Based on the "lung-gut axis" theory, this study explored the effects of Maxing Kugan Decoction(Mxd) on inflammation and intestinal barrier and flora in rats with bleomycin-induced idiopathic pulmonary fibrosis(IPF). A total of 24 male SD rats were randomly divided into four groups: a control group, a model group, a positive control group and an Mxd treatment group, with 6 rats in each group. After 5 days of quarantine and adaptive feeding, the IPF pathological model was induced by intratracheal instillation of bleomycin under laryngoscopic assistance in the model group, positive control group, and Mxd treatment group. Gastric gavage was initiated after successful modeling, and all SD rats were sacrificed on the 15th day post gavage. HE staining and Masson staining were used to observe histopathological changes of lung tissue, while HE staining was adopted to evaluate jejunal pathological changes. Enzyme-linked immunosorbent assay(ELISA) was performed to detect the serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in rats. AB-PAS staining was employed to determine the number of goblet cells in jejunal mucosal tissue. Immunofluorescence assay was used to detect the expression of zonula occludens-1(ZO-1) and occludin in rat jejunum, and 16S rDNA sequencing was conducted to analyze the intestinal microbiome of all rats. The results showed that the model group exhibited severe damage to jejunal mucosa and lung tissue accompanied by massive inflammatory cell infiltration, while the two treatment groups demonstrated partial structural defects with a small amount of inflammatory cell infiltration in the lungs and jejuna of rats. Compared with the control group, the model group showed significantly decreased body weight, number of goblet cells, and expression of ZO-1 and occludin proteins(P<0.01), while these indicators were notably increased after intervention in the two treatment groups(P<0.05 or P<0.01). According to 16S rDNA sequencing results, Mxd could regulate the richness and diversity of intestinal flora in rats. KEGG pathway analysis indicated that Mxd regulated pathways such as oxidative phosphorylation, amino sugar, and nucleotide sugar metabolism of intestinal flora in rats. In conclusion, the alteration of intestinal microbiome may be one of the potential mechanisms underlying the therapeutic effect of Mxd on IPF. Mxd can regulate the structure of intestinal microbiome, increase the abundance of beneficial bacteria, and reduce the number of harmful bacteria, as well as protect intestinal barrier and inhibit inflammatory response.

Acute lung injury (ALI) is a life-threatening inflammatory syndrome with limited pharmacological treatment options. Kumatakenin, a plant-derived flavonoid with recognized anti-inflammatory potential, has not been explored in inflammatory lung injury. Here, we investigated the protective effect of Kumatakenin in lipopolysaccharide (LPS)-induced ALI and examined the associated mechanism. Kumatakenin markedly alleviated lung injury, as evidenced by improved histopathology, reduced pulmonary edema, and decreased inflammatory cytokine production. It also attenuated neutrophil accumulation and activation in the lung, accompanied by suppression of neutrophil extracellular trap formation and oxidative stress. Mechanistically, Kumatakenin increased PRL2 protein abundance without altering its mRNA expression, suggesting post-transcriptional regulation. This effect was associated with reduced CMA-related PRL2 turnover, as indicated by decreased LAMP2A expression and weakened interaction of PRL2 with Hsc70 and LAMP2A. Moreover, pharmacological activation of CMA with QX77 largely reversed the effects of Kumatakenin on PRL2 protein abundance, oxidative stress, and NET formation. Collectively, these findings indicate that Kumatakenin alleviates LPS-induced ALI by interrupting neutrophil-driven inflammatory amplification and, at least in part, suppressing CMA-associated PRL2 degradation. This study highlights Kumatakenin as a promising natural lead compound for inflammatory lung disorders and identifies the CMA/PRL2 axis as a candidate therapeutic pathway.

