Article
Biochemistry & Molecular Biology
Iqra Sarfraz, Azhar Rasul, Farhat Jabeen, Tayyaba Sultana, Sevki Adem
Summary: This study identified ellagic acid, silibinin, curcumin, and resveratrol as potential inhibitors of PKM2 through enzymatic-assay-based screening. These compounds showed different inhibitory effects on PKM2 and demonstrated potential as targeted-cancer therapies.
Article
Oncology
Susi Zhu, Yeye Guo, Xu Zhang, Hong Liu, Mingzhu Yin, Xiang Chen, Cong Peng
Summary: PKM2 plays a crucial role in tumor metabolism and its dysregulation is associated with cancer development and progression. Researchers are investigating the function and therapeutic potential of PKM2 in cancer, particularly its interactions with lncRNAs. The role of PKM2 in the tumor microenvironment (TME) is also being studied for its implications in cancer therapy.
Review
Biochemistry & Molecular Biology
Guan-Jun Yang, Jia Wu, Chung-Hang Leung, Dik-Lung Ma, Jiong Chen
Summary: Glycolysis is a crucial step for cellular respiration, and PKM2 plays a key role in tumor cell metabolism and proliferation. Through both aerobic glycolysis and non-metabolic pathways, PKM2 contributes to leukemic proliferation, differentiation, and drug resistance.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Gastroenterology & Hepatology
Diyu Chen, Hao Wu, Xiaode Feng, Yunhao Chen, Zhen Lv, Vishnu Goutham Kota, Junru Chen, Wenxuan Wu, Yuejie Lu, Hua Liu, Yanpeng Zhang, Shusen Zheng, Jian Wu
Summary: This study identified CNRIP1 as a putative tumor suppressor in ICC, with low expression associated with poor prognosis. A CpG island site named CNRIP1 MS-2 was found to contribute to CNRIP1 down-regulation, and CNRIP1 was shown to inhibit tumor cell migration, invasion, and proliferation by suppressing PKM2 activity. Furthermore, overexpression of CNRIP1 activated Parkin, leading to PKM2 degradation in ICC cells. These findings suggest CNRIP1 as a potential biomarker for predicting tumor recurrence in ICC patients and highlight a therapeutic approach targeting the CNRIP1/Parkin/PKM2 pathway.
Review
Biochemistry & Molecular Biology
Lindsey Carlsen, Shengliang Zhang, Xiaobing Tian, Arielle De La Cruz, Andrew George, Taylor E. E. Arnoff, Wafik S. S. El-Deiry
Summary: p53 is a transcription factor that regulates tumor suppressor genes. Mutations in p53 are common in human cancers and can impact immune responses. p53 can induce different cellular responses such as apoptosis, cell cycle arrest, and DNA damage repair by regulating target genes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yeon Su Park, Joo Hee Han, Jae Hyeon Park, Ji Soo Choi, Seung Hyeon Kim, Hyung Sik Kim
Summary: Diabetic nephropathy is a common complication of diabetes, which often leads to end-stage renal disease with a high mortality rate. Current research focuses on identifying non-invasive biomarkers for early detection of diabetic nephropathy. This study found that the protein pyruvate kinase M2 (PKM2) can be detected in the urine of diabetic patients and may serve as a new biomarker for early diagnosis of diabetic nephropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Pavels Dimitrijevs, Marina Makrecka-Kuka, Agnieszka Bogucka, Marko Hyvonen, Teodors Pantelejevs, Pavel Arsenyan
