Hereditas最新文献

Objective: To investigate Jianpi Qutan Decoction (JPQT)'s effects on hepatic lipid metabolism via the PPARα-CPT1α pathway.

Methods: Eight male C57BL/6J mice served as controls; 32 ApoE^-/- mice were randomized into atherosclerosis (AS), atorvastatin calcium (AC), and low/medium/high-dose JPQT groups. Prior to the intervention, therapeutic targets of JPQT were analyzed using network pharmacology to provide a theoretical basis for subsequent experiments. The AS model was induced by a 12-week high-fat diet. Hepatic triglyceride (TG) and cholesterol (TC) were measured via GPO-PAP. Glucose tolerance (GTT) and insulin tolerance (ITT) were assessed. Pro-inflammatory cytokines were analyzed by ELISA/colorimetry. Fatty acid metabolism enzymes were evaluated using kits. PPARα-CPT1α pathway mRNA and protein expression were quantified via qPCR and Western blot.

Results: JPQT and AC reduced aortic plaque lipid deposition. JPQT significantly lowered hepatic TG/TC, blood glucose, insulin, and inflammation. It modulated fatty acid metabolism by promoting ACC phosphorylation, suppressing FAS and FFA while elevating FAβO, with dose-dependent efficacy. Additionally, JPQT upregulated PPARα, CPT1α, and ACOX1 mRNA and protein expression in the liver.

Conclusion: JPQT may improves lipid metabolism and reduces AS progression by activating the PPARα-CPT1α pathway, with higher doses yielding stronger effects.

Background: Sepsis is a life-threatening syndrome characterized by organ dysfunction. The kidney is one of the earliest organs to be injured during sepsis. Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) was shown to play a critical role in immune responses. BMAL1 deregulation is related to sepsis-induced injury. Thus, correct understanding of the molecular mechanism of BMAL1 in sepsis-induced acute kidney injury (AKI) may be importance for seeking effective targeted therapy.

Methods: Lipopolysaccharide (LPS)-induced renal tubular epithelial cells (HK-2 cells) and a sepsis-AKI model established in C57BL/6 mice using cecal ligation and puncture (CLP) were used for functional analyses. In vitro analyses were conducted using EdU assay, flow cytometry, MTT assay and ELISA, respectively. Levels of mRNA and protein expression were using qRT-PCR and western blotting. Cellular ubiquitination analyzed the ubiquitination effect of USP10 on BMAL1. The binding of HOXA5 to BMAL1 promoter was verified using Chromatin immunoprecipitation and Luciferase reporter assays.

Results: BMAL1 overexpression reversed LPS-induced apoptosis, inflammation and ferroptosis in HK-2 cells, as well as attenuated sepsis-induced AKI in mouse models. Mechanistically, USP10 bound to BMAL1 and positively modulated BMAL1 expression by reducing BMAL1 ubiquitination. In addition, HOXA5 induced BMAL1 transcription. Moreover, USP10 or HOXA5 overexpression reversed LPS-induced apoptosis, inflammation and ferroptosis in HK-2 cells, which could be rescued by BMAL1 decrease.

Conclusion: BMAL1 overexpression mediated by USP10-induced deubiquitination or HOXA5-induced transcription can attenuate sepsis-induced acute kidney injury, recommending a novel insight for the prevention of sepsis-induced AKI.

Background: The incidence of diabetic peripheral neuropathy (DPN) is increasing every year for type 2 diabetes mellitus (T2DM) patients, and diabetic polyneuropathy is a common type.

Objective: To quantify and analyze the factors associated with diabetic polyneuropathy using the virtual tissue imaging quantification (VTIQ) technique.

Method: 182 patients with T2DM, 137 patients with diabetic polyneuropathy, and 198 healthy volunteers were included in this retrospective cross-sectional diagnostic study. Sciatic neuropathy was evaluated through Doppler ultrasound examination with a VTIQ quantitative analysis system to acquire elastic modulus, cross-sectional area (CSA) and shear wave velocity (SWV). Nerve conduction velocity (NCV) was also evaluated via neurophysiological examination. Logistic regression was used to analyze odds ratios (OR) related diabetic polyneuropathy. The diagnostic accuracy of the VTIQ technique-acquired index on diabetic polyneuropathy was analyzed using the receiver operating characteristic (ROC) curve.

Results: VTIQ technique-acquired indexes all differed significantly among three study groups, among which Elastic modulus and CSA were independently related to diabetic polyneuropathy risk according to the logistic regression analysis. NCV was also an independent risk factor for diabetic polyneuropathy. ROC analysis revealed that Elastic modulus, CSA and NCV can distinguish diabetic polyneuropathy patients from T2DM cases with the AUC of 0.797, 0.654 and 0.775 respectively. But their combination achieved the highest diagnostic value (AUC = 0.883). CSA and SWV of the sciatic nerve are positively correlated with visual analog scale (VAS) scores.

Conclusion: VTIQ technology contributes to the diagnosis of diabetic polyneuropathy, it can improve the diagnostic value of neurophysiological examination on sciatic neuropathy for T2DM patients.

