Article
Biochemistry & Molecular Biology
Hiromitsu Kunimi, Deokho Lee, Mari Ibuki, Yusaku Katada, Kazuno Negishi, Kazuo Tsubota, Toshihide Kurihara
Summary: In this study, using retina-specific Hif-1 alpha conditional knockout (cKO) mice revealed that the reduction of Hif-1 alpha can lead to a decrease in inner retinal neurodegeneration. Experiments showed that depletion of Bnip3 in retinal neurons can have neuroprotective effects, supporting the critical role of the HIF-1 alpha/BNIP3 pathway in inner retinal neurodegeneration.
Article
Biochemistry & Molecular Biology
Wenguang He, Sarah Batty-Stuart, Jeffrey E. Lee, Michael Ohh
Summary: The study demonstrates that both hydroxyprolines in HIF-1 alpha ODD bind to the same interface on VHL with similar affinity; VHL binding affinity to ODD remains relatively unchanged whether one or two hydroxyprolines are present; ODD with two hydroxyprolines can accommodate two VHLs, and the ubiquitination rate is comparable between ODD with one or two hydroxyprolines. However, the two hydroxyprolines show distinct contributions to the intracellular stability of HIF-1 alpha ODD.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Zhihao Zhao, Jun Yan, Ke Ling, Rui Shi, Rui Lv, Baoqing Nie, Jian Liu
Summary: This study introduces a new strategy of building a ROS FET to address the challenge of tumor hypoxia, achieving effective tumor ablation both in vitro and in vivo. The mechanism of changing tumor hypoxia is revealed, creating a conceptually novel method for maximizing ROS damages for cancer treatment.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Integrative & Complementary Medicine
Kui-Yuan Peng, Tz-Chong Chou
Summary: Osthole exhibits inhibitory effects on hypoxic colon cancer cells by activating the UPR signaling pathway and inducing apoptosis.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2022)
Article
Environmental Sciences
Ke Xu, Chao Lu, Xiaoyu Ren, Jing Wang, Peng Xu, Yingang Zhang
Summary: The study revealed that in a hypoxic environment, mitophagy-related proteins HIF-1α and BNIP3 were up-regulated, resisting DEX-induced apoptosis and offering a new direction for the treatment of GIOFH.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shengyu Hao, Fan Li, Pan Jiang, Jian Gao
Summary: This study found that CIH-induced HIF-1 alpha expression may activate ATAD2, which may play a role in lung cancer aggressiveness through mtROS and stemness in lung cancer cells.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Multidisciplinary Sciences
Angela Bononi, Qian Wang, Alicia A. Zolondick, Fang Bai, Mika Steele-Tanji, Joelle S. Suarez, Sandra Pastorino, Abigail Sipes, Valentina Signorato, Angelica Ferro, Flavia Novelli, Jin-Hee Kim, Michael Minaai, Yasutaka Takinishi, Laura Pellegrini, Andrea Napolitano, Ronghui Xu, Christine Farrar, Chandra Goparaju, Cristian Bassi, Massimo Negrini, Ian Pagano, Greg Sakamoto, Giovanni Gaudino, Harvey I. Pass, Jose N. Onuchic, Haining Yang, Michele Carbone
Summary: This study investigates the paradoxical finding that individuals with germline BAP1 mutations develop less aggressive mesotheliomas. The research shows that biallelic BAP1 mutations result in a reduction of HIF-1 alpha activity in mesothelioma cells and hypoxic tissues, leading to reduced aggressiveness and improved survival in these patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Dentistry, Oral Surgery & Medicine
Xiao-Hong Guo, Ming-Yu Wu, Gang Zhao, Feng-Hua Wu, Yun-Dan Xu, Ming-Zhu Yin, Lei Xiang
Summary: Adiponectin (APN) expression is upregulated in tongue squamous cell carcinoma (TSCC) tissues, and APN resistance occurs under hypoxia. HIF-1 alpha is identified as the transcription factor of APN, and recombinant globular APN (gAPN) application leads to a regenerative feedback of HIF-1 alpha, contributing to APN resistance. Combined treatment of HIF-1 alpha blockade and gAPN shows a synergistic antitumor effect in TSCC.