INTRODUCTION:Acute Lung Injury (ALI) is a serious complication of many diseases and can progress to Acute Respiratory Distress Syndrome (ARDS) without intervention. The current study aimed to determine the effect of Maxing Kugan Decoction (MXKGD) on an Oleic Acid (OA)-induced rat model of ALI while also exploring the regulatory effects of MXKGD on the PI3K/AKT signaling pathway and gut microbiota. METHODS:Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry (UPLC-QTOF/MS) was employed to determine the chemical ingredients of MXKGD. The therapeutic effects of different doses of MXKGD in treating OA-induced ALI were investigated using histopathology, ELISA assays, and immunofluorescence analysis. Additionally, network pharmacology and 16S rRNA sequencing were utilized to explore the underlying mechanisms of MXKGD in ALI treatment. RESULTS:Through UPLC-QTOF/MS analysis, a total of 104 compounds were identified in MXKGD, including flavonoids, alkaloids, triterpenoids, glycosides, organic acids, and cyclic peptides. Pharmacodynamic results demonstrated that MXKGD could mitigate histomorphological changes in OA-induced ALI, suppress inflammation and oxidative stress, while promoting the proliferation and differentiation of alveolar type II (AT II) cells to repair the alveolar epithelial-microvascular endothelial barrier. Network pharmacology, molecular docking, and subsequent experimental validation revealed that MXKGD upregulates the expression of p-PI3K and p-AKT proteins, thereby activating the PI3K/AKT signaling pathway. Furthermore, MXKGD rebalanced the disturbance of gut microbiota and associated metabolic levels of short-chain fatty acids (SCFAs) to regulate the inflammatory response. DISCUSSION:This study suggests that MXKGD exerts anti-inflammatory effects and protects the alveolar epithelial- microvascular endothelial barrier in ALI models by activating the PI3K/AKT signaling pathway and modulating the abundance of beneficial gut bacteria. However, further metabolomic experiments are required to confirm its precise mechanism of action. CONCLUSION:The data indicate that MXKGD can effectively inhibit the development of ALI by reducing inflammation and regulating the balance of intestinal microbiota. MXKGD may serve as a potential new therapeutic option for treating ALI.

Angelica sinensis (AS) is a widely used medicinal and culinary herb frequently considered critical in traditional prescriptions. Modern pharmacological studies have validated its beneficial effects, including nourishing, blood activation, anti-inflammatory and analgesic properties, liver and kidney protection, and tumor inhibition. Due to the lack of existing reviews on AS in treating digestive system tumors (DS-T), this study investigated the pharmacological effects of AS and its primary active components in combating DS-T from three main perspectives. First, we have summarized its mechanisms for treating various DS-T by analyzing in vitro and in vivo experimental studies. Second, we analyzed frequently used radiotherapy drugs and determined the potential of AS and its active ingredients to reduce toxicity and enhance efficacy. Additionally, AS can be integrated into both regular and medicated diets, thereby effectively preventing tumor development and facilitating post-surgery and radiotherapy recovery. In conclusion, AS exhibits potential as an anti-DS-T drug, providing a theoretical foundation for daily dietary and clinical medicinal use and offering insights for future scientific research and innovation.

Vascular dementia (VaD) ranks as the second most prevalent subtype of dementia, surpassed only by Alzheimer’s disease (AD). The maintenance of neurological function and cerebral homeostasis critically depends on precisely regulated blood flow within the intricately organized cerebrovascular network. Disruptions in cerebral hemodynamics may impair neurovascular homeostasis, thereby inducing pathophysiological cascades characterized by oxidative stress, neuroinflammation, and neuronal degeneration. Emerging evidence identifies cerebrovascular dysregulation and impaired neurovascular coupling (NVC) as primary pathogenic mechanisms underlying VaD, emphasizing the necessity to elucidate their complex interplay. Cerebrovascular endothelial cells exhibit remarkable heterogeneity, serving dual roles as both architectural components of the blood–brain barrier (BBB) and functional regulators of NVC. Furthermore, pericytes residing abluminal on capillary endothelia demonstrate critical involvement in hemodynamic modulation through contractile regulation of microvascular tone, while concurrently maintaining BBB integrity through dynamic paracrine signaling. This study examines cerebrovascular endothelial-neuronal interactions within the neurovascular unit (NVU) framework, analyzing their bidirectional regulatory mechanisms and therapeutic potential in cognitive dysfunction remediation. The pathophysiological progression of VaD manifests through multiple interdependent pathways, including cerebral hypoperfusion, oxidative stress cascades, neuroinflammatory responses, mitochondrial dysregulation, and electrolyte homeostasis perturbations. Through three interventional axes: (1) BBB fortification strategies; (2) cerebral hemodynamic optimization and NVC enhancement; (3) nanotherapeutic platforms integrating endothelial-specific molecular targets we systematically evaluate endothelial-centric therapeutic paradigms. This multi-modal approach proposes novel mechanistic insights and clinical translation frameworks for VaD management.