Summary: Changes in cancer metabolic pathways provide an opportunity for targeted elimination of tumor cells. The design and mechanism of action of a novel class of selective PKM2 inhibitors as anti-cancer agents are reported. Compound 5c is the most active with IC50 = 0.35 +/- 0.07 μM, downregulating PKM2 mRNA expression and inducing oxidative burst, making it cytotoxic for various cancer types. Isoselenazolium chlorides inhibit PKM2 by inducing a functionally deficient tetrameric assembly and displaying a competitive inhibitor character. The discovery of robust PKM2 inhibitors is not only valuable for anticancer therapy, but also crucial for studying the role of PKM2 in cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Yun-zi Liu, Ming-yuan Xu, Xiao-yu Dai, Lang Yan, Lei Li, Rui-zhen Zhu, Li-jun Ren, Ji-qian-zhu Zhang, Xiao-fang Zhang, Jin-feng Li, Yi-jun Tian, Wen-jing Shi, Ye-qiang Liu, Chun-lei Jiang, Jiang-bo Zhu, Ji-kuai Chen
Summary: PKM2, highly expressed in psoriatic epidermis, plays a crucial role in promoting glycolytic metabolism and cell proliferation in psoriatic keratinocytes. Inhibition of PKM2 or glycolysis effectively suppresses keratinocyte proliferation, suggesting PKM2 as a potential therapeutic target for psoriasis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Ganesh Satyanarayana, Ravi Chakra Turaga, Malvika Sharma, Siming Wang, Falguni Mishra, Guangda Peng, Xiaonan Deng, Jenny Yang, Zhi-Ren Liu
Summary: This study reveals that differentiation of myofibroblasts upregulates pyruvate kinase M2 (PKM2) and promotes PKM2 dimerization, which slows glycolysis and facilitates collagen synthesis and secretion. PKM2 activator inhibits progression of liver, lung, and pancreatic fibrosis in mouse models, while increasing NADPH production to protect myofibroblasts from apoptosis.
Article
Multidisciplinary Sciences
Raji R. Nair, Joshua Hsu, Justin T. Jacob, Christopher M. Pineda, Ryan P. Hobbs, Pierre A. Coulombe
Summary: The high levels of the intermediate filament protein keratin 17 (K17) are associated with poor prognoses for several human carcinomas. Lack of K17 delays onset of tumorigenesis in mouse models and K17 impacts chromatin architecture, gene expression, and cell proliferation in the nucleus of tumor keratinocytes. The presence of nuclear-localized K17 is required for early stages of DNA damage and repair cascade, affecting cell survival and leading to poor clinical outcomes in human carcinomas.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Xiangling Ren, Xinyuan Huang, Qiong Wu, Longfei Tan, Changhui Fu, Yi Chen, Xianwei Meng
Summary: Metal organic frameworks were found to inhibit the activity of pyruvate kinase in tumor cells, with nanoscale ZIF-8 showing the ability to inhibit glycolysis. The inhibitory effect is attributed to the zinc ions in ZIF-8, which has an IC50 one percent of that of zinc ion. This novel enzyme inhibitor holds promise for cancer therapy.
CHINESE CHEMICAL LETTERS
(2021)
Article
Oncology
Apisada Jiso, Philipp Demuth, Madeleine Bachowsky, Manuel Haas, Nina Seiwert, Daniel Heylmann, Birgit Rasenberger, Markus Christmann, Lea Dietrich, Thomas Brunner, Riyanti, Till F. Schaeberle, Anuchit Plubrukarn, Joerg Fahrer
Summary: Merosesquiterpenes show promise as potential therapeutic agents for colorectal cancer, as they induce DNA damage, trigger apoptosis, and exhibit cytotoxic activity against CRC cell lines and tumor organoids. Their efficacy is observed in both wild-type and mutant p53 CRC cells, making them a potential candidate for CRC chemotherapy.
Review
Chemistry, Medicinal
Ali H. El-Far, Soad K. Al Jaouni, Xiaotao Li, Junjiang Fu
Summary: Glycolysis is a primary energy source for cancer growth and metastasis, and inhibiting glycolysis is an effective cancer control strategy. PKM2, a key glycolytic enzyme, is overexpressed in various cancer types, and natural PKM2 inhibitors have potential therapeutic effects.