Article
Multidisciplinary Sciences
Fang Zheng, Jianing Chen, Xiaoqian Zhang, Zifeng Wang, Jiewen Chen, Xiaorong Lin, Hongyan Huang, Wenkui Fu, Jing Liang, Wei Wu, Bo Li, Herui Yao, Hai Hu, Erwei Song
Summary: The study demonstrates a crucial positive feed-forward loop between HIFAL, the HIF1alpha antisense long non-coding RNA, and HIF1alpha, which is essential for metabolic reprogramming and tumourigenesis mediated by HIF1alpha.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Sichao Guo, Eric Cosky, Fengwu Li, Longfei Guan, Yu Ji, Wenjing Wei, Changya Peng, Xiaokun Geng, Yuchuan Ding
Summary: C + P, partially depending on hypothermia, attenuates hyperglycolysis and NOX activation through HIF-1? regulation.
Article
Engineering, Environmental
Lu Ding, Yanyu Zhao, Huihui Li, Qiujuan Zhang, Weiting Yang, Bo Fu, Qinhe Pan
Summary: Fluorescent probes with in-situ visual feature have gained attention for detecting doxycycline (DC), a widely used tetracycline antibiotic in animal husbandry. Bovine serum albumin-capped gold nanoclusters (BSA-AuNCs) were used as a ratiometric fluorescent probe to selectively detect DC among tetracycline antibiotics. BSA-AuNCs showed the highest response toward DC, with simple synthesis, short response time (1 min), and low detection limit. This work proposes an efficient strategy for designing fluorescent probes to selectively detect DC among tetracycline antibiotics.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Medicine, Research & Experimental
Tingting Dai, Lingchang Li, Wei Qi, Bojia Liu, Ziyu Jiang, Jie Song, Haiqing Hua
Summary: Balano-phorin B inhibits the proliferation and growth of liver cancer cells by suppressing glycolysis, which is achieved through an HIF-1 alpha-dependent pathway and the ubiquitin-proteasome pathway.
Article
Cell Biology
Alena Shmakova, Mark Frost, Michael Batie, Niall S. Kenneth, Sonia Rocha
Summary: PBRM1 interacts with HIF-1α mRNA and the m6A reader protein YTHDF2, playing a crucial role in controlling HIF-1α activity and protein levels. These findings suggest a novel SWI/SNF-independent function for PBRM1 in the epitranscriptome machinery and its involvement in regulating hypoxia signaling pathways.
Article
Environmental Sciences
Shuang Liu, Mingyue Yin, Luoting Sun, Yue Jiao, Yaoqi Zheng, Lilong Yan
Summary: In this study, the detrimental effect of tetracycline (TC) on anammox reactor performance was investigated, and the mitigation of TC inhibition by iron-loaded sludge biochar (Fe-BC) was explored. Fe-BC increased the activity of anammox sludge by promoting the secretion of extracellular polymeric substances (EPS) and mediating the electron transfer process. Furthermore, Fe-BC improved the abundance of specific functional genes and the relative abundance of Candidatus Brocadia, enhancing the anammox process.
Article
Biochemistry & Molecular Biology
Lijiang Ji, Weixing Shen, Feng Zhang, Jie Qian, Jie Jiang, Liping Weng, Jiani Tan, Liu Li, Yugen Chen, Haibo Cheng, Dongdong Sun
Summary: The study found that worenine can affect the glucose metabolism and glycolysis of colorectal cancer cells, with anti-cancer effects and the ability to reverse the Warburg effect. The results suggest that worenine may target HIF-1 alpha to inhibit the growth and proliferation of colorectal cancer cells.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2021)
Review
Biochemistry & Molecular Biology
Stephanie Baah, Mark Laws, Khondaker Miraz Rahman
Summary: ADCs are a family of targeted therapeutic agents for cancer treatment, with over 80 currently in clinical development and 11 approved by the FDA. They offer enhanced targeting of cancer cells and reduced toxic side effects compared to traditional approaches, making them an attractive prospect in oncology research.