Angelica sinensis (AS) is a widely used medicinal and culinary herb frequently considered critical in traditional prescriptions. Modern pharmacological studies have validated its beneficial effects, including nourishing, blood activation, anti-inflammatory and analgesic properties, liver and kidney protection, and tumor inhibition. Due to the lack of existing reviews on AS in treating digestive system tumors (DS-T), this study investigated the pharmacological effects of AS and its primary active components in combating DS-T from three main perspectives. First, we have summarized its mechanisms for treating various DS-T by analyzing in vitro and in vivo experimental studies. Second, we analyzed frequently used radiotherapy drugs and determined the potential of AS and its active ingredients to reduce toxicity and enhance efficacy. Additionally, AS can be integrated into both regular and medicated diets, thereby effectively preventing tumor development and facilitating post-surgery and radiotherapy recovery. In conclusion, AS exhibits potential as an anti-DS-T drug, providing a theoretical foundation for daily dietary and clinical medicinal use and offering insights for future scientific research and innovation.

BACKGROUNDS:Acute lung injury (ALI) is a lethal condition characterized by uncontrolled pulmonary inflammatory responses, with high morbidity and mortality rates that pose a significant threat to patient health. The persistent retention of neutrophils in lung tissue and subsequent inflammatory damage represents a primary mechanism underlying the early onset of ALI disorders. In recent years, pharmaceutical research targeting these pathological processes has garnered considerable attention. Traditional Chinese medicines (TCM) and their active ingredients, known for their safety and stability, show promising potential in treating ALI through their ability to modulate neutrophil function via multiple pathways. PURPOSE:This review examines the mechanisms of neutrophil involvement in the pathogenesis of ALI, investigates potential therapeutic targets and pathways through which Chinese medicines and their active ingredients regulate neutrophil function, and provides a theoretical foundation for developing novel clinical treatment strategies. METHODS:A comprehensive literature search was conducted using multiple databases, including Science Direct, PubMed, Google Scholar, and Web of Science. Search terms included 'lung injury,' 'acute lung injury,' 'inflammatory lung injury,' 'inflammation,' 'active ingredient,' 'herbal,' 'traditional Chinese medicine,' 'mechanism,' 'drug,' and 'neutrophils.' The selected literature was systematically categorized and analyzed. RESULTS:Our review reveals that TCM and active ingredients influence neutrophil function through four primary mechanisms to impede ALI progression: 1) reduction of neutrophil-mediated uncontrolled inflammatory responses by suppressing neutrophil hyperactivation and inhibiting neutrophil migration and infiltration; 2) attenuation of lung tissue inflammatory damage by inhibiting neutrophil-produced cytotoxic substances, including elastase granules, neutrophil extracellular traps (NETs), and reactive oxygen species (ROS); 3) suppression of inflammatory responses by decreasing the secretion of neutrophil-derived cytokines, such as interleukin (IL) -1β, IL-6 and tumor necrosis factor-alpha (TNF-α); and 4) enhancement of neutrophil phagocytosis and accelerate the removal of apoptotic neutrophils to eliminate harmful pathogens and promote late-stage tissue repair. These findings demonstrate that Chinese medicines and their active ingredients exhibit significant therapeutic potential in ALI disorders through the modulation of neutrophil function, providing a robust theoretical framework for their clinical applications. CONCLUSION:Traditional Chinese medicines and their active ingredients demonstrate significant anti-inflammatory efficacy through multiple mechanisms of neutrophil function regulation, showing considerable promise for the treatment of ALI with broad clinical applications.

