PI3K-Akt Signaling Research Articles

Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification.

Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown. In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments. Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes. Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes. This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.

Decoding the role of HIF-1α in immunoregulation in Litopenaeus vannamei under hypoxic stress

Hypoxia poses a significant challenge to aquatic organisms, especially Litopenaeus vannamei (L. vannamei), which play a vital role in the global aquaculture industry. Hypoxia-inducible factor 1α (HIF-1α) is a pivotal regulator of the organism's adaptation to hypoxic conditions. To understand of how HIF-1α affects the immunity of L. vannamei under hypoxic conditions, we conducted a thorough study involving various approaches. These included observing tissue morphology, analyzing the expression of immune-related genes, assessing the activities of immune-related enzymes, and exploring immune-related pathways. Our study revealed that RNA interference (RNAi)-mediated knockdown of HIF-1α markedly reduced HIF-1α expression in the gill (75 to 95%), whereas the reduction ranged from 2 to 43% in the hepatopancreas. Knockdown of HIF-1α resulted in increased damage to both gill and hepatopancreatic tissues in hypoxic conditions. Additionally, immune-related genes, including Astakine (AST), Hemocyanin (HC), and Ferritin (FT), as well as immune-related enzymes such as Acid Phosphatase (ACP), Alkaline Phosphatase (AKP), and Phenoloxidase (PO), exhibited intricate regulatory patterns in response to hypoxia stress following the knockdown of HIF-1α. Transcriptome analysis revealed that HIF-1α knockdown significantly impacts multiple signaling pathways, including the JAK-STAT signaling pathway, Th17 cell differentiation pathways, PI3K-Akt signaling pathway, ErbB signaling pathway, MAPK signaling pathway, chemokine signaling pathway, ribosomal pathways, apoptosis, lysosomes and arachidonic acid metabolism. These alterations disrupt the organism's immune balance and interfere with normal metabolic processes, potentially leading to various immune-related diseases. We speculate that the weakened immune response resulting from HIF-1 inhibition is due to the reduced metabolic capacity, and the existence of a direct regulatory relationship between them requires further exploration. This study greatly advances our understanding of the vital role that HIF-1α plays in regulating immune responses in shrimp under hypoxic conditions, thereby deepening our comprehension of this critical biological mechanism.

Effect of synchronicity of amino acid supply on the synthesis of protein in C2C12 myotubes cultured in vitro

Previous studies inferred that the synthesis rate/efficiency of protein in body tissue is probably affected by synchronicity of different amino acid (AA) supply in its metabolic pool. In order to further observe the influence of synchronicity of AA supply on the synthesis of protein in cell level, a cell culture experiment in vitro was conducted with C2C12 myotubes. C2C12 myotubes were cultured for 24 h, meanwhile the culture medium was replaced for each 8 h. Those myotubes were subjected to 3 treatments (1 for controlled and 2 for tested), control myotubes were cultured with same normal complete medium within the whole 24 h, and the 2 tested myotubes were cultured with asynchronous amino acid supply medium in which the levels of different AAs (Lysine, threonine, methionine, leucine, valine and glutamic acid) either increased and then decreased or decreased and then increased, at different replaced medium time point (at 0, 8, and 16 h). However, during the whole experiment period all the 3 treated myotubes received same amount of each AA. The sample of the myotubes were used for myotube morphology, protein, AA, and proteomic analysis. The results showed that asynchronous AA nutrition affect the synthesis and degradation of myotube proteins, and the AAAS in the medium increase, thus decreasing the synthesis rate of myotube proteins (p < 0.05) and decreasing the diameter of myotubes (p < 0.05). The process of reduced protein synthesis affects the PI3K-AKT and FoxO signaling pathway by downregulating the levels of IRS1 and EGFR, and the degradation amplitude is greater than the synthesis amplitude. Therefore, this study further revealed the effect of the asynchronous supply of amino acids on myotube protein synthesis and the underlying mechanism and provided a theoretical reference for the precision of nutrition to animals.

LncBNIP3 Inhibits Bovine Intramuscular Preadipocyte Differentiation via the PI3K-Akt and PPAR Signaling Pathways.

