek Jantz, Carlos T. Moraes
Summary: This study shows the potential of using mitoARCUS, a mitochondrial-targeted gene editing platform, to specifically eliminate mutant mtDNA with a m.5024C>T mutation in the mt-tRNA(Ala) gene. MitoARCUS was successful in robustly eliminating mutant mtDNA in the liver and skeletal muscle of mice, demonstrating its promise as a powerful tool for the treatment of heteroplasmic mitochondrial DNA mutations.
NATURE COMMUNICATIONS
(2021)
Review
Biology
Anis Javadi, Mohammad Reza Nikhbakht, Javad Ghasemian Yadegari, Auob Rustamzadeh, Mohsen Mohammadi, Alireza Shirazinejad, Saleh Azadbakht, Zahra Abdi
Summary: The study focuses on the radioactive role of natural and chemical substances on human and animal subjects. It is found that radiation exposure can lead to the production of reactive oxygen species (ROS), causing damage to DNA and body tissues when the body's antioxidant systems are insufficient to neutralize free radicals. Therefore, the use of alternative substances to reduce and inhibit free radicals is necessary.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qinqin Tian, Xianlin Lu, Wei He
Summary: SO2 and its derivatives play a crucial role in antioxidation and anticorrosion of food and medicine. Abnormal levels of SO2 can lead to various biological diseases, making it necessary to develop suitable tools for monitoring SO2 in mitochondria. This research introduces DHX-1 and DHX-2 as fluorescent probes that exhibit near-infrared fluorescence response towards endogenous and exogenous SO2, showing high selectivity, sensitivity, and low cytotoxicity. DHX-1 and DHX-2 successfully detected SO2 in HeLa cells, zebrafish, and even mice.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Gyeongmin Lee, Hyo Rin Kang, Aro Kim, Jong-Hyeon Park, Min Ja Lee, Su-Mi Kim
Summary: This study investigated the antiviral effects of GS-9620 against foot-and-mouth disease virus (FMDV). It was found that GS-9620 inhibited the virus in swine cells and induced the production of interferons and cytokines, providing early protection. Furthermore, the combination of GS-9620 with an inactivated vaccine was highly effective.
ANTIVIRAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Jiashu Xie, Zhengqiang Wang
Summary: The study examined the potential of Remdesivir and its parent nucleoside GS-441524 as oral drugs for treating COVID-19. Results showed that Remdesivir had poor stability in vitro, while GS-441524 exhibited better metabolic stability and oral bioavailability, indicating its potential as a promising oral antiviral drug for COVID-19 treatment.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Nga-Lai Sou, Yu-Hsuan Huang, Der-Yuan Chen, Yi-Ming Chen, Feng-Yao Tang, Hsin-An Ko, Yi-Hsuan Fan, Yi-Ying Lin, Yi-Cheng Wang, Hui-Ming Chih, Barry Shane, Wen-Nan Huang, En-Pei Isabel Chiang
Summary: MTX specifically depletes mitochondrial 1C supply, which can be ameliorated by folinate supplementation in certain pathways but not in hepatic transmethylation. It is important to carefully address the systematic and tissue-specific formate depletion induced by MTX.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ji Min Lee, Jung Wook Hwang, Mi Jin Kim, Sang Youn Jung, Kyung-Soo Kim, Eun Hee Ahn, Kyunghoon Min, Yong-Soo Choi
Summary: The study investigated the therapeutic effects of mitochondrial transplantation in a tendinopathy model by restoring damaged tenocytes and modulating inflammatory responses. Results indicated that mitochondrial transplantation could reduce oxidative stress, restore mitochondrial membrane potential, and downregulate fission markers in damaged tendon cells. Furthermore, the treatment showed promising results in reducing inflammation and promoting collagen production in a rat model of tendinopathy.
Article
Engineering, Biomedical
You Jung Kang, Claire K. Holley, Mohammad Reza Abidian, Achuthamangalam B. Madhankumar, James Connor, Sheereen Majd
Summary: The study developed a novel drug carrier for glioma tumors and demonstrated its significant therapeutic effects in vitro and in vivo. IL13-conjugated Dp44mT-NPs showed excellent toxicity towards glioma cells, with minimal impact on healthy brain microvascular endothelial cells.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Quan Tao, Di Zhang, Qianqian Zhang, Chuang Liu, Sheng Ye, Yanqiu Feng, Ruiyuan Liu
Summary: This study developed a mitochondrial-targeted nitroxide, TPP-PROXYL, to scavenge reactive oxygen species (ROS) and visualize oxidative stress reactions using MRI. Experimental results confirmed that TPP-PROXYL could target mitochondria, reduce ROS levels, and protect mitochondria from damage in live cells. In vivo experiments demonstrated that TPP-PROXYL could improve the survival rate of mice and inhibit kidney damage during AKI treatment. MR imaging technology further verified the ROS scavenging capabilities and renal damage reduction of TPP-PROXYL. Overall, this research highlights the potential of TPP-PROXYL as a powerful platform for ROS scavenging, treatment, and MR imaging of AKI.
