Curcumin Suppresses Colon Cancer In Vitro and In Vivo

Objective: To discuss In Vitro and In Vivo the effects of curcumin on colon cancer. Material and Methods: SW620 cell and nude mice with tumor were respectively divided into 3 groups: NC, low, middle, high and 5-Fu groups. Measuring the cell activity by MTT, the cell cycle and cell apoptosis using flow cytometry and relative proteins by WB assay in cell experiment. Evaluating tumor volume and weight, cell apoptosis rate by TUNEL assay and relative proteins by Immunohistochemistry (IHC). Results: Compared with NC group, the SW620 cell activity was significantly depressed with cell apoptosis and G1 phase rates increasing and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by WB assay; In Vivo study, the tumor volume and size were significantly suppressed and positive cell number were significantly up-regulation in curcumin treated groups with dose-dependent, and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by IHC. Conclusions: Curcumin had anti-tumor effects to colon cancer via regulation PI3K/AKT/P53 pathway In Vivo and vitro study.

Nrf2 Improves Airway Goblet Cell Metaplasia in Chronic Obstructive Pulmonary Disease (COPD) and Its Mechanism

Objective: The aim of our research was to evaluate Nrf2 in COPD treatment and relative mechanism by vivo study. Materials: The mice were divided into Normal, Model and CCL16 groups. Measuring Pathology and goblet cell number by HE or AB/PAS staining; Evaluating apoptosis cell number by TUNEL assay; using flow separation to analysis inflammatory cells in difference groups; MAPK and NF-κB(p65) protein expression were evaluated by IHC assay in tissues; Total protein concentration of MUC5AC, Nrf2, Bax and Bcl-2 were evaluated by WB assay. Results: Compared with Normal group, the pathology was deteriorate and goblet cell number were significantly up-regulation in Model group, apoptosis goblet cell number were significantly depressed (P < 0.001), lympbocyte rate and hypertrophic rate were significantly down-regulation and Eosinophils rate, Macrophage rate and Neutrophils rate were significantly up-regulation (P < 0.001, respectively) in Model group. By IHC assay, MAPK and NF-κB(p65) proteins expression significantly increased (P < 0.001, respectively) in Model group; by WB assay, MUC5AC and Bcl-2 protein expression were significantly up-regulation and Nrf2 and Bax proteins expression were significantly down-regulation (P < 0.001, respectively) in Model group. Nrf2 supplement, the COPD were significantly improved with relative inflammatory cells rates significantly improving and relative proteins improving. Conclusion: Nrf2 could improve COPD by inducing goblet cell apoptosis increasing via regulation MAPK/NF-κB(p65) pathway in vivo study.

Effects of Long Noncoding RNA TUG1 (Taurine Up-Regulated Gene 1) on Growth and Metastasis of the Non-Small Cell Lung Cancer and Its Mechanism

Objective: Our research was to discuss effects and mechanism of lncRNA TUG1 in NSCLC by vitro study. Methods: A549 and H1299 cells were divided into NC, pcDNA 3.1 and lncRNA TUG1 groups. Measuring cell proliferation using CCK-8 assay, cell apoptosis by flow cytometry, invasion cell number by transwell and wound healing rate by wound healing assay. Relative gene and protein expressions by RT-qPCR and WB assay. Results: Compared with NC group, the cell proliferation rate, invasion cell number and wound healing rate were significantly depressed in A549 and H1299 cell lines (P < 0.001, respectively). By RT-qPCR and WB assay, lncRNA TUG1 gene expression were significantly increased (P < 0.001, respectively); E-cadherin gene and protein expression were significantly up-regulation, and N-cadherin and Vimentin gene and protein expressions were significantly depressed compared with those of NC group in A549 and H1299 cell lines (P < 0.001, respectively). Conclusion: lncRNA TUG1 had effects to suppress NSCLC cell biological activities by regulation EMT relative gene and proteins expression in vivo study.

Research on the Enhancement Mechanism of Dihydromyricetin on the Inhibitory Role of Cisplatin Towards Breast Cancer Cell Activity

Objective: The purpose of our study was to evaluate Enhancement Mechanism of Dihydromyricetin (DMY) on the Inhibitory Role of Cisplatin Towards Breast Cancer Cell Activity. Materials and Methods: The MCF-7 were divided into NC, DMY, Cis and DMY+Cis groups. Using relative methods (MTT, TUNEL, Transwell, flow cytometry and wound healing) to evaluate MCF-7 cell biological activities including cell viability, apoptosis, invasion cell number and wound healing rate. The relative proteins expressions including FOXO-1, Noxa, Bim, Cyto C, Caspase-3, Caspase-9 and Apaf-1 were evaluated by WB assay. Results: MCF-7 cell viability, invasion cell number and wound healing rates were significantly depressed and apoptosis rate were significantly increased in DMY, Cis and DMY+Cis groups (P < 0.01, respectively). Compared with Cis group, cell viability, invasion cell number and wound healing rates were significantly depressed and apoptosis rate were significantly increased in DMY+Cis group (P < 0.05, respectively). Conclusion: Dihydromyricetin can effectively enhance the inhibitory effect of cisplatin on breast cancer cells.