This study aimed to investigate the therapeutic effects of Qingzao Jiufei Decoction (QJD) on idiopathic pulmonary fibrosis (IPF) and its regulatory mechanism involving the TGF-β/Smad signaling pathway. Rats were divided into six groups: control, model, pifenidone (PFD), QJD Low Dose (QJD-L), QJD Medium Dose (QJD-M), and QJD High Dose (QJD-H). IPF was induced using bleomycin. Histopathological and ultrastructural changes in the lung tissue were analyzed. Levels of α-smooth muscle actin (α-SMA), collagen I (COL-1), fibronectin (FN1), TGF-β1, Smad2/3, and p-Smad2/3 proteins were measured. A TGF-β1-induced HFL-1 cell model was used to investigate the effects of QJD on the expression of α-SMA, COL-1, and FN1. Additionally, the TGF-β1 signaling agonist SRI-011381 was used to further determine the role of the TGF-β/Smad signaling pathway. Results: In vivo, compared with the control group, rats in the model group showed significantly reduced dietary and water intake, along with an increased lung coefficient. Lung tissue showed infiltration of inflammatory cells, thickening of alveolar walls, and marked signs of fibrosis. Additionally, edematous alveolar type II epithelial cells with severe fibrosis were observed, characterized by swollen and deformed intracellular organelle structures and a reduced number of rough endoplasmic reticulum. Levels of α-SMA, COL-1, FN1, TGF-β1, and p-Smad2/3 were significantly elevated. Treatment with QJD or PFD markedly alleviated BLM-induced symptoms. In vitro, whereas TGF-β1 induction significantly upregulated the expression of FN1, COL-1, and α-SMA, these effects were significantly attenuated by QJD treatment. Activation of the TGF-β/Smad signaling pathway with the TGF-β1 agonist SRI-011381 increased FN1, COL-1, and α-SMA expression and aggravated pulmonary fibrosis. However, QJD reversed the fibrotic effects induced by SRI-011381, suggesting that QJD ameliorates pulmonary fibrosis by inhibiting TGF-β/Smad signaling pathway. The findings of this study suggest that QJD attenuates and reverses the progression of pulmonary fibrosis by modulating the TGF-β/Smad signaling pathway.

Liver injury is a common complication associated with colitis. 10-hydroxy-2-decenoic acid (10-HDA), a bioactive component found in royal jelly, is recognized for its significant anti-inflammatory properties. In this study, a colitis-associated liver injury model was induced in C57BL/6 mice by administering 2.5 % dextran sulfate sodium (DSS) for 7 days. Mice were randomly assigned to control, DSS, and DSS + 10-HDA groups. The bioavailability of 10-HDA was confirmed through mass spectrometry analysis. Our results indicate that 10-HDA significantly mitigated DSS-induced hepatic injury, as evidenced by reduced histopathological scores, decreased liver enzyme levels, and lower concentrations of inflammatory cytokines. Furthermore, 10-HDA effectively downregulated the expression of TLR9 and alleviated the activation of pyroptosis-associated proteins, including NLRP3, NLRP1, ASC, and N-GSDMD. Overall, 10-HDA ameliorates DSS-induced liver injury in the ulcerative colitis (UC) model by modulating NLRP1/NLRP3-mediated pyroptosis and regulating the immune response, highlighting the therapeutic potential of 10-HDA in managing hepatic complications associated with UC.

Background/Objectives: Momordica charantia L. (M. charantia), a widely cultivated and frequently consumed medicinal plant, is utilized in traditional medicine. Cucurbitane-type triterpenoids, significant saponin components of M. charantia, exhibit hypoglycemic effects; however, the underlying mechanisms remain unclear. Methods: This study utilized comprehensive network pharmacology to identify potential components of M. charantia cucurbitane-type triterpenoids that may influence type 2 diabetes mellitus (T2DM). Additionally, molecular docking and molecular dynamics studies were performed to assess the stability of the interactions between the selected components and key targets. Results: In total, 22 candidate active components of M. charantia cucurbitane-type triterpenoids and 1165 disease targets for T2DM were identified through database screening. Molecular docking and molecular dynamics simulations were conducted for five key components (Kuguacin J, 25-O-methylkaravilagenin D, Momordicine I, momordic acid, and Kuguacin S) and three key targets (AKT1, IL6, and SRC), and the results demonstrated stable binding. The experimental results indicate that the interactions between momordic acid-AKT1 and momordic acid-IL6 are stable. Conclusions: Momordic acid may play a crucial role in M. charantia’s regulation of T2DM, and AKT1 and IL6 seem to be key targets for the therapeutic action of M. charantia in managing T2DM.

