Bioinformatics analyses of gene expression profile identify key genes and functional pathways involved in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.

Bromelain-decorated hybrid nanoparticles based on lactobionic acid-conjugated chitosan for in vitro anti-tumor study.

In this work, lactobionic acid-modified chitosan (CLA) was chosen as an initial material to prepare tumor-targeted nanoparticles (CLA NPs). To improve the nanoparticles' tumor penetration ability, bromelain was then decorated on the surface of CLA NPs to give CLAB NPs. The micromorphology of CLA and CLAB NPs was observed by transmission electron microscopy and scanning electron microscopy. The stability of CLA and CLAB NPs was then investigated at different pH values (4.0-9.0) and physiological environment by dynamic light scattering. Doxorubicin as a model drug was successfully encapsulated into these two nanoparticles and drug release profiles were also investigated at pH 5.5, 6.5 and 7.4, respectively. Cellular uptake and MTT results against HepG2 and SH-SY5Y cells demonstrated that the LA-conjugated tumor-targeting NPs can be efficiently internalized into hepatoma carcinoma cells, leading to higher cytotoxicity than free doxorubicin. CLAB NPs show considerable cell cytotoxicity and are expected to improve the penetration ability and therapeutic effect in the subsequent in vivo studies.

[Matrine effects on JM cells by inhibiting proliferation and inducing apoptosis].

OBJECTIVE: To study effects of matrine on JM cell strain. METHOD: Morphologic changes were observed under light microscope with Wright-Giemsa staining, fluorescence microscope with Hoechst 33,258 staining and electron microscope. Alteration of cell cycle of different dose treating groups at the fourth day and 0.8 mg.mL-1 treatment group at the first, second, third, fourth day was analyzed by Flow cytometry. DNA ladder was detected with gel electrophoresis. RESULT: From the third day after treatment of matrine, typical apoptosis features of cells were observed under light microscope and electron microscope in all test groups, and the features were more prominent with the time prolonging. At fourth day, flow cytometry analysis showed that there were sub-G1 peaks in all groups. From 0.1, 0.2, 0.4, 0.6 to 0.8 g.L-1 treatment groups, the rate of apoptotic cells to total cells were 3.1%, 2. 5%, 13.3%, 40.4%, 48.6%, respectively, and what in the control group was 1.4%; the rate of S phase cells to total cells was 28.9%, 26.1%, 27.7%, 0.9%, 14.2%, what in the control group was 30.4%; the rate of G1 phase cells to total cells was 63. 2%, 67.5%, 68.1%, 75.2%, 83.6%, what in the control group was 41.8%; From the first, second, third to fourth day, the rate of apoptotic cells to total cells of 0.8 mg.mL-1 treatment group were 3.0%, 3.7%, 9.1%, 48.6%, respectively; the rate of S phase cells to total cells was 28.6%, 17.5%, 19.1%, 14.2%; the rate of G1 phase cells to total cells were 45.5%, 77.3%, 77.2%, 83.6%. Gel electrophoresis displayed "DNA ladder" in 0.4, 0.6, 0.8 g.L-1 groups, while 0.1 and 0.2 g.L-1 groups didn't show such result. CONCLUSION: Matrine can repress DNA synthesis and arrest JM cell strain at G1 phase, sequentially inhibiting the proliferation of the cell. Besides, this alkaloid can induce the apoptosis of JM cells.

Bioactive compounds from Cornus officinalis fruits and their effects on diabetic nephropathy.

ETHNOPARMACOLOGICAL RELEVANCE: The fruit of Cornus officinalis, called "Shanzhuyu", a traditional medicine in China, is used for the treatment of kidney diseases, including diabetic nephropathy. The aim of this study is to investigate the anti-diabetic nephropathy activity of Shanzhuyu and the active compounds in the fruit. MATERIALS AND METHODS: The air dried fruit of Cornus officinalis was extracted in 80% EtOH, the obtained residue was fractioned on D101 resin column eluted with H2O/EtOH solution to get five crude fractions (fr. A-E). The anti-diabetic nephropathy activity of fractions (fr. A-E) was evaluated in vitro by inhibiting the expression of collagen IV (Col V), fibronectin (FN) and IL-6 in high-glucose-induced mesangial cells. By preliminary bio-assay screenings, repeated column chromatography on fraction B-D led the isolation of 22 compounds, whose structures were determined by extensive spectroscopic analysis, and the anti-diabetic nephropathy activity of the isolated compounds was also evaluated. RESULTS: Two new iridoid glucosides, logmalicids A and B (1 and 2), together with 20 known compounds (3-22) were isolated from the extract of Shanzhuyu under the bioassay-guided screenings. The anti-diabetic nephropathy activity assay displayed that fractions A, D and E could significantly inhibit the production of Col IV; fractions A and C could significantly inhibit the expression of FN and IL-6 in the high-glucose-stimulated mesangial cells at concentration of 50 µg/mL; and loganin (3) and its derivatives (1 and 2) could significantly inhibit the expression of FN and IL-6 at concentration of 10 µM, respectively. CONCLUSIONS: The results suggested that loganin and its derivatives were the active compounds in Cornus officinalis fruit (Shanzhuyu) on diabetic nephropathy. This study further supported the traditional use of Shanzhuyu to treat diabetic nephropathy and related kidney diseases.

Two new neolignans from Patrinia scabra with potent cytotoxic activity against HeLa and MNK-45 cells.

Two new neolignans, patrineolignan A (1) and patrineolignan B (2), together with seven known lignans, were isolated from the 90 % aqueous EtOH extract of the roots of Patrinia scabra. Their structures were elucidated on the basis of spectroscopic data (HRESIMS, IR, 1D and 2D NMR) and comparison with literature data. The two new neolignans were evaluated in vitro for cytotoxic properties against human cervical carcinoma HeLa cell line and gastric carcinoma MNK-45 cell line using the microculture tetrazolium assay, and both 1 and 2 exhibited strongly cytotoxic activity against the two tumor cell lines.

Novel norlignan glucosides from rhizomes of Curculigo sinensis.

Eight norlignan glucosides, including two novel skeleton-rearranged compounds, sinenside A (1) and B (2), and six known compounds, crassifoside D (3), capituloside (4), a mixture of (1S,2R)-1-O-methylnyasicoside (5), (1R,2R)-1-O-methylisonyasicoside (6), and a mixture of (1S,2R)-1-O-methylcurculigine (7) and (1R,2R)-1-O-methylisocurculigine (8), were isolated from the rhizomes of Curculigo sinensis. Compounds 3-8 were isolated for the first time from this plant. Structures of the isolated compounds were established by spectroscopic analysis, including UV, IR, HRESI-MS, and 1D/2D NMR, and hydrolysis experiments. The free radical scavenging activity of the isolated compounds was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. All the isolated compounds showed strong radical scavenging activities.

Ternary liquid-liquid equilibria measurement for epoxidized soybean oil + acetic acid + water.

Liquid-liquid equilibria (LLE) data were measured for ternary system epoxidized soybean oil (ESO) + acetic acid + water at 313.15, 323.15 and 333.15 K, respectively. The consistency of the measured LLE data was tested, using Othmer-Tobias correlation and root-mean-square deviation (sigma) in mass fraction of water in the lower phase and average value of the absolute difference (AAD) between experimental mass fraction of epoxidized soybean oil in the upper phase and that calculated using Othmer-Tobias correlation.