Bone Marrow Stromal Cells Promotes Morphological Senescence of Prostate Cancer Cells and Inhibits Metastasis Associated 1 Gene Level

This study assessed the mechanism of Bone Marrow Stromal Cells (BMSCs) in prostate cancer (PC) and its effect on MTA-1 gene and PC cell senescence. PC-3 cells were assigned into QL group (prostate cancer group: normal culture) and GS group (BMSCs group: treated with BMSCs) followed by analysis of MTA-1 level, cell senescence, apoptosis and invasion. MTA-1 level in QL group (0.83±0.07) was significantly higher than GS group (0.14±0.02) (P < 0.05), indicating that BMSCs had an inhibitory effect on MTA-1 expression. Similar change of MTA-l mRNA was also found with higher level in QL group than GS group (P < 0.05). Cell senescence was found in QS group but not QL group, indicating that BMSCs promote cell senescence. Compared with GS group, QL group has a higher cell number in G0/G1 (67.13±6.45%) and S (19.59±3.35%) than GS group (G0/G1:50.51±2.19% and S: 11.42±1.61%) but lower G2/M (QL: 15.97±3.59% versus GS: 32.25±3.24%). QL group had significantly lower cell apoptosis rate at 35 h (5.21±1.2%) and 45 h (3.97±0.95%) than GS group at 35 h (17.85±1.23%), 45 h (10.21±1.26%) with elevated number of invasions. In conclusion, BMSCs promote PC-3 cell senescence and apoptosis by inhibiting the expression of MTA-1 and reduce cell invasion ability.

miR-29b-3p’s Effects on Prostate Cancer

Objection: Our research wanted to discuss miR-29b-3p in PCa occurrence and development and relative mechanisms. Methods: Collecting adjacent and cancer tissues from prostate cancer patients and measuring miR-29b-3p expressions by RT-qPCR and ISH assay. Using DU145 and PC3 cell lines which the miR-29b-3p were high expression in our study. Using miR inhibitor to knockdown miR-29b-3p in DU145 and PC3. Using CCK-8 and flow cytometry to measure cell proliferation and cell apoptosis, invasion cell number by transwell and wound healing rate by wound healing assay. The relative proteins expressions were measured using WB assay. p-AKT nuclear levels were evaluated using Cell immunofluorescence test. Using dual-luciferase reporter gene assay to analysis correlation miR-29b-3p and PTEN. Results: miR-29b-3p gene significantly increased. miR-29b-3p knockdown had effects to depress cell proliferation, increase cell apoptosis, depress invasion cells number and wound healing rates. PTEN proteins were significantly up-regulation and p-AKT and MMP-9 proteins expressions were significantly down-regulation (P < 0.001, respectively). And p-AKT nuclear volume were significantly depressed. And miR-29b-3p could target PTEN. Conclusion: miR-29b-3p played an oncology gene in prostate cancer via regulation PTEN/AKT pathway in vitro study.

Club Cell Secretion Protein 16 (CC16) Improve Chronic Obstructive Pulmonary Disease In Vivo Study

Purpose: The purpose of this study was to evaluate CC16 in COPD treatment and relative mechanism by vivo study. Materials and methods: The mice were divided into Normal, Model and CC16 groups. Measuring Pathology and goblet cell number by HE or AB/PAS staining; Evaluating apoptosis cell number by TUNEL assay; using flow separation to analysis inflammatory cells in difference groups; MAPK and NF-κB(p65) protein expression were evaluated by IHC assay in tissues; Total protein concentration of MUC5AC, CC16, Bax and Bcl-2 were evaluated by Western Blot (WB) assay. Results: Compared with Normal group, the pathology was deteriorate and goblet cell number were significantly up-regulation in Model group, apoptosis goblet cell number were significantly depressed (P < 0.001), lympbocyte rate and hypertrophic rate were significantly down-regulation and Eosinophils rate, Macrophage rate and Neutrophils rate were significantly up-regulation (P < 0.001, respectively) in Model group. By IHC assay, MAPK and NF-κB(p65) proteins expression were significantly increased (P < 0.001, respectively) in Model group; by WB assay, MUC5AC and Bcl-2 protein expression were significantly up-regulation and CC16 and Bax proteins expression were significantly down-regulation (P < 0.001, respectively) in Model group. CC16 supplement, the COPD were significantly improved with relative inflammatory cells rates significantly improving and relative proteins improving. Conclusion: CC16 could improve COPD by inducing goblet cell apoptosis increasing via regulation MAPK/NF-κB(p65) pathway In Vivo study.