Acute lung injury (ALI) is a severe inflammatory lung disorder that requires effective therapeutic strategies. Ephedrine (EPH) is the main active component found in medicinal plants of the Ephedra genus and is commonly used to modulate inflammatory responses in various diseases. Hypoxia-inducible factor 1-alpha (HIF1α) is a subunit of hypoxia-inducible factor 1 (HIF1), which plays a critical regulatory role in cellular responses under hypoxic conditions. Moreover, the degradation pathway of HIF1α is regulated by the deubiquitinase Ovarian Tumour Domain-containing Ubiquitin Aldehyde Binding Protein 1 (OTUB1). The aim of this study is to investigate the therapeutic effects of EPH on ALI and its potential therapeutic mechanism. We utilised a lipopolysaccharide (LPS)-induced ALI mouse model and employed various methods for evaluation. Ultimately, our research findings demonstrate that EPH exhibits anti-ALI effects, with the involvement of HIF1α and OTUB1 in the pharmacological actions of EPH. In conclusion, our study results demonstrate that EPH exhibits anti-ALI effects and exerts its protective effects through modulation of the OTUB1 and HIF1α pathways. Our research findings not only lay the foundation for expanding the medicinal applications of EPH but also provide direction for seeking improved treatment strategies for ALI.

Traditional Chinese medicine (TCM) syndromes play a vital role in treating diabetes, and genetics have long been recognized as influcing factor of diabetes. This study aimed to confirm the latent classes of TCM syndromes in type 2 diabetes mellitus (T2DM) patients and to explore the association between genetic risk and those TCM syndromes classes. A total of 1045 T2DM patients from the Ningxia province of China were included in this study. The TCM syndromes scale was used to collect the syndrome differentiation information. Seven gene polymorphisms were assessed using standard procedures. Latent class analysis was used to determine unobserved classes of TCM syndromes. Multinomial logistic regression was employed to examine the relationships between gene risk and classes of TCM syndromes. The optimal number of latent classes was 3, labeled as blood stasis, phlegm dampness and depression heat, and blood deficiency and damp heat type. Almost 12% of the sample belonged to the blood deficiency and damp heat group. Participants with higher levels of gene risk score (RRR = 1.85, 95% CI: 1.18, 2.90) were more likely to have blood deficiency and damp heat type than those with lower levels of gene risk score. The findings provides a molecular biology basis for the objective study of TCM syndromes in T2DM and achieved a combination of macro and micro levels, and also provides a reference for patients to undergo syndrome differentiation and personalized intervention.

ObjectivesTrigonella foenum-graecum L. (HLB) exhibits promising pharmacological properties for the treatment of type 2 diabetic nephropathy (DN). This study aims to enhance the understanding of HLB’s pharmacodynamic effects and elucidate the mechanisms underlying its therapeutic potential in DN.MethodsThe pharmacodynamic effects of HLB were initially evaluated in a murine DN model through the oral administration of an aqueous extract of HLB. The primary bioactive constituents were subsequently identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Network pharmacology analysis was integrated with these data to uncover potential molecular targets of HLB in DN. Key renal metabolites were profiled using untargeted metabolomics, followed by metabolic pathway enrichment analysis conducted with the MetaboAnalyst 6.0 platform, which facilitated the identification of relevant metabolic pathways through which HLB modulates DN. Finally, quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot (WB) techniques were employed to validate the expression levels of key genes and proteins, thereby confirming the molecular mechanisms underlying the effects of HLB in DN.ResultsAnimal experiments indicated that HLB significantly improved blood glucose regulation and renal function while reducing oxidative stress and abnormalities in lipid metabolism in diabetic mice. A total of 34 compounds and 159 potential therapeutic targets were identified as key active components of HLB. The untargeted metabolomics analysis revealed 61 critical metabolites, among which the PI3K-Akt-ERK signaling pathway—known to be involved in diabetes—was highlighted as a crucial pathway. QRT-PCR and WB analyses demonstrated that HLB upregulated the expression of MAPK1, MAPK3, AKT1, and PI3K.ConclusionThese results suggest that HLB may alleviate DN by modulating oxidative stress and lipid metabolism. Its effects are likely mediated through the PI3K-Akt-ERK signaling pathway, along with the upregulation of MAPK1, MAPK3, AKT1, and PI3K expression. This study lays the groundwork for further investigations into the molecular mechanisms underlying HLB’s action in DN.

