Promotion of apoptosis in melanoma cells by taxifolin through the PI3K/AKT signaling pathway: Screening of natural products using WGCNA and CMAP platforms.

Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.

Orientin alleviates the inflammatory response in psoriasis like dermatitis in BALB/c mice by inhibiting the MAPK signaling pathway.

BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.

Comprehensive Analysis of Enhancer RNAs Identifies LINC00689 and ELFN1-AS1 as Novel Prognostic Biomarkers in Uveal Melanoma.

Enhancer RNAs (eRNAs) have emerged as key players in the pathology of several tumors, including uveal melanoma. Here, we aimed to explore the prognostic values of eRNAs in uveal melanoma (UVM) patients. The expressing data and survival data of UVM patients were downloaded from TCGA and GSE22138 datasets. The Kaplan-Meier methods with the log-rank test were applied to screen survival-related eRNAs in UVM. GEPIA was applied to analyze the associations between expressions of eRNA and disease-free survival. KEGG assays were applied to explore the potential signaling pathways of the key eRNA. The prognostic values of eRNAs were further explored by multivariate assays by the R package survival. The eRNAs were validated in pan-cancer. In this study, we identified 89 survival-related eRNAs in UVM based on TCGA datasets. Based on GSE22138 datasets, we found 27 survival-related eRNAs in UVM. Only two eRNAs (LINC00689 and ELFN1-AS1) were overlapped in both two datasets. The results of multivariate analysis revealed that both LINC00689 and ELFN1-AS1 were independent prognostic factors in UVM patients. The pan-cancer validation results further confirmed the prognostic values of LINC00689 and ELFN1-AS1 in eight tumors. Overall, we identified two novel UVM-related eRNAs, LINC00689 and ELFN1-AS1 which may serve as prognostic and diagnostic biomarkers of UVM patients for clinical decision-making.

Eupafolin induces autophagy and apoptosis in B-cell non-Hodgkin lymphomas.

OBJECTIVES: Eupafolin, an extract from Artemisia princeps, possesses multiple pharmacological activities. However, the effect of eupafolin on B-cell non-Hodgkin lymphomas is currently unknown. In this study, we report that eupafolin shows anticancer activity against B-cell non-Hodgkin lymphomas cell line, OCI-LY-3. METHODS: A CCK-8 assay was used to detect the proliferation inhibition of OCI-LY-3 cells treated with additional concentrations of eupafolin. Flow cytometric analysis method of the cell apoptosis was detected after cells stained with Annexin-V-FITC/PI according to the manufacturer's instructions. The proteins in the cell were detected by western blot after treatment with eupafolin. KEY FINDINGS: Eupafolin induced apoptosis in this cell line evidenced by the caspases activation, cleavage of PARP and downregulation of Bcl-2 and Bcl-xl. Eupafolin-induced autophagy was verified by accumulation of LC3-II and beclin-1. Eupafolin induced autophagy promoting apoptosis by the treatment of eupafolin combined with autophagy inhibitors 3-methyladenine and bafilomycin A1, respectively. Moreover, we disclose that the expression levels of p-Akt, p-mTOR,p-P70S6K and p-4EBP1 decrease in the Akt/mTOR signalling pathway, and the expression levels of proteins in the NF-ΚB signalling pathway, such as p-p65, p-IκBα, is downregulation. CONCLUSIONS: Together, these results provide crucial evidences explaining the antitumour activity of eupafolin in human NHL cell line, OCI-LY-3.

[Application of intervertebral foramen endoscopy BEIS technique in the lumbar spine surgery failure syndrome over 60 years old].

