Article
Multidisciplinary Sciences
Hanli Guo, Weifeng Yin, Ziling Zou, Chao Zhang, Minghui Sun, Lingtian Min, Lei Yang, Lingyi Kong
Summary: The study found that quercitrin promoted cell proliferation and delayed extracellular matrix degradation by regulating MMP13 and collagen II gene and protein expressions. Additionally, quercitrin activated the Phosphatidylinositol 3-kinase p110a (p110a)/AKT/mTOR signaling pathway by targeting p110a.
JOURNAL OF ADVANCED RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Fen-Fen Yang, Ming-Shan Shuai, Xiang Guan, Mao Zhang, Qing-Qing Zhang, Xiao-Zhong Fu, Zong-Qin Li, Da-Peng Wang, Meng Zhou, Yuan-Yong Yang, Ting Liu, Bin He, Yong-Long Zhao
Summary: Multi-drug-resistant microbial pathogens pose a serious global health problem. Developing novel antibacterial drugs is urgent and important. In this study, we synthesized 29 indirubin-3'-monoximes based on the active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan and evaluated their antibacterial activities. The results showed that some indirubin-3'-monoximes exhibited potent antibacterial activity against Staphylococcus aureus, including a certain synergistic effect with levofloxacin.
Article
Biochemistry & Molecular Biology
Chengbin Yang, Mingzhu Lu, Yi Chen, Ruiqing Xiang, Tianze Qiu, Yu Jia, Yongtai Yang, Xiaofeng Liu, Mingli Deng, Yun Ling, Yaming Zhou
Summary: Breast cancer is the cancer with the highest incidence globally, and the newly designed 7-azaindole derivatives FD2054 and FD2078 are potent PI3K inhibitors with promising antiproliferative activity against MCF-7 and MDA-MB-231 breast cancer cell lines, showing potential as candidates for anticancer drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Stefanie Deinhardt-Emmer, Laura Jaeckel, Clio Haering, Sarah Boettcher, Janine J. Wilden, Brigitte Glueck, Regine Heller, Michaela Schmidtke, Mirijam Koch, Bettina Loeffler, Stephan Ludwig, Christina Ehrhardt
Summary: The PI3K inhibitor Pictilisib has been identified as a potent inhibitor of IV propagation, showing reduced viral titers and inflammatory response in the lungs, making it a promising candidate for anti-IV therapies. Repurposing previously approved substances is a cost-effective and efficient way for the development of novel antiviral strategies.
Article
Oncology
Riyad Adnan Almaimani, Akhmed Aslam, Jawwad Ahmad, Mahmoud Zaki El-Readi, Mohamed E. El-Boshy, Abdelghany H. Abdelghany, Shakir Idris, Mai Alhadrami, Mohammad Althubiti, Hussain A. Almasmoum, Mazen M. Ghaith, Mohamed E. Elzubeir, Safaa Yehia Eid, Bassem Refaat
Summary: This study measured the potential beneficial effects of adding metformin and/or active vitamin D to the main cytotoxic drug used for treating colon cancer. The results demonstrated that metformin had superior anticancer effects and ameliorated the effects of chemotherapy. Additionally, the triple treatment with the drugs showed the best inhibition of cancer progression.
Article
Biochemistry & Molecular Biology
Sasja Blokzijl-Franke, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil, Jeroen den Hertog
Summary: The study found that HSPCs in mutant zebrafish embryos lacking pten function exhibited death during development, which could be rescued by inhibiting PI3K, while inhibiting PI3K in wild-type embryos also induced HSPC death. PI3K signaling tightly controls HSPC survival, with both up- and downregulation of the signaling pathway reducing stemness of HSPCs.
