Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence.

Nuclear decoupling and softening are the main cellular mechanisms to resist mechanical stress-induced nuclear/DNA damage, however, its molecular mechanisms remain much unknown. Our recent study of Hutchinson-Gilford progeria syndrome (HGPS) disease revealed the role of nuclear membrane protein Sun2 in mediating nuclear damages and cellular senescence in progeria cells. However, the potential role of Sun2 in mechanical stress-induced nuclear damage and its correlation with nuclear decoupling and softening is still not clear. By applying cyclic mechanical stretch to mesenchymal stromal cells (MSCs) of WT and Zmpset24-/- mice (Z24-/-, a model for HGPS), we observed much increased nuclear damage in Z24-/- MSCs, which also featured elevated Sun2 expression, RhoA activation, F-actin polymerization and nuclear stiffness, indicating the compromised nuclear decoupling capacity. Suppression of Sun2 with siRNA effectively reduced nuclear/DNA damages caused by mechanical stretch, which was mediated by increased nuclear decoupling and softening, and consequently improved nuclear deformability. Our results reveal that Sun2 is greatly involved in mediating mechanical stress-induced nuclear damage by regulating nuclear mechanical properties, and Sun2 suppression can be a novel therapeutic target for treating progeria aging or aging-related diseases.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

BACKGROUND: "Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. METHODS: We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. RESULTS: All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. CONCLUSIONS: Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

Enhancing anti-tumor efficacy and immune memory by combining 3p-GPC-3 siRNA treatment with PD-1 blockade in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate and presents a major challenge for human health. Activation of multiple oncogenes has been reported to be strongly associated with the progression of HCC. Moreover, the immunosuppressive tumor microenvironment (TME) and the host immune system are also implicated in the development of malignant HCC tumors. Glypican-3 (GPC-3), a proteoglycan involved in the regulation of cell proliferation and apoptosis, is aberrantly expressed in HCC. We synthesized a short 5'-triphosphate (3p) RNA targeting GPC-3, 3p-GPC-3 siRNA, and found that it effectively inhibited subcutaneous HCC growth by raising type I IFN levels in tumor cells and serum and promoting tumor cell apoptosis. Moreover, 3p-GPC-3 siRNA was able to enhance the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells while reducing the proportion of regulatory T cells (Tregs) in the TME. Most intriguingly, a blocking anti-PD-1 antibody improved the anti-tumor effect of 3p-GPC-3 siRNA, predominantly by activating the immune response, reversing immune exhaustion, and improving immune memory. Our study suggests that the combination of 3p-GPC-3 siRNA administration and PD-1 blockade may represent a promising therapeutic strategy for HCC.

Balanced below- and above-ground growth improved yield and water productivity by cultivar renewal for winter wheat.

Breeding cultivars that can maintain high production and water productivity (WP) under various growing conditions would be important for mitigating freshwater shortage problems. Experiments were carried out to assess the changes in yield and WP of different cultivars by breeding and traits related to the changes using tubes with 1.05 m depth and 19.2 cm inner diameter buried in the field located in the North China Plain. Six winter wheat cultivars released from the 1970s to 2010s were assessed under three water levels for three seasons. The results indicated that yield was on average improved by 19.9% and WP by 21.5% under the three water levels for the three seasons for the cultivar released in the 2010s as compared with that released in the 1970s. The performance of the six cultivars was relatively stable across the experimental duration. The improvement in yield was mainly attributed to the maintenance of higher photosynthetic capacity during the reproductive growth stage and greater above-ground biomass accumulation. These improvements were larger under wet conditions than that under dry conditions, indicating that the yield potential was increased by cultivar renewal. Traits related to yield and WP improvements included the increased harvest index and reduced root: shoot ratio. New cultivars reduced the redundancy in root proliferation in the topsoil layer, which did not compromise the efficient utilization of soil moisture but reduced the metabolic input in root growth. Balanced above- and below-ground growth resulted in a significant improvement in root efficiency at grain yield level up to 40% from the cultivars released in the 1970s to those recently released. The results from this study indicated that the improved efficiency in both the above- and below-parts played important roles in enhancing crop production and resource use efficiency.

Multi-slice spiral computed tomography in differential diagnosis of gastric stromal tumors and benign gastric polyps, and gastric stromal tumor risk stratification assessment.