PHYTOTHERAPY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Shuang Zhao, Yili Sun, Xicheng Wu, Yongqiang Yang, Kerui Fan, Kai Hu, Yasha Qin, Kexin Li, Ling Lin, Kun Chen, Yuhua Ma, Min Zhu, Gang Liu, Li Zhang
Summary: This study found that SIRT1 activator can reduce the level of PKM2 in lethal endotoxemia, thereby alleviating inflammatory response and organ injury.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yanting Yang, Xiuhong Zhu, Guohua Yu, Jinbo Ma
Summary: This study demonstrates that Pyxinol can mitigate cisplatin-induced renal injury by attenuating DNA damage response and tubular cell apoptosis. Furthermore, Pyxinol can enhance the in vivo anti-tumor efficacy of cisplatin against xenograft tumors in nude mice. The combination of Pyxinol with cisplatin may represent a beneficial adjunct therapy for cisplatin-based chemotherapeutic regimens in the clinic.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jiao Yang Lu, Wei Tao Huang, Kexuan Zhou, Xiaoli Zhao, Shuqing Yang, Liqiu Xia, Xuezhi Ding
Summary: The fatty chain in microbial-derived amphiphilic CLP bacillomycin Lb (B-Lb) was found to be key in maintaining self-assembled form and antitumor activity, with its supramolecular assemblies serving as a novel cell death inducer. This study will promote the construction of customized CLP micro/nanostructures and the design of new antitumor drugs based on structure-activity relationship.
Article
Fisheries
Yahui Yang, Duo Jin, Wensu Long, Ximiao Lai, Yunjun Sun, Feng Zhai, Pan Wang, Xixun Zhou, Yibo Hu, Liqiu Xia, Ganfeng Yi
Summary: The strain Z1-26 of Streptomyces lateritius, isolated from soil samples, exhibited broad-spectrum antibacterial activity against various fish pathogens. Feeding crucian carp with strain Z1-26 resulted in improved growth performance, antioxidant capacity, and immune response. In addition, Z1-26 supplementation significantly enhanced the survival rate of fish infected with Aeromonas hydrophila. Whole genome analysis revealed the presence of multiple gene clusters in strain Z1-26, indicating its potential as a candidate probiotic for controlling bacterial diseases in aquaculture.
JOURNAL OF FISH DISEASES
(2023)
Article
Fisheries
Shijia Yang, Duo Jin, Hui Li, Lingzhi Jiang, Jun Cui, Weitao Huang, Jie Rang, YunLong Li, Liqiu Xia
Summary: In this study, a new strain of Paenibacillus polymyxa S3 with antibacterial activity against various fish pathogens was screened and evaluated for its probiotic function. The strain was found to colonize and distribute in grass carp, improving their growth rate, antioxidant capacity, immune function, and survival rate against Aeromonas hydrophila infection.
JOURNAL OF FISH DISEASES
(2023)
Article
Fisheries
Hu Yang, Jia Li, Huizhong Xu, Chunfeng Peng, Jun Cui, Shengbiao Hu, Liqiu Xia, Youming Zhang
Summary: This study investigated the antioomycete effect, mechanism, and application of acidic electrolytic water (AEW) on Saprolegnia. The results showed that AEW had an antioomycete effect on both Saprolegnia mycelium and spores. AEW mainly affected the normal physiological function of mycelium by destroying the cell membrane structure and causing content leakage. AEW has potential application to prevent and control saprolegniasis in the aquaculture industry.
