From the databases TCMSP, TCMID, PubChem, PharmMapper, GeneCards, and OMIM, collect disease-related targets and compounds, and identify genes shared between them. The functional enrichment of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was determined using R statistical software. Utilizing intracerebroventricular injection of lipopolysaccharide (LPS), a POCD mouse model was generated, allowing for the observation of hippocampal tissue morphological changes. Hematoxylin-eosin (HE) staining, Western blot, immunofluorescence, and TUNEL assays were subsequently employed to corroborate these observations with the results of the network pharmacological enrichment analysis.
The investigation into POCD enhancement through EWB strategies resulted in 110 potential targets. GO analysis revealed 117 enriched items, and 113 KEGG pathways were also found. Significantly, the SIRT1/p53 signaling pathway displayed a link to the occurrence of POCD. Core target proteins IL-6, CASP3, VEGFA, EGFR, and ESR1 display low-energy stable conformations upon interaction with quercetin, kaempferol, vestitol, -sitosterol, and 7-methoxy-2-methyl isoflavone present in EWB. Mouse experiments demonstrated a notable difference in hippocampal apoptosis rates between the EWB group and the POCD model group, with the EWB group showing a significant increase in apoptosis and a significant reduction in Acetyl-p53 protein levels (P<0.005).
The multi-pronged approach of EWB, targeting multiple components, pathways, and targets, improves POCD through synergistic interactions. see more Studies have validated that EWB can elevate the incidence of POCD by influencing the expression levels of genes linked to the SIRT1/p53 signaling system, which presents a novel therapeutic objective and theoretical framework for treating POCD.
EWB's positive impact on POCD stems from its multi-faceted approach involving the synergistic interaction of multiple components, targets, and pathways. Through comprehensive studies, it has been proven that EWB can improve the manifestation of POCD by adjusting the expression of genes in the SIRT1/p53 pathway, offering a new avenue for targeting and managing POCD.
While enzalutamide and abiraterone acetate are employed in current therapies for castration-resistant prostate cancer (CRPC), targeting the androgen receptor (AR) transcription axis, these treatments are often transient and quickly face resistance. see more In addition to other prostate cancers, neuroendocrine prostate cancer (NEPC) presents as a lethal form of the disease, exhibiting independence from the AR pathway and lacking a standard treatment. QDT, a traditional Chinese medicine formula, demonstrates various pharmacological activities, frequently used for treating diverse ailments such as prostatitis, which might contribute to the development of prostate cancer.
The research project seeks to understand the anti-tumor activity and the possible mechanisms through which QDT operates in prostate cancer.
To facilitate research on CRPC prostate cancer, models involving cell lines and xenograft mice were established. To understand how TCMs affected cancer growth and spread, researchers used the CCK-8, wound-healing, and PC3-xenograft mouse model. The study of QDT toxicity across a range of major organs was facilitated by the application of H&E staining. Applying network pharmacology, the compound-target network was scrutinized. Patient prognosis in prostate cancer was correlated with QDT targets, leveraging multiple patient cohorts for analysis. To evaluate the expression of related proteins and mRNA, we performed western blot and real-time PCR experiments. The application of CRISPR-Cas13 technology resulted in the gene knockdown.
Through the integration of functional screening, network pharmacology analysis, CRISPR-Cas13-directed RNA targeting, and molecular validation across various prostate cancer models and clinical samples, we demonstrated that Qingdai Decoction (QDT), a traditional Chinese medicine, inhibited cancer growth in advanced prostate cancer models in both laboratory and live animal studies, independently of the androgen receptor, by impacting NOS3, TGFB1, and NCOA2.
This investigation not only established QDT as a novel therapeutic agent for advanced prostate cancer but also presented a comprehensive integrative research framework for exploring the functions and mechanisms of Traditional Chinese Medicines in treating various ailments.
This study not only introduced QDT as a novel treatment option for lethal-stage prostate cancer, but also presented a profound integrative research model to investigate the mechanisms and roles of Traditional Chinese Medicines in the treatment of other diseases.
The impact of ischemic stroke (IS) encompasses a high degree of illness and a high number of deaths. see more Past research from our group indicated that the bioactive compounds within the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) show a range of therapeutic effects on nervous system conditions. Undoubtedly, the consequences of CT imaging on the blood-brain barrier (BBB) in the period after ischemic stroke (IS) are yet to be fully elucidated.
This investigation aimed to identify the curative properties of CT in treating IS and explore the underlying mechanisms at play.
The injury observed in the rat model mimicked middle cerebral artery occlusion (MCAO). Seven consecutive daily gavage administrations of CT were given at the dosages of 50, 100, and 200 mg/kg/day. Researchers used network pharmacology to foresee the pathways and potential targets of CT in relation to IS, and experimental studies corroborated the importance of these identified targets.