The Maxing Kugan Decoction (MKD) is a traditional Chinese medicine prescription specifically designed for respiratory infectious diseases in the northwest region, particularly targeting influenza during the winter and spring seasons. While its clinical efficacy has been established, there is a significant gap in its toxicological safety. This study aims to evaluate the subacute oral toxicity of MKD in rats, focusing on its effects on food consumption, weight, vital signs, haematological parameters, and organ histology. To determine subacute oral toxicity, MKD was administered by gavage at 12.6, 25.2, or 50.4 g/kg/day to male and female rats for 90 days. Meanwhile, the general behavior, body weight, food intake, urine routine parameters, blood biochemical, hematological parameters, coagulation parameters, organ coefficients and organ histopathology were recorded and analyzed. The results showed that experimental rats were healthy and displayed no evidence of toxicity. Furthermore, no mortality or abnormalities in general conditions, including diet and weight, were noted. While the levels of a few indicators changed during administration, their levels remained within the normal range and were not correlated with dose or gender. Overall, no toxicological significance was recorded. Meanwhile, histopathological analysis did not identify abnormal pathological changes in tissue structure and cell morphology across organs, and no significant delayed toxic reactions were detected during the remission period. Overall, our results indicated that oral administration of 50.4 g/kg (60 times the clinical dose in humans) of MKD for three months is safe for SD rats and is not associated with toxic side effects.

Objective: The Traditional Chinese Medicine Qingzao Jiufei Tang decoction (QZJFD) is effective for the treatment of idiopathic pulmonary fibrosis (IPF). In this study, we explored the anti-pulmonary fibrosis effect of QZJFD and the underlying mechanism. Methods: The effects of QZJFD at low, medium, and high doses were investigated in a rat model of lung fibrosis induced by tracheal injection of bleomycin; pirfenidone was included as a positive control. Serum levels of interleukin-6 (IL-6), tumor necrosis factors (TNF-α), and IL-1β in rats were detected by enzyme-linked immunosorbent assay (ELISA). Expression of α-smooth muscle actin (α-SMA), TGF-β1, p-Jun N-terminal kinase (p-JNK), JNK, p-P38 mitogen-activated protein kinase (MAPK), P38 MAPK, collagen I, and fibronectin-1 (FN1) in lung tissues was detected by immunofluorescence labeling and western blot analysis. Results: QZJFD contained 209 main components and 575 corresponding targets. In total, 3875 disease action targets were related to IPF, with 308 common targets shared by drugs and diseases. The key targets included albumin (ALB), recombinant protein, TNF, IL-6, and tumor protein p53. In total, 3061 items were identified in the gene ontology enrichment analysis ( P < .05) and 197 signaling pathways in the Kyoto encyclopedia of genes and genomes ( P < .05), including MAPK, calcium, advanced glycosylation end products - receptors, TNF, and IL-17. Molecular docking simulation showed that the 2 predominant compounds of QZJFD, naringenin, and kaempferol, bound with high affinity to ALB. Serum levels of IL-6, TNF-α, and IL-1β and the expression levels of α-SMA, TGF-β1, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues were significantly increased in the model rats ( P < .001). After treatment with pirfenidone and QZJFD at the medium and high doses, serum levels of IL-6, TNF-α, and IL-1β and expression levels of α-SMA, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues of rats were significantly lower than those in the model group ( P < .05). Conclusions: QZJFD may exert antifibrotic and anti-inflammatory effects that improve the status of IPF by regulating the MAPK signaling pathway.

