Regulatory mechanism of the Glabrene against non-small cell lung cancer by suppressing FGFR3.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3. METHODS: HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p-ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E-cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E-cadherin, ERK1/2, and p-ERK1/2 were detected via qPCR and Western blot. IGF-1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA). RESULTS: This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over-expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF-1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p-ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p-ERK1/2 expression, as well as contents of IGF-1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E-cadherin. CONCLUSION: Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial-mesenchymal transition (EMT).

Traditional Chinese Medicine Prolongs Progression-Free Survival and Enhances Therapeutic Effects in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)Treated Non-Small-Cell Lung Cancer (NSCLC) Patients Harboring EGFR Mutations.

BACKGROUND Lung cancer is the most common cause of cancer-associated deaths worldwide. This study aimed to investigate the efficacy and safety of Traditional Chinese Medicine combining EGFR-TKIs in treatment of NSCLC patients harboring EGFR mutations. MATERIAL AND METHODS This study involved 153 advanced-stage NSCLC patients harboring EGFR mutations. Patients were divided into a Control group (administered EGFR-TKI, n=61) and an Experimental group (administered Traditional Chinese Medicine combining EGFR and TKI, n=92). Progression-free survival (PFS) was evaluated for exon 19 deletion and/or 21 deletion patients. Disease control rate (DCR) was assessed to observe therapeutic effects. Adverse effects, including rashes, diarrhea, ALT/AST increase, dental ulcers, and onychia lateralis, were also evaluated. RESULTS TCM combining EGFR-TKI (90.11%) demonstrated no DCR improvement compared to single EGFR-TKI (83.33%) (p>0.05). Median PFS (mPFS) of TCM combining EGFR-TKI (13 months) was significantly longer compared to that in the single EGFR-TKI group (8.8 months) (p=0.001). For 19DEL mutant NSCLC, the mPFS (11 months) in TCM combining EGFR-TKI was significantly longer compared to single EGFR-TKI (8.5 months) (p=0.007). The mPFS of L858 mutant NSCLC patients in EGFR-TKI combining CTM (14 months) was significantly longer compared to single EGFR-TKI (9.5 months) (p=0.015). TCM combining EGFR-TKI was more inclined to prolong mPFS of NSCLC with exon 21 deletion. TCM combining EGFR-TKI illustrated no additional adverse effects in NSCLC patients (p=0.956). CONCLUSIONS Application of Traditional Chinese Medicine prolonged progression-free survival and enhanced therapeutic effect in NSCLC patients harboring EGFR mutations receiving EGFR-TKI treatment. Meanwhile, adjunctive Chinese medicine combining EGFR-TKI in NSCLC with EGFR mutations caused no adverse effects.

Modulation of protease-activated receptor expression by Porphyromonas gingivalis in human gingival epithelial cells.

BACKGROUND: Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in mediating inflammation, pain and other functions. The oral pathogen Porphyromonas gingivalis (P. gingivalis) secretes proteases that activate PARs. The aim of this study was to elucidate the role of PARs in the pathogenesis of chronic periodontitis by expression analysis of PARs in human gingival epithelial cells (GECs) before and after P. gingivalis supernatants treatment. METHODS: GECs were isolated from healthy human gingival tissue samples. The expression of PARs in GECs was determined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. The effect of P. gingivalis proteases was investigated by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and flow cytometry. RESULTS: PAR-1, PAR-2, and PAR-3 were expressed in GECs. PAR-4 was not found by both RT-PCR and flow cytometry. Analysis of gene expression using QRT-PCR showed an up-regulation of PAR-2 mRNA in comparison to the untreated control cells (P < 0.05). In contrast, the mRNA expressions of PAR-1 and PAR-3 were significantly down-regulated (P > 0.05) in response to P. gingivalis supernatant compared to that in unstimulated control cells. This effect was abrogated by the protease inhibitor TLCK (P < 0.05). The results of flow cytometry indicated PARs protein levels consistent with mRNA levels in the results of QRT-PCR. CONCLUSIONS: Our study shows that PAR-1, PAR-2 and PAR-3 are expressed in GECs. P. gingivalis proteases play a role in the regulation of innate immune responses in GECs. GECs use PARs to recognize P. gingivalis and mediate cell responses involved in innate immunity.

Application of 3D Whole-Brain Texture Analysis and the Feature Selection Method Based on within-Class Scatter in the Classification and Diagnosis of Alzheimer's Disease.

BACKGROUND: Patients with mild cognitive impairment (MCI) are a high-risk group for Alzheimer's disease (AD). Thus, a reliable prediction of the conversion from MCI to AD based on three-dimensional (3D) texture features of MRI images could help doctors in developing effective treatment protocols. METHODS: The 3D texture features of the whole-brain were deduced based on the gray-level co-occurrence matrix. Then, the embedded feature selection method based on least squares loss and within-class scatter (LSWCS) was employed to select the optimal subsets of features that were used for binary classification (AD, MCI_C, MCI_S, normal control in pairs) based on SVM. A tenfold cross validation was repeated ten times for each classification. LASSO, fused_LASSO, and group LASSO are used in feature selection step for comparison. RESULTS: The accuracy and the selected features are the focus of clinical diagnosis reports, indicating that the feature selection algorithm is effective.