The MCAO group's results highlighted a worsening of neurological dysfunction and a breakdown in the blood-brain barrier. Ultimately, CT's impact was seen in the improvement of BBB integrity and neurological function, while providing defense against cerebral ischemia injury. Microglia-mediated neuroinflammation was highlighted by network pharmacology studies as a possible mechanism implicated in IS. Further studies corroborated that MCAO triggered ischemic stroke (IS) by prompting the generation of inflammatory factors and the penetration of microglia. Neuroinflammation was observed to be influenced by CT through the modulation of microglial M1-M2 polarization.
The observed effects of CT suggest its potential to reduce MCAO-induced ischemic stroke, thereby modifying microglia's involvement in neuroinflammation. The findings, based on theoretical and experimental analysis, highlight the effectiveness of CT therapy and innovative strategies for the prevention and treatment of cerebral ischemic injuries.
The results hinted that CT might govern microglia-mediated neuroinflammatory responses, lessening the ischemic stroke size induced by MCAO. CT therapy's efficacy and novel prevention/treatment concepts for cerebral ischemia are supported by both theoretical and experimental results.
The Traditional Chinese Medicine known as Psoraleae Fructus is renowned for its capacity to invigorate the kidneys and fortify their essence, effectively treating conditions like osteoporosis and diarrhea. Although beneficial, its application is hampered by the possibility of multiple-organ injury.
To characterize the ethanol extract of salt-processed Psoraleae Fructus (EEPF), this study aimed to systematically investigate its acute oral toxicity and elucidate the mechanism behind its acute hepatotoxicity.
UHPLC-HRMS analysis was applied in this study to the task of determining the composition of the components. In an acute oral toxicity test, Kunming mice were given oral gavage doses of EEPF, varying from 385 g/kg to 7800 g/kg. A study of EEPF-induced acute hepatotoxicity and its underlying mechanisms encompassed measurements of body weight, organ indexes, biochemical analysis, morphological examination, histopathological investigation, oxidative stress markers, TUNEL assay results, and the mRNA and protein expression of the NLRP3/ASC/Caspase-1/GSDMD signaling pathway.
EEPf analysis showed that 107 compounds, including psoralen and isopsoralen, were present. Through the acute oral toxicity test, the LD was observed.
A EEPF concentration of 1595 grams per kilogram was found in the Kunming mouse sample. In terms of body weight, there was no discernable difference between the surviving mice and the control group at the culmination of the observation period. The organ indexes of the heart, liver, spleen, lung, and kidney remained statistically equivalent, with no significant differences observed. Despite other potential effects, the morphological and histopathological changes within the organs of high-dose mice pointed to liver and kidney as the key sites of EEPF toxicity. The observed damage included hepatocyte degeneration with lipid inclusions and protein casts in kidney tissue. The confirmation was validated by the substantial increases in liver and kidney function indicators, including AST, ALT, LDH, BUN, and Crea. In addition, the liver and kidney showcased a substantial increase in MDA, an oxidative stress marker, while significant decreases were evident in SOD, CAT, GSH-Px (liver-specific), and GSH. Additionally, EEPF prompted an upsurge in TUNEL-positive cells and mRNA and protein expression of NLRP3, Caspase-1, ASC, and GSDMD within the liver, further characterized by an increase in IL-1 and IL-18 protein expression. A crucial finding in the cell viability test was that the particular caspase-1 inhibitor successfully reversed EEPF-induced cell death in Hep-G2 cells.
A comprehensive review of the 107 elements of EEPF was conducted in this study. An acute oral toxicity study provided information on the lethal dose.
Among Kunming mice, the EEPF level reached 1595 grams per kilogram, potentially leading to significant toxic effects primarily in the liver and kidneys. The liver incurred injury due to oxidative stress and pyroptotic damage via the NLRP3/ASC/Caspase-1/GSDMD signaling pathway's activity.
This study sought to understand the 107 individual compounds that make up EEPF. The oral toxicity assessment of EEPF, using acute exposure in Kunming mice, yielded an LD50 value of 1595 g/kg, suggesting the liver and kidneys as potential primary sites of toxicity. The NLRP3/ASC/Caspase-1/GSDMD pathway, through oxidative stress and pyroptotic damage, contributed to liver injury.
Related posts:
- Cerebral venous nose thrombosis in the toddler using serious lymphoblastic the leukemia disease
- Referral styles pertaining to catheter-directed thrombolysis pertaining to iliofemoral deep venous thrombosis.
- Low Pipe Existing Calculated Tomography Venography pertaining to Patients Along with Strong Abnormal vein Thrombosis with the Reduced Extremities - Analysis Along with Venous Ultrasonography.
- Wingspan Stenting regarding Pointing to Severe In-Stent Stenosis of an Closed-Cell Stent soon after Stent-Assisted Coiling of your
- Deep Venous Thrombosis in the Affected individual which has a Reasonable Pretest Likelihood as well as a Bad D-Dimer Test: Overview of your Analytic Algorithms