Intramuscular fat (IMF) content is an economic trait in beef cattle that improves the meat quality. Studies have highlighted the correlation between long noncoding RNAs (lncRNAs) and IMF development. In this study, lncBNIP3 knockdown promoted bovine intramuscular preadipocyte differentiation. RNA-seq analysis of intramuscular preadipocytes with lncBNIP3 knockdown identified 230 differentially expressed genes. The PI3K-Akt and PPAR signaling pathways were enriched. lncBNIP3 interference promoted mRNA and protein expression of key genes in PI3K-Akt signaling pathway. LncBNIP3 interference reversed the effects of an AKT-inhibitor MK-2206 on Akt protein expression and lipid droplet accumulation, promoted mRNA and protein expression of essential genes in the PPAR signaling pathway, and ameliorated the inhibitory effects of a PPARg antagonist GW9662 on lipid accumulation. Therefore, lncBNIP3 inhibition of bovine intramuscular preadipocyte differentiation is likely mediated via the PI3K-Akt and PPAR signaling pathways. This study identified a valuable lncRNA with functional roles in IMF accumulation and revealed new strategies to improve beef quality.

Insights into the Therapeutic Potential of Active Ingredients of Citri Reticulatae Pericarpium in Combatting Sarcopenia: An In Silico Approach

Sarcopenia is a systemic medical disorder characterized by a gradual decline in muscular strength, function, and skeletal muscle mass. Currently, there is no medication specifically approved for the treatment of this condition. Therefore, the identification of new pharmacological targets may offer opportunities for the development of novel therapeutic strategies. The current in silico study investigated the active ingredients and the mode of action of Citri Reticulatae Pericarpium (CRP) in addressing sarcopenia. The active ingredients of CRP and the potential targets of CRP and sarcopenia were determined using various databases. The STRING platform was utilized to construct a protein–protein interaction network, and the key intersecting targets were enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Molecular docking was used to determine the binding interactions of the active ingredients with the hub targets. The binding affinities obtained from molecular docking were subsequently validated through molecular dynamics simulation analyses. Five active ingredients and 45 key intersecting targets between CRP and sarcopenia were identified. AKT1, IL6, TP53, MMP9, ESR1, NFKB1, MTOR, IGF1R, ALB, and NFE2L2 were identified as the hub targets with the highest degree node in the protein–protein interaction network. The results indicated that the targets were mainly enriched in PIK3-AKT, HIF-1, and longevity-regulating pathways. The active ingredients showed a greater interaction affinity with the hub targets, as indicated by the results of molecular docking and molecular dynamics simulations. Our findings suggest that the active ingredients of Citri Reticulatae Pericarpium, particularly Sitosterol and Hesperetin, have the potential to improve sarcopenia by interacting with AKT1 and MTOR proteins through the PI3K-AKT signaling pathway.

Bioinformatics and network pharmacology discover the molecular mechanism of Liuwei Dihuang pills in treating cerebral palsy.

A collection of chronic central motor, postural, and activity restriction symptoms are referred to as cerebral palsy (CP). Previous research suggests that a number of perinatal variables, including hypoxia, may be linked to CP. And the pathophysiological process that causes brain injury in growing fetuses is mostly caused by amniotic fluid infection and intra-amniotic inflammation. Still, there is still much to learn about the molecular mechanism of CP. The goal of this study was to identify the molecular mechanism of Liuwei Dihuang pill (LWDHP) in the treatment of CP using network pharmacology and bioinformatics. The Chinese medicine database provided the LWDHP components and targets, the CP illness gene data set was gathered from a disease, and the expression profile of children with CP was chosen from anther database. Using the Kyoto Encyclopedia of Genes and Genomes and gene ontology databases, a network of interactions between proteins was created, and functional enrichment analysis was carried out. Analysis of traditional Chinese medicine found that the key active ingredients of LWDHP are quercetin, Stigmasterol and kaempferol. Through enrichment analysis, it was found that the hub genes for LWDHP treatment of CP are CXCL8, MMP9, EGF, PTGS2, SPP1, BCL2L1, MMP1, and AR. K EGG analysis found that LWDHP treatment of CP mainly regulates PI3K-Akt signaling pathway, IL-17 signaling pathway, Jak-STAT signaling pathway, NF-kappa B signaling pathway, etc. To summarize, LWDHP regulates immunological and inflammatory variables through a variety of components, targets, and signaling pathways, which plays a significant role in the development and management of CP.

