Fengwen Huang

All Publications

• Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum. Communications biology Huang, F., Baset, A., Bello, S. T., Chen, X., He, J. 2025; 8 (1): 153

  Abstract

  It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region.

  View details for DOI 10.1038/s42003-025-07597-9

  View details for PubMedID 39893259

  View details for PubMedCentralID PMC11787286

• Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses. Cell reports Su, J., Huang, F., Tian, Y., Tian, R., Qianqian, G., Bello, S. T., Zeng, D., Jendrichovsky, P., Lau, C. G., Xiong, W., Yu, D., Tortorella, M., Chen, X., He, J. 2023; 42 (12): 113467

  Abstract

  The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.

  View details for DOI 10.1016/j.celrep.2023.113467

  View details for PubMedID 37979171

• Neuropeptide cholecystokinin: a key neuromodulator for hippocampal functions. Neural regeneration research Huang, F., Bello, S. T. 2025; 20 (7): 1991-1992

  View details for DOI 10.4103/NRR.NRR-D-24-00465

  View details for PubMedID 39254553

  View details for PubMedCentralID PMC11691480

• Shedding light on subiculum's role in human brain disorders. Brain research bulletin Baset, A., Huang, F. 2024; 214: 110993

  Abstract

  Subiculum is a pivotal output component of the hippocampal formation, a structure often overlooked in neuroscientific research. Here, this review aims to explore the role of the subiculum in various brain disorders, shedding light on its significance within the functional-neuroanatomical perspective on neurological diseases. The subiculum's involvement in multiple brain disorders was thoroughly examined. In Alzheimer's disease, subiculum alterations precede cognitive decline, while in epilepsy, the subiculum plays a critical role in seizure initiation. Stress involves the subiculum's impact on the hypothalamic-pituitary-adrenocortical axis. Moreover, the subiculum exhibits structural and functional changes in anxiety, schizophrenia, and Parkinson's disease, contributing to cognitive deficits. Bipolar disorder is linked to subiculum structural abnormalities, while autism spectrum disorder reveals an alteration of inward deformation in the subiculum. Lastly, frontotemporal dementia shows volumetric differences in the subiculum, emphasizing its contribution to the disorder's complexity. Taken together, this review consolidates existing knowledge on the subiculum's role in brain disorders, and may facilitate future research, diagnostic strategies, and therapeutic interventions for various neurological conditions.

  View details for DOI 10.1016/j.brainresbull.2024.110993

  View details for PubMedID 38825254

• Investigation of Bucillamine as anti-COVID-19 drug: DFT study, molecular docking, molecular dynamic simulation and ADMET analysis. Journal of biomolecular structure & dynamics Huang, F., Chen, C. 2024; 42 (1): 34-42

  Abstract

  The novel coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is a global health pandemic beginning in early December 2019 in Wuhan, Hubei province, China. The effective drug target among coronaviruses is the SARS-CoV-2 main protease (Mpro), because of its crucial role in processing viral polyproteins translated from the viral RNA. In this study, the bioactivity of the selected thiol drug named Bucillamine (BUC) was evaluated as a potential drug for COVID-19 treatment by using computational modeling strategies. First, the molecular electrostatic potential density (ESP) calculation was performed to estimate the chemically active atoms of BUC. Additionally, BUC was docked to the Mpro (PDB: 6LU7) to evaluate the protein-ligand binding affinities. Besides, the estimated ESP results by density functional theory (DFT) were used to illustrate the molecular docking findings. Moreover, the frontier orbitals analysis was calculated to determine the charge transfer between the Mpro and BUC. Then, the stability of protein-ligand complex was subjected to the molecular dynamic simulations. Finally, an in silico study was performed to predict drug-likeness and absorption, distribution, metabolism, excretion and toxicity profiles (ADMET) of BUC. These results propose that BUC can be a potential drug candidate against the COVID-19 disease progression.Communicated by Ramaswamy H. Sarma.