AQUACULTURE INTERNATIONAL
(2023)
Article
Cardiac & Cardiovascular Systems
Kevin R. Bersell, Tao Yang, Jonathan D. Mosley, Andrew M. Glazer, Andrew T. Hale, Dmytro O. Kryshtal, Kyungsoo Kim, Jeffrey D. Steimle, Jonathan D. Brown, Joe-Elie Salem, Courtney C. Campbell, Charles C. Hong, Quinn S. Wells, Amanda N. Johnson, Laura Short, Marcia A. Blair, Elijah R. Behr, Evmorfia Petropoulou, Yalda Jamshidi, Mark D. Benson, Michelle J. Keyes, Debby Ngo, Ramachandran S. Vasan, Qiong Yang, Robert E. Gerszten, Christian Shaffer, Shan Parikh, Quanhu Sheng, Prince J. Kannankeril, Ivan P. Moskowitz, John D. York, Thomas J. Wang, Bjorn C. Knollmann, Dan M. Roden
Summary: Brugada syndrome (BrS) is caused by loss-of-function variants in the SCN5A gene, but a family with BrS and a rare TBX5 variant has been identified. The study found that the TBX5 variant decreased SCN5A transcription, resulting in enhanced late sodium current (I-Na) and other electrophysiological abnormalities. Additionally, abnormal PDGF/PI3K signaling was found to be associated with the development of Brugada syndrome.
Article
Fisheries
Junzhi Zhang, Ziqing Wang, Yong Shi, Liqiu Xia, Yi Hu, Lei Zhong
Summary: In this study, the protective effects of chlorogenic acid (CGA) supplementation on oxidative stress-induced damage in channel catfish were investigated. It was found that consumption of oxidized fish oil led to decreased growth performance, disrupted intestinal structure, hepatic oxidative stress, and inflammation, as well as impaired muscle development and skin coloration in the catfish. However, supplementation of CGA in the diet partially counteracted these negative effects, improving growth performance, intestinal structure, hepatic antioxidant capacity, and skin coloration. Overall, CGA shows great potential as an aquatic feed additive for channel catfish.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Jinzhi Zhao, Yi Yang, Hua Xu, Jianxujie Zheng, Chengpin Shen, Tian Chen, Tao Wang, Bing Wang, Jia Yi, Dan Zhao, Enhui Wu, Qin Qin, Li Xia, Liang Qiao
Summary: DirectDIA method shows superior performance in quantitative metaproteomics, providing valuable insights into the metabolic protein profiles of intestinal microbiota and related diseases.
NPJ BIOFILMS AND MICROBIOMES
(2023)
Article
Cell Biology
Chih-Ling Wang, Rika Ohkubo, Wei-Chieh Mu, Wei Chen, Jiang Lan Fan, Zehan Song, Ayane Maruichi, Peter H. Sudmant, Angela O. Pisco, Dena B. Dubal, Na Ji, Danica Chen
Summary: Aging leads to a decline in neural stem cells, neurogenesis, and cognitive function. Recent evidence shows disrupted adult neurogenesis in the hippocampus of patients with neurodegenerative disorders. Single-cell RNA sequencing reveals that mitochondrial protein folding stress is prominent in activated neural stem cells/neural progenitors in the neurogenic niche, and it increases with aging, leading to dysregulated cell cycle and mitochondrial activity. This stress compromises neural stem cell maintenance and reduces neurogenesis, resulting in neural hyperactivity and impaired cognitive function. Reducing mitochondrial protein folding stress improves neurogenesis and cognitive function in old mice, suggesting a potential approach to alleviate aging-associated cognitive decline.
