Liquiritin alleviates spinal cord injury through suppression of inflammation, oxidative stress, and cell apoptosis in a rat model

Purpose: Liquiritin is an extract from Glycyrrhiza Radix, one of the oldest traditional Chinese herbal medicines, which is commonly used to treat various injuries and swellings. This study is aimed to determine whether liquiritin can protect spinal cord injuries (SCIs) from secondary injuries. Methods: A rat SCI model was established. After liquiritin treatment, the neural-function of Rats was determined by Basso, Beattie and Bresnahan (BBB) scores, paw withdrawal threshold (PWT), and thermal withdrawal latency (PWL). The effects of anti-inflammation, anti-oxidation, and anti-apoptosis of liquiritin were also examined in the rats with SCI. Moreover, the activities of several signaling elements, such as, inflammation-associated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), toll-like receptor 4 (TLR4), proliferative-related p38 mitogen-activated protein kinases (MAPK) and myeloid differentiation primary response 88 (MyD88) which was involved in the TLR4 signaling, were used for further investigation of the underlying molecular mechanisms. Results: Liquiritin improved locomotor function recovery, alleviated allodynia and hyperalgesia, and decreased water content of spinal cord in SCI rats. Also, liquiritin reduced SCI–induced inflammatory responses by decreasing the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-6. Liquiritin inhibited SCI–induced oxidative stress by decreasing malondialdehyde (MDA) level and increasing the levels of uperoxide dismutase (SOD) (p < 0.05), glutathione (GSH) (p < 0.01), and GSH-PX (p < 0.001). In addition, liquiritin alleviated spinal cord injury (SCI) –induced apoptosis of neural cells by decreasing the expression of cleaved caspase-9, -3 and cleaved poly ADP-ribose polymerase (PARP). Finally, liquiritin decreased spinal cord injury (SCI) -induced up-regulation of TLR4/MyD88/NF-κB and p38 MAPK signaling cascades. Conclusion: Liquiritin exerts protective role in SCI by reducing excessive inflammation, suppressing oxidative stress, and inhibiting neural cell apoptosis in a rat model of SCI. Thus, the agent can potentially be used for the management of SC

pLMFPPred: a novel approach for accurate prediction of functional peptides integrating embedding from pre-trained protein language model and imbalanced learning

Functional peptides have the potential to treat a variety of diseases. Their good therapeutic efficacy and low toxicity make them ideal therapeutic agents. Artificial intelligence-based computational strategies can help quickly identify new functional peptides from collections of protein sequences and discover their different functions.Using protein language model-based embeddings (ESM-2), we developed a tool called pLMFPPred (Protein Language Model-based Functional Peptide Predictor) for predicting functional peptides and identifying toxic peptides. We also introduced SMOTE-TOMEK data synthesis sampling and Shapley value-based feature selection techniques to relieve data imbalance issues and reduce computational costs. On a validated independent test set, pLMFPPred achieved accuracy, Area under the curve - Receiver Operating Characteristics, and F1-Score values of 0.974, 0.99, and 0.974, respectively. Comparative experiments show that pLMFPPred outperforms current methods for predicting functional peptides.The experimental results suggest that the proposed method (pLMFPPred) can provide better performance in terms of Accuracy, Area under the curve - Receiver Operating Characteristics, and F1-Score than existing methods. pLMFPPred has achieved good performance in predicting functional peptides and represents a new computational method for predicting functional peptides.Comment: 20 pages, 5 figures,under revie