  View details for DOI 10.1080/07391102.2023.2192791

  View details for PubMedID 36995042

• Protocol for induction of heterosynaptic long-term potentiation in the mouse hippocampus via dual-opsin stimulation technique. STAR protocols Huang, F., Bello, S. T., Baset, A., Chen, X., He, J. 2024; 5 (1): 102860

  Abstract

  Cholecystokinin (CCK) is the most abundant neuropeptide that broadly regulates the physiological status of animals. Here, we present a two-color laser theta burst stimulation (L-TBS) protocol for simultaneous activation of Schaffer collateral and perforant pathway in the hippocampus of CCK Cre mice. We describe steps for heterosynaptic long-term potentiation induction by L-TBS. This technique allows for the examination of the neurotransmitter roles in synaptic modulation and facilitates the exploration of pathological mechanisms in genetic models of brain disorders in mice. For complete details on the use and execution of this protocol, please refer to Su et al.1.

  View details for DOI 10.1016/j.xpro.2024.102860

  View details for PubMedID 38306268

  View details for PubMedCentralID PMC10847677

• Insights into the interaction between the kusaginin and bovine serum albumin: Multi-spectroscopic techniques and computational approaches. Journal of molecular recognition : JMR Huang, F., Chen, C. 2023; 36 (3): e3003

  Abstract

  Kusaginin, as a phenylethanoid glycoside, which has exhibited wide antioxidant and antimicrobial properties. The molecular mechanism underlying the broad biological activities of kusaginin has not yet been well documented. In this paper, the interaction of kusaginin with bovine serum albumin (BSA) has been explored by fluorescence spectra, UV-vis absorption spectra, and circular dichroism (CD) spectra along with computational approaches. The fluorescence experiments showed that kusaginin could strongly quench the intrinsic fluorescence of BSA through both dynamic and static quenching mechanisms. The thermodynamic analysis suggested that hydrophobic force was the main force in stabilizing the BSA-kusaginin complex. In addition, conformation changes of BSA were observed from three-dimensional and synchronous fluorescence spectra, UV spectra, and CD spectra under experimental conditions. All these experimental results have been complemented and validated by the molecular docking and dynamic simulation studies, which revealed that kusaginin was bound on the hydrophobic cavity in subdomain IIA of BSA and formed a stable BSA-kusaginin complex. Finally, density functional theory (DFT) calculation further implied that hydrogen bonds also support stabilizing the BSA-kusaginin complex. This research may aid in understanding the pharmacological characteristics of kusaginin and provide a vital reference modeling for the design of analogues drugs.

  View details for DOI 10.1002/jmr.3003

  View details for PubMedID 36519271

• Comparative studies on DNA-binding and in vitro antitumor activity of enantiomeric ruthenium(II) complexes. Journal of inorganic biochemistry Hong, W. X., Huang, F., Huan, T., Xu, X., Han, Q., Wang, G., Xu, H., Duan, S., Duan, Y., Long, X., Liu, Y., Hu, Z. 2018; 180: 54-60

  Abstract

  A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)2PBIP]2+ {bpy=2,2'-bipyridine, PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. The systematic comparative studies between two enantiomers on their DNA binding-behaviors with calf thymus DNA (CT DNA) were carried out by viscosity measurements, spectrophotometric methods and molecular simulation technology. Additional assays were performed to explore the cytotoxicity of the ruthenium(II) enantiomers against tumor cell lines. DNA-binding studies show that both the enantiomers can bind to CT DNA via intercalative mode, and the Δ form binds to CT DNA more strongly than the Λ form does. Molecular simulation further shows that both the two enantiomers intercalate between base pairs of DNA in minor groove, and that the Δ form intercalates into DNA more deeply than the Λ form does. In addition, the cell proliferation assays show that the Δ form induces a greater cytotoxicity than the Λ form on human cervical cancer HeLa cells, which is positive correlated with the results in DNA binding studies and molecular docking, and implies that the DNA binding affinities of ruthenium(II) polypyridyl complexes might be constitute to the part of their anticancer mechanisms.