Article
Biology
Mark D. Allen, Stefan M. Freund, Mark Bycroft, Giovanna Zinzalla
Summary: The crystal structure of the N-terminus of SWI/SNF chromatin remodelling factor subunit BAF155 was determined, revealing an interconnected structure of MarR-like, BRCT, and chromodomains. The study shows potential effects of cancer-associated missense mutations and suggests a binding site and target for small molecule inhibitors, offering a new strategy to target SWI/SNF complexes.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fatema Tabassum, Choudhury Mahmood Hasan, Mohammad Mehedi Masud, Shirin Jamshidi, Khondaker Miraz Rahman, Monira Ahsan
Summary: Two previously undescribed indole alkaloids were isolated from the leaves of Ravenia spectabilis Engl., with 3,5-diprenyl indole exhibiting the highest cytotoxicity against human cervical cancer, pancreatic adenocarcinoma, and lung cancer cell lines. Molecular modelling studies suggested DNA intercalation as the mode of action of these compounds.
Article
Microbiology
Asad Hamad, Yiyuan Chen, Mohsin A. Khan, Shirin Jamshidi, Naima Saeed, Melanie Clifford, Charlotte Hind, J. Mark Sutton, Khondaker Miraz Rahman
Summary: In this study, a new class of antifungal agents, the Schiff bases of sulphonamides, showed activity against various Candida species, including multidrug-resistant strains causing Candidemia. These novel compounds have drug-like properties and potential for optimization with medicinal chemistry techniques to develop more potent analogs for pre-clinical evaluation.
Review
Pharmacology & Pharmacy
Md Mahbub Hasan, Mark Laws, Peiqin Jin, Khondaker Miraz Rahman
Summary: ADCs utilize mAbs as carriers for cytotoxic payloads to target cells expressing specific antigens, but face challenges such as immunogenicity and variable drug-antibody ratios. Recent innovations and careful considerations are key to overcoming these issues and developing more effective ADC therapeutics.
DRUG DISCOVERY TODAY
(2022)
Review
Biochemistry & Molecular Biology
Mark Laws, Peiqin Jin, Khondaker Miraz Rahman
Summary: Tuberculosis, caused by Mycobacterium tuberculosis, remains a major global health threat and efforts to combat drug-resistant strains are crucial. Developing efflux pump inhibitors as adjunct therapy is a key strategy in addressing resistance in TB.
TRENDS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Aqeel Imran, Muhammad Tariq Shehzad, Syed Jawad Ali Shah, Taha al Adhami, Mark Laws, Khondaker Miraz Rahman, Rima D. Alharthy, Imtiaz Ali Khan, Zahid Shafiq, Jamshed Iqbal
Summary: The role of aldose reductase (ALR2) in causing diabetic complications is well-studied. In this study, a series of N-substituted thiosemicarbazones with added phenolic moieties were synthesized, and compound 3m showed strong and selective ALR2 inhibitory activity in vitro as well as promising antioxidant activity. Molecular docking studies and molecular dynamics simulations confirmed the stable interactions between 3m and ALR2. Therefore, N-substituted thiosemicarbazones are potential drug candidates for selective inhibition of ALR2 and treatment of diabetic complications.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Aqeel Imran, Muhammad Tariq Shehzad, Syed Jawad Ali Shah, Mark Laws, Taha al-Adhami, Khondaker Miraz Rahman, Imtiaz Ali Khan, Zahid Shafiq, Jamshed Iqbal
Summary: Diabetic complications are caused by overexpression of aldose reductase, leading to oxidative stress and formation of advanced glycation end products. Current aldose reductase inhibitors have failed due to toxicity and poor pharmacokinetic profiles. This study developed thiosemicarbazone derivatives as selective inhibitors of ALR2 with antioxidant and antiglycation potential. Among the synthesized compounds, 3c showed strong and selective inhibition of ALR2, as well as good antioxidant and antiglycative properties.
