Combinatorial Chemistry & High Throughput Screening - Online First

In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC).

The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRT-PCR.

A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC.

This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.

Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).

Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting.

Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the anti-inflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells.

Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.

The incidence of depression is increasing year by year, and Zhizichi Decoction(ZZCD)has shown significant efficiency in the clinical treatment of mild depression, but its mechanism of action is still unclear. In this research, network pharmacology and metagenomics combined and metabolomics were used as research methods to explain the scientific connotation of the antidepressant effect of ZZCD from the aspects of the overall effect of organisms and microbial structure and function.

The rat model of depression was established by chronic unpredictable mild stress (CUMS), and the improvement of depressive symptoms was evaluated by behavioral and histopathological methods. Network pharmacology predicted possible targets and important pathways of ZZCD. Metabolomics revealed its possible related biological pathways. Metagenomics showed the disturbance of ZZCD on intestinal microbial diversity structure and associated biological functions in depressed rats.

ZZCD can improve the behavioral performance of CUMS rats, and can significantly regulate the content of 5-HT, NE and other neurotransmitters in serum and brain tissue, and improve the damaged state of neurons in the hippocampus. Network pharmacology predicts that it mainly acts on biological processes such as inflammatory response and oxidative stress response. Metabolomics found that it affected metabolic pathways such as amino acid metabolism and lipid metabolism. The results of metagenomics showed that it significantly regulated the abundance of Firmicutes and Bacteroidetes. The above results predicted that it may affect signaling pathways such as the nervous system, inflammatory diseases and cell processing.

ZZCD may play an antidepressant role by regulating intestinal probiotics, energy metabolism, and inflammation reduction. This provides a scientific basis for the clinical application of ZZCD in traditional Chinese medicine and also makes it an optional alternative for the treatment of depression.

RA is a recurrent autoimmune disease that has significant adverse effects on the physical and mental health of patients. Traditional Chinese medicine has shown significant advantages in the prevention and treatment of RA. Numerous clinical and experimental studies have confirmed that traditional Chinese medicine components have clear therapeutic effects and minimal adverse reactions in treating RA. The research on traditional Chinese medicine for the prevention and treatment of RA has become a hot topic in the field of autoimmune diseases.

The related references about the mechanisms and Q-markers of anti-RA of traditional Chinese medicine in this review were collected from Willy, SpringLink, Web of Science, Elsevier, PubMed, SciFinder, Scopus, ACS publications, Baidu Scholar, Google Scholar, and CNKI.

The traditional Chinese medicine components such as terpenoids, flavonoids, and alkaloids have significant anti-RA effects, and their mechanisms are mainly to inhibit NF-κB signaling pathway, inhibit the proliferation of RA fibroblasts like synovial cells, and regulate Th1/Th2 cell balance, and so on. Predicting and studying the Q-markers of traditional Chinese medicine anti-RA by plant phylogeny and chemical componentss, traditional medicinal properties, pharmacokinetics, component measurability, correlation between composition and efficacy, and gut microbiota will provide scientific foundations for the research and further development of anti-RA traditional Chinese medicine.

The active components of traditional Chinese medicine exhibited the characteristic of multiple mechanisms in the treatment of RA, such as terpenoids had anti-angiogenesis effects, flavonoids had anti-inflammatory and cartilage protective effects, and alkaloids had anti-inflammatory and analgesic effects. The proposal of Q-markers for anti-RA provided new research ideas for promoting the development of new drugs for anti-RA and ensuring the safety and effectiveness of clinical medications.

Disulfidptosis is a new metabolic-related regulated cell death associated with cancer growth. This study aimed to investigate the molecular mechanisms associated with disulfidptosis in skin cutaneous melanoma (SKCM) and establish a disulfidptosis-related gene signature for prognostic prediction in SKCM.

Disulfidptosis-associated genes were identified from RNA-seq data of SKCM. A risk score signature was developed and validated through univariate Cox and LASSO analyses. Additionally, the immune microenvironment related to the risk score signature was investigated. Finally, a disulfidptosis-related genes-transcription factor -miRNA network was developed, and the expression levels of five disulfidptosis-related genes were initially verified in SKCM cell lines.

A total of 107 disulfidptosis-related differentially expressed genes in SKCM samples were identified. A ten-disulfidptosis-gene signature was established, including BIN2, CCL3L3, CCL8, CD79A, CIITA, CXCR3, DEFB1, GPR171, IL2RB, and SOCS1. The SKCM samples were divided into high- and low-risk groups, of which samples in the low-risk group showed better survival performance. The receiver operating characteristic curve analysis confirmed the good potency of the disulfidptosis-related gene prognostic model. Except for DEFB1, the other nine genes were positively related with T cell CD8+, T cell CD4+ memory activated, T cell gamma delta, NK cell activated, and macrophage M1, and they were all negatively related with NK cell resting, macrophage M0, macrophage M2, and mast cell activated. Finally, we verified downregulated levels of SOCS1 and DEFB1 and upregulated CXCR3, BIN2, and CCL3L3 in A875 and A375.

We successfully established ten disulfidptosis-related genes' prediction prognostic signatures for SKCM patients.