  View details for DOI 10.1016/j.jinorgbio.2017.11.024

  View details for PubMedID 29245062

• Assessment of pollutions and identification of sources of heavy metals in sediments from west coast of Shenzhen, China. Environmental science and pollution research international Huang, F., Xu, Y., Tan, Z., Wu, Z., Xu, H., Shen, L., Xu, X., Han, Q., Guo, H., Hu, Z. 2018; 25 (4): 3647-3656

  Abstract

  The sediment samples were collected from eight sites located in the Pearl River Estuary and the Shenzhen Bay of the west coast of Shenzhen. The distributions of the seven elements Zn, Cr, Hg, Cu, Cd, Pb and As have been analyzed, and their pollution degrees, corresponding potential ecological risks and source identifications have been studied using geo-accumulation index, potential ecological risk index and integrated multivariate statistical methods, respectively. Based on the calculated geo-accumulation indices, the contamination levels of all elements in the Pearl River Estuary are similar to those in the Shenzhen Bay, reflecting that these elements in the study areas have similar sources because of the adequate seawater exchange. The calculated potential ecological risk indices suggest that Cd and Hg are at considerable and moderate risk, respectively. Multivariate statistical analyses further reveal that Zn, Hg, Cd and Pb originated from industrial wastewater, while Cr and Cu are mainly from both industrial wastewater and agricultural sources, and As is mainly from natural source. These research results provide baseline information for both the coastal environment management and the worldwide heavy metal distribution and assessment.

  View details for DOI 10.1007/s11356-017-0362-y

  View details for PubMedID 29164465

• Conformation change of trypsin induced by acteoside as studied using multiple spectroscopic and molecular docking methods INTERNATIONAL JOURNAL OF FOOD PROPERTIES Wu, Z., Huang, F., Chen, Y., Xu, H., Meti, M. D., Fan, Y., Han, Q. G., Tang, H., He, Z., Hu, Z. 2018; 21 (1): 316-327

  View details for DOI 10.1080/10942912.2018.1454944

  View details for Web of Science ID 000435544000001

• Study on interaction between curcumin and pepsin by spectroscopic and docking methods. International journal of biological macromolecules Ying, M., Huang, F., Ye, H., Xu, H., Shen, L., Huan, T., Huang, S., Xie, J., Tian, S., Hu, Z., He, Z., Lu, J., Zhou, K. 2015; 79: 201-8

  Abstract

  The interaction between curcumin and pepsin was investigated by fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD), and molecular docking. Under physiological pH value in stomach, the fluorescence of pepsin can be quenched effectively by curcumin via a combined quenching process. Binding constant (Ka) and binding site number (n) of curcumin to pepsin were obtained. According to the theory of Förster's non-radiation energy transfer, the distance r between pepsin and curcumin was found to be 2.45 nm within the curcumin-pepsin complex, which implies that the energy transfer occurs between curcumin and pepsin, leading to the quenching of pepsin fluorescence. Fluorescence experiments also suggest that curcumin is located more closely to tryptophan residues than tyrosine residues. CD spectra together with UV-vis absorbance studies show that binding of curcumin to pepsin results in the extension of peptide strands of pepsin with loss of some β-sheet structures. Thermodynamic parameters calculated from the binding constants at different temperatures reveal that hydrophobic force plays a major role in stabilizing the curcumin-pepsin complex. In addition, docking results support the above experimental findings and suggest the possible hydrogen bonds of curcumin with Thr-77, Thr-218, and Glu-287 of pepsin, which help further stabilize the curcumin-pepsin complex.

  View details for DOI 10.1016/j.ijbiomac.2015.04.057

  View details for PubMedID 25940524