Predictive potentials of glycosylation-related genes in glioma prognosis and their correlation with immune infiltration.

Glycosylation is currently considered to be an important hallmark of cancer. However, the characterization of glycosylation-related gene sets has not been comprehensively analyzed in glioma, and the relationship between glycosylation-related genes and glioma prognosis has not been elucidated. Here, we firstly found that the glycosylation-related differentially expressed genes in glioma patients were engaged in biological functions related to glioma progression revealed by enrichment analysis. Then seven glycosylation genes (BGN, C1GALT1C1L, GALNT13, SDC1, SERPINA1, SPTBN5 and TUBA1C) associated with glioma prognosis were screened out by consensus clustering, principal component analysis, Lasso regression, and univariate and multivariate Cox regression analysis using the TCGA-GTEx database. A glycosylation-related prognostic signature was developed and validated using CGGA database data with significantly accurate prediction on glioma prognosis, which showed better capacity to predict the prognosis of glioma patients than clinicopathological factors do. GSEA enrichment analysis based on the risk score further revealed that patients in the high-risk group were involved in immune-related pathways such as cytokine signaling, inflammatory responses, and immune regulation, as well as glycan synthesis and metabolic function. Immuno-correlation analysis revealed that a variety of immune cell infiltrations, such as Macrophage, activated dendritic cell, Regulatory T cell (Treg), and Natural killer cell, were increased in the high-risk group. Moreover, functional experiments were performed to evaluate the roles of risk genes in the cell viability and cell number of glioma U87 and U251 cells, which demonstrated that silencing BGN, SDC1, SERPINA1, TUBA1C, C1GALT1C1L and SPTBN5 could inhibit the growth and viability of glioma cells. These findings strengthened the prognostic potentials of our predictive signature in glioma. In conclusion, this prognostic model composed of 7 glycosylation-related genes distinguishes well the high-risk glioma patients, which might potentially serve as caner biomarkers for disease diagnosis and treatment.

Salidroside protects RGC from pyroptosis in diabetes-induced retinopathy associated with NLRP3, NFEZL2 and NGKB1, revealed by network pharmacology analysis and experimental validation.

OBJECTIVE: To investigate the effect of salidroside (SAL) in protecting retinal ganglion cell (RGC) from pyroptosis and explore associated molecular network mechanism in diabetic retinapathy (DR) rats. METHODS: HE, Nissl and immunofluorescence staining were used to observe the retinal morphological change, and the related target genes for salidroside, DR and pyroptosis were downloaded from GeneCard database. Then Venny, PPI, GO, KEGG analysis and molecular docking were used to reveal molecular network mechanism of SAL in inhibiting the pyroptosis of RGC. Lastly, all hub genes were confirmed by using qPCR. RESULTS: HE and Nissl staining showed that SAL could improve the pathological structure known as pyroptosis in diabetic retina, and the fluorescence detection of pyroptosis marker in DM group was the strongest, while they decreased in the SAL group(P < 0.05)). Network pharmacological analysis showed 6 intersecting genes were obtained by venny analysis. GO and KEGG analysis showed 9 biological process, 3 molecular function and 3 signaling pathways were involved. Importantly, molecular docking showed that NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1 could combine with salidroside, and qPCR validates the convincible change of CASP3, NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1. CONCLUSION: Salidroside can significantly improve diabetes-inducedRGC pyrotosis in retina, in which, the underlying mechanism is associated with the NLRP3, NFEZL2 and NGKB1 regulation.

Microarray analysis of lncRNAs and mRNAs in spinal cord contusion rats with iPSC-derived A2B5+ oligodendrocyte precursor cells transplantation.