Prolonged Survival of Neutrophils Induced by Tumor-Derived G-CSF/GM-CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma.

Tumor-associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor-derived G-CSF and GM-CSF through the activation of the PI3K-AKT signaling pathway, upregulation of anti-apoptotic Mcl-1 expression, and downregulation of activated Caspase-3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G-CSF and GM-CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.

Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up-Regulating Methyltransferaseand IncreasingSpata, Bcl, and Pik3Series GenesMethylationLevel.

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treatingmale infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI.A total of 52 chemical ingredients were identified from WZYZD.HEand TUNEL staining demonstrated that WZYZD can markedly alleviate OLI.Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencingproved that WZYZD can markedly upregulate the methylated level of Spata, Bcl,and Pik3series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL-2 and PI3K-AKT signaling pathways. The immunofluorescence assay of BCL-2 and SPATA18 proved the aforementioned results.The potential mechanism of WZYZD in treating OLImainly involved recruiting methyltransferase DNMT3A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of Spata, Bcl, and Pik3series genes.

Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulations Reveal the Mechanisms of Cinnamomum tamala in Diabetic Nephropathy Treatment: An In Silico Study

Diabetic nephropathy (DN) is a serious diabetes-related complication leading to kidney damage. Cinnamomum tamala (CT), traditionally used in managing diabetes and kidney disorders, has shown potential in treating DN, although its active compounds and mechanisms are not fully understood. This study aims to identify CT’s bioactive compounds and explore their therapeutic mechanisms in DN. Active compounds in CT were identified using the Indian Medicinal Plants, Phytochemicals and Therapeutics database, and their potential targets were predicted with PharmMapper. DN-related targets were sourced from GeneCards, and therapeutic targets were identified by intersecting the compound–target and disease–target data. Bioinformatics analyses, including the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment studies, were performed on these targets. A protein–protein interaction network was constructed using STRING and Cytoscape. Molecular docking and dynamics simulations validated the most promising compound–target interactions. Six active compounds in CT were identified, along with 347 potential therapeutic targets, of which 70 were DN-relevant. Key targets like MMP9, EGFR, and AKT1 were highlighted, and the PPAR and PI3K-AKT signaling pathways were identified as the primary mechanisms through which CT may treat DN. CT shows promise in treating DN by modulating key pathways related to cellular development, inflammation, and metabolism.

CXCL12/CXCR4 Axis Promotes the Chemotaxis and Phagocytosis of B Cells through the PI3K-AKT Signaling Pathway in an Early Vertebrate.

Chemokines play crucial roles in the regulation of immune cell migration and development. The CXCL12/CXCR4 axis has been extensively studied in mammals, but its regulatory mechanism in teleost fish remains unclear. In this study, we used Nile tilapia (Oreochromis niloticus) as a teleost model to investigate the mediation of the CXCL12/CXCR4 axis in IgM+ B cells. Our findings demonstrate that the CXCL12/CXCR4 axis exhibits chemotactic activity on IgM+ B cells and promotes the phagocytosis of IgM+ B cells. Blocking CXCR4 severely impairs the chemotaxis and phagocytosis of IgM+ B cells invitro and reduces the percentages and numbers of IgM+ B cells that migrate to peripheral blood after pathogen infection invivo. This reduction in migration leads to a decrease in the inflammatory response, an increase in tissue bacterial load, and a decrease in survival rate. We also discovered that the evolutionarily conserved PI3K-AKT signaling pathway and Girdin are involved in the immune response during Streptococcus agalactiae infection. Inhibitors of the PI3K-AKT signaling pathway prevent the chemotaxis and phagocytosis of IgM+ B cells, impair the expression and phosphorylation levels of related proteins invitro, and prevent IgM+ B cells chemotaxis into the peripheral blood after pathogen infection invivo. Furthermore, CXCR4 blocking significantly downregulates the expression of AKT and Girdin. Overall, our study reveals the regulatory mechanism of the CXCL12/CXCR4 axis on IgM+ B cells via the PI3K-AKT signaling pathway in tilapia, suggesting that the functions of the CXCL12/CXCR4 axis in B cells may be conserved between mammals and teleost fish.