FREE RADICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Anastasiia S. Obozina, Elena N. Komedchikova, Olga A. Kolesnikova, Anna M. Iureva, Vera L. Kovalenko, Fedor A. Zavalko, Tatiana V. Rozhnikova, Ekaterina D. Tereshina, Elizaveta N. Mochalova, Victoria O. Shipunova
Summary: Targeted nanoparticles from various origins have potential as diagnostic and therapeutic tools, but currently no FDA-approved targeted drug formulations exist due to effectiveness and production challenges. Self-assembling protein nanoparticles offer a solution by encoding proteins in DNA and allowing for standardized production. This review focuses on targeted self-assembling protein nanoparticles based on various proteins, discussing their applications in targeted delivery and providing a critical assessment of their efficacy in biomedicine.
Article
Pharmacology & Pharmacy
Sanjay Arora, Jagdish Singh
Summary: The research demonstrated a brain-targeted nanoparticle delivery system for vgf gene, showing significant transfection in the mouse brain for the treatment of Alzheimer's disease. This method utilized surface functionalization and lipid conjugation for efficient brain-targeted transfection, with promising results in vivo.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pediatrics
Chhinder P. Sodhi, Peter Wipf, Yukihiro Yamaguchi, William B. Fulton, Mark Kovler, Diego F. Nino, Qinjie Zhou, Emilyn Banfield, Adam D. Werts, Mitchell R. Ladd, Rachael H. Buck, Karen C. Goehring, Thomas Prindle, Sanxia Wang, Hongpeng Jia, Peng Lu, David J. Hackam
Summary: The study showed that human milk oligosaccharides 2'-FL and 6'-SL can prevent NEC through inhibition of TLR4 signaling, while lactose cannot. The results indicate that these HMOs reduced NEC occurrence in mouse and piglet models.
PEDIATRIC RESEARCH
(2021)
Article
Endocrinology & Metabolism
Nicolas Manzke Glanzel, Mateus Grings, Nevton Teixeira da Rosa-Junior, Leila Maria Cereta de Carvalho, Al-Walid Mohsen, Peter Wipf, Moacir Wajner, Jerry Vockley, Guilhian Leipnitz
Summary: Sulfite oxidase (SO) deficiency causes tissue sulfite accumulation and patients present with seizures and neurological damage. Treatment is mainly supportive. Study shows that treatment with JP4-039 can prevent or attenuate oxidative stress and apoptosis induced by sulfite injection.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Chemistry, Medicinal
Soledad Natalia Gonzalez, Jonathan J. Mills, Dante Maugeri, Christopher Olaya, Breana L. Laguera, Jeffrey R. Enders, Julian Sherman, Ana Rodriguez, Joshua G. Pierce, Juan Jose Cazzulo, Edward L. D'Antonio
Summary: The study discovered a competitive inhibitor Compound B targeting ribose 5-phosphate isomerase type B (RPI-B), which exhibited significant trypanocidal activity against T. cruzi infective life-stages. By targeting the active site residue Cys-69, this inhibitor provided a proof-of-concept for the development of next generation inhibitors with potential prodrug groups to treat Chagas' disease in the future.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Organic
Ettore J. Rastelli, Doris Yue, Caroline Millard, Peter Wipf
Summary: The polypropylene continuous-photoflow cell developed through 3D printing is cost-effective and suitable for photo-oxygenation reactions using ambient air as the sole co-reactant. It offers the benefits of scalability and a short residence time under blue LED light, which minimizes the formation of dark, insoluble decomposition products.
Article
Biochemistry & Molecular Biology
Yasaman Hamedani, Rayane Brinck Teixeira, Catherine Karbasiafshar, Peter Wipf, Sankha Bhowmick, M. Ruhul Abid
Summary: The study demonstrates that electrospinning methods can be utilized to load mitochondria-targeted antioxidants onto biocompatible nanofibrous scaffolds, preserving their antioxidant properties upon release and improving cell function.
