Effect of Mechanical Microenvironment on Collagen Self-Assembly In Vitro.

Collagen, as a structural protein, is widely distributed in the human body. Many factors influence collagen self-assembly in vitro, including physical-chemical conditions and mechanical microenvironment, and play a key role in driving the structure and arrangement. However, the exact mechanism is unknown. The purpose of this paper is to investigate the changes in the structure and morphology of collagen self-assembly in vitro under mechanical microenvironment, as well as the critical role of hyaluronic acid in this process. Using bovine type I collagen as the research object, collagen solution is loaded into tensile and stress-strain gradient devices. The morphology and distribution of collagen is observed using an atomic force microscope while changing the concentration of collagen solution, mechanical loading strength, tensile speed, and ratio of collagen to hyaluronic acid. The results demonstrate that the mechanics field governs collagen fibers and changes their orientation. Stress magnifies the differences in results caused by different stress concentrations and sizes, and hyaluronic acid improves collagen fiber orientation. This research is critical for expanding the use of collagen-based biomaterials in tissue engineering.

Weighted gene co-expression network analysis identifies RHOH and TRAF1 as key candidate genes for psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is inflammatory arthritis associated with psoriasis, which involves the axial joint and the distal interphalangeal joints. Its clinical features are varied, often resulting in delayed diagnosis and treatment. Improved knowledge about disease mechanisms will catalyze the rapid development of effective targeted therapies for this disease. The perturbations in the gene co-expression network may not be detected by the differential expression analysis of the microarray. This study aims to identify key modules and hub genes in psoriatic arthritis-applied WGCNA (weighted gene co-expression network analysis) on a microarray. METHODS: This study downloaded the array data of GSE61281 from the gene expression overview (GEO) database, which includes 20 psoriatic arthritis samples and 12 healthy controls. The analysis was performed with the WGCNA package. Gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these key modules. Candidate hub genes were identified using GS and MM measures, Cytoscape, and the online database STRING. RESULTS: A total of 10 co-expression modules were constructed. The lightcyan module was identified as the key module. GO and KEGG pathway analyses were mainly enriched in dephosphorylation, regulation of small GTPase-mediated signal transduction, Ras signaling pathway, MAPK signaling pathway, and vascular smooth muscle contraction. Two hub genes, RHOH/TRAF1, were selected. CONCLUSIONS: This finding may indicate that RHOH/TRAF1 play a critical role in the pathogenesis of PsA. This is one of the first studies in PsA using WGCNA, which may provide a new research direction for further understanding of the molecular mechanism and clinical application of PsA. Key points • The WGCNA method was applied to the expression profile microarray of psoriatic arthritis and the co-expression module was constructed. • Identify the key modules by combining the onset time of psoriasis in patients with psoriatic arthritis. • Three screening methods are used to identify and verify hub genes of key modules.

Bioinformatic evidences and analysis of putative biomarkers in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. Aberrant expression of genes plays important role in the procession of PDAC. The analysis of gene expression profile will contribute to the research of carcinoma mechanism. OBJECTIVE: This present study is focused to investigate the differentially expressed genes (DEGs) from 3 PDAC microarray datasets, which would provide candidate genes for putative biomarkers to understand the mechanism of PDAC and potential targets of treatment. METHOD: Based on the overlap genes obtained from 3 GEO datasets, the hub genes were identified using STRING and Cytoscape plugin MCODE. The enrichment and function analysis were applied using DAVID. The protein-protein interaction network was performed using cBioPortal and UCSC Xena. The Oncomine was finally used to determine the candidate gene by analyzing their expression between pancreas sample and PDAC sample. RESULTS: 25 hub genes were selected from a total of 1006 DEGs from 3 GEO datasets, consisting of 14 upregulated genes and 11 downregulated genes. The overall decline of hub gene expression enriched in G1 phase of cell cycle in other subtypes of pancreatic cancer. Oncomine database was ultimately performed to determine the 8 candidate genes, including CXCL5, CCL20, NMU, F2R, ANXA1, EDNRA, LPAR6, and GNA15. CONCLUSIONS: Conclusively, 8 candidate genes would become the potential PDAC combined biomarkers for diagnosis and therapeutic strategies.

Chromium(VI) promotes cell migration through targeting epithelial-mesenchymal transition in prostate cancer.

