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Radix Chimonanthi Pracecocis (RCP), also known as Tiekuaizi, widely used by the Miao community in Guizhou, exhibits diverse biological activities and holds promise for the treatment of osteoarthritis (OA). However, there is a lack of contemporary pharmacological research in this area. This study aims to explore the potential of targets and mechanisms of RCP in the treatment of OA. The chemical components of RCP were identified using UPLC-MS/MS, and active components were determined based on the Lipinski rule. RCP and OA-related targets were retrieved from public databases such as TCMSP and GeneCards. Network pharmacology approaches were employed to identify key genes. The limma package (version 3.40.2) in R 4.3.2 was used to screen for differentially expressed genes (DEGs) between OA and healthy individuals in GSE82107. DEGs were analyzed using an independent sample t -test and receiver operating characteristic analysis in GraphPad Prism 9.5.1. Additionally, molecular docking (SYBYL2.1.1) was used to analyze the binding interactions between the active components and target proteins. Finally, we established a papain-induced osteoarthritis (OA) rat model and treated it with RCP aqueous extract by gavage. We validated relevant indicators using real-time fluorescence quantitative polymerase chain reaction, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays. Seven active components and 53 targets were identified. The results of GO and KEGG enrichment analyses confirmed the significant role of RCP in the regulation of pyroptosis. Hypoxia-inducible factor-1α (HIF-1α) was identified as a key gene involved in the main biological functions. Molecular docking analysis revealed that Praecoxin, Isofraxidin, Esculin, and Naringenin can bind to the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) (T-Score >5). Additionally, Praecoxin can bind to HIF-1α (T-Score >5). In vivo experiments demonstrated that RCP significantly affects the NLRP3 inflammasome, which is regulated by the HIF-1α pathway. RCP inhibited pyroptosis and reduced synovial inflammation. This study confirmed the efficacy of RCP aqueous extract in the treatment of OA and identified seven active components (esculin, dihydrokaempferol, naringenin, praecoxin, carnosol, hydroxyvalerenic acid, isofraxidin) that may play an anti-pyroptosis role in the treatment of OA by downregulating the expression of HIF-1α and NLRP3 inflammasome. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that Millettia pulchra flavonoids (MPF) exhibit protective effects on myocardial ischemia reperfusion injury (MI/RI) in isolated rat hearts and show anti-oxidative, anti-hypoxic and anti-stress properties. Methods: In this study, the cardioprotective effects of MPF on myocardial ischemia and its underlying mechanisms were investigated by a hypoxia/ reoxygenation (H/R) injury model in vitro and a rat MI/RI model in vivo. Results: We found that the lactate dehydrogenase (LDH) and inducible nitric oxide synthase (iNOS) activities were decreased in the MPF pretreatment group, whereas the activities of constructional nitric oxide synthase (cNOS), total nitric oxide synthase (tNOS), Na+-K+-ATPase and Ca2+-Mg2+-ATPase were significantly increased. In addition, the cardiocytes were denser in the MPF groups than in the control group. The mortality rate and apoptosis rate of cardiocytes were significantly decreased. Furthermore, pretreatment with MPF in vivo significantly improved the hemodynamics, decreased malondialdehyde (MDA) abundance, increased the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the expression of the Bax protein and ratio Bax/Bc1-2 ration. Conclusions: These results suggest that MPF is an attractive protective substance in myocardial ischemia due to its negative effects on heart rate and ionotropy, reduction of myocardial oxidative damage and modulation of gene expression associated with apoptosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Effect and mechanism of Yulangsan flavonoid (YLSF) on rat myocardial ischemia/reperfusion injury (MI/RI) has been investigated. Methods: Sprague-Dawley (SD) rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered) and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS) were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1) mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS), caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS) as well as constitutive nitric oxide synthase (cNOS). Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Nanog plays a key role in stem cell self-renewal and pluripotency differentiation in embryonic stem cells ( ESCs). Recently, some studies reported that abnormal expression of Nanog could be detected in several tumors, indicating that Nanog might be related to tumor development. However, studies on the correlation between Nanog expression and esophageal cancer are sparse. Methods: In this study, we established two esophageal cancer cell lines 9706-Nanog and 9706-shNanog which stably expressed Nanog and Nanog-short-hairpin RNA (shRNA) genes. Results: We found that Nanog expression could promote the proliferation and invasiveness of the cancer cells, and inhibit the apoptosis. We also treated 9706-Nanog, EC9706 and 9706-shNanog cell lines with cisplatin and evaluated the drug sensitivity of the three cell lines. We found that the sensitivity of cisplatin was decreased with increased expression of Nanog. The expression of MDR-1 was also increased in 9706Nanog cells. Conclusions: Nanog may play an important role in human esophageal cancer development, and could be used as a therapeutic target in esophageal cancer treatment. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study aimed to improve the conventional rat burn wound model and to validate its utility. In total, 60 Sprague‐Dawley rats were divided equally into the control and experimental groups. Altogether, 60 burn wound models with zones of stasis were created in each group. Gross visual assessments of the burn wounds were performed at 0, 24, and 48 hours after burn creation. The rates of necrosis in the zones of stasis were calculated, and the blood flow from the wounds was examined. Wound tissues were collected 48 hours after the burn and subjected to hematoxylin and eosin staining to determine whether the models were successfully established. The model success rates were calculated. The success rate of the burn wound models was significantly different between the control group and the experimental group (93.33% [56/60] vs 100%; P =.042). The Cronbach's alpha values and the respective correlation coefficients indicated that the stability of the zones of stasis in the models on the two sides of the spine was higher in the experimental group than in the control group. The standard deviations of the rate of necrosis, blood flow, and density of necrotic cells and apoptosis cell density, and inflammatory factor content in the zones of stasis were smaller in the experimental group than in the control group at 48 hours after model construction. This suggested that the stability of repeated procedures was higher in the experimental group than in the control group. The novel device for creating burns in animal models facilitated the effective creation of zones of stasis for rat burn wound models. Both the model success rate and stability were higher compared with the conventional model construction method. In addition, the use of the novel device can better align with the requirements of self‐controlled studies. [ABSTRACT FROM AUTHOR]

Background. Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL), represents a rare subtype of T-cell lymphomas with aggressive clinical behavior and is relatively resistant to chemotherapy. However, there is relatively poor understanding of molecular pathogenesis of multidrug resistance in ENKTL. Here, we aimed to explore the biological roles and potential mechanism of IL-13 and ABCC4 in multidrug resistance of NK/T-cell lymphoma. Methods. ELISA analysis was used to determine the level of serum IL-13 and immunohistochemical analysis was applied to detect the ABCC4 expression level in patients with human NK/T-cell lymphoma. Western blot assay was employed to measure the expression of ABCC4 in cells. Lenti-sh-ABCC4 viruses were constructed to knock down ABCC4 in YTS cells. CCK-8 assay and flow cytometric analysis were performed to detect the effects of IL-13 and ABCC4 on cell proliferation and apoptosis. CCK-8 assay was conducted to detect the effect of IL-13 and ABCC4 on cell sensitivity to adriamycin (ADM) in YTS cells. Results. Levels of serum IL-13 and ABCC4 expression were observed to be upregulated in patients with human NK/T-cell lymphoma. Moreover, ABCC4 protein expression was also increased in NK/T-cell lymphoma YTS cells compared to the normal NK cells. Interestingly, IL-13 promoted ABCC4 expression in YTS cells. IL-13 promoted proliferation and suppressed apoptosis of YTS cells and reversed the effects of ABCC4 knockdown on promotive proliferation and inhibitory apoptosis. In addition, IL-13 enhanced YTS cell chemotherapy resistance to ADM by promoting ABCC4 expression. Conclusion. Our findings concluded that IL-13 inhibited chemotherapy sensitivity of NK/T-cell lymphoma cells by regulating ABCC4, disrupting which may effectively improve the therapy protocols against resistant NK/T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Exenatide could reduce blood glucose and alleviate cognitive dysfunction induced by diabetes mellitus (DM). In the present study, a diabetic model was established in Sprague-Dawley rats to further explore the mechanism of exenatide on diabetes-induced cognitive impairment. Notably, the model rats performed poorly in the Morris water maze test and had more apoptotic neurons compared with the control rats. By contrast, exenatide attenuated cognitive impairment and inhibited neuronal apoptosis in the DM rat model. To explore the neuroprotective mechanisms of exenatide, western blotting was performed to detect the expression levels of markers of endoplasmic reticulum stress, including cytochrome c (Cyt-c), Caspase-3, JNK and c-JUN, in hippocampal tissue. Reverse transcription-quantitative PCR was also performed to measure the mRNA expression levels of Cyt-c and Caspase-3. After 16 weeks of treatment, exenatide treatment downregulated Cyt-c, Caspase-3, phosphorylated (p)-JNK and p-c-JUN expression in the hippocampal tissue of diabetic rats. Moreover, Cyt-c, Caspase-3, JNK and JUN expression levels were detected following treatment with a specific inhibitor of JNK (SP600125). The results revealed that SP600125 had similar inhibitory effects on the JNK pathway and ERS-related protein expression (Cyt-t, Caspase-3, p-JNK and p-c-JUN). These results suggested that exenatide improved cognitive dysfunction in DM rats and that the underlying mechanism may be associated with inhibiting apoptosis by suppressing the activation of JNK/c-JUN. [ABSTRACT FROM AUTHOR]

Highlights: [•] Expression of Six1 in breast cancer cells correlates with their resistance to paclitaxel. [•] Six1 confers resistance to paclitaxel in breast cancer cells. [•] Six1 overexpression inhibits paclitaxel-induced apoptosis. [Copyright &y& Elsevier]