Fingolimod Rescues Memory and Improves Pathological Hallmarks in the 3xTg-AD Model of Alzheimer’s Disease

Therapeutic strategies for Alzheimer’s disease (AD) have largely focused on the regulation of amyloid pathology while those targeting tau pathology, and inflammatory mechanisms are less explored. In this regard, drugs with multimodal and concurrent targeting of Aβ, tau, and inflammatory processes may offer advantages. Here, we investigate one such candidate drug in the triple transgenic 3xTg-AD mouse model of AD, namely the disease-modifying oral neuroimmunomodulatory therapeutic used in patients with multiple sclerosis, called fingolimod. In this study, administration of fingolimod was initiated after behavioral symptoms are known to emerge, at 6 months of age. Treatment continued to 12 months when behavioral tests were performed and thereafter histological and biochemical analysis was conducted on postmortem tissue. The results demonstrate that fingolimod reverses deficits in spatial working memory at 8 and 12 months of age as measured by novel object location and Morris water maze tests. Inflammation in the brain is alleviated as demonstrated by reduced Iba1-positive and CD3-positive cell number, less ramified microglial morphology, and improved cytokine profile. Finally, treatment with fingolimod was shown to reduce phosphorylated tau and APP levels in the hippocampus and cortex. These results highlight the potential of fingolimod as a multimodal therapeutic for the treatment of AD.

Bcl-XL but Not Bcl-2 Is a Potential Target in Medulloblastoma Therapy

Medulloblastoma (MB) is the most common solid tumour in children and, despite current treatment with a rather aggressive combination therapy, accounts for 10% of all deaths associated with paediatric cancer. Breaking the tumour cells’ intrinsic resistance to therapy-induced cell death should lead to less aggressive and more effective treatment options. In other tumour entities, this has been achieved by modulating the balance between the various pro- and anti-apoptotic members of the Bcl-2 family with small molecule inhibitors. To evaluate the therapeutic benefits of ABT-199 (Venetoclax), a Bcl-2 inhibitor, and ABT-263 (Navitoclax), a dual Bcl-XL/Bcl-2 inhibitor, increasingly more relevant model systems were investigated. Starting from established MB cell lines, progressing to primary patient-derived material and finally an experimental tumour system imbedded in an organic environment were chosen. Assessment of the metabolic activity (a surrogate readout for population viability), the induction of DNA fragmentation (apoptosis) and changes in cell number (the combined effect of alterations in proliferation and cell death induction) revealed that ABT-263, but not ABT-199, is a promising candidate for combination therapy, synergizing with cell death-inducing stimuli. Interestingly, in the experimental tumour setting, the sensitizing effect of ABT-263 seems to be predominantly mediated via an anti-proliferative and not a pro-apoptotic effect, opening a future line of investigation. Our data show that modulation of specific members of the Bcl-2 family might be a promising therapeutic addition for the treatment of MB.

A New RING Finger Protein, PLANT ARCHITECTURE and GRAIN NUMBER 1, Affects Plant Architecture and Grain Yield in Rice

Developing methods for increasing the biomass and improving the plant architecture is important for crop improvement. We herein describe a gene belonging to the RING_Ubox (RING (Really Interesting New Gene) finger domain and U-box domain) superfamily, PLANT ARCHITECTURE and GRAIN NUMBER 1 (PAGN1), which regulates the number of grains per panicle, the plant height, and the number of tillers. We used the CRISPR/Cas9 system to introduce loss-of-function mutations to OsPAGN1. Compared with the control plants, the resulting pagn1 mutant plants had a higher grain yield because of increases in the plant height and in the number of tillers and grains per panicle. Thus, OsPAGN1 may be useful for the genetic improvement of plant architecture and yield. An examination of evolutionary relationships revealed that OsPAGN1 is highly conserved in rice. We demonstrated that OsPAGN1 can interact directly with OsCNR10 (CELL NUMBER REGULATOR10), which negatively regulates the number of rice grains per panicle. A transcriptome analysis indicated that silencing OsPAGN1 affects the levels of active cytokinins in rice. Therefore, our findings have clarified the OsPAGN1 functions related to rice growth and grain development.