The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/STAT3/Arginase-1 Signaling Pathway.

OBJECTIVE: This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis. METHODS: C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway. RESULTS: After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway. CONCLUSION: After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

CCDC43 as a potential therapeutic target of Tian Yang Wan for the treatment of hepatocellular carcinoma by activating the hippo pathway.

Introduction: Hepatocellular carcinoma (HCC) prevalence is rising annually, but the existing treatment strategies are limited; therefore, it is crucial to explore new therapeutic approaches. Methods: Here, we investigate the potential anti-cancer mechanism of an herbal medicine called Tian Yang Wan (TYW) in the treatment of HCC. The relationship of CCDC43 with immunity and cell death was analyzed by bioinformatics. Confirming the tumor suppressor effect of TYW on HCC cells by proliferation, invasion, migration and apoptosis assays. Results: First, we analyzed by proteomics that CCDC43 expression was downregulated after TYW administration and promoted the hippo pathway. Then, a large sample's transcriptome study demonstrated that elevated CCDC43 expression was strongly correlated with clinical traits and a bad prognosis in HCC patients. Next, we observed through multiple advanced algorithms that CCDC43 is involved in a variety of oncology and immunology related pathways. Notably, we found higher tumor immune microenvironment with high CCDC43 expression. Furthermore, we demonstrated that CCDC43 is associated with immune checkpoints and found that it is a sensitive indicator of a large number of chemotherapeutic agents. Subsequently, we conducted experimental investigations to demonstrate the capacity of TYW to impede proliferation and migration, while inducing apoptosis in human HCC cell lines. Finally, we performed analysis of two cell death patterns which showed CCDC43 to be strongly correlated with multiple ferroptosis factors and cuproptosis factors. Discusion: In conclusion, our study comprehensively examined the prognostic, immunological, and therapeutic implications of CCDC43 in HCC, thereby elucidating the therapeutic mechanism of action in TYW.

Network pharmacology analysis of the mechanism of our hospital's experiential prescription in the treatment of Guillain Barré syndrome.

BACKGROUND: This study aimed to explore the active ingredients and potential mechanism of our hospital's Guillain-Barré syndrome (GBS) experiential prescription in the treatment of GBS based on network pharmacology. METHODS: The traditional Chinese medicine system pharmacology (TCMSP) database was used to screen the active ingredients of the eight traditional Chinese medicines (TCMs) of the GBS-experiential prescription, and the Online Mendelian Inheritance in Man (OMIM), GeneCards, and MalaCards databases were used to obtain GBS-related gene targets. The common targets of the experiential prescriptions and GBS-related gene targets were acquired and imported into the STRING database to obtain the protein interaction relationship. Gene oncology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the major mechanism of this prescription. RESULTS: The formula contained at least 154 potential active ingredients and a total of 4,270 unique targets, among which a total of 158 GBS-related disease targets and 70 common targets were found. The key targets included EGFR (Epidermal Growth Factor Receptor), TNF (Tumor Necrosis Factor), ITGAL (Integrin Subunit Alpha L), and CEBPA (CCAAT/Enhancer-Binding Protein Alpha), CPT2 (Carnitine Palmitoyltransferase 2), CRP (C-reactive protein), ICAM1 (Intercellular Adhesion Molecule 1), IL6 (interleukin 6), and PECAM1 (Platelet and Endothelial Cell Adhesion Molecule 1), CREBBP (CREB Binding Protein), etc. The GO enrichment analysis results revealed 116 terms, and the KEGG signaling pathway enrichment analysis results yielded 61 pathways, including influenza A, hepatitis B, malaria, etc. CONCLUSIONS: The development of GBS and the mechanism underlying the effects of the GBS-experiential prescription have common and complex targets, which are worthy of in-depth exploration.

Tumor-induced perturbations of cytokines and immune cell networks.

Until recently, the intrinsically high level of cross-talk between immune cells, the complexity of immune cell development, and the pleiotropic nature of cytokine signaling have hampered progress in understanding the mechanisms of immunosuppression by which tumor cells circumvent native and adaptive immune responses. One technology that has helped to shed light on this complex signaling network is the cytokine antibody array, which facilitates simultaneous screening of dozens to hundreds of secreted signal proteins in complex biological samples. The combined applications of traditional methods of molecular and cell biology with the high-content, high-throughput screening capabilities of cytokine antibody arrays and other multiplexed immunoassays have revealed a complex mechanism that involves multiple cytokine signals contributed not just by tumor cells but by stromal cells and a wide spectrum of immune cell types. This review will summarize the interactions among cancerous and immune cell types, as well as the key cytokine signals that are required for tumors to survive immunoediting in a dormant state or to grow and spread by escaping it. Additionally, it will present examples of how probing secreted cell-cell signal networks in the tumor microenvironment (TME) with cytokine screens have contributed to our current understanding of these processes and discuss the implications of this understanding to antitumor therapies.

[Relationship of TCM syndrome differentiation and manifestation of electrophysiology in patients with peripheral diabetic neuropathy].

OBJECTIVE: To study the relationship between TCM syndrome type and electrophysiological changes of nerves in patients with peripheral diabetic neuropathy (PDN). METHODS: TCM syndrome differentiation of 87 patients with PDN were performed, and the sensory nerve conduction velocity (SCV) of common peroneal nerve and the motor nerve conduction velocity (MCV) of sural nerve were measured as well using surface electrodes. RESULTS: Patients of yang-deficiency type showed the slowest MCV and SCV as well as the lowest compound muscular action potential (CMAP) and sensory nerve action potential (SNAP), with significant difference as compared with those in patients of qi-insufficiency type, heat type, and dampness type, respectively; also significant slower MCV and SCV and lower SNAP than those in patients with blood stasis type. Besides, the SCV and SNAP level in patients with yang-deficiency type were lower as compared with those in patients with yin-deficiency type (all P < 0.05). CONCLUSION: Obvious changes of MCV and SCV could be found in PDN patients of TCM yang-deficiency syndrome, so the abnormal velocity of nerve conduction could be taken as a referential index for diagnosis of patients belonging to that type.