BACKGROUND: The biological characteristics of gastric stromal tumors are complex, and their incidence has increased in recent years. Gastric stromal tumors (GST) have potential malignant tendencies, and the probability of transformation into malignant tumors is as high as 20%-30%. AIM: To investigate the value of multi-slice spiral computed tomography (MSCT) in the differential diagnosis of GST and benign gastric polyps, and GST risk stratification assessment. METHODS: We included 64 patients with GST (GST group) and 60 with benign gastric polyps (control group), confirmed by pathological examination after surgery in PLA General Hospital, from January 2016 to June 2021. The differences in the MSCT imaging characteristic parameters and enhanced CT values between the two groups before surgery were compared. According to the National Institutes of Health's standard, GST is divided into low- and high-risk groups for MSCT imaging characteristic parameters and enhanced CT values. RESULTS: The incidences of extraluminal growth, blurred boundaries, and ulceration in the GST group were significantly higher than those in the control group (P < 0.05). The CT values and enhanced peak CT values in the arterial phase in the CST group were higher than those in the control group (P < 0.05). The MSCT differential diagnosis of GST and gastric polyp sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and areas under the curve (AUCs) were 73.44 %, 83.33%, 26.56%, 16.67%, 0.784, respectively. The receiver operating characteristic curves were plotted with the arterial CT value and enhanced peak CT value, with a statistical difference. The results showed that the sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and AUC value of arterial CT in the differential diagnosis of GST and gastric polyps were 80.18%, 62.20%, 19.82%, 37.80%, and 0.710, respectively. The sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and AUC value of the enhanced peak CT value in the differential diagnosis of GST and gastric polyps were 67.63%, 60.40%, 32.37%, 39.60%, and 0.710, respectively. The incidence of blurred lesion boundaries and ulceration in the high-risk group was significantly higher than that in the low-risk group (P < 0.05). The arterial phase and enhanced peak CT values in the high-risk group were significantly higher than those in the low-risk group (P < 0.05). CONCLUSION: Presurgical MSCT examination has important value in the differential diagnosis of GST and gastric benign polyps and can effectively evaluate the risk grade of GST patients.

LncRNA MAFG-AS1 deregulated in breast cancer affects autophagy and progression of breast cancer by interacting with miR-3612 and FKBP4 invitro.

PURPOSE: We aimed to explore the function and competing endogenous RNA (ceRNA) pathway of MAFG-AS1 in breast cancer. METHODS: qRT-PCR assay identified the expression of MAFG-AS1, miR-3612 and FKBP4. We used Western blot analysis to test the autophagy related protein levels in breast cancer cells. Functional assays such as Cell Counting Kit-8 (CCK8) assay, BrdU proliferation assay, Caspase-3 activity detection were used to identify the function of MAFG-AS1, miR-3612 and FKBP4 in breast cancer cells. Mechanism assays were used to verify the interacting relationship among MAFG-AS1, miR-3612 and FKBP4, including RNA pull down assay, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. RESULTS: MAFG-AS1 and FKBP4 were both up-regulated in breast cancer tissues. MAFG-AS1 could function as an oncogene in breast cancer to activate cell proliferation, and inhibit cell apoptosis and autophagy. Meanwhile, MAFG-AS1 could sponge miR-3612 to elevate the expression of FKBP4. Besides, FKBP4 could activate the cell proliferation and inhibit cell apoptosis and autophagy, which could relieve the inhibitory effect of miR-3612 on breast cancer cells. CONCLUSION: MAFG-AS1 could activate breast cancer progression via modulating miR-3612/FKBP4 axis in vitro.

Histone H3.3 G34-mutant Diffuse Gliomas in Adults.

The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P<0.001). Overall, 19 of the 30 patients were diagnosed of glioblastoma with the primitive neuronal component, and 8 were glioblastoma. The molecular profiling analysis revealed higher frequencies of Olig-2 loss of expression, TP53 mutation, ATRX mutation, PDGFRA mutation, and MGMT promoter methylation (P<0.05) in H3.3 G34-mutant gliomas than IDH/H3 wild-type gliomas. No TERT promoter mutation and only 1 case of EGFR amplification were detected in the H3.3 G34-mutant cohort, the frequencies of which were significantly higher in the IDH/H3 wild-type cohort. A dismal prognosis was observed in H3.3 G34-mutant patients comparing to IDH/H3 wild-type cohort (overall survival: 14 vs. 22 mo; P=0.026). Univariate and multivariate analyses showed that the extent of resection and TP53 mutation were independently affecting prognosis. The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.

A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7.