Article
Pharmacology & Pharmacy
Mohamed E. Shaker, Hesham A. M. Gomaa, Sara H. Hazem, Mohamed A. Abdelgawad, Mohamed El-Mesery, Ahmed A. Shaaban
Summary: The study investigated the role of PI3K alpha in hepatic sterile inflammation caused by APAP-overdose and found that the selective modulation of PI3K alpha activity by alpelisib can inhibit the inflammatory response and immune cell infiltration. Alpelisib reduced the escalation of liver function biomarkers and hepatic necroinflammation score, as well as apoptosis and proliferation in liver hepatocytes induced by APAP. It also limited the overproduction of pro-inflammatory cytokines and the activation of several signal transduction proteins.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Yantao Cai, Chuyu Li, Fang Peng, Shuanghong Yin, Huiyi Liang, Jiyan Su, Lin Li, Anping Yang, Hui Liu, Chuansheng Yang, Dixian Luo, Chenglai Xia
Summary: This study demonstrates that hsa_circRNA_0001400 is highly expressed in cervical cancer tissues. The hsa_circRNA_0001400_siRNA promotes apoptosis and inhibits cell cycle and migration of cervical cancer cells. Moreover, hsa_circRNA_0001400_siRNA also inhibits the growth and angiogenesis of SiHa xenografts in nude mice.
FRONTIERS IN GENETICS
(2021)
Article
Pharmacology & Pharmacy
Yan Luo, Liwei Liu, Jihua Zhao, Yue Jiao, Meiyu Zhang, Guangli Xu, Yumao Jiang
Summary: In this study, it was found that inhibition of the PI3K/AKT1 signaling pathway by sinomenine (SIN) induces apoptosis in hepatocellular carcinoma (HCC) cells and inhibits cell proliferation. These findings provide a new direction for the treatment of HCC.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Multidisciplinary Sciences
Shota Shimizu, Kazuaki Yoshioka, Sho Aki, Yoh Takuwa
Summary: PI3K-C2 alpha is essential for clathrin-mediated endocytosis of the gamma-secretase complex, facilitating the cleavage of endocytosed Notch1 by the gamma-secretase complex to generate NICD1 in ECs.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Aya A. Farahat, Eman M. Samir, Mayssoune Y. Zaki, Rabah A. T. Serya, Hatem A. Abdel-Aziz
Summary: The novel pyrazolo[3,4-b]pyridine compounds exhibit potent antiproliferative activity against HepG2 and HeLa cells, with compounds 14a and 14d showing the most efficacy. These compounds can also induce cell cycle disturbance and apoptosis in HepG2 cells. Furthermore, compounds 9h and 14d are identified as the most efficient antiproliferative agents in a screening of the NCI 60-cell line panel. Additionally, some compounds show good inhibitory action against the cellular pathway regulator p38 alpha kinase.
ARCHIV DER PHARMAZIE
(2022)
Article
Immunology
Gregory R. Tintinger, Annette J. Theron, Helen C. Steel, Moloko C. Cholo, Jan G. Nel, Charles Feldman, Ronald Anderson
Summary: The study investigated the impact of bedaquiline on platelet activation and found that it exerts anti-platelet effects by inhibiting ADP-activated expression of CD62P, aggregation, and Ca2+ mobilization, possibly through its action on PI3-K. These anti-platelet effects may help mitigate the risk of TB-associated cardiovascular disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Wanvisa Udomsinprasert, Tachatra Ungsudechachai, Supawit Wunthong, Supakorn Yuttanarad, Jiraphun Jittikoon, Sittisak Honsawek
Summary: This study investigated the clinical and pathological effects of Galectin-3 on inflammation in knee osteoarthritis (OA). The results showed increased levels of Galectin-3 in the synovial fluid and plasma of knee OA patients, which were significantly associated with disease severity and indicators of body composition, physical performance, knee pain, and disability. Further analysis revealed that Galectin-3 exerted an inflammatory action in knee OA synoviocytes, stimulating the production of inflammatory factors and regulating gene expressions related to inflammation and cartilage degeneration.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Seiichi Okabe, Yuko Tanaka, Akihiko Gotoh
Summary: The study demonstrated that the dual inhibitor CUDC-907 targeting PI3K and HDAC could effectively suppress myeloma cells by inhibiting HDAC activity and reducing the expression of key proteins involved in cancer cell survival. Combination treatment of myeloma cells with CUDC-907 and carfilzomib showed increased cytotoxicity, indicating a potential strategy to enhance the effects of proteasome inhibitors against MM cells.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Kangfa Huang, Chengde Li, Fenglei Gao, Yushan Fan, Fanwen Zeng, Li Meng, Li Li, Shouquan Zhang, Hengxi Wei
Summary: The study demonstrated that EGCG promotes the in vitro maturation and embryo development following IVF of porcine oocytes. The protective effects of EGCG on the oocytes may be associated with its antioxidant and anti-apoptosis properties.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Neurosciences
Svenja L. Kreis, Heiko J. Luhmann, Dumitru Ciolac, Sergiu Groppa, Muthuraman Muthuraman
Summary: This study investigated the connectivity between premotor and primary motor cortex in humans and between caudal and rostral forelimb areas in mice, revealing strong relationships between spectral power, functional connectivity, and effective connectivity.