Background: Lung cancer ranks among the most prevalent malignancies globally, with non-small cell lung cancer (NSCLC) constituting the predominant subtype. Currently, there are limitations in the treatment options and prognostic evaluation for NSCLC. Hsa_circ_0071271, a non-coding RNA, has an unclear expression and mechanism in NSCLC treatment. In this study, the impacts of hsa_circ_0071271 on NSCLC progression/prognosis and the possible mechanism of its inhibitory role in NSCLC progression through miR-23a-5p were investigated.

Methods: This investigation employed RT-qPCR to initially determine the expression levels of hsa_circ_0071271 in NSCLC tissues and cell lines. To evaluate the clinical significance of hsa_circ_0071271, ROC curve analysis, Kaplan-Meier survival analysis, and Cox regression were conducted. The impact of hsa_circ_0071271 knockdown on NSCLC cell lines A549 and CALU3 was examined through CCK-8 assays, flow cytometry, and transwell assays, corresponding to cell proliferation, apoptosis, and migration/invasion. The dual-luciferase reporter assay was used to examine the relationships between miR-23a-5p and hsa_circ_0071271, as well as between PTEN and miR-23a-5p. Pearson correlation analysis was conducted to assess the correlation between PTEN and miR-23a-5p. Subsequent experiments with CCK-8, flow cytometry, and transwell assays were carried out to explore how hsa_circ_0071271 regulates miR-23a-5p/PTEN and thereby affects NSCLC cell proliferation, apoptosis, migration, and invasion.

Results: Hsa_circ_0071271 was expressed highly in NSCLC tissues and multiple cell lines. Hsa_circ_0071271 effectively distinguishes tumor tissues from normal ones and is associated with patient survival rates. Knocking down hsa_circ_0071271 inhibits NSCLC cell proliferation and migration/invasion while promoting apoptosis. The study also revealed an interaction between hsa_circ_0071271 and miR-23a-5p, as well as between PTEN and miR-23a-5p, with their expression levels showing a significant negative correlation. Further experiments indicated that hsa_circ_0071271 regulates miR-23a-5p/PTEN to suppress NSCLC cell proliferation, migration, and invasion and promote apoptosis.

Conclusions: Regulating miR-23a-5p/PTEN by hsa_circ_0071271 knockdown has been found to inhibit NSCLC cell proliferation, migration and invasion, as well as promote apoptosis.

Background: Sepsis is a life-threatening systemic inflammatory response triggered by infection. The rapid progression of the disease necessitates early diagnosis and precise intervention, making the identification of reliable biomarkers and therapeutic targets crucial for improving clinical outcomes and reducing sepsis-related mortality.

Aim: Exploring miR-142-5p as a novel diagnostic biomarker for sepsis and its therapeutic potential via targeting CXCL8.

Methods: The expression levels of inflammatory factors (IL-6, TNF-α, IL-1β) and miR-142-5p in the serum of patients with sepsis and healthy controls were detected by ELISA and qPCR methods respectively. The diagnostic potential of miR-142-5p was evaluated using Pearson correlation, ROC curve, and logistic regression analyses. Bioinformatic prediction and dual-luciferase assays identified CXCL8 as a target, while LPS-induced models and cell transfection experiments investigated miR-142-5p's therapeutic effects through CXCL8 regulation.

Results: Sepsis patients exhibited significantly decreased miR-142-5p expression, inversely correlating with inflammatory markers (IL-6, TNF-α, IL-1β). ROC analysis showed excellent diagnostic value (AUC = 0.917). Pearson correlations indicated significant clinical associations, while logistic regression identified miR-142-5p as an independent protective factor (HR = 0.498, 95% CI:0.282-0.882, P = 0.017). LPS models confirmed miR-142-5p's anti-inflammatory effects through cytokine suppression, with knockdown showing opposite effects. Mechanistically, dual-luciferase and transfection assays verified CXCL8 as a direct target mediating these effects.

Conclusion: miR-142-5p may alleviate sepsis by targeting CXCL8-mediated inflammation, suggesting its potential as a diagnostic biomarker and therapeutic target.

Background: We aim to employ single-cell RNA (scRNA) sequencing technology to investigate potential regulatory mechanism of Danggui Buxue Tang (DBT) in wound healing for its utilization in post-anal fistula surgery recovery.

Methods: Fistula-like wound model in mice was established and administered DBT to assess its effects. Mice were divided into control and DBT groups and collected samples on the first day and 7th day after model establishment. The DBT was prepared from Astragalus membranaceus and Angelica sinensis. ScRNA sequencing was performed on each group.

Results: Our results showed that DBT treatment obviously reduced wound area in mice with anal fistula through activation of OPN/PI3K/Akt/eNOS signaling. Furthermore, the results of scRNA sequencing showed that all cells were clustered into 7 types, and the macrophages were categorized into 13 distinct clusters. In the early stages of wound formation, M1-like macrophages (M1C1) abundant in both groups at day1. However, by day 7 post-injury, the DBT-treated group exhibited a reduction in the infiltration of M1-like macrophages (M1C1) compared to the model group. Conversely, the proportion of M2-like macrophages (M2C3) showed a marked increase in the DBT group at day 7, while decreasing in the model group. Pseudo-time trajectory analysis confirmed that DBT treatment modulates macrophage polarization, potentially enhancing the wound healing process by promoting a transition from pro-inflammatory to anti-inflammatory macrophage populations.

Conclusion: DBT has the potential to accelerate wound healing after anal fistula by promoting M2 macrophage polarization, likely through activation of the PI3K/Akt signaling pathway.