Endometrial cancer (EC) is one of the most frequent gynecological tumors, and chemoresistance is a major obstacle to improving the prognosis of EC patients. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have recently emerged as crucial chemoresistance regulators that alter the levels of downstream target genes. Multidrug Resistance Protein 7 (MRP-7/ABCC10) is an ATP-binding cassette transporter that causes the resistance to anti-cancer drugs. The purpose of this research is to determine whether MRP-7 has a role in mediating the sensitivity of EC cells to paclitaxel and whether the expression of MRP-7 is regulated by miR-98 and lncRNA NEAT1. We reported that the levels of MRP-7 were significantly increased in EC tissues and associated with an unfavorable prognosis. Downregulation of MRP-7 in EC cells sensitized these cells to paclitaxel and reduced cell invasion. PLAUR serves as a downstream molecule of MRP-7 and facilitates paclitaxel resistance and EC cell invasiveness. Moreover, miR-98 serves as a tumor suppressor to inhibit MRP-7 expression, leading to the repression of paclitaxel resistance. Furthermore, a novel lncRNA, NEAT1, was identified as a suppressor of miR-98, and NEAT1 could upregulate MRP-7 levels by reducing the expression of miR-98. Taken together, these findings demonstrate that upregulation of MRP-7 and NEAT1, and downregulation of miR-98 have important roles in conferring paclitaxel resistance to EC cells. The modulation of these molecules may help overcome the chemoresistance against paclitaxel in EC cells.

Correlation between rs13347 polymorphism of CD44 gene and the risk of occurring breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: With the attention paid to the heritability of breast cancer, the search for the genetic susceptibility gene of breast cancer has become a hot spot. At present, a number of studies have explored the relationship between rs13347 polymorphism of cluster of differentiation 44 (CD44) gene and breast cancer, but the research conclusions are inconsistent. Therefore, we will use this meta-analysis to explore the role of this gene polymorphism in breast cancer susceptibility. METHODS: The search time is set from the establishment of the database in March 2021 in this study. The search database include China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and China Biology Medicine disc, PubMed, EMBASE, Web of Science and the Cochrane Library. The subjects are observational studies on the relationship between rs13347 polymorphism of CD44 gene and breast cancer (including case-control study, cross-sectional study and a cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by two researchers independently. The data are statistically analyzed by Stata 16.0 software. RESULTS: Based on the existing studies, this study will systematically evaluate the relationship between CD44 gene rs13347 polymorphism and breast cancer. CONCLUSION: This study will provide evidence-based medical evidence to clarify the role of CD44 gene polymorphism in breast cancer, and provide help for the early detection and preventive intervention of breast cancer. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WBC7F.

Long non-coding RNA (lncRNA) HOXB-AS3 promotes cell proliferation and inhibits apoptosis by regulating ADAM9 expression through targeting miR-498-5p in endometrial carcinoma.

OBJECTIVE: Long non-coding RNA (lncRNA) expression is closely related to the pathogenesis and progression of various tumors. In this study, we investigated the mechanisms of lncRNA HOXB cluster antisense RNA 3 (HOXB-AS3), miRNA(miR)-498-5p, and disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) in endometrial carcinoma (EC) cells. METHODS: The expression levels of lncRNA HOXB-AS3 in EC tissues and cells were detected using RT-qPCR assays. The effects of HOXB-AS3 knockdown on EC cell proliferation and apoptosis were measured using CCK-8 assays, colony formation assays, and flow cytometry. In addition, putative miR-498-5p binding sites were identified in HOXB-AS3 and ADAM9. The targeted relationships were further verified using dual-luciferase reporter and RNA pull-down assays. RESULTS: HOXB-AS3 expression was upregulated in EC tissues and cells. EC cell proliferation and viability decreased significantly in HOXB-AS3 knockdown groups. A putative miR-498-5p binding site in HOXB-AS3 was verified. Inhibition of miR-498-5p rescued the effects of HOXB-AS3 knockdown on cell proliferation and apoptosis. Finally, ADAM9 was verified as a direct target gene of miR-498-5p. CONCLUSIONS: Our results suggest that lncRNA HOXB-AS3 is highly expressed in EC tissues and cells. Downregulation of HOXB-AS3 inhibits cell proliferation and promotes apoptosis in EC cells. HOXB-AS3 can upregulate ADAM9 expression by sponging miR-498-5p.

The effects of cages implantation on surgical and adjacent segmental intervertebral foramina.