Astragaloside IV and cycloastragenol promote liver regeneration through regulation of hepatic oxidative homeostasis and glucose/lipid metabolism

BackgroundThe regenerative capacity of the liver is pivotal for mitigating various forms of liver injury and requires the rapid proliferation of hepatocytes. Aquaporin-9 (AQP9) provides vital support for hepatocyte proliferation by preserving hydrogen peroxide (H2O2) oxidative balance and glucose/lipid metabolism equilibrium within hepatocytes. Our previous study demonstrated that Radix Astragali (RA) decoction promotes liver regeneration by upregulating hepatic expression of AQP9, possibly via two major active constituents: astragaloside IV (AS-IV) and cycloastragenol (CAG). PurposeTo verify that upregulated AQP9 expression in hepatocytes maintains liver oxidative balance and glucose/lipid metabolism homeostasis, and is the main pharmacological mechanism by which AS-IV and CAG promote liver regeneration. Study Design/MethodsEffects of AS-IV and CAG on liver regeneration were scrutinized using a mouse model of 70 % partial hepatectomy (PHx). AQP9-targeted liver regeneration mediated by AS-IV and CAG was verified using AQP9 gene knockout mice (AQP9−/−). The AQP9 protein expression pattern in hepatocytes was determined using tdTomato-tagged AQP9 transgenic mice (AQP9-RFP). Potential mechanisms of AS-IV and CAG on liver regeneration were studied using real-time quantitative PCR, immunoblotting, staining with hematoxylin and eosin, oil red O, and periodic acid-Schiff, and immunofluorescence, immunohistochemistry, HyPerRed fluorescence, and biochemical analyses. ResultsAS-IV and CAG promoted substantial liver regeneration and increased hepatic AQP9 expression in wild-type mice (AQP9+/+) following 70 % PHx, but had no discernible benefits in AQP9−/- mice. Both saponin compounds also helped maintain oxidative homeostasis by reducing levels of oxidative stress markers (reactive oxygen species [ROS], H2O2, and malondialdehyde) and elevating levels of ROS scavengers (glutathione and superoxide dismutase) in AQP9+/+ mice post-70 % PHx. This further activated the PI3K-AKT and insulin signaling pathways, thereby fostering liver regeneration. Furthermore, AS-IV and CAG both promoted hepatocyte glycerol uptake, increased gluconeogenesis, facilitated lipolysis, reduced glycolysis, and inhibited glycogen deposition, thus ensuring the energy supply required for liver regeneration. ConclusionThis research is the first to demonstrate AS-IV and CAG as major active ingredients of RA that promote liver regeneration by upregulating hepatocyte AQP9 expression, improving hepatocyte glucose/lipid metabolism, and reducing oxidative stress damage, constituting a crucial pharmacological mechanism underlying the liver-protective effects of RA. The augmentation of hepatocyte AQP9 expression underscores an important aspect of the Qi-tonifying effect of RA. This study establishes AQP9 as an effective target for regulation of liver regeneration and provides a universal strategy for clinical drug intervention aimed at enhancing liver regeneration.

Exploration of the clinical characteristics and potential mechanisms of liver injury induced by proton pump inhibitors

ABSTRACT Background and aims Data related to clinical characteristics and potential mechanisms of proton pump inhibitors (PPIs)-related liver injury are sparse, thus the purpose of this study is to summarize the clinical features and molecular mechanisms of PPIs-induced liver injury. Methods We collected case report on liver injury induced by PPIs in English and Chinese for retrospective analysis. Clinical and pathological data and outcomes were obtained and analyzed. Network pharmacology and molecular docking techniques were employed to examine the mechanism. Result Twenty-three patients with PPIs-induced liver injury were enrolled. PPIs-induced liver injury is a rare adverse reaction, ranging from asymptomatic elevated transaminases to fulminant liver failure. Omeprazole was the drug with the highest number of associated reports. The most common symptom was fatigue. The most common liver injury pattern was hepatocellular injury. A total of 13 intersection targets of PPIs and liver injury were screened, and the top 10 targets were included, and the PI3K-Akt signaling pathway was significantly enriched. The results of molecular docking implied that the PPIs could combine well with key targets. Conclusion Patients receiving long-term treatment with PPIs should consider monitoring liver function. PPIs exhibit considerable capacity in liver injury via especially the PI3K-Akt signaling pathway.

Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of Guanxin Shutong capsule in treating heart failure.

The Guanxin Shutong capsule (GXST), a traditional Chinese medicine, is commonly used for treating cardiovascular disease, it has shown efficacy in improving symptoms and enhancing the quality of life for patients with heart failure (HF). However, the specific mechanism of action of GXST in HF remains unclear. In this study, we employed a comprehensive approach combining network pharmacology, molecular dynamics (MD) simulations, and in vitro validations to investigate the potential targets and molecular mechanisms of GXST against HF. We collected active ingredients and target genes of GXST, as well as related genes of HF, from multiple public databases. Using bioinformatics analysis, we constructed networks of ingredients-disease-targets and performed functional annotations of the core targets. MD simulations were conducted to verify the binding between the core protein-ligand complexes. In vitro evaluations, including cell proliferation, apoptosis, and protein expression in human umbilical vein endothelial cells (HUVECs) and H9C2 cells were treated with GXST, were performed for pharmacodynamics evaluation. Network analysis revealed 320 intersection genes and 74 active ingredients in the Herbs-ingredients-target genes-disease network. We identified key active ingredients and target genes that overlapped. The KEGG pathways of the intersection genes were primarily enriched in the PI3K-Akt signaling pathway and apoptosis. The protein-protein interaction network highlighted proteins such as AKT1, VEGFR2, and eNOS. MD simulations confirmed stable docking and lower binding energy between 4 identified ingredients (kaempferol, quercetin, (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl) chroman-4-one, and ellagic acid) and their respective core proteins (VEGFR2, eNOS, and AKT). In vitro experiments demonstrated the protective effects of GXST against H2O2-induced apoptosis in both HUVECs and H9C2 cells. Notably, consistent with the in silico predictions, GXST effectively activates the VEGFR2/AKT/eNOS signaling pathways in HUVECs. This study provides insights into the underlying mechanism of GXST's therapeutic effects in heart failure. The involvement of the VEGFR2/AKT/eNOS signaling pathways suggests their importance in further elucidating and applying GXST in the clinical treatment of heart failure.

Microarray analysis of microRNA profiles for assessing the therapeutic effects of sodium thiosulfate on end-stage renal disease combined with coronary artery calcification.

Coronary artery calcification (CAC) is a common complication in patients with end-stage renal disease (ESRD), which causes of increased cardiovascular mortality in maintenance hemodialysis patients. This study examined how sodium thiosulfate (STS) treatment affects the microRNA (miRNA) expression profiles of ESRD patients combined with CAC. A total of 18 patients with ESRD complicated with CAC were assigned to a control group that received conservative treatment or a test group that received STS treatment. The 2 groups were then sub-divided into a CGBT group (control group before treatment), TGBT group (test group before treatment), CGAT group (control group after treatment), and TGAT group (test group after treatment). Samples of peripheral venous blood were collected for analysis of biochemical indexes (hs-CRP, ALB, CHO, TG, Ca, P, BUN, Cr, bALP, iPTH, and FGF23) and used to screen for differentially expressed miRNAs that were displayed by hierarchical clustering and in a volcano plot. The functional roles of miRNA target genes were analyzed by Gene Ontology and Kyoto Encycolopedia of Genes and Genomes pathway analyses. Several miRNAs in serum samples were identified using quantitative real time PCR. STS treatment did not significantly change the biochemical indexes. A microarray analysis identified 67 miRNAs that were differentially expressed in the TGAT group vs. the TGBT group, and 28 -miRNAs that were differentially expressed in the CGAT group vs. the CGBT group. The miRNA target genes were associated with signal transduction, transcriptional regulation, cytoplasm and protein binding processes, the MAPK signaling pathway, PI3K-Akt signaling pathway, and various pathways in cancer. Validation experiments confirmed the suppressive effect of STS treatment on miR-337-5p/miR-409-5p expression and the promotive effect of STS on miR-376a-3p expression. MiR-337-5p/miR-409-5p/miR-376a-3p might be key regulators involved with the therapeutic effects of STS treatment in ESRD patients associated with arterial calcification.

