Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.

Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.