Spinal cord injury (SCI) is a severe complication of spinal trauma with high disability and mortality rates. Effective therapeutic methods to alleviate neurobehavioural deficits in patients with SCI are still lacking. In this study, we established a spinal cord contusion (SCC) model in adult Sprague Dawley rats. Induced pluripotent stem cell-derived A2B5+ oligodendrocyte precursor cells (iP-A2B5+OPCs) were obtained from mouse embryonic fibroblasts and injected into the lesion sites of SCC rats. Serological testing and magnetic resonance imaging were employed to determine the effect of iP-A2B5+OPCs cell therapy. The Basso-Beattie-Bresnahan score and inclined plane test were performed on days 1, 3, 7, and 14 after cell transplantation, respectively. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were detected by microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyse the biological functions of these lncRNAs and mRNAs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify variations in the expression of crucial target genes. The results demonstrated that induced pluripotent stem cells exhibited embryonic stem cell-like morphology and could differentiate into diverse neural cells dominated by oligodendrocytes. The neurobehavioural performance of rats treated with iP-A2B5+OPCs transplantation was better than that of rats with SCC without cell transplantation. Notably, we found that 22 lncRNAs and 42 mRNAs were concurrently altered after cell transplantation, and the key lncRNA (NR_037671) and target gene (Cntnap5a) were identified in the iP-A2B5+OPCs group. Moreover, RT-qPCR revealed that iP-A2B5+OPCs transplantation reversed the downregulation of NR_037671 induced by SCC. Our findings indicated that iP-A2B5+OPCs transplantation effectively improves neurological function recovery after SCC, and the mechanism might be related to alterations in the expression of lncRNAs and mRNAs, such as NR_037671 and Cntnap5a.

Two new diterpenoids from Excoecaria acerifolia.

A new tigliane diterpenoid, acerifolin A (1), and a new isopimarane diterpenoid, acerifolin B (2), together with two known compounds, were isolated from Excoecaria acerifolia. Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control.

Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy.

To investigate the effect of scutellarin (SCU) in diabetic retinopathy (DR) and explore the associated molecular network mechanism. The animal model of DR was established from diabetic mellitus (DM) rats by intraperitoneally injected streptozotocin (STZ) at dosage 55 mg/kg. Meanwhile, SCU was intraperitoneally administrated to protect retina from cell pyroptosis induced by DM, and cell pyroptosis was detected by using HE, Nissl staining, and immunofluorescence recognition. Moreover, the hub gene involving in pyroptosis in DR was screened by bioinformatics and network pharmacology, designated as Venny intersection screen, GO and KEGG analysis, PPI protein interaction, and molecular docking. Lastly, the expressional change of hub genes were validated with experimental detection. Cell pyroptosis of the DR, specifically in retina ganglion cells (RGC), was induced in DM rats; SCU administration results in significant inhibition in the cell pyroptosis in DR. Mechanically, 4084 genes related to DR were screened from GeneCards and OMIM databases, and 120 SCU therapeutic targets were obtained, by using GeneCards, TCMSP with Swiss Target Prediction databases. Moreover, 357 targets related to pyroptosis were found using GenenCards database, and Drug, disease and phenotypic targets were analyzed online using the Draw Venn Diagram website, and 12 cross targets were obtained. Through GO function and KEGG pathway enrichment analysis, 659 BP related items, 7 CC related items, 30 MF related items, and 70 signal pathways were screened out; Of these, eleven proteins screened from cross-target PPI network were subsequently docked with the SCU, and their expressions including caspase-1, IL-1ß, IL-18, GSDMD and NLRP3 in RGC indicated by immunofluorescence, and the mRNA expression for caspase-1 in DR indicated by quantitative PCR, were successfully validated. SCU can effectively protect RGC pyroptosis in DR, and underlying mechanisms are involved in the inhibition of caspase-1, GSDMD, NLRP3, IL-1ß and IL-18. Our findings therefore provide crucial evidence to support the clinic practice of SCU for the treatment of DR, and explained the underlying molecular network mechanism.

Knockdown of interleukin-6 plays a neuroprotective role against hypoxia-ischemia in neonatal rats via inhibition of caspase 3 and Bcl-2-associated X protein signaling pathway.

This study aimed to investigate the role of interleukin-6 (IL-6) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (NHIE). Sprague-Dawley (SD) rats were used for the establishment of hypoxic-ischemic (HI) model. The Zea-Longa scoring was used to evaluate the extent of the neurological deficits. Triphenyl tetrazolium chloride (TTC) staining was used to measure the volume of infarction in the brain following HI protocol. The expression of IL-6 in the cortex and/or hippocampus at multiple time points after HI was examined by immunohistochemistry, western blotting and immunofluorescence. Moreover, small interfering RNAs (siRNA) were used to inhibit the expression of IL-6 in-vitro and in-vivo, and the concomitant expression of the Bcl-2 associated X protein (BAX) and caspase 3 was also measured. HI induced a significant brain damage, and these pathological changes were accompanied by IL-6 upregulation which was found localized in cortical neurons. The inhibition of IL-6 expression fostered neuronal and axonal growth, and a reduction in cellular apoptosis in cortical neuronal cultures, and cortex and hippocampus of neonatal rats. The expression of apoptotic markers such as BAX and caspase 3 was closely associated with IL-6. Downregulation of IL-6 could ameliorate HI-induced deficiencies by mediating the expression of caspase 3 and BAX.

