screening-traditional-chinese-medicine-compounds-for-inhibiting-uchl3

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Deubiquitinating enzymes&#160;(DUBs) play a pivotal role in modulating ubiquitination homeostasis, with UCHL3 being an archetypal cysteine DUB intricately ...

China Academy Of Chinese Medical Sciences

Substrate stiffness, as a critical mechanical factor, has been proven to be an important regulator of biological responses, cellular functions, and disease occurrence. However, the effects of substrate stiffness on the phenotypes and drug responses of neural cells remain largely unknown. In this study, polydimethylsiloxane (PDMS) substrates with different stiffnesses were employed to establish the mechanical microenvironment of tissues of different organs. We studied the influences of stiffness on neural cell phenotypes, including cell viability, cell cycle, cytoskeleton structures, cell stiffness, and drug responses of neural cells for hormesis and therapeutic efficacy in neurodegenerative disorders (NDD). The results showed that the greater the range of maximum stimulatory responses, the bigger the width of the stimulatory dosage and the higher the range of maximum neuroprotective activities of hormetic chemicals in neural cells grown on the soft substrate commensurable to the stiffness of the brain, indicating that neural cells on a rigid substrate are resistant to hormetic and neuroprotective effects of hormetic chemicals against 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model. The sensitivity of neural cells on the soft substrate to drug response was attributed to the increased cell viability rate, cell cycle progression, actin stress fibers, focal adhesion formation, and decreased cell stiffness. The promoting effect of the soft substrate and the enhanced hormetic and neuroprotective effect of hormetic chemicals on soft substrates in PC12 cells were confirmed to be mediated by the upregulated EGFR/PI3K/AKT signaling pathway by RNA-Seq and bioinformatics analysis. This study demonstrates that the biomechanical properties of the neural microenvironment play important roles in cell phenotypes and drug responses of neural cells in vitro and suggests that substrate stiffness should be considered in the anti-NDD drug design and treatment.

Exploration of the Effects of Substrate Stiffness on Biological Responses of Neural Cells and Their Mechanisms.

Postherpetic neuralgia (PHN), the most common complication of herpes zoster, brings about a health-care burden at both the individual and societal levels. External therapy of Chinese medicine (ETCM) is an effective treatment of PHN generally available in China, yet there is incomplete evidence to evaluate the efficacy and safety of it.

External therapy of Chinese medicine for postherpetic neuralgia: A protocol for systematic review and meta-analysis.

Fu Fang Gang Liu (FFGL) is an effective formula for treating wart proliferation caused by human papillomavirus (HPV) infection and has the potential to treat HPV-related cancers. However, scientific evidence of its anti-tumor activity against cervical cancer, the most common cancer caused by HPV, is lacking.

Fu Fang Gang Liu aqueous extract inhibits the proliferation of HeLa cells by causing deoxyribonucleic acid damage.

Condyloma acuminatum (CA) is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective externally administered prescription used to treat CA; however, its molecular mechanism remains unclear. This study aimed to identify and experimentally validate the major active ingredients and prospective targets of FFGL.

Mechanisms of action of Fu Fang Gang Liu liquid in treating condyloma acuminatum by network pharmacology and experimental validation.

Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein-protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.

Exploring the mechanism of Liang Xue Wu Hua Tang in the treatment of rosacea via network pharmacology and molecular docking.

Chronic spontaneous urticaria (CSU) is a common chronic inflammatory skin disease that manifests as itching and wheals, seriously affecting quality of life. Clinical observations and previous research trials have shown that acupuncture is safe and effective for the treatment of CSU. However, there are problems, such as a short duration of action and frequent treatment. Compared with traditional acupuncture, acupoint catgut embedding (ACE) has the advantages of a longer effect and higher compliance. Clinical trials are needed to prove its efficacy and mechanism of action.

Efficacy and Mechanism of Acupoint Catgut Embedding in the Treatment of Chronic Spontaneous Urticaria: Protocol for a Randomized Double-Blind Placebo-Controlled Trial.

Previous studies have suggested a potential correlation between psoriasis (PS) and ulcerative colitis (UC). However, studies exploring the shared mechanisms of both diseases remain limited. Current treatments primarily involve using immunosuppressive drugs, which can lead to potential side effects and drug resistance. Traditional Chinese medicine has demonstrated favorable efficacy in treating UC and PS with fewer side effects. This study aims to elucidate the shared biological mechanisms underlying UC and PS and to predict natural compounds effective for treating both disorders.

Exploring shared mechanisms between ulcerative colitis and psoriasis and predicting therapeutic natural compounds through bioinformatics and molecular docking.

Zhu Fan

Guanganmen Hospital

China Academy Of Chinese Medical Sciences

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Zhu Fan

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China Academy Of Chinese Medical Sciences

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Guanganmen Hospital