Article
Biology
George Procopiou, Paul J. M. Jackson, Daniella di Mascio, Jennifer L. Auer, Chris Pepper, Khondaker Miraz Rahman, Keith R. Fox, David E. Thurston
Summary: Antibody-drug conjugates (ADCs) are increasingly important in cancer treatment, and novel payloads with new mechanisms of action are in demand for enhanced therapeutic efficacy. A class of DNA-crosslinking payloads, which selectively alkylate bases in the DNA molecule, has been developed and shown to have sequence-specific cytotoxicity. When conjugated to an antibody, the ADC exhibits significant antitumor activity and high tolerability.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Kate L. Arkless, Dingxin Pan, Manu Shankar-Hari, Richard T. Amison, Clive P. Page, Khondaker Miraz Rahman, Simon C. Pitchford
Summary: This study compared the effects of ADP, Ap3A, NAD(+), ADP-ribose, and Up4A on platelet functions, and found that these endogenous nucleotides can modulate platelet's inflammatory functions through activating P2Y(1) receptors, but have different effects on thrombotic functions. Molecular docking analysis revealed distinct differences in amino acid interactions and depth of fit within the binding pocket between these nucleotides and ADP.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Infectious Diseases
Pietro Picconi, Charlotte K. Hind, J. Mark Sutton, Khondaker Miraz Rahman
Summary: Finding new antibiotic classes against multidrug-resistant bacteria is urgently needed. Pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have recently been identified as a new broad-spectrum antibiotic class with activity against Gram-negative bacteria. By replacing the active imine moiety of lead PBD compounds with amide, non-DNA binding and noncytotoxic dilactam analogues were obtained to improve the safety potential of this class.
Article
Biochemistry & Molecular Biology
Lindsay Evans, Anita Kotar, Martina Valentini, Alain Filloux, Shirin Jamshidi, Janez Plavec, Khondaker Miraz Rahman, Ramon Vilar
Summary: This study discovered three stable guanine-quadruplex structures in the genome of Pseudomonas aeruginosa and demonstrated that small molecules can stabilize these structures under physiological conditions. These findings could be important for the development of new antibiotics to combat antimicrobial resistance.
RSC CHEMICAL BIOLOGY
(2023)
Review
Infectious Diseases
Anusha Gauba, Khondaker Miraz Rahman
Summary: Multidrug-resistant Gram-negative bacterial infections pose a serious global healthcare and economic threat. The lack of new therapies and the increasing resistance levels call for urgent research and development of novel targeted therapies. Efforts have been made to combat antibiotic resistance by targeting specific mechanisms, but further research is needed to understand the precise mechanisms and explore narrow-spectrum targeted therapies.
Article
Biochemistry & Molecular Biology
Asha Mary Joseph, Kazi Nahar, Saheli Daw, Md. Mahbub Hasan, Rebecca Lo, Tung B. K. Le, Khondaker Miraz Rahman, Anjana Badrinarayanan
Summary: Pyrrolobenzodiazepines (PBDs) are DNA binding compounds with anti-tumor and anti-bacterial activity. Chemical modifications can enhance their DNA binding and efficacy. Our study shows that PBD monomers cause DNA damage and kill bacteria, and repairing these damages rely on error-free mechanisms.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
K. R. Shahriar, M. E. Hossain, K. M. Rahman, M. Ahsan, C. M. Hasan
Summary: A new cyclohexanone derivative named stipularone was isolated from the leaves of Bridelia stipularis and characterized using NMR spectroscopy and HR-ESI-MS. Additionally, four known compounds were identified by comparing their spectra with published results, and the chemotaxonomic significance of the isolated compounds was discussed.
CHEMISTRY OF NATURAL COMPOUNDS
(2021)