The role of microglia in Alzheimer's disease and progress of treatment.

Microglia are permanent immune cells of the central nervous system. Microglia play an important role in the pathological process of Alzheimer's disease (AD). They are mainly involved in the uptake and clearance of amyloid-ß (Aß), as well as the formation of neuroinflammation. We found that overactivated microglia increase Aß and Tau, and Aß and Tau in turn act as activators of microglia. Additionally, various cytokines and proteins, high cholesterol, and telomere shortening are all associated with microglia activation. More activated microglia induce the release of inflammatory and anti-inflammatory factors to regulate inflammation, while microglia express multiple homologous receptors that bind to neuroimmunomodulators to prevent microglia overactivation. Moreover, aging of the body promotes neuroinflammation by increasing the response to IFN-γ (interferon-γ), and aging of the microglia themselves promotes AD by inducing the accumulation of large amounts of iron and reducing autophagy by regulating protein levels. Cognitive dysfunction occurs when activated microglia induce an increase in beta oligomers, promoting the production of pro-inflammatory factors that alter the shape, composition, and density of synapses. Based on their correlation, microglia-mediated AD therapy as well as the corresponding targets and drugs are discussed. In contrast to similar reviews, this article also summarizes some novel microglia-mediated AD treatment methods over the recent years.

Tabernaecorymine A, an 18-normonoterpenoid indole alkaloid with antibacterial activity from Tabernaemontana corymbosa.

Tabernaecorymine A, an 18-normonoterpenoid indole alkaloid with conjugated (E)-3-aminoacrylaldehyde fragment was obtained from the stem bark of Tabernaemontana corymbosa. Its structure was elucidated by extensive spectroscopic data analyses, and further verified by ACD/structure elucidator, electronic circular dichroism (ECD) analyses and density functional theory (DFT) chemical shift predictions. The compound exhibited significant antibacterial bioactivity against Streptococcus dysgalactiae with an MIC value of 3.12 µg/mL, which is better than the plant drug berberine.

Brain structure analysis of different age groups of Diannan small-ear pigs.

The objective of the study is to investigate the brain development and atrophy of Diannan small-ear pigs in different ages using magnetic resonance imaging (MRI). A total of 12 Diannan small-ear pigs were included and divided into the young group, adult group, and middle-and-old age (M&O) group according to their age. The brain structure of pigs was scanned using MRI, and the brain data obtained were statistically analyzed by signal conversion and image reconstruction. Compared with the young group, the signals of most brain structures in the adult group and M&O group were significantly decreased (p < 0.05). Compared with the adult group, the signal intensity of the right caudate nucleus and the right lateral ventricle in the M&O group was significantly increased, while the signal intensity of other regions was almost significantly decreased (p < 0.05). Compared with the young group, both adult and M&O groups had some degree of brain atrophy. Brain atrophy in the precuneus and the inferior temporal gyrus was more predominant in the M&O group in comparison with the adult group. The present study demonstrated that the brain signal of Diannan small-ear pigs gradually diminished with age, while the degree of brain atrophy was the opposite, providing the basic data on the brain of Diannan small-ear pigs.

New oxindole alkaloids with selective osteoclast inhibitory activity from Gelsemium elegans.

A new alkaloid 14-hydroxygelseziridine (1), along with four known oxindoles (2-5), was isolated and characterized from the well-known toxic medicine Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemistry calculations. Structurally, new compound 1 has a three membered oxygen ring at N-4/C-20. All compounds were tested for osteoclast (MOC-1) inhibitory activity in vitro. Compound 2 exhibited the selective osteoclast inhibitory activity. Flow cytometry revealed that the apoptosis of osteoclasts induced by 2. Furthermore, the PCR bioassay suggested that compound 2 may activate the apoptotic pathway of osteoclasts by reducing the expression of IL-6 and c-Jun, and increasing caspase 9. This work provided the evidence for the rationality as the traditional treatment for bone related diseases of G. elegans, and shed a new light on its further research.

Monoterpene indole N-oxide alkaloids from Tabernaemontana corymbosa and their antimicrobial activity.