Evaluation and Analysis of Traditional Chinese Medicine Treatment of Bovine Viral Diarrhea/Mucosal Disease Based on Network Pharmacology and In Vitro Studies

Background Bovine viral diarrhea/mucosal disease (BVD-MD) is widely distributed worldwide. The disease causes serious economic losses to animal husbandry every year. Finding targeted antiviral drugs proves to be an effective strategy. Purpose This study was based on network pharmacology and in vitro studies to analyze the potential of traditional Chinese medicine (TCM) in the treatment of BVD-MD. Methods The intersection targets between TCM and the disease were identified. Network topology analysis and protein–protein interaction (PPIs) networks were performed. Intersection targets were analyzed for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The molecular docking and molecular dynamics simulation methods were used to reveal the degree of binding of core components to key target genes. Characterization of the anti-Bovine viral diarrhea virus (BVDV) effect of TCM by cytotoxicity and in vitro studies. Results The results revealed the selection of five key Chinese medicines, along with 206 targets associated with BVD-MD. The toll-like receptor, PI3K-AKT, and tumor necrosis factor (TNF) signaling pathways were closely related to the five TCMs. AKT1, EGFR, HSP90AA1, and MAPK1 had good binding with quercetin, the core component of Chinese medicine. Molecular dynamics analysis showed that quercetin exhibited complex stability with AKT1. In vitro studies have demonstrated that the inhibitory effect of quercetin on BVDV is mainly in the initial phase. Quercetin inhibited the expression of AKT1. Conclusion The mechanism of BVDV inhibition by the core Chinese medicines is closely related to MAPK1, AKT1, TNF, and HSP90AA1, with the reduction of AKT1 ultimately affecting viral expression.

Exploring the Mechanism of Centipeda minima in Treating Nasopharyngeal Carcinoma Based on Network Pharmacology.

Centipeda minima (CM) is a traditional Chinese herbal medicine used for the treatment of sinusitis and rhinitis, and it possesses anti-cancer properties. However, the mechanism of CM in the treatment of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the mechanism of CM in the treatment of NPC using a network pharmacology approach. The active components and targets of CM and NPC were screened using TCMSP, SwissTarget, and GeneCards database. The association between CM components and NPC targets or pathways was analyzed using String, Cytoscape 3.9.1, David 6.7, and AutoDock Vina. The Sangerbox platform was used to conduct differential expression and Kaplan-Meier survival analysis of core genes. We identified 17 active compounds of CM and 146 corresponding targeted proteins in NPC. These targets may modulate pathways in cancer, PI3K-Akt, apoptosis, prolactin, relaxin, and TNF signaling. The top 5 core genes of the PPI network were found to be AKT1, STAT3, CASP3, EGFR, and SRC, which may be the main targets of CM in treating NPC. Molecular docking confirmed the binding energies of quercetin with CASP3, 8-Hydroxy-9,10-diisobutyryloxythymol with AKT1, and plenolin with AKT1, which were particularly low, suggesting robust and stable interactions. The expression levels of AKT1, CASP3, EGFR, SRC, MMP9, CCND1, and PTGS2 were significantly higher in head and neck squamous cell carcinoma (HNSC) samples compared to normal samples. In addition, the hub genes could predict the prognosis of HNSC as the Kaplan-Meier survival curve showed that patients with lower expressions of AKT1, STAT3, CASP3, EGFR, MMP9, ESR1, PTGS2, and PPARG had better overall survival. By conducting a network pharmacology approach, we revealed the main ingredients, key targets, and regulatory pathways of Centipeda minima in the treatment of NPC.

High soybean dietary supplementation with quercetin improves antioxidant capacity of spotted sea bass Lateolabrax maculatus