LncRNA PCNAP1 Promotes Hepatoma Cell Proliferation through Targeting miR-340-5p and is Associated with Patient Survival.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes poor outcome. Dysregulation of long noncoding RNA (lncRNA) is involved in HCC. Upregulation of the lncRNA PCNAP1 has been reported to promote HBV-infectious HCC growth, but its clinical significance and underlying mechanisms in HCC development remain unclear. Here, we report that PCNAP1 expression is increased in both HBV-infectious and noninfectious HCC tissues compared with matched normal tissues, and its upregulation correlates with poor survival rates of HCC patients. Furthermore, we found that PCNAP1 promotes HCC cell proliferation through acting as a competitive endogenous RNA (ceRNA) to sponge miR-340-5p, which has been reported to directly inhibit ATF7 expression in HCC cells. Moreover, the PCNAP1/miR-340-5p/ATF7 signaling associates with the poor survival rates of HCC patients. Collectively, our findings suggest that the PCNAP1/miR-340-5p/ATF7 signaling may be a potential biomarker for the prognosis of HCC patients and a potential therapeutic target for HCC.

Application of Generalized Split Linearized Bregman Iteration algorithm for Alzheimer's disease prediction.

In this paper, we applied a novel method for the detection of Alzheimer's disease (AD) based on a structural magnetic resonance imaging (sMRI) dataset. Specifically, the method involved a new classification algorithm of machine learning, named Generalized Split Linearized Bregman Iteration (GSplit LBI). It combines logistic regression and structural sparsity regularizations. In the study, 57 AD patients and 47 normal controls (NCs) were enrolled. We first extracted the entire brain gray matter volume values of all subjects and then used GSplit LBI to build a predictive classification model with a 10-fold full cross-validation method. The model accuracy achieved 90.44%. To further verify which voxels in the dataset have greater impact on the prediction results, we ranked the weight parameters and obtained the top 6% of the model parameters. To verify the generalization of model prediction and the stability of feature selection, we performed a cross-test on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and a Chinese dataset and achieved good performances on different cohorts. Conclusively, based on the sMRI dataset, our algorithm not only had good performance in a local cohort with high accuracy but also had good generalization of model prediction and stability of feature selection in different cohorts.

Clinical effects of the method for warming the middle-jiao and strengthening the spleen on gastric mucosa repair in chronic gastritis patients.

OBJECTIVE: To observe clinical effects of the method for warming the middle-jiao and strengthening the spleen on gastric mucosa repair in chronic gastritis patients. METHODS: The 42 cases of the treatment group were orally adiministered Yiweikang Capsule; while the other 25 cases in the control group were orally given Wenweishu Capsule. Both the groups were observed for 2 months. RESULTS: The total effective rate in the treatment group was obviously higher than that of the control group (P < 0.05), with statistical significance shown by the TCM symptom score, gastroscopic examination and the HP test (P < 0.05 or P < 0.01). CONCLUSIONS: Yiweikang Capsule is an effective medicine for chronic gastritis.

Protease-activated receptors expression in gingiva in periodontal health and disease.

OBJECTIVE: Protease-activated receptors (PARs) are a unique class of receptors which are implicated in mediating inflammation, pain and other functions. The aim of this study was to elucidate the role of PARs in the pathogenesis of chronic periodontitis by differential expression analysis of PARs in the gingival tissues of chronic periodontitis patients compared with those of healthy control individuals. DESIGN: Gingival tissue specimens were collected from chronic periodontitis patients (n=20) and control individuals (n=20). The expression of PAR-1, -2, -3 and -4 was determined in these tissues by immunohistochemistry and differential expression between the two groups was investigated by quantitative real-time reverse transcription-polymerase chain reaction analysis. RESULTS: PAR-1, -2, -3 and -4 were expressed in all gingival tissues. A significant overexpression of PAR-3 was detected in chronic periodontitis-affected tissues compared to healthy gingival tissues. However, expression of PAR-2 was decreased in periodontal lesions. CONCLUSIONS: Our study shows that PAR-1, -2, -3 and -4 are expressed in both healthy and inflamed gingival tissues. Furthermore, PAR-2 and PAR-3 may contribute to the inflammatory responses associated with chronic periodontitis.

[Expressions of protease-activated receptors in human gingival fibroblasts and its functions in periodontitis].

OBJECTIVE: To investigate the expression types of protease-activated receptors(PAR) in human gingival fibroblasts(HGF) and the functions of PAR in periodontitis. METHODS: Primary HGF were cultured.Reverse transcription PCR(RT-PCR) was used to detect the expression of PAR in HGF. Recombinant gingipain R (rRgp) was applied to HGF. The change of PAR expression on the cell surface was analyzed by real-time quantitative RT-PCR, and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of the interleukin (IL)-6 production from HGF. The results of RT-PCR and ELISA were statistically analyzed using the two independent samples t-test of SPSS10.0 software. RESULTS: HGF expressed PAR-1 and PAR-3. The expression of PAR-1 and PAR-3 changed after two rRgp treatment with HGF cells. The relative expression of PAR-1 was decreased from 1.04 ± 0.31 to 0.67 ± 0.11 and 0.31 ± 0.11. The relative expression of PAR-3 was decreased from 1.01 ± 0.44 to 0.79 ± 0.13 and 0.44 ± 0.12(P < 0.05). The level of IL-6 was increased after rRgp treatment for 8 h. The control group was (18.77 ± 4.09) µg/L, the rRgp treatment groups were (179.36 ± 15.81) and (320.56 ± 26.19) µg/L respectively. CONCLUSIONS: HGF expressed PAR-1 and PAR-3 and were involved in periodontal inflammation.