OBJECTION: The overarching goal of our research was to compare the clinical and radiological outcomes with different sizes of cages implantation in anterior cervical discectomy and fusion (ACDF), and to evaluate the effects on surgical and adjacent segmental intervertebral foramina. METHODS: The clinical data of 61 patients were analyzed retrospectively. The radiological data included the surgical intervertebral disk space height before (H0) and after surgery (H), the preoperative mean height of adjacent segments (Hm), the area and height of the surgical and adjacent segment foramen, the surgical segmental Cobb angle (α1), and C2-7Cobb angle (α2). The calculation of clinical data was conducted by Japanese Orthopaedic Association Scores (JOA), the recovery rate of JOA scores and visual analog scales (VAS). In accordance with the different ranges of distraction (H/Hm), patients were classified into three groups: group A (H/Hm<1.20, n=13), group B (1.20≤H/Hm≤1.80, n=37), and group C (H/Hm>1.80, n=11). RESULTS: After the operation and at the final follow-up, our data has demonstrated that the area and height of surgical segmental foramen all increased by comparing those of preoperation in three groups (all P<0.05). However, except for a decrease in group C (all P<0.05), the adjacent segmental foramina showed no significant changes (all P>0.05). The area and height of the surgical segment foramen and the distraction degree were positively correlated (0

Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10.

MicroRNAs (miRNAs/miRs) are important biomarkers for the progression of intervertebral disc degeneration (IDD). We investigated the role of miR-30d in IDD progression through its interactions with forkhead box O3 (FOXO3) and C-X-C motif ligand 10 (CXCL10). We first measured the expression of miR-30d, FOXO3, and CXCL10 in NP cells cultured from IDD patients. RNA-immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were then employed to test the relationship among miR-30d, FOXO3, and CXCL10. Besides, gain- and loss-of function approaches were performed to assess the functional roles of miR-30d and FOXO3 in IDD in vitro and in vivo. We found high expression of miR-30d and CXCL10 and low expression of FOXO3 in IDD. We showed that miR-30d specifically targeted FOXO3, and that down-regulation of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by increasing the expression of FOXO3. Besides, FOXO3 inhibited apoptosis of NP cells by downregulation of CXCL10 expression. Moreover, inhibition of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by decreasing CXCL10. Furthermore, findings in the mouse IDD model confirmed the inhibitory role of decreased miR-30d in IDD progression. Thus, we show that downregulation of miR-30d could promote the proliferation of NP cells by increasing FOXO3 and decreasing CXCL10 expression, which may provide a novel therapeutic target for IDD.

Automatic deep learning-based colorectal adenoma detection system and its similarities with pathologists.

OBJECTIVES: The microscopic evaluation of slides has been gradually moving towards all digital in recent years, leading to the possibility for computer-aided diagnosis. It is worthwhile to know the similarities between deep learning models and pathologists before we put them into practical scenarios. The simple criteria of colorectal adenoma diagnosis make it to be a perfect testbed for this study. DESIGN: The deep learning model was trained by 177 accurately labelled training slides (156 with adenoma). The detailed labelling was performed on a self-developed annotation system based on iPad. We built the model based on DeepLab v2 with ResNet-34. The model performance was tested on 194 test slides and compared with five pathologists. Furthermore, the generalisation ability of the learning model was tested by extra 168 slides (111 with adenoma) collected from two other hospitals. RESULTS: The deep learning model achieved an area under the curve of 0.92 and obtained a slide-level accuracy of over 90% on slides from two other hospitals. The performance was on par with the performance of experienced pathologists, exceeding the average pathologist. By investigating the feature maps and cases misdiagnosed by the model, we found the concordance of thinking process in diagnosis between the deep learning model and pathologists. CONCLUSIONS: The deep learning model for colorectal adenoma diagnosis is quite similar to pathologists. It is on-par with pathologists' performance, makes similar mistakes and learns rational reasoning logics. Meanwhile, it obtains high accuracy on slides collected from different hospitals with significant staining configuration variations.

Clinically applicable histopathological diagnosis system for gastric cancer detection using deep learning.

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.

Magnetic resonance imaging features of minimal-fat angiomyolipoma and causes of preoperative misdiagnosis.

BACKGROUND: Minimal-fat angiomyolipoma (mf-AML) is often misdiagnosed as renal cell carcinoma before surgery. AIM: To analyze the magnetic resonance imaging (MRI) features of mf-AML and the causes of misdiagnosis by MRI before operation. METHODS: A retrospective analysis was performed on ten patients with mf-AML confirmed by surgical pathology, all of whom underwent preoperative MRI examination to analyze the morphological characteristics and MRI signals of the tumor. RESULTS: MRI revealed a circular-like mass in 4/10 (40%) patients, an oval mass in 6/10 patients (60%), a mass with a capsule in 9/10 patients (90%), and a mass with a lipid component in 7/10 patients (70%). The diameter of the masses in all ten patients was from 11 to 47 mm; the diameter was between 11 mm and 40 mm in 8/10 (80%) patients and between 40 mm and 47 mm in 2/10 (20%) patients. CONCLUSION: An oval morphological characteristic is strong evidence for the diagnosis of mf-AML, while a capsule and lipids are atypical manifestations of mf-AML.