This study aimed to examine the effect of quercetin (QUE) on the antioxidant capacity of spotted sea bass that were fed a high soybean meal diet. 44 % fish meal was used as a healthy control, and soybean meal instead of 50 % fish meal induced a negative reaction. On this basis, 0.25, 0.50, 0.75, and 1.00 g/kg QUE were added, respectively. A total of 540 spotted sea bass were randomly allocated into 6 groups and provided with diets that corresponded to their respective groups for a duration of 56 days. The results showed a significant decrease in the antioxidant capacity of spotted sea bass fed a high soybean meal diet. The inclusion of QUE considerably improved the antioxidant capacity of spotted sea bass. This was evidenced by the notable rise in glutathione (GSH) levels in the intestine and liver, as well as the elevated levels of catalase (CAT) and total antioxidant capacity (T-AOC) in the liver. Furthermore, transcriptome results showed that the S-transferase (GST) gene in the glutathione metabolism pathway was significantly down-regulated by high soybean meal, while with the addition of QUE, noteworthy alterations in genes associated with the PI3K-Akt signaling pathway, Foxo signaling pathway, and AMPK signaling pathway. These signaling pathways are involved in signal transduction, apoptosis, and oxidative stress. On the other hand, genes related to energy metabolism, such as phosphoenolpyruvate carboxykinase (PEPCK), were observed to be upregulated. These pathways could potentially contribute to the antioxidant properties of QUE.

Comparative Transcriptomic Profiling of Brain and Liver in Phoenix Barbs (Spinibarbus denticulatus denticulatus) with Differential Growth Rates

Phoenix barb (Spinibarbus denticulatus denticulatus) is a notable fish species in South China and is valued for its ecological and economic importance. To elucidate the molecular basis underlying its growth, we collected transcriptome profiles from the brains and livers of individual fish with different growth rates and compared differentially expressed genes (DEGs) at 3 and 9 months after hatching (MAH). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the pathways associated with growth were predominantly enriched in fatty acid biosynthesis, AMPK signaling, PI3K-Akt signaling, estrogen signaling, and protein metabolism. Notably, a greater number of DEGs from the fast-growing group were associated with these pathways at the early growth stage (3 MAH) than at the later stage (9 MAH). Real-time quantitative PCR results further validated that the genes involved in these pathways exhibited higher expression levels in fast-growing samples. This study enhances our understanding of the genetic mechanisms underlying growth rate differences and provides valuable genetic resources for future growth-related molecular breeding programs of phoenix barbs.

Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.

SPECC1 as a pan-cancer biomarker: unraveling its role in drug sensitivity and resistance mechanisms

Previous studies have shown a relationship between SPECC1 and the prognosis of breast cancer, indicating a potential function for SPECC1 in the initiation and progression of cancer. However, the role played by SPECC1 in other tumors is not yet known. Therefore, we used bioinformatics techniques to conduct a thorough investigation into the possible mechanism of SPECC1 in pan-cancer, analyzing data reported in the literature as well as databases such as GTEx and CCLE, cBioportal, TCGA, and UCSC XENA. Comparing the results with matching normal tissues, the majority of cancers, including pancreatic adenocarcinoma (PAAD) and breast invasive carcinoma (BRCA), exhibited higher levels of SPECC1, while hepatocellular carcinoma (HCC) showed lower expression levels. SPECC1 was also found to be genetically mutated in endometrial cancer, sarcoma, and esophageal cancer. The prognosis of lung adenocarcinoma, kidney papillary cell carcinoma, and breast cancer is highly correlated with dysregulation of SPECC1 expression. This work helps guide clinical therapy by highlighting the sensitivity of tumor-treating medicines and the prognostic importance of SPECC1 in various malignancies. KEGG pathway enrichment analysis revealed focused adhesion, collagen-containing extracellular matrix (collagen), and the primary enrichment domains for SPECC1-related genes. These findings were obtained through gene annotation (GO) examination of SPECC1 expression. Primary mediators of the cytokine-cytokine receptor interaction include PICOC1-associated genes, cell-substrate junction genes, and extracellular matrix containing collagen. PICOC1-associated genes primarily mediate the PI3K-AKT signaling pathway. Drug sensitivity assay showed that SPECC1 high-expressing cell lines were more sensitive to docetaxel, doxorubicin, etc. In conclusion, the current study shows how SPECC1 is expressed in different cancers and how this expression relates to the prognosis of the tumor. It also revealed the mutations and copy number variations of SPECC1 in various tumors and its potential involvement in cellular pathway regulatory networks and cytological processes. This study examines the relationship between immune genes, cellular infiltration, and immunological scores in the tumor microenvironment, which explain the severity of the disease. This study looks at the response of SPEC1 expression to anticancer therapy. Explains the prognostic significance and drug response of SPECC-1.