Review
Neurosciences
Heiko J. Luhmann
Summary: This review article provides a brief summary of the novel technologies, challenges, current understanding, and open questions in the field of neurophysiology of the developing cerebral cortex in rodents. The use of high-density multi-electrode arrays and genetically encoded calcium indicators has allowed the recording of neuronal activity in large cortical networks, revealing surprising patterns of cortical and subcortical activity during early development. However, the functional roles of these activity patterns and their impact on cortical maturation are not yet fully understood. Future research will focus on targeted genetic manipulations and optogenetics to elucidate the function of early cortical circuits and their role in the generation of activity patterns.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Chia-Fang Wang, Jenq-Wei Yang, Zi-Hui Zhuang, Hsiang-Wei Hsing, Heiko J. Luhmann, Shen-Ju Chou
Summary: This study revealed a bottom-up feedback mechanism for regulating the development of TCAs, which involves feedback signals from L4 neurons and the regulation by Lhx2 and Sema7a.
Article
Neurosciences
Jens R. Vandevelde, Jenq-Wei Yang, Steffen Albrecht, Henry Lam, Paul Kaufmann, Heiko J. Luhmann, Maik C. Stuettgen
Summary: Through multi-electrode recordings and behavioral detection, we investigated the importance of different cell types and layers in the brain for the perception of sensory stimuli. Our findings indicate that the highest sensitivity is observed in layer 4, and inhibitory neurons show higher sensitivity compared to excitatory neurons across all layers. Mice perform better when they are not moving, which is reflected by increased firing rates in response to stimuli at the neuronal level.
Article
Neurosciences
Linbi Cai, Jenq-Wei Yang, Chia-Fang Wang, Shen-Ju Chou, Heiko J. Luhmann, Theofanis Karayannis
Summary: The whiskers of rodents play a crucial role in providing tactile information for navigation and object exploration. This study investigates the developmental engagement of different cortical areas in processing whisker stimuli. The researchers find that the primary sensory cortex is activated by sensory stimuli shortly after birth, while the secondary somatosensory area begins to process this information at the end of the first postnatal week. Additionally, the study uncovers a developmental window when information transfer between these cortical areas reaches mature function.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Davide Warm, Davide Bassetti, Jonas Schroer, Heiko J. Luhmann, Anne Sinning
Summary: The early occurrence of calcium transients is strongly linked to neuronal survival, with silent neurons exhibiting a higher probability of cell death. Activity of neighboring neurons in local clusters exerts a pro-survival effect, while networks with a high modular topology are associated with lower cell death rates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Renata Rose, Nicolas Peschke, Elena Nigi, Marton Gelleri, Sandra Ritz, Christoph Cremer, Heiko J. Luhmann, Anne Sinning
Summary: Chromatin compaction in the neuronal nucleus occurs before apoptosis execution and plays a critical role in the outcome of apoptotic cell death.