Enhanced Anti-melanoma Efficacy of a Pim-3-Targeting Bifunctional Small Hairpin RNA via Single-Stranded RNA-Mediated Activation of Plasmacytoid Dendritic Cells.

Melanoma is the most serious type of skin cancer. The immunosuppressive tumor microenvironment and aberrant expression of some proto-oncogenes are the main cause of melanoma development. We have constructed a single-stranded RNA (ssRNA)-Pim-3-small hairpin RNA (shRNA) dual-function vector, which activates the toll-like receptor (TLR)7 to stimulate the antitumor immune response through ssRNA fragments and simultaneously silences the proto-oncogene Pim-3 to intensify apoptosis of the tumor cells via shRNA. Here, we found that therapy with the ssRNA-Pim-3-shRNA dual-function vector not only promotes the apoptosis and inhibits the proliferation of B16F10 melanoma cells by inhibiting the expression of Pim-3 but also enhances the activation of CD8+ T cells and natural killer (NK) cells and simultaneously reduces the proportion of intratumoral regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Together, these features effectively inhibit the growth of melanoma. Intriguingly, the bifunctional therapeutic effect that reverses the tumor immunosuppressive microenvironment is dependent on the activation of plasmacytoid dendritic cells (pDCs) and the secretion of type I interferon (IFN). Our study suggests that ssRNA-Pim-3-shRNA dual-function therapy is expected to become a promising therapeutic strategy for melanoma and other solid tumors with immunosuppressive microenvironment.

Enhanced Treatment Effects of Tilmicosin Against Staphylococcus aureus Cow Mastitis by Self-Assembly Sodium Alginate-Chitosan Nanogel.

The Staphylococcus aureus (S. aureus) cow mastitis causes great losses to the cow industry. In order to improve the treatment effect of tilmicosin against cow mastitis, the combination of solid lipid nanoparticle (SLN) technology with in situ hydrogel technology was used to prepare the self-assembly tilmicosin nanogel (TIL-nanogel). The physicochemical characteristics, in vitro release, antibacterial activity and in vivo treatment efficacy of TIL-SLNs and TIL-nanogel were studied, respectively. The results showed the loading capacity (LC), encapsulation efficiency (EE), size, zeta potential and poly dispersion index (PDI) of TIL-nanogel were 23.33 ± 0.77%, 67.89 ± 3.01%, 431.57 ± 12.87 nm, 8.3 ± 0.06 mv and, 0.424 ± 0.032, respectively. The TIL-nanogel showed stronger sustained release in vitro than TIL-SLNs and commercial injection. The cure rate of half dosage and normal dosage of TIL-nanogel was 58.3% and 75.0%, which was higher than that of commercial injection (50.0%) at normal dosage. The results suggest that the treatment dosage of tilmicosin for cow mastitis could be reduced by TIL-nanogel. The novel TIL-nanogel will be beneficial by decreasing the usage of tilmicosin and the treatment costs of cow mastitis.

Columbamine suppresses the proliferation and malignization of colon cancer cells via abolishing Wnt/ß-catenin signaling pathway.

BACKGROUND: Colon cancer is one of the most common malignancies worldwide. Because of the side effects and defects in tolerance of chemotherapy, it is necessary to discover new drugs for colon cancer treatment. Columbamine has been identified as an effective anti-osteosarcoma compound with only minor side effects. In this study, we analyzed the anticancer effect of columbamine on colon cancer. METHODS: Human colon cancer cell lines were treatment with columbamine. MTT assay, colony formation assay, apoptosis detection and tumorigenicity assay were performed to detect the protective effect of columbamine on colon cancer development. Western blot assay and luciferase reporter assay were conducted to investigate the potential mechanism of the columbamine treatment. RESULTS: Columbamine significantly inhibited the proliferation, migration, invasion process of colon cancer cells, and dramatically promoted the apoptosis rate of colon cancer cells to further suppress the development of colon cancer to tumor. Both the signaling transducing and key factors expression of Wnt/ß-catenin signaling pathway were obviously repressed by columbamine treatment in a dose-dependent manner. CONCLUSION: The present study indicated that columbamine exerts its anti-tumor effect in colon cancer cells through abolishing Wnt/ß-catenin signaling pathway. Columbamine may be a new therapy compound for colon cancer.