Review
Chemistry, Multidisciplinary
M. Alejandro Valdes-Pena, Nicholas P. Massaro, You-Chen Lin, Joshua G. Pierce
Summary: Antimicrobial resistance poses a significant threat to human health and requires urgent action. Natural products present a valuable source for identifying antibiotics with the potential to combat resistance. Research efforts focused on marine natural products with activity against multidrug-resistant pathogens offer promising new therapeutic options.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Nicholas P. Massaro, Joshua G. Pierce
Summary: A rapid synthesis approach has been developed for the core structures of crinane and haemanthamine using a multicomponent method. The modularity of core synthesis in this work overcomes existing challenges and provides a pathway for exploring site-selective oxidation to expand the range of accessible molecules.
TETRAHEDRON LETTERS
(2021)
Article
Biochemistry & Molecular Biology
John S. Lazo, Elizabeth R. Sharlow, Robert Cornelison, Duncan J. Hart, Danielle C. Llaneza, Anna J. Mendelson, Ettore J. Rastelli, Nikhil R. Tasker, Charles N. Landen, Peter Wipf
Summary: High grade serous ovarian cancer often becomes drug resistant and recurrent. A study showed that high expression of Protein Tyrosine Phosphatase of Regenerating Liver-3 (PRL3) is associated with poor patient survival in both early and late stages of ovarian cancer. A potent allosteric small molecule PTP4A3 inhibitor, JMS-053, was found to reduce high grade serous ovarian cancer cell survival. Results also showed that controlling PTP4A3 can affect cell migration and the inhibitor JMS-053 can lead to reduced cell migration.
Article
Engineering, Biomedical
C. T. Moody, A. E. Brown, N. P. Massaro, A. S. Patel, P. A. Agarwalla, A. M. Simpson, A. C. Brown, H. Zheng, J. G. Pierce, Y. Brudno
Summary: Alginate hydrogels are widely used in drug delivery, regenerative medicine, and tissue engineering due to their biocompatibility and chemical versatility. This study proposes a modification method that restores carboxyl groups in alginate, which can improve the gelation, mechanics, tissue retention, and drug-capturing capabilities of the hydrogels.
ACTA BIOMATERIALIA
(2022)
Article
Chemistry, Organic
Zhanhao Liang, You-Chen Lin, Joshua G. Pierce
Summary: Ansalactam A is a natural product with a unique structure that presents a significant synthetic challenge. Researchers have reported a synthetic method for constructing its key structure for the first time, enabling access to Ansalactam A.
Article
Biochemistry & Molecular Biology
Keishla M. Rodriguez-Graciani, Xavier R. Chapa-Dubocq, Esteban J. Ayala-Arroyo, Ivana Chaves-Negron, Sehwan Jang, Nataliya Chorna, Taber S. Maskrey, Peter Wipf, Sabzali Javadov
Summary: In this study, the metabolome of H9c2 cardioblasts during RSL3-induced ferroptosis was elucidated using gas chromatography-mass spectrometry. The results showed that RSL3 decreased the levels of amino acids involved in glutathione synthesis and increased the levels of saturated fatty acids. RSL3 also significantly altered the levels of mitochondrial tricarboxylic acid cycle intermediates. Furthermore, ferrostatin-1, XJB-5-131, and TSM-1005-44 protected against RSL3-induced cell death and preserved the metabolomic profile of the cells.
Article
Chemistry, Multidisciplinary
Sharda Pandit, Sandeep Palvai, Nicholas P. Massaro, Joshua G. Pierce, Yevgeny Brudno
Summary: The method of creating materials-free intratumoral drug depots through Tissue-Reactive Anchoring Pharmaceuticals (TRAPs) has the potential to achieve sustained drug delivery in desmoplastic tumor tissues, providing a promising approach for the treatment of localized diseases.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Joshua G. Pierce, Xiang Qiu
Summary: In this study, a stereoselective 15-step synthesis of Bipolamine I was reported, which can serve as a method to access other polypyrrole natural products and key analogues. This research is of great significance for the study of semi-synthetic indolizidine alkaloids.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Editorial Material
Multidisciplinary Sciences
Nicholas P. R. Onuska, Joshua G. Pierce
Article
Biochemistry & Molecular Biology
Merlin Airik, Haley Arbore, Elizabeth Childs, Amy B. Huynh, Yu Leng Phua, Chi Wei Chen, Katherine Aird, Sivakama Bharathi, Bob Zhang, Peter Conlon, Stanislav Kmoch, Kendrah Kidd, Anthony J. Bleyer, Jerry Vockley, Eric Goetzman, Peter Wipf, Rannar Airik
Summary: Karyomegalic interstitial nephritis (KIN) is a genetic kidney disease caused by recessive mutations in the FAN1 DNA repair enzyme. The disease is characterized by genomic instability and mitotic abnormalities in tubular epithelial cells. Hypersensitivity to endogenous reactive oxygen species (ROS) is identified as a key factor in the pathogenesis of KIN, leading to chronic oxidative and double-strand DNA damage.