OBJECTIVE: To evaluate the mid-term efficacy of radiofrequency ablation of nucleus pulposus by intervertebral foramen endoscopy BEIS technique in the treatment of lumbar spine surgery failure syndrome over 60 years old. METHODS: The clinical data of 40 patients over 60 years old with lumbar spine surgery failure syndrome admitted from January 2010 to January 2015 were retrospectively analyzed. Among them, there were 34 males and 6 females, aged from 60 to 76 years old with an average of 66 years, the courses of disease ranged from 10 months to 4 years. The patients were divided into two groups (BEIS group and revision group) according to the different surgery. The intervertebral foramen endoscopy BEIS technique and the transforaminal lumbar interbody fusion (TLIF) were performed in BEIS group and revision group respectively. There was no significant difference in general data such as sex, age, course of disease, surgical segment between two groups(P>0.05). The operation time, intraoperative bleeding volume, bed rest time after operation and hospitalization time were observed between two groups. At preoperative, postoperative 1 month, 1 year, 3 years, visual analogue scale(VAS) and Japanese Orthopaedic Association Score(JOA) were used to compare the efficacy. RESULTS: The operation time, intraoperative bleeding volume, bed rest time after operation and hospitalization time in BEIS group were (60.2±10.3) min, (60.1±4.5) ml, (2.2±1.5) d, (4.04±1.40) d, respectively, which were significantly lower than those of revision group (P<0.05). The VAS and JOA scores of the two groups at different time after operation were significantly improved (P<0.05), and there was statistically significant difference between two groups (P<0.05). CONCLUSIONS: Radiofrequency ablation of nucleus pulposus by intervertebral foramen endoscopy BEIS technique is more effective than TLIF revision in the treatment of lumbar spine surgery failure syndrome over 60 years old. It has advantages of shorter operation time, less bleeding, shorter bed rest after operation and hospitalization time, and is worthy of clinical promotion.

[Effects of dihydroartemisinin on radiosensitivity of Raji cells].

OBJECTIVE: To study the effects of dihydroartemisinin (DHA) on radiation sensitivity of Raji cells, and explore its mechanisms. METHODS: CCK8 was used to determine the effect of DHA on cell viability of Raji cells; apoptosis, intracellular reactive oxygen speies(ROS) and mitochondrial membrane potential of Raji cells were detected by flow cytometry; and the protein expressions of protein kinase B(AKT), phospho-rylated-protein kinase B(p-AKT), Bcl-2 and Bax were determined by Western blot. RESULTS: The cells were randomly divided into four groups:control group, DHA(5µmol/L DHA), irradiation(IR, 4 Gy), IR+DHA group (4 Gy IR+5 µmol/L DHA). Compared with the other three groups, cells in DHA+IR group exhibited lower mitochondrial membrane potential (P<0.01). While the intracellular ROS content and apoptosis rate of Raji cells in DHA+IR group were increased significantly(P<0.01). In addition, compared with the other three groups, there was no significant difference in the expression of AKT, but the phosphorylation of AKT protein were significantly inhibited and the expression of Bcl-2 protein was markedly decreased. However, the expressions of Bax and Cleaved-Caspase-3 protein were markedly increased. CONCLUSIONS: DHA might activate the mitochondrial apoptotic signal via inhibiting phosphoinositide 3-kinase (PI3K/AKT) pathway and increase oxidative stress to enhance the radiosensitivity of Raji cells.

An analysis of the current status of hospital emergency preparedness for infectious disease outbreaks in Beijing, China.

BACKGROUND: In the event of a large-scale infectious disease outbreak, hospitals will play a critical role. The objective of our study is to understand the current status of hospitals preparedness for infectious disease outbreaks in Beijing and to provide basic information for infectious disease prevention and control in hospitals. METHODS: One hundred fifty-two secondary and tertiary care hospitals in Beijing were surveyed by a standardized questionnaire. Data related to hospital demographic information and their emergency plans, laboratory diagnosis capacity, medical treatment procedures for infectious diseases, stockpiles of drugs and personal protective equipment, and staff training were collected. RESULTS: Responses were received from 134 (88.2%) of the 152 hospitals surveyed. Overall, hospitals reported that the number of physicians and nurses in infectious disease accounted for only 1.8% of the total physicians and 2.5% of the total nurses, and surgery beds accounted for 8.5% of all the fixed beds. Approximately 93.3% of the hospitals surveyed reported that they had an emergency plan, and none of those reported that their laboratories were able to isolate and identify all 8 kinds of common pathogens of infectious diseases: 22.4% of the hospitals had medical treatment procedures for all these infectious diseases, 23.1% had stored specific drugs for treatment, 2.2% had all personal protective equipment, and 30.6% reported that their health care staff had been trained in hospital emergency preparedness for infectious diseases. In general, emergency preparedness for infectious diseases in tertiary care hospitals was better than that in secondary care hospitals; the preparedness at general hospitals was better than that at specialized hospitals; and that at teaching hospitals was better than that at nonteaching hospitals. CONCLUSION: Emergency preparedness for infectious disease at hospitals in Beijing was in an early stage of development during this survey. Comprehensive measures should be developed and implemented to enhance their capacity for infectious disease emergency.