Background: Gan-song Yin (GSY) is originated from the scripture "Gan-song Pills", a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless. Methods: Firstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis. Results: With the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR , JUN , MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein. Conclusions: Network pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

Background: Studies have shown a close association between trouble sleeping and obesity in older adults. However, no studies have explored the underlying mechanism of this relationship. The present study was designed to evaluate the roles of depressive symptoms and cognitive function in the association between trouble sleeping and obesity in older American adults. Methods: A cross-sectional study with 2575 participants (>= 60 years old) in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 was used for analysis. Obesity, depressive symptoms, and cognitive function (including Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST)) were objectively measured, and trouble sleeping was assessed using a self-reported questionnaire. The moderated mediation analysis was conducted by Hayes' PROCESS macro. Results: Trouble sleeping was positively associated with obesity among older adults. Depressive symptoms partially and indirectly mediated this association, and DSST moderated the association between trouble sleeping and depressive symptoms. Trouble sleeping had a lower impact on depressive symptoms in older adults with higher cognitive function. Limitations: The cross-sectional design prevents making causal inferences, and part of self-reported information was not objective enough. Conclusion: Cognitive function moderated the mediation of depressive symptoms on the indirect, positive association between trouble sleeping and obesity; hence, incorporating methods to strengthen cognitive function and alleviate depressive symptoms may help weak the link between trouble sleeping and obesity among older adults.

Purpose Network pharmacology and molecular docking were uesd to forecast the related effect targets and potential signal pathways of Rhubarb and Agastache rugosa in curing renal cancer. Methods Searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the effective ingredients and targets of Rhubarb and Agastache rugosa, the differential genes related to renal cancer were obtained by searching GEO database. Construct the regulatory networks and protein-protein interaction(PPI) networks using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed based on Metascape database, the gene set was analyzed by GSEA. The active components and core genes were molecular docked, and the core genes were analyzed for clinical correlation and immune infiltration. Finally, in order to verify the results of network pharmacological analysis, we performed cell experiments with 786-O cells and ACHN cells in vitro. Results The top six core genes, EGFR, HSP90AA1, MMP9, KDR, CA9, and LDHA, were identified by network pharmacological analysis; and Rhubarb and Agastache rugosa was predicted to play a role in the PI3K/Akt/mTOR pathway through central carbon metabolism in cancer. Cellular experiments showed that Rhubarb and Agastache rugosa restrained the proliferation of 786-O and ACHN cells, induced apoptosis, arrested the cell cycle, and reduced the colony forming ability of cells. qRT-PCR results showed that the expression of core targets of EGFR, HSP90AA1, MMP9, KDR, CA9, and LDHA were significantly down-regulated. Western blot results showed that the protein expression levels of EGFR, p-PI3K, PI3K, p-Akt/Akt, and p-mTOR/mTOR were significantly down-regulated. Discuss The core targets in the effective components of Rhubarb and Agastache rugosa may be to inhibit the development and proliferation of renal carcinoma cells through the PI3K/Akt/mTOR pathways.

Amygdalins (AMY) from bitter almonds are distinguished by their anti-inflammatory, antibacterial and antioxidant properties, but their role in the treatment of acute lung injury (ALI) and their mechanisms need to be clarified. We sought to investigate whether AMY provides protection against lipopolysaccharide (LPS)-induced ALI in mice and explore the mechanisms of its protection. Results showed that AMY effectively alleviated LPS-induced ALI in a dose-dependent manner by reducing in vivo lung wet/dry ratio, lung/body weight ratio, and myeloperoxidase (MPO). In addition, AMY can significantly reduce lung histopathological injury, decreased bronchoalveolar lavage fluid (BALF) lymphocyte, neutrophil, and monocyte numbers, and decreased the secretion of inflammatory cytokines IL-6, IL-1β, and TNF-α. Through transcriptome sequencing, AMY was found to effectively reduce the mRNA level of CD5L in mice. In AAV-CD5L transfected mice, CD5L overexpression was found to block the protective effect of AMY in LPS-induced ALI mice. It was revealed that AMY inhibited NF-κB entry into the nucleus to reduce iNOS by targeting CD5L. Taken together, AMY can effectively reduce lung inflammation and alleviate ALI, and is a potential novel protective agent against LPS-induced ALI.