Tabernaemontana corymbosa is a traditional folk medicine. In our research, six monoterpene indole N-oxide alkaloids and their parent alkaloids were obtained from the stem bark of T. corymbosa, including seven new alkaloids (1-7) and five known alkaloids (8-12). Their structures and absolute configurations were elucidated by extensive spectroscopy, quantum chemical calculations, and DP4+ probability analyses. The antimicrobial activity of the obtained compounds was evaluated, among which alkaloids 4, 8, 12 showed significant antimicrobial activity against Staphylococcus aureus with an MIC value of 6.25 µg/mL, while alkaloids 11, 12 showed moderate antimicrobial activity against Bacillus subtilis with an MIC value of 25 µg/mL.

Alstoscholarisine K, an Antimicrobial Indole from Gall-Induced Leaves of Alstonia scholaris.

Alstoscholarisine K, an indole alkaloid with eight chiral carbons and featuring a novel 6/5/6/6/6/6/6/5 octacyclic architecture, was found to be specific to the gall-infected leaves of Alstonia scholaris. Its structure was elucidated by spectroscopy, computational analysis, and single-crystal X-ray diffraction. The unusual highly fused cage-like pyrrolo[1,2-a]pyrimidine structure with an additional -C4N unit is possibly derived from a combination of monoterpenoid indole and polyamine pathways. The fascinating compound exhibited significant antibacterial bioactivities by targeting cell membranes.

Mitigating the Microcracks of High-Ni Oxides by In Situ Formation of Binder between Anisotropic Grains for Lithium-Ion Batteries.

Increasing attention has been paid to layered high-Ni oxides with high capacity as a promising cathode for high-energy lithium-ion batteries. However, the undesirable microcracks in secondary particles usually occur due to the volume changes of anisotropic primary grains during cycles, which lead to the decay of electrochemical performance. Here, for the first time, a functional electrolyte with di-sec-butoxyaluminoxytriethoxysilane additive integrating the functions of silane and aluminate is proposed to in situ form the binder-like filler between anisotropic primary grains for mitigating the microcracks of high-Ni oxides. It is demonstrated that Li-containing aluminosilicate as a glue layer between the gaps of grains and as a coating layer on the surface of the grains is generated, and these features further enhance the interfacial bonding and surface stability of anisotropic primary grains. Consequently, the microcracks along with side reactions and phase transitions of high-Ni oxides are mitigated. As anticipated, the electrochemical performance and thermal stability of high-Ni oxides are improved, and there is also a capacity retention of 75.4% even after 300 cycles and large reversible capacity of ∼160 mA h g-1 at 5 C. The functional electrolyte offers a simple, efficient, and scalable method to promote the electrochemical properties and applicability of high-Ni oxide cathodes in high-energy lithium-ion batteries.

Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice.

AIM: To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. METHODS: 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. RESULTS: Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. CONCLUSION: Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

Saikosaponin A protects against dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis, one of the most important inflammatory bowel diseases, affects millions of people worldwide. The aim of this study was to investigate the effects of Saikosaponin A on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were treated with 2.5% DSS for 5 d to induce acute colitis. Saikosaponin A was given 3 d before and during DSS treatment by intragastric administration. The results showed that Saikosaponin A significantly inhibited DSS-induced body weight loss and shortening of colon length. DSS-induced colonic histological changes and MPO activity were also prevented by treatment of Saikosaponin A. The levels of TNF-α and IL-1ß were increased by DSS and dose-dependently inhibited by Saikosaponin A. Furthermore, Saikosaponin A significantly inhibited DSS-induced NF-κB activation and up-regulated the expression of LXRα. Taken together, our results indicated that Saikosaponin A had protective effects against DSS-induced colitis. Saikosaponin A protected DSS-induced colitis through inhibiting inflammatory response.

Nepenthe-Like Indole Alkaloids with Antimicrobial Activity from Ervatamia chinensis.

Two monoterpenoid indole alkaloid erchinines A (1) and B (2), possessing unique 1,4-diazepine fused with oxazolidine architecture and three hemiaminals, were isolated from Ervatamia chinensis. Their structures were elucidated on the basis of intensive spectroscopic analysis, and a plausible biosynthetic pathway from ibogaine was proposed. Both compounds exhibited significant antimicrobial activity against Trichophyton rubrum and Bacillus subtilis, and their activities were comparable to the first line antifungal drug griseofulvin and antibiotic cefotaxime.