Article
Oncology
Xiao-Na Zhu, Yu-Sheng Wei, Qian Yang, Hao-Ran Liu, Zhe Zhi, Di Zhu, Li Xia, Deng-Li Hong, Yun Yu, Guo-Qiang Chen
Summary: In this study, it was found that FBXO22 is highly expressed in MLLr AML and promotes AML progression by targeting BACH1 for degradation. Knockdown of FBXO22 leads to increased apoptosis in MLLr leukemia cells and reduced LSCs in serial transplantations. Targeting FBXO22 could be an ideal strategy to eradicate LSCs without affecting normal hematopoiesis.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Reza Mohebi, Dongyu Wang, Emily S. Lau, Juhi K. Parekh, Norrina Allen, Bruce M. Psaty, Emelia J. Benjamin, Daniel Levy, Thomas J. Wang, Sanjiv J. Shah, John S. Gottdiener, James L. Januzzi, Jennifer E. Ho
Summary: This study compares the prevalence and prognosis of heart failure (HF) stages according to the 2013 and 2022 ACC/AHA/HFSA definitions. The new standards result in a substantial shift of individuals from stage A to stage B, and those in stage B have a higher risk of progression to symptomatic HF.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Ecology
Joana L. Rocha, Pedro Silva, Nuno Santos, Monia Nakamura, Sandra Afonso, Abdeljebbar Qninba, Zbyszek Boratynski, Peter H. Sudmant, Jose C. Brito, Rasmus Nielsen, Raquel Godinho
Summary: Analysis of whole genomes of four fox species shows that introgression facilitated adaptation to the hot arid environment of the Sahara Desert and suggests renal water homeostasis as a mechanism of adaptation in the extreme desert specialist species.
NATURE ECOLOGY & EVOLUTION
(2023)
Article
Biology
Li Wan, Peilei Hu, Lili Zhang, Zhao-Xi Wang, Joy Fleming, Bo Ni, Jianjun Luo, Cha-Xiang Guan, Liqiong Bai, Yunhong Tan, Haican Liu, Na Li, Tongyang Xiao, Hua Bai, Yong-An Zhang, Xian-En Zhang, Kanglin Wan, Lijun Bi, Songying Ouyang, Hongtai Zhang
Summary: A multi-omic analysis of 11 Mycobacterium tuberculosis (Mtb) isolates with different drug resistance profiles leads to the discovery of Rv3094c, an enzyme capable of activating the clinically relevant Mtb drug, ethionamide.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemical Research Methods
Chen-Shan Chin, Sairam Behera, Asif Khalak, Fritz J. Sedlazeck, Peter H. Sudmant, Justin Wagner, Justin M. Zook
Summary: By using PGR-TK, we can analyze complex genome structures and haplotype variations. We demonstrate the capability of PGR-TK in analyzing the class II major histocompatibility complex, Y-chromosome genes associated with male infertility, and X-chromosome genes linked to eye disorders. Furthermore, we showcase its application in 395 complex repetitive medically important genes, highlighting its ability to resolve complex variations in previously unanalyzable regions of the genome.
Article
Hematology
Li-Xue Yang, Cheng-Tao Zhang, Meng-Ying Yang, Xue-Hong Zhang, Hong-Chen Liu, Chen -Hui Luo, Yue Jiang, Zhang-Man Wang, Zhong-Yin Yang, Zhao -Peng Shi, Yi-Ci Yang, Ruo-Qu Wei, Li Zhou, Jun Mi, Ai -Wu Zhou, Zhi-Rong Yao, Li Xia, Jin-Song Yan, Ying Lu
Summary: Single-cell RNA sequencing revealed a subset of complement C1Q(+) macrophage-like leukemia cells enriched in the skin of AML patients with EMI. C1Q expression was associated with adverse prognosis and mediated communication with fibroblasts, promoting tissue infiltration and survival under chemotherapy stress. Hence, C1Q serves as a marker for poor prognosis in AML and represents a promising therapeutic target for EMI.
Meeting Abstract
Gastroenterology & Hepatology
Marc Monachese, Jennifer M. Kolb, Kenneth J. Chang, Alyssa Y. Choi, Sagar Shah, Thomas J. Wang, Ahmad Bazarbashi, Ali Zakaria, Pushpak Taunk, Ali M. Abbas, Pedro Cortes, Michael B. Wallace, Bhaumik Brahmbhatt, Natalie D. Cosgrove, Wenjing Cai, David P. Lee, Prashant Kedia, Marvin Ryou, Jason B. Samarasena