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.

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.

miR-129 Regulates Cell Viability in Alzheimer’s Disease Through Targeting Amyloid Precursor Protein (APP)

This study intends to explore miR-129’s effect on cell viability of Alzheimer’s disease by regulating the target gene APP. The hippocampal neurons were assigned into model group (MO group); mimetic group (SI group); inhibitor group (IN group) followed by analysis of hippocampal neuronal cell proliferation and activity, APP protein content, miR-129 expression and cell apoptosis by CCK-8 assay, Western blot method, MTT assay, qRT-PCR and flow cytometry. miR-129 expression of hippocampal neurons in IN group was lowest. Compared with IN and MO groups, SI group had significantly increased miR-129 level and reduced number of hippocampal neuron apoptosis (P < 0.05). Compared with IN group, MO group had significantly reduced cell apoptosis (P < 0.05). SI group had highest number of hippocampal neurons proliferation followed by IN group. SI group had highest OD value followed by MO group and IN group. The cell activity of SI group was higher than that of IN group and MO group (both P < 0.05). Compared with SI group, rat neuron activity in MO group was significantly higher than IN group (P < 0.05). The APP protein expression of hippocampal neuron cells in SI group was lowest followed by MO group and IN group (P < 0.05). In conclusion, the low miR-129 expression can inhibit the activity of hippocampal neurons possibly through up-regulation of APP protein content.

Prognostic Biomarkers and Therapeutic Targets Identification Among CXC Chemokines in the Colon Adenocarcinoma Microenvironment

Background: COAD is among the most prevalent malignancy, with a very high incidence rate. Crosstalk between cancer and interstitial cells significantly affects cancer development, modulated partly by chemokines production. When present in the tumor microenvironment, CXC chemokines have been shown to regulate tumor cell activity and influence immune cell transport, resulting in anti-tumor immune mechanisms and influencing the outcomes of the patient; nonetheless, the CXC chemokines expression levels in COAD, as well as their prognostic significance, have not yet been established.Methods: This study used UALCAN, GeneMANIA, STRING, TRRUST, cBioPortal, TIMER, and GEPIA,Results: The expression of CXC1/2/3/5/6/11/12/13/14/16/17 in COAD patients was shown to be significantly correlated with the pathological stage. A considerably improved prognosis was observed in patients with low transcriptional levels of CXCL9/10/11. Differentially expressed CXC chemokines exert roles that are predominantly correlated with the chemokine signaling pathway and interactions of cytokine–cytokine receptors. Our findings indicated that the transcriptional factors, including SP1, RELA, and NFKB1 are essential for the production of CXC chemokines. Furthermore, we discovered a substantial association between the CXC chemokines production and infiltration of 6 kinds of immune cells (CD8+ T cells, dendritic cells, B cells, CD4+ T cells, neutrophils, and macrophages,). Conclusions: These findings might be useful in identifying prognostic indicators and immunotherapeutic targets for colon cancer.

The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

Effect of antioxidants and growth regulators on shoot organogenesis in the apical meristem culture of Fragaria × ananassa (Duchesne ex Weston) Duchesne ex Rozier

The initiation of strawberries into in vitro culture is known to be complicated by the inhibition of organogenesis by phenolic oxidation products. An important role in this process is given to the selection of growth regulators that increase meristematic cell activity and shoot proliferation at the stage of organogenesis induction. The present study aims to obtain a viable apical meristem culture of garden strawberry and to study the effect of different antioxidants (reduced glutathione (RG); a new preparation, i.e., a mechanical composite (MC) on the basis of biogenic silicon and green tea catechins and plant growth regulators (6-benzylaminopurine; thidiazuron) on the initiation of axillary shoot formation in strawberry meristem culture. Terminal buds containing an apical meristem and two leaf primordia isolated from the stolons of two garden strawberry cultivars (Sunny Meadow and Festival Chamomile) were used as primary explants for the initiation of strawberries into in vitro culture. It was found for the first time that the MC exhibits higher antioxidant activity as compared to reduced glutathione, reduces darkening of initial explants, as well as enhancing regeneration up to 13.0% at p ≤ 0.05. Furthermore, the best effect on the formation of microshoots per explant is observed toward the end of material introduction into in vitro culture when combining the MC with growth regulators in the culture medium. Here, the effect of strawberry cultivar on explant regeneration and the number of microshoots per explant are insignificant. It is concluded that the procedure for using the MC as an effective antioxidant during material initiation into the culture can be applied to the large-scale in vitro propagation of garden strawberries. Moreover, the technology for obtaining the MC from plant waste is environmentally friendly, which is a significant advantage for its use in in vitro technologies.

KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population

The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. Through regulation of natural killer (NK) cell activity KIRs participate in tumour surveillance and clearing viral infections. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Inferring KIR gene content from genetic variant data is therefore desirable for immunogenetic analysis, particularly in the context of growing biobank genome data collections that rely on genotyping by microarray. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 807 Finnish biobank samples genotyped for 5900 KIR-region SNPs and analysed for KIR gene content with targeted sequencing. Cross-validation results demonstrate a high mean overall accuracy of 98.5% (95% CI [97.0–99.2]%) which compares favourably with previous methods including short-read sequencing based approaches.

hMSCs Migrate under the Chemotaxis of CXCL-13 and Enhance Islet B Cell Activity through p-AKT Signaling Pathway in High-Glucose Environment

As a common clinical chronic disease, the incidence of diabetes is increasing year by year. According to the latest statistics from the International Diabetes Federation, as of 2019, the global prevalence of diabetes has reached 8.3%. This study aims to investigate the effect of CXCL-13 on the migration ability of human mesenchymal stem cells (hMSCs) and to clarify the specific molecular mechanism of the protective effect of hMSCs on islet B cells. The hMSCs were cultured in high-glucose environment, and the effect of CXCL-13 on the migration ability of hMSCs was determined by Transwell experiment. After coculture of hMSCs and islet B cells, the activity of cells was detected by CCK8 assay, the expression of Ki-67 in cells was detected by RT-PCR, and the expression of P53 was detected by Western blot to investigate the effect of hMSCs on the proliferation and apoptosis of islet B cells. The effect of hMSCs on the function of islet B cells was determined by glucose stimulated insulin secretion experiment. Transwell experiment results showed that CXCL-13 could promote the migration of hMSCs to islet B cells in high-glucose environment. The results of CCK-8 showed that the cell activity in the coculture group was significantly higher than that of the other groups, and RT-PCR showed that the expression of Ki-67 was significantly increased in the coculture group of hMSCs and islet B cells. The results of Western blot showed that the expression of P53 was significantly decreased in the coculture group, and the glucose stimulated insulin secretion test showed that insulin secretion was significantly increased. It was found that after the inhibition of ATK, cell activity was significantly reduced, and apoptosis was significantly increased. Meanwhile, the expression of Ki-67 was inhibited, the expression of P-53 was significantly increased, and insulin secretion was significantly reduced. To sum up, in a high-glucose environment, CXCL-13 effectively promoted the migration of hMSCs, and hMSCs protected the activity and function of islet B cells through Akt signaling pathway.

An emergent temporal basis set robustly supports cerebellar time-series learning

Learning plays a key role in the function of many neural circuits. The cerebellum is considered a learning machine essential for time interval estimation underlying motor coordination and other behaviors. Theoretical work has proposed that the cerebellar input recipient structure, the granule cell layer (GCL), performs pattern separation of inputs that facilitates learning in Purkinje cells (P-cells). However, the relationship between input reformatting and learning outcomes has remained debated, with roles emphasized for pattern separation features from sparsification to decorrelation. We took a novel approach by training a minimalist model of the cerebellar cortex to learn complex time-series data from naturalistic inputs, in contrast to traditional classification tasks. The model robustly produced temporal basis sets from naturalistic inputs, and the resultant GCL output supported learning of temporally complex target functions. Learning favored surprisingly dense granule cell activity, yet the key statistical features in GCL population activity that drove learning differed from those seen previously for classification tasks. Moreover, different cerebellar tasks were supported by diverse pattern separation features that matched the demands of the tasks. These findings advance testable hypotheses for mechanisms of temporal basis set formation and predict that population statistics of granule cell activity may differ across cerebellar regions to support distinct behaviors.