Purpose: Depression is common in Parkinson's disease (PD) and is correlated with the severity of motor deficits and quality of life. The present study aimed to investigate alterations in the structural brain network related to depression in Parkinson's disease (d-PD) and their correlations with structural impairments of white matter (WM).Materials and Methods: Data were acquired from the Parkinson Progression Markers Initiative (PPMI) database. A total of 84 de novo and drug-naïve PD patients were screened and classified into two groups according to the 15-item Geriatric Depression Scale (GDS-15): d-PD (n = 28) and nondepression in PD (nd-PD, n = 56). Additionally, 37 healthy controls (HC) were screened. All subjects underwent DTI and 3D-T1WI on a 3.0 T MR scanner. Individual structural brain networks were constructed and analyses were performed using graph theory and network-based statistics (NBS) at both global and local levels. Differences in global topological properties were explored among the three groups. The association models between node and edge changes and the GDS-15 were constructed to detect regions that were specifically correlated with d-PD. Tract-based spatial statistics (TBSS) was used to detect structural impairments of WM between the d-PD and nd-PD groups. The correlations between altered global topological properties and structural impairments were analyzed in the d-PD group.Results: The global efficiency and characteristic path length of the structural brain network were impaired in the d-PD group compared with those in the nd-PD and HC groups. Thirteen nodes and 1 subnetwork with 10 nodes and 12 edges specifically correlated with d-PD were detected. The left hippocampus, left parahippocampal, left lingual, left middle occipital, left inferior occipital, left fusiform, left middle temporal, and left inferior temporal regions were all involved in the results of node and edge analysis. No WM microstructural impairments were identified in the d-PD group.Conclusion: Our study suggests that the integration of the structural brain network is impaired with disrupted connectivity of limbic system and visual system in the de novo and drug-naïve d-PD patients.The topological properties assessing integration of the structural brain network can serve as a potential objective neuroimaging marker for early diagnosis of d-PD.

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Objective: To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms.Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot.Results: Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention.Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.

Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.

Background: Emodin, one of the most dominant components of the traditional Chinese medicine rhubarb, has been utilized to treat acute pancreatitis (AP). Acute lung injury (ALI) is one of the most common complications of acute pancreatitis, leading to a serious mortality rate. However, the specific mechanism of emodin in the treatment of AP-associated lung injury remains unclear. Therefore, we investigated the protective roles of emodin in AP-ALI and its underlying mechanisms in two clinically relevant experimental AP models.Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into sham, AP, Ac‐YVAD‐CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed through H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot. Results: Emodin, similar to the positive control AYC, significantly alleviated pancreatic and lung damage in rats and mice. Additionally, emodin decreased the pyroptotic rates of AMs, inflammatory cytokines, and the lactate dehydrogenase level. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention. Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which is at least partially due to the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling ways.