COMMUNICATIONS BIOLOGY
(2022)
Article
Anatomy & Morphology
Levente Gellert, Heiko J. Luhmann, Werner Kilb
Summary: The functional connections between S1 and M1 or S2 are not confined to the same cortical area, but exist already at the day of birth between adjacent cortical areas. These connections play an important role in the development of sensorimotor integration.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Multidisciplinary Sciences
Fahimeh Yeganeh, Beate Knauer, Roberta Guimaraes Backhaus, Jenq-Wei Yang, Albrecht Stroh, Heiko J. Luhmann, Maik C. Stuettgen
Summary: Inhibitory interneurons, particularly PV+ interneurons, play a crucial role in regulating network activity and processing sensory information. By using optogenetic silencing of PV+ interneurons in the barrel cortex of PVCre mice, researchers found that these cells contribute to the temporal discrimination and spatio-temporal representation of sensory stimuli by reducing ongoing spiking activity and improving signal-to-noise ratio.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jonas Schroer, Davide Warm, Federico De Rosa, Heiko J. Luhmann, Anne Sinning
Summary: During early brain development, the BAX/BCL-2 pathway plays a role in regulating cortical neuron removal, with electrical activity serving as a set point of regulation. The upregulation of BAX and downregulation of BCL-2 during the first postnatal week result in a high BAX/BCL-2 ratio, contributing to neuronal death rates. Pharmacological blockade of activity leads to upregulation of Bax, while elevated activity leads to increased BCL-2 expression, indicating the modulation of BAX/BCL-2 expression by electrical activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Heiko J. Luhmann
Summary: This review article provides an overview of the molecular, cellular, and network mechanisms underlying focal seizures in neocortical networks with developmental malformations. Neocortical malformations are a large variety of structural abnormalities associated with epilepsy and other neurological and psychiatric disorders. Animal models and state-of-the-art techniques have contributed to our understanding of neocortical hyperexcitability in developmental disorders. Additionally, molecular biological and electro-physiological techniques have provided insights into the subcellular, cellular, and network mechanisms of focal seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Physiology
Heiko J. Luhmann
Summary: The neocortical network is composed of excitatory and inhibitory neurons, organized in microcircuits that provide various types of neural connections and influences. This network is activated by specific inputs from thalamic nuclei, subcortical regions, and cortico-cortical projections. Different types of neurons in the neocortex have unique firing patterns, synaptic connectivity, and dynamics of their interactions. Repetitive stimulation can activate or inactivate microcircuits within the neocortex. Specific networks within the neocortex generate synchronized activity patterns that contribute to higher cognitive function and behavior. This review provides an overview of the current understanding of the structure and function of the neocortical network.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Psychiatry
Margaryta Tevosian, Hristo Todorov, Ermelinda Lomazzo, Laura Bindila, Natsuo Ueda, Davide Bassetti, Davide Warm, Sergei Kirischuk, Heiko J. Luhmann, Susanne Gerber, Beat Lutz
Summary: AEA is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, playing a protective role against the development of pathological states after prolonged stress exposure. In a study using a genetically modified mouse line, deficiency of the AEA synthesizing enzyme NAPE-PLD in neurons activated during chronic stress led to increased anxiety-like behavior. The molecular mechanisms underlying this phenotype may involve desensitization of the HPA axis, disinhibition of the amygdala by the prefrontal cortex, and altered neuroplasticity in the hippocampus and prefrontal cortex.
TRANSLATIONAL PSYCHIATRY
(2023)
Review
Multidisciplinary Sciences
Daniela Mirzac, Svenja L. Kreis, Heiko J. Luhmann, Gabriel Gonzalez-Escamilla, Sergiu Groppa
Summary: In this article, recent experimental and clinical studies on Parkinson's disease are reviewed, focusing on abnormal neuronal activity and pathological network oscillations and their underlying mechanisms and modulation. The aim is to enhance understanding of the progression of Parkinson's disease pathology and the timing of symptom manifestation. Mechanistic insights on the generation of aberrant oscillatory activity within the cortico-basal ganglia circuits are presented, along with discussions on the advantages, limitations, and differential applicability of available PD animal models, and suggestions for transferring knowledge on disease pathology into future research and clinical applications.
Article
Neurosciences
Aniello Lombardi, Qiang Wang, Maik C. Stuettgen, Thomas Mittmann, Heiko J. Luhmann, Werner Kilb
Summary: This study investigates the role of short-term synaptic plasticity (STP) in excitatory and inhibitory synapses in the cortical layer 2/3 of mice. The results show that burst stimulation leads to short-term depression (STD) in both excitatory and inhibitory synapses, with stronger depression observed in inhibitory synapses and longer decay time.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)