Chromium (Cr) is widely used in industry, making its toxicity a matter of concern. Although hexavalent Cr [Cr(VI)] can promote cancer cell proliferation in several cancers, there is little evidence implicating Cr(VI) in cancer cell migration, especially in prostate cancer. We show that the Cr concentration is higher in the serum of prostate cancer patients, and is closely associated with unfavorable outcomes for the patients. Additionally, low dose trivalent Cr [Cr(III)] exposure has no obvious carcinogenic effects in prostate cancer. However, Cr(VI) can promote proliferation and invasion of prostate cancer cell line PC3 cells in vitro and in vivo. In seeking the molecular mechanism of Cr(VI) exposure on cancer progression, we found that Cr(VI) could down-regulate the epithelial protein marker, E-cadherin, and up-regulate mesenchymal protein markers, such as N-cadherin and Snail. Together, these data indicate that Cr(VI) is a newly verified carcinogen in prostate cancer, and can promote cell migration by affecting the Epithelial-Mesenchymal Transition (EMT) pathway. Thus, inhibition of Cr(VI)-EMT signaling is a prospective approach toward limiting prostate tumor progression.

Analysis of the relationship between morphology of intervertebral disc and some correlated factors following discography in patients with chronic low back pain.

OBJECTIVE: To evaluate the diagnostic effectiveness of discography in discogenic low back pain (LBP). METHODS: Ninety-six cases of chronic LBP with or without referred thigh pain were enrolled in this study. All these cases received CT scan following discography once conservative treatment for at least 6 months had failed. There were 42 men and 54 women, aged from 24 to 67 years (average 46.4). Discography was performed on 218 discs. The positive discs were classified morphologically according to the Dallas Discogram Description (DDD). RESULTS: (i) The 56 cases (58.3%) which were positive on discography were divided into two subgroups of age less or more than 50 years. Positive rates for the two subgroups were 33.3% and 66.7%, respectively; (ii) one hundred and twenty-two discs, of which 62 (50.8%) were positive on discography, showed morphologic abnormality, whereas all the discography positive discs showed morphologic abnormality. No complication related to discography was found in any case. CONCLUSION: (i) Compared with the younger patients, older LBP patients have a lower positive rate of discography despite the presence of more serious degenerative disc changes; (ii) outer layer disruption of the annulus fibrous correlates with positive discography; (iii) MRI intensity changes are not specific in diagnosing discogenic pain. Additional discography is needed to identify the painful disc; and (iv) the contrast volume injected into discs can be affected by a variety of factors which restrict its diagnostic value.

[Instant and fatigue stability analysis of anterior lumbar interbody fusion with stand-alone cage].

OBJECTIVE: To investigate the spinal segment instant and fatigue stability of anterior lumbar interbody fusion with stand-alone cage. METHODS: The vertebrae L4 and S1 of 6 human lumbar specimens (L3 - S1) were embedded with dental base acrylic resin powder and fixed on mechanical machine, and the L4/L5 and L5/S1 disk spaces were left active. The 6 specimens underwent mechanical test as control group first, and then used as experimental group with a cage implanted in L5/S1. Instant instability was tested in three directions: flexion, extension, and lateral bend. The relative movement of L4/L5 and L5/S1 was recorded. Fatigue instability was tested after 50 000 times of flexion-extension movement, and the relative displacement between the cage and S1 was recorded. RESULT: In the three directions of flexion, extension, and lateral bend, the relative movements of L5/S1 in the experimental group were 0. 83 +/- 0.26 degrees, 1.60 +/- 0.19 degrees, and 0.72 +/- 0.20 degrees respectively, all significantly decreased than those of the control group (3.60 +/- 0.30 degrees, 4.82 +/- 0.34 degrees, and 3.80 +/- 0.28 degrees respectively, all P < 0.01). The relative movement of L4/L5 of the experimental group were 5.82 +/- 0.36 degrees, 5.38 +/- 0.30 degrees, and 4.96 +/- 0.29 degrees in the three directions respectively, all significantly higher than those of the control group (4.16 +/- 0.33 degrees, 4.02 +/- 0.30 degrees, and 3.48 +/- 0.34 degrees respectively, all P <0.01). After 50 000 times of flexion-extension fatigue movement, the relative displacement between the cage and S1 was zero. CONCLUSION: Anterior lumbar interbody fusion with a stand-alone cage has excellent instant and fatigue stability, which can provide enough stability for clinical bone fusion without other internal fixation.