The overall survival rate of patients with hepatocellular carcinoma (HCC) has remained unchanged over the last several decades. Therefore, novel drugs and therapies are required for HCC treatment. Isoliquiritigenin (ISL), a natural flavonoid predominantly isolated from the traditional Chinese medicine Glycyrrhizae Radix (Licorice), has a high anticancer potential and broad application value in various cancers. Here, we aimed to investigate the anticancer role of ISL in the HCC cell line Hep3B. Functional analysis revealed that ISL inhibited the proliferation of Hep3B cells by causing G1/S cell cycle arrest in vitro. Meanwhile, the inhibitory effect of ISL on proliferation was also observed in vivo. Further analysis revealed that ISL could suppress the migration and metastasis of Hep3B cells in vitro and in vivo. Mechanistic analysis revealed that ISL inhibited cyclin D1 and up-regulated the proteins P21, P27 that negatively regulate the cell cycle. Furthermore, ISL induced apoptosis while inhibiting cell cycle transition. In addition, phosphatidylinositol 3′-kinase/protein kinase B (PI3K/AKT) signal pathway was suppressed by ISL treatment, and the epithelial marker E-cadherin was up-regulated when the mesenchymal markers Vimentin and N-cadherin were down-regulated. In brief, our findings suggest that ISL could be a promising agent for preventing HCC tumorigenesis and metastasis.
The effective management and therapies for Parkinson’s disease (PD) require appropriate clinical evaluation. The Parkinson’s KinetiGraph (PKG) is a wearable sensor system that can monitor the motion characteristics of PD objectively and continuously. This study was aimed to assess the correlations between PKG data and clinical scores of bradykinesia, rigidity, tremor, and fluctuation. It also aims to explore the application value of identifying early motor symptoms. An observational study of 100 PD patients wearing the PKG for ≥ 6 days was performed. It provides a series of data, such as the bradykinesia score (BKS), percent time tremor (PTT), dyskinesia score (DKS), and fluctuation and dyskinesia score (FDS). PKG data and UPDRS scores were analyzed, including UPDRS III total scores, UPDRS III-bradykinesia scores (UPDRS III-B: items 23–26, 31), UPDRS III-rigidity scores (UPDRS III-R: item 22), and scores from the Wearing-off Questionnaire (WOQ-9). This study shows that there was significant correlation between BKS and UPDRS III scores, including UPDRS III total scores, UPDRS III-B, and UPDRS III-R scores ( r = 0.479–0.588, p ≤ 0.001), especially in the early-stage group ( r = 0.682, p < 0.001). Furthermore, we found that BKS in patients with left-sided onset (33.57 ± 5.14, n = 37) is more serious than in patients with right-sided onset (29.87 ± 6.86, n = 26). Our findings support the feasibility of using the PKG to detect abnormal movements, especially bradykinesia in PD. It is suitable for the early detection, remote monitoring, and timely treatment of PD symptoms.
Background: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. Methods: Middle-aged wild-type (WT) C57BL/6 and CX3CR1 −/− mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. Results: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1 −/− S group, the CX3CR1 −/− SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. Conclusions: These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Background Laryngeal squamous cell carcinoma (LSCC) remains one of the most common respiratory tumors worldwide. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) is a member of the inhibitor-of-apoptosis protein family. BIRC5 plays an important role in various types of cell proliferation, differentiation, migration and invasion. However, the specific role of BIRC5 in LSCC remains unclear. Methods To provide a prognostic biomarker for LSCC, we screened the prognostic genes of LSCC via bioinformatics. PPI network and KEGG pathways were used to select hub genes. Clinical prognoses were performed using a Kaplan–Meier plotter and Cox proportional-hazard analysis. BIRC5 expression in LSCC tissues and cell lines were detected by RT-PCR, Western blot and Immunohistochemistry (IHC). Cell proliferation, cell cycle and cell apoptosis were detected with Cell Counting Kit-8 (CCK-8) and Flow Cytometry assay, respectively. Results Here, BIRC5 was strongly correlated with higher tumor grade and differentiation. BIRC5 was highly expressed in LSCC tissues when compared with normal tissues and increased expression of BIRC5 was associated with overall survival in LSCC patients. The suppression of BIRC5 induced cell apoptosis and cell cycle arrest, thereby inhibiting the proliferation of LSCC cells. The survival analysis confirmed that higher level of BIRC5 expression predicted poor prognosis of LSCC patients. BIRC5 may act as an oncogene of LSCC development and was suggested as